Paternal Diabetes Has No Significant Impact on Pregnancy Success Rates, Study Reveals

Denmark: A nationwide study has shed new light on the impact of paternal diabetes mellitus on pregnancy outcomes, revealing significant insights into reproductive health. Conducted across a diverse cohort undergoing reproductive treatments, the research offers a comprehensive analysis of how paternal health conditions, specifically diabetes, influence the success of pregnancies.

The cohort study analyzing 101,875 embryo transfers found that paternal diabetes mellitus does not markedly reduce the likelihood of achieving a successful pregnancy outcome.

“For paternal type 1 diabetes (T1D), the adjusted odds ratios for biochemical pregnancy, clinical pregnancy & live birth were 0.97, 1.08, and 0.75, respectively. For type 2 diabetes (T2D), the odds ratios were 0.80, 0.67, and 1.03, and for mixed-type diabetes, 0.95, 1.31, and 1.19,” the researchers reported in Andrology Journal.

Approximately 15% of all pregnancies result in pregnancy loss. While most research has concentrated on maternal factors, there is limited understanding of how paternal factors impact the likelihood of a successful pregnancy. To fill this knowledge gap, Anne-Sofie Sønnichsen-Dreehsen, Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark, and colleagues aim to evaluate the chance of clinical pregnancy, biochemical pregnancy, and live-born children in couples where the male partner has diabetes mellitus (DM).

For this purpose, the researchers performed a nationwide cohort study. It included couples undergoing assisted reproductive technology treatment from 2006 to 2019. he exposed cohorts comprised embryo transfers in couples with paternal T1DM, T2DM, or mixed type DM (TMDM).

The exposed cohorts comprised embryo transfers in couples with paternal type 1 DM (T1DM), type 2 DM (T2DM), or mixed type DM (TMDM). The unexposed cohort included embryo transfers in couples without paternal DM.

The following were the key findings of the study:

  • A total of 101,875 embryo transfers were included. Of these, 503 males had T1DM, 225 males had T2DM, 263 males had TMDM, and 100,884 did not have DM.
  • For paternal T1DM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy, and live-born child were 0.97, 1.08, and 0.75, respectively.
  • For paternal T2DM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy, and live-born child were 0.80, 0.67, and 1.03, respectively.
  • For the paternal TMDM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy, and livebirth were 0.95, 1.31, and 1.19, respectively.

The study found that paternal diabetes mellitus did not reduce the likelihood of achieving pregnancy or having a live-born child compared to couples without paternal diabetes.

“While these results are reassuring, further research is needed to confirm these findings. Future studies should include data on male lifestyle factors, such as smoking and alcohol use, as well as clinical parameters like the severity and management of diabetes, before drawing definitive conclusions,” the researchers concluded.

Reference:

Sønnichsen-Dreehsen, S., Fedder, J., Wod, M., Thorarinsson, C. T., & Nørgård, B. M. The association between paternal diabetes mellitus and successful pregnancy—Examined in a nationwide population undergoing reproductive treatment. Andrology. https://doi.org/10.1111/andr.13702

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Enhanced Postpartum Enoxaparin Protocol Reduces Wound Hematomas with Unchanged Thromboembolic Risk: JAMA

USA: In the realm of obstetric care, the management of thromboprophylaxis remains a critical area of focus to mitigate the risk of venous thromboembolism (VTE) among pregnant women. Recent studies have underscored the importance of tailored protocols that balance efficacy with safety. This prompted a comparative analysis between a more selective approach and a standard risk-stratified protocol using heparin-based treatments.

The retrospective observational study published in JAMA revealed decreased rates of wound hematomas without evidence of increased rates of postpartum thromboembolic events with a more selective protocol for postpartum enoxaparin.

“A more selective protocol for chemoprophylaxis resulted in a decrease in heparin (enoxaparin) administration (16% versus 8%),” the researchers reported.

“The selective protocol for postpartum enoxaparin was linked with a wound hematoma reduction (0.7% versus 0.3% in the selective protocol group; adjusted odds ratio, 0.38) without evidence of an increase in venous thromboembolism (VTE; 0.1% versus 0.1% in the selective protocol group; adjusted odds ratio, 0.40).”

