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Practice valuation
Too often, physicians are not receiving a fair return on the equity they have worked so hard to build over several decades, either because they have waited too long and must accept what is offered, or because they simply take the buyer’s word for their practice’s value. Don’t put yourself in either of those positions, and don’t entertain any offers until you obtain an objective appraisal from a neutral party.
Of course, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in 750 words; but three basic yardsticks are essential for determining the equity, or book value, of a practice:
- Tangible assets. Equipment, cash, accounts receivable, and other property owned by the practice.
- Liabilities. Accounts payable, outstanding loans, and anything else owed to others.
- Intangible assets. Sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.
Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.
Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons why patients come back (if in fact they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etcetera), the extent and strength of the referral base, and the presence of supplemental income streams, such as clinical research.
It is also important to determine to what extent intangible assets are transferable. For example, unique skills with a laser, neurotoxins, or filler substances, or extraordinary personal charisma, may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.
Once again there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.
Two newer techniques that some consider a better estimate of intangible assets are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings (and thus its overall value) are.
Asset-based valuation is the most popular, but by no means the only method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not its income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.
Whatever methods are used, it is important that the appraisal be done by an experienced and independent financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Too often, physicians are not receiving a fair return on the equity they have worked so hard to build over several decades, either because they have waited too long and must accept what is offered, or because they simply take the buyer’s word for their practice’s value. Don’t put yourself in either of those positions, and don’t entertain any offers until you obtain an objective appraisal from a neutral party.
Of course, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in 750 words; but three basic yardsticks are essential for determining the equity, or book value, of a practice:
- Tangible assets. Equipment, cash, accounts receivable, and other property owned by the practice.
- Liabilities. Accounts payable, outstanding loans, and anything else owed to others.
- Intangible assets. Sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.
Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.
Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons why patients come back (if in fact they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etcetera), the extent and strength of the referral base, and the presence of supplemental income streams, such as clinical research.
It is also important to determine to what extent intangible assets are transferable. For example, unique skills with a laser, neurotoxins, or filler substances, or extraordinary personal charisma, may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.
Once again there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.
Two newer techniques that some consider a better estimate of intangible assets are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings (and thus its overall value) are.
Asset-based valuation is the most popular, but by no means the only method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not its income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.
Whatever methods are used, it is important that the appraisal be done by an experienced and independent financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Too often, physicians are not receiving a fair return on the equity they have worked so hard to build over several decades, either because they have waited too long and must accept what is offered, or because they simply take the buyer’s word for their practice’s value. Don’t put yourself in either of those positions, and don’t entertain any offers until you obtain an objective appraisal from a neutral party.
Of course, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in 750 words; but three basic yardsticks are essential for determining the equity, or book value, of a practice:
- Tangible assets. Equipment, cash, accounts receivable, and other property owned by the practice.
- Liabilities. Accounts payable, outstanding loans, and anything else owed to others.
- Intangible assets. Sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.
Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.
Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons why patients come back (if in fact they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etcetera), the extent and strength of the referral base, and the presence of supplemental income streams, such as clinical research.
It is also important to determine to what extent intangible assets are transferable. For example, unique skills with a laser, neurotoxins, or filler substances, or extraordinary personal charisma, may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.
Once again there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.
Two newer techniques that some consider a better estimate of intangible assets are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings (and thus its overall value) are.
Asset-based valuation is the most popular, but by no means the only method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not its income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.
Whatever methods are used, it is important that the appraisal be done by an experienced and independent financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Symptoms of fatigue and abdominal pain
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Crohn disease.
Crohn disease is a chronic inflammatory bowel disease that is becoming increasingly prevalent worldwide. It is estimated to affect three to 20 persons per 100,000. When not effectively managed, Crohn disease is associated with substantial morbidity and significant impairments in lifestyle and daily activities during flares and remissions. It is characterized by a transmural granulomatous inflammation that can affect any part of the gastrointestinal tract — usually, the ileum, colon, or both.
Abdominal pain, diarrhea, weight loss, and fatigue are often prominent symptoms in patients with Crohn disease. Crampy or steady right lower quadrant or periumbilical pain may develop; the pain both precedes and may be partially relieved by defecation. Diarrhea is frequently intermittent and is not usually grossly bloody. Diffuse abdominal pain accompanied by mucus, blood, and pus in the stool may be reported by patients if the colon is involved. Involvement of the small intestine usually presents with evidence of malabsorption, including diarrhea, abdominal pain, weight loss, and anorexia, which may be subtle early in the disease course. Anorexia, nausea, and vomiting are more common in patients with gastroduodenal involvement, whereas debilitating perirectal pain, malodorous discharge from a fistula, and disfiguring scars from active disease or previous surgery may be present in patients with perianal disease. Patients may also present with symptoms suggestive of intestinal obstruction, or with anemia, recurrent fistulas, or fever.
As stated in guidelines from the American Gastroenterological Association (AGA), multiple streams of information, including history and physical examination, laboratory tests, endoscopy results, pathology findings, and radiographic tests, must be incorporated to arrive at a clinical diagnosis of Crohn disease. In most cases, the presence of chronic intestinal inflammation solidifies a diagnosis of Crohn disease. However, it can be challenging to differentiate Crohn disease from ulcerative colitis, particularly when the inflammation is confined to the colon. Bleeding is much more common in ulcerative colitis than in Crohn disease, whereas intestinal obstruction is common in Crohn disease and uncommon in ulcerative colitis. Fistulae and perianal disease are common in Crohn disease but are absent or rare in ulcerative colitis. Moreover, weight loss is typical in patients with Crohn disease but is uncommon in ulcerative colitis.
Additional diagnostic clues for Crohn disease include discontinuous involvement with skip areas; sparing of the rectum; deep, linear, or serpiginous ulcers of the colon; strictures; fistulas; or granulomatous inflammation. Only a small percentage of patients have granulomas on biopsy. The presence of ileitis in a patient with extensive colitis (ie, backwash ileitis) can also make determining the inflammatory bowel disease subtype challenging.
Arthropathy (both axial and peripheral) is a classic extraintestinal manifestation of Crohn disease, as are dermatologic manifestations (including pyoderma gangrenosum and erythema nodosum); ocular manifestations (including uveitis, scleritis, and episcleritis); and hepatobiliary disease (ie, primary sclerosing cholangitis). Less common extraintestinal complications of Crohn disease include:
• Thromboembolism (both venous and arterial)
• Metabolic bone diseases
• Osteonecrosis
• Cholelithiasis
• Nephrolithiasis.
Only 20%-30% of patients with Crohn disease will have a nonprogressive or indolent course. Clinical features that are associated with a high risk for progressive disease burden include young age at diagnosis, initial extensive bowel involvement, ileal or ileocolonic involvement, perianal or severe rectal disease, and a penetrating or stenosis disease phenotype.
According to the AGA's Clinical Care Pathway for Crohn Disease, clinical laboratory testing in a patient with symptoms of Crohn disease should include:
• Complete blood cell count (anemia and leukocytosis are the most common abnormalities seen)
• C-reactive protein (not a specific marker, but may correlate with disease activity in a subset of patients)
• Comprehensive metabolic panel
• Fecal calprotectin (may correlate with intestinal inflammation; can help distinguish inflammatory bowel disorders from irritable bowel syndrome)
• Erythrocyte sedimentation rate (may be elevated in some patients; not a specific marker)
Ileocolonoscopy with biopsies should be performed in the evaluation of patients with suspected Crohn disease, and disease distribution and severity should be documented at the time of diagnosis. Biopsies of uninvolved mucosa are recommended to identify the extent of histologic disease.
Consult the AGA guidelines for more extensive details on the workup for Crohn disease, including indications for additional imaging and phenotypic classification.
