Category: Medicine

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1:1 Ratio Of Plasma, RBCs Appears Best For Hemorrhaging Trauma Patients

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.”

Source : Medscape

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DVT Risk Decreases After Bariatric Surgery

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.

SOURCE: http://bit.ly/358SLvo Annals of Surgery, online December 17, 2019.

Source : Medscape

 

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Increased Risk Of ‘OA’ Incase Of Knee Injury In Young-age

Injuring a knee in youth dramatically increases the risk for osteoarthritis, researchers say.

Knees injured at age 25 to 34 years were six times more likely to develop osteoarthritis within 11 years, reported Barbara Snoeker, from Lund University in Sweden, and colleagues in an article published online December 11 in the British Journal of Sports Medicine.

The risk for osteoarthritis varied with the type of injury. “Of all injury types, cruciate ligament injuries, meniscal tears and intra-articular fractures yielded the highest estimates of increased risk,” they write.

Previous studies have identified knee injury during adolescence and young adulthood as an important risk factor for osteoarthritis. But most of these studies used retrospective analysis, and those that relied on patients’ recall may be particularly unreliable, the researchers say.

There are too few studies in young people to yield reliable estimates of the magnitude of risk, they add. In addition, the existing studies have focused mostly on cruciate ligament and meniscal tears, leaving open questions about other types of knee injury.

To fill this gap, Snoeker and colleagues analyzed data from the Skåne Health Register, which includes all healthcare consultations involving the 1.3 million people who live in Skåne, Sweden. They identified 5500 people who were 25 to 34 years of age when they were diagnosed with a knee injury for the first time from 1999 to 2007. The study excluded people with existing osteoarthritis.

The researchers compared this cohort with 143,788 people of the same age range who had not injured a knee during this period but were in the database as a result of unrelated medical consultations.

After 19 years, 11.3% of the people with injured knees were diagnosed with knee osteoarthritis, compared with 4.0% of the people who had no knee injuries.

After adjusting for age, sex, residential area, education, income, diabetes, obesity, and hypertension, the hazard ratio (HR) for osteoarthritis in the injured knees compared with the uninjured knees was 5.7 11 years after the injury. The adjusted HR ratio after 11 years was 5.3 for men and 6.5 for women.

For people younger than 30 years, the adjusted HR was 7.6, whereas for people older than 30 years, it was 4.7 after 11 years. This reflects the lower baseline risk for osteoarthritis in younger people, the researchers explain.

The adjusted HRs after 11 years varied with the type of knee injury. The adjusted HRs were 8.2 for cruciate ligament injury, 7.6 for meniscal tear, 7.0 for a fracture of the upper end of the tibia/patella, 6.5 for injury to multiple structures, 5.9 for a dislocation, 5.2 for a cartilage tear/other injury, 4.9 for collateral ligament injury, and 3.2 for contusion.

On average, people with a cruciate ligament injury developed osteoarthritis 16 months faster than people without knee injuries who also developed osteoarthritis. For meniscal tears, the difference was 12 months, and for fractures, 8 months.

The researchers were surprised there was not a bigger difference in disease-free time. They speculate that those people without injuries who developed osteoarthritis must have had some other risk factor, such as a genetic predisposition or obesity.

“To the best of our knowledge, our study is the first that used a cohort from the general population of young adults to estimate the risk of a wide variety of knee injuries on the development of clinically-evident knee [osteoarthritis],” the researchers write.

Source : Medscape

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Acupuncture & Acupressure Helps In Pain Management In Cancer Patients

Acupuncture and acupressure may reduce pain in cancer patients and help decrease use of pain drugs, including opioids, according to new findings.

A systematic review of 17 randomized clinical trials and a meta-analysis of 14 trials found a significant association between real acupuncture, as compared to sham acupuncture, and a reduction in pain.

In addition, acupuncture was associated with less use of analgesics.

Overall, the evidence level was “moderate,” say the authors.

“Cancer pain is inadequately managed clinically due to limited and effective therapeutic options,” explained study author Charlie Changli Xue, PhD, School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia. “This study demonstrated that acupuncture and acupressure should be considered as an option in clinical setting, particularly when pharmacotherapy alone has not offered adequate relief.”

Acupuncture and acupressure should be better integrated into practice guidelines for patients with cancer pain, he told Medscape Medical News. “Acupuncture/acupressure can be delivered by doctors with adequate acupuncture training or qualified acupuncturists accredited by regulatory bodies or members of reputable professional associations,” he said.

The study was published online December 19 in JAMA Oncology.

