Excessive insulin due to childhood sedentariness may raise risk of type 2 diabetes: Study

An increase in sedentary time from childhood is associated with a significant increase in blood insulin concentration, a new study shows. However, light physical activity could reduce the risk of excess insulin and insulin resistance. The study was conducted in collaboration between the Universities of Bristol and Exeter, and the University of Eastern Finland, and the results were published in the Journal of Clinical Endocrinology and Metabolism.

Based on the University of Bristol’s Children of the 90s data, the study included 792 children followed up from 11 to 24 years of age. At baseline they spent an average of 6 hours per day in sedentary activities, which increased to 9 hours per day during the follow-up. This increase in sedentary time was associated with continuously higher insulin levels in fasting blood, especially among youths with overweight and obesity, whose risk of excess insulin increased by 20%. On the contrary, an average of light physical activity (LPA) of 3-4 hours per day throughout the follow-up decreased the risk of excess insulin by 20%. Higher LPA was also associated with lower insulin resistance.

Participating in moderate-to-vigorous physical activity (MVPA) showed signs of reducing insulin but to a much smaller extent.

Earlier results from the same cohort have linked sedentariness to fat obesity, dyslipidaemia, inflammation, and premature vascular damage. The researchers have also observed a vicious cycle of obesity and worsening insulin resistance.

Light physical activity is now emerging as an effective approach to reversing the deleterious effect of childhood sedentariness. However, whether long-term exposure to LPA from childhood reduces excess glucose, insulin, and insulin resistance has not been examined before. This is because only a few studies have repeatedly measured all these in a large population of healthy youth.

The current study is the largest and the longest follow-up accelerometer-measured movement behaviour and glucose, insulin, and insulin resistance study in the world. The participants wore accelerometer devices on their waists at ages 11, 15, and 24 years for 4–7 days and had fasting glucose and insulin measurements at ages 15, 17, and 24 years. Their fasting blood samples were also repeatedly measured for high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and high-sensitivity C-reactive protein. Blood pressure, heart rate, smoking status, socio-economic status, and family history of cardiovascular disease were controlled for in the analyses.

“Calling a spade a spade, our recent studies have identified childhood sedentariness as a monster that threatens the young population across the globe, no thanks to excessive screen use, “ says Andrew Agbaje, an award-winning physician and associate professor (docent) of clinical epidemiology and child health at the University of Eastern Finland.

“Sedentariness should be recognised as one of the twenty-first century independent causes of excess insulin, fat obesity, high lipid levels, inflammation, and arterial stiffness. 3–4 hours of LPA per day is critically important to antagonising childhood sedentariness. While we await the update of the current World Health Organization’s physical activity guideline, which does not include an LPA recommendation, public health experts, health policymakers, health journalists, paediatricians, and parents should encourage kids to participate in LPA daily.”

Reference:

Andrew O Agbaje, The Interactive Effects of Sedentary Time, Physical Activity, and Fat Mass on Insulin Resistance in the Young Population, The Journal of Clinical Endocrinology & Metabolism, 2024;, dgae135, https://doi.org/10.1210/clinem/dgae135.

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Accelerated Aging May Increase Risk of Early-onset Cancers in Younger Generations, states study

SAN DIEGO – Accelerated aging was more common in recent birth cohorts and was associated with increased incidence of early-onset solid tumors, according to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2024, held April 5-10.

“Multiple cancer types are becoming increasingly common among younger adults in the United States and globally,” said Ruiyi Tian, MPH, a graduate student in the lab of Yin Cao, ScD, MPH at Washington University School of Medicine in St. Louis. “Understanding the factors driving this increase will be key to improving the prevention or early detection of cancers in younger and future generations.”

Tian and colleagues hypothesized that increased biological age, indicative of accelerated aging, may contribute to the development of early-onset cancers, often defined as cancers diagnosed in adults younger than 55 years. In contrast to chronological age—which measures how long a person has been alive—biological age refers to the condition of a person’s body and physiological processes and is considered modifiable, Tian explained.

“Unlike chronological age, biological age may be influenced by factors such as diet, physical activity, mental health, and environmental stressors,” she added. “Accumulating evidence suggests that the younger generations may be aging more swiftly than anticipated, likely due to earlier exposure to various risk factors and environmental insults. However, the impact of accelerated aging on early-onset cancer development remains unclear.” 

To examine the association between biological age and cancer risk in younger individuals, Tian and colleagues examined data of 148,724 individuals housed in the U.K. Biobank database. They calculated each participant’s biological age using nine biomarkers found in blood: albumin, alkaline phosphatase, creatinine, C-reactive protein, glucose, mean corpuscular volume, red cell distribution width, white blood cell count, and lymphocyte proportion. Individuals whose biological age was higher than their chronological age were defined as having accelerated aging. 

Tian and colleagues first evaluated accelerated aging across birth cohorts and found that individuals born in or after 1965 had a 17% higher likelihood of accelerated aging than those born between 1950 and 1954. They then evaluated the association between accelerated aging and the risk of early-onset cancers. They found that each standard deviation increase in accelerated aging was associated with a 42% increased risk of early-onset lung cancer, a 22% increased risk of early-onset gastrointestinal cancer, and a 36% increased risk of early-onset uterine cancer. Accelerated aging did not significantly impact the risk of late-onset lung cancer (defined here as cancer diagnosed after age 55), but it was associated with a 16% and 23% increased risk of late-onset gastrointestinal and uterine cancers, respectively.

“By examining the relationship between accelerating aging and the risk of early-onset cancers, we provide a fresh perspective on the shared etiology of early-onset cancers,” Tian said. “If validated, our findings suggest that interventions to slow biological aging could be a new avenue for cancer prevention, and screening efforts tailored to younger individuals with signs of accelerated aging could help detect cancers early.”

Future research from Tian and colleagues will aim to uncover the mechanisms driving accelerated aging and early-onset cancers to develop precision cancer prevention strategies.

A limitation of the study is that all participants were from the United Kingdom, which may limit the generalizability of the findings to populations with different genetic backgrounds, lifestyles, and environmental exposures. Tian noted that validation in diverse populations is needed.

The study was supported by the National Institutes of Health. Tian declares no conflicts of interest.

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S. persica chewing sticks and toothbrush, and standard toothbrush equally reliable in controlling plaque and gingivitis: Study

S. persica chewing sticks and toothbrush, and standard toothbrush equally reliable in controlling plaque and gingivitis suggests a new study published in the BMC Complementary Medicine and Therapies.

The values of plant-based products have taken on an expanding relevance in dentistry. Salvadora persica chewing stick (miswak) has been practiced for centuries and is recommended by the World Health Organization as a customary oral hygiene tool. The therapeutic effects of S. persica chewing stick are contributed by its mechanical cleansing action, active chemicals released, or the combination of these two actions. However, the S. persica chewing stick in its natural form can be difficult to maneuver in certain parts of the mouth. This concern has inspired the innovation of the S. persica toothbrush that is designed to merge the ease of use of a toothbrush with the beneficial natural properties of S. persica preserved in its bristle. The present study aimed to compare the clinical effectiveness between S. persica toothbrush, S. persica chewing stick and the standard toothbrush in plaque and gingivitis control. In this single-blinded and parallel randomized controlled trial, 78 participants were randomly divided into three groups to either use (i) S. persica toothbrush (MTB); (ii) S. persica chewing stick (MCS); or (iii) standard toothbrush (STB) in a standardized manner for three weeks. Plaque Index (PI) and Periodontal Inflamed Surface Area (PISA) values, measuring plaque levels and severity of gingivitis, respectively, were evaluated at baseline, one- and three-week post-interventions. Results: The MCS group showed a significant improvement in the mean PISA values of the anterior teeth compared to the MTB and STB groups (MCS: from 16.35 ± 10.03 to 3.41 ± 1.14; MTB: from 25.20 ± 14.01 to 3.57 ± 1.19; STB: from 26.54 ± 8.64 to 6.17 ± 0.86; p < .050). All three groups reported significant improvements (p < .001) in the plaque levels and the severity of gingivitis from baseline to three weeks after the intervention. Following correct techniques, S. persica toothbrush and chewing sticks are as effective as the standard toothbrush in plaque control and gingival health, which represent the reputed anti-plaque and anti-gingivitis properties of S. persica.

Reference:

Azizan, N.F., Mohd, N., Nik Azis, N.M. et al. Effectiveness of Salvadora persica toothbrush and Salvadora persica chewing stick in plaque and gingivitis control: a randomized control trial. BMC Complement Med Ther 23, 456 (2023). https://doi.org/10.1186/s12906-023-04295-z

Keywords:

S. persica, chewing sticks, toothbrush, standard toothbrush, equally reliable, controlling, plaque, gingivitis, study, BMC Complementary Medicine and Therapies, Azizan, N.F., Mohd, N., Nik Azis, N.M, Biofilm, Inflammation, Natural product, Oral hygiene, Salvadora persica

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Anemia may contribute to higher female mortality during heart surgery: JACC

USA: Women are at higher risk of death when undergoing heart bypass surgery than men. Researchers at Weill Cornell Medicine have determined that this disparity is mediated, to a large extent, by intraoperative anemia-the loss of red blood cells during surgery.

The study, published on March 5, in the Journal of the American College of Cardiology, suggests that strategies for minimizing anemia that occurs during this procedure could lead to better outcomes for women with cardiovascular disease.

This study set out to discover why women are less likely to survive coronary artery bypass grafting, a surgical procedure for restoring blood flow to the heart. The team, led by senior author Dr. Mario Gaudino, the Stephen and Suzanne Weiss Professor in Cardiothoracic Surgery at Weill Cornell Medicine, analyzed information obtained from the Society of Thoracic Surgeons Adult Cardiac Surgery Database on more than one million patients. Dr. Lamia Harik, fellow in Cardiothoracic Surgery Research at Weill Cornell Medicine, was first author on the paper.

They examined patient demographics (such as age and ethnicity), risk factors (including disease severity, previous heart attacks and the co-occurrence of other health conditions) and surgical data (including the time spent on the bypass machine and the volume of the components of blood, such as red blood cells).

Crunching the numbers, Dr. Gaudino and his team previously confirmed that women had a higher mortality associated with the procedure than men: 2.8 percent versus 1.7 percent, a nearly 50 percent difference. Now, using sophisticated statistical analyses to assess all the possible variables, the researchers found that a substantial portion of this enhanced risk—38 percent—could be attributed to severe intraoperative anemia.

This depletion of red blood cells is an inevitable side effect of using blood-diluting fluids to prime the heart-lung bypass machine that takes over the job of pumping blood throughout the body during surgery. Women may be even more susceptible to the effects of intraoperative anemia because they tend to arrive in surgery with lower red blood cell counts and have smaller body size compared to their male counterparts.

The study does not establish that intraoperative anemia is causing greater female mortality, but the two factors are associated. It suggests that clinicians and researchers should consider interventions to prevent or minimize severe intraoperative anemia, which can lead to dangerously reduced oxygen delivery to the body’s tissues, including the heart.

Using heart-lung bypass machines with shorter circuits, for example, would limit the volume of blood-diluting solution needed to run the pump. Randomized trials to assess whether methods for curtailing anemia could improve outcomes for women undergoing heart bypass surgery are “urgently needed,” wrote Dr. Gaudino, who is also a cardiovascular surgeon at NewYork-Presbyterian/Weill Cornell Medical Center.

References: Lamia Harik et al, Intraoperative Anemia Mediates Sex Disparity in Operative Mortality After Coronary Artery Bypass Grafting, Journal of the American College of Cardiology (2024). DOI: 10.1016/j.jacc.2023.12.032 10.1001/jamasurg.2022.8156 Journal information: Journal of the American College of Cardiology

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Microwave Ablation promising treatment alternative for patients with multifocal papillary thyroid carcinoma: Study

A recent study published in the Radiology journal illuminated the effectiveness of Microwave Ablation (MWA) as a promising treatment alternative for patients with multifocal papillary thyroid carcinoma (PTC). PTC is traditionally managed with surgical resection (SR) which often leads to a loss of thyroid function that raises concern about the quality of life of the patients post-treatment. This study compared the outcomes of MWA with SR and suggested that MWA preserves thyroid function and presents a minimally invasive option for patients.

This study was conducted across 10 medical centers from May 2015 to December 2021 and included a total of 775 patients who were diagnosed with T1N0M0 multifocal PTC through preoperative ultrasonography (US). This research utilized the propensity score matching and meticulously compared the progression-free survival (PFS) rates and complication rates between the patients who underwent MWA and the individuals who were subjected to SR.

The outcomes were observed over a median span of 20 to 26 months which revealed compelling evidence in favor of MWA. The procedure demonstrated significant advantages that included less blood loss, shorter incision lengths and reduced durations of both the procedure itself and hospital stays that highlighted its efficiency and patient-friendly nature. Also, the study found no significant difference in overall and 1-, 3- and 5-year PFS rates between the two groups that indicated the efficacy of MWA in controlling the disease progression is comparable to that of the traditional surgical approach. The results found low complication rates associated with MWA. SR resulted in permanent hoarