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How Are Lesions and Seizures Related?
ANSWER
The correct answer is tuberous sclerosis (choice “d”), a genetic disorder affecting cellular differentiation and proliferation. As a result, hamartomas commonly form in organs such as the brain.
Von Recklinghausen disease (choice “a”; also known as neurofibromatosis type 1) presents with hyperpigmented macules and patches called café au lait macules. These and other findings differentiate it considerably from tuberous sclerosis.
“No unifying explanation” (choice “b”) is incorrect, because, as stated above, there is a unifying explanation for these findings!
Vitiligo (choice “c”) involves hypopigmented macules and patches. However, it does not present with some of the other findings seen in this case.
DISCUSSION
Tuberous sclerosis was first described in 1862 by von Recklinghausen, who noted the collection of findings we now term tuberous sclerosis complex (TSC) due to the wide variation in presentation.
In the United States, TSC occurs in an estimated one in 6,000 to one in 30,000 newborns. Usually, it manifests when the child is between ages 2 and 6, but genetic penetrance is highly variable—a major reason for the shift to the use of the term complex with this condition. (This case, with its late presentation, illustrates this variability.)
In about 60% of cases, TSC is transmitted in autosomal dominant mode, although at least 20% of cases may be due to spontaneous mutations. It has not shown any racial or gender predilections. Up to 90% of TSC patients will present with seizures, and 60% to 70% of those affected will demonstrate some developmental disability.
Skin is affected in at least 70% of TSC cases. This patient typifies the common dermatologic findings: dart-shaped hypopigmented macules (known as mountain ash leaf spots) and fleshy facial papules in the nasolabial region (originally called adenoma sebaceum and now called angiofibromas). Periungal fibromas are also common. Other major diagnostic criteria for TSC include cortical tubers seen on imaging and retinal hamartomas. Minor diagnostic criteria include pits in dental enamel and gingival fibromas.
Definitive diagnosis depends on identification of either two major manifestations or one major and two minor findings. There are no blood tests to confirm the diagnosis. In terms of treatment, the various elements that comprise TSC can be dealt with (eg, control of seizures and destruction or modification of skin lesions).
This patient received a diagnosis of TSC. She was returned to her primary care provider, who referred her for additional imaging of her lungs and heart and for ophthalmologic evaluation of her retinas. Genetic counseling was also arranged. With her seizures under control, she was able to continue matriculation through high school.
ANSWER
The correct answer is tuberous sclerosis (choice “d”), a genetic disorder affecting cellular differentiation and proliferation. As a result, hamartomas commonly form in organs such as the brain.
Von Recklinghausen disease (choice “a”; also known as neurofibromatosis type 1) presents with hyperpigmented macules and patches called café au lait macules. These and other findings differentiate it considerably from tuberous sclerosis.
“No unifying explanation” (choice “b”) is incorrect, because, as stated above, there is a unifying explanation for these findings!
Vitiligo (choice “c”) involves hypopigmented macules and patches. However, it does not present with some of the other findings seen in this case.
DISCUSSION
Tuberous sclerosis was first described in 1862 by von Recklinghausen, who noted the collection of findings we now term tuberous sclerosis complex (TSC) due to the wide variation in presentation.
In the United States, TSC occurs in an estimated one in 6,000 to one in 30,000 newborns. Usually, it manifests when the child is between ages 2 and 6, but genetic penetrance is highly variable—a major reason for the shift to the use of the term complex with this condition. (This case, with its late presentation, illustrates this variability.)
In about 60% of cases, TSC is transmitted in autosomal dominant mode, although at least 20% of cases may be due to spontaneous mutations. It has not shown any racial or gender predilections. Up to 90% of TSC patients will present with seizures, and 60% to 70% of those affected will demonstrate some developmental disability.
Skin is affected in at least 70% of TSC cases. This patient typifies the common dermatologic findings: dart-shaped hypopigmented macules (known as mountain ash leaf spots) and fleshy facial papules in the nasolabial region (originally called adenoma sebaceum and now called angiofibromas). Periungal fibromas are also common. Other major diagnostic criteria for TSC include cortical tubers seen on imaging and retinal hamartomas. Minor diagnostic criteria include pits in dental enamel and gingival fibromas.
Definitive diagnosis depends on identification of either two major manifestations or one major and two minor findings. There are no blood tests to confirm the diagnosis. In terms of treatment, the various elements that comprise TSC can be dealt with (eg, control of seizures and destruction or modification of skin lesions).
This patient received a diagnosis of TSC. She was returned to her primary care provider, who referred her for additional imaging of her lungs and heart and for ophthalmologic evaluation of her retinas. Genetic counseling was also arranged. With her seizures under control, she was able to continue matriculation through high school.
ANSWER
The correct answer is tuberous sclerosis (choice “d”), a genetic disorder affecting cellular differentiation and proliferation. As a result, hamartomas commonly form in organs such as the brain.
Von Recklinghausen disease (choice “a”; also known as neurofibromatosis type 1) presents with hyperpigmented macules and patches called café au lait macules. These and other findings differentiate it considerably from tuberous sclerosis.
“No unifying explanation” (choice “b”) is incorrect, because, as stated above, there is a unifying explanation for these findings!
Vitiligo (choice “c”) involves hypopigmented macules and patches. However, it does not present with some of the other findings seen in this case.
DISCUSSION
Tuberous sclerosis was first described in 1862 by von Recklinghausen, who noted the collection of findings we now term tuberous sclerosis complex (TSC) due to the wide variation in presentation.
In the United States, TSC occurs in an estimated one in 6,000 to one in 30,000 newborns. Usually, it manifests when the child is between ages 2 and 6, but genetic penetrance is highly variable—a major reason for the shift to the use of the term complex with this condition. (This case, with its late presentation, illustrates this variability.)
In about 60% of cases, TSC is transmitted in autosomal dominant mode, although at least 20% of cases may be due to spontaneous mutations. It has not shown any racial or gender predilections. Up to 90% of TSC patients will present with seizures, and 60% to 70% of those affected will demonstrate some developmental disability.
Skin is affected in at least 70% of TSC cases. This patient typifies the common dermatologic findings: dart-shaped hypopigmented macules (known as mountain ash leaf spots) and fleshy facial papules in the nasolabial region (originally called adenoma sebaceum and now called angiofibromas). Periungal fibromas are also common. Other major diagnostic criteria for TSC include cortical tubers seen on imaging and retinal hamartomas. Minor diagnostic criteria include pits in dental enamel and gingival fibromas.
Definitive diagnosis depends on identification of either two major manifestations or one major and two minor findings. There are no blood tests to confirm the diagnosis. In terms of treatment, the various elements that comprise TSC can be dealt with (eg, control of seizures and destruction or modification of skin lesions).
This patient received a diagnosis of TSC. She was returned to her primary care provider, who referred her for additional imaging of her lungs and heart and for ophthalmologic evaluation of her retinas. Genetic counseling was also arranged. With her seizures under control, she was able to continue matriculation through high school.
The parents of this 16-year-old girl first noticed the “spots” on their daughter’s thigh when she was 2. At that time, they expressed mild concern to the child’s pediatrician, who advised them to watch the lesions for change. In the absence of any, the spots were essentially ignored. But recently—and alarmingly—the patient experienced two grand mal seizures. Three months ago, she was hospitalized and underwent a thorough examination and workup, including imaging studies of the brain. These revealed presumed neural tumors, which are being followed with serial imaging. In the meantime, her primary care provider recommends a visit to dermatology for evaluation of the child’s skin—including the aforementioned spots on her thigh. Her parents deny any family history of similar problems with skin or seizures. The spots are located on the patient’s right lateral thigh. The largest is a dart-shaped 4 x 2.5–cm hypopigmented patch. It is surrounded by much smaller (< 1 cm in diameter) but similarly hypopigmented macules. The large lesion is symmetrical but has slightly serrated borders. Examination elsewhere reveals periungual fibromas on two of 10 fingers. Odd fleshy papules are noted in the bilateral nasolabial areas.
Man’s Heart Rhythm Has Been “Strange”
ANSWER
The ECG reveals sinus bradycardia with second-degree atrioventricular (AV) block (Mobitz I), also known as Wenckebach block.
Mobitz I heart block often occurs with reversible reasons of conduction block at the level of the AV node. While the P-P intervals remain constant, conduction fatigue within the AV node results in the P-R interval becoming progressively longer, until the AV node completely blocks conduction from the atria to the ventricles. The process then repeats itself in a pattern of P to QRS groups.
In this case, there are three P waves for every two QRS complexes, resulting in a 3:2 pattern. The PR interval is longest prior to the blocked QRS and shortest immediately after it. The diagnosis of sinus bradycardia results from a constant P-P interval of 58 beats/min.
Further questioning of the patient revealed that he had inadvertently doubled his dose of metoprolol. Correcting this resulted in the return of normal sinus rhythm.
ANSWER
The ECG reveals sinus bradycardia with second-degree atrioventricular (AV) block (Mobitz I), also known as Wenckebach block.
Mobitz I heart block often occurs with reversible reasons of conduction block at the level of the AV node. While the P-P intervals remain constant, conduction fatigue within the AV node results in the P-R interval becoming progressively longer, until the AV node completely blocks conduction from the atria to the ventricles. The process then repeats itself in a pattern of P to QRS groups.
In this case, there are three P waves for every two QRS complexes, resulting in a 3:2 pattern. The PR interval is longest prior to the blocked QRS and shortest immediately after it. The diagnosis of sinus bradycardia results from a constant P-P interval of 58 beats/min.
Further questioning of the patient revealed that he had inadvertently doubled his dose of metoprolol. Correcting this resulted in the return of normal sinus rhythm.
