MDedge Surgery

The family of a man who died from a rare and feared complication of head and neck cancer has filed a $34 million lawsuit against the medical center where he was treated, alleging that his death would have been avoided had there been better communication between the surgical oncologist and the treatment team.

The patient was a 49-year-old man who was experiencing chronic pain in his right ear. He saw a local ear, nose, and throat specialist, who could find no apparent cause after conducting a physical exam.

A CT scan revealed a 1.4-cm mass in the right pharyngeal space. A 1.6-cm lymph node in the right retropharyngeal/parapharyngeal carotid space was affected.

The following week, the patient underwent a positron-emission tomography scan and was subsequently referred to a head and neck surgical oncologist.

The surgeon performed a right radical tonsillectomy and pharyngectomy. During the surgery, the patient experienced significant bleeding complications. The surgeon was able to remove the tonsillar mass but could not resect the affected lymph node, owing to its proximity to the carotid artery. The affected lymph node was not removed, and the patient was informed that the problem would be addressed at another time.

Pathology revealed stage III squamous cell carcinoma (T3N0M0) that was HPV/p16 positive.

According to the lawsuit, which was reported in Expert Witness Newsletter, a critical error occurred.

The surgical oncologist apparently did not clearly communicate the situation to the rest of the clinicians involved in the patient’s care. The patient was treated as if the entire cancer had been surgically resected. He never underwent follow-up surgery to address the enlarged lymph node.

Because the care team believed that the patient had undergone a complete surgical resection, follow-up treatment consisted of radiotherapy without concurrent chemotherapy.

The patient underwent radiotherapy to a dose of 60 Gy over 30 treatment days.

About 5 months later, the patient once again presented with ear pain on the right side and difficulty speaking. Imaging showed that there was recurrence of a mass in his right parapharyngeal carotid space. Biopsy results indicated recurrent/progressive squamous cell carcinoma. The patient underwent a second round of radiotherapy. This time, he received concurrent chemotherapy.

Four months later, the patient presented to the emergency department complaining of episodes of syncope. Imaging revealed that the mass in his right parapharyngeal carotid space had increased in size, causing carotid stenosis. The patient was hospitalized for 4 days and was treated with steroids. The day after his discharge, he died at home.
 

Carotid blowout syndrome due to negligence

An autopsy was performed, and the cause of death was determined to be an acute massive bleed secondary to perforation of the right artery, which was “encased by a partially necrotic poorly differentiated squamous cell carcinoma.” This is known as carotid blowout syndrome.

After his death, the patient’s family contacted an attorney, who hired several expert witnesses to review the case. The alleged negligence by the head and neck oncologist was described as follows:

• There was a failure to appropriately assess the patient’s neck anatomy, and the entire tumor was not surgically removed.
• Frank disease tissue was left behind, and the disease subsequently progressed.
• The surgery was never completed; the cancer progressed and ultimately took the patient’s life.
• There was a failure to communicate the fact that the cancer had not been completely resected.

The alleged negligence by the radiation oncologist was described as follows:

• There was a failure to realize that the tumor had not been completely resected.
• The patient was given a suboptimal radiation dose of 60 Gy, which would have been appropriate only had the tumor been completely resected.
• There was a failure to give a radiation dose of 70 Gy (ie, the appropriate dose for remaining tumor).

The medical oncologist was alleged to have been negligent because chemotherapy was not given when indicated.
 

Very high stakes

None of the treating physicians were named in the lawsuit. Only the medical center where the treatment was given was named. The center is affiliated with an Ivy League university.

The patient was an extremely wealthy man who had worked as an insurance executive and investor. His premature death resulted in the loss of a massive amount of earnings, and the plaintiffs asked for a sum of $34 million as compensation. Because doctors do not carry insurance sufficient to cover that amount and generally do not have personal assets of that amount, the plaintiff targeted the hospital.

“The plaintiff knows that the physicians will never be able to pay an 8-figure settlement, so instead they go after the hospital itself,” says the newsletter. “The physicians simply become pawns in a protracted legal game.”

The lawsuit was settled out of court in 2021 for an undisclosed amount.

A version of this article first appeared on Medscape.com.

The family of a man who died from a rare and feared complication of head and neck cancer has filed a $34 million lawsuit against the medical center where he was treated, alleging that his death would have been avoided had there been better communication between the surgical oncologist and the treatment team.

The patient was a 49-year-old man who was experiencing chronic pain in his right ear. He saw a local ear, nose, and throat specialist, who could find no apparent cause after conducting a physical exam.

A CT scan revealed a 1.4-cm mass in the right pharyngeal space. A 1.6-cm lymph node in the right retropharyngeal/parapharyngeal carotid space was affected.

The following week, the patient underwent a positron-emission tomography scan and was subsequently referred to a head and neck surgical oncologist.

The surgeon performed a right radical tonsillectomy and pharyngectomy. During the surgery, the patient experienced significant bleeding complications. The surgeon was able to remove the tonsillar mass but could not resect the affected lymph node, owing to its proximity to the carotid artery. The affected lymph node was not removed, and the patient was informed that the problem would be addressed at another time.

Pathology revealed stage III squamous cell carcinoma (T3N0M0) that was HPV/p16 positive.

According to the lawsuit, which was reported in Expert Witness Newsletter, a critical error occurred.

The surgical oncologist apparently did not clearly communicate the situation to the rest of the clinicians involved in the patient’s care. The patient was treated as if the entire cancer had been surgically resected. He never underwent follow-up surgery to address the enlarged lymph node.

Because the care team believed that the patient had undergone a complete surgical resection, follow-up treatment consisted of radiotherapy without concurrent chemotherapy.

The patient underwent radiotherapy to a dose of 60 Gy over 30 treatment days.

About 5 months later, the patient once again presented with ear pain on the right side and difficulty speaking. Imaging showed that there was recurrence of a mass in his right parapharyngeal carotid space. Biopsy results indicated recurrent/progressive squamous cell carcinoma. The patient underwent a second round of radiotherapy. This time, he received concurrent chemotherapy.

Four months later, the patient presented to the emergency department complaining of episodes of syncope. Imaging revealed that the mass in his right parapharyngeal carotid space had increased in size, causing carotid stenosis. The patient was hospitalized for 4 days and was treated with steroids. The day after his discharge, he died at home.
 

Carotid blowout syndrome due to negligence

An autopsy was performed, and the cause of death was determined to be an acute massive bleed secondary to perforation of the right artery, which was “encased by a partially necrotic poorly differentiated squamous cell carcinoma.” This is known as carotid blowout syndrome.

After his death, the patient’s family contacted an attorney, who hired several expert witnesses to review the case. The alleged negligence by the head and neck oncologist was described as follows:

• There was a failure to appropriately assess the patient’s neck anatomy, and the entire tumor was not surgically removed.
• Frank disease tissue was left behind, and the disease subsequently progressed.
• The surgery was never completed; the cancer progressed and ultimately took the patient’s life.
• There was a failure to communicate the fact that the cancer had not been completely resected.

The alleged negligence by the radiation oncologist was described as follows:

• There was a failure to realize that the tumor had not been completely resected.
• The patient was given a suboptimal radiation dose of 60 Gy, which would have been appropriate only had the tumor been completely resected.
• There was a failure to give a radiation dose of 70 Gy (ie, the appropriate dose for remaining tumor).

The medical oncologist was alleged to have been negligent because chemotherapy was not given when indicated.
 

Very high stakes

None of the treating physicians were named in the lawsuit. Only the medical center where the treatment was given was named. The center is affiliated with an Ivy League university.

The patient was an extremely wealthy man who had worked as an insurance executive and investor. His premature death resulted in the loss of a massive amount of earnings, and the plaintiffs asked for a sum of $34 million as compensation. Because doctors do not carry insurance sufficient to cover that amount and generally do not have personal assets of that amount, the plaintiff targeted the hospital.

“The plaintiff knows that the physicians will never be able to pay an 8-figure settlement, so instead they go after the hospital itself,” says the newsletter. “The physicians simply become pawns in a protracted legal game.”

The lawsuit was settled out of court in 2021 for an undisclosed amount.

A version of this article first appeared on Medscape.com.

The family of a man who died from a rare and feared complication of head and neck cancer has filed a $34 million lawsuit against the medical center where he was treated, alleging that his death would have been avoided had there been better communication between the surgical oncologist and the treatment team.

The patient was a 49-year-old man who was experiencing chronic pain in his right ear. He saw a local ear, nose, and throat specialist, who could find no apparent cause after conducting a physical exam.

A CT scan revealed a 1.4-cm mass in the right pharyngeal space. A 1.6-cm lymph node in the right retropharyngeal/parapharyngeal carotid space was affected.

The following week, the patient underwent a positron-emission tomography scan and was subsequently referred to a head and neck surgical oncologist.

The surgeon performed a right radical tonsillectomy and pharyngectomy. During the surgery, the patient experienced significant bleeding complications. The surgeon was able to remove the tonsillar mass but could not resect the affected lymph node, owing to its proximity to the carotid artery. The affected lymph node was not removed, and the patient was informed that the problem would be addressed at another time.

