Selective Enoxaparin Protocol Reduces Wound Hematomas Without Raising Postpartum VTE Risks: JAMA

USA: The approach to thromboprophylaxis—preventing blood clot formation—has long been a critical consideration in obstetric care due to the increased risk expectant mothers face.

A recent study has demonstrated two strategies: the traditional standard risk-stratified heparin-based protocol versus a newer, more selective approach. Both techniques mitigate the risk of venous thromboembolism (VTE), a potentially life-threatening complication during pregnancy and the postpartum period.

The retrospective observational study, published in JAMA, found that a more selective protocol for postpartum enoxaparin was associated with reduced rates of wound hematomas without evidence of increased rates of postpartum thromboembolic events.

A more selective protocol for chemoprophylaxis led to a decrease in heparin (enoxaparin) administration (16% versus 8%), the researchers reported. The selective protocol for postpartum enoxaparin was associated with a reduction in wound hematoma (0.7% versus 0.3% in the selective protocol group; adjusted odds ratio, 0.38) without evidence of a rise in VTE (0.1% versus 0.1% in the selective protocol group; adjusted odds ratio, 0.40).

In 2016, a pregnancy-related VTE prophylaxis protocol was adopted based on American College of Obstetricians and Gynecologists guidelines that recommended postpartum heparin-based chemoprophylaxis (enoxaparin) based on a risk-stratified algorithm.

In 2021, a more selective risk-stratified approach was implemented in response to higher occurrences of wound hematomas, despite no significant decrease in VTE with the existing protocol. In the study, Macie L. Champion, St David’s Medical Center, Austin, Texas, and colleagues aimed to evaluate outcomes of the more selective risk-stratified approach to heparin-based obstetric thromboprophylaxis (enoxaparin) protocol.

The retrospective observational study included 17,489 patients who gave birth at a single tertiary care center in the southeast US. Data collection was between 2016 and 2018 for the original protocol period, and between December 1, 2021, and May 31, 2023, for the more selective protocol period. Patients receiving outpatient anticoagulation for active VTE or deemed at high VTE risk during pregnancy were excluded from the study.

The study compared outcomes between two postpartum VTE chemoprophylaxis protocols: the standard risk-stratified protocol and the more selective protocol. The primary outcome measured was the clinical diagnosis of wound hematoma within six weeks after childbirth. Secondary outcomes included new diagnoses of VTE within the same postpartum period. Researchers analyzed baseline characteristics and outcomes across both protocol groups and calculated adjusted odds ratios with 95% confidence intervals, using the original protocol group as the reference point for comparison.

The study led to the following findings:

  • Of 17 489 patients included in the analysis, 71% were in the original protocol group, and 29% 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), specifically due to a lower rate of superficial wound hematomas (0.6% versus 0.3%).
  • There was no significant increase in VTE or individual types of VTE (0.1% versus 0.1%; aOR, 0.40).

“Our findings showed that implementing a more selective risk-stratified approach in an enoxaparin thromboprophylaxis protocol for venous thromboembolism was linked to lower rates of wound hematomas, without a corresponding increase in 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. 2024;332(4):310–317. doi:10.1001/jama.2024.8684

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Higher consumption of fruits during midlife associated with lower odds of depressive symptoms at late-life, suggests study

Populations are rapidly ageing worldwide, and there is an increased prevalence of late-life depressive symptoms among older adults, which include depressed feelings, lack of pleasure, delayed cognitive processing and reduced volitional activity, often accompanied by loss of appetite, insomnia, poor concentration, and increased fatigue. This has been related to underlying neurodegenerative changes in the brain associated with ageing. The growing imperative to keep older adults in good health has spurred extensive research into approaches that could prevent late-life depression, and accumulating evidence has revealed the plausible role of dietary factors in protecting against depression in ageing. Could specific diet or food items consumed earlier in life have an impact on mental well-being in later years?

In a longitudinal study conducted by the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), involving 13,738 participants from the large population-based Singapore Chinese Health Study that tracked participants through their mid-life to later life spanning about 20 years, researchers found that participants who consumed higher quantities of fruits earlier in life exhibited a reduced likelihood of experiencing depressive symptoms later in life.