In 2016, an institute adopted a pregnancy-related VTE prophylaxis based on American College of Obstetricians and Gynecologists guidelines recommending postpartum heparin-based chemoprophylaxis (enoxaparin) based on a risk-stratified algorithm. Using this protocol, a more selective risk-stratified approach was adopted in 2021 in response to increased wound hematomas without significant reduction in VTE.

Against the above background, Macie L. Champion, Center for Women’s Reproductive Health at the University of Alabama at Birmingham, and colleagues aimed to evaluate outcomes of the more selective risk-stratified approach to heparin-based obstetric thromboprophylaxis (enoxaparin) protocol.

For this purpose, the researchers included 17,489 patients who delivered at a single tertiary care center in the southeast US between 2016 and 2018 (original protocol) and between 2021 and 2023 (more selective protocol). It excluded patients receiving outpatient anticoagulation for active VTE or high VTE risk during pregnancy.

The study’s main focus was on identifying wound hematomas diagnosed clinically within six weeks after childbirth. Additionally, it aimed to detect new cases of venous thromboembolism during the same postpartum period. The analysis included comparing baseline characteristics and outcomes across different groups, and adjusted odds ratios were calculated for both primary and secondary outcomes, using the original protocol group as the reference point.

The following were the key findings of the study:

  • Of 17 489 patients included in the analysis, 12 430 were in the original protocol group, and 5029 were in the more selective group.
  • Rates of chemoprophylaxis decreased from 16% (original protocol) to 8% (more selective protocol).
  • Patients in the more selective group were more likely to be older, be married, and have obesity or other comorbidities (hypertension, diabetes, cardiac disease).
  • Compared with the original protocol, the more selective protocol was associated with a decrease in any wound hematoma (0.7% vs 0.3%; adjusted odds ratio [aOR], 0.38), particularly due to a lower rate of superficial wound hematomas (0.6% vs 0.3%; aOR, 0.43).
  • There was no significant increase in VTE or individual types of VTE (0.1% vs 0.1%; aOR, 0.40).

“The findings showed that a more selective risk-stratified approach to an enoxaparin thromboprophylaxis protocol for venous thromboembolism was associated with reduced rates of wound hematomas without increased postpartum VTE rates,” the researchers concluded.

Reference:

Champion ML, Blanchard CT, Lu MY, et al. A More Selective vs a Standard Risk-Stratified, Heparin-Based, Obstetric Thromboprophylaxis Protocol. JAMA. Published online June 27, 2024. doi:10.1001/jama.2024.8684

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Cholecystectomy not always necessary for gallstones and abdominal pain, States JAMA study

Each year, 100,000 people visit their doctor with abdominal pain, with approximately 30,000 of them diagnosed with gallstones. The standard treatment for these patients is a laparoscopic cholecystectomy. Since the 1990s, the number of surgeries has increased exponentially, despite the lack of clear international criteria. As a result, gallbladder removal is one of the most common surgeries in the Netherlands, yet it is not always effective against pain: about one-third of patients continue to experience abdominal pain after cholecystectomy. The procedure has long been an example of inappropriate care, but this is now changing.

In a 2019 study conducted by Radboud university medical center, patients with abdominal pain due to gallstones were divided into two groups. One group received the standard treatment of cholecystectomy, while the other group received a restrictive selection strategy, with surgery considered only after evaluating various pain symptoms. The number of surgeries in the restrictive strategy group decreased, but one year later, one-third of patients in both groups still had abdominal pain. Based on this study, researchers recommended caution with cholecystectomy in patients with gallstones and abdominal pain.

Five-year follow-up

The researchers re-evaluated the patients five years later. The results of this study conducted in 24 Dutch hospitals are now published in JAMA Surgery. Daan Comes, physician-researcher and lead author, explained: ‘We wanted to investigate the long-term effects of a restrictive strategy to this surgery in this group of patients. Therefore, we contacted over a thousand patients by phone. They completed questionnaires, and we reviewed their medical records.’