Pathology revealed stage III squamous cell carcinoma (T3N0M0) that was HPV/p16 positive.

According to the lawsuit, which was reported in Expert Witness Newsletter, a critical error occurred.

The surgical oncologist apparently did not clearly communicate the situation to the rest of the clinicians involved in the patient’s care. The patient was treated as if the entire cancer had been surgically resected. He never underwent follow-up surgery to address the enlarged lymph node.

Because the care team believed that the patient had undergone a complete surgical resection, follow-up treatment consisted of radiotherapy without concurrent chemotherapy.

The patient underwent radiotherapy to a dose of 60 Gy over 30 treatment days.

About 5 months later, the patient once again presented with ear pain on the right side and difficulty speaking. Imaging showed that there was recurrence of a mass in his right parapharyngeal carotid space. Biopsy results indicated recurrent/progressive squamous cell carcinoma. The patient underwent a second round of radiotherapy. This time, he received concurrent chemotherapy.

Four months later, the patient presented to the emergency department complaining of episodes of syncope. Imaging revealed that the mass in his right parapharyngeal carotid space had increased in size, causing carotid stenosis. The patient was hospitalized for 4 days and was treated with steroids. The day after his discharge, he died at home.
 

Carotid blowout syndrome due to negligence

An autopsy was performed, and the cause of death was determined to be an acute massive bleed secondary to perforation of the right artery, which was “encased by a partially necrotic poorly differentiated squamous cell carcinoma.” This is known as carotid blowout syndrome.

After his death, the patient’s family contacted an attorney, who hired several expert witnesses to review the case. The alleged negligence by the head and neck oncologist was described as follows:

• There was a failure to appropriately assess the patient’s neck anatomy, and the entire tumor was not surgically removed.
• Frank disease tissue was left behind, and the disease subsequently progressed.
• The surgery was never completed; the cancer progressed and ultimately took the patient’s life.
• There was a failure to communicate the fact that the cancer had not been completely resected.

The alleged negligence by the radiation oncologist was described as follows:

• There was a failure to realize that the tumor had not been completely resected.
• The patient was given a suboptimal radiation dose of 60 Gy, which would have been appropriate only had the tumor been completely resected.
• There was a failure to give a radiation dose of 70 Gy (ie, the appropriate dose for remaining tumor).

The medical oncologist was alleged to have been negligent because chemotherapy was not given when indicated.
 

Very high stakes

None of the treating physicians were named in the lawsuit. Only the medical center where the treatment was given was named. The center is affiliated with an Ivy League university.

The patient was an extremely wealthy man who had worked as an insurance executive and investor. His premature death resulted in the loss of a massive amount of earnings, and the plaintiffs asked for a sum of $34 million as compensation. Because doctors do not carry insurance sufficient to cover that amount and generally do not have personal assets of that amount, the plaintiff targeted the hospital.

“The plaintiff knows that the physicians will never be able to pay an 8-figure settlement, so instead they go after the hospital itself,” says the newsletter. “The physicians simply become pawns in a protracted legal game.”

The lawsuit was settled out of court in 2021 for an undisclosed amount.

A version of this article first appeared on Medscape.com.

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

To the Editor:

The tumor necrosis factor α inhibitor adalimumab is the only US Food and Drug Administration–approved treatment of hidradenitis suppurativa (HS). Although 50.6% of patients fulfilled Hidradenitis Suppurativa Clinical Response criteria with adalimumab at 12 weeks, many responders were not satisfied with their disease control, and secondary loss of Hidradenitis Suppurativa Clinical Response fulfillment occurred in 15.9% of patients within approximately 3 years.¹ Without other US Food and Drug Administration–approved HS treatments, some dermatologists have combined adalimumab with methotrexate (MTX) and/or mycophenolate mofetil (MMF) to attempt to increase the duration of satisfactory disease control while on adalimumab. Combining tumor necrosis factor α inhibitors with oral immunosuppressants is a well-established approach in psoriasis, psoriatic arthritis, and inflammatory bowel disease; however, to the best of our knowledge, this approach has not been studied for HS.^2,3

To assess whether there is a role for combining adalimumab with MTX and/or MMF in the treatment of HS, we performed a single-institution retrospective chart review at the University of Connecticut Department of Dermatology to determine whether patients receiving combination therapy stayed on adalimumab longer than those who received adalimumab monotherapy. All patients receiving adalimumab for the treatment of HS with at least 1 follow-up visit 3 or more months after treatment initiation were included. Duration of treatment with adalimumab was defined as the length of time between initiation and termination of adalimumab, regardless of flares, adverse events, or addition of adjuvant therapy that occurred during this time span. Because standardized rating scales measuring the severity of HS at this time are not recorded routinely at our institution, treatment duration with adalimumab was used as a surrogate for measuring therapeutic success. Additionally, treatment duration is a meaningful end point, as patients with HS may require indefinite treatment. Patients were eligible for inclusion if they were receiving adalimumab for the treatment of HS. Patients were excluded if they were lost to follow-up or had received adalimumab for less than 6 months, as data suggest that biologics do not reach peak effect for up to 6 months in HS.⁴

We identified 116 eligible patients with HS, 32 of whom received combination therapy. Five patients received 40 mg of adalimumab every other week, and 111 patients received 40 mg of adalimumab each week. Patients receiving oral immunosuppressants were more likely to be male and as likely to be biologic naïve compared to patients on monotherapy (Table). The average weekly dose of MTX was 14.63 mg, and the average daily dose of MMF was 1000 mg. The average number of days between starting adalimumab and starting an oral immunosuppressant was 114.5 (SD, 217; median, 0) days. Reasons for discontinuation of adalimumab included insufficient response, noncompliance, dislike of injections, adverse events, fear of adverse events, other medical issues unrelated to HS, and insurance coverage issues. Patients who ended treatment with adalimumab owing to insurance coverage issues were still included in our study because insurance coverage remains a major determinant of treatment choice in HS and is relevant to the dynamics of medical decision-making.

Statistical analysis was conducted on all patients inclusive of any reason for discontinuation to avoid bias in the calculation of treatment duration. Cox regression analysis was conducted for all independent variables and was noncontributory. Kaplan-Meier methodology was used to assess the duration of treatment of adalimumab with and without concomitant oral immunosuppressants, and quartile survival times were calculated. Quartile survival time is the time point after adalimumab initiation at which 25% of patients have discontinued adalimumab. We chose quartile survival time instead of average treatment duration to adequately power this study, given our small patient pool.

Although patients receiving adalimumab with oral immunosuppressants had a longer quartile treatment duration (450 days; 95% CI, 185-1800) than the group without oral immunosuppressants (360 days; 95% CI, 200-700), neither MTX nor MMF was shown to significantly prolong duration of therapy with adalimumab (log-rank test: P=.12). Additionally, patients receiving combination therapy were just as likely to discontinue adalimumab as those on monotherapy (χ² test: P=.93). Patients who took both MTX and MMF at different times did show a statistically significant increase in adalimumab quartile treatment duration (1710 days; 95% CI, 1620 [upper limit not calculable]), but this is likely because these patients were kept on adalimumab while trialing adjunctive medications.

The results of our study indicate that MTX and MMF do not prolong duration of adalimumab therapy, which suggests that adalimumab combination therapy with MTX and MMF may not improve HS more than adalimumab alone, and/or partial responders to adalimumab monotherapy are unlikely to be converted to satisfactory responders with the addition of oral immunosuppressants. Limitations of our study include that it was retrospective, used treatment duration as a surrogate for objective efficacy measures, and relied on a single-institution data source. Additionally, owing to our small sample size, we were unable to account for certain potential confounders, including patient weight and insurance status. Future controlled prospective studies using objective end points are needed to further elucidate whether oral immunosuppressants have a role as an adjunct in the treatment of HS.