ANSWER
The ECG reveals sinus bradycardia with second-degree atrioventricular (AV) block (Mobitz I), also known as Wenckebach block.
Mobitz I heart block often occurs with reversible reasons of conduction block at the level of the AV node. While the P-P intervals remain constant, conduction fatigue within the AV node results in the P-R interval becoming progressively longer, until the AV node completely blocks conduction from the atria to the ventricles. The process then repeats itself in a pattern of P to QRS groups.
In this case, there are three P waves for every two QRS complexes, resulting in a 3:2 pattern. The PR interval is longest prior to the blocked QRS and shortest immediately after it. The diagnosis of sinus bradycardia results from a constant P-P interval of 58 beats/min.
Further questioning of the patient revealed that he had inadvertently doubled his dose of metoprolol. Correcting this resulted in the return of normal sinus rhythm.
A 74-year-old man presents to your outpatient clinic for a routine appointment. He’s been your patient for years, but you’ve had difficulty convincing him of the importance of taking his hypertension medications regularly. For the most part, he has been compliant; however, recently, with finances becoming tight toward the end of the month, he often takes his β-blocker and diuretic every other day in order to stretch his prescription before refilling it. His health has remained excellent since you last saw him a year ago. However, while performing a review of systems, you learn that his heart rhythm has been “funny” in the past two weeks. He states it hasn’t affected his ability to perform his daily activities, including farming, but it was just “strange.” He denies chest pain, shortness of breath, dizziness, syncope or near-syncope, and peripheral edema. He still manages his 450-acre farm, as he has for most of his adult life. Medical history includes hypertension but no angina, MI, or other cardiac disease. Surgical history is remarkable for a right inguinal hernia repair, an appendectomy, and a right hip replacement. His medications include furosemide, potassium chloride, and metoprolol. He has no known drug allergies and does not use recreational drugs or naturopathic herbs. The patient has been a widower for 12 years. His two sons live nearby and help him on his farm. Due to his religious affiliation, he has never used alcohol or tobacco. Review of systems is remarkable for palpitations and an occasional skipped beat. Vital signs include a blood pressure of 108/58 mm Hg; pulse, 50 beats/min and “irregular”; respiratory rate, 14 breaths/min-1; temperature, 98.4°F; and O2 saturation, 96% on room air. His weight is 176 lb and his height, 74 in. Physical exam reveals a pulse that is regularly irregular at a rate of 56 beats/min. There are no murmurs, rubs, or gallops. The neck veins are not distended, and there is no peripheral edema. His lungs are clear to auscultation, and the remainder of his physical exam is unchanged from his previous visit. Given the change in his heart rhythm since his previous visit, you order an ECG and note the following: a ventricular rate of 44 beats/min; PR interval, not measured; QRS duration, 106 ms; QT/QTc interval, 484/413 ms; P axis, 65°; R axis, 11°; and T axis, 6°. What is your interpretation of this ECG?
SSTI guidelines stress diagnostic skill, careful treatment
New practice guidelines on skin and soft tissue infections from the Infectious Diseases Society of America stress careful clinical attention to the type of infection, the epidemiological setting in which the infection occurred, the health status of the patient, and the selection and dosage of the most appropriate treatment agents.
The guidelines, published online June 18 in Clinical Infectious Diseases (doi:10.1093/cid/ciu296), update those issued by IDSA in 2005 and cover everything from preventing infections caused by animal bites in healthy hosts to life-threatening infections in immunocompromised patients. They also emphasize accurate identification of pathogens, stressing that clinical presentations can be very similar.
"This is not one of those guidelines that boils complex issues down to a choice between a couple of different drugs or combinations of drugs," said Dr. Dennis Stevens of the Department of Veterans Affairs in Boise, Idaho, the guidelines’ lead author. "Skin and soft tissue infections [SSTIs] have multiple causes and different presentations, depending upon the immune status of the host. Here it’s much more complicated and really requires an astute physician to consider a number of things."
The guidelines, drafted by a 10-member panel, offer a novel algorithm for management of nonpurulent and purulent infections that aims to define a pathway for mild, moderate, and severe infections in each category. For example, no antibiotic is recommended for a purulent infection – only incision and drainage – if the patient has no signs of systemic involvement.
For moderate cases of purulent infection with some systemic involvement, incision and drainage should be followed by culture and sensitivity testing, the guidelines say, listing two antibiotics, trimethoprim-sulfamethoxazole and doxycycline, as appropriate for empiric treatment, while trimethoprim-sulfamethoxazole is recommended if the pathogen is found to be methicillin-resistant Staphylococcus aureus (MRSA) and dicloxacillin or cephalexin if it is methicillin-susceptible S. aureus (MSSA).
The purpose of the algorithm, expressed in the guidelines in chart form, "is to make the physician think," Dr. Stevens said in an interview. "There is a huge move to try and monitor antibiotic stewardship to prevent resistance, and we’re just trying to get the clinician to think of tier 1, tier 2, and tier 3 approaches, depending not only on the bug, but on how sick the patient is. Instead of a knee-jerk approach treating everybody with highly expensive IV antibiotics, [the algorithm] provides a clear pathway to treat appropriately."
In people with an abscess who have failed antibiotic treatment, are immunocompromised, or have fever and elevated white blood cell counts or other evidence of severe infection, "we’re not going to gamble," Dr. Stevens said, adding that the guidelines recommend prompt treatment using "an antibiotic that gets all of these organisms, including resistant ones." Newly approved agents dalbavancin and tedizolid are effective in treating SSTIs caused by MRSA, the guidelines note.
The guidelines are intended for use by clinicians in emergency departments, family practice, internal medicine, general surgery, orthopedics, gynecology, dermatology, infectious disease, and oncology.
Another algorithm charted in the guidelines covers wound infections following surgeries, which can involve multiple pathogens. The algorithm provides simple clinical clues as to which require antibiotics, a simple opening of the suture line, "or a full-court press for the kind of devastating infections that occur within the first 48 hours," Dr. Stevens said. Additional recommendations address infections that can occur in individuals receiving treatment for cancer or receiving immunosuppressant medications, or those who have had an organ transplant or who have HIV/AIDS.
Immunocompromised patients, Dr. Stevens said, are among the most challenging to treat because they may have a history of extensive antibiotic exposure, are likely to have infections with resistant bacteria, and often see involvement with fungal and parasitic agents that might be considered innocuous in normal individuals. "This is the first time physicians will have some decent guidelines about how to approach the problem of skin and soft tissue infections in these kinds of patients," he noted.
The guidelines’ development was funded by the IDSA. Dr. Stevens reported no conflicts of interest. Panel member Alan L. Bisno disclosed receiving honoraria from UpToDate, while five other members – Dr. Henry F. Chambers, Dr. E. Patchen Dellinger, Dr. Ellie J. C. Goldstein, Dr. Sherwood L. Gorbach, and Dr. Sheldon L. Kaplan – disclosed financial relationships with pharmaceutical manufacturers.
Skin and soft tissue infections are one of the most common causes for patient evaluation in emergency departments and are common reasons for consultations by surgeons. SSTIs occur across a broad continuum of severity and often require only antimicrobial therapy (such as cellulitis), but they may be fulminate and life-threatening necrotizing infections that require aggressive surgical intervention. The guidelines provided by a distinguished group of clinicians from the Infectious Diseases Society of America provide an excellent organizational framework to understand this heterogenous collection of infections and provide a meaningful structure to direct management.
Several points in these guidelines deserve emphasis. First, considerable discussion in the guidelines has focused on the immunocompromised patient with SSTIs, and appropriately so. A broader consideration might have been to also include those patients with health care-associated exposure in addition to clinical immunosuppression. About 40 million hospitalizations occur annually in the United State, which makes over 3 million patients within 30 days of discharge. A larger number of patients have had recent antibiotic exposure. About 1.5 million patients are in chronic care facilities and nearly 500,000 are receiving chronic hemodialysis. Accordingly, immunocompromised and health care-associated patient exposures require that assumptions about the microbiology of SSTIs have "sensitivity" to the resistant pathogens (such as MRSA) not traditionally typical of community-acquired infections.
Second, the guidelines refer to the use of Gram stains for directing antimicrobial therapy. Although the Gram stain does not have the high-technology flare of contemporary health care, it remains a useful tool in differentiating pathogens, especially in necrotizing SSTIs.
Of the major microbiological presentations of necrotizing SSTIs, Streptococcus pyogenes is a gram-positive cocci in chains, Staphylococcus aureus is a gram-positive cocci in clusters, Clostridium perfringens is a gram-positive rod, and polymicrobial infections will have an assortment of different morphologic and gram-staining characteristics in identified bacteria. Aeromonas hydrophilia and Vibrio vulnificus will appear as gram-negative rods in those necrotizing SSTIs associated with fresh or salt-water recreational exposure. The Gram stain provides immediate direction for therapy when culture results will often be too late for a meaningful impact on patient care. Unfortunately, many hospitals have abandoned the use of Gram stains for clinical specimens.
Finally, prompt diagnosis of necrotizing SSTIs is essential. A cause of potentially preventable morbidity and deaths is a delay in the recognition of necrotizing SSTIs and the need for urgent surgical debridement. Necrotizing SSTIs are common issues in medicolegal actions because of the issue of failure to make the timely diagnosis. The hallmark of necrotizing SSTIs is pain out of proportion to the inciting injury. Trivial cutaneous injuries that are associated with an advancing perimeter of palpable tenderness and induration are necrotizing SSTIs until proven otherwise. Importantly, S. pyogenes in particular is associated with "metastatic" infection. Patients with soft-tissue contusions, joint effusions, and even fractures may have blood-borne streptococcal contamination of the injury site and yield a necrotizing infection without any cutaneous source of microbial contamination.
