Transplanted kidneys from deceased donors who had acute kidney injury (AKI) show no differences in short- or long-term failure, or graft rejection, compared with those that came from donors without AKI, in some of the strongest evidence on the issue to date.
Yet many organs from donors with AKI still go unused in the United States, according to the study authors.
“We estimate there may hundreds of kidneys with AKI each year that are going unused but could be transplanted,” senior author Chirag Parikh, MD, PhD, said in a press statement.
“Therefore, we are urging the transplant community to bring AKI kidneys into the donor pool with more confidence,” said Parikh, who is director of the Division of Nephrology at the Johns Hopkins University School of Medicine, in Baltimore, Maryland.
Previous research, including a recent study from Parikh’s team reported by Medscape Medical News, has supported the use of select AKI kidneys in transplantation, and many centers do transplant such organs.
However, studies on the issue have often involved smaller sample sizes and data are meanwhile lacking on the allocation of such kidneys.
Comparing Transplanted Kidneys From Those With AKI to Those Without
For the new study, published online January 8 in JAMA Network Open by Caroline Liu, MHS, also of Johns Hopkins, and colleagues, researchers evaluated data from 6722 deceased donors with AKI and 15,310 deceased donors without AKI from 2010 to 2013 who donated at least one kidney for transplant.
AKI was defined as having at least a 50%, or 0.3-mg/dL, increase in terminal serum creatinine level from admission.
Using a 1:1 propensity score-matched analysis, donors with and without AKI, and their corresponding kidney recipients, were matched, allowing for accurate comparison of characteristics including age, sex, ethnicity, AKI stage, and other medical conditions.
The deceased donors were a mean age of 40.4 years; 63% were males, and most had AKI stage 1 (69%), followed by stage 2 (21%) and stage 3 (10%). Of the 25,323 recipients that were analyzed, 61% were males and their mean age was 52 years.
At a median follow-up of 5 years (range, 4-6), there were no significant differences between those who received AKI kidneys and the non-AKI kidneys in terms of death-censored graft failure (hazard ratio [HR], 1.01; 95% CI, 0.95 – 1.08) or all-cause graft failure (HR, 0.97; 95% CI, 0.93 – 1.02).
Those receiving AKI kidneys did have significantly higher rates of developing delayed graft function (29% vs 22%; P < .001), which the authors note is consistent with previous studies.
The findings were consistent regardless of the AKI stage of the donor.
Rates of primary nonfunction among recipients were low (120 of 25,323; 0.5%), regardless of donor AKI status.
The authors note that although delayed graft function is an important issue in transplantation, the outcomes are typically similar between AKI and non-AKI kidney recipients.
“Although delayed graft function requires interventions (eg, additional dialysis sessions, modified initial immunosuppression regimens, and closer recipient monitoring) during initial follow-up, the lack of sustained risk suggests that recovery after delayed graft function is comparable between AKI and non-AKI kidneys, without substantial long-term sequelae,” they write.
More Than a Third of AKI Kidneys Go Unused
When further looking at the allocation of AKI kidneys, the authors found that among 17,468 (85%) of 20,550 AKI kidneys that were available and harvested over the 3-year study period, only 12,711 (61.8%) were transplanted.
Of the more than 7000 kidneys that remained, 3030 were never procured and 4757 were discarded after recovery.
“This means almost 8000 organs were either rejected after procurement or never obtained at all simply because the donors had acute kidney injury,” Parikh said in the statement issued by Johns Hopkins.
The authors note the allocation rates are consistent with the national discard or rejection rate for all potential donor kidneys, which is approximately 18%, and the rate jumps to about 30% for AKI kidneys.
Nearly 9000 of the approximately 95,000 Americans with end-stage renal disease who are awaiting organs drop off the list each year because of death or deteriorating health, according to data from the US Department of Health & Human Services.
