https://www.technologyreview.com/2022/05/17/1052334/anti-aging-drugs-treat-covid-19/
Day: 05/27/2022
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No association found between mode of birth, risk for food allergy
Whether infants were born via vaginal or cesarean delivery did not lead to meaningful differences in likelihood of food allergy at age 12 months, according to a study published in The Journal of Allergy and Clinical Immunology.
The lack of likelihood persisted regardless of onset of labor or whether cesarean deliveries were elected or emergent, Anne Currell, MEpi, a researcher in population health at Murdoch Children’s Research Institute in Parkville, Victoria, Australia, and colleagues wrote.
The researchers examined 2,045 infants born between September 2007 and August 2011 in the Melbourne area from the HealthNuts population-based longitudinal study, where parents completed questionnaires and infants underwent skin prick testing, oral food challenges and blood collection.
Of the included infants, 70% were delivered vaginally, 12.5% were born by cesarean section after the onset of labor and 17.5% were born by cesarean section before the onset of labor. Also, 14.9% of births were emergency cesarean sections, and 15.2% were elective cesarean sections.
Overall, 13% of infants were sensitized to food and 18.7% had food allergy.
Food allergy occurred among 12.7% of infants born via cesarean delivery and 13.2% of those born vaginally, indicating no evidence of an association between type of delivery and risk for any food allergy (adjusted OR = 0.95; 95% CI, 0.7-1.3), including to egg (aOR = 0.8; 95% CI, 0.57-1.13) or peanut (aOR = 1.11; 95% CI, 0.69-1.91).
However, food allergy occurred among more children born by cesarean section after labor had started (14.2%) than those born vaginally (13.3%) or via cesarean without labor (11%), but adjusted models showed no association between labor and risk for any food allergy, including egg or peanut allergy.
Fewer infants born via emergency cesarean section experienced food allergy (11.2%) than those born via elective cesarean section (13.4%) or vaginal delivery (13.3%), but adjusted models indicating no risk for any food allergy — egg or peanut included — based on these qualifications.
The researchers additionally found no evidence for increased risks for food allergy based on breastfeeding, older siblings, a pet dog or maternal history of allergy, with similar results for egg and peanut allergies.
Similarly, the researchers continued, there was no evidence of an association between mode of cesarean birth (with or without labor, or elective or emergency cesarean) and risk for food, egg or peanut sensitization compared with vaginal delivery.
The researchers noted the microbial exposure hypothesis, which proposes that altered exposure to microbes and infections early in life could predispose infants to allergic disease, with mode of delivery potentially influencing the microbiome.
However, the researchers wrote, their results suggest that gut colonization may begin in utero and have an impact on the infant’s microbiome and on risks for allergic disease, not just mode of delivery.
Caregivers can consider these findings, the researchers continued, in advising patients about the benefits and risks that come with cesarean delivery and in reassuring them that their infants are not likely to be at increased risk for food allergy.
Reference:
- Caesarean births not linked to increased risk of food allergy during infancy. https://www.mcri.edu.au/news/caesarean-births-not-linked-increased-risk-food-allergy-during-infancy. Posted May 19, 2022. Accessed May 19, 2022.
PERSPECTIVE
The authors demonstrated that elective or emergency cesarean delivery with or without labor was not associated with the risk for food allergy development at age 12 months in HealthNuts cohort participants. One of the strengths of this study was its use of OFC tests to confirm food allergies.
Although there was no significant difference, infants born through vaginal delivery had a higher proportion of egg allergy development compared with those born through cesarean delivery in this study. On the other hand, the proportion of peanut allergy development was higher in those born through cesarean delivery compared with those born through vaginal delivery.
Our nested case-control trial of SPADE study participants also demonstrated that only a proportion of hen’s egg sensitization development at 6 months of age was higher among infants born through vaginal delivery compared with those born through cesarean delivery. The effect of delivery mode on the development of food allergy might differ between food allergens.
In addition, although there were no significant differences, the authors demonstrated that cesarean delivery with labor had higher proportions of egg allergy and peanut allergy development compared with cesarean delivery without labor. Our analysis revealed that participants who developed food sensitization had longer labor durations than those without food sensitization. Furthermore, longer labor durations were significantly associated with a higher proportion of participants with food sensitization.