Because monitoring the progression of SSTIs is so important in differentiating necrotizing infections, I would only take to task the recommendation for the use of corticosteroids in treatment of cellulitic infections. Pharmacologic immunosuppression of the patient with an active SSTI in the interest of providing symptomatic relief compromises the clinical evaluation of disease progression.
In summary, the guidelines and the two algorithms for managing community-acquired and surgical incision infections are very useful for providing surgical clinicians direction in patient management. The increased incidence of S. aureus-associated necrotizing SSTIs and the emergence of community-associated MRSA over the last 20 years indicate that this is a dynamic area with changing characteristics. The changing pattern of pathogens and antimicrobial choices require a more frequent updating of these important guidelines for patient management.
Dr. Donald E. Fry is an ACS Fellow, executive vice-president for clinical outcomes management of MPA Inc. of Chicago, adjunct professor of surgery at the Northwestern University in Chicago, and professor emeritus of surgery at the University of New Mexico. He is a fellow of the Infectious Diseases Society of America, a past president of the Surgical Infection Society, and associate editor of the journal Surgical Infections.
Skin and soft tissue infections are one of the most common causes for patient evaluation in emergency departments and are common reasons for consultations by surgeons. SSTIs occur across a broad continuum of severity and often require only antimicrobial therapy (such as cellulitis), but they may be fulminate and life-threatening necrotizing infections that require aggressive surgical intervention. The guidelines provided by a distinguished group of clinicians from the Infectious Diseases Society of America provide an excellent organizational framework to understand this heterogenous collection of infections and provide a meaningful structure to direct management.
Several points in these guidelines deserve emphasis. First, considerable discussion in the guidelines has focused on the immunocompromised patient with SSTIs, and appropriately so. A broader consideration might have been to also include those patients with health care-associated exposure in addition to clinical immunosuppression. About 40 million hospitalizations occur annually in the United State, which makes over 3 million patients within 30 days of discharge. A larger number of patients have had recent antibiotic exposure. About 1.5 million patients are in chronic care facilities and nearly 500,000 are receiving chronic hemodialysis. Accordingly, immunocompromised and health care-associated patient exposures require that assumptions about the microbiology of SSTIs have "sensitivity" to the resistant pathogens (such as MRSA) not traditionally typical of community-acquired infections.
Second, the guidelines refer to the use of Gram stains for directing antimicrobial therapy. Although the Gram stain does not have the high-technology flare of contemporary health care, it remains a useful tool in differentiating pathogens, especially in necrotizing SSTIs.
Of the major microbiological presentations of necrotizing SSTIs, Streptococcus pyogenes is a gram-positive cocci in chains, Staphylococcus aureus is a gram-positive cocci in clusters, Clostridium perfringens is a gram-positive rod, and polymicrobial infections will have an assortment of different morphologic and gram-staining characteristics in identified bacteria. Aeromonas hydrophilia and Vibrio vulnificus will appear as gram-negative rods in those necrotizing SSTIs associated with fresh or salt-water recreational exposure. The Gram stain provides immediate direction for therapy when culture results will often be too late for a meaningful impact on patient care. Unfortunately, many hospitals have abandoned the use of Gram stains for clinical specimens.
Finally, prompt diagnosis of necrotizing SSTIs is essential. A cause of potentially preventable morbidity and deaths is a delay in the recognition of necrotizing SSTIs and the need for urgent surgical debridement. Necrotizing SSTIs are common issues in medicolegal actions because of the issue of failure to make the timely diagnosis. The hallmark of necrotizing SSTIs is pain out of proportion to the inciting injury. Trivial cutaneous injuries that are associated with an advancing perimeter of palpable tenderness and induration are necrotizing SSTIs until proven otherwise. Importantly, S. pyogenes in particular is associated with "metastatic" infection. Patients with soft-tissue contusions, joint effusions, and even fractures may have blood-borne streptococcal contamination of the injury site and yield a necrotizing infection without any cutaneous source of microbial contamination.
Because monitoring the progression of SSTIs is so important in differentiating necrotizing infections, I would only take to task the recommendation for the use of corticosteroids in treatment of cellulitic infections. Pharmacologic immunosuppression of the patient with an active SSTI in the interest of providing symptomatic relief compromises the clinical evaluation of disease progression.
In summary, the guidelines and the two algorithms for managing community-acquired and surgical incision infections are very useful for providing surgical clinicians direction in patient management. The increased incidence of S. aureus-associated necrotizing SSTIs and the emergence of community-associated MRSA over the last 20 years indicate that this is a dynamic area with changing characteristics. The changing pattern of pathogens and antimicrobial choices require a more frequent updating of these important guidelines for patient management.
Dr. Donald E. Fry is an ACS Fellow, executive vice-president for clinical outcomes management of MPA Inc. of Chicago, adjunct professor of surgery at the Northwestern University in Chicago, and professor emeritus of surgery at the University of New Mexico. He is a fellow of the Infectious Diseases Society of America, a past president of the Surgical Infection Society, and associate editor of the journal Surgical Infections.
Skin and soft tissue infections are one of the most common causes for patient evaluation in emergency departments and are common reasons for consultations by surgeons. SSTIs occur across a broad continuum of severity and often require only antimicrobial therapy (such as cellulitis), but they may be fulminate and life-threatening necrotizing infections that require aggressive surgical intervention. The guidelines provided by a distinguished group of clinicians from the Infectious Diseases Society of America provide an excellent organizational framework to understand this heterogenous collection of infections and provide a meaningful structure to direct management.
Several points in these guidelines deserve emphasis. First, considerable discussion in the guidelines has focused on the immunocompromised patient with SSTIs, and appropriately so. A broader consideration might have been to also include those patients with health care-associated exposure in addition to clinical immunosuppression. About 40 million hospitalizations occur annually in the United State, which makes over 3 million patients within 30 days of discharge. A larger number of patients have had recent antibiotic exposure. About 1.5 million patients are in chronic care facilities and nearly 500,000 are receiving chronic hemodialysis. Accordingly, immunocompromised and health care-associated patient exposures require that assumptions about the microbiology of SSTIs have "sensitivity" to the resistant pathogens (such as MRSA) not traditionally typical of community-acquired infections.
Second, the guidelines refer to the use of Gram stains for directing antimicrobial therapy. Although the Gram stain does not have the high-technology flare of contemporary health care, it remains a useful tool in differentiating pathogens, especially in necrotizing SSTIs.
Of the major microbiological presentations of necrotizing SSTIs, Streptococcus pyogenes is a gram-positive cocci in chains, Staphylococcus aureus is a gram-positive cocci in clusters, Clostridium perfringens is a gram-positive rod, and polymicrobial infections will have an assortment of different morphologic and gram-staining characteristics in identified bacteria. Aeromonas hydrophilia and Vibrio vulnificus will appear as gram-negative rods in those necrotizing SSTIs associated with fresh or salt-water recreational exposure. The Gram stain provides immediate direction for therapy when culture results will often be too late for a meaningful impact on patient care. Unfortunately, many hospitals have abandoned the use of Gram stains for clinical specimens.
Finally, prompt diagnosis of necrotizing SSTIs is essential. A cause of potentially preventable morbidity and deaths is a delay in the recognition of necrotizing SSTIs and the need for urgent surgical debridement. Necrotizing SSTIs are common issues in medicolegal actions because of the issue of failure to make the timely diagnosis. The hallmark of necrotizing SSTIs is pain out of proportion to the inciting injury. Trivial cutaneous injuries that are associated with an advancing perimeter of palpable tenderness and induration are necrotizing SSTIs until proven otherwise. Importantly, S. pyogenes in particular is associated with "metastatic" infection. Patients with soft-tissue contusions, joint effusions, and even fractures may have blood-borne streptococcal contamination of the injury site and yield a necrotizing infection without any cutaneous source of microbial contamination.
Because monitoring the progression of SSTIs is so important in differentiating necrotizing infections, I would only take to task the recommendation for the use of corticosteroids in treatment of cellulitic infections. Pharmacologic immunosuppression of the patient with an active SSTI in the interest of providing symptomatic relief compromises the clinical evaluation of disease progression.
In summary, the guidelines and the two algorithms for managing community-acquired and surgical incision infections are very useful for providing surgical clinicians direction in patient management. The increased incidence of S. aureus-associated necrotizing SSTIs and the emergence of community-associated MRSA over the last 20 years indicate that this is a dynamic area with changing characteristics. The changing pattern of pathogens and antimicrobial choices require a more frequent updating of these important guidelines for patient management.
Dr. Donald E. Fry is an ACS Fellow, executive vice-president for clinical outcomes management of MPA Inc. of Chicago, adjunct professor of surgery at the Northwestern University in Chicago, and professor emeritus of surgery at the University of New Mexico. He is a fellow of the Infectious Diseases Society of America, a past president of the Surgical Infection Society, and associate editor of the journal Surgical Infections.
New practice guidelines on skin and soft tissue infections from the Infectious Diseases Society of America stress careful clinical attention to the type of infection, the epidemiological setting in which the infection occurred, the health status of the patient, and the selection and dosage of the most appropriate treatment agents.
The guidelines, published online June 18 in Clinical Infectious Diseases (doi:10.1093/cid/ciu296), update those issued by IDSA in 2005 and cover everything from preventing infections caused by animal bites in healthy hosts to life-threatening infections in immunocompromised patients. They also emphasize accurate identification of pathogens, stressing that clinical presentations can be very similar.