To the Editor:

The tumor necrosis factor α inhibitor adalimumab is the only US Food and Drug Administration–approved treatment of hidradenitis suppurativa (HS). Although 50.6% of patients fulfilled Hidradenitis Suppurativa Clinical Response criteria with adalimumab at 12 weeks, many responders were not satisfied with their disease control, and secondary loss of Hidradenitis Suppurativa Clinical Response fulfillment occurred in 15.9% of patients within approximately 3 years.¹ Without other US Food and Drug Administration–approved HS treatments, some dermatologists have combined adalimumab with methotrexate (MTX) and/or mycophenolate mofetil (MMF) to attempt to increase the duration of satisfactory disease control while on adalimumab. Combining tumor necrosis factor α inhibitors with oral immunosuppressants is a well-established approach in psoriasis, psoriatic arthritis, and inflammatory bowel disease; however, to the best of our knowledge, this approach has not been studied for HS.^2,3

To assess whether there is a role for combining adalimumab with MTX and/or MMF in the treatment of HS, we performed a single-institution retrospective chart review at the University of Connecticut Department of Dermatology to determine whether patients receiving combination therapy stayed on adalimumab longer than those who received adalimumab monotherapy. All patients receiving adalimumab for the treatment of HS with at least 1 follow-up visit 3 or more months after treatment initiation were included. Duration of treatment with adalimumab was defined as the length of time between initiation and termination of adalimumab, regardless of flares, adverse events, or addition of adjuvant therapy that occurred during this time span. Because standardized rating scales measuring the severity of HS at this time are not recorded routinely at our institution, treatment duration with adalimumab was used as a surrogate for measuring therapeutic success. Additionally, treatment duration is a meaningful end point, as patients with HS may require indefinite treatment. Patients were eligible for inclusion if they were receiving adalimumab for the treatment of HS. Patients were excluded if they were lost to follow-up or had received adalimumab for less than 6 months, as data suggest that biologics do not reach peak effect for up to 6 months in HS.⁴

We identified 116 eligible patients with HS, 32 of whom received combination therapy. Five patients received 40 mg of adalimumab every other week, and 111 patients received 40 mg of adalimumab each week. Patients receiving oral immunosuppressants were more likely to be male and as likely to be biologic naïve compared to patients on monotherapy (Table). The average weekly dose of MTX was 14.63 mg, and the average daily dose of MMF was 1000 mg. The average number of days between starting adalimumab and starting an oral immunosuppressant was 114.5 (SD, 217; median, 0) days. Reasons for discontinuation of adalimumab included insufficient response, noncompliance, dislike of injections, adverse events, fear of adverse events, other medical issues unrelated to HS, and insurance coverage issues. Patients who ended treatment with adalimumab owing to insurance coverage issues were still included in our study because insurance coverage remains a major determinant of treatment choice in HS and is relevant to the dynamics of medical decision-making.

Statistical analysis was conducted on all patients inclusive of any reason for discontinuation to avoid bias in the calculation of treatment duration. Cox regression analysis was conducted for all independent variables and was noncontributory. Kaplan-Meier methodology was used to assess the duration of treatment of adalimumab with and without concomitant oral immunosuppressants, and quartile survival times were calculated. Quartile survival time is the time point after adalimumab initiation at which 25% of patients have discontinued adalimumab. We chose quartile survival time instead of average treatment duration to adequately power this study, given our small patient pool.

Although patients receiving adalimumab with oral immunosuppressants had a longer quartile treatment duration (450 days; 95% CI, 185-1800) than the group without oral immunosuppressants (360 days; 95% CI, 200-700), neither MTX nor MMF was shown to significantly prolong duration of therapy with adalimumab (log-rank test: P=.12). Additionally, patients receiving combination therapy were just as likely to discontinue adalimumab as those on monotherapy (χ² test: P=.93). Patients who took both MTX and MMF at different times did show a statistically significant increase in adalimumab quartile treatment duration (1710 days; 95% CI, 1620 [upper limit not calculable]), but this is likely because these patients were kept on adalimumab while trialing adjunctive medications.

The results of our study indicate that MTX and MMF do not prolong duration of adalimumab therapy, which suggests that adalimumab combination therapy with MTX and MMF may not improve HS more than adalimumab alone, and/or partial responders to adalimumab monotherapy are unlikely to be converted to satisfactory responders with the addition of oral immunosuppressants. Limitations of our study include that it was retrospective, used treatment duration as a surrogate for objective efficacy measures, and relied on a single-institution data source. Additionally, owing to our small sample size, we were unable to account for certain potential confounders, including patient weight and insurance status. Future controlled prospective studies using objective end points are needed to further elucidate whether oral immunosuppressants have a role as an adjunct in the treatment of HS.

To the Editor:

The tumor necrosis factor α inhibitor adalimumab is the only US Food and Drug Administration–approved treatment of hidradenitis suppurativa (HS). Although 50.6% of patients fulfilled Hidradenitis Suppurativa Clinical Response criteria with adalimumab at 12 weeks, many responders were not satisfied with their disease control, and secondary loss of Hidradenitis Suppurativa Clinical Response fulfillment occurred in 15.9% of patients within approximately 3 years.¹ Without other US Food and Drug Administration–approved HS treatments, some dermatologists have combined adalimumab with methotrexate (MTX) and/or mycophenolate mofetil (MMF) to attempt to increase the duration of satisfactory disease control while on adalimumab. Combining tumor necrosis factor α inhibitors with oral immunosuppressants is a well-established approach in psoriasis, psoriatic arthritis, and inflammatory bowel disease; however, to the best of our knowledge, this approach has not been studied for HS.^2,3

To assess whether there is a role for combining adalimumab with MTX and/or MMF in the treatment of HS, we performed a single-institution retrospective chart review at the University of Connecticut Department of Dermatology to determine whether patients receiving combination therapy stayed on adalimumab longer than those who received adalimumab monotherapy. All patients receiving adalimumab for the treatment of HS with at least 1 follow-up visit 3 or more months after treatment initiation were included. Duration of treatment with adalimumab was defined as the length of time between initiation and termination of adalimumab, regardless of flares, adverse events, or addition of adjuvant therapy that occurred during this time span. Because standardized rating scales measuring the severity of HS at this time are not recorded routinely at our institution, treatment duration with adalimumab was used as a surrogate for measuring therapeutic success. Additionally, treatment duration is a meaningful end point, as patients with HS may require indefinite treatment. Patients were eligible for inclusion if they were receiving adalimumab for the treatment of HS. Patients were excluded if they were lost to follow-up or had received adalimumab for less than 6 months, as data suggest that biologics do not reach peak effect for up to 6 months in HS.⁴

We identified 116 eligible patients with HS, 32 of whom received combination therapy. Five patients received 40 mg of adalimumab every other week, and 111 patients received 40 mg of adalimumab each week. Patients receiving oral immunosuppressants were more likely to be male and as likely to be biologic naïve compared to patients on monotherapy (Table). The average weekly dose of MTX was 14.63 mg, and the average daily dose of MMF was 1000 mg. The average number of days between starting adalimumab and starting an oral immunosuppressant was 114.5 (SD, 217; median, 0) days. Reasons for discontinuation of adalimumab included insufficient response, noncompliance, dislike of injections, adverse events, fear of adverse events, other medical issues unrelated to HS, and insurance coverage issues. Patients who ended treatment with adalimumab owing to insurance coverage issues were still included in our study because insurance coverage remains a major determinant of treatment choice in HS and is relevant to the dynamics of medical decision-making.

Statistical analysis was conducted on all patients inclusive of any reason for discontinuation to avoid bias in the calculation of treatment duration. Cox regression analysis was conducted for all independent variables and was noncontributory. Kaplan-Meier methodology was used to assess the duration of treatment of adalimumab with and without concomitant oral immunosuppressants, and quartile survival times were calculated. Quartile survival time is the time point after adalimumab initiation at which 25% of patients have discontinued adalimumab. We chose quartile survival time instead of average treatment duration to adequately power this study, given our small patient pool.

Although patients receiving adalimumab with oral immunosuppressants had a longer quartile treatment duration (450 days; 95% CI, 185-1800) than the group without oral immunosuppressants (360 days; 95% CI, 200-700), neither MTX nor MMF was shown to significantly prolong duration of therapy with adalimumab (log-rank test: P=.12). Additionally, patients receiving combination therapy were just as likely to discontinue adalimumab as those on monotherapy (χ² test: P=.93). Patients who took both MTX and MMF at different times did show a statistically significant increase in adalimumab quartile treatment duration (1710 days; 95% CI, 1620 [upper limit not calculable]), but this is likely because these patients were kept on adalimumab while trialing adjunctive medications.

The results of our study indicate that MTX and MMF do not prolong duration of adalimumab therapy, which suggests that adalimumab combination therapy with MTX and MMF may not improve HS more than adalimumab alone, and/or partial responders to adalimumab monotherapy are unlikely to be converted to satisfactory responders with the addition of oral immunosuppressants. Limitations of our study include that it was retrospective, used treatment duration as a surrogate for objective efficacy measures, and relied on a single-institution data source. Additionally, owing to our small sample size, we were unable to account for certain potential confounders, including patient weight and insurance status. Future controlled prospective studies using objective end points are needed to further elucidate whether oral immunosuppressants have a role as an adjunct in the treatment of HS.

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

A version of this article first appeared on WebMD.com.

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

A version of this article first appeared on WebMD.com.

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

A version of this article first appeared on WebMD.com.

Music plus mushrooms equals therapy

Magic mushrooms have been used recreationally and medicinally for thousands of years, but researchers have found adding music could be a game changer in antidepressant treatment.

chrissmith12/Pixabay

The ingredient that makes these mushrooms so magical is psilocybin. It works well for the clinical treatment of mental health conditions and some forms of depression because the “trip” can be contained to one work day, making it easy to administer under supervision. With the accompaniment of music, scientists have found that psilocybin evokes emotion.

This recent study, presented at the European College of Neuropsychopharmacology Congress in Lisbon, tested participants’ emotional response to music before and after the psilocybin. Ketanserin, an antihypertensive drug, was used to test against the effects of psilocybin. The scientist played Mozart and Elgar and found that participants on psilocybin had an emotional response increase of 60%. That response was even greater, compared with ketanserin, which actually lessened the emotional response to music.