The authors studied a total of 14 fruits most commonly consumed in Singapore and found that the consumption of most fruits, including oranges, tangerines, bananas, papayas, watermelons, apple and honey melon, was associated with reduced likelihood of depression. The association could possibly be the high levels of antioxidants and anti-inflammatory micronutrients in fruits — such as vitamin C, carotenoids and flavonoids — which have been shown to reduce oxidative stress and inhibit inflammatory processes in the body that may affect the development of depression. Consumption of vegetables, on the other hand, was found to have no association with the likelihood of depressive symptoms. The findings, published in the Journal of Nutrition, Health and Aging, provide valuable insights into the potential benefits of eating sufficient fruits in mitigating depressive symptoms later in life.

Professor Koh Woon Puay from the Healthy Longevity Translational Research Programme at NUS Medicine and Principal Investigator of the study, said, “Our study underscores the importance of fruit consumption as a preventive measure against ageing-related depression. In our study population, participants who had at least 3 servings of fruits a day, compared to those with less than one serving a day, were able to reduce the likelihood of ageing-related depression significantly by at least 21%. This can be achieved by eating one to two servings of fruits after every meal. We did not see any difference in our results between fruits with high and low glycemic index. Hence, for those with diabetes, they can choose fruits with low glycemic index that will not raise blood sugars as much as those with high index.”

At the initial stage of the study from 1993 to 1998, when participants were of average age of 51 years, they were asked to answer a structured questionnaire on how often they consumed a standard serving size of each food item daily, for 14 fruits and 25 vegetables. In 2014 to 2016, when participants were of average age of 73 years, depressive symptoms were examined using a standard test (Geriatric Depression Scale) and 3,180 (23.1%) participants who reported having five or more symptoms were considered to have depression in our study. After adjusting for factors that could potentially confound the relationship, including medical history, smoking status, level of physical activity, sleep duration, and ageing-related factors, the team found that higher consumption of fruits, but not vegetables, was associated with lower odds of depressive symptoms in a stepwise manner.

Prof Koh added, “Our study aimed to examine the relationship of mid-life consumption of fruits and vegetables with the risk of depressive symptoms in late life.Although other studies have also examined the associations of fruits and vegetables with risk of depression, there are inconsistencies in the results, and many of them were done in Western populations. To our best knowledge, ours is the largest population-based study in an Asian population to study this association.”

These findings suggest that promoting fruit consumption for individuals in mid adulthood, typically defined as ages 40 to 65 years, could yield long-term benefits for their mental well-being at late adulthood beyond 65 years. Hence, the study’s results hold significant implications for public health education and initiatives to make fruits more accessible for the general population. Following the study, the research team is looking into the association of other modifiable behavioural factors, such as sleep duration, smoking and other dietary factors, with the mental health of older adults.

Reference:

Huiqi Li, Li-Ting Sheng, Aizhen Jin, An Pan, Woon-Puay Koh. Association between consumption of fruits and vegetables in midlife and depressive symptoms in late life: the Singapore Chinese Health Study. The Journal of nutrition, health and aging, 2024; 28 (6): 100275 DOI: 10.1016/j.jnha.2024.100275.

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Frailty can effectively indicate adverse perioperative outcomes in percutaneous nephrolithotomy: Study

A recent study published in Urolithiasis journal revealed that frailty is a major predictor of negative perioperative outcomes in older patients undergoing percutaneous nephrolithotomy (PCNL) which highlights the critical need to identify and address frailty in this population.

Kidney stones represent a significant health concern, particularly among older adults, with a notably higher prevalence in males over the age of 60. The development of kidney stones is influenced by several risk factors, including male sex, hypertension, obesity, diabetes, and various lifestyle choices. The complications associated with kidney stones can be severe, leading to conditions such as cardiovascular disease, chronic kidney disease, and end-stage renal disease. Among the treatment options, percutaneous nephrolithotomy stands out as the preferred method for managing complex kidney stones due to its high success rate and its ability to achieve a stone-free state, outperforming other treatments like shockwave lithotripsy and ureteroscopy.

The primary objective of this study is to assess the impact of frailty on perioperative outcomes in patients aged 60 and above who underwent PCNL. To achieve this, the study analyzes data from the US Nationwide Inpatient Sample (NIS) database, covering the years 2010 to 2020. The goal is to understand how frailty influences key perioperative outcomes within this older patient demographic.

The study employs a comprehensive methodology, classifying patients into low, medium, and high frailty risk groups using the hospital frailty risk score (HFRS). A total of 30,829 patients were included in the analysis, with the study focusing on various outcomes such as in-hospital mortality, unfavorable discharge, prolonged hospital stays, transfusion needs, hospital costs, and complications.