"This is not one of those guidelines that boils complex issues down to a choice between a couple of different drugs or combinations of drugs," said Dr. Dennis Stevens of the Department of Veterans Affairs in Boise, Idaho, the guidelines’ lead author. "Skin and soft tissue infections [SSTIs] have multiple causes and different presentations, depending upon the immune status of the host. Here it’s much more complicated and really requires an astute physician to consider a number of things."
The guidelines, drafted by a 10-member panel, offer a novel algorithm for management of nonpurulent and purulent infections that aims to define a pathway for mild, moderate, and severe infections in each category. For example, no antibiotic is recommended for a purulent infection – only incision and drainage – if the patient has no signs of systemic involvement.
For moderate cases of purulent infection with some systemic involvement, incision and drainage should be followed by culture and sensitivity testing, the guidelines say, listing two antibiotics, trimethoprim-sulfamethoxazole and doxycycline, as appropriate for empiric treatment, while trimethoprim-sulfamethoxazole is recommended if the pathogen is found to be methicillin-resistant Staphylococcus aureus (MRSA) and dicloxacillin or cephalexin if it is methicillin-susceptible S. aureus (MSSA).
The purpose of the algorithm, expressed in the guidelines in chart form, "is to make the physician think," Dr. Stevens said in an interview. "There is a huge move to try and monitor antibiotic stewardship to prevent resistance, and we’re just trying to get the clinician to think of tier 1, tier 2, and tier 3 approaches, depending not only on the bug, but on how sick the patient is. Instead of a knee-jerk approach treating everybody with highly expensive IV antibiotics, [the algorithm] provides a clear pathway to treat appropriately."
In people with an abscess who have failed antibiotic treatment, are immunocompromised, or have fever and elevated white blood cell counts or other evidence of severe infection, "we’re not going to gamble," Dr. Stevens said, adding that the guidelines recommend prompt treatment using "an antibiotic that gets all of these organisms, including resistant ones." Newly approved agents dalbavancin and tedizolid are effective in treating SSTIs caused by MRSA, the guidelines note.
The guidelines are intended for use by clinicians in emergency departments, family practice, internal medicine, general surgery, orthopedics, gynecology, dermatology, infectious disease, and oncology.
Another algorithm charted in the guidelines covers wound infections following surgeries, which can involve multiple pathogens. The algorithm provides simple clinical clues as to which require antibiotics, a simple opening of the suture line, "or a full-court press for the kind of devastating infections that occur within the first 48 hours," Dr. Stevens said. Additional recommendations address infections that can occur in individuals receiving treatment for cancer or receiving immunosuppressant medications, or those who have had an organ transplant or who have HIV/AIDS.
Immunocompromised patients, Dr. Stevens said, are among the most challenging to treat because they may have a history of extensive antibiotic exposure, are likely to have infections with resistant bacteria, and often see involvement with fungal and parasitic agents that might be considered innocuous in normal individuals. "This is the first time physicians will have some decent guidelines about how to approach the problem of skin and soft tissue infections in these kinds of patients," he noted.
The guidelines’ development was funded by the IDSA. Dr. Stevens reported no conflicts of interest. Panel member Alan L. Bisno disclosed receiving honoraria from UpToDate, while five other members – Dr. Henry F. Chambers, Dr. E. Patchen Dellinger, Dr. Ellie J. C. Goldstein, Dr. Sherwood L. Gorbach, and Dr. Sheldon L. Kaplan – disclosed financial relationships with pharmaceutical manufacturers.
New practice guidelines on skin and soft tissue infections from the Infectious Diseases Society of America stress careful clinical attention to the type of infection, the epidemiological setting in which the infection occurred, the health status of the patient, and the selection and dosage of the most appropriate treatment agents.
The guidelines, published online June 18 in Clinical Infectious Diseases (doi:10.1093/cid/ciu296), update those issued by IDSA in 2005 and cover everything from preventing infections caused by animal bites in healthy hosts to life-threatening infections in immunocompromised patients. They also emphasize accurate identification of pathogens, stressing that clinical presentations can be very similar.
"This is not one of those guidelines that boils complex issues down to a choice between a couple of different drugs or combinations of drugs," said Dr. Dennis Stevens of the Department of Veterans Affairs in Boise, Idaho, the guidelines’ lead author. "Skin and soft tissue infections [SSTIs] have multiple causes and different presentations, depending upon the immune status of the host. Here it’s much more complicated and really requires an astute physician to consider a number of things."
The guidelines, drafted by a 10-member panel, offer a novel algorithm for management of nonpurulent and purulent infections that aims to define a pathway for mild, moderate, and severe infections in each category. For example, no antibiotic is recommended for a purulent infection – only incision and drainage – if the patient has no signs of systemic involvement.
For moderate cases of purulent infection with some systemic involvement, incision and drainage should be followed by culture and sensitivity testing, the guidelines say, listing two antibiotics, trimethoprim-sulfamethoxazole and doxycycline, as appropriate for empiric treatment, while trimethoprim-sulfamethoxazole is recommended if the pathogen is found to be methicillin-resistant Staphylococcus aureus (MRSA) and dicloxacillin or cephalexin if it is methicillin-susceptible S. aureus (MSSA).
The purpose of the algorithm, expressed in the guidelines in chart form, "is to make the physician think," Dr. Stevens said in an interview. "There is a huge move to try and monitor antibiotic stewardship to prevent resistance, and we’re just trying to get the clinician to think of tier 1, tier 2, and tier 3 approaches, depending not only on the bug, but on how sick the patient is. Instead of a knee-jerk approach treating everybody with highly expensive IV antibiotics, [the algorithm] provides a clear pathway to treat appropriately."
In people with an abscess who have failed antibiotic treatment, are immunocompromised, or have fever and elevated white blood cell counts or other evidence of severe infection, "we’re not going to gamble," Dr. Stevens said, adding that the guidelines recommend prompt treatment using "an antibiotic that gets all of these organisms, including resistant ones." Newly approved agents dalbavancin and tedizolid are effective in treating SSTIs caused by MRSA, the guidelines note.
The guidelines are intended for use by clinicians in emergency departments, family practice, internal medicine, general surgery, orthopedics, gynecology, dermatology, infectious disease, and oncology.
Another algorithm charted in the guidelines covers wound infections following surgeries, which can involve multiple pathogens. The algorithm provides simple clinical clues as to which require antibiotics, a simple opening of the suture line, "or a full-court press for the kind of devastating infections that occur within the first 48 hours," Dr. Stevens said. Additional recommendations address infections that can occur in individuals receiving treatment for cancer or receiving immunosuppressant medications, or those who have had an organ transplant or who have HIV/AIDS.
Immunocompromised patients, Dr. Stevens said, are among the most challenging to treat because they may have a history of extensive antibiotic exposure, are likely to have infections with resistant bacteria, and often see involvement with fungal and parasitic agents that might be considered innocuous in normal individuals. "This is the first time physicians will have some decent guidelines about how to approach the problem of skin and soft tissue infections in these kinds of patients," he noted.
The guidelines’ development was funded by the IDSA. Dr. Stevens reported no conflicts of interest. Panel member Alan L. Bisno disclosed receiving honoraria from UpToDate, while five other members – Dr. Henry F. Chambers, Dr. E. Patchen Dellinger, Dr. Ellie J. C. Goldstein, Dr. Sherwood L. Gorbach, and Dr. Sheldon L. Kaplan – disclosed financial relationships with pharmaceutical manufacturers.
FROM CLINICAL INFECTIOUS DISEASES
Thalidomide offers short-term efficacy in HHT
MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.
All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.
Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.
“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.
“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”
Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.
She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.
Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.
For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.
For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.
Response and relapse
The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).
Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.
“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.
“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”
However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.
Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.
Safety and tolerability
Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.
The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).
There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.
There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection. 
MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.
All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.
Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.
“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.
“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”
Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.
She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.
Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.
For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.
For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.
Response and relapse
The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).
Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.
“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.
“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”
However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.
Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.
Safety and tolerability
Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.
The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).
There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.
There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection.
MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.
All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.
Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.
“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.
“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”
Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.
She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.
Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.
For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.
For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.
Response and relapse
The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).
Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.
“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.
“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”
However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.
Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.
Safety and tolerability
Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.
The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).
There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.
There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection.
Bariatric surgery and alcohol use disorder
As obesity continues to ravage the health of the United States, bariatric surgery offers an effective strategy for individual patients suffering from medical complications.
When performed in adults with a body mass index of at least 30 kg/m2, bariatric surgery is associated with a mean weight loss of 20%-35% of baseline weight at 2-3 years. Bariatric surgery is associated with greater reductions in obesity comorbidities, compared with lifestyle intervention and supervised weight loss. Contemporary bariatric surgeries include Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, biliopancreatic diversion with duodenal switch, sleeve gastrectomy, and mini–gastric bypass.
Bariatric surgical procedures affect weight loss through two mechanisms: malabsorption and restriction. Such alterations in human physiology can change the absorption of common drugs of addiction, such as alcohol. This can increase the risk for problem drinking behaviors.
Wendy C. King, Ph.D., of the department of epidemiology at the University of Pittsburgh and her colleagues conducted an analysis of data from 1,945 patients in a cohort who underwent bariatric surgery in 10 U.S. hospitals. Symptoms of alcohol use disorder (AUD) were assessed pre- and postoperatively (JAMA 2012;307:2516-25).
The prevalence of AUD was significantly higher at 2 years postoperatively (9.6%), compared with the preoperative period (7.6%; P less than .01). Factors associated with a higher risk of postoperative AUD included male gender, younger age, smoking, regular alcohol consumption, a history of AUD, recreational drug use, low social support, and receiving Roux-en-Y gastric bypass.