What did they find? The number of patients with pain had not decreased over the years: still, only two-thirds of the patients were pain-free. However, therestrictive strategy approach led to fewer unnecessary cholecystectomies. ‘In the restrictive selection group, we did not observe more complications from gallstones or surgery than in the other group. It seems that a restrictive selection strategy is feasible, but only for the right patients.’

Better selection criteria

For better insight into identifying the right patient group, Radboudumc developed a decision rule in 2021 based on scientific research and patient data. Surgeon and principal investigator Philip de Reuver stated, ‘It was found that intense, episodic pain is a strong indication for surgery. Additionally, a previous abdominal surgery or the presence of other symptoms, such as bloating, heartburn, and persistent pain, are reasons to be cautious about surgery.’

With this knowledge, doctors and patients can make better-informed decisions. ‘Patients with recurrent biliary colic certainly benefit from this surgery. However, more than a third of patients with gallstones also have symptoms of dyspepsia and irritable bowel syndrome. In those cases, this surgery is not helpful. We should really rule out these conditions before proceeding with a cholecystectomy.’

Therefore, De Reuver is starting a follow-up study on the effect of a lifestyle intervention in patients with abdominal pain and gallstones, where the decision rule indicates that surgery would have limited benefits. He expects the lifestyle intervention to improve patients’ health, quality of life, and reduce pain. ‘In the Netherlands, about 65 patients undergo gallbladder surgery every day. That’s a bus full. If we can reduce that number, we save costs and capacity while maintaining the quality of life. That’s fantastic,’ said De Reuver.

Do you have abdominal pain and gallstones?

If you have abdominal pain and gallstones, it is important to discuss your symptoms thoroughly with your doctor and decide together if gallbladder surgery is the right choice. An initial step might be to adjust your diet, reduce fat intake, and see if the symptoms subside. There are various decision aids available with all the information about the surgery, possible complications, and long-term effects. Review a decision aid before consulting your doctor.

Reference:

Comes DJ, Wennmacker SZ, Latenstein CSS, et al. Restrictive Strategy vs Usual Care for Cholecystectomy in Patients With Abdominal Pain and Gallstones: 5-Year Follow-Up of the SECURE Randomized Clinical Trial. JAMA Surg. Published online August 21, 2024. doi:10.1001/jamasurg.2024.3080

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Breakthrough Study: Comparing Plantar Wart Treatments and Ensuring Clear Results with Dermoscopy

Egypt: A recent prospective, randomized study has shed new light on effective treatments for recalcitrant plantar warts, comparing intralesional combined digoxin and furosemide against intralesional 5-fluorouracil. Plantar warts, caused by the human papillomavirus (HPV), can be particularly stubborn and resistant to traditional treatments, making them a significant challenge for patients and dermatologists.

The study, published in the Archives of Dermatological Research, revealed near equivalent safety and efficacy of intralesional injection of 5-fluorouarcil and combined digoxin and furosemide for plantar wart treatment. Dermoscopy aids in accurately assessing the complete clearance of warts.

“Each treatment achieved an 80% clinical response rate, with approximately 40% and 33.3% achieving complete wart clearance, respectively,” the researchers reported.

Many therapeutic modalities exist for plantar warts, however, their treatment remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were safe and effective, however, no comparison study between them was done. Considering this, Nourhan Anis, Zagazig University, Zagazig, Egypt, and colleagues aimed to evaluate the efficacy of both therapies in treating plantar warts.

The study included 90 adult patients with multiple recalcitrant plantar warts. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated dermoscopically and clinically.

The following were the key findings of the study:

  • Clinical response was reported in 80% of patients of the combined digoxin and furosemide group with 40% complete response and in 80% of patients of the 5-fluorouarcil group with 33.3% complete response.
  • For safety and efficacy, there was no statistically significant difference between the two groups.

In conclusion, both intralesional injections of 5-fluorouracil and combined digoxin and furosemide demonstrate nearly equivalent efficacy and safety in treating plantar warts. The researchers recommend incorporating dermoscopy into wart treatment to accurately determine treatment endpoints, thereby reducing the likelihood of recurrence.