Several reports have indicated that cesarean delivery can elevate the risk for food sensitization and food allergy compared with vaginal delivery. However, our study and Currell and colleagues showed that cesarean delivery might not elevate the risk for food sensitization and food allergy.
Several important potential confounders such as indication of cesarean delivery, labor duration, levels of stress hormone and microbiota should be considered in future research.
Bariatric surgery improves diabetes remission, reduces cardiometabolic risk
Compared with conventional treatment, bariatric surgery was superior in achieving remission of prediabetes and type 2 diabetes and reducing cardiometabolic risks for patients with obesity, researchers reported in Obesity Medicine.
According to Antônio Carlos Sobral Sousa, MD, PhD, FACC, head of cardiology at the Federal University of Sergipe in Brazil, and fellow researchers, sparse data in the literature suggest whether bariatric surgery would produce better outcomes relative to long-term diabetes comorbidities among Public Healthcare System users in Brazil. The researchers conducted the study to determine the remission of type 2 diabetes and the reduction of cardiometabolic risk at 5 years among patients with obesity and type 2 diabetes who received bariatric surgery and were followed in the Public Healthcare System.
The observational, retrospective, single-center study included 38 patients who received conventional medical treatment and 33 patients who received bariatric surgery. Researchers assessed socioeconomic, lifestyle, anthropometric, biochemical, medication, cardiovascular and glycemic parameters. Baseline characteristics between groups were comparable. Overall, 91.6% of patients were women, and the mean age was 46.1 years. Among those who received bariatric surgery, there was a mean 28.3-month wait to receive surgery, and 93.9% underwent gastric bypass.
Antônio Carlos Sobral Sousa
Results indicated that patients who received bariatric surgery demonstrated a higher level of educational achievement (P = .001), a higher prevalence of social drinking (P = .006) and a higher BMI (P < .001) compared with the conventional approach arm.
At 5 years, 66.7% of patients receiving bariatric surgery had complete remission of type 2 diabetes and 60.6% had remission of cardiometabolic risks, whereas in the conventional treatment arm, 2.6% of patients had remission of type 2 diabetes and 18.4% had remission of cardiometabolic risks (P < .0001 for both).
“Bariatric surgery is superior to conventional treatment in promoting remission of prediabetes/type 2 diabetes, reducing cardiometabolic risk and the number of drugs used, in addition to improving the biochemical and anthropometric markers of patients with obesity and type 2 diabetes,” de Almeida and colleagues concluded. “Future studies might analyze how long after bariatric surgery these benefits achieved in the first 5 years remain in individuals with low socio-educational levels.”
PERSPECTIVE
Sousa and colleagues examined the 5-year outcomes of bariatric surgery vs. conventional medical treatment of type 2 diabetes in Brazilian patients with class 3 obesity in an observational, retrospective study. Due to the observational nature of the study, there were significant differences at baseline in that the patients receiving surgery were far heavier than the medical group. Indeed, the BMI at baseline in the surgery group was 50 kg/m2 and that of the medical group was about 42 kg/m2. However, other cardiometabolic factors, including glucose, lipid and blood pressure levels, were similar at baseline, and a majority of participants were female.
At 5 years of follow-up, the primarily gastric bypass surgery group had over 60% of participants achieving full remission of type 2 diabetes and dramatic reduction in cardiovascular disease risk scores as well as the need for diabetes and CV agents. The rates of diabetes remission are far higher than other published randomized controlled studies of bariatric surgery for diabetes and may reflect that these subjects had greater severity of obesity and less severe diabetes and were predominantly female with more preoperative counseling than the conventional medical treatment group. However, this is a small nonrandomized trial that shows greater remission in the Brazilian cohort.
Further studies examining the impact of bariatric surgery with respect to gender and racial differences are needed. The impact of surgery in more severe diabetes with moderate obesity are also warranted. Regardless, bariatric surgery seems to have durable benefits for patients with type 2 diabetes and obesity up to 5 years. Whether these benefits translate to reduction in microvascular and macrovascular events related to diabetes is not known.
Sangeeta Kashyap, MD
Healio | Endocrine Today Co-Editor
Physician Scientist, Endocrinology Institute
Professor of Medicine
Cleveland Clinic Lerner College of Medicine
Hormone monitoring may play role in remote miscarriage management
Human chorionic gonadotropin — or hCG — may indicate successful medical management of early pregnancy loss remotely, although more research is needed to confirm this, according to a study in Obstetrics & Gynecology.