AUD can disqualify patients from bariatric surgery – but 7.6% of patients in this survey (taken independently of clinical care) reported it. The authors noted that a 2% increase in AUD associated with bariatric surgery translates into 2,000 additional people with AUD each year.
This is particularly problematic for this population, because a large number of calories are associated with alcohol intake, and alcohol intake can lower inhibitions for other types of eating behaviors – all of which can lead to weight regain.
So, what do we do?
I think it may be helpful to take alcohol use histories in the patients we are seeing in bariatric surgery follow-up, especially those who appear to be regaining weight. Some patients may not be aware of this connection. For the patients who I have told about this relationship, they recognize it, which may be the first step toward dealing with it.
Dr. Ebbert is a professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.
As obesity continues to ravage the health of the United States, bariatric surgery offers an effective strategy for individual patients suffering from medical complications.
When performed in adults with a body mass index of at least 30 kg/m2, bariatric surgery is associated with a mean weight loss of 20%-35% of baseline weight at 2-3 years. Bariatric surgery is associated with greater reductions in obesity comorbidities, compared with lifestyle intervention and supervised weight loss. Contemporary bariatric surgeries include Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, biliopancreatic diversion with duodenal switch, sleeve gastrectomy, and mini–gastric bypass.
Bariatric surgical procedures affect weight loss through two mechanisms: malabsorption and restriction. Such alterations in human physiology can change the absorption of common drugs of addiction, such as alcohol. This can increase the risk for problem drinking behaviors.
Wendy C. King, Ph.D., of the department of epidemiology at the University of Pittsburgh and her colleagues conducted an analysis of data from 1,945 patients in a cohort who underwent bariatric surgery in 10 U.S. hospitals. Symptoms of alcohol use disorder (AUD) were assessed pre- and postoperatively (JAMA 2012;307:2516-25).
The prevalence of AUD was significantly higher at 2 years postoperatively (9.6%), compared with the preoperative period (7.6%; P less than .01). Factors associated with a higher risk of postoperative AUD included male gender, younger age, smoking, regular alcohol consumption, a history of AUD, recreational drug use, low social support, and receiving Roux-en-Y gastric bypass.
AUD can disqualify patients from bariatric surgery – but 7.6% of patients in this survey (taken independently of clinical care) reported it. The authors noted that a 2% increase in AUD associated with bariatric surgery translates into 2,000 additional people with AUD each year.
This is particularly problematic for this population, because a large number of calories are associated with alcohol intake, and alcohol intake can lower inhibitions for other types of eating behaviors – all of which can lead to weight regain.
So, what do we do?
I think it may be helpful to take alcohol use histories in the patients we are seeing in bariatric surgery follow-up, especially those who appear to be regaining weight. Some patients may not be aware of this connection. For the patients who I have told about this relationship, they recognize it, which may be the first step toward dealing with it.
Dr. Ebbert is a professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.
As obesity continues to ravage the health of the United States, bariatric surgery offers an effective strategy for individual patients suffering from medical complications.
When performed in adults with a body mass index of at least 30 kg/m2, bariatric surgery is associated with a mean weight loss of 20%-35% of baseline weight at 2-3 years. Bariatric surgery is associated with greater reductions in obesity comorbidities, compared with lifestyle intervention and supervised weight loss. Contemporary bariatric surgeries include Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, biliopancreatic diversion with duodenal switch, sleeve gastrectomy, and mini–gastric bypass.
Bariatric surgical procedures affect weight loss through two mechanisms: malabsorption and restriction. Such alterations in human physiology can change the absorption of common drugs of addiction, such as alcohol. This can increase the risk for problem drinking behaviors.
Wendy C. King, Ph.D., of the department of epidemiology at the University of Pittsburgh and her colleagues conducted an analysis of data from 1,945 patients in a cohort who underwent bariatric surgery in 10 U.S. hospitals. Symptoms of alcohol use disorder (AUD) were assessed pre- and postoperatively (JAMA 2012;307:2516-25).
The prevalence of AUD was significantly higher at 2 years postoperatively (9.6%), compared with the preoperative period (7.6%; P less than .01). Factors associated with a higher risk of postoperative AUD included male gender, younger age, smoking, regular alcohol consumption, a history of AUD, recreational drug use, low social support, and receiving Roux-en-Y gastric bypass.
AUD can disqualify patients from bariatric surgery – but 7.6% of patients in this survey (taken independently of clinical care) reported it. The authors noted that a 2% increase in AUD associated with bariatric surgery translates into 2,000 additional people with AUD each year.
This is particularly problematic for this population, because a large number of calories are associated with alcohol intake, and alcohol intake can lower inhibitions for other types of eating behaviors – all of which can lead to weight regain.
So, what do we do?
I think it may be helpful to take alcohol use histories in the patients we are seeing in bariatric surgery follow-up, especially those who appear to be regaining weight. Some patients may not be aware of this connection. For the patients who I have told about this relationship, they recognize it, which may be the first step toward dealing with it.
Dr. Ebbert is a professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.
Long-term complications after ALL minimal, study shows
Credit: Bill Branson
Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.
The team said this is because current therapies are less harsh than their predecessors.
Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.
Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.
“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.
He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.
The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.
Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.
Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.
Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.
Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.
Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.
While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.
“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”
Credit: Bill Branson
Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.
The team said this is because current therapies are less harsh than their predecessors.
Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.
Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.
“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.
He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.
The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.
Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.
Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.
Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.
Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.
Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.
While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.
“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”
Credit: Bill Branson
Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.
The team said this is because current therapies are less harsh than their predecessors.
Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.
Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.
“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.
He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.
The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.
Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.
Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.
Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.
Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.
Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.
While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.
“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”
Team reports new method of chemo delivery
Credit: Kathy Atkinson
Researchers have devised a novel way to deliver chemotherapy drugs “on demand,” according to a paper published in Proceedings of the National Academy of Sciences.
The team loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release the drug.
Like many other injectable gels, this one gradually releases a low level of the drug by diffusion over time. But the new hydrogel differs from others in a key way.
Researchers previously applied ultrasound to gels to temporarily increase doses of drug, but that approach was a one-shot deal, as the ultrasound was used to destroy those gels.
In the current study, the researchers used ultrasound to temporarily disrupt the gel so that it released short, high-dose bursts of the drug. But when they stopped the ultrasound, the hydrogels self-healed.
By closing back up, they were ready to go for the next “on demand” drug burst, providing a way to administer drugs with a greater level of control than was possible before.
The researchers also demonstrated in lab cultures and in mouse models of breast cancer that the pulsed, ultrasound-triggered hydrogel approach to drug delivery was more effective at stopping the growth of tumor cells than traditional, sustained-release drug therapy.
“Our approach counters the whole idea of sustained drug release and offers a double whammy,” said study author David J. Mooney, PhD, of the Harvard School of Engineering and Applied Sciences in Boston.
“We have shown that we can use the hydrogels repeatedly and turn the drug pulses on and off at will, and that the drug bursts in concert with the baseline low-level drug delivery seems to be particularly effective in killing cancer cells.”
Self-healing hydrogel
Key to the researchers’ success in designing a hydrogel that self-heals was choosing the right kind of hydrogel with the right kind of drug and applying the right intensity of ultrasound.
“We were able to trigger our system with a level of ultrasound that was much lower than high-intensity focused ultrasound that is used clinically to heat and destroy tumors,” said study author Cathal Kearney, PhD, of the Royal College of Surgeons in Ireland. “The careful selection of materials and properties make it a reversible process.”
The team carried out the majority of their work for this study with a gel made out of alginate, a natural polysaccharide from algae that is held together with calcium ions.
In a series of tests, they found that, with the right level of ultrasound, the bonds break up and enable the gel to release its drug cargo. But as long as the gel is in the presence of more calcium, the bonds reform and the gel self-heals.
Drug testing
Once the researchers knew the gel would self-heal, they tested out a drug they suspected it would hold well: the chemotherapy drug mitoxantrone.
Sure enough, the ultrasound triggered the gel to release the blue-colored drug, as indicated by the newly blue color of the surrounding medium. Just a single ultrasound dose was effective, and the gel reformed after it was disrupted, making multiple cycles possible.
Next, the team tested the treatment in mouse models of breast cancer. They injected the drug-laden gel close to the tumors.
Over the course of 6 months, the mice that received a low-level, sustained release of the drug with a daily concentrated pulse of ultrasound (2.5 minutes) fared significantly better than mice treated the same but without ultrasound.
In contrast to controls, the tumors in the ultrasound-treated mice did not grow substantially. And the mice survived for an additional 80 days.
Potential applications
The researchers believe their technique could help improve cancer treatment and other therapies requiring drugs to be delivered at the right place and the right time—from post-surgery pain medications to protein-based drugs that require daily injections.
It requires an initial injection of the hydrogel, but the approach could be a much less traumatic, minimally invasive, and more effective method of drug delivery than current methods, Dr Mooney said.
The researchers also found their hydrogel can release cargo other than drugs, including proteins and condensed plasmid DNA. This lays the groundwork for using these hydrogels for tissue regeneration and gene therapy.
Dr Mooney said he and his colleagues plan to explore these potential applications, as well as the possibility of unleashing 2 different drugs independently from the same hydrogel.
Credit: Kathy Atkinson
Researchers have devised a novel way to deliver chemotherapy drugs “on demand,” according to a paper published in Proceedings of the National Academy of Sciences.
The team loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release the drug.
Like many other injectable gels, this one gradually releases a low level of the drug by diffusion over time. But the new hydrogel differs from others in a key way.
Researchers previously applied ultrasound to gels to temporarily increase doses of drug, but that approach was a one-shot deal, as the ultrasound was used to destroy those gels.