Further research should focus on larger patient cohorts, expanding the evaluation to include more treatment sessions, and comparing the intralesional administration of combined digoxin and furosemide with topical application. Additionally, larger studies with extended follow-up periods are needed to assess potential recurrences and confirm long-term efficacy.

The findings of this study are expected to influence clinical practices, offering dermatologists and patients alike new hope in effectively combating persistent plantar warts. As research continues to evolve, the focus remains on refining treatment approaches to enhance outcomes and quality of life for individuals affected by these troublesome skin lesions.

Reference:

khattab, F., Essam, R., Elhadidy, R.F. et al. Intralesional combined digoxin and furosemide versus intralesional 5-flurouracil for the treatment of recalcitrant plantar warts: a prospective, randomized study. Arch Dermatol Res 316, 411 (2024). https://doi.org/10.1007/s00403-024-03014-z

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PTSD Management Might Lower Risk of Complications in Veterans with Diabetes: JAMA

A new study published in the Journal of American Medical Association found that reducing symptoms of posttraumatic stress disorder (PTSD) may lower the risk of adverse outcomes in veterans with comorbid type 2 diabetes (T2D). This research by the U.S. Veterans Health Administration (VHA) examined data from over a decade and illuminates the potential benefits of managing PTSD in reducing complications associated with diabetes.

The study analyzed medical records of 10,002 veterans aged 18 to 80 years from October 1, 2011 to September 30, 2022, all of whom had been diagnosed with both PTSD and T2D. The cohort predominantly consisted of men (87.2%), with a significant portion being older than 50 years (65.3%). The participants were diverse, with 62.7% identifying as White, 31.6% as Black, and 5.7% as other races.

This research wanted determine whether veterans who showed improvement in PTSD symptoms experienced better outcomes in managing their diabetes when compared to the participants with persistent PTSD symptoms. PTSD improvement was measured using the PTSD Checklist, with a score of less than 33 indicating significant symptom reduction.

The findings of this study suggest that managing PTSD could be beneficial in lowering the risk of certain diabetes-related complications. Before controlling for various factors, the incidence rates of major diabetes outcomes like insulin initiation, poor glycemic control, microvascular complications and all-cause mortality, were similar between veterans who improved their PTSD symptoms and the individuals who did not.

However, the results showed that veterans who no longer met PTSD diagnostic criteria had a reduced risk of microvascular complications by 8% when compared to the patients with persistent PTSD symptoms after adjusting for confounding factors. This association suggests that PTSD might be a modifiable risk factor, particularly in relation to the management of diabetes complications.

Further analysis revealed that the impact of PTSD improvement varied among different groups. The veterans aged 18 to 49 who no longer met PTSD criteria had a 31% lower risk of starting insulin and a striking 61% reduction in the risk of all-cause mortality. Also, among veterans without depression, the individuals who no longer met PTSD criteria had a 27% lower risk of requiring insulin.

Overall, the study highlights the potential benefits of effectively managing PTSD symptoms in veterans with T2D. While the findings indicate a modest reduction in microvascular complications, they also underline the importance of addressing PTSD as a modifiable risk factor in the broader management of diabetes.

Source:

Scherrer, J. F., Salas, J., Wang, W., Freedland, K. E., Lustman, P. J., Schnurr, P. P., Cohen, B. E., Jaffe, A. S., & Friedman, M. J. (2024). Posttraumatic Stress Disorder and Type 2 Diabetes Outcomes in Veterans. In JAMA Network Open (Vol. 7, Issue 8, p. e2427569). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2024.27569

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Cavitated Carious Lesions More Common in Maxillary Incisors and Molars in Both Arches in Preschool Children, finds study

Cavitated Carious Lesions More Common in Maxillary Incisors and Molars in Both Arches in Preschool Children, finds study published in the Journal of Evidence-Based Dental Practice.