More than 70% of patients with cancer experience pain, but it is inadequately controlled in nearly half of patients, note the authors. The current opioid crisis in the United States has exacerbated challenges in pain management, and there has been an increasing interest in nonpharmacologic interventions to relieve pain. Both the American Society for Clinical Oncology and the National Comprehensive Cancer Network have recommended the use of nonpharmacologic methods for managing pain, including acupuncture, despite inconsistent results in studies.

The authors point out that although 20 systematic reviews have established an association between acupuncture and cancer pain relief, none reached a definitive conclusion. But more recent rigorous randomized clinical trials were not included in previous systematic reviews.

Reduction in Pain

In this study, Xue and colleagues conducted an analysis of published randomized clinical trials in order to evaluate the relationship between acupuncture and acupressure and pain reduction in cancer patients.

A total of 17 randomized trials were included in the systematic review or qualitative synthesis. Of these, results of 14 studies, which included 920 patients, were pooled through a meta-analysis. The studies were conducted globally; seven (41%) were conducted in China, six (35%) in the United States, and one (6%) each in Australia, Brazil, France, and Korea.

Of the 17 studies, nine (53%) were sham controlled, and eight (47%) were open-label trials.

Random-effects modeling was used to calculate the effect sizes of the randomized clinical trials that were included.

With regard to pain intensity, pooled results from seven blinded randomized studies that were deemed high quality by the study authors showed an association between pain reduction and real acupuncture vs sham acupuncture (mean difference, −1.38 points; 95% confidence interval [CI], −2.13 to −0.64; I 2 = 81%).

Results from six open-label trials showed that, in comparison with analgesics, pain intensity was reduced when acupuncture was combined with acupressure (mean difference, −1.44 points; 95% CI, −1.98 to −0.89; I 2 = 92%). A significant reduction in pain without heterogeneity was seen in three studies that compared acupuncture with control persons who were on a wait list (mean difference,−1.63 points; 95% CI,−2.14 to −1.13). The evidence grade was moderate because of the substantial heterogeneity among studies, say the authors.

Two of the open-label studies without heterogeneity reported that a maintenance dose of analgesics was administered during the trial period. Pooled results showed that there was a significant decrease in the dose of analgesics among patients who received acupuncture plus analgesic therapy in comparison with the patients who received only analgesics (mean difference, −30.00 mg morphine equivalent daily dose; 95% CI, −37.5 mg to −22.5 mg).

Integrating acupuncture into pain and symptom management plans for cancer patients remains a challenge. Factors include the cost of treatments and lack of insurance coverage. Both have been identified as major barriers to the use of acupuncture.

“While action is needed from insurance companies to reconsider their position — the inclusion of acupuncture for the such patients — I think, in longer term, research is also needed to demonstrate value for money by including acupuncture/acupressure for rebate,” said Xue. “As stated in the paper, we encourage further trials on specific types of cancer to further improve the level of evidence to support better clinical decision making and to assist the insurance companies’ decision making for inclusion of acupuncture/acupressure into plans.”

Source : Medscape

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Triple Negative Breast Cancer Outcomes Can Be Predicted By Blood Markers

Biomarkers of residual disease detected in the blood at surgery following neoadjuvant chemotherapy can identify which patients with triple-negative breast cancer will have a better outcome at 2 years and which will do much worse, a phase 2 randomized controlled trial indicates.

“What we know with triple-negative breast cancer is that these cancers tend to recur at a very high rate, particularly peaking in the first 3 years after surgery, and this causes an untenable situation for our patients, who live in constant fear and uncertainty of their cancer recurring after chemotherapy and surgery,” Milan Radovich, PhD, associate professor of surgery and medical and molecular genetics, Indiana University School of Medicine in Indianapolis, said at a press briefing here at the San Antonio Breast Cancer Symposium (SABCS) 2019.

“We found that the detection of circulating tumor DNA (ctDNA) as well as circulating tumor cells (CTCs) in early-stage, triple-negative breast cancer after neoadjuvant chemotherapy is an independent predictor of disease recurrence and represents, we think, an important, novel stratification factor for post-neoadjuvant trials,” he added.

The BRE12-158 trial involved 151 patients with early-stage, triple-negative breast cancer in whom there was evidence of residual disease at surgery following neoadjuvant chemotherapy.

“The first marker we focused on was a marker called ctDNA,” Radovich noted. As he explained, ctDNA is DNA that is shed from tumors into the circulation, where next-generation sequencing techniques can be used to noninvasively detect the DNA in a simple blood draw.

Investigators also studied CTCs, which are live tumor cells that float in the circulation, where, again, sensitive techniques can be used to detect them in the blood.

“ctDNA was successfully sequenced in 150 patients…. 148 of the 150 sequenced patients had clinical follow-up,” the investigators point out.

Genomic or DNA sequencing was conducted by Foundation Medicine using the FoundationOne Liquid assay, which provides profiles for 70 commonly mutated oncogenes.