In recent years, outcomes in Crohn disease have improved, which is probably the result of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer. As noted above, Crohn disease includes multiple phenotypes, characterized by the Montreal Classification as stricturing, penetrating, inflammatory (nonstricturing and nonpenetrating), and perianal disease. Each of these phenotypes can present with a range in severity from mild to severe disease.
In general, therapeutic recommendations for patients are based on disease location, disease severity, disease-associated complications, and future disease prognosis and are individualized according to the symptomatic response and tolerance. Current therapeutic approaches should be considered a sequential continuum to treat acute disease or induce clinical remission, then maintain response or remission. Pharmacologic options include antidiarrheal agents, anti-inflammatory therapies (eg, sulfasalazine, mesalamine), corticosteroids (a short course for severe disease), biologic therapies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, ustekinumab), and occasionally immunosuppressive agents (tacrolimus, mycophenolate mofetil). In addition to their 2014 guidelines on the management of Crohn disease in adults, the AGA recently released guidelines specific to the medical management of moderate to severe luminal and fistulizing Crohn disease.
Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX
Bhupinder S. Anand, MD, has disclosed no relevant financial relationships
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Crohn disease.
Crohn disease is a chronic inflammatory bowel disease that is becoming increasingly prevalent worldwide. It is estimated to affect three to 20 persons per 100,000. When not effectively managed, Crohn disease is associated with substantial morbidity and significant impairments in lifestyle and daily activities during flares and remissions. It is characterized by a transmural granulomatous inflammation that can affect any part of the gastrointestinal tract — usually, the ileum, colon, or both.
Abdominal pain, diarrhea, weight loss, and fatigue are often prominent symptoms in patients with Crohn disease. Crampy or steady right lower quadrant or periumbilical pain may develop; the pain both precedes and may be partially relieved by defecation. Diarrhea is frequently intermittent and is not usually grossly bloody. Diffuse abdominal pain accompanied by mucus, blood, and pus in the stool may be reported by patients if the colon is involved. Involvement of the small intestine usually presents with evidence of malabsorption, including diarrhea, abdominal pain, weight loss, and anorexia, which may be subtle early in the disease course. Anorexia, nausea, and vomiting are more common in patients with gastroduodenal involvement, whereas debilitating perirectal pain, malodorous discharge from a fistula, and disfiguring scars from active disease or previous surgery may be present in patients with perianal disease. Patients may also present with symptoms suggestive of intestinal obstruction, or with anemia, recurrent fistulas, or fever.
As stated in guidelines from the American Gastroenterological Association (AGA), multiple streams of information, including history and physical examination, laboratory tests, endoscopy results, pathology findings, and radiographic tests, must be incorporated to arrive at a clinical diagnosis of Crohn disease. In most cases, the presence of chronic intestinal inflammation solidifies a diagnosis of Crohn disease. However, it can be challenging to differentiate Crohn disease from ulcerative colitis, particularly when the inflammation is confined to the colon. Bleeding is much more common in ulcerative colitis than in Crohn disease, whereas intestinal obstruction is common in Crohn disease and uncommon in ulcerative colitis. Fistulae and perianal disease are common in Crohn disease but are absent or rare in ulcerative colitis. Moreover, weight loss is typical in patients with Crohn disease but is uncommon in ulcerative colitis.
Additional diagnostic clues for Crohn disease include discontinuous involvement with skip areas; sparing of the rectum; deep, linear, or serpiginous ulcers of the colon; strictures; fistulas; or granulomatous inflammation. Only a small percentage of patients have granulomas on biopsy. The presence of ileitis in a patient with extensive colitis (ie, backwash ileitis) can also make determining the inflammatory bowel disease subtype challenging.
Arthropathy (both axial and peripheral) is a classic extraintestinal manifestation of Crohn disease, as are dermatologic manifestations (including pyoderma gangrenosum and erythema nodosum); ocular manifestations (including uveitis, scleritis, and episcleritis); and hepatobiliary disease (ie, primary sclerosing cholangitis). Less common extraintestinal complications of Crohn disease include:
• Thromboembolism (both venous and arterial)
• Metabolic bone diseases
• Osteonecrosis
• Cholelithiasis
• Nephrolithiasis.
Only 20%-30% of patients with Crohn disease will have a nonprogressive or indolent course. Clinical features that are associated with a high risk for progressive disease burden include young age at diagnosis, initial extensive bowel involvement, ileal or ileocolonic involvement, perianal or severe rectal disease, and a penetrating or stenosis disease phenotype.
According to the AGA's Clinical Care Pathway for Crohn Disease, clinical laboratory testing in a patient with symptoms of Crohn disease should include:
• Complete blood cell count (anemia and leukocytosis are the most common abnormalities seen)
• C-reactive protein (not a specific marker, but may correlate with disease activity in a subset of patients)
• Comprehensive metabolic panel
• Fecal calprotectin (may correlate with intestinal inflammation; can help distinguish inflammatory bowel disorders from irritable bowel syndrome)
• Erythrocyte sedimentation rate (may be elevated in some patients; not a specific marker)
Ileocolonoscopy with biopsies should be performed in the evaluation of patients with suspected Crohn disease, and disease distribution and severity should be documented at the time of diagnosis. Biopsies of uninvolved mucosa are recommended to identify the extent of histologic disease.
Consult the AGA guidelines for more extensive details on the workup for Crohn disease, including indications for additional imaging and phenotypic classification.
In recent years, outcomes in Crohn disease have improved, which is probably the result of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer. As noted above, Crohn disease includes multiple phenotypes, characterized by the Montreal Classification as stricturing, penetrating, inflammatory (nonstricturing and nonpenetrating), and perianal disease. Each of these phenotypes can present with a range in severity from mild to severe disease.
In general, therapeutic recommendations for patients are based on disease location, disease severity, disease-associated complications, and future disease prognosis and are individualized according to the symptomatic response and tolerance. Current therapeutic approaches should be considered a sequential continuum to treat acute disease or induce clinical remission, then maintain response or remission. Pharmacologic options include antidiarrheal agents, anti-inflammatory therapies (eg, sulfasalazine, mesalamine), corticosteroids (a short course for severe disease), biologic therapies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, ustekinumab), and occasionally immunosuppressive agents (tacrolimus, mycophenolate mofetil). In addition to their 2014 guidelines on the management of Crohn disease in adults, the AGA recently released guidelines specific to the medical management of moderate to severe luminal and fistulizing Crohn disease.
Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX
Bhupinder S. Anand, MD, has disclosed no relevant financial relationships
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Crohn disease.
Crohn disease is a chronic inflammatory bowel disease that is becoming increasingly prevalent worldwide. It is estimated to affect three to 20 persons per 100,000. When not effectively managed, Crohn disease is associated with substantial morbidity and significant impairments in lifestyle and daily activities during flares and remissions. It is characterized by a transmural granulomatous inflammation that can affect any part of the gastrointestinal tract — usually, the ileum, colon, or both.
Abdominal pain, diarrhea, weight loss, and fatigue are often prominent symptoms in patients with Crohn disease. Crampy or steady right lower quadrant or periumbilical pain may develop; the pain both precedes and may be partially relieved by defecation. Diarrhea is frequently intermittent and is not usually grossly bloody. Diffuse abdominal pain accompanied by mucus, blood, and pus in the stool may be reported by patients if the colon is involved. Involvement of the small intestine usually presents with evidence of malabsorption, including diarrhea, abdominal pain, weight loss, and anorexia, which may be subtle early in the disease course. Anorexia, nausea, and vomiting are more common in patients with gastroduodenal involvement, whereas debilitating perirectal pain, malodorous discharge from a fistula, and disfiguring scars from active disease or previous surgery may be present in patients with perianal disease. Patients may also present with symptoms suggestive of intestinal obstruction, or with anemia, recurrent fistulas, or fever.