This systematic review aimed to describe and evaluate the caries patterns among the 21st century preschool children globally. Six electronic databases (Pubmed, Embase, Medline, Web of Science, EBSCOhost, and Scopus) were searched using predetermined terms. Dual independent screening of all retrieved abstracts was performed to identify studies conducted after year 2000 and the caries pattern among preschool children was investigated. Data regarding the prevalence of caries by tooth type and surface were extracted. Meta-analyses, subgroup analyses and meta-regression were carried out with the statistics software Stata using the random-effects model. Results: A total of 2642 records were screened, and 43 observational studies were finally included. Cavitated caries lesions were commonly found in the maxillary incisors and molars in both arches among preschool children. The highest caries prevalence was found in the maxillary central incisors (29.1%, 95%CI: 25.5%-32.7%) and the mandibular second molars (28.5%, 95%CI: 24.7%-32.3%), while the mandibular lateral incisors had the lowest prevalence (1.7%, 95%CI: 1.5%-2.0%). Occlusal surfaces of the mandibular molars were the most frequently affected by caries, whereas caries hardly affected the lingual surfaces of lower anterior teeth. Caries pattern on the left and right sides was symmetrical. The overall caries prevalence was significantly higher in the maxillary teeth. Caries prevalence was higher in the older children, whereas the caries pattern was not significantly different among children from countries with different human and economic development levels. Cavitated carious lesions were more commonly observed in the maxillary incisors and molars in both arches. The prevalence of caries varies significantly with child’s age and primary tooth type. However, preschool children exhibit a similar pattern of caries, regardless of the time, socioeconomic status or geographical location.

Keywords: Early childhood caries; Dental caries; Primary tooth; Prevalence; Caries distribution; Social inequality

Reference:

Shuyang He, Madeline Jun Yu Yon, Fei Liu, Edward Chin Man Lo, Cynthia Kar Yung Yiu, Chun Hung Chu, Phoebe Pui Ying Lam. PREVALENCE OF CARIES PATTERNS IN THE 21ST CENTURY PRESCHOOL CHILDREN: A SYSTEMATIC REVIEW AND META-ANALYSIS. Journal of Evidence-Based Dental Practice. Volume 24, Issue 3,

2024, 101992, ISSN 1532-3382,

https://doi.org/10.1016/j.jebdp.2024.101992.

(https://www.sciencedirect.com/science/article/pii/S1532338224000332)

Keywords:

Cavitated, Carious, Lesions, More, Common, Maxillary, Incisors, Molars, Both, Arches, Preschool, Children, finds, study, Journal of Evidence-Based Dental Practice, Shuyang He, Madeline Jun Yu Yon, Fei Liu, Edward Chin Man Lo, Cynthia Kar Yung Yiu, Chun Hung Chu, Phoebe Pui Ying Lam

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Larger stones, positive urine culture and higher Comorbidity Index predict urinary septic shock after PCNL: Study

Larger stones, positive preoperative urine culture and higher Comorbidity Index may predict urinary septic shock after PCNL suggests a study published in the International Brazilian Journal of Urology.

The study was done to identify risk factors for urinary septic shock in patients who underwent percutaneous nephrolithotomy (PCNL). Data from PCNL procedures performed between January 2009 and February 2020 were retrospectively analyzed. The study included all patients over 18 years old with kidney stones larger than 15 mm who underwent PCNL. Patients who underwent mini-PCNL or combined surgeries, such as ureteroscopy or bilateral procedures, were not included in the study. Logistic regression was conducted to determine the risk factors for urinary septic shock within 30 days post-operation in patients who underwent PCNL. RESULTS: Urinary septic shock was observed in 8 out of the 1,424 patients analyzed (0.56%). The presence of comorbidities, evaluated using the Charlson Comorbidity Index (CCI) (OR 1.46 [CI 95% 1.15-1.86], p=0.01), larger stones (41.0 mm [IQR 30.0-47.5 mm] vs. 24.0 mm [IQR 17.0-35.0 mm], OR 1.03 [CI 95% 1.01-1.06], p=0.04), and a positive preoperative urine culture (OR 8.53 [CI 95% 1.71-42.45], p < 0.01) were shown to significantly increase the risk of postoperative urinary septic shock. Patients with a CCI > 2, larger stones (≥ 35 mm), and a positive preoperative urine culture were at even higher risk of urinary septic shock (OR 15.40 [CI 95% 1.77-134.21], p=0.01). Patients with larger stones, positive preoperative urine culture, and a higher CCI are at risk for urinary septic shock after PCNL. These findings are of utmost importance for optimizing the perioperative care of these patients to prevent life-threatening complications.