“This shows that combination of psilocybin and music has a strong emotional effect, and we believe that this will be important for the therapeutic application of psychedelics if they are approved for clinical use,” said lead researcher Dea Siggaard Stenbæk of the University of Copenhagen.

Professor David J. Nutt of Imperial College in London, who was not involved in the study, said that it supports the use of music for treatment efficacy with psychedelics and suggested that the next step is to “optimise this approach probably through individualising and personalising music tracks in therapy.”

Cue the 1960s LSD music montage.
 

Chicken ‘white striping is not a disease’

Have you ever sliced open a new pack of chicken breasts to start dinner and noticed white fatty lines running through the chicken? Maybe you thought it was just some extra fat to trim off, but the Humane League calls it “white striping disease.”

rawpixel

Chicken is the No. 1 meat consumed by Americans, so it’s not surprising that chickens are factory farmed and raised to be ready for slaughter quickly, according to CBSNews.com, which reported that the Humane League claims white striping is found in 70% of the chicken in popular grocery stores. The league expressed concern for the chickens’ welfare as they are bred to grow bigger quickly, which is causing the white striping and increasing the fat content of the meat by as much as 224%.

The National Chicken Council told CBS that the league’s findings were unscientific. A spokesperson said, “White striping is not a disease. It is a quality factor in chicken breast meat caused by deposits of fat in the muscle during the bird’s growth and development.” He went on to say that severe white striping happens in 3%-6% of birds, which are mostly used in further processed products, not in chicken breast packages.

Somehow, that’s not making us feel any better.
 

The itsy bitsy spider lets us all down

Most people do not like spiders. That’s too bad, because spiders are generally nothing but helpful little creatures that prey upon annoying flies and other pests. Then there’s the silk they produce. The ancient Romans used it to treat conditions such as warts and skin lesions. Spiders wrap their eggs in silk to protect them from harmful bacteria.

Simon Fruergaard

Of course, we can hardly trust the medical opinions of people from 2,000 years ago, but modern-day studies have not definitively proved whether or not spider silk has any antimicrobial properties.

To settle the matter once and for all, researchers from Denmark built a silk-harvesting machine using the most famous of Danish inventions: Legos. The contraption, sort of a paddle wheel, pulled the silk from several different species of spider pinned down by the researchers. The silk was then tested against three different bacteria species, including good old Escherichia coli.

Unfortunately for our spider friends, their silk has no antimicrobial activity. The researchers suspected that any such activity seen in previous studies was actually caused by improper control for the solvents used to extract the silk; those solvents can have antimicrobial properties on their own. As for protecting their eggs, rather than killing bacteria, the silk likely provides a physical barrier alone.

It is bad news for spiders on the benefit-to-humanity front, but look at the bright side: If their silk had antimicrobial activity, we’d have to start farming them to acquire more silk. And that’s no good. Spiders deserve to roam free, hunt as they please, and drop down on your head from the ceiling.
 

Anxiety and allergies: Cause, effect, confusion

We’re big fans of science, but as longtime, totally impartial (Science rules!) observers of science’s medical realm, we can see that the day-to-day process of practicing the scientific method occasionally gets a bit messy. And no, we’re not talking about COVID-19.

pxfuel

We’re talking allergies. We’re talking mental health. We’re talking allergic disease and mental health.

We’re talking about a pair of press releases we came across during our never-ending search for material to educate, entertain, and astound our fabulously wonderful and loyal readers. (We say that, of course, in the most impartial way possible.)

The first release was titled, “Allergies including asthma and hay fever not linked to mental health traits” and covered research from the University of Bristol (England). The investigators were trying to determine if “allergic diseases actually causes mental health traits including anxiety, depression, bipolar disorder, and schizophrenia, or vice versa,” according to the release.

What they found, however, was “little evidence of a causal relationship between the onset of allergic disease and mental health.” Again, this is the press release talking.

The second release seemed to suggest the exact opposite: “Study uncovers link between allergies and mental health conditions.” That got our attention. A little more reading revealed that “people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism.”

One of the investigators was quoted as saying, “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”

Did you notice the “vice versa”? Did you notice that it appeared in quotes from both releases? We did, so we took a closer look at the source. The second release covered a group of investigators from the University of Bristol – the same group, and the same study, in fact, as the first one.

So there you have it. One study, two press releases, and one confused journalist. Thank you, science.

Music plus mushrooms equals therapy

Magic mushrooms have been used recreationally and medicinally for thousands of years, but researchers have found adding music could be a game changer in antidepressant treatment.

chrissmith12/Pixabay

The ingredient that makes these mushrooms so magical is psilocybin. It works well for the clinical treatment of mental health conditions and some forms of depression because the “trip” can be contained to one work day, making it easy to administer under supervision. With the accompaniment of music, scientists have found that psilocybin evokes emotion.

This recent study, presented at the European College of Neuropsychopharmacology Congress in Lisbon, tested participants’ emotional response to music before and after the psilocybin. Ketanserin, an antihypertensive drug, was used to test against the effects of psilocybin. The scientist played Mozart and Elgar and found that participants on psilocybin had an emotional response increase of 60%. That response was even greater, compared with ketanserin, which actually lessened the emotional response to music.

“This shows that combination of psilocybin and music has a strong emotional effect, and we believe that this will be important for the therapeutic application of psychedelics if they are approved for clinical use,” said lead researcher Dea Siggaard Stenbæk of the University of Copenhagen.

Professor David J. Nutt of Imperial College in London, who was not involved in the study, said that it supports the use of music for treatment efficacy with psychedelics and suggested that the next step is to “optimise this approach probably through individualising and personalising music tracks in therapy.”

Cue the 1960s LSD music montage.
 

Chicken ‘white striping is not a disease’

Have you ever sliced open a new pack of chicken breasts to start dinner and noticed white fatty lines running through the chicken? Maybe you thought it was just some extra fat to trim off, but the Humane League calls it “white striping disease.”

rawpixel

Chicken is the No. 1 meat consumed by Americans, so it’s not surprising that chickens are factory farmed and raised to be ready for slaughter quickly, according to CBSNews.com, which reported that the Humane League claims white striping is found in 70% of the chicken in popular grocery stores. The league expressed concern for the chickens’ welfare as they are bred to grow bigger quickly, which is causing the white striping and increasing the fat content of the meat by as much as 224%.

The National Chicken Council told CBS that the league’s findings were unscientific. A spokesperson said, “White striping is not a disease. It is a quality factor in chicken breast meat caused by deposits of fat in the muscle during the bird’s growth and development.” He went on to say that severe white striping happens in 3%-6% of birds, which are mostly used in further processed products, not in chicken breast packages.

Somehow, that’s not making us feel any better.
 

The itsy bitsy spider lets us all down

Most people do not like spiders. That’s too bad, because spiders are generally nothing but helpful little creatures that prey upon annoying flies and other pests. Then there’s the silk they produce. The ancient Romans used it to treat conditions such as warts and skin lesions. Spiders wrap their eggs in silk to protect them from harmful bacteria.

Simon Fruergaard

Of course, we can hardly trust the medical opinions of people from 2,000 years ago, but modern-day studies have not definitively proved whether or not spider silk has any antimicrobial properties.

To settle the matter once and for all, researchers from Denmark built a silk-harvesting machine using the most famous of Danish inventions: Legos. The contraption, sort of a paddle wheel, pulled the silk from several different species of spider pinned down by the researchers. The silk was then tested against three different bacteria species, including good old Escherichia coli.

Unfortunately for our spider friends, their silk has no antimicrobial activity. The researchers suspected that any such activity seen in previous studies was actually caused by improper control for the solvents used to extract the silk; those solvents can have antimicrobial properties on their own. As for protecting their eggs, rather than killing bacteria, the silk likely provides a physical barrier alone.

It is bad news for spiders on the benefit-to-humanity front, but look at the bright side: If their silk had antimicrobial activity, we’d have to start farming them to acquire more silk. And that’s no good. Spiders deserve to roam free, hunt as they please, and drop down on your head from the ceiling.
 

Anxiety and allergies: Cause, effect, confusion

We’re big fans of science, but as longtime, totally impartial (Science rules!) observers of science’s medical realm, we can see that the day-to-day process of practicing the scientific method occasionally gets a bit messy. And no, we’re not talking about COVID-19.

pxfuel

We’re talking allergies. We’re talking mental health. We’re talking allergic disease and mental health.

We’re talking about a pair of press releases we came across during our never-ending search for material to educate, entertain, and astound our fabulously wonderful and loyal readers. (We say that, of course, in the most impartial way possible.)

The first release was titled, “Allergies including asthma and hay fever not linked to mental health traits” and covered research from the University of Bristol (England). The investigators were trying to determine if “allergic diseases actually causes mental health traits including anxiety, depression, bipolar disorder, and schizophrenia, or vice versa,” according to the release.

What they found, however, was “little evidence of a causal relationship between the onset of allergic disease and mental health.” Again, this is the press release talking.

The second release seemed to suggest the exact opposite: “Study uncovers link between allergies and mental health conditions.” That got our attention. A little more reading revealed that “people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism.”