In the current study, the researchers used ultrasound to temporarily disrupt the gel so that it released short, high-dose bursts of the drug. But when they stopped the ultrasound, the hydrogels self-healed.
By closing back up, they were ready to go for the next “on demand” drug burst, providing a way to administer drugs with a greater level of control than was possible before.
The researchers also demonstrated in lab cultures and in mouse models of breast cancer that the pulsed, ultrasound-triggered hydrogel approach to drug delivery was more effective at stopping the growth of tumor cells than traditional, sustained-release drug therapy.
“Our approach counters the whole idea of sustained drug release and offers a double whammy,” said study author David J. Mooney, PhD, of the Harvard School of Engineering and Applied Sciences in Boston.
“We have shown that we can use the hydrogels repeatedly and turn the drug pulses on and off at will, and that the drug bursts in concert with the baseline low-level drug delivery seems to be particularly effective in killing cancer cells.”
Self-healing hydrogel
Key to the researchers’ success in designing a hydrogel that self-heals was choosing the right kind of hydrogel with the right kind of drug and applying the right intensity of ultrasound.
“We were able to trigger our system with a level of ultrasound that was much lower than high-intensity focused ultrasound that is used clinically to heat and destroy tumors,” said study author Cathal Kearney, PhD, of the Royal College of Surgeons in Ireland. “The careful selection of materials and properties make it a reversible process.”
The team carried out the majority of their work for this study with a gel made out of alginate, a natural polysaccharide from algae that is held together with calcium ions.
In a series of tests, they found that, with the right level of ultrasound, the bonds break up and enable the gel to release its drug cargo. But as long as the gel is in the presence of more calcium, the bonds reform and the gel self-heals.
Drug testing
Once the researchers knew the gel would self-heal, they tested out a drug they suspected it would hold well: the chemotherapy drug mitoxantrone.
Sure enough, the ultrasound triggered the gel to release the blue-colored drug, as indicated by the newly blue color of the surrounding medium. Just a single ultrasound dose was effective, and the gel reformed after it was disrupted, making multiple cycles possible.
Next, the team tested the treatment in mouse models of breast cancer. They injected the drug-laden gel close to the tumors.
Over the course of 6 months, the mice that received a low-level, sustained release of the drug with a daily concentrated pulse of ultrasound (2.5 minutes) fared significantly better than mice treated the same but without ultrasound.
In contrast to controls, the tumors in the ultrasound-treated mice did not grow substantially. And the mice survived for an additional 80 days.
Potential applications
The researchers believe their technique could help improve cancer treatment and other therapies requiring drugs to be delivered at the right place and the right time—from post-surgery pain medications to protein-based drugs that require daily injections.
It requires an initial injection of the hydrogel, but the approach could be a much less traumatic, minimally invasive, and more effective method of drug delivery than current methods, Dr Mooney said.
The researchers also found their hydrogel can release cargo other than drugs, including proteins and condensed plasmid DNA. This lays the groundwork for using these hydrogels for tissue regeneration and gene therapy.
Dr Mooney said he and his colleagues plan to explore these potential applications, as well as the possibility of unleashing 2 different drugs independently from the same hydrogel.
Credit: Kathy Atkinson
Researchers have devised a novel way to deliver chemotherapy drugs “on demand,” according to a paper published in Proceedings of the National Academy of Sciences.
The team loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release the drug.
Like many other injectable gels, this one gradually releases a low level of the drug by diffusion over time. But the new hydrogel differs from others in a key way.
Researchers previously applied ultrasound to gels to temporarily increase doses of drug, but that approach was a one-shot deal, as the ultrasound was used to destroy those gels.
In the current study, the researchers used ultrasound to temporarily disrupt the gel so that it released short, high-dose bursts of the drug. But when they stopped the ultrasound, the hydrogels self-healed.
By closing back up, they were ready to go for the next “on demand” drug burst, providing a way to administer drugs with a greater level of control than was possible before.
The researchers also demonstrated in lab cultures and in mouse models of breast cancer that the pulsed, ultrasound-triggered hydrogel approach to drug delivery was more effective at stopping the growth of tumor cells than traditional, sustained-release drug therapy.
“Our approach counters the whole idea of sustained drug release and offers a double whammy,” said study author David J. Mooney, PhD, of the Harvard School of Engineering and Applied Sciences in Boston.
“We have shown that we can use the hydrogels repeatedly and turn the drug pulses on and off at will, and that the drug bursts in concert with the baseline low-level drug delivery seems to be particularly effective in killing cancer cells.”
Self-healing hydrogel
Key to the researchers’ success in designing a hydrogel that self-heals was choosing the right kind of hydrogel with the right kind of drug and applying the right intensity of ultrasound.
“We were able to trigger our system with a level of ultrasound that was much lower than high-intensity focused ultrasound that is used clinically to heat and destroy tumors,” said study author Cathal Kearney, PhD, of the Royal College of Surgeons in Ireland. “The careful selection of materials and properties make it a reversible process.”
The team carried out the majority of their work for this study with a gel made out of alginate, a natural polysaccharide from algae that is held together with calcium ions.
In a series of tests, they found that, with the right level of ultrasound, the bonds break up and enable the gel to release its drug cargo. But as long as the gel is in the presence of more calcium, the bonds reform and the gel self-heals.
Drug testing
Once the researchers knew the gel would self-heal, they tested out a drug they suspected it would hold well: the chemotherapy drug mitoxantrone.
Sure enough, the ultrasound triggered the gel to release the blue-colored drug, as indicated by the newly blue color of the surrounding medium. Just a single ultrasound dose was effective, and the gel reformed after it was disrupted, making multiple cycles possible.
Next, the team tested the treatment in mouse models of breast cancer. They injected the drug-laden gel close to the tumors.
Over the course of 6 months, the mice that received a low-level, sustained release of the drug with a daily concentrated pulse of ultrasound (2.5 minutes) fared significantly better than mice treated the same but without ultrasound.
In contrast to controls, the tumors in the ultrasound-treated mice did not grow substantially. And the mice survived for an additional 80 days.
Potential applications
The researchers believe their technique could help improve cancer treatment and other therapies requiring drugs to be delivered at the right place and the right time—from post-surgery pain medications to protein-based drugs that require daily injections.
It requires an initial injection of the hydrogel, but the approach could be a much less traumatic, minimally invasive, and more effective method of drug delivery than current methods, Dr Mooney said.
The researchers also found their hydrogel can release cargo other than drugs, including proteins and condensed plasmid DNA. This lays the groundwork for using these hydrogels for tissue regeneration and gene therapy.
Dr Mooney said he and his colleagues plan to explore these potential applications, as well as the possibility of unleashing 2 different drugs independently from the same hydrogel.
Team reports new method of chemo delivery
Credit: Kathy Atkinson
Researchers have devised a novel way to deliver chemotherapy drugs “on demand,” according to a paper published in Proceedings of the National Academy of Sciences.
The team loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release the drug.
Like many other injectable gels, this one gradually releases a low level of the drug by diffusion over time. But the new hydrogel differs from others in a key way.
Researchers previously applied ultrasound to gels to temporarily increase doses of drug, but that approach was a one-shot deal, as the ultrasound was used to destroy those gels.
In the current study, the researchers used ultrasound to temporarily disrupt the gel so that it released short, high-dose bursts of the drug. But when they stopped the ultrasound, the hydrogels self-healed.
By closing back up, they were ready to go for the next “on demand” drug burst, providing a way to administer drugs with a greater level of control than was possible before.
The researchers also demonstrated in lab cultures and in mouse models of breast cancer that the pulsed, ultrasound-triggered hydrogel approach to drug delivery was more effective at stopping the growth of tumor cells than traditional, sustained-release drug therapy.
“Our approach counters the whole idea of sustained drug release and offers a double whammy,” said study author David J. Mooney, PhD, of the Harvard School of Engineering and Applied Sciences in Boston.
“We have shown that we can use the hydrogels repeatedly and turn the drug pulses on and off at will, and that the drug bursts in concert with the baseline low-level drug delivery seems to be particularly effective in killing cancer cells.”
Self-healing hydrogel
Key to the researchers’ success in designing a hydrogel that self-heals was choosing the right kind of hydrogel with the right kind of drug and applying the right intensity of ultrasound.
“We were able to trigger our system with a level of ultrasound that was much lower than high-intensity focused ultrasound that is used clinically to heat and destroy tumors,” said study author Cathal Kearney, PhD, of the Royal College of Surgeons in Ireland. “The careful selection of materials and properties make it a reversible process.”
The team carried out the majority of their work for this study with a gel made out of alginate, a natural polysaccharide from algae that is held together with calcium ions.
In a series of tests, they found that, with the right level of ultrasound, the bonds break up and enable the gel to release its drug cargo. But as long as the gel is in the presence of more calcium, the bonds reform and the gel self-heals.
Drug testing
Once the researchers knew the gel would self-heal, they tested out a drug they suspected it would hold well: the chemotherapy drug mitoxantrone.
Sure enough, the ultrasound triggered the gel to release the blue-colored drug, as indicated by the newly blue color of the surrounding medium. Just a single ultrasound dose was effective, and the gel reformed after it was disrupted, making multiple cycles possible.
Next, the team tested the treatment in mouse models of breast cancer. They injected the drug-laden gel close to the tumors.
Over the course of 6 months, the mice that received a low-level, sustained release of the drug with a daily concentrated pulse of ultrasound (2.5 minutes) fared significantly better than mice treated the same but without ultrasound.
In contrast to controls, the tumors in the ultrasound-treated mice did not grow substantially. And the mice survived for an additional 80 days.
Potential applications
The researchers believe their technique could help improve cancer treatment and other therapies requiring drugs to be delivered at the right place and the right time—from post-surgery pain medications to protein-based drugs that require daily injections.