As stated in guidelines from the American Gastroenterological Association (AGA), multiple streams of information, including history and physical examination, laboratory tests, endoscopy results, pathology findings, and radiographic tests, must be incorporated to arrive at a clinical diagnosis of Crohn disease. In most cases, the presence of chronic intestinal inflammation solidifies a diagnosis of Crohn disease. However, it can be challenging to differentiate Crohn disease from ulcerative colitis, particularly when the inflammation is confined to the colon. Bleeding is much more common in ulcerative colitis than in Crohn disease, whereas intestinal obstruction is common in Crohn disease and uncommon in ulcerative colitis. Fistulae and perianal disease are common in Crohn disease but are absent or rare in ulcerative colitis. Moreover, weight loss is typical in patients with Crohn disease but is uncommon in ulcerative colitis.
Additional diagnostic clues for Crohn disease include discontinuous involvement with skip areas; sparing of the rectum; deep, linear, or serpiginous ulcers of the colon; strictures; fistulas; or granulomatous inflammation. Only a small percentage of patients have granulomas on biopsy. The presence of ileitis in a patient with extensive colitis (ie, backwash ileitis) can also make determining the inflammatory bowel disease subtype challenging.
Arthropathy (both axial and peripheral) is a classic extraintestinal manifestation of Crohn disease, as are dermatologic manifestations (including pyoderma gangrenosum and erythema nodosum); ocular manifestations (including uveitis, scleritis, and episcleritis); and hepatobiliary disease (ie, primary sclerosing cholangitis). Less common extraintestinal complications of Crohn disease include:
• Thromboembolism (both venous and arterial)
• Metabolic bone diseases
• Osteonecrosis
• Cholelithiasis
• Nephrolithiasis.
Only 20%-30% of patients with Crohn disease will have a nonprogressive or indolent course. Clinical features that are associated with a high risk for progressive disease burden include young age at diagnosis, initial extensive bowel involvement, ileal or ileocolonic involvement, perianal or severe rectal disease, and a penetrating or stenosis disease phenotype.
According to the AGA's Clinical Care Pathway for Crohn Disease, clinical laboratory testing in a patient with symptoms of Crohn disease should include:
• Complete blood cell count (anemia and leukocytosis are the most common abnormalities seen)
• C-reactive protein (not a specific marker, but may correlate with disease activity in a subset of patients)
• Comprehensive metabolic panel
• Fecal calprotectin (may correlate with intestinal inflammation; can help distinguish inflammatory bowel disorders from irritable bowel syndrome)
• Erythrocyte sedimentation rate (may be elevated in some patients; not a specific marker)
Ileocolonoscopy with biopsies should be performed in the evaluation of patients with suspected Crohn disease, and disease distribution and severity should be documented at the time of diagnosis. Biopsies of uninvolved mucosa are recommended to identify the extent of histologic disease.
Consult the AGA guidelines for more extensive details on the workup for Crohn disease, including indications for additional imaging and phenotypic classification.
In recent years, outcomes in Crohn disease have improved, which is probably the result of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer. As noted above, Crohn disease includes multiple phenotypes, characterized by the Montreal Classification as stricturing, penetrating, inflammatory (nonstricturing and nonpenetrating), and perianal disease. Each of these phenotypes can present with a range in severity from mild to severe disease.
In general, therapeutic recommendations for patients are based on disease location, disease severity, disease-associated complications, and future disease prognosis and are individualized according to the symptomatic response and tolerance. Current therapeutic approaches should be considered a sequential continuum to treat acute disease or induce clinical remission, then maintain response or remission. Pharmacologic options include antidiarrheal agents, anti-inflammatory therapies (eg, sulfasalazine, mesalamine), corticosteroids (a short course for severe disease), biologic therapies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, ustekinumab), and occasionally immunosuppressive agents (tacrolimus, mycophenolate mofetil). In addition to their 2014 guidelines on the management of Crohn disease in adults, the AGA recently released guidelines specific to the medical management of moderate to severe luminal and fistulizing Crohn disease.
Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX
Bhupinder S. Anand, MD, has disclosed no relevant financial relationships
An 18-year-old man presents with increasing fatigue, prolonged diarrhea, and intermittent abdominal pain. The patient is nearly 6 months into his freshman year at the local university, where he resides. He states that his symptoms began approximately 12 weeks earlier. He describes passing an average of eight to 10 watery stools per day, including nocturnal diarrhea, with no noticeable blood or mucus and no rectal urgency. The patient has lost 13 lb since his symptoms began, which he attributes to the diarrhea and to adjusting to dormitory life and institutional meals. He also notes a slight decrease in appetite. His symptoms typically begin within an hour of awakening, after he has had his morning meal. The patient admits to smoking and occasional use of cannabis. He is not taking any medications or over-the-counter products.
Physical examination revealed a blood pressure of 120/70 mm Hg, pulse of 74 beats/min, and temperature of 98.4 °F (37 °C). His weight is 139 lb and his height is 5 ft 10 in. Diffuse abdominal tenderness is present; inspection of the perianal region and rectal examination are normal. There is a positive first-degree family history of type 2 diabetes, hypertension, and inflammatory bowel disease. His paternal grandmother died of colon cancer at 77 years of age and his maternal grandfather died of ischemic stroke at 82 years of age.
Laboratory findings are all within the normal range and stool testing excludes infectious etiologies. Subsequent endoscopic findings include multiple colonic ulcers longitudinally arranged with a cobblestone appearance.
New study shows natural immunity to COVID has enduring strength
It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.
“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals,
This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.
One key caveat: This research does not include people from the later part of the pandemic.
This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”
The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.
An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.
“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
A focus on earlier strains
Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.
Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.
The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.
The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.
To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.
They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.
These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.
Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
Protection linked to obesity
Another finding that ran against the scientific grain was the data about obesity.
There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m2.
This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.
“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.
“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
Before the boosters
Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.
“Again, not the current situation.”
“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.
A version of this article first appeared on Medscape.com.
It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.
“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals,
This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.
One key caveat: This research does not include people from the later part of the pandemic.
This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”
The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.
An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.
“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
A focus on earlier strains
Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.
Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.
The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.
The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.
To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.
They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.
These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.
Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
Protection linked to obesity
Another finding that ran against the scientific grain was the data about obesity.
There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m2.
This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.
“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.
“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
Before the boosters
Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.
“Again, not the current situation.”
“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.
A version of this article first appeared on Medscape.com.
It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.
“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals,
This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.
One key caveat: This research does not include people from the later part of the pandemic.
This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”
The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.
An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.
“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
A focus on earlier strains
Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.
Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.
The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.
The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.
To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.
They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.
These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.
Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
Protection linked to obesity
Another finding that ran against the scientific grain was the data about obesity.
There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m2.
This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.
“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.
“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
Before the boosters
Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.
“Again, not the current situation.”
“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.
A version of this article first appeared on Medscape.com.
Too much marijuana can make you unpleasantly, dangerously sick
At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.
For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.
Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.
Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.
“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.
To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.
“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”
Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.
“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”
Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.
The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.
Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.
“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.
She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”
Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.
Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.
The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.
“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
Genetic risk factors?
One mystery is why some regular marijuana users get this syndrome while others do not.
“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”
Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.
They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.
The results are not final but could help guide future research, Dr. Russo said.
“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.
Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.
“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
Battling disbelief
Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.
“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.
“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.
Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.
Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.
“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.
People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.
Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.
“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.
Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
What recent research reveals
Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.
So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.
Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.
An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.
Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.
“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.
The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
Cannabis conspiracy theories
“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.
Some “myth busting” is in order, he said.
For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
The state of recreational and medical marijuana
Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.
One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.
“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.
In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.
Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.
“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.
Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”
“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.
“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”
A version of this article first appeared on Medscape.com.
At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.
For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.
Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.
Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.
“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.
To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.
“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”
Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.
“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”
Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.
The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.
Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.
“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.
She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”
Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.
Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.
The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.
“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
Genetic risk factors?
One mystery is why some regular marijuana users get this syndrome while others do not.
“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”
Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.
They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.
The results are not final but could help guide future research, Dr. Russo said.
“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.
Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.
“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
Battling disbelief
Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.
“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.
“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.
Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.
Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.
“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.
People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.
Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.
“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.
Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
What recent research reveals
Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.
So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.
Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.
An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.
Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.
“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.
The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
Cannabis conspiracy theories
“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.
Some “myth busting” is in order, he said.
For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
The state of recreational and medical marijuana
Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.
One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.
“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.
In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.
Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.
“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.
Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”
“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.
“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”
A version of this article first appeared on Medscape.com.
At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.
For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.
Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.
Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.
“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.
To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.
“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”
Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.
“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”
Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.
The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.
Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.
“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.
She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”
Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.
Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.
The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.
“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
Genetic risk factors?
One mystery is why some regular marijuana users get this syndrome while others do not.
“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”
Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.
They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.
The results are not final but could help guide future research, Dr. Russo said.
“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.
Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.
“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
Battling disbelief
Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.
“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.
“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.
Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.
Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.
“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.
People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.
Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.
“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.
Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
What recent research reveals
Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.
So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.
Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.
An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.
Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.
“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.
The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
Cannabis conspiracy theories
“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.
Some “myth busting” is in order, he said.
For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
The state of recreational and medical marijuana
Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.
One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.
“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.
In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.
Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.
“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.
Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”
“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.
“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”
A version of this article first appeared on Medscape.com.
To a perfect day
Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.
If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.
What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.
Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.
Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.
Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.
If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.
What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.
Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.
Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.
Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.
If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.
What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.
Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.
Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.
Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
Crohn Disease: Presentation and Diagnosis
A third person living with HIV has been cured by transplant
In a first,Berlin Patient and the London Patient – to be cured through a transplant.
If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.
The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.
But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.
The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.
In this case, the physicians treating her used both.
“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.
Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.
One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.
This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.
“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”
The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.
“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.
“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.
And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”
Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.
But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.
For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.
“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”
Now the challenge is to move from a single case to making cure available to other people living with HIV.
The case also got cure researchers thinking.
Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.
Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”
For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.
“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”
Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.
“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”
When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.
“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”
The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a first,Berlin Patient and the London Patient – to be cured through a transplant.
If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.
The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.
But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.
The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.
In this case, the physicians treating her used both.
“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.
Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.
One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.
This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.
“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”
The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.
“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.
“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.
And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”
Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.
But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.
For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.
“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”
Now the challenge is to move from a single case to making cure available to other people living with HIV.
The case also got cure researchers thinking.
Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.
Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”
For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.
“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”
Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.
“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”
When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.
“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”
The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a first,Berlin Patient and the London Patient – to be cured through a transplant.
If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.
The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.
But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.
The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.
In this case, the physicians treating her used both.
“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.
Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.
One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.
This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.
“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”
The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.
“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.
“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.
And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”
Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.
But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.
For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.
“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”
Now the challenge is to move from a single case to making cure available to other people living with HIV.
The case also got cure researchers thinking.
Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.
Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”
For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.
“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”
Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.
“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”
When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.
“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”
The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CROI 2022
Eighteen-year study shows inconsistencies in treating, classifying JIA
“Children are not little adults” is a common refrain in pediatric medicine, but when it comes to a condition like juvenile idiopathic arthritis (JIA), rheumatologists might be better off treating pediatric and adult rheumatic disease more similarly.
A recent study published in Arthritis Care & Research followed children diagnosed with JIA for 18 years. Although not the first long-term study to examine children with JIA, it is unique in that it took place “during a time where biologic DMARDs [disease-modifying antirheumatic drugs] were emerging as a fundamental therapy in the management of children with JIA,” said Dawn M. Wahezi, MD, chief of the division of pediatric rheumatology at the Children’s Hospital at Montefiore in New York, who was not involved with the study.
Additionally, the study highlights the International League of Associations for Rheumatology (ILAR) consensus-based classification criteria as an imperfect method to categorize patients with JIA.
Mia Glerup, MD, PhD, of the department of pediatrics at Aarhus (Denmark) University Hospital and colleagues prospectively analyzed 373 patients from Denmark, Norway, Sweden, and Finland with new-onset JIA between 1997 and 2000 and evaluated them at baseline, 8 years, and 18 years. At each visit, the researchers collected data on demographics, disease activity, ILAR category, treatment, and blood samples.
Patients in the cohort were mostly girls (66.7%) with a median age of 5.9 years at onset. Approximately one-third (34.8%) of patients were antinuclear antibody (ANA) positive and 21.6% were HLA-B27 positive. The most common JIA categories at baseline were persistent oligoarthritis (53.9%), polyarticular rheumatoid factor (RF) negative (21.1%), and undifferentiated arthritis (10.2%).
Dr. Glerup and colleagues found that the proportion of patients not receiving DMARDs declined from 73.2% at baseline to 59.7% at 8 years, and then rose again to 70% at 18 years (risk ratio, 1.3; P = .003). The group of 103 patients who used conventional DMARDs (cDMARDs) either as monotherapy or in combination with a biologic DMARD (bDMARD) at 8 years dwindled to 44 (42.7%) at 18 years (RR, 0.4; P < .001), whereas 32 of 52 patients (61.5%) using bDMARDs at 8 years were still taking them at 18 years (RR, 0.6; P = .02). Across the whole study, 14.7% of patients never received any JIA treatment, and 33 of 85 patients (38.8%) on continuous DMARDs developed uveitis during the study period.
Overall, 62.7% of patients received DMARDs at least once, including 89.7% with polyarticular RF negative, 77.3% with oligoarticular extended, 76.9% with systemic, 75.7% with juvenile enthesitis-related arthritis (ERA), 66.7% with polyarticular RF-positive, 65.2% with juvenile psoriatic arthritis (JPsA), 58.9% with undifferentiated JIA, and 27.6% of patients with persistent oligoarticular disease.
The median number of active joints dropped from 3 (range, 1-30) at baseline to 0 at 8 years (range, 0-13), whereas the median cumulative number of affected joints rose from 3 at baseline (range, 1-30) to 6 at 8 years (range, 1-41). At last follow-up, the median number of active joints was 0 (range, 0-5) and median cumulative number of affected joints was 7 (range, 1-47). The percentage of patients in remission barely changed from 52% at 8 years to 51% at 18.
Some patients also changed ILAR categories during the study period, with 7% shifting between baseline and 8 years, and 11% shifting between 8-year and 18-year follow-up. Compared with baseline, by the 18-year follow-up time point there was a significant decrease in the number of patients categorized as oligoarticular (230 vs. 197 patients; P = .02), a significant increase in patients in the psoriatic ILAR category (8 vs. 28 patients; P < .001), and a nonsignificant increase in the number of patients in the undifferentiated category (45 vs. 63 patients; P = .06).
“Almost half of the changes in the distribution between the ILAR categories were caused by updated information on heredity in a first-degree relative obtained at the follow-up visits,” Dr. Glerup and colleagues write.
The results of the long-term study show that patients are “likely to remain in remission – with the converse also evident, as patients still with evidence of disease activity at 8 years after disease onset were more likely to have refractory disease,” Dr. Wahezi said.
Commenting on the study’s findings, Lisa F. Imundo, MD, director of adolescent rheumatology at Columbia University Medical Center in New York, said they are “great news to be able to give parents of young kids with arthritis.” However, she questioned whether the results are generalizable to populations of patients “who are in the worst prognostic group.”
For example, a substantial proportion of patients were classified under the oligoarticular category. “That’s already a group that we know from experience tends to have a better outcome than some of the other groups of JIA,” she said.
“That kind of weaves its way through the whole study, because then they show a lot of patients have come off their medication. Patients who had more severe disease in more joints would be less likely, I think, to just stop their medication and stop going to doctors,” Dr. Imundo explained.
Although the study is valuable for its long-term follow-up, there is also a question of generalizability across a more diverse ethnic and racial group. The authors do not elaborate on the racial breakdown of their patients, Dr. Imundo said, “so we’re going to have to assume that the vast majority are going to [have] Caucasian Nordic ethnic background, and that goes along with them having this high percentage of HLA-B27 positivity, which is a gene that’s more prevalent in northern European populations.”
Jonathan Hausmann, MD, a pediatric and adult rheumatologist at Boston Children’s Hospital, Boston,, told this news organization that he believes the overall conclusions from the study – that JIA persists over time and that ILAR classification is a somewhat imprecise measure of assessing JIA types in children – would be generalizable to other groups.
However, long-term registries evaluating JIA in more diverse populations, such as the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, could confirm these results, said Dr. Hausmann, who is a registry informatics associate with CARRA and was not associated with the research.
Long-term management of JIA
In an accompanying editorial, Jaime Guzman, MD, MSc, and Ross E. Petty, MD, PhD, of British Columbia Children’s Hospital and the University of British Columbia, Vancouver, said a rheumatologist’s interpretation of the study would be tied to what they learned about children with arthritis in medical school. They would see the glass as “half full” if children who achieved remission stayed in remission if they learned that a child might end up outgrowing JIA but potentially develop lifelong disability, whereas others may focus on the outcome of approximately half of patients not achieving remission.
“When I was going through medical school, I remember learning that JIA is a disease of children, and typically, they outgrow it as they become adults,” Dr. Hausmann said. “I think this study and many other studies have shown that that’s actually not the case – that, in fact, it may be a majority of kids continue having active disease even through adulthood.”
If a rheumatologist knows JIA is likely to continue into adulthood, “that’s huge,” Dr. Hausmann said. “That means when we first diagnose patients with JIA as kids, we need to set expectations with the families that this may not just go away; this may be something that could be more lifelong.”
Education on the part of the patient, their parents, and their clinician on the expected trajectory of the disease is critical so that children can continue their own care as they transition to adulthood, Dr. Hausmann explained. “The earlier the kids develop the skills to discuss their medicines, their side effects, the better they’ll be able to transition to adult medicine,” he said.
For the patients who go into remission and stay in remission, the message is also important. “To have the reassurance that a lot of those kids won’t be having active joint symptoms or need to be on medication, that’s a huge positive message that can get out there, so I think that’s great,” Dr. Imundo said.
Time to move on from ILAR classification?
Another big takeaway from the study was how patients’ ILAR classification changed across the 18-year follow-up. First proposed in 1995, the JIA ILAR classification has been revised several times for clarification purposes. In its current form, the ILAR classification considers a patient’s history when categorizing JIA types but also includes factors such as immediate family history. This system of assessing JIA has been criticized and there are initiatives to create a new JIA classification system to replace it.
“The ILAR criteria were designed to classify patients 6 months after disease onset in an attempt to find some commonality in clinical phenotypes, prognosis, and suggested management,” Dr. Wahezi said. “While there continues to be debate as to whether we can improve our classification of JIA patients, it is not surprising that phenotypes may evolve over time as new clinical features develop. As pediatric rheumatologists, we are well accustomed to having to modify management plans as children manifest with new clinical features over time.”
Although the percentage of patients who switched ILAR classifications over the study period was “much higher” than she would have thought, Dr. Imundo said it was the reasons provided in the study that seemed odd to her. “The classification scheme relies on your family history, like someone else in your family now has psoriasis, so your arthritis classification changes,” she explained.
“We want to head toward a much more unified classification scheme, a simpler one. We now understand that some of the diseases that we see in pediatrics are really the equivalent or same disease in adults,” she said.
“Most of the pediatric categories of JIA have distinct adult correlates,” Dr. Hausmann agreed. RF-positive polyarthritis in children and rheumatoid arthritis in adults are correlated, as are systemic JIA and adult-onset Still’s disease, he explained. “That has been borne out also by genetic susceptibility studies that the genetic predispositions to systemic arthritis in children is the same as the genetic predisposition to adult-onset Still’s disease in adults. By and large, there are a lot of similarities between the two.
“I think we need to incorporate some of that knowledge in better classifying kids with JIA so that we can find the best treatments and the best outcomes, and we can provide information to families about the expected course of the disease over time so that can inform our discussions.”
Some pediatric rheumatologists accept the classification system is flawed, but not all concur with the degree to which these problems impact patient care. “While the ILAR classification criteria may be subject to criticism, it does provide general context and prognostic implications for patients and families,” Dr. Wahezi said.
“The medicines certainly are very similar across the JIA categories, so the implications are not as broad” when classification changes,” Dr. Hausmann said. “But it certainly shows that there are things that we still don’t know. I think classification is actually pretty important because it might give you a sense of how persistent the disease will be.”
Dr. Imundo said the ILAR classification’s “time is limited,” and rheumatologists may soon need to adopt a new way of classifying children with rheumatic disease – “a more data-driven, genetics-driven scheme.”
“These categories are so imperfect, and the patients are changing. I feel like that says to me, let’s find something that’s more predictive that really helps us a little better than what we have now,” she said.
The study had no specific funding. The authors of the study and the editorial have disclosed no relevant financial relationships. Dr. Hausmann reports receiving salary support from CARRA. Dr. Imundo and Dr. Wahezi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“Children are not little adults” is a common refrain in pediatric medicine, but when it comes to a condition like juvenile idiopathic arthritis (JIA), rheumatologists might be better off treating pediatric and adult rheumatic disease more similarly.
A recent study published in Arthritis Care & Research followed children diagnosed with JIA for 18 years. Although not the first long-term study to examine children with JIA, it is unique in that it took place “during a time where biologic DMARDs [disease-modifying antirheumatic drugs] were emerging as a fundamental therapy in the management of children with JIA,” said Dawn M. Wahezi, MD, chief of the division of pediatric rheumatology at the Children’s Hospital at Montefiore in New York, who was not involved with the study.
Additionally, the study highlights the International League of Associations for Rheumatology (ILAR) consensus-based classification criteria as an imperfect method to categorize patients with JIA.
Mia Glerup, MD, PhD, of the department of pediatrics at Aarhus (Denmark) University Hospital and colleagues prospectively analyzed 373 patients from Denmark, Norway, Sweden, and Finland with new-onset JIA between 1997 and 2000 and evaluated them at baseline, 8 years, and 18 years. At each visit, the researchers collected data on demographics, disease activity, ILAR category, treatment, and blood samples.
Patients in the cohort were mostly girls (66.7%) with a median age of 5.9 years at onset. Approximately one-third (34.8%) of patients were antinuclear antibody (ANA) positive and 21.6% were HLA-B27 positive. The most common JIA categories at baseline were persistent oligoarthritis (53.9%), polyarticular rheumatoid factor (RF) negative (21.1%), and undifferentiated arthritis (10.2%).
Dr. Glerup and colleagues found that the proportion of patients not receiving DMARDs declined from 73.2% at baseline to 59.7% at 8 years, and then rose again to 70% at 18 years (risk ratio, 1.3; P = .003). The group of 103 patients who used conventional DMARDs (cDMARDs) either as monotherapy or in combination with a biologic DMARD (bDMARD) at 8 years dwindled to 44 (42.7%) at 18 years (RR, 0.4; P < .001), whereas 32 of 52 patients (61.5%) using bDMARDs at 8 years were still taking them at 18 years (RR, 0.6; P = .02). Across the whole study, 14.7% of patients never received any JIA treatment, and 33 of 85 patients (38.8%) on continuous DMARDs developed uveitis during the study period.
Overall, 62.7% of patients received DMARDs at least once, including 89.7% with polyarticular RF negative, 77.3% with oligoarticular extended, 76.9% with systemic, 75.7% with juvenile enthesitis-related arthritis (ERA), 66.7% with polyarticular RF-positive, 65.2% with juvenile psoriatic arthritis (JPsA), 58.9% with undifferentiated JIA, and 27.6% of patients with persistent oligoarticular disease.
The median number of active joints dropped from 3 (range, 1-30) at baseline to 0 at 8 years (range, 0-13), whereas the median cumulative number of affected joints rose from 3 at baseline (range, 1-30) to 6 at 8 years (range, 1-41). At last follow-up, the median number of active joints was 0 (range, 0-5) and median cumulative number of affected joints was 7 (range, 1-47). The percentage of patients in remission barely changed from 52% at 8 years to 51% at 18.
Some patients also changed ILAR categories during the study period, with 7% shifting between baseline and 8 years, and 11% shifting between 8-year and 18-year follow-up. Compared with baseline, by the 18-year follow-up time point there was a significant decrease in the number of patients categorized as oligoarticular (230 vs. 197 patients; P = .02), a significant increase in patients in the psoriatic ILAR category (8 vs. 28 patients; P < .001), and a nonsignificant increase in the number of patients in the undifferentiated category (45 vs. 63 patients; P = .06).
“Almost half of the changes in the distribution between the ILAR categories were caused by updated information on heredity in a first-degree relative obtained at the follow-up visits,” Dr. Glerup and colleagues write.
The results of the long-term study show that patients are “likely to remain in remission – with the converse also evident, as patients still with evidence of disease activity at 8 years after disease onset were more likely to have refractory disease,” Dr. Wahezi said.
Commenting on the study’s findings, Lisa F. Imundo, MD, director of adolescent rheumatology at Columbia University Medical Center in New York, said they are “great news to be able to give parents of young kids with arthritis.” However, she questioned whether the results are generalizable to populations of patients “who are in the worst prognostic group.”
For example, a substantial proportion of patients were classified under the oligoarticular category. “That’s already a group that we know from experience tends to have a better outcome than some of the other groups of JIA,” she said.
“That kind of weaves its way through the whole study, because then they show a lot of patients have come off their medication. Patients who had more severe disease in more joints would be less likely, I think, to just stop their medication and stop going to doctors,” Dr. Imundo explained.
Although the study is valuable for its long-term follow-up, there is also a question of generalizability across a more diverse ethnic and racial group. The authors do not elaborate on the racial breakdown of their patients, Dr. Imundo said, “so we’re going to have to assume that the vast majority are going to [have] Caucasian Nordic ethnic background, and that goes along with them having this high percentage of HLA-B27 positivity, which is a gene that’s more prevalent in northern European populations.”
Jonathan Hausmann, MD, a pediatric and adult rheumatologist at Boston Children’s Hospital, Boston,, told this news organization that he believes the overall conclusions from the study – that JIA persists over time and that ILAR classification is a somewhat imprecise measure of assessing JIA types in children – would be generalizable to other groups.
However, long-term registries evaluating JIA in more diverse populations, such as the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, could confirm these results, said Dr. Hausmann, who is a registry informatics associate with CARRA and was not associated with the research.
Long-term management of JIA
In an accompanying editorial, Jaime Guzman, MD, MSc, and Ross E. Petty, MD, PhD, of British Columbia Children’s Hospital and the University of British Columbia, Vancouver, said a rheumatologist’s interpretation of the study would be tied to what they learned about children with arthritis in medical school. They would see the glass as “half full” if children who achieved remission stayed in remission if they learned that a child might end up outgrowing JIA but potentially develop lifelong disability, whereas others may focus on the outcome of approximately half of patients not achieving remission.
“When I was going through medical school, I remember learning that JIA is a disease of children, and typically, they outgrow it as they become adults,” Dr. Hausmann said. “I think this study and many other studies have shown that that’s actually not the case – that, in fact, it may be a majority of kids continue having active disease even through adulthood.”
If a rheumatologist knows JIA is likely to continue into adulthood, “that’s huge,” Dr. Hausmann said. “That means when we first diagnose patients with JIA as kids, we need to set expectations with the families that this may not just go away; this may be something that could be more lifelong.”
Education on the part of the patient, their parents, and their clinician on the expected trajectory of the disease is critical so that children can continue their own care as they transition to adulthood, Dr. Hausmann explained. “The earlier the kids develop the skills to discuss their medicines, their side effects, the better they’ll be able to transition to adult medicine,” he said.
For the patients who go into remission and stay in remission, the message is also important. “To have the reassurance that a lot of those kids won’t be having active joint symptoms or need to be on medication, that’s a huge positive message that can get out there, so I think that’s great,” Dr. Imundo said.
Time to move on from ILAR classification?
Another big takeaway from the study was how patients’ ILAR classification changed across the 18-year follow-up. First proposed in 1995, the JIA ILAR classification has been revised several times for clarification purposes. In its current form, the ILAR classification considers a patient’s history when categorizing JIA types but also includes factors such as immediate family history. This system of assessing JIA has been criticized and there are initiatives to create a new JIA classification system to replace it.
“The ILAR criteria were designed to classify patients 6 months after disease onset in an attempt to find some commonality in clinical phenotypes, prognosis, and suggested management,” Dr. Wahezi said. “While there continues to be debate as to whether we can improve our classification of JIA patients, it is not surprising that phenotypes may evolve over time as new clinical features develop. As pediatric rheumatologists, we are well accustomed to having to modify management plans as children manifest with new clinical features over time.”
Although the percentage of patients who switched ILAR classifications over the study period was “much higher” than she would have thought, Dr. Imundo said it was the reasons provided in the study that seemed odd to her. “The classification scheme relies on your family history, like someone else in your family now has psoriasis, so your arthritis classification changes,” she explained.
“We want to head toward a much more unified classification scheme, a simpler one. We now understand that some of the diseases that we see in pediatrics are really the equivalent or same disease in adults,” she said.
“Most of the pediatric categories of JIA have distinct adult correlates,” Dr. Hausmann agreed. RF-positive polyarthritis in children and rheumatoid arthritis in adults are correlated, as are systemic JIA and adult-onset Still’s disease, he explained. “That has been borne out also by genetic susceptibility studies that the genetic predispositions to systemic arthritis in children is the same as the genetic predisposition to adult-onset Still’s disease in adults. By and large, there are a lot of similarities between the two.
“I think we need to incorporate some of that knowledge in better classifying kids with JIA so that we can find the best treatments and the best outcomes, and we can provide information to families about the expected course of the disease over time so that can inform our discussions.”
Some pediatric rheumatologists accept the classification system is flawed, but not all concur with the degree to which these problems impact patient care. “While the ILAR classification criteria may be subject to criticism, it does provide general context and prognostic implications for patients and families,” Dr. Wahezi said.
“The medicines certainly are very similar across the JIA categories, so the implications are not as broad” when classification changes,” Dr. Hausmann said. “But it certainly shows that there are things that we still don’t know. I think classification is actually pretty important because it might give you a sense of how persistent the disease will be.”
Dr. Imundo said the ILAR classification’s “time is limited,” and rheumatologists may soon need to adopt a new way of classifying children with rheumatic disease – “a more data-driven, genetics-driven scheme.”
“These categories are so imperfect, and the patients are changing. I feel like that says to me, let’s find something that’s more predictive that really helps us a little better than what we have now,” she said.
The study had no specific funding. The authors of the study and the editorial have disclosed no relevant financial relationships. Dr. Hausmann reports receiving salary support from CARRA. Dr. Imundo and Dr. Wahezi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“Children are not little adults” is a common refrain in pediatric medicine, but when it comes to a condition like juvenile idiopathic arthritis (JIA), rheumatologists might be better off treating pediatric and adult rheumatic disease more similarly.
A recent study published in Arthritis Care & Research followed children diagnosed with JIA for 18 years. Although not the first long-term study to examine children with JIA, it is unique in that it took place “during a time where biologic DMARDs [disease-modifying antirheumatic drugs] were emerging as a fundamental therapy in the management of children with JIA,” said Dawn M. Wahezi, MD, chief of the division of pediatric rheumatology at the Children’s Hospital at Montefiore in New York, who was not involved with the study.