Meanwhile, the need for donor kidneys is rising at 8% per year, and the availability of organs is not increasing at a similar rate, according to data from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
“From our study’s findings, we believe that the transplant community should continue to use deceased donor AKI kidneys and consider research to investigate whether currently discarded AKI kidneys from deceased donors without substantial comorbidities can be used more effectively,” the authors conclude.
Hospitals must take steps to control exposure to reproductive hazards in the surgical workplace, according to the authors of a new review.
Female surgeons face higher rates of pregnancy complications and infertility than women in the general population, Dr. Matilda Anderson of Western Health Surgical Department, in Footscray, Australia, and Dr. Rose H. Goldman of Harvard Medical School, in Boston, note in JAMA Surgery.
While the fact that woman surgeons have their first child later, on average, than the general population may be a contributing factor, the authors add, “the association of occupational reproductive hazards with infertility and pregnancy complications in this population has not been adequately explored or defined.”
They discuss potential reproductive hazards in operating rooms, including radiation, surgical smoke, working conditions, sharps injury, anesthetic gases and toxic agents used interoperatively, and make evidence-based recommendations for reducing exposure.
Steps the authors list to limit radiation exposure include adhering to ALARA (“as low as reasonably achievable radiation exposure”) principles, mandating use of personal protective garments or shielding, and requiring pregnant women to use a fetal dosimeter and be checked monthly.
While no studies have looked at the reproductive effects of surgical-smoke exposure, Dr. Anderson and Dr. Goldman note, individual smoke components have been linked to infertility and worse maternal and fetal outcomes.
They recommend installing and maintaining ventilating systems in operating rooms, mandating smoke evacuation rather than room suction, and considering the use of high filtration masks during standard surgery and N95 respirators for operations that generate aerosols.
The authors also state that both male and female surgeons actively trying to conceive should avoid working in operative settings where hyperthermic intraperitoneal chemotherapy (HIPEC) is being used.
“At a minimum, workplaces need to comply with existing guidelines or standards, recognizing that these may not be protective for reproductive outcomes, and so that it may be wise to do more. Alternative work duties and/or conditions should be readily available. Priority should be given to controlling exposure rather than restricting surgeons’ activity,” the authors state.
“Given the limited data regarding operating room hazards and reproductive outcomes, as well as introduction of new operating room environmental exposures, more research is needed to define their reproductive effects, as well as effective and practical interventions to reduce exposure. In addition, prospective studies of women of reproductive age are needed to measure exposure levels and accurately record pregnancy outcomes,” they conclude.
Compared with kidney transplantation alone, simultaneous pancreas-kidney (SPK) transplantation was associated with an almost twofold lower 10-year mortality among type 1 diabetics, in a retrospective study.
“Patients with type 1 diabetes and end-stage renal failure experience inferior survival while on dialysis,” Dr. Johan W. de Fijter of Leiden University Medical Center in the Netherlands told Reuters Health by email. “These patients benefit most from a pre-emptive (i.e., before initiation of dialysis) kidney transplantation, in essence requiring availability of a suitable living donor.”
“The results of this (Netherlands) nationwide evaluation provides evidence that additional restoration of endogenous insulin secretion resulted in significantly better overall patient survival beyond (that seen in) recipients of a living kidney transplant alone,” he said.
The study included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy or received a first kidney transplant between 1986 and 2016.
As reported in Diabetes Care, of the 996 who received new kidneys, 42% received a deceased-donor kidney; 16%, a living-donor kidney; and 42%, an SPK transplant. The mean ages at transplantation were 50, 48, and 42 years, respectively.
Mean age at start of dialysis was 59 years for patients who stayed on chronic maintenance dialysis and 44 years for transplant recipients.
Crude survival was highest in SPK recipients and lowest in recipients of a deceased-donor kidney. Median survival time was 7.3 years for deceased-donor kidney recipients; 10.5 years for living-donor kidney recipients; and 16.5 years for SPK recipients.
SPK recipients with a functioning pancreas graft at one year (91%) had the highest survival (median 17.4 years).
Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios for 10- and 20-year all-cause mortality for living-donor kidney recipients were 0.79 and 0.98, and for SPK recipients, 0.67 and 0.79.
Further, a treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 and 0.69, respectively.
Summing up, the authors state, “Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate.”
Dr. de Fijter said, “These results support the mandatory exchange of combined pancreas-kidney transplants in case donors with a suitable pancreas are identified. A second key issue is early referral of type 1 diabetics for timely pre-transplant work-up and placement on the active SPK waiting list (eGFR <20 ml/min/1.73m2), well before the need of a vascular access and initiation of dialysis. In the current cohort, over 30% of patients received a preemptive SPK transplant.”
Availability of SPK compared with kidney transplant alone, “is a relevant consideration in view of the scarcity of organs available for transplantation, especially from deceased donors,” he added. “Currently, the main restriction is the donor age, which is generally kept under 56 years,” and the age limit is the same for recipients.
Dr. Ron Shapiro, surgical director of the Kidney and Pancreas Transplant Program at Mount Sinai’s Recanati/Miller Transplantation Institute in New York City, commented in an email to Reuters Health, “The superior survival with SPK has been well described in the literature, and this…analysis confirms previous studies.”
“The concern has always been that there is a selection bias, in that younger and healthier patients get the combined procedure, and older and less healthy patients get just the kidney,” he noted. “In the U.S., approximately 1,000 pancreases are transplanted annually, compared to 19,000 kidneys. Younger, better-risk diabetic patients are already routinely listed for SPK (or living donor kidney transplant with pancreas after kidney transplant).”
“There are only enough pancreases to take care of 0.1% of diabetics, so we are dealing with a very small number of organs,” he added.
One of the success stories in recent years in the treatment of metastatic, hormone-receptor positive breast cancer has been the addition of drugs acting as inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) on top of endocrine therapy. Three such drugs are now available — palbociclib (Ibrance, Pfizer), ribociclib (Kisqali, Novartis), and abemaciclib (Verzenio, Lilly). However, many patients also respond well to endocrine therapy alone — without the extra cost and extra toxicity of adding on a CDK4/6 inhibitor.
So a pressing clinical question is which patients should get these new drugs?
In search of an answer to this question, researchers from the US Food and Drug Administration (FDA) investigated whether it was possible to identify patients who respond and those who do not.
To do so, the team conducted the first comprehensive pooled data analysis of randomized clinical trials of all marketed CDK4/6 inhibitors to assess efficacy in subgroups of patients with metastatic disease that is hormone-receptor positive.
The idea was to evaluate treatment effects in “less common” clinicopathological subgroups of patients, who are widely “believed to have differing degrees of endocrine sensitivity,” write the authors, led by Jennifer Gao, MD, of the FDA’s Center for Drug Evaluation and Research, Office of Oncologic Diseases.
The team speculated that some subgroups would have lesser benefit from the new drugs.
However, they found that the addition of CDK4/6 inhibitors to endocrine therapy “seemed to benefit all clinicopathological subgroups of interest in this pooled analysis,” the authors conclude.
The study was published online December 16 in the Lancet Oncology.
Approached for comment, Saroj Niraula, MD, from the University of Manitoba and CancerCare Manitoba, said that these researchers asked a “noble question,” but their finding “did not add a lot to what we already know.”
Most notably, “the study has not identified those who can be spared the combination,” Niraula told Medscape Medical News.
Niraula explained that study was unable to identify patients for whom endocrine therapy alone might result in similar outcomes to endocrine therapy plus a CDK4/6 inhibitor.
“It’s an excellent study and a commendable use of the FDA’s privileged access to individual-level patient data” he said, adding that it is a “strong” meta-analysis.
The study “adds value” to the literature because some of the prognostic subgroups analyzed have results in keeping with the primary data in terms of having significantly improved outcomes, he commented.
“We still don’t know the answer to the most important question with CDK4/6 inhibitors which is: What is most sensible sequence of use of CDK4/6 inhibitors in treatment of metastatic breast cancer,” he added.