It requires an initial injection of the hydrogel, but the approach could be a much less traumatic, minimally invasive, and more effective method of drug delivery than current methods, Dr Mooney said.
The researchers also found their hydrogel can release cargo other than drugs, including proteins and condensed plasmid DNA. This lays the groundwork for using these hydrogels for tissue regeneration and gene therapy.
Dr Mooney said he and his colleagues plan to explore these potential applications, as well as the possibility of unleashing 2 different drugs independently from the same hydrogel.
Credit: Kathy Atkinson
Researchers have devised a novel way to deliver chemotherapy drugs “on demand,” according to a paper published in Proceedings of the National Academy of Sciences.
The team loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release the drug.
Like many other injectable gels, this one gradually releases a low level of the drug by diffusion over time. But the new hydrogel differs from others in a key way.
Researchers previously applied ultrasound to gels to temporarily increase doses of drug, but that approach was a one-shot deal, as the ultrasound was used to destroy those gels.
In the current study, the researchers used ultrasound to temporarily disrupt the gel so that it released short, high-dose bursts of the drug. But when they stopped the ultrasound, the hydrogels self-healed.
By closing back up, they were ready to go for the next “on demand” drug burst, providing a way to administer drugs with a greater level of control than was possible before.
The researchers also demonstrated in lab cultures and in mouse models of breast cancer that the pulsed, ultrasound-triggered hydrogel approach to drug delivery was more effective at stopping the growth of tumor cells than traditional, sustained-release drug therapy.
“Our approach counters the whole idea of sustained drug release and offers a double whammy,” said study author David J. Mooney, PhD, of the Harvard School of Engineering and Applied Sciences in Boston.
“We have shown that we can use the hydrogels repeatedly and turn the drug pulses on and off at will, and that the drug bursts in concert with the baseline low-level drug delivery seems to be particularly effective in killing cancer cells.”
Self-healing hydrogel
Key to the researchers’ success in designing a hydrogel that self-heals was choosing the right kind of hydrogel with the right kind of drug and applying the right intensity of ultrasound.
“We were able to trigger our system with a level of ultrasound that was much lower than high-intensity focused ultrasound that is used clinically to heat and destroy tumors,” said study author Cathal Kearney, PhD, of the Royal College of Surgeons in Ireland. “The careful selection of materials and properties make it a reversible process.”
The team carried out the majority of their work for this study with a gel made out of alginate, a natural polysaccharide from algae that is held together with calcium ions.
In a series of tests, they found that, with the right level of ultrasound, the bonds break up and enable the gel to release its drug cargo. But as long as the gel is in the presence of more calcium, the bonds reform and the gel self-heals.
Drug testing
Once the researchers knew the gel would self-heal, they tested out a drug they suspected it would hold well: the chemotherapy drug mitoxantrone.
Sure enough, the ultrasound triggered the gel to release the blue-colored drug, as indicated by the newly blue color of the surrounding medium. Just a single ultrasound dose was effective, and the gel reformed after it was disrupted, making multiple cycles possible.
Next, the team tested the treatment in mouse models of breast cancer. They injected the drug-laden gel close to the tumors.
Over the course of 6 months, the mice that received a low-level, sustained release of the drug with a daily concentrated pulse of ultrasound (2.5 minutes) fared significantly better than mice treated the same but without ultrasound.
In contrast to controls, the tumors in the ultrasound-treated mice did not grow substantially. And the mice survived for an additional 80 days.
Potential applications
The researchers believe their technique could help improve cancer treatment and other therapies requiring drugs to be delivered at the right place and the right time—from post-surgery pain medications to protein-based drugs that require daily injections.
It requires an initial injection of the hydrogel, but the approach could be a much less traumatic, minimally invasive, and more effective method of drug delivery than current methods, Dr Mooney said.
The researchers also found their hydrogel can release cargo other than drugs, including proteins and condensed plasmid DNA. This lays the groundwork for using these hydrogels for tissue regeneration and gene therapy.
Dr Mooney said he and his colleagues plan to explore these potential applications, as well as the possibility of unleashing 2 different drugs independently from the same hydrogel.
Credit: Kathy Atkinson
Researchers have devised a novel way to deliver chemotherapy drugs “on demand,” according to a paper published in Proceedings of the National Academy of Sciences.
The team loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release the drug.
Like many other injectable gels, this one gradually releases a low level of the drug by diffusion over time. But the new hydrogel differs from others in a key way.
Researchers previously applied ultrasound to gels to temporarily increase doses of drug, but that approach was a one-shot deal, as the ultrasound was used to destroy those gels.
In the current study, the researchers used ultrasound to temporarily disrupt the gel so that it released short, high-dose bursts of the drug. But when they stopped the ultrasound, the hydrogels self-healed.
By closing back up, they were ready to go for the next “on demand” drug burst, providing a way to administer drugs with a greater level of control than was possible before.
The researchers also demonstrated in lab cultures and in mouse models of breast cancer that the pulsed, ultrasound-triggered hydrogel approach to drug delivery was more effective at stopping the growth of tumor cells than traditional, sustained-release drug therapy.
“Our approach counters the whole idea of sustained drug release and offers a double whammy,” said study author David J. Mooney, PhD, of the Harvard School of Engineering and Applied Sciences in Boston.
“We have shown that we can use the hydrogels repeatedly and turn the drug pulses on and off at will, and that the drug bursts in concert with the baseline low-level drug delivery seems to be particularly effective in killing cancer cells.”
Self-healing hydrogel
Key to the researchers’ success in designing a hydrogel that self-heals was choosing the right kind of hydrogel with the right kind of drug and applying the right intensity of ultrasound.
“We were able to trigger our system with a level of ultrasound that was much lower than high-intensity focused ultrasound that is used clinically to heat and destroy tumors,” said study author Cathal Kearney, PhD, of the Royal College of Surgeons in Ireland. “The careful selection of materials and properties make it a reversible process.”
The team carried out the majority of their work for this study with a gel made out of alginate, a natural polysaccharide from algae that is held together with calcium ions.
In a series of tests, they found that, with the right level of ultrasound, the bonds break up and enable the gel to release its drug cargo. But as long as the gel is in the presence of more calcium, the bonds reform and the gel self-heals.
Drug testing
Once the researchers knew the gel would self-heal, they tested out a drug they suspected it would hold well: the chemotherapy drug mitoxantrone.
Sure enough, the ultrasound triggered the gel to release the blue-colored drug, as indicated by the newly blue color of the surrounding medium. Just a single ultrasound dose was effective, and the gel reformed after it was disrupted, making multiple cycles possible.
Next, the team tested the treatment in mouse models of breast cancer. They injected the drug-laden gel close to the tumors.
Over the course of 6 months, the mice that received a low-level, sustained release of the drug with a daily concentrated pulse of ultrasound (2.5 minutes) fared significantly better than mice treated the same but without ultrasound.
In contrast to controls, the tumors in the ultrasound-treated mice did not grow substantially. And the mice survived for an additional 80 days.
Potential applications
The researchers believe their technique could help improve cancer treatment and other therapies requiring drugs to be delivered at the right place and the right time—from post-surgery pain medications to protein-based drugs that require daily injections.
It requires an initial injection of the hydrogel, but the approach could be a much less traumatic, minimally invasive, and more effective method of drug delivery than current methods, Dr Mooney said.
The researchers also found their hydrogel can release cargo other than drugs, including proteins and condensed plasmid DNA. This lays the groundwork for using these hydrogels for tissue regeneration and gene therapy.
Dr Mooney said he and his colleagues plan to explore these potential applications, as well as the possibility of unleashing 2 different drugs independently from the same hydrogel.
Risk of Vehicle Accidents for Returning Military
Motor vehicle crashes (MVCs) account for almost one-third of deaths among service members every year. One study showed that within 6 months after deployment, military personnel had a 13% increase in at-fault accidents.
Using data from the Millennium Cohort Study and the Military Health System Data Repository, researchers from the Naval Health Research Center in San Diego, California, investigated possible risk factors.The researchers looked at both demographic and military-specific data, including service branch, health status (such as hearing loss and hours of sleep), and whether the individual had been diagnosed with depression, pain, or anxiety.
Of the 13,620 service members included in the study, 6,800 reported combat experiences; 107 had a MVC within 6 months following deployment.
Service members who had an MVC within 6 months postdeployment were more likely to report combat experiences, have more than one deployment, and be deployed for more than 365 cumulative days. Women, service members born after 1980, enlisted rank, African Americans, and those with baseline physical health symptoms and problem drinking were among those at greater risk. After adjusting for all variables, combat experiences nearly doubled the risk, and 3 or more deployments nearly tripled the risk of a MVC in the 6 months after deployment.
The researchers did not find an association between physical health symptoms, such as hearing loss, headache, or confusion, and MVCs, nor did they find a link between mental health symptoms and the severity of scores. That suggests that physical and mental health may not be the primary contributors to the association. In fact, the researchers say, the link between deployment and crashes may be multifactorial. For instance, service members may engage in risky driving behavior to recreate the emotions felt during combat. Although this study did not include questions about the use of seat belts, alcohol while driving, speeding, or other risk-taking behaviors, the researchers point to other studies that say that military personnel may not wear seat belts and may speed because that is what they got used to during deployment. The researchers also say that those who have participated in military combat may be inherent risk takers.
Multiple deployments, the researchers suggest, may instill “greater levels of risky driving behaviors that accumulate over time.” Length of deployment was not as crucial, which may mean that returning home more frequently puts service members in the driver’s seat more often.
The data suggest that a critical “window of time” may exist for preventing MVCs among the recently deployed. The researchers advocate intervention strategies early in the transition home.