“Medical abortion uses the same medication regimen — a combination of mifepristone and misoprostol — as medical management of miscarriage,” Andrea H. Roe, MD, MPH, an assistant professor of OB/GYN at the Pennsylvania Hospital in Philadelphia, told Healio. “However, after medical abortion, there are well-validated protocols that allow patients to follow up with a blood draw to confirm resolution of the pregnancy, rather than needing to follow up in person. We wanted to see if we could determine a pregnancy hormone pattern after medical management of miscarriage that would allow patients to have the same type of remote follow-up.”
Roe and colleagues analyzed data collected in a randomized controlled trial conducted to evaluate different combinations of medication management of miscarriage between 5 and 12 weeks’ gestation. For their analysis, the researchers evaluated serum hCG levels at baseline and between 1 to 4 days after treatment to predict whether participants had successfully passed their pregnancy.
Among 233 participants, 184 (79%) had successful treatment. Of these, 100 received mifepristone and misoprostol and 84 received misoprostol alone. At baseline, the median hCG level was 11,225 mIU/mL (range, 205 mIU/mL-224,581 mIU/mL), with no significant differences between groups.
The median hCG decline for participants who received mifepristone and misoprostol was 82.2% (95% CI, 78.8%-84.2%) in participants with successful treatment and 66.9% (95% CI, 42.1-84.6%) in those with unsuccessful pretreatment. The decline was significantly greater in participants who had success (P = .02).
In participants who received misoprostol alone, hCG decreased by a median of 83.8% (95% CI, 80.3%-85.7%) and 47.6% (95% CI, 36%-53.6%) in participants who had successful and failed treatment, respectively. Again, participants with successful treatment had a significantly greater decline in hCG compared with those who had failed treatment (P < .01).
While treatment success was associated with a greater percent hCG decline, the researchers could not determine a definitive threshold that predicted treatment success.
“Although the mifepristone/misoprostol regimen was associated with a steeper decline in hCG levels, it was actually even harder to use hCG to predict successes and failures in this group compared with the misoprostol-only group,” Roe said.
Roe said future studies should determine what levels of and decreases in hCG indicate the success of miscarriage treatment.
“More research is needed to see if assessing hCG at a different time point would more accurately identify success and failure after treatment,” she said. “Miscarriage is common and can be a very distressing experience; expanding this and other follow-up options would allow patients to have more flexibility and privacy during this time.”
PERSPECTIVE
Katharine O’Connell White, MD, MPH
The COVID-19 pandemic accelerated efforts to reduce the need for in-person follow-up after abortion and early pregnancy loss. While the use of hCG level assessments after medication abortion has been validated, no such guidance exists for miscarriage. The authors presciently collected hCG data as part of a larger randomized trial of mifepristone pretreatment for early pregnancy loss medication management.
The study found that hCG levels decline more quickly with successful medication treatment, as expected. Yet the authors could not determine an hCG threshold that could consistently predict treatment success. Follow-up hCG levels were obtained between days 1 and 4 after misoprostol administration, where we may expect variation in results. Yet given the wide confidence intervals around the difference between success and failure in each group, it is unlikely that more consistent timing of hCG follow-up would have yielded an accurate threshold.
Future studies should examine the impact of mifepristone pretreatment on hCG resolution, any correlation between symptomatology and hCG decline, and whether later serum hCG follow-up — such as 7 or 14 days after misoprostol administration — may yield a clinically useful threshold. Follow-up at 30 days may permit urine pregnancy testing in lieu of serum testing but may be too long for patient or provider comfort. I agree with the authors that more evidence is needed to determine the optimal regimen for remote follow-up of medication management of miscarriage.
Katharine O’Connell White, MD, MPH
Associate Professor of OB/GYN, Boston University School of Medicine
Author of Your Guide to Miscarriage and Pregnancy Loss
Taller adults may have higher risk for colorectal cancer, adenoma
Greater adult-attained height correlated with increased risk for colorectal cancer and adenoma, according to a meta-analysis published in Cancer, Epidemiology, Biomarkers & Prevention.
Researchers from Johns Hopkins School of Medicine arrived at the finding after adjusting for demographic, socioeconomic, behavioral and other known risk factors.
“Tallness is an overlooked risk factor for several adverse health conditions and is not on the radar for doctors to bear in mind when evaluating health maintenance and prevention. Those who are considered tall for their culture should be considered for earlier screening for colorectal adenomas than the general population,” Gerard E. Mullin, MD, associate professor of medicine and director of Johns Hopkins Hospital Integrative GI Nutrition Services at The Johns Hopkins School of Medicine, told Healio.
Background
Mullin and colleagues pursued the research because the influence of anthropometric characteristics on colorectal neoplasia biology was unclear.
“We knew that there were modifiable factors such as smoking, alcohol use and processed meat consumption that raised the risk for digestive tract cancers that are not considered by doctors in screening for colon cancer, but what about nonmodifiable factors?” Mullin said. “We knew that certain conditions with excessive body size and tallness, such as acromegaly and Klinefelter syndrome, raised risk for colon cancer — but what about basketball players and athletes?”
Mullin said the thought first occurred to him years ago when he was at a New York Yankees baseball game and their 36-year-old outfielder, Darryl Strawberry, was taken out of a playoff game due to advanced colon cancer.
“That was the first time I had heard of a young person with advanced colon cancer,” Mullin said. “I saw him at a vegan restaurant in Miami in 2019 and he looked healthy and fit. It wasn’t his diet. I wondered if it was his height and began to look for a link in the literature and was struck that there were positive studies on many digestive tract cancers. So, we focused on a possible line of colon cancer and attained tallness.”
Methodology
Mullin and colleagues searched MEDLINE, EMBASE, the Cochrane Library and Web of Science for studies on the association between adult-attained height and colorectal cancer or adenoma. They identified 47 observational studies involving 280,644 colorectal cancer and 14,139 colorectal adenoma cases. The researchers also gathered original data from the Johns Hopkins Colon Biofilm study, which enrolled 1,459 adults who received outpatient colonoscopies.
Researchers estimated HRs and ORs of colorectal cancer/adenoma with increased height using random-effects meta-analysis.
Key findings
Thirty-three studies had data for colorectal cancer incidence per 10 cm increase in height — 19 yielded an HR of 1.14 (95% CI, 1.11-1.17) and 14 an OR of 1.09 (95% CI, 1.05-1.13).
In addition, 26 studies had data comparing colorectal cancer incidence between individuals within the highest vs. the lowest height percentile — 19 showed an HR of 1.24 (95% CI, 1.19-1.3) and seven an OR of 1.07 (95% CI, 0.92-1.25). Four studies had data assessing colorectal adenoma incidence per 10 cm increase in height, showing an overall OR of 1.06 (95% CI, 1-1.12).
Mullin told Healio that the positive adenoma data surprised researchers.
“Most of all that the apparent magnitude of risk was comparable to the risk of frequent processed red meat consumption, cigarette smoking or moderate alcohol consumption,” Mullin said. “We controlled for many of the risk factors for adenoma and colon cancer, such as family history, inflammatory bowel disease and even diet, and found attained height as an independent risk factor.”
Implications
As a result of their findings, Mullin and colleagues recommended that height be considered a risk factor for colorectal cancer screening. They added that more research is necessary to define the tallness risk parameters that can translate the finding into the clinical care setting.
Mullin suggested research into the use of DNA stool testing for neoplasia in tall individuals, testing their positivity with age-matched controls.
“It also would be interesting to see if there is a factorial interaction of attained height with the aforementioned modifiable factors, such as diet, and/or nonmodifiable ones, such as genetic,” Mullin said.
‘All of us need to be vigilant’: Steps to combat growing NAFLD, NASH epidemic
The incidence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis continues to rise with obesity and type 2 diabetes, and all clinicians must screen patients at high cardiometabolic risk, according to a speaker.
Approximately 30% to 37% of U.S. adults have nonalcoholic fatty liver disease, known as NAFLD, and about 8-12% have nonalcoholic steatohepatitis (NASH), which leads to fibrosis and liver failure and a leading indication for liver transplant, Christos S. Mantzoros, MD, DSc, PhD, professor of medicine at Harvard Medical School and chief of endocrinology at VA Boston Healthcare System, said during a presentation at the Heart in Diabetes CME Conference. Often such patients are not diagnosed until serious liver or cardiometabolic complications develop, Mantzoros said.