The findings of the study reveal that high frailty risk is significantly associated with poorer perioperative outcomes. Specifically, patients with a high frailty risk exhibited increased rates of in-hospital mortality, higher rates of unfavorable discharge, longer hospital stays, a greater need for transfusions, more complications, and higher total hospital costs. Frailty emerges as a strong predictor of adverse outcomes, highlighting the need for meticulous management of frail older patients undergoing PCNL.

In discussing the results, the study underscores the critical importance of recognizing and managing frailty in older patients to improve perioperative outcomes. Incorporating frailty assessments into preoperative evaluations could significantly enhance the predictive accuracy for in-hospital mortality and other complications, thereby improving patient care and outcomes.

Overall, frailty is a significant prognostic indicator of adverse outcomes in older patients undergoing PCNL. It is essential for medical professionals to consider frailty when planning and executing treatment for kidney stones in older adults to mitigate risks and enhance recovery. This study emphasizes the critical role of frailty in determining surgical outcomes, suggesting that tailored care plans are vital for this vulnerable population.

Source:

Chien, Y.-C., Chen, P.-H., & Chang, Y.-J. (2024). Impact of frailty on perioperative outcomes following percutaneous nephrolithotomy in older persons: evidence from the US Nationwide Inpatient Sample. In Urolithiasis (Vol. 52, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1007/s00240-024-01595-y

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Extended Mesenteric Resection Not Superior for Reducing Crohn’s Disease Recurrence, reveals research

Recently, researchers have recorded that even the shortened mesenteric resection does not lower the rate of postoperative onset of Crohn’s disease as compared to conventional mesenteric sparing resection. This study has been published by Eline M L et al in the recent issue of The Lancet: Gastroenterology and Hepatology.

Some retrospective data have shown that conduct of resection of involved mesentery in an ileocolic resection may lead to better outcomes in Crohn’s disease. However, no prospective data have been available based on controlled trials. This is a controlled international trial conducted to compare conventional mesenteric sparing resection with extended mesenteric resection in terms of their impact on recurrence postoperatively in Crohn’s disease patients.

The trial was conducted in six hospitals and tertiary care centers of the Netherlands and Italy. The study included patients more than 16 years old proven to have Crohn’s disease of the terminal ileum or ileocolic region (L1 or L3 disease) from endoscopy. Availability of recent imaging (ultrasound, MRI, or CT enterography) within the last three months was mandatory. And patients with the prospect of undergoing primary ileocolic resection with ileocolic anastomosis were also at random 1:1 to either extended mesenteric resection or conventional mesenteric sparing resection. The primary endpoint 6 months post-surgery is an endoscopic recurrence. Analyses excluded patients without an anastomosis, with postoperative diagnosis other than Crohn’s disease, or who withdrew consent.

The key findings of the study were:

  • From February 19, 2020, to April 24, 2023, 217 patients were assessed for eligibility.

  • Seventy-eight were excluded, leaving 139 enrolled patients who were randomized to extended mesenteric resection (n=71) or mesenteric sparing resection (n=68).

  • Post-randomization exclusions included withdrawal of consent (n=2), postoperative non-Crohn’s diagnosis (n=2), and no anastomosis (n=2).

  • Two patients were lost to follow-up, and two deviated from the protocol. The baseline analysis included 133 patients (67 in the extended group and 66 in the sparing group), with a median age of 36 years (IQR 25–54), and 43% were male.

  • No difference at 6 months post-surgery (42% in extended group vs. 43% in sparing group; relative risk 0.985, 95% CI 0.663–1.464; p=1.0).

  • Anastomotic leakage occurred in 8% of extended resection patients versus 2% in the sparing group within 30 days post-surgery.

  • Clavien-Dindo grade IIIa or higher complications were reported in 11% of extended resection patients and 8% of sparing resection patients.

The conclusion was that there was no benefit or advantage to an extended mesenteric resection in preventing recurrences over and above conventional mesenteric-sparing resections. Recurrence rates, endoscopy, and anastomotic leakages were balanced in both groups, and the rate of severe complications supported the safety and efficacy of the MR resection recommended in the current guidelines.

Extended mesenteric resection is not better than conventional mesenteric-sparing resection with respect to the reduction of endoscopic recurrence in Crohn’s disease. The results of this study would further strengthen the recommendation of mesenteric-sparing resection as the elective method of managing Crohn’s disease, and wherein effective treatment is achieved with decreased complications.

Reference:

van der Does de Willebois, E. M. L., Bellato, V., Duijvestein, M., van der Bilt, J. D. W., van Dongen, K., Spinelli, A., D’Haens, G. R., Mundt, M. W., Furfaro, F., Danese, S., Vignali, A., Bemelman, W. A., Buskens, C. J., Carvello, M., Van Dieren, S., Frontali, A., Govaert, J., Hompes, R., Koot, B., … Zwaveling, S. (2024). Effect of mesenteric sparing or extended resection in primary ileocolic resection for Crohn’s disease on postoperative endoscopic recurrence (SPICY): an international, randomised controlled trial. The Lancet. Gastroenterology & Hepatology. https://doi.org/10.1016/s2468-1253(24)00097-9

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Could Botox make walking easier in children with cerebral palsy?

A recent randomized clinical trial published in Developmental Medicine & Child Neurology assessed whether injections of botulinumtoxin-A in calf muscles benefit children with cerebral palsy.

“We hypothesized that injections with botulinumtoxin-A in the calf muscles would make walking easier, caused by improved ankle joint functioning following spasticity reduction,” the authors wrote.

In the trial, one botulinumtoxin-A treatment was not superior to placebo in making walking easier (measured as a reduction in energy cost or improved walking capacity); however, there was some evidence of a delayed improvement in energy cost. Moreover, there was some evidence of a decrease in calf pain intensity. No serious adverse events related to botulinumtoxin-A treatment were recorded.

Reference:

Does botulinum toxin A make walking easier in children with cerebral palsy? A Randomized Clinical Trial, Developmental Medicine & Child Neurology (2024). DOI: 10.1111/dmcn.16038.

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D-dimer to fibrinogen ratio Promising Biomarker for Pulmonary Embolism Diagnosis in Postpartum Women: Study

China: A recent study published in BMC Pregnancy and Childbirth has revealed a higher diagnostic value of the D-dimer to fibrinogen ratio (DFR) than the D-dimer for postpartum women with suspected pulmonary embolism.

“Using either the neutrophil-to-lymphocyte ratio or the platelet-to-lymphocyte ratio in combination with the D-dimer to-fibrinogen ratio is an effective strategy for ruling out pulmonary embolism, the researchers reported.

Pulmonary embolism is a common disease tied to high morbidity and mortality. Its diagnosis is challenging due to diverse clinical presentations and the lack of specific biomarkers. Xiaohua Liu, Tongji University, Shanghai, P.R. China, and colleagues aimed to investigate the diagnostic value of pulmonary embolism for postpartum women by D-dimer to fibrinogen ratio, and it combined with neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio.

For this purpose, the researchers selected 537 women with suspected pulmonary embolism as the research subjects from the Shanghai First Maternity and Infant Hospital between 2019 and 2022.

The study applied the D-dimer to fibrinogen ratio, combined with either the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio, to assess the clinical likelihood of pulmonary embolism. The positive predictive value of both scores was calculated using computed tomography pulmonary arteriography as the gold standard.

The diagnostic efficacy of the D-dimer to fibrinogen ratio, in conjunction with the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio, was assessed using parameters such as area under the curve, sensitivity, specificity, and other indicators on the receiver operating characteristic curve.

The following were the key findings of the study:

· Among the 502 women included for analysis, 38.65% were definitely diagnosed with pulmonary embolism.

· The positive predictive values of D-dimer to fibrinogen ratio and it combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio were 70.1%, 50.5%, and 56.5%, respectively in the postpartum women, the area under the curve for the D-dimer to fibrinogen ratio and it combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio were 0.606, 0.624, and 0.639, respectively.

· The negative predictive values of D-dimer to fibrinogen ratio, combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio, were 50.5%, 70.1%, and 69.8%, respectively.

In postpartum women, the D-dimer to fibrinogen ratio proves to be a valuable biomarker for diagnosing pulmonary embolism, which could potentially minimize unnecessary testing. When combined with NLR or PLR, DFR becomes particularly useful in ruling out pulmonary embolism.

“The adoption of DFR may aid in identifying high-risk postpartum women, thereby assisting clinicians in making informed treatment decisions and potentially enhancing patient outcomes,” the researchers wrote.

The study’s limitations include its cross-sectional design, which prevents establishing causal relationships and conducting longitudinal predictive assessments of DFR in postpartum pulmonary embolism. Additionally, the relatively small sample size may restrict the generalizability of the findings.

“Further validation through multicenter prospective studies with larger cohorts is needed to confirm the diagnostic effectiveness of DFR,” they concluded.

Reference:

Zhou, W., Qu, C., Liu, X. et al. Diagnostic value of D-dimer to fibrinogen ratio for pulmonary embolism in postpartum women. BMC Pregnancy Childbirth 24, 482 (2024). https://doi.org/10.1186/s12884-024-06670-1

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Trifarotene cream may reduce acne-induced post-inflammatory hyperpigmentation across all skin types: Study

Researchers have found in a recent study that trifarotene combined with a skincare regimen significantly improves acne-induced hyperpigmentation (AIH) in patients with moderate acne vulgaris (AV). A recent phase IV clinical trial demonstrates that integrating trifarotene with a holistic skincare approach not only enhances the management of acne but also contributes to noticeable improvements in hyperpigmentation. This study was published in the International Journal of Dermatology by Andrew A. and colleagues.

Acne vulgaris (AV) frequently results in acne-induced hyperpigmentation (AIH), a condition that can persist even after the resolution of active acne. Trifarotene, a topical retinoid, has shown promise in addressing pigmentation issues associated with acne. This study aimed to evaluate the effectiveness of trifarotene in combination with a skincare regimen—which includes a moisturizer, cleanser, and sunscreen—compared to a vehicle treatment alone, over a 24-week period.

This double-blind, parallel-group phase IV study involved 123 participants aged 13–35 years with moderate AV and AIH. The study consisted of two treatment arms: one with 50 μg/g trifarotene cream and a skincare regimen. The outcome measures adopted were AIH overall disease severity and post-acne hyperpigmentation index, acne lesion counts, and patient-reported outcomes. Standard safety assessments were also made.

The key findings of the study were as follows:

  • At Week 12, trifarotene significantly improved from baseline in ODS score (−1.6 vs. −1.1, P = 0.03). At Week 24, both were similar, forming the primary endpoint.

  • At Week 24, the mean change in PAHPI score demonstrated a greater decrease with trifarotene versus vehicle (−18.9% vs. −11.3%, P < 0.01).

  • It had been observed that at week 12, the change in acne lesion counts was more reduced with trifarotene than with the vehicle, and at week 24, the reduction showed statistically significant results with (P < 0.05).

  • At weeks 12 and 24, with trifarotene, higher success rates were observed, which showed statistically considerable results where the (p< 0.05).

  • The patients responded that the contraceptive regimen contributed to reduced irritation, which has facilitated better adherence to the treatment protocol.

  • Improvement in pigmentation and erythema was observed in all types of skin.

  • AEs occurred more frequently in the vehicle group, 30.2%, than in patients who were treated with trifarotene (16.7%).

The findings of the study confirmed that trifarotene, in association with a complete skincare regiment, has remarkable benefits in the management of acne-induced hyperpigmentation. That means evidence of effectiveness of the combination was reflected in the improved ODS and PAHPI scores, reduction in the number of lesions, and adequate satisfaction among the patients. Moreover, lesser adverse events by trifarotene make it even more safe for the management of acne and its related pigmentary disorders.

In summary, trifarotene with skincare was more effective and better tolerated in acne-induced hyperpigmentation than vehicle treatment. The study thus supports the use of trifarotene in multifaceted acne management strategies for the improvement of patient outcome and satisfaction measures.

Reference:

Alexis, A., Del Rosso, J. Q., Forman, S., Martorell, A., Browning, J., Laquer, V., Desai, S. R., York, J. P., Chavda, R., Dhawan, S., Moore, A. Y., & Stein-Gold, L. (2024). Importance of treating acne sequelae in skin of color: 6‐month phase IV study of trifarotene with an appropriate skincare routine including UV protection in acne‐induced post‐inflammatory hyperpigmentation. International Journal of Dermatology, 63(6), 806–815. https://doi.org/10.1111/ijd.17189

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Risankizumab improves clinical remission rates of moderate to high active ulcerative colitis, finds research

A recent research published in the Journal of American Medical Association found that risankizumab improved clinical remission rates in an induction and maintenance study for individuals with moderate to high active ulcerative colitis.

Risankizumab is a monoclonal antibody that targets the p19 component of IL-23 specifically and its therapeutic benefits in treating ulcerative colitis are uncertain. Thus, this study by Edouard Louis and colleagues assessed the safety and effectiveness of risankizumab when used as an induction and maintenance treatment for individuals with ulcerative colitis.