Source
Woodall KA, Jacobson IG, Crum-Cianflone NF. Am J Prev Med. 2014;46(4):350–358.
doi: 10.1016/j.amepre.2013.11.015.
Motor vehicle crashes (MVCs) account for almost one-third of deaths among service members every year. One study showed that within 6 months after deployment, military personnel had a 13% increase in at-fault accidents.
Using data from the Millennium Cohort Study and the Military Health System Data Repository, researchers from the Naval Health Research Center in San Diego, California, investigated possible risk factors.The researchers looked at both demographic and military-specific data, including service branch, health status (such as hearing loss and hours of sleep), and whether the individual had been diagnosed with depression, pain, or anxiety.
Of the 13,620 service members included in the study, 6,800 reported combat experiences; 107 had a MVC within 6 months following deployment.
Service members who had an MVC within 6 months postdeployment were more likely to report combat experiences, have more than one deployment, and be deployed for more than 365 cumulative days. Women, service members born after 1980, enlisted rank, African Americans, and those with baseline physical health symptoms and problem drinking were among those at greater risk. After adjusting for all variables, combat experiences nearly doubled the risk, and 3 or more deployments nearly tripled the risk of a MVC in the 6 months after deployment.
The researchers did not find an association between physical health symptoms, such as hearing loss, headache, or confusion, and MVCs, nor did they find a link between mental health symptoms and the severity of scores. That suggests that physical and mental health may not be the primary contributors to the association. In fact, the researchers say, the link between deployment and crashes may be multifactorial. For instance, service members may engage in risky driving behavior to recreate the emotions felt during combat. Although this study did not include questions about the use of seat belts, alcohol while driving, speeding, or other risk-taking behaviors, the researchers point to other studies that say that military personnel may not wear seat belts and may speed because that is what they got used to during deployment. The researchers also say that those who have participated in military combat may be inherent risk takers.
Multiple deployments, the researchers suggest, may instill “greater levels of risky driving behaviors that accumulate over time.” Length of deployment was not as crucial, which may mean that returning home more frequently puts service members in the driver’s seat more often.
The data suggest that a critical “window of time” may exist for preventing MVCs among the recently deployed. The researchers advocate intervention strategies early in the transition home.
Source
Woodall KA, Jacobson IG, Crum-Cianflone NF. Am J Prev Med. 2014;46(4):350–358.
doi: 10.1016/j.amepre.2013.11.015.
Motor vehicle crashes (MVCs) account for almost one-third of deaths among service members every year. One study showed that within 6 months after deployment, military personnel had a 13% increase in at-fault accidents.
Using data from the Millennium Cohort Study and the Military Health System Data Repository, researchers from the Naval Health Research Center in San Diego, California, investigated possible risk factors.The researchers looked at both demographic and military-specific data, including service branch, health status (such as hearing loss and hours of sleep), and whether the individual had been diagnosed with depression, pain, or anxiety.
Of the 13,620 service members included in the study, 6,800 reported combat experiences; 107 had a MVC within 6 months following deployment.
Service members who had an MVC within 6 months postdeployment were more likely to report combat experiences, have more than one deployment, and be deployed for more than 365 cumulative days. Women, service members born after 1980, enlisted rank, African Americans, and those with baseline physical health symptoms and problem drinking were among those at greater risk. After adjusting for all variables, combat experiences nearly doubled the risk, and 3 or more deployments nearly tripled the risk of a MVC in the 6 months after deployment.
The researchers did not find an association between physical health symptoms, such as hearing loss, headache, or confusion, and MVCs, nor did they find a link between mental health symptoms and the severity of scores. That suggests that physical and mental health may not be the primary contributors to the association. In fact, the researchers say, the link between deployment and crashes may be multifactorial. For instance, service members may engage in risky driving behavior to recreate the emotions felt during combat. Although this study did not include questions about the use of seat belts, alcohol while driving, speeding, or other risk-taking behaviors, the researchers point to other studies that say that military personnel may not wear seat belts and may speed because that is what they got used to during deployment. The researchers also say that those who have participated in military combat may be inherent risk takers.
Multiple deployments, the researchers suggest, may instill “greater levels of risky driving behaviors that accumulate over time.” Length of deployment was not as crucial, which may mean that returning home more frequently puts service members in the driver’s seat more often.
The data suggest that a critical “window of time” may exist for preventing MVCs among the recently deployed. The researchers advocate intervention strategies early in the transition home.
Source
Woodall KA, Jacobson IG, Crum-Cianflone NF. Am J Prev Med. 2014;46(4):350–358.
doi: 10.1016/j.amepre.2013.11.015.
Predicting problems in families of cancer patients
Credit: Rhoda Baer
A new analysis suggests family dysfunction is the greatest predictor of emotional and behavioral problems among children who have a parent with cancer.
Other variables, such as the child’s age, did not predict the risk as accurately.
And illness-related factors, such as the parent’s prognosis, did not appear to have an impact at all.
Birgit Möller, PhD, of the University Medical Center Hamburg-Eppendorf in Germany, and her colleagues reported these findings in Cancer.
The researchers evaluated 235 families in which at least 1 parent was diagnosed with cancer. This included 402 parents and 324 children aged 11 to 21 years. Parents and children completed questionnaires that assessed emotional and behavioral health.
Responses suggested that children of cancer patients have higher-than-average levels of emotional and behavioral symptoms.
The overall mean values for emotional and behavioral problems—from both the parents’ and children’s perspectives—were significantly higher in the study population than the average values from a representative non-cancer population.
General family functioning was the strongest predictor of children’s symptom status from both the parents’ and child’s perspectives.
The effects of the child’s age and gender on behavioral and emotional symptoms varied according to the subject asked. But none of the respondents reported an association between child adjustment and illness-related factors such as poor prognoses or recurrent illness.
Dr Möller noted that screening for child mental health problems, family dysfunction, and parental depression can be easily adopted into cancer care so that families in need of support can be identified.
“Additional training of oncologists, interdisciplinary approaches, and family-based mental health liaison services are recommended to meet the needs of minor
children and their families and to minimize negative long-term effects in children,” she said.
Dr Möller and her team have developed a preventive counseling program—called the Children of Somatically Ill Parents (COSIP) program—that focuses on family communication, involvement of family members, flexible problem solving, mutual support, and parenting issues.
Credit: Rhoda Baer
A new analysis suggests family dysfunction is the greatest predictor of emotional and behavioral problems among children who have a parent with cancer.
Other variables, such as the child’s age, did not predict the risk as accurately.
And illness-related factors, such as the parent’s prognosis, did not appear to have an impact at all.
Birgit Möller, PhD, of the University Medical Center Hamburg-Eppendorf in Germany, and her colleagues reported these findings in Cancer.
The researchers evaluated 235 families in which at least 1 parent was diagnosed with cancer. This included 402 parents and 324 children aged 11 to 21 years. Parents and children completed questionnaires that assessed emotional and behavioral health.
Responses suggested that children of cancer patients have higher-than-average levels of emotional and behavioral symptoms.
The overall mean values for emotional and behavioral problems—from both the parents’ and children’s perspectives—were significantly higher in the study population than the average values from a representative non-cancer population.
General family functioning was the strongest predictor of children’s symptom status from both the parents’ and child’s perspectives.
The effects of the child’s age and gender on behavioral and emotional symptoms varied according to the subject asked. But none of the respondents reported an association between child adjustment and illness-related factors such as poor prognoses or recurrent illness.
Dr Möller noted that screening for child mental health problems, family dysfunction, and parental depression can be easily adopted into cancer care so that families in need of support can be identified.
“Additional training of oncologists, interdisciplinary approaches, and family-based mental health liaison services are recommended to meet the needs of minor
children and their families and to minimize negative long-term effects in children,” she said.
Dr Möller and her team have developed a preventive counseling program—called the Children of Somatically Ill Parents (COSIP) program—that focuses on family communication, involvement of family members, flexible problem solving, mutual support, and parenting issues.
Credit: Rhoda Baer
A new analysis suggests family dysfunction is the greatest predictor of emotional and behavioral problems among children who have a parent with cancer.
Other variables, such as the child’s age, did not predict the risk as accurately.
And illness-related factors, such as the parent’s prognosis, did not appear to have an impact at all.
Birgit Möller, PhD, of the University Medical Center Hamburg-Eppendorf in Germany, and her colleagues reported these findings in Cancer.
The researchers evaluated 235 families in which at least 1 parent was diagnosed with cancer. This included 402 parents and 324 children aged 11 to 21 years. Parents and children completed questionnaires that assessed emotional and behavioral health.
Responses suggested that children of cancer patients have higher-than-average levels of emotional and behavioral symptoms.
The overall mean values for emotional and behavioral problems—from both the parents’ and children’s perspectives—were significantly higher in the study population than the average values from a representative non-cancer population.
General family functioning was the strongest predictor of children’s symptom status from both the parents’ and child’s perspectives.
The effects of the child’s age and gender on behavioral and emotional symptoms varied according to the subject asked. But none of the respondents reported an association between child adjustment and illness-related factors such as poor prognoses or recurrent illness.
Dr Möller noted that screening for child mental health problems, family dysfunction, and parental depression can be easily adopted into cancer care so that families in need of support can be identified.
“Additional training of oncologists, interdisciplinary approaches, and family-based mental health liaison services are recommended to meet the needs of minor
children and their families and to minimize negative long-term effects in children,” she said.
Dr Möller and her team have developed a preventive counseling program—called the Children of Somatically Ill Parents (COSIP) program—that focuses on family communication, involvement of family members, flexible problem solving, mutual support, and parenting issues.