Reference:

Danilovic, Alexandre, et al. “High-risk Patients for Septic Shock After Percutaneous Nephrolithotomy.” International Braz J Urol : Official Journal of the Brazilian Society of Urology, vol. 50, no. 5, 2024, pp. 561-571.

Keywords:

Larger stones, positive, preoperative, urine culture, higher, Comorbidity Index, predict, urinary, septic, shock, PCNL, study

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Intermittent Fasting may Reduce Inflammation and improve Cognition in relapsing-remitting multiple sclerosis: Study

Researchers defined intermittent fasting as 500-calorie fasting twice a week and determined it to be a safe and effective dietary strategy in patients with relapsing-remitting multiple sclerosis. A study on this by Ghezzi and colleagues has been published in the Journal of Neurology Neurosurgery and Psychiatry. A small randomized trial showed reductions in the proinflammatory adipokine leptin, which correlated with improvements in cognitive processing speed and immune function. The results implicate dietary interventions as ancillary to the management of MS symptoms and a reduction in disease activity.

Multiple sclerosis is a chronic autoimmune disorder characterized by inflammation and neurodegeneration in the central nervous system. Diet is of considerable interest to a large proportion of patients with MS, although there is little evidence for its effect on the course of the disease. Leptin represents an adipokine released by adipose tissue and is involved in MS pathology; its levels are increased in the cerebrospinal fluid and serum of patients with MS. Because it has proinflammatory properties and is associated with the risk of MS, the researchers investigated whether intermittent calorie restriction might reduce leptin levels and if this would improve clinical outcomes in relapsing-remitting MS.

This study was carried out at the Washington University School of Medicine in St. Louis from 2018 to 2021 and enrolled 42 patients with relapsing-remitting MS who were randomized to either an intermittent fasting group or a control group. Thirty-four patients completed the trial: 17 in each group. The primary outcome measure was a reduction in leptin levels in the serum at 12 weeks.

Those in the intermittent fasting arm were asked to restrict their daily caloric intake to 500 or fewer calories on two consecutive days a week. On days of actual fasting, participants were permitted to take non-starchy vegetables, non-caloric beverages, and a very small amount of oil. On non-fasting days, the subjects were encouraged to maintain their usual diet but with portion size recommendations. The participants in the control arm were asked to maintain their usual diet but were further advised to eat vegetables every day to ensure that the two groups consumed similar amounts of vegetables.

Key Findings

  • In the intermittent fasting group, after 12 weeks, the level of leptin was significantly reduced to the control group, adding to a positive metabolic-inflammatory profile in patients with MS.

  • At 12 weeks, the fasting group had higher scores on the Symbol Digit Modality Test, indicative of faster cognitive processing.

  • It also showed a 6-week increase in CD45RO+ regulatory T-cells in the fasting group, which may be related to some immune benefits of the diet.

  • The adherence to the fasting regimen was very good, with the participants following it 99.5% of the time for the first 6 weeks and 97.2% during the second 6 weeks.

  • There were no grade 3 or higher adverse events reported. Mild headache and fatigue noted on fasting days did not lead to discontinuation.

The findings enhance the current knowledge base on the role of diet as an adjunctive strategy for MS. Intermittent-fasting was associated with reductions in the pro-inflammatory marker circulating leptin, pointing to the potential for even moderate dietary changes to exert changes in disease pathways in MS. While small, the trial showed high compliance and positive effects on cognitive function and immune markers. A current clinical trial, FOOD for MS, is underway, which will ascertain potential benefits in more detail, including longer-term outcomes, such as MRI findings and thorough functional assessment.