Additionally, the study highlights the International League of Associations for Rheumatology (ILAR) consensus-based classification criteria as an imperfect method to categorize patients with JIA.
Mia Glerup, MD, PhD, of the department of pediatrics at Aarhus (Denmark) University Hospital and colleagues prospectively analyzed 373 patients from Denmark, Norway, Sweden, and Finland with new-onset JIA between 1997 and 2000 and evaluated them at baseline, 8 years, and 18 years. At each visit, the researchers collected data on demographics, disease activity, ILAR category, treatment, and blood samples.
Patients in the cohort were mostly girls (66.7%) with a median age of 5.9 years at onset. Approximately one-third (34.8%) of patients were antinuclear antibody (ANA) positive and 21.6% were HLA-B27 positive. The most common JIA categories at baseline were persistent oligoarthritis (53.9%), polyarticular rheumatoid factor (RF) negative (21.1%), and undifferentiated arthritis (10.2%).
Dr. Glerup and colleagues found that the proportion of patients not receiving DMARDs declined from 73.2% at baseline to 59.7% at 8 years, and then rose again to 70% at 18 years (risk ratio, 1.3; P = .003). The group of 103 patients who used conventional DMARDs (cDMARDs) either as monotherapy or in combination with a biologic DMARD (bDMARD) at 8 years dwindled to 44 (42.7%) at 18 years (RR, 0.4; P < .001), whereas 32 of 52 patients (61.5%) using bDMARDs at 8 years were still taking them at 18 years (RR, 0.6; P = .02). Across the whole study, 14.7% of patients never received any JIA treatment, and 33 of 85 patients (38.8%) on continuous DMARDs developed uveitis during the study period.
Overall, 62.7% of patients received DMARDs at least once, including 89.7% with polyarticular RF negative, 77.3% with oligoarticular extended, 76.9% with systemic, 75.7% with juvenile enthesitis-related arthritis (ERA), 66.7% with polyarticular RF-positive, 65.2% with juvenile psoriatic arthritis (JPsA), 58.9% with undifferentiated JIA, and 27.6% of patients with persistent oligoarticular disease.
The median number of active joints dropped from 3 (range, 1-30) at baseline to 0 at 8 years (range, 0-13), whereas the median cumulative number of affected joints rose from 3 at baseline (range, 1-30) to 6 at 8 years (range, 1-41). At last follow-up, the median number of active joints was 0 (range, 0-5) and median cumulative number of affected joints was 7 (range, 1-47). The percentage of patients in remission barely changed from 52% at 8 years to 51% at 18.
Some patients also changed ILAR categories during the study period, with 7% shifting between baseline and 8 years, and 11% shifting between 8-year and 18-year follow-up. Compared with baseline, by the 18-year follow-up time point there was a significant decrease in the number of patients categorized as oligoarticular (230 vs. 197 patients; P = .02), a significant increase in patients in the psoriatic ILAR category (8 vs. 28 patients; P < .001), and a nonsignificant increase in the number of patients in the undifferentiated category (45 vs. 63 patients; P = .06).
“Almost half of the changes in the distribution between the ILAR categories were caused by updated information on heredity in a first-degree relative obtained at the follow-up visits,” Dr. Glerup and colleagues write.
The results of the long-term study show that patients are “likely to remain in remission – with the converse also evident, as patients still with evidence of disease activity at 8 years after disease onset were more likely to have refractory disease,” Dr. Wahezi said.
Commenting on the study’s findings, Lisa F. Imundo, MD, director of adolescent rheumatology at Columbia University Medical Center in New York, said they are “great news to be able to give parents of young kids with arthritis.” However, she questioned whether the results are generalizable to populations of patients “who are in the worst prognostic group.”
For example, a substantial proportion of patients were classified under the oligoarticular category. “That’s already a group that we know from experience tends to have a better outcome than some of the other groups of JIA,” she said.
“That kind of weaves its way through the whole study, because then they show a lot of patients have come off their medication. Patients who had more severe disease in more joints would be less likely, I think, to just stop their medication and stop going to doctors,” Dr. Imundo explained.
Although the study is valuable for its long-term follow-up, there is also a question of generalizability across a more diverse ethnic and racial group. The authors do not elaborate on the racial breakdown of their patients, Dr. Imundo said, “so we’re going to have to assume that the vast majority are going to [have] Caucasian Nordic ethnic background, and that goes along with them having this high percentage of HLA-B27 positivity, which is a gene that’s more prevalent in northern European populations.”
Jonathan Hausmann, MD, a pediatric and adult rheumatologist at Boston Children’s Hospital, Boston,, told this news organization that he believes the overall conclusions from the study – that JIA persists over time and that ILAR classification is a somewhat imprecise measure of assessing JIA types in children – would be generalizable to other groups.
However, long-term registries evaluating JIA in more diverse populations, such as the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, could confirm these results, said Dr. Hausmann, who is a registry informatics associate with CARRA and was not associated with the research.
Long-term management of JIA
In an accompanying editorial, Jaime Guzman, MD, MSc, and Ross E. Petty, MD, PhD, of British Columbia Children’s Hospital and the University of British Columbia, Vancouver, said a rheumatologist’s interpretation of the study would be tied to what they learned about children with arthritis in medical school. They would see the glass as “half full” if children who achieved remission stayed in remission if they learned that a child might end up outgrowing JIA but potentially develop lifelong disability, whereas others may focus on the outcome of approximately half of patients not achieving remission.
“When I was going through medical school, I remember learning that JIA is a disease of children, and typically, they outgrow it as they become adults,” Dr. Hausmann said. “I think this study and many other studies have shown that that’s actually not the case – that, in fact, it may be a majority of kids continue having active disease even through adulthood.”
If a rheumatologist knows JIA is likely to continue into adulthood, “that’s huge,” Dr. Hausmann said. “That means when we first diagnose patients with JIA as kids, we need to set expectations with the families that this may not just go away; this may be something that could be more lifelong.”
Education on the part of the patient, their parents, and their clinician on the expected trajectory of the disease is critical so that children can continue their own care as they transition to adulthood, Dr. Hausmann explained. “The earlier the kids develop the skills to discuss their medicines, their side effects, the better they’ll be able to transition to adult medicine,” he said.
For the patients who go into remission and stay in remission, the message is also important. “To have the reassurance that a lot of those kids won’t be having active joint symptoms or need to be on medication, that’s a huge positive message that can get out there, so I think that’s great,” Dr. Imundo said.
Time to move on from ILAR classification?
Another big takeaway from the study was how patients’ ILAR classification changed across the 18-year follow-up. First proposed in 1995, the JIA ILAR classification has been revised several times for clarification purposes. In its current form, the ILAR classification considers a patient’s history when categorizing JIA types but also includes factors such as immediate family history. This system of assessing JIA has been criticized and there are initiatives to create a new JIA classification system to replace it.
“The ILAR criteria were designed to classify patients 6 months after disease onset in an attempt to find some commonality in clinical phenotypes, prognosis, and suggested management,” Dr. Wahezi said. “While there continues to be debate as to whether we can improve our classification of JIA patients, it is not surprising that phenotypes may evolve over time as new clinical features develop. As pediatric rheumatologists, we are well accustomed to having to modify management plans as children manifest with new clinical features over time.”
Although the percentage of patients who switched ILAR classifications over the study period was “much higher” than she would have thought, Dr. Imundo said it was the reasons provided in the study that seemed odd to her. “The classification scheme relies on your family history, like someone else in your family now has psoriasis, so your arthritis classification changes,” she explained.
“We want to head toward a much more unified classification scheme, a simpler one. We now understand that some of the diseases that we see in pediatrics are really the equivalent or same disease in adults,” she said.