There were two phase 3 randomized clinical studies with a total of 977 patients  enrolled in the induction study between November 5, 2020, and August 4, 2022 (with a final follow-up scheduled for May 16, 2023). 754 individuals were enrolled in the maintenance study between August 28, 2018, and March 30, 2022 (with a final follow-up scheduled for April 11, 2023). The patients who had moderate to severe active ulcerative colitis with no previous exposure to risankizumab and had a history of intolerance or poor response to one or more conventional medicines, advanced therapies, or both types of therapy met the eligibility requirements.

In the induction experiment, the participants were randomized 2:1 to intravenously receive either 1200 mg of risankizumab or a placebo at weeks 0, 4, and 8. The patients who experienced a clinical response (as measured by the modified Mayo score) following intravenous risankizumab treatment were randomized 1:1:1 to receive either 360 mg of risankizumab or subcutaneous treatment with 180 mg or or placebo every eight weeks for 52 weeks as part of the maintenance trial. In the induction phase, the primary endpoint was clinical remission at week 12, and in the maintenance study, it was at week 52.

Among the 975 patients examined in the induction study, the clinical remission rates at week 12 were 20/325 (6.2%) for placebo and 132/650 (20.3%) for 1200 mg of risankizumab. The maintenance study included 548 patients. At week 52, the clinical remission rates were 46/183 (25.1%) for placebo, 70/186 (37.6%) for 360 mg of risankizumab and 72/179 (40.2%) for 180 mg of risankizumab. In the therapy groups, no undesirable indicators were seen. Risankizumab increased the rates of clinical remission in individuals with moderate to high active ulcerative colitis in both an induction study and a maintenance trial.

Reference:

Louis, E., Schreiber, S., Panaccione, R., Bossuyt, P., Biedermann, L., Colombel, J.-F., Parkes, G., Peyrin-Biroulet, L., D’Haens, G., Hisamatsu, T., Siegmund, B., Wu, K., Boland, B. S., Melmed, G. Y., Armuzzi, A., Levine, P., Kalabic, J., Chen, S., … Cheng, L. (2024). Risankizumab for Ulcerative Colitis. In JAMA. American Medical Association (AMA). https://doi.org/10.1001/jama.2024.12414

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Research spotlight: Anxiety and depression are important risk factors for dangerous deep vein blood clots

Rachel Rosovsky, MD, MPH, director of Thrombosis Research and co-chair of the Thrombosis Committee at Massachusetts General Hospital and an associate professor of Medicine at Harvard Medical School, is lead author of a new study in the American Journal of Hematology; Anxiety and Depression Are Associated With Heightened Risk of Incident Deep Vein Thrombosis: Mediation Through Stress-Related Neural Mechanisms.

Ahmed Tawakol, MD, a physician investigator in the Division of Cardiology at Mass General and an associate professor of Medicine at Harvard Medical School, is senior author of the study.

What Question Were You Investigating with This Study?

Deep vein thrombosis (DVT) is a serious condition in which a blood clot forms in a deep vein in your body. We wanted to learn more about the association between anxiety and depression and DVT and understand the potential mechanisms behind this association.

What Were the Results?

Using a large clinical biobank of over 100,000 participants, we observed that an existing history of anxiety disorder and/or depression significantly elevated the risk of incident DVT.

We also found that anxiety disorders and/or depression may increase DVT risk through heightened activation of stress-related pathways.

We observed that increased stress neural activity, increased systemic inflammation, and impaired autonomic nervous system function mediated the effect of both anxiety disorders and depression on DVT, even after robust adjustments.

Based on our findings, anxiety disorders and depression should be viewed as important and independent risk factors for DVT, and our findings invite further investigation into whether behavioral and pharmacological strategies to treat anxiety disorders and depression can attenuate this risk.

What are the Clinical Implications and Next Steps?

Given the link between anxiety disorders, depression, stress-related neural activity (SNA), and the subsequent development of DVT, future studies should investigate the impact of reducing SNA on this pathway.

Specifically, future studies could test whether targeting SNA with interventions that may reduce SNA (i.e., exercise and stress reduction techniques) will reduce the risk of incident DVT and even the risk recurrent DVT.

Reference:

Rachel P. Rosovsky, Kenechukwu Mezue, Charbel Gharios, Giovanni Civieri, Alexander Cardeiro, Hadil Zureigat, Hui Chong Lau, Roger K. Pitman, Lisa Shin, Shady Abohashem, Michael T. Osborne, Farouc A. Jaffer, Ahmed Tawakol, Anxiety and depression are associated with heightened risk of incident deep vein thrombosis: Mediation through stress-related neural mechanisms, American Journal of Hematology, https://doi.org/10.1002/ajh.27427.

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Common respiratory infections may render immunity against COVID-19 infection, suggests study

Analyzing nasal swabs taken during the pandemic, researchers at Yale School of Medicine suggest that the frequent presence of other viruses and bacteria may have helped to protect children from the worst effects of COVID-19 by boosting their immune systems. Their results will be published in the Journal of Experimental Medicine (JEM).

Children are generally more susceptible than adults to respiratory infections such as the common cold, and yet, for unknown reasons, the SARS-CoV-2 virus tends to cause less severe symptoms in children than in adults, resulting in lower rates of hospitalization and death during the COVID-19 pandemic. The innate immune system provides the first line of defense against viruses and bacteria, quickly producing a variety of anti-viral and proinflammatory proteins to fend off infection while the body develops other, more targeted, immune responses such as antibodies. Studies have shown that, compared with adults, the innate immune system is more active in the nasal passages of children and might therefore be better at blocking the early stages of SARS-CoV-2 infection. But the reason for this increased activity is unknown.

“Prior work suggested that heightened nasal innate immunity in children was due to intrinsic biological mechanisms inherent to their age,” says Ellen F. Foxman, associate professor of Laboratory Medicine and Immunobiology at Yale School of Medicine and the senior author of the new JEM study. “But we thought it could also be due to the high burden of respiratory viruses and bacterial infections in children.”

To investigate whether frequent respiratory infections are responsible for elevating nasal innate immunity in children, Foxman and colleagues re-analyzed more than 600 nasal swabs originally taken during the pandemic from pediatric patients about to undergo elective surgery or emergency room evaluation. Initially tested only for the presence of SARS-CoV-2, Foxman and colleagues re-screened the samples for 19 different respiratory viruses and bacteria, as well as measuring the levels of antiviral and inflammatory proteins produced by the innate immune system.

The researchers found that many children—even those without any symptoms—were infected with respiratory pathogens other than SARS-CoV-2. This was especially true for younger children, with viruses or infection-causing bacteria being detected in around 50% of asymptomatic patients under five years old. Children with higher levels of respiratory pathogens showed higher levels of nasal innate immune activity, regardless of whether they were toddlers or teenagers.

To further investigate the relationship between respiratory infections and nasal innate immunity, Foxman’s team compared nasal swabs taken from healthy one-year-olds at both a routine well-child checkup and a follow-up appointment one to two weeks later. Over half of the children tested positive for a respiratory virus on one of their two visits to the pediatrician, indicating that they had either acquired or cleared an infection in the intervening period. In almost every case, the child’s innate immune activity was higher at the time they were infected and lower at the time when they were virus free.

“This reveals that nasal antiviral defenses are not continually on high alert in young children but are activated in response to acquisition of a respiratory virus, even when that virus is not causing symptoms,” says Foxman.

Taken together, the study’s results indicate that the innate immune system is often highly activated in the nasal passages of children because they are frequently infected with relatively benign pathogens, such as the rhinoviruses responsible for the common cold. Foxman speculates that young children have more infections with common seasonal viruses than adults because they have less immunological protection from prior exposures (such as antibodies). However, since SARS-CoV-2 was a new virus to the human population, neither adults nor children had prior protection when the COVID-19 pandemic began. In this situation, activation of generalized antiviral defenses in children by other infections may have helped to fight off the initial stages of SARS-CoV-2 infection, leading to less severe outcomes in children compared with adults.

“We have identified respiratory viruses and bacteria as key drivers of the enhanced nasal innate immunity in children,” Foxman says. “Our results compel further study of how seasonal respiratory viruses and nasal bacteria impact disease severity of COVID-19 and pediatric immune responses in general.”

Reference:

Timothy A. Watkins, Alex B. Green, Julien A.R. Amat, Nagarjuna R. Cheemarla, Katrin Hänsel, Richard Lozano, Sarah N. Dudgeon, Gregory Germain, Marie L. Landry, Wade L. Schulz, High burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children, Journal of Experimental Medicine, https://doi.org/10.1084/jem.20230911

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