“In our society, as the prevalence of obesity goes up, the prevalence of type 2 diabetes goes up, and the prevalence of NAFLD and steatosis goes up,” Mantzoros said. “The NASH epidemic is part of a cardiometabolic disease group. All of us need to be vigilant to make the diagnosis and to prevent and treat it. All of us need to apply all of the tools we have when we make the diagnosis.”
In the U.S., about 7 in 10 people with diabetes will have NAFLD, Mantzoros said, whereas up to 80% of people with NASH will have metabolic syndrome, leading to type 2 diabetes over time. Additionally, these risk factors lead to cardiovascular morbidity and mortality, he said.
“NAFLD and NASH are common, especially among people with obesity, diabetes and metabolic syndrome, and unfortunately most of the time it remains undiagnosed,” Mantzoros told Healio. “We need to think about it, screen and treat it.”
Strategies to treat NAFLD, prevent NASH
There are currently no FDA-approved therapies specifically for NASH; however, Mantzoros highlighted several strategies that can reduce fat in the liver and inflammation:
- Weight loss is associated with mild to moderate improvement in NASH, though maintaining weight loss is very challenging, Mantzoros said. The Mediterranean diet is inversely associated with liver steatosis and decreases 10-year CV risk in NAFLD, according to evidence from the ATTICA prospective cohort study recently published in Clinical Nutrition. “In a meta-analysis we put together, we do know that if we follow a Mediterranean diet or Dietary Approaches to Stop Hypertension (DASH) diet, lowering total fat or saturated fat — even if high in monounsaturated fat — we decreased risk for NAFLD and CVD,” Mantzoros said. Similar outcomes are expected in response to the DASH diet.
- Bariatric surgery and endoscopic devices have demonstrated improvement in NASH and metabolic syndrome, but evidence for fibrosis improvement is limited, Mantzoros said. “We know from several studies that if we decrease weight by 10% for 1 year, there is NASH resolution in more than 90% of the cases, fibrosis regression in 80% and steatosis improvement in 100% of cases,” Mantzoros said. “Today, we can do this only with bariatric surgery. In the future, we hope we will be able to do this with new anti-obesity drugs.”
- Irrespective of the statin used, data show improvements with statin therapy in lipid levels and inflammation, as well as an improvement in NAFLD and NASH. “In an editorial we recently published in Metabolism, we recommend that patients continue statin therapies, unless one has late stage of the disease,” Mantzoros said. “Statins should not be discontinued.”
- Some diabetes therapies show promise. Pioglitazone improves liver histology in patients with and without type 2 diabetes with biopsy-proven NASH, and may be used to treat those patients, Mantzoros said. Currently, it is premature to consider GLP-1 receptor agonists or SGLT2 inhibitors to specifically treat liver disease in people with NAFLD or NASH, though data shows the agents can lead to weight loss and decrease steatosis. “They do not improve fibrosis to the degree that we want,” Mantzoros said. “We need larger, longer studies with stronger GLP-1 analogues or combination therapies.”
“When adipose tissue storage is exceeded, triglycerides will be stored in muscle and the liver and this leads to insulin resistance, metabolic syndrome, and not only CVD, chronic kidney disease or diabetes, but also NAFLD,” Mantzoros said. “In addition to lifestyle intervention, many of the same medications [used in diabetes] are expected to be used to treat NAFLD.”
A call to action
As Healio previously reported, eight professional societies issued a joint report on the dangers associated with NAFLD and NASH in July, calling on clinicians to work together across specialties and align treatment strategies.
“We need to realize that this is not a disease only for hepatologists,” Mantzoros said. “Cardiometabolic experts, endocrinologists and primary care physicians need to focus on this epidemic along with nutritionists and exercise physiologists. So many patients who come to our offices go unrecognized.”
Mantzoros said patients must be screened for NAFLD and NASH at the primary care level and diagnosed early to avoid serious complications. Similarly, the joint report also notes that most patients with NAFLD — and many with NASH — have a low risk for clinically significant fibrosis and should be managed by primary care providers.
“We must optimize management with the tools that we have at our disposal today,” Mantzoros said. “Industry and academia need to work together on improving new treatments for this metabolic disorder. There is more coming soon from our working group in terms of recommendations, algorithms, and pathways to follow.”
HIV an independent risk factor for nonalcoholic steatohepatitis
A study of more than 1,300 women demonstrated that HIV is an independent risk factor for nonalcoholic steatohepatitis with significant nonalcoholic fatty liver disease activity and fibrosis, researchers reported.
“Nonalcoholic fatty liver disease (NAFLD) is common among people with and without HIV and is a leading cause of liver-related morbidity and mortality,” Jennifer C. Price, MD, PhD, associate professor of medicine at the University of California, San Francisco, told Healio. “However, most patients with NAFLD do not go on to develop cirrhosis.”
According to Price, the FibroScan-AST (FAST) score can identify patients at risk for developing cirrhosis, or those with nonalcoholic steatohepatitis with an elevated NAFLD activity score and significant liver fibrosis.
“The advantage of the FAST score is that it does not require liver biopsy,” Price said. “We conducted this study to see if HIV was independently associated with higher risk of an elevated FAST score in a cohort of women with and without HIV.”
Jennifer C. Price
Price and colleagues assessed 1,309 women without history of chronic viral hepatitis at 10 U.S. sites 928 with HIV and 381 who were HIV negative — and evaluated associations between HIV, demographic, lifestyle and metabolic factors with a FAST score higher than 0.35, which is considered elevated.
Women with HIV were more likely to have an elevated FAST score compared with those without HIV (6.3% vs 1.8%; P = .001). The researchers calculated that HIV infection was associated with 3.7-fold higher odds of elevated FAST score (P = .002), whereas a greater waist circumference was associated with 1.7-fold higher odds per each 10 cm (P < .001).
The study also showed that undetectable HIV RNA and current protease inhibitor use were independently associated with lower odds of elevated FAST score.
“HIV may increase the risk of more advanced NAFLD histology and liver disease progression,” Price said. “Unsuppressed HIV viral load and increased waist circumference are risk factors for elevated FAST in women, underscoring the importance of ART adherence and weight management in clinical practice.”
Women’s CV risk increases with age, not reproductive stage
Menopausal women tend to have worse cardiovascular risk profiles than premenopausal women, but 5-year increases in CV risk factors are not dependent on reproductive stage, according to data from the CoLaus study.
Pedro Marques-Vidal, MD, PhD, associate professor in the department of nuclear medicine at Lausanne University Hospital, University of Lausanne, Switzerland, and colleagues conducted the prospective, population‐based cohort CoLaus study to better understand whether changes in women’s CVD risk factors differ by reproductive stage independently of underlying aging trajectories.
Study participants included women who did not use hormone therapy and were followed from 2003 to 2012 for a mean of 5.6 years. Researchers classified women into four categories based on baseline and follow-up comparisons of their menstruation status: premenopausal, menopausal transition, early postmenopausal ( 5 years) and late postmenopausal (> 5 years).
Pedro Marques-Vidal
Researchers used repeated measures of fasting lipids, glucose and CV inflammatory markers for longitudinal analysis, with premenopausal women serving as a reference category, and adjusted analyses for age, medication use and lifestyle factors.
The study featured data from 1,710 women who were aged 35 to 75 years.
The analysis revealed that changes in CVD risk factors did not differ in the other three menopausal categories compared with premenopausal women.
When researchers used age as a predictor variable and adjusted for menopause status, they found that most CVD risk factors rose, whereas interleukin‐6 and interleukin‐1 beta decreased with advancing age.
“All women increase their cardiovascular risk as they get older, and in our study, we found no differences in cardiovascular risk changes comparing women in advanced reproductive stages with premenopausal women,” researchers wrote. “This highlights the strong association between chronological age and the cumulative deleterious effects in CVD risk for women. More longitudinal studies that use novel biomarkers for ovarian age are still needed to disentangle the association between menopause and CVD risk in postmenopausal women and women in the menopause transition. … It would be prudent to do screening and preventive measures during menopause transition as these are also ageing women with inherent cardiovascular risks. Cardiovascular preventive measures should target not only postmenopausal women, but also women in the transition phase while waiting for more conclusive evidence.”
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