“Most of the pediatric categories of JIA have distinct adult correlates,” Dr. Hausmann agreed. RF-positive polyarthritis in children and rheumatoid arthritis in adults are correlated, as are systemic JIA and adult-onset Still’s disease, he explained. “That has been borne out also by genetic susceptibility studies that the genetic predispositions to systemic arthritis in children is the same as the genetic predisposition to adult-onset Still’s disease in adults. By and large, there are a lot of similarities between the two.
“I think we need to incorporate some of that knowledge in better classifying kids with JIA so that we can find the best treatments and the best outcomes, and we can provide information to families about the expected course of the disease over time so that can inform our discussions.”
Some pediatric rheumatologists accept the classification system is flawed, but not all concur with the degree to which these problems impact patient care. “While the ILAR classification criteria may be subject to criticism, it does provide general context and prognostic implications for patients and families,” Dr. Wahezi said.
“The medicines certainly are very similar across the JIA categories, so the implications are not as broad” when classification changes,” Dr. Hausmann said. “But it certainly shows that there are things that we still don’t know. I think classification is actually pretty important because it might give you a sense of how persistent the disease will be.”
Dr. Imundo said the ILAR classification’s “time is limited,” and rheumatologists may soon need to adopt a new way of classifying children with rheumatic disease – “a more data-driven, genetics-driven scheme.”
“These categories are so imperfect, and the patients are changing. I feel like that says to me, let’s find something that’s more predictive that really helps us a little better than what we have now,” she said.
The study had no specific funding. The authors of the study and the editorial have disclosed no relevant financial relationships. Dr. Hausmann reports receiving salary support from CARRA. Dr. Imundo and Dr. Wahezi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ARTHRITIS CARE & RESEARCH
Unfavorable intermediate-risk prostate cancer: EBRT plus BT improve survival
Key clinical point: External beam radiotherapy (EBRT) plus brachytherapy (BT) boost improves survival in patients with unfavorable intermediate-risk prostate cancer vs. brachytherapy alone.
Major finding: The median follow-up was 68 months. In weight-adjusted analysis, EBRT plus BT (hazard ratio [HR] 0.82; P = .000005) vs. BT alone significantly improves overall survival (OS). At 10 years, the OS rate was 62.4% and 69.3% in the BT alone and EBRT plus BT groups, respectively (P < .0001).
Study details: This was a retrospective study of 11,721 patients with unfavorable intermediate-risk prostate cancer diagnosed between 2004 and 2015. The patients received either definitive BT without androgen deprivation therapy (ADT), BT with ADT, EBRT with ADT, or EBRT with BT and ADT.
Disclosures: This work was supported by Washington University in St. Louis Medical School and Barnes Jewish Hospital. The authors received advisory/consulting/scientific fees and honoraria outside this work.
Source: Andruska N et al. Brachytherapy. 2022 (Feb 2). Doi: 10.1016/j.brachy.2021.12.008.
Key clinical point: External beam radiotherapy (EBRT) plus brachytherapy (BT) boost improves survival in patients with unfavorable intermediate-risk prostate cancer vs. brachytherapy alone.
Major finding: The median follow-up was 68 months. In weight-adjusted analysis, EBRT plus BT (hazard ratio [HR] 0.82; P = .000005) vs. BT alone significantly improves overall survival (OS). At 10 years, the OS rate was 62.4% and 69.3% in the BT alone and EBRT plus BT groups, respectively (P < .0001).
Study details: This was a retrospective study of 11,721 patients with unfavorable intermediate-risk prostate cancer diagnosed between 2004 and 2015. The patients received either definitive BT without androgen deprivation therapy (ADT), BT with ADT, EBRT with ADT, or EBRT with BT and ADT.
Disclosures: This work was supported by Washington University in St. Louis Medical School and Barnes Jewish Hospital. The authors received advisory/consulting/scientific fees and honoraria outside this work.
Source: Andruska N et al. Brachytherapy. 2022 (Feb 2). Doi: 10.1016/j.brachy.2021.12.008.
Key clinical point: External beam radiotherapy (EBRT) plus brachytherapy (BT) boost improves survival in patients with unfavorable intermediate-risk prostate cancer vs. brachytherapy alone.
Major finding: The median follow-up was 68 months. In weight-adjusted analysis, EBRT plus BT (hazard ratio [HR] 0.82; P = .000005) vs. BT alone significantly improves overall survival (OS). At 10 years, the OS rate was 62.4% and 69.3% in the BT alone and EBRT plus BT groups, respectively (P < .0001).
Study details: This was a retrospective study of 11,721 patients with unfavorable intermediate-risk prostate cancer diagnosed between 2004 and 2015. The patients received either definitive BT without androgen deprivation therapy (ADT), BT with ADT, EBRT with ADT, or EBRT with BT and ADT.
Disclosures: This work was supported by Washington University in St. Louis Medical School and Barnes Jewish Hospital. The authors received advisory/consulting/scientific fees and honoraria outside this work.
Source: Andruska N et al. Brachytherapy. 2022 (Feb 2). Doi: 10.1016/j.brachy.2021.12.008.
Intermediate-/high-risk prostate cancer: Focal HIFU provides good control
Key clinical point: Focal high-intensity focused ultrasound (HIFU) shows good cancer control in patients with nonmetastatic prostate cancer.
Major finding: At 7 years, failure-free survival was 69% (95% CI 64%-74%). In patients with intermediate- and high-risk cancers, failure-free survival at 7 years was 68% (95% CI 62%-75%) and 65% (95% CI 56%-74%), respectively.
Study details: This was a study of 1,379 patients with nonmetastatic prostate cancer including intermediate- (65%) and high-risk (28%) categories from a prospective registry who received focal therapy using HIFU during 2005-2020.
Disclosures: This work was supported by Sonacare Inc. The authors received research funding, consulting/advisory fees, and travel grants. Some of the authors were paid proctors to give training on the procedures.
Source: Reddy D et al. Eur Urol. 2022 (Feb 3). Doi: 10.1016/j.eururo.2022.01.005.
Key clinical point: Focal high-intensity focused ultrasound (HIFU) shows good cancer control in patients with nonmetastatic prostate cancer.
Major finding: At 7 years, failure-free survival was 69% (95% CI 64%-74%). In patients with intermediate- and high-risk cancers, failure-free survival at 7 years was 68% (95% CI 62%-75%) and 65% (95% CI 56%-74%), respectively.
Study details: This was a study of 1,379 patients with nonmetastatic prostate cancer including intermediate- (65%) and high-risk (28%) categories from a prospective registry who received focal therapy using HIFU during 2005-2020.
Disclosures: This work was supported by Sonacare Inc. The authors received research funding, consulting/advisory fees, and travel grants. Some of the authors were paid proctors to give training on the procedures.
Source: Reddy D et al. Eur Urol. 2022 (Feb 3). Doi: 10.1016/j.eururo.2022.01.005.
Key clinical point: Focal high-intensity focused ultrasound (HIFU) shows good cancer control in patients with nonmetastatic prostate cancer.
Major finding: At 7 years, failure-free survival was 69% (95% CI 64%-74%). In patients with intermediate- and high-risk cancers, failure-free survival at 7 years was 68% (95% CI 62%-75%) and 65% (95% CI 56%-74%), respectively.
Study details: This was a study of 1,379 patients with nonmetastatic prostate cancer including intermediate- (65%) and high-risk (28%) categories from a prospective registry who received focal therapy using HIFU during 2005-2020.
Disclosures: This work was supported by Sonacare Inc. The authors received research funding, consulting/advisory fees, and travel grants. Some of the authors were paid proctors to give training on the procedures.
Source: Reddy D et al. Eur Urol. 2022 (Feb 3). Doi: 10.1016/j.eururo.2022.01.005.