In sum, the authors demonstrate in this study that intermittent fasting represents a feasible and probably beneficial dietary strategy for patients with relapsing-remitting MS. By lowering proinflammatory markers and improving cognitive and immune functions, IF might become a useful addendum to MS therapies available today. However, larger and longer studies are needed to confirm such findings and flesh out the broader implications of dietary interventions in MS management.

Reference:

Ghezzi, L., Tosti, V., Shi, L., Cantoni, C., Mikesell, R., Lancia, S., Zhou, Y., Obert, K., Dula, C., Sen, M. K., Ge, A., Tolentino, M., Bollman, B., Don, A. S., Matarese, G., Colamatteo, A., La Rocca, C., Lepore, M. T., Raji, C. A., … Piccio, L. (2024). Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry, jnnp-2024-333465. https://doi.org/10.1136/jnnp-2024-333465

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Rheumatoid arthritis was linked to increased risk of lung cancer: Study

A new study published in the journal of Arthritis & Rheumatology observed an almost 3-fold greater risk of lung cancer was related with rheumatoid arthritis (RA)-interstitial lung disease (ILD). The patients with RA have had decreased pain, impairment, or loss of function as conventional therapies have improved. However, comorbidities including cancer, infections, and cardiovascular disease remain a danger to RA patients, increasing their disease burden and shortening their life expectancy.

Pulmonary involvement is one of the most prevalent extra-articular symptoms of RA, with a prevalence rate of 5% to 30%, sometimes as high as 67%, in RA patients. In addition to being a prevalent pulmonary symptom in RA patients, interstitial lung disease is also linked to an increased risk of lung cancer. Thus, this study by Rebecca Brooks and colleagues assessed the risk of lung cancer in patients with rheumatoid arthritis and RA-interstitial lung disease.

Between 2000 and 2019, a matched cohort study of RA and RA-ILD was conducted retrospectively inside the Veterans Health Administration (VA). The validated administrative-based algorithms were used to identify RA and RA-ILD patients, who were subsequently matched (up to 1:10) with those without RA based on factors including age, gender, and VA membership year. The National Death Index and a VA oncology database were used to identify lung cancer cases. When evaluating the risk of lung cancer in matched people, conditional Cox regression models  were employed to account factors such as race, ethnicity, smoking status, exposure to Agent Orange, and comorbidity load. There were several sensitivity assessments carried out.

In this study, 72,795 RA and 633,937 non-RA participants were matched and there were 17,099 incident lung cancer cases over 4,481,323 patient-years. An elevated risk of lung cancer was shown to be independently correlated with RA in both incident and never-smoker populations. Prevalent RA-ILD (n=757) was observed to be more significantly linked with lung cancer risk than RA without ILD, when compared to non-RA controls. Similar results were obtained from analyses of both frequent and incident RA-ILD.

Overall, an estimated threefold greater risk was related with RA-ILD, where RA was linked to an elevated risk of lung cancer of over 50%. To reduce the burden caused by the primary cause of cancer-related mortality, increased surveillance for lung cancer in RA (particularly RA-ILD), may prove to be an effective tactic.

Reference:

Brooks, R. T., Luedders, B., Wheeler, A., Johnson, T. M., Yang, Y., Roul, P., Ganti, A. K., Singh, N., Sauer, B. C., Cannon, G. W., Baker, J. F., Mikuls, T. R., & England, B. R. (2024). The Risk of Lung Cancer in Rheumatoid Arthritis and Rheumatoid Arthritis‐Associated Interstitial Lung Disease. In Arthritis & Rheumatology. Wiley. https://doi.org/10.1002/art.42961

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Common fatty acid may help restore healthy vaginal bacteria after infection, reports study

More than half of women globally experience bacterial vaginosis (BV)-an imbalance of naturally occurring microbes in the female genital tract-at least once in their life. The condition can cause painful symptoms and vaginal discharge, and although treatable with antibiotics, it frequently comes back within a short time. If left untreated, BV can lead to problems with pregnancy and an increased risk of sexually transmitted infections, including HIV.