One of the investigators was quoted as saying, “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”

Did you notice the “vice versa”? Did you notice that it appeared in quotes from both releases? We did, so we took a closer look at the source. The second release covered a group of investigators from the University of Bristol – the same group, and the same study, in fact, as the first one.

So there you have it. One study, two press releases, and one confused journalist. Thank you, science.

Music plus mushrooms equals therapy

Magic mushrooms have been used recreationally and medicinally for thousands of years, but researchers have found adding music could be a game changer in antidepressant treatment.

chrissmith12/Pixabay

The ingredient that makes these mushrooms so magical is psilocybin. It works well for the clinical treatment of mental health conditions and some forms of depression because the “trip” can be contained to one work day, making it easy to administer under supervision. With the accompaniment of music, scientists have found that psilocybin evokes emotion.

This recent study, presented at the European College of Neuropsychopharmacology Congress in Lisbon, tested participants’ emotional response to music before and after the psilocybin. Ketanserin, an antihypertensive drug, was used to test against the effects of psilocybin. The scientist played Mozart and Elgar and found that participants on psilocybin had an emotional response increase of 60%. That response was even greater, compared with ketanserin, which actually lessened the emotional response to music.

“This shows that combination of psilocybin and music has a strong emotional effect, and we believe that this will be important for the therapeutic application of psychedelics if they are approved for clinical use,” said lead researcher Dea Siggaard Stenbæk of the University of Copenhagen.

Professor David J. Nutt of Imperial College in London, who was not involved in the study, said that it supports the use of music for treatment efficacy with psychedelics and suggested that the next step is to “optimise this approach probably through individualising and personalising music tracks in therapy.”

Cue the 1960s LSD music montage.
 

Chicken ‘white striping is not a disease’

Have you ever sliced open a new pack of chicken breasts to start dinner and noticed white fatty lines running through the chicken? Maybe you thought it was just some extra fat to trim off, but the Humane League calls it “white striping disease.”

rawpixel

Chicken is the No. 1 meat consumed by Americans, so it’s not surprising that chickens are factory farmed and raised to be ready for slaughter quickly, according to CBSNews.com, which reported that the Humane League claims white striping is found in 70% of the chicken in popular grocery stores. The league expressed concern for the chickens’ welfare as they are bred to grow bigger quickly, which is causing the white striping and increasing the fat content of the meat by as much as 224%.

The National Chicken Council told CBS that the league’s findings were unscientific. A spokesperson said, “White striping is not a disease. It is a quality factor in chicken breast meat caused by deposits of fat in the muscle during the bird’s growth and development.” He went on to say that severe white striping happens in 3%-6% of birds, which are mostly used in further processed products, not in chicken breast packages.

Somehow, that’s not making us feel any better.
 

The itsy bitsy spider lets us all down

Most people do not like spiders. That’s too bad, because spiders are generally nothing but helpful little creatures that prey upon annoying flies and other pests. Then there’s the silk they produce. The ancient Romans used it to treat conditions such as warts and skin lesions. Spiders wrap their eggs in silk to protect them from harmful bacteria.

Simon Fruergaard

Of course, we can hardly trust the medical opinions of people from 2,000 years ago, but modern-day studies have not definitively proved whether or not spider silk has any antimicrobial properties.

To settle the matter once and for all, researchers from Denmark built a silk-harvesting machine using the most famous of Danish inventions: Legos. The contraption, sort of a paddle wheel, pulled the silk from several different species of spider pinned down by the researchers. The silk was then tested against three different bacteria species, including good old Escherichia coli.

Unfortunately for our spider friends, their silk has no antimicrobial activity. The researchers suspected that any such activity seen in previous studies was actually caused by improper control for the solvents used to extract the silk; those solvents can have antimicrobial properties on their own. As for protecting their eggs, rather than killing bacteria, the silk likely provides a physical barrier alone.

It is bad news for spiders on the benefit-to-humanity front, but look at the bright side: If their silk had antimicrobial activity, we’d have to start farming them to acquire more silk. And that’s no good. Spiders deserve to roam free, hunt as they please, and drop down on your head from the ceiling.
 

Anxiety and allergies: Cause, effect, confusion

We’re big fans of science, but as longtime, totally impartial (Science rules!) observers of science’s medical realm, we can see that the day-to-day process of practicing the scientific method occasionally gets a bit messy. And no, we’re not talking about COVID-19.

pxfuel

We’re talking allergies. We’re talking mental health. We’re talking allergic disease and mental health.

We’re talking about a pair of press releases we came across during our never-ending search for material to educate, entertain, and astound our fabulously wonderful and loyal readers. (We say that, of course, in the most impartial way possible.)

The first release was titled, “Allergies including asthma and hay fever not linked to mental health traits” and covered research from the University of Bristol (England). The investigators were trying to determine if “allergic diseases actually causes mental health traits including anxiety, depression, bipolar disorder, and schizophrenia, or vice versa,” according to the release.

What they found, however, was “little evidence of a causal relationship between the onset of allergic disease and mental health.” Again, this is the press release talking.

The second release seemed to suggest the exact opposite: “Study uncovers link between allergies and mental health conditions.” That got our attention. A little more reading revealed that “people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism.”

One of the investigators was quoted as saying, “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”

Did you notice the “vice versa”? Did you notice that it appeared in quotes from both releases? We did, so we took a closer look at the source. The second release covered a group of investigators from the University of Bristol – the same group, and the same study, in fact, as the first one.

So there you have it. One study, two press releases, and one confused journalist. Thank you, science.

Hidradenitis suppurativa (HS) is a debilitating chronic condition that often is recalcitrant to first-line treatments, and mechanisms underlying its pathology remain unclear. Existing data suggest a multifactorial etiology with different pathophysiologic contributors, including genetic, hormonal, and immune dysregulation factors. At this time, only one medication (adalimumab) is US Food and Drug Administration approved for HS, but multiple medical and procedural therapies are available.¹ Herein, we discuss the concept of treatment stacking, or the combination of unique therapeutic modalities—an approach we believe is key to optimizing management of HS patients.

Stacking Treatments for HS

Unlike psoriasis, in which a single biologic agent may provide 100% clearance (psoriasis area and severity index 100 [PASI 100]) without adjuvant treatment,^2,3 the field of HS currently lacks medications that are efficacious to that degree of success as monotherapy. In HS, the benchmark for a positive treatment outcome is Hidradenitis Suppurativa Clinical Response 50 (HiSCR50),⁴ a 50% reduction in inflammatory lesion count—a far less stringent marker for disease improvement. Thus, providers should design HS treatment regimens with a model of combining therapies and shift away from monotherapy. Targeting different pathophysiologic pathways by stacking multiple treatments may provide synergistic benefits for HS patients. Treatment stacking is a familiar concept in acne; for instance, patients who benefit tremendously from isotretinoin may still require a hormone-modulating treatment (eg, spironolactone) to attain optimal results.

Adherence to a rigid treatment algorithm based on disease severity limits the potential to create comprehensive regimens that account for unique patient characteristics and clinical manifestations. When evaluating an HS patient, providers should systematically consider each pathophysiologic factor and target the ones that appear to be most involved in that particular patient. The North American HS guidelines illustrate this point by supporting use of several treatments across different Hurley stages, such as recommending hormonal treatment in patients with Hurley stages 1, 2, or 3.¹ Of note, treatment stacking also includes procedural therapies. Surgeons typically prefer a patient’s disease management to be optimized prior to surgery, including reduced drainage and inflammation. In addition, even after surgery, patients often still require medical management to prevent continued disease worsening.

Treatment Pathways for HS

A multimodal approach with treatment stacking (Figure) can be useful to all HS patients, from those with the mildest to the most severe disease. Modifiable pathophysiologic factors and examples of their targeted treatments include (1) follicular occlusion (eg, oral retinoids), (2) metabolic dysfunction (eg, metformin), (3) hormones (eg, oral contraceptive pills, spironolactone, finasteride), (4) dysbiosis (eg, antibiotics such as clindamycin and rifampin combination therapy), (5) immune dysregulation (eg, biologic agents), and (6) friction/irritation (eg, weight loss, clothing recommendations).

Combining treatments from different pathways enables potentiation of individual treatment efficacies. A female patient with only a few HS nodules that flare with menses may be well controlled with spironolactone as her only systemic agent; however, she still may benefit from use of an antiseptic wash, topical clindamycin, and lifestyle changes such as weight loss and reduction of mechanical irritation. A patient with severe recalcitrant HS could notably benefit from concomitant biologic, systemic antibiotic, and hormonal/metabolic treatments. If disease control is still inadequate, agents within the same class can be switched (eg, choosing a different biologic) or other disease-modifying agents such as colchicine also can be added. The goal is to create an effective treatment toolbox with therapies targeting different pathophysiologic arms of HS and working together in synergy. Each tool can be refined by modifying dosing frequency and duration of use to strive for optimal response. At this time, the literature on HS combination therapy is sparse. A retrospective study of 31 patients reported promising combinations, including isotretinoin with spironolactone for mild disease, isotretinoin or doxycycline with adalimumab for moderate disease, and cyclosporine with adalimumab for severe disease.⁵ Larger prospective studies on clinical response to different combination regimens are warranted.