Niraula lobbied for using single-agent endocrine therapy initially in appropriate metastatic patients and suggests saving CDK4/6 inhibitors for progression. Later-line use is also supported by current data, he said. “Efficacy results appear stronger in the second-line setting from the data we have so far,” he said.
Study Details
The meta-analysis encompassed seven phase 3 clinical trials with a total of 4200 patients with advanced disease randomized to CDK4/6 inhibitors plus endocrine therapy or placebo plus endocrine therapy (in both the first-line and second-line settings). Endocrine therapies included letrozole or anastrozole (aromatase inhibitors) or fulvestrant, but excluded tamoxifen. All studies had a primary endpoint of progression-free survival (PFS).
In the pooled analysis, the difference in estimated median PFS between all patients who received CDK4/6 inhibitors and those given placebo was 8.8 months (hazard ratio [HR], 0.59).
At a median follow-up of 22.6 months, 993 (24%) of the 4200 patients had died, with an estimated overall survival HR of 0.89.
Notably, the PFS survival results favored the CDK4/6 inhibitor group in all clinicopathological subgroups.
In the subgroup analysis, patients with disease-free interval of up to 12 months (n = 180) had the most notable benefit in the CDK4/6 inhibitor group, with a difference in estimated median PFS of 5.8 months in favor of a CDK4/6 inhibitor plus an aromatase inhibitor vs placebo plus an aromatase inhibitor.
The study authors conclude: “Further research is needed to identify patient subgroups for whom endocrine therapy alone might be appropriate for first-line or second-line treatment of hormone receptor-positive, HER2-negative metastatic breast cancer.”
Study is “Clearly Important”
The new work is “clearly important,” say Giuseppe Curigliano, MD, University of Milan, Italy, and Sibylle Loibl, MD, German Breast Group, Frankfurt, Germany, in an accompanying editorial.
The editorialists observe that the efficacy analysis was carried out in less common subgroups of patients with breast cancer that cannot be well analyzed in single trials due to their small numbers. These included women with progesterone receptor negative disease; those with a disease-free interval up to 12 months; de-novo metastatic, lobular histology, and bone-only disease; those with visceral metastases; and patients aged 40 years or younger.
The editorialists would like to expand that list, saying “other subgroups might also be of interest.”
For example, they suggest that the analysis could be boosted by comparing patients with primary vs secondary endocrine resistance.
Patients with primary endocrine resistance include those with relapse during the first 2 years of adjuvant endocrine therapy or have progressive disease within the first 6 months of first-line endocrine therapy for metastatic breast cancer, while on endocrine therapy.
Patients with secondary endocrine resistance include those who relapse while on adjuvant endocrine therapy after the first 2 years, relapse within 12 months of completing adjuvant endocrine therapy, or have progressive disease at least 6 months after initiating endocrine therapy for metastatic breast cancer, while on endocrine therapy.
Furthermore, identifying patients with varying degrees of endocrine responsiveness according to the minimum cutoff of estrogen receptor expression (> 1% to 100%) “could help to select true non-responders,” they add.
There’s a lot of work to be done with regard to optimizing the use of CDK4/6 inhibitors, the editorialist comment.
“Across all CDK4/6 inhibitor studies, we still need to further characterize the overall survival outcomes and other exploratory efficacy endpoints in those subgroups of patients with more favorable prognostic factors,” they write.
Those include patients who have not previously received endocrine therapy, those with bone-only disease, and those with late recurrence.
Such data, say the pair, “could help to address the question of whether or not CDK4/6 inhibitors should be used as first-line treatment in combination with estrogen therapy or following initial estrogen therapy alone.”
They single out the ongoing SONIA study as being potentially helpful. The study aims evaluate whether the sequence of an aromatase inhibitor plus CDK4/6 in first line, followed by fulvestrant in second line, is superior to the sequence of an aromatase inhibitor in first line followed by fulvestrant plus CDK4/6 in second line.