A team of researchers at the Broad Institute of MIT and Harvard; the Ragon Institute of Mass General Brigham, MIT, and Harvard; and St. Jude Children’s Research Hospital have discovered that oleic acid, one of the most abundant fatty acids in the body, restores a healthy balance of vaginal microbes in a laboratory model of BV.

Their findings, published in Cell, demonstrate that oleic acid and several other unsaturated long-chain fatty acids (uLCFAs), which are critical components of cell membranes and can have antimicrobial properties, simultaneously inhibit the growth of vaginal microbes associated with negative health effects and promote other species associated with a healthier female genital tract. Treatments that promote this balance of microbes could one day help prevent repeat vaginal infections in people.

“Current treatment methods work as well as a coinflip, and that hasn’t changed in more than 40 years of medical practice, so new methods are needed to help patients” said first author Meilin Zhu, who recently graduated with a PhD from the labs of Paul Blainey, a Broad core institute member and MIT professor, and Doug Kwon, a core member of the Ragon Institute, associate professor of medicine at Harvard Medical School, and an infectious disease physician at the Massachusetts General Hospital, both co-senior authors on the paper.

“I’m so proud of this team and the partnership we formed to follow the science and set up some major positive impacts on women’s health,” Blainey said. “This is an amazing story of keen observation, serendipitous discovery, and the hard work that real scientific rigor demands.”

Metabolic differences

The human female genital tract is naturally colonized by microbial species in the Lactobacillus genus. Treating BV with antibiotics can shift the balance of lactobacilli toward an overabundance of Lactobacillus iners, a bacterial species that creates an environment that is more susceptible to BV recurrence.

Zhu sought methods of promoting Lactobacillus crispatus, a species that creates a more stable microbiome than L. iners. She planned to use a large-scale screen developed in the Blainey lab to study the impacts of different compounds on the bacteria.

But Zhu discovered an important clue even before she began the screening. A component of the culture medium used to grow lactobacilli in the lab was disrupting the screening tool, but the bacteria would not grow in culture without it. While troubleshooting the issue, Zhu found that many of the lactobacilli required an ingredient in the medium-oleic acid-to thrive. When she cultured different strains of lactobacilli with oleic acid, she found that oleic acid inhibited growth of L. iners, the detrimental bacteria, and simultaneously promoted the growth of strains associated with healthier microbiota such as L. crispatus.

Using RNA sequencing and working with the Broad’s Metabolomics Platform and collaborators at St. Jude’s, the team identified a group of genes involved in processing uLCFAs that are present only in the non-Lactobacillus iners species. One of these genes encodes the enzyme oleate hydratase, which sequesters uLCFAs, a scarce resource, into a form only bacteria with this enzyme can use. Another of the genes encodes a fatty acid efflux pump that is necessary for bacteria to withstand high concentrations of oleic acid.

“We used state-of-the-art genetics tools that a lot of researchers in vaginal microbiology haven’t had access to, even though they’re the gold standard for any mechanistic study,” Zhu said. “It’s a good step forward for the field.” She added that the field of vaginal microbiology does not receive the same resources as other areas of microbiology.

The team also modeled how oleic acid might affect the vaginal microbiome of BV patients by culturing bacteria associated with BV together with L. iners and L. crispatus. Oleic acid effectively inhibited growth of L. iners as well as most BV-associated bacteria, including some strains resistant to standard antibiotic treatment. This indicates oleic acid may be an effective way to restore a stable, healthy microbiome in the female genital tract after BV.

“This study is an important example of how understanding core metabolic requirements and functions of key bacteria can lead directly to new therapies that allow us to modify the microbiome for improved health,” said co-senior author Seth Bloom, an infectious diseases instructor at the Massachusetts General Hospital.

At the Ragon Institute, Kwon’s lab is working to move this research toward a human clinical trial.

“We believe there is exciting potential to translate these findings to durably alter the vaginal microbiome to improve BV treatment and reduce adverse health outcomes for women globally,” Kwon said.

Reference:

Meilin Zhu, Matthew W. Frank, Christopher D. Radka, Paul C. Blainey, Seth M. Bloom, Douglas S. Kwon,  Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment, Cell, https://doi.org/10.1016/j.cell.2024.07.029.

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