Optimizing Therapy for HS and Its Comorbidities

Additional considerations may further optimize treatment plans. Some therapies benefit all patients; for example, providers should counsel all HS patients on healthy weight management, optimized clothing choices,⁶ and friction reduction in the intertriginous folds. Providers also may consider adding therapies with faster onset of efficacy as a bridge to long-term, slower-onset therapies. For instance, female HS patients with menstrual flares who are prescribed spironolactone also may benefit from a course of systemic antibiotics, which typically provides more prompt relief. Treatment regimens also can concomitantly treat HS and its comorbidities.⁷ For example, metformin serves a dual purpose in HS patients with diabetes mellitus, and adalimumab in patients with both HS and inflammatory bowel disease.

Final Thoughts

The last decade has seen tremendous growth in HS research⁸ coupled with a remarkable expansion in the therapeutic pipeline.⁹ However, currently no single therapy for HS can guarantee satisfactory disease remission or durability of remission. The contrast between clinical trials and real-world practice should be acknowledged; the former often is restrictive in design with monotherapy and allowance of very limited concomitant treatments, such as topical or oral antibiotics. This limits our ability to draw conclusions regarding the additive synergistic potential of different therapeutics in combination. In clinical practice, we are not restricted by monotherapy trial protocols. As we await new tools, treatment stacking allows for creating a framework to best utilize the tools that are available to us.

Although HS has continued to affect the lives of many patients, improved understanding of underlying pathophysiology and a well-placed sense of urgency from all stakeholders (ie, patients, clinicians, researchers, industry partners) has pushed this field forward. Until our therapeutic armamentarium has expanded to include highly efficacious monotherapy options, providers should consider treatment stacking for every HS patient.

Hidradenitis suppurativa (HS) is a debilitating chronic condition that often is recalcitrant to first-line treatments, and mechanisms underlying its pathology remain unclear. Existing data suggest a multifactorial etiology with different pathophysiologic contributors, including genetic, hormonal, and immune dysregulation factors. At this time, only one medication (adalimumab) is US Food and Drug Administration approved for HS, but multiple medical and procedural therapies are available.¹ Herein, we discuss the concept of treatment stacking, or the combination of unique therapeutic modalities—an approach we believe is key to optimizing management of HS patients.

Stacking Treatments for HS

Unlike psoriasis, in which a single biologic agent may provide 100% clearance (psoriasis area and severity index 100 [PASI 100]) without adjuvant treatment,^2,3 the field of HS currently lacks medications that are efficacious to that degree of success as monotherapy. In HS, the benchmark for a positive treatment outcome is Hidradenitis Suppurativa Clinical Response 50 (HiSCR50),⁴ a 50% reduction in inflammatory lesion count—a far less stringent marker for disease improvement. Thus, providers should design HS treatment regimens with a model of combining therapies and shift away from monotherapy. Targeting different pathophysiologic pathways by stacking multiple treatments may provide synergistic benefits for HS patients. Treatment stacking is a familiar concept in acne; for instance, patients who benefit tremendously from isotretinoin may still require a hormone-modulating treatment (eg, spironolactone) to attain optimal results.

Adherence to a rigid treatment algorithm based on disease severity limits the potential to create comprehensive regimens that account for unique patient characteristics and clinical manifestations. When evaluating an HS patient, providers should systematically consider each pathophysiologic factor and target the ones that appear to be most involved in that particular patient. The North American HS guidelines illustrate this point by supporting use of several treatments across different Hurley stages, such as recommending hormonal treatment in patients with Hurley stages 1, 2, or 3.¹ Of note, treatment stacking also includes procedural therapies. Surgeons typically prefer a patient’s disease management to be optimized prior to surgery, including reduced drainage and inflammation. In addition, even after surgery, patients often still require medical management to prevent continued disease worsening.

Treatment Pathways for HS

A multimodal approach with treatment stacking (Figure) can be useful to all HS patients, from those with the mildest to the most severe disease. Modifiable pathophysiologic factors and examples of their targeted treatments include (1) follicular occlusion (eg, oral retinoids), (2) metabolic dysfunction (eg, metformin), (3) hormones (eg, oral contraceptive pills, spironolactone, finasteride), (4) dysbiosis (eg, antibiotics such as clindamycin and rifampin combination therapy), (5) immune dysregulation (eg, biologic agents), and (6) friction/irritation (eg, weight loss, clothing recommendations).

Combining treatments from different pathways enables potentiation of individual treatment efficacies. A female patient with only a few HS nodules that flare with menses may be well controlled with spironolactone as her only systemic agent; however, she still may benefit from use of an antiseptic wash, topical clindamycin, and lifestyle changes such as weight loss and reduction of mechanical irritation. A patient with severe recalcitrant HS could notably benefit from concomitant biologic, systemic antibiotic, and hormonal/metabolic treatments. If disease control is still inadequate, agents within the same class can be switched (eg, choosing a different biologic) or other disease-modifying agents such as colchicine also can be added. The goal is to create an effective treatment toolbox with therapies targeting different pathophysiologic arms of HS and working together in synergy. Each tool can be refined by modifying dosing frequency and duration of use to strive for optimal response. At this time, the literature on HS combination therapy is sparse. A retrospective study of 31 patients reported promising combinations, including isotretinoin with spironolactone for mild disease, isotretinoin or doxycycline with adalimumab for moderate disease, and cyclosporine with adalimumab for severe disease.⁵ Larger prospective studies on clinical response to different combination regimens are warranted.

Optimizing Therapy for HS and Its Comorbidities

Additional considerations may further optimize treatment plans. Some therapies benefit all patients; for example, providers should counsel all HS patients on healthy weight management, optimized clothing choices,⁶ and friction reduction in the intertriginous folds. Providers also may consider adding therapies with faster onset of efficacy as a bridge to long-term, slower-onset therapies. For instance, female HS patients with menstrual flares who are prescribed spironolactone also may benefit from a course of systemic antibiotics, which typically provides more prompt relief. Treatment regimens also can concomitantly treat HS and its comorbidities.⁷ For example, metformin serves a dual purpose in HS patients with diabetes mellitus, and adalimumab in patients with both HS and inflammatory bowel disease.

Final Thoughts

The last decade has seen tremendous growth in HS research⁸ coupled with a remarkable expansion in the therapeutic pipeline.⁹ However, currently no single therapy for HS can guarantee satisfactory disease remission or durability of remission. The contrast between clinical trials and real-world practice should be acknowledged; the former often is restrictive in design with monotherapy and allowance of very limited concomitant treatments, such as topical or oral antibiotics. This limits our ability to draw conclusions regarding the additive synergistic potential of different therapeutics in combination. In clinical practice, we are not restricted by monotherapy trial protocols. As we await new tools, treatment stacking allows for creating a framework to best utilize the tools that are available to us.

Although HS has continued to affect the lives of many patients, improved understanding of underlying pathophysiology and a well-placed sense of urgency from all stakeholders (ie, patients, clinicians, researchers, industry partners) has pushed this field forward. Until our therapeutic armamentarium has expanded to include highly efficacious monotherapy options, providers should consider treatment stacking for every HS patient.

Hidradenitis suppurativa (HS) is a debilitating chronic condition that often is recalcitrant to first-line treatments, and mechanisms underlying its pathology remain unclear. Existing data suggest a multifactorial etiology with different pathophysiologic contributors, including genetic, hormonal, and immune dysregulation factors. At this time, only one medication (adalimumab) is US Food and Drug Administration approved for HS, but multiple medical and procedural therapies are available.¹ Herein, we discuss the concept of treatment stacking, or the combination of unique therapeutic modalities—an approach we believe is key to optimizing management of HS patients.

Stacking Treatments for HS

Unlike psoriasis, in which a single biologic agent may provide 100% clearance (psoriasis area and severity index 100 [PASI 100]) without adjuvant treatment,^2,3 the field of HS currently lacks medications that are efficacious to that degree of success as monotherapy. In HS, the benchmark for a positive treatment outcome is Hidradenitis Suppurativa Clinical Response 50 (HiSCR50),⁴ a 50% reduction in inflammatory lesion count—a far less stringent marker for disease improvement. Thus, providers should design HS treatment regimens with a model of combining therapies and shift away from monotherapy. Targeting different pathophysiologic pathways by stacking multiple treatments may provide synergistic benefits for HS patients. Treatment stacking is a familiar concept in acne; for instance, patients who benefit tremendously from isotretinoin may still require a hormone-modulating treatment (eg, spironolactone) to attain optimal results.