Following genomic sequencing, patients were randomly assigned to receive either genomically directed therapeutics or the investigative physician’s choice of therapy.

Plasma samples of both ctDNA and CTCs were collected at cycle 1, day 1 in the genomically directed therapies arm. In the control arm, they were collected at the patient’s first routine visit.

Investigators then correlated the presence of mutated ctDNA with distant disease-free survival (DDFS) and overall survival in both univariate and multivariate analyses.

Striking Results

“Results were absolutely striking,” Radovich said.

“Patients who were positive for ctDNA in their circulation after surgery had a significantly inferior DDFS compared to patients who were ctDNA negative,” he emphasized.

At 17.2 months’ follow-up, the median DDFS rate was almost threefold higher for ctDNA-negative patients, which had not been reached at the time of data analysis, vs a median DDFS of 32.5 months in ctDNA-positive patients.

At 2 years, estimated DDFS rates were 56% for the ctDNA-positive patients vs 81% for ctDNA-negative patients (P = .005).

“The addition of CTC adds complementary information to ctDNA for detection of minimal residual disease,” Radovich continued.

For patients who tested negative to both biomarkers, the 2-year DDFS rate was more than fivefold higher, at 89%, compared to 52% for patients who tested positive for both biomarkers (P = .009).

Importantly, for the subgroup of patients who tested negative for both ctDNA and CTCs, outcomes were still significantly superior to those of other groups, even though some of them were at very high risk for relapse, as determined on the basis of standard clinical variables, Radovich emphasized.

The risk for mortality among patients who tested positive for ctDNA was also almost threefold higher than it was for those who tested negative for ctDNA (P = .022), the investigators add.

“At the end of the day, we want to use tests where we can actually act on results,” coinvestigator Bryan Schneider, MD, professor of medicine and medical and molecular genetics, Indiana University School of Medicine, and senior author of the study, told Medscape Medical News.

“We already know that the risk of relapse in these patients is really high, so the ability to take that information and understand whether we can act on it in a clinically meaningful way is really important,” he added.

Hence, investigators are now planning the BRE18-334 trial, also known as the PERSEVERE trial, another phase 2 study in which patients with triple-negative disease with minimal residual disease at surgery who test positive for ctDNA will be treated with a genomically directed, post-neoadjuvant therapy.

The therapy will target actionable genomic markers detected on sequencing among ctDNA-positive patients. Those who have no actionable tumor targets or who are ctDNA negative will be assigned to standard of care.

“The goal of our trial is not to prolong survival, it is to try and go for cure — we are going to use this ctDNA information and actual germline alternations to improve the cure rate,” Schneider said.

“And we feel our patients will be very motivated to participate, especially if they know there is a high risk of their cancer coming back,” he added.

Asked to comment on the study’s findings, the press briefing moderator, Virginia Kaklamani, MD, UT Health, San Antonio, Texas, said that she does not like disclosing test results to a patient when she can’t act on them.

“That is why we do clinical trials,” Kaklamani said. “We need this information so we can do clinical research and figure out if we can salvage these patients with our novel therapies and maybe make a difference to their outcomes,” she added.

Radovich concurred, saying that although he believes it is important that they now have the technology that can identify which patients with triple-negative breast cancer will do poorly, “I think the more important thing now is that we have to learn how to act on it,” he said.

Source : Medscape

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Ultra-Processed Food Now Linked To Type II DM

High consumption of so-called ultra-processed foods is associated with an increased risk of type 2 diabetes, independent of other risk factors including weight and nutritional quality of the diet, a new study indicates. The results suggest a possible modifiable target for prevention of diabetes, say the authors.

“To our knowledge, although ultra-processed foods consumption was previously found to be associated with increased risks of cancer, cardiovascular diseases, mortality, depressive symptoms, and metabolic disorders, no prior prospective epidemiological study had evaluated their association with type 2 diabetes risk,” write Bernard Srour, PharmD, MPH, PhD, and colleagues in their article published online today in JAMA Internal Medicine.

The study involved 104,707 participants in the ongoing, web-based NutriNet-Santé study in France, the majority of whom were women (79.2% vs 20.8%).

Participants, who were a mean baseline age of 42 years, provided repeated 24-hour dietary records on their consumption of more than 3500 food items. They also reported on major health events, including type 2 diabetes; the findings were further confirmed using medication reimbursement data.

Rates of type 2 diabetes among the lowest and highest ultra-processed foods consumers were 113 and 166 per 100,000 person-years, respectively.

Over a median follow-up of 6 years, the consumption of ultra-processed foods was found to be associated with a significantly higher risk of type 2 diabetes, with a hazard ratio (HR) of 1.15 for each 10% increase of ultra-processed foods in the diet.