The editorialists also mention early stage disease — that is, the potential use of CDK4/6 inhibitors in the adjuvant setting. Large ongoing studies in this setting, they say, “will provide additional insights into improved patient selection and personalized treatment approaches.”
Some doctors stay away from social media because they see numerous potential risks.
Physicians in particular are vulnerable on social media. They face strict restrictions on patient privacy, the need to present absolutely correct medical information, and pressure to present a public image that is above reproach.
However, these concerns don’t mean you have to give up on social media. They just mean that you need to understand the specific risks and take measures against them.
With social media, more than ever, people need to exercise discretion. You can surmise most of the precautions you should take by using common sense. Always take a moment to think about the implications of what you are about to do.
Here are some of the common social media pitfalls for doctors:
1. Not Recognizing the Viral Nature of Social Media
Social media operates like a megaphone. It can amplify a stray comment across many channels, go viral, and suddenly reach tens of thousands of people.
Any mistake or misstatement you make can be very hard to erase. You can take down an ill-conceived post, but it may already be too late. It may have been passed along in screenshots and other means.
For example, a St. Louis ob-gyn complained on Facebook about a particular patient’s tardiness with appointments. Someone posted a screenshot of the physician’s post to her hospital’s Facebook page, and many patients reacted. The hospital determined that her comments did not violate the patient’s privacy and she kept her job, but her very public comments made her look bad.
2. Violating Patients’ Privacy
Social media’s emphasis on being transparent and personal provides many opportunities for a patient’s privacy to be violated. Risky situations include crowdsourcing the diagnosis of a patient with colleagues, highlighting patients’ cases on a practice website, and posting photos where a patient’s face or patient information inadvertently shows up in the background.
Potential violations happen fairly often. In a study of 271 medical blogs written by doctors and nurses, 45 (16.6%) gave sufficient information for patients to identify their doctors or themselves. Three of the blogs showed recognizable images of patients.
You can violate privacy without making any obvious identification, such as a patient’s name or face. Patients can be identified when connected to an unusual accident, a rare condition, or admission to a certain hospital or unit. In addition to violating the Health Insurance Portability and Accountability Act (HIPAA) or a state privacy law, these breaches can prompt an action by the state medical board and even result in the loss of your job.
Several years ago, a doctor posted her frustrations with a trauma patient. Although she did not name him, she gave enough information to identify him. As a result, she was fired from the hospital, reprimanded by the state medical board, and fined $500.
It’s a good idea not to refer to a particular patient at all, but if you must do so, eliminate such specifics as the patient’s age, the name of the hospital, or the circumstances of an accident. If you are concerned that the person’s identity could still be revealed, such as with a rare condition, don’t use social media; instead, send the information directly to a specific colleague.
When physicians share radiologic images or dermatologic samples of patients, they must remove all identification from them, including written remarks, birthmarks, scars, tattoos, jewelry, and unique surroundings.
If you want to identify your patients for marketing or other purposes, you’ll need their written consent. The consent form should include the purpose of the identification, who is authorized to make it and when, information on patient’s right to revoke the authorization, and the patient’s signature. Have an attorney approve the wording.
3. Responding to Patients’ “Friend” Requests
Patients occasionally send Facebook friend requests to their doctors, and doctors may regret having to turn them down. After all, having a positive relationship with your physician promotes confidence, encourages compliance with treatment, and may even aid healing.
In one study about doctors receiving friend requests, 42% said they would not always reject them. But having a patient on your personal Facebook page is never a good idea. On your page, they could reach anyone in your network of friends, view your personal photographs, or read your personal blog.
These patients could also begin asking you for medical advice, which could lead to a HIPAA violation. Or perhaps they might seek a romantic relationship, which, if not stopped, could prompt disciplinary action by your medical board.
The solution is to set up two Facebook pages: one that is private for your family and friends, and one that is professional for your patients and the general public. You can take similar steps on other social media such as Twitter and Instagram.