Adherence to a rigid treatment algorithm based on disease severity limits the potential to create comprehensive regimens that account for unique patient characteristics and clinical manifestations. When evaluating an HS patient, providers should systematically consider each pathophysiologic factor and target the ones that appear to be most involved in that particular patient. The North American HS guidelines illustrate this point by supporting use of several treatments across different Hurley stages, such as recommending hormonal treatment in patients with Hurley stages 1, 2, or 3.¹ Of note, treatment stacking also includes procedural therapies. Surgeons typically prefer a patient’s disease management to be optimized prior to surgery, including reduced drainage and inflammation. In addition, even after surgery, patients often still require medical management to prevent continued disease worsening.

Treatment Pathways for HS

A multimodal approach with treatment stacking (Figure) can be useful to all HS patients, from those with the mildest to the most severe disease. Modifiable pathophysiologic factors and examples of their targeted treatments include (1) follicular occlusion (eg, oral retinoids), (2) metabolic dysfunction (eg, metformin), (3) hormones (eg, oral contraceptive pills, spironolactone, finasteride), (4) dysbiosis (eg, antibiotics such as clindamycin and rifampin combination therapy), (5) immune dysregulation (eg, biologic agents), and (6) friction/irritation (eg, weight loss, clothing recommendations).

Combining treatments from different pathways enables potentiation of individual treatment efficacies. A female patient with only a few HS nodules that flare with menses may be well controlled with spironolactone as her only systemic agent; however, she still may benefit from use of an antiseptic wash, topical clindamycin, and lifestyle changes such as weight loss and reduction of mechanical irritation. A patient with severe recalcitrant HS could notably benefit from concomitant biologic, systemic antibiotic, and hormonal/metabolic treatments. If disease control is still inadequate, agents within the same class can be switched (eg, choosing a different biologic) or other disease-modifying agents such as colchicine also can be added. The goal is to create an effective treatment toolbox with therapies targeting different pathophysiologic arms of HS and working together in synergy. Each tool can be refined by modifying dosing frequency and duration of use to strive for optimal response. At this time, the literature on HS combination therapy is sparse. A retrospective study of 31 patients reported promising combinations, including isotretinoin with spironolactone for mild disease, isotretinoin or doxycycline with adalimumab for moderate disease, and cyclosporine with adalimumab for severe disease.⁵ Larger prospective studies on clinical response to different combination regimens are warranted.

Optimizing Therapy for HS and Its Comorbidities

Additional considerations may further optimize treatment plans. Some therapies benefit all patients; for example, providers should counsel all HS patients on healthy weight management, optimized clothing choices,⁶ and friction reduction in the intertriginous folds. Providers also may consider adding therapies with faster onset of efficacy as a bridge to long-term, slower-onset therapies. For instance, female HS patients with menstrual flares who are prescribed spironolactone also may benefit from a course of systemic antibiotics, which typically provides more prompt relief. Treatment regimens also can concomitantly treat HS and its comorbidities.⁷ For example, metformin serves a dual purpose in HS patients with diabetes mellitus, and adalimumab in patients with both HS and inflammatory bowel disease.

Final Thoughts

The last decade has seen tremendous growth in HS research⁸ coupled with a remarkable expansion in the therapeutic pipeline.⁹ However, currently no single therapy for HS can guarantee satisfactory disease remission or durability of remission. The contrast between clinical trials and real-world practice should be acknowledged; the former often is restrictive in design with monotherapy and allowance of very limited concomitant treatments, such as topical or oral antibiotics. This limits our ability to draw conclusions regarding the additive synergistic potential of different therapeutics in combination. In clinical practice, we are not restricted by monotherapy trial protocols. As we await new tools, treatment stacking allows for creating a framework to best utilize the tools that are available to us.

Although HS has continued to affect the lives of many patients, improved understanding of underlying pathophysiology and a well-placed sense of urgency from all stakeholders (ie, patients, clinicians, researchers, industry partners) has pushed this field forward. Until our therapeutic armamentarium has expanded to include highly efficacious monotherapy options, providers should consider treatment stacking for every HS patient.

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

A version of this article first appeared on WebMD.com.

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

A version of this article first appeared on WebMD.com.

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

A version of this article first appeared on WebMD.com.

Bone marrow derived autologous cell therapy (ACT) has been shown to significantly reduce the rate of major amputation at 5 years in people with diabetes who developed critical limb-threatening ischemia (CLTI).

In a study of 130 patients, 64% of 42 patients who were treated conservatively needed a major amputation at 5 years versus just 30% of 45 patients who had been treated with ACT (P = .011).

This compared favorably to the results seen with repeated percutaneous angioplasty (re-PTA), where just 20.9% of 43 patients underwent limb salvage (P = .002 vs. conservative therapy).

Furthermore, amputation-free survival was significantly longer in both active groups, Michal Dubský, MD, PhD, FRSPH, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Dubský, of the Institute for Clinical and Experimental Medicine and Charles University in Prague, also reported that fewer patients who had undergone re-PTA or ACT than conservative treatment had died by 5 years (25.8% and 35.6%, respectively, vs. 61.9%), but that the difference was significant only for the revascularization procedure (P = .012).

Based on these findings, “we believe that autologous cell therapy seems to be an appropriate alternative to repeated PTA even for patients with no-option chronic limb-threatening ischemia,” he said.

“This is a very important area,” said Andrew J.M. Boulton, MBBS, MD, FRCP, who chaired the oral abstract presentation session during which the findings were presented.

“It is very difficult to get an evidence base from randomized studies in this area, because of the nature of the patients: They’re very sick and we all deal with them in our clinics very regularly,” added Dr. Boulton, professor of medicine within the division of diabetes, endocrinology and gastroenterology at the University of Manchester (England).

Dr. Boulton called the findings a “very important addition to what we know.”
 

New option for no-option CLTI

CLTI is associated with persistent pain at rest, ulcers, and gangrene, and can be the end result of longstanding peripheral arterial disease. Within the first year of presentation, there’s a 30% chance of having a major amputation and a 25% chance of dying.

Importantly, said Dr. Dubský, “there is a big difference in this diagnosis” between patients with diabetes and those without. For instance, CLTI is more diffuse in patients with diabetes than in those without, different arteries are affected and the sclerosis seen can be more rigid and “full of calcium.”

While surgery to improve blood flow is the standard of care, not everyone is suitable. Bypass surgery or endovascular procedures can be performed in only 40%-50% of patients, and even then a therapeutic effect may be seen in only a quarter of patients.

“We need some new therapeutic modalities for this diagnosis, and one of them could be autologous cell therapy,” said Dr. Dubský.
 

Study details

Dr. Dubský and coinvestigators consecutively recruited 130 patients with diabetic foot and CLTI who had been seen at their clinic over a 5-year period. Of these, 87 had not been eligible for standard revascularization and underwent ACT or were treated conservatively.

Of the patients who were not eligible for standard revascularization (‘no-option CLTI), 45 had undergone ACT and 42 had been treated conservatively. Dr. Dubský acknowledged that “his study was not prospective and randomized.”

All patients in the study had at least one unsuccessful revascularization procedure and diabetic foot ulcers, and low tissue oxygenation. The latter was defined as transcutaneous oxygen pressure (TcPO₂) of below 30 mm Hg.

There were little differences in demographic characteristics between the treatment groups, the average age ranged from 62 to 67 years, there were more men (70%-80%) than women; most patients (90%) had type 2 diabetes for at least 20 years. There were similar rates of ischemic heart disease, hypertension, dialysis, and immunosuppressive therapy.

There were no differences in baseline values of TcPO₂ between the groups, and similar improvements were seen in both the ACT and re-PTA groups versus conservative group.
 

ACT in practice

With such promising results, what about the practicalities of harvesting a patient’s bone marrow to make the ACT?

“Bone marrow harvesting usually takes about 20 minutes,” Dr. Dubský said. It then takes another 45 minutes to separate the cells and make the cell suspension, and then maybe another 10 minutes or so to administer this to the patient, which is done by injecting into the calf muscles and small muscles of the foot, aided by computed tomography. The whole process may take up to 2 hours, he said.

“Patients are under local or general anesthesia, so there is no pain during the procedure,” Dr. Dubský reassured. “Afterwards we sometimes see small hematoma[s], with low-intensity pain that responds well to usual analgesic therapy.”

Computed tomography was used to help guide the injections, which was advantageous, Dr. Boulton pointed out, because it was “less invasive than angioplasty in these very sick people with very distal lesions, many of whom already have renal problems.”

“It is surprising though, that everybody had re-PTA and not one had vascular surgery,” he suggested. Dr. Boulton added, however: “These are very important observations; they help us a lot in an area where there’s unlikely to be a full RCT.”

The next step in this research is to see if combining ACT and re-PTA could lead to even better results.

The study was funded by the Czech Republic Ministry of Health. Dr. Dubský had nothing to disclose. Dr. Boulton made no statement about his conflicts of interest.

Bone marrow derived autologous cell therapy (ACT) has been shown to significantly reduce the rate of major amputation at 5 years in people with diabetes who developed critical limb-threatening ischemia (CLTI).

In a study of 130 patients, 64% of 42 patients who were treated conservatively needed a major amputation at 5 years versus just 30% of 45 patients who had been treated with ACT (P = .011).

This compared favorably to the results seen with repeated percutaneous angioplasty (re-PTA), where just 20.9% of 43 patients underwent limb salvage (P = .002 vs. conservative therapy).

Furthermore, amputation-free survival was significantly longer in both active groups, Michal Dubský, MD, PhD, FRSPH, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Dubský, of the Institute for Clinical and Experimental Medicine and Charles University in Prague, also reported that fewer patients who had undergone re-PTA or ACT than conservative treatment had died by 5 years (25.8% and 35.6%, respectively, vs. 61.9%), but that the difference was significant only for the revascularization procedure (P = .012).

Based on these findings, “we believe that autologous cell therapy seems to be an appropriate alternative to repeated PTA even for patients with no-option chronic limb-threatening ischemia,” he said.

“This is a very important area,” said Andrew J.M. Boulton, MBBS, MD, FRCP, who chaired the oral abstract presentation session during which the findings were presented.

“It is very difficult to get an evidence base from randomized studies in this area, because of the nature of the patients: They’re very sick and we all deal with them in our clinics very regularly,” added Dr. Boulton, professor of medicine within the division of diabetes, endocrinology and gastroenterology at the University of Manchester (England).

Dr. Boulton called the findings a “very important addition to what we know.”
 

New option for no-option CLTI

CLTI is associated with persistent pain at rest, ulcers, and gangrene, and can be the end result of longstanding peripheral arterial disease. Within the first year of presentation, there’s a 30% chance of having a major amputation and a 25% chance of dying.

Importantly, said Dr. Dubský, “there is a big difference in this diagnosis” between patients with diabetes and those without. For instance, CLTI is more diffuse in patients with diabetes than in those without, different arteries are affected and the sclerosis seen can be more rigid and “full of calcium.”

While surgery to improve blood flow is the standard of care, not everyone is suitable. Bypass surgery or endovascular procedures can be performed in only 40%-50% of patients, and even then a therapeutic effect may be seen in only a quarter of patients.

“We need some new therapeutic modalities for this diagnosis, and one of them could be autologous cell therapy,” said Dr. Dubský.
 

Study details

Dr. Dubský and coinvestigators consecutively recruited 130 patients with diabetic foot and CLTI who had been seen at their clinic over a 5-year period. Of these, 87 had not been eligible for standard revascularization and underwent ACT or were treated conservatively.

Of the patients who were not eligible for standard revascularization (‘no-option CLTI), 45 had undergone ACT and 42 had been treated conservatively. Dr. Dubský acknowledged that “his study was not prospective and randomized.”

All patients in the study had at least one unsuccessful revascularization procedure and diabetic foot ulcers, and low tissue oxygenation. The latter was defined as transcutaneous oxygen pressure (TcPO₂) of below 30 mm Hg.

There were little differences in demographic characteristics between the treatment groups, the average age ranged from 62 to 67 years, there were more men (70%-80%) than women; most patients (90%) had type 2 diabetes for at least 20 years. There were similar rates of ischemic heart disease, hypertension, dialysis, and immunosuppressive therapy.

There were no differences in baseline values of TcPO₂ between the groups, and similar improvements were seen in both the ACT and re-PTA groups versus conservative group.
 

ACT in practice

With such promising results, what about the practicalities of harvesting a patient’s bone marrow to make the ACT?

“Bone marrow harvesting usually takes about 20 minutes,” Dr. Dubský said. It then takes another 45 minutes to separate the cells and make the cell suspension, and then maybe another 10 minutes or so to administer this to the patient, which is done by injecting into the calf muscles and small muscles of the foot, aided by computed tomography. The whole process may take up to 2 hours, he said.

“Patients are under local or general anesthesia, so there is no pain during the procedure,” Dr. Dubský reassured. “Afterwards we sometimes see small hematoma[s], with low-intensity pain that responds well to usual analgesic therapy.”

Computed tomography was used to help guide the injections, which was advantageous, Dr. Boulton pointed out, because it was “less invasive than angioplasty in these very sick people with very distal lesions, many of whom already have renal problems.”

“It is surprising though, that everybody had re-PTA and not one had vascular surgery,” he suggested. Dr. Boulton added, however: “These are very important observations; they help us a lot in an area where there’s unlikely to be a full RCT.”

The next step in this research is to see if combining ACT and re-PTA could lead to even better results.

The study was funded by the Czech Republic Ministry of Health. Dr. Dubský had nothing to disclose. Dr. Boulton made no statement about his conflicts of interest.

Bone marrow derived autologous cell therapy (ACT) has been shown to significantly reduce the rate of major amputation at 5 years in people with diabetes who developed critical limb-threatening ischemia (CLTI).

In a study of 130 patients, 64% of 42 patients who were treated conservatively needed a major amputation at 5 years versus just 30% of 45 patients who had been treated with ACT (P = .011).

This compared favorably to the results seen with repeated percutaneous angioplasty (re-PTA), where just 20.9% of 43 patients underwent limb salvage (P = .002 vs. conservative therapy).

Furthermore, amputation-free survival was significantly longer in both active groups, Michal Dubský, MD, PhD, FRSPH, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Dubský, of the Institute for Clinical and Experimental Medicine and Charles University in Prague, also reported that fewer patients who had undergone re-PTA or ACT than conservative treatment had died by 5 years (25.8% and 35.6%, respectively, vs. 61.9%), but that the difference was significant only for the revascularization procedure (P = .012).

Based on these findings, “we believe that autologous cell therapy seems to be an appropriate alternative to repeated PTA even for patients with no-option chronic limb-threatening ischemia,” he said.

“This is a very important area,” said Andrew J.M. Boulton, MBBS, MD, FRCP, who chaired the oral abstract presentation session during which the findings were presented.

“It is very difficult to get an evidence base from randomized studies in this area, because of the nature of the patients: They’re very sick and we all deal with them in our clinics very regularly,” added Dr. Boulton, professor of medicine within the division of diabetes, endocrinology and gastroenterology at the University of Manchester (England).

Dr. Boulton called the findings a “very important addition to what we know.”
 

New option for no-option CLTI

CLTI is associated with persistent pain at rest, ulcers, and gangrene, and can be the end result of longstanding peripheral arterial disease. Within the first year of presentation, there’s a 30% chance of having a major amputation and a 25% chance of dying.

Importantly, said Dr. Dubský, “there is a big difference in this diagnosis” between patients with diabetes and those without. For instance, CLTI is more diffuse in patients with diabetes than in those without, different arteries are affected and the sclerosis seen can be more rigid and “full of calcium.”

While surgery to improve blood flow is the standard of care, not everyone is suitable. Bypass surgery or endovascular procedures can be performed in only 40%-50% of patients, and even then a therapeutic effect may be seen in only a quarter of patients.

“We need some new therapeutic modalities for this diagnosis, and one of them could be autologous cell therapy,” said Dr. Dubský.
 

Study details

Dr. Dubský and coinvestigators consecutively recruited 130 patients with diabetic foot and CLTI who had been seen at their clinic over a 5-year period. Of these, 87 had not been eligible for standard revascularization and underwent ACT or were treated conservatively.

Of the patients who were not eligible for standard revascularization (‘no-option CLTI), 45 had undergone ACT and 42 had been treated conservatively. Dr. Dubský acknowledged that “his study was not prospective and randomized.”

All patients in the study had at least one unsuccessful revascularization procedure and diabetic foot ulcers, and low tissue oxygenation. The latter was defined as transcutaneous oxygen pressure (TcPO₂) of below 30 mm Hg.

There were little differences in demographic characteristics between the treatment groups, the average age ranged from 62 to 67 years, there were more men (70%-80%) than women; most patients (90%) had type 2 diabetes for at least 20 years. There were similar rates of ischemic heart disease, hypertension, dialysis, and immunosuppressive therapy.

There were no differences in baseline values of TcPO₂ between the groups, and similar improvements were seen in both the ACT and re-PTA groups versus conservative group.
 

ACT in practice

With such promising results, what about the practicalities of harvesting a patient’s bone marrow to make the ACT?

“Bone marrow harvesting usually takes about 20 minutes,” Dr. Dubský said. It then takes another 45 minutes to separate the cells and make the cell suspension, and then maybe another 10 minutes or so to administer this to the patient, which is done by injecting into the calf muscles and small muscles of the foot, aided by computed tomography. The whole process may take up to 2 hours, he said.

“Patients are under local or general anesthesia, so there is no pain during the procedure,” Dr. Dubský reassured. “Afterwards we sometimes see small hematoma[s], with low-intensity pain that responds well to usual analgesic therapy.”

Computed tomography was used to help guide the injections, which was advantageous, Dr. Boulton pointed out, because it was “less invasive than angioplasty in these very sick people with very distal lesions, many of whom already have renal problems.”

“It is surprising though, that everybody had re-PTA and not one had vascular surgery,” he suggested. Dr. Boulton added, however: “These are very important observations; they help us a lot in an area where there’s unlikely to be a full RCT.”

The next step in this research is to see if combining ACT and re-PTA could lead to even better results.

The study was funded by the Czech Republic Ministry of Health. Dr. Dubský had nothing to disclose. Dr. Boulton made no statement about his conflicts of interest.