The study was supported by the French Ministry of Health, Public Health France, National Institute of Health and Medical Research (INSERM), National Institute for Agricultural Research (INRA), National Conservatory of Arts and Trades (CNAM), and the University of Paris.

Highly Processed Foods Association With Diabetes, Not Just Weight Gain

The results remained significant after adjusting for factors including nutritional quality of the diet, other metabolic comorbidities (HR, 1.13), and importantly, weight change (HR, 1.13).

A recent National Institutes of Health study, also reported by Medscape Medical News, linked consumption of highly processed foods to overeating and weight gain, but these latest findings suggest effects independent of weight gain linking this type of food to diabetes risk, say the French researchers.

“Even if participants did not gain weight during follow-up, they were at risk of developing diabetes if their ultra-processed [food] consumption was higher,” Srour, of the Nutritional Epidemiology Research Team, INSERM, INRA, University of Paris, France, told Medscape Medical News.

The absolute amount of ultra-processed foods consumption, in terms of grams per day, was further associated with type 2 diabetes risk, even after adjusting for the intake of unprocessed or minimally processed foods (HR, 1.05 for a 100 g/day increase).

“Even though the consumption of un- or minimally processed foods is associated with a lower type 2 diabetes risk, the association between ultra-processed foods and a higher risk of type 2 diabetes is not fully due to a lower simultaneous consumption of un/minimally processed food,” Srour noted.

As also recently reported by Medscape Medical News, Srour and colleagues published work, also from the NutriNet-Santé study, showing a 10% higher intake of ultra-processed foods and beverages was associated with about a 12% increased risk of cardiovascular disease, coronary heart disease, and cerebrovascular disease over approximately 5 years.

The team has also reported links between ultra-processed foods and an increased risk of cancer, mortality, depressive symptoms, and inflammatory bowel syndrome.

Proposed Mechanisms Range From Poor Nutrition to Chemical Additives

Srour and colleagues propose a variety of mechanisms that might explain the link between higher consumption of ultra-processed foods and risk of type 2 diabetes.

In terms of nutrition, processed foods are known to have poorer quality, containing higher levels of sodium, energy, fat, and sugar, and they are lower in fiber, while also commonly having a higher glycemic index, the authors note.

Other mechanisms, however, may include alteration of gut microbiota and endocrine disruption because of the food production process and packaging.  

Processed food products, for instance, often have longer shelf-lives because of the use of preservatives, and therefore have longer exposure to harmful chemicals such as endocrine-disrupting phthalates and bisphenol A, the latter of which was associated with type 2 diabetes risk in a recent meta-analysis.

Other physical and chemical processes, such as high-temperature heating, are associated with the production of contaminants posing health risks, such as acrylamide, found mainly in fried potatoes, biscuits, cakes, and coffee, which have been associated with insulin resistance.

“Ultra-processed foods usually go through several physical and chemical processes such as extruding, molding, pre-frying, (or) hydrogenation, possibly leading to the production of new compounds with potential cardiometabolic disruption properties,” the authors write.

“They also typically contain food substances of no or rare culinary use (eg, some varieties of refined sugars, hydrogenated oils) and various types of cosmetic additives (eg, emulsifiers, sweeteners, thickening agents, colorants), with cardiometabolic effects postulated for some,” they continue.

Highly Processed Foods: “We Continue to Eat Them”

Leading ultra-processed food culprits include sugary and artificially sweetened sodas, energy drinks, industrial dairy desserts and milkshakes, fats and sauces, sugary products, such as candies and chocolate, and processed meat, a well-known risk factor for type 2 diabetes, Srour noted.

And even putting aside mechanisms for their role in disease, one thing appears clear from a recent small, but intriguing, study: ultra-processed foods are designed to make us want more, and so far manufacturers are succeeding in their aim to increase consumption.

As discussed in a recent Medscape commentary, the study involved volunteers who were given ultra-processed diets for 2 weeks and diets with unprocessed foods for a separate 2 weeks, with equally abundant portions of food in each arm.

Remarkably, when on the ultra-processed foods diet, participants consumed an average of 500 calories/day more than on the unprocessed diet and gained about a kilogram along the way, while they lost about a kilogram during the unprocessed foods period.

The study underscores that “through feats of science and engineering, corporations have created foods that smack us right in the pleasure centers of the brain, and we continue to eat them even after we shouldn’t,” noted F. Perry Wilson, MD, an assistant professor in the Department of Medicine, Yale School of Medicine, New Haven, Connecticut, the author of a commentary.

“Maybe this is one of those things that if we simply acknowledge, we can avoid,” Wilson concluded.

Source : Medscape