4. Giving Specific Medical Advice to Patients
When people respond to your posts providing general advice on treatment, they often ask about their own specific case. It’s never wise to respond to these questions. Your reply and subsequent back-and-forth messaging could become a HIPAA violation.
It’s also possible that your reply could form the legal basis of a physician–patient relationship. If the patient thinks your advice led to some injury, you might be sued for malpractice.
When patients ask for specific advice, suggest that they come in for an office visit. You can also add a boilerplate statement to your blog that you won’t address specific patient care issues through social media.
5. Posting Unprofessional Behavior
On their Facebook pages, some doctors leave comments and photos that show them in an unprofessional light, without thinking about the consequences. They don’t seem to realize that patients, employers, and potential employers could view these posts.
In a study of Facebook pages of newly minted urologists, 40% had potentially objectionable content, including profanity, drunkenness, unprofessional behavior at work or meetings, and sexually suggestive poses or clothing.
Think about all the people who might view these posts, and what their reactions might be. In a survey of job recruiters, 55% had reconsidered job candidates on the basis of their social media profiles, usually in an unfavorable way.
The best solution is to simply stop posting such material. However, even fairly innocent photos of a doctor holding a beer can at a professional meeting or hanging out on the beach during a vacation might prompt unfavorable reactions from some patients.
The answer, again, is to have a personal page that is separate from your professional page. On Facebook, you can also adjust your privacy settings, which allow sharing with just a small group of friends. But keep in mind that privacy settings can often be porous.
6. Making Unprofessional Statements on Social Media
Social media is bristling with strong opinions on everything from politics and race to electronic health records. Some people think they are protected by a pseudonym, but it can be fairly easy to detect their identity.
Comments about race or gender, in particular, can go viral and lead to firings or resignations. When a Texas doctor commented that “female physicians do not work as hard,” he was forced to give up his leadership positions at a large practice. And when a Colorado anesthesiologist posted racist comments about Michelle Obama, she was forced to resign from her health system.
Some physicians think public posts are an appropriate place to dump on patients. In the study of 271 doctors’ blogs, 48 portrayed patients negatively, including one that stated, “She was a stupid, lazy, selfish woman all of which characteristics are personal problems, not medical issues or barriers to care.”
Patients don’t like negative comments in general, even if they’re not directed at them. A recent study found that healthcare professionals who posted even one negative comment on Facebook seemed to have lost credibility among potential patients.
The obvious solution is to stop using social media as your private diary. Keep animosities to yourself. And if you come across a post that is abusive of you, be polite and civil. In many cases, others will come to your defense, and the abusive commenter will drop out of the conversation.
If you find yourself writing a post in anger, set it aside before sending it. Review it after you have calmed down, or have a colleague review it.
7. Violating Employers’ Restrictions on Social Media Use
Practices, hospitals, and health systems have all kinds of restrictions on use of social media, and it would be useful for you to know about them before you go to work there. These restrictions may be too onerous if you are a heavy social media user.
Many organizations ban use of social media on workplace computers, and they may actually block access to it on their computers. But they can’t block access through your smartphone or laptop, so they set down rules about social media use in general.
Some employers go further and retain the right to take control of your social media activities. The Cleveland Clinic’s social media policy, for example, states that it “reserves the right to monitor, prohibit, restrict, block, suspend, terminate, delete, or discontinue your access to any Social Media Site, at any time, without notice and for any reason and in its sole discretion.”
Some organizations want you to present material in a certain manner. Massachusetts General Hospital states that although you can post views that are inconsistent with hospital policy, you should not at the same time reveal that you work for the hospital. The hospital also advises to write in the first person and indicate that your statements are your personal opinion.
8. Not Revealing Conflicts of Interest on Social Media
Blog writers rarely disclose conflicts of interest. In a study of blogs written by health professionals, 11% contained endorsement of specific healthcare products, and none of those provided disclosures.
State medical boards see this as a problem. When writing about a product or procedure, “physicians must reveal any existing conflicts of interest and they should be honest about their credentials as a physician,” according to the Federation of State Medical Boards.
The Federal Trade Commission also requires disclosure of material connections between advertisers and endorsers, which can take the form of payments or free products.
9. Behavior That Blunts Your Impact
The following social media behavior won’t lead to fines or firings, but they can create negative impressions about yourself.
Making it all about you. Some people use social media to talk about themselves — how they felt today and what they had for lunch — and they wonder why no one visits their page.
Social media is about sharing. Remember to post, tag, like, comment, and share your friends’ content. Showing interest in others is a good way to get others to show interest in you.
LinkedIn is a great place to give recommendations and endorsements of colleagues. To endorse someone, click on one of the skills that colleagues list on their profiles. Recommendations are long-form endorsements of one’s quality of work. In this way, you can create an economy of favors.
Be sure to update your profile. Your profile is an important resource for prospective patients. Outdated practice profiles may create the impression that you’re out of touch and may not be worth keeping up with. If your practice has added new doctors and new locations, it’s time to update your profile.
Also, make sure all your profiles across social media are consistent. Conflicting information could make your practice look a little sketchy. Potential patients are looking for a practice they can trust.
10. Posting Too Much.
Many busy doctors post too little and don’t get a strong following, but there are also people who post too much. If your followers are getting too many posts, they don’t have a chance to enjoy each post, and they may begin to ignore your content. Two to three posts a week usually suffices.
Social media presents a variety of considerations that prompt many physicians to steer clear of it. But this new modality has become too important to ignore, and physicians can learn how to avoid its potential pitfalls.
A 1:1 ratio of fresh frozen plasma to packed red blood cells (FFP:pRBC) is associated with the lowest 24-hour mortality in trauma patients needing massive transfusion, according to a study of data from a nationwide cohort.
Lower FFP:pRBC ratios, such as 1:2 or 1:3, were associated with mortality increases, researchers report in the Journal of the American College of Surgeons.
“Until a larger randomized controlled study is performed, we suggest the use of a 1:1 FFP:pRBC ratio rather than a 1:2 ratio in the massively transfused trauma patient,” Dr. Haytham Kaafarani of Massachusetts General Hospital, in Boston, and colleagues write.
Theirs is the largest national study of massively transfused hemorrhaging trauma patients, and the largest to show a statistically significant mortality benefit of the 1:1 FFP:pRBC ratio versus lower ratios, they note.
Dr. Jeremy W. Cannon, an associate professor of surgery at the University of Pennsylvania’s Perelman School of Medicine, in Philadelphia, who was not involved in the study, called the work “very important” and highlighted its sound methodology in a phone interview with Reuters Health. He also said the authors had “zeroed in on the patients who have the highest risk of dying of hemorrhage.”
The findings contrast with those of the 2015 randomized PROPPR study, which found no significant difference in 24-hour or 30-day survival between patients who received 1:1:1 versus 1:1:2 ratios of FFP:platelets:pRBC. However, exsanguination, the predominant cause of death in the first 24 hours, was significantly less likely in the 1:1:1 group.
The new results suggest that “the correct interpretation of the well-known PROPPR trial is perhaps that the 1:1:1 ratio is indeed superior” and that PROPPR’s failure to show that might have been due to a type-II error (a false negative) and a smaller patient sample than was needed.
Drawing from the American College of Surgeons Trauma Quality Improvement Program 2013-2016 database, Dr. Kaafarani’s team identified all trauma patients age 18 and older who needed at least 10 units (3,000 cc) of pRBC and at least one unit (300 cc) of FFP within 24 hours of admission.
They included 4,427 patients with a mean age of 41 (79% male), most of whom received transfusions with a 1:1 (31%), 1:2 (41%) or 1:3 (11%) FFP:pRBC ratio.
The 1:1 subgroup had the highest mean injury-severity-scale score and the highest proportions of pelvic and gastrointestinal injuries. Patients in higher-ratio subgroups spent significantly more time in the emergency department and required laparotomy and embolization significantly more often than those in other cohorts.
When compared with the 1:1 ratio subgroup, the odds of mortality increased to 1.23 for a 1:2 ratio, 2.11 for 1:4 and as high as 4.11 for 1:5 (all P<0.05).
In the study’s most important finding, Dr. Kaafarani told Reuters Health by email, “we showed that 1:1 is statistically better than 1:2, which the PROPPR trial failed to do, likely because of insufficient number of patients.”
Dr. John B. Holcomb, a professor of surgery at the University of Alabama at Birmingham and lead author of the PROPPR report, told Reuters Health by email, “It is disconcerting that a substantial portion of massively transfused patients still receive less than optimal transfusion ratios.”
He noted the difficulty in reaching a balanced ratio of plasma, platelets and RBCs quickly in bleeding patients and pointed to the authors’ mention of a trend in recent studies suggesting whole blood transfusion. Whole blood, Dr. Holcomb said, “always delivers a perfectly balanced ratio, includes platelets and fibrinogen in addition to plasma and RBCs, and is cheaper than individual components.”
Bariatric surgery is associated with a significant decrease in the long-term risk of venous thromboembolic events (VTEs), principally deep vein thrombosis (DVT), according to findings from the UK Clinical Practice Research Datalink (CPRD).
Obesity is associated with a 2- to 3-fold increased risk of VTEs, including pulmonary embolism and DVT. Surgery is also a risk factor for VTE, and the long-term effect of bariatric surgery on VTE remains unclear.
Dr. Maddalena Ardissino from Imperial College London and colleagues analyzed data from 8146 obese patients, including 4073 who had undergone bariatric surgery and 4073 matched controls.
During a median follow-up of 10.7 years, the adjusted rates of VTE were significantly lower in the bariatric surgery group (1.7%) than in the control group (4.4%), with a number needed to treat (NNT) to prevent 1 VTE of 37, according to the online report in Annals of Surgery.
This difference was driven by significant differences in DVT events (1.1% after bariatric surgery versus 3.4% among controls), whereas the rate of pulmonary embolism events did not differ significantly between the groups.
All-cause mortality was significantly lower in the bariatric surgery group (1.3%) than in the control group (4%).
The strongest reduction in VTE risk was observed in patients with class II obesity (BMI 35-40), with a smaller effect in patients with class I obesity (BMI 30-35), and no significant reduction in patients with class III obesity (BMI above 40).
“Overall, this study adds to the rapidly growing pool of evidence that highlights the wide-ranging metabolic, clinical, and lifestyle benefits of bariatric surgery for the management of patients with obesity and provides new knowledge regarding its effect on lowering long-term VTEs in this high-risk population,” the researchers conclude.
Dr. Jon C. Gould from Medical College of Wisconsin, in Milwaukee, who has researched various aspects of bariatric surgery, told Reuters Health by email, “The body of literature outlining the long-term benefits of bariatric surgery from a health, quality of life, and cost perspective is robust. This is one more example of a positive impact of bariatric surgery over a very long term.”
“In many parts of the United States, access to bariatric surgery is limited by arbitrary insurance exclusions,” he said. “This is short-sighted. Far less than 1% of the eligible population undergoes a bariatric procedure in the U.S., mostly due to these access issues.”
Dr. Shaun Daly from University of California Irvine Medical Center, in Orange, who recently reported risk factors for VTE after bariatric surgery, told Reuters Health by email, “While there is a known increased risk of short-term VTE in obese patients undergoing weight-loss surgery, the long-term reduction in VTE, specifically DVT, appears to outweigh this risk and improves overall health and risk in obese patients.”
“Surgery reduces long-term VTE risk compared to matched obese individuals, (but) the long-term risk in both these populations remains higher than the general non-obese population, and a high level of suspicion needs to be maintained in any obese patient with potential signs and symptoms of VTE disease, post-surgery or not,” he said.
Dr. Ardissino did not respond to a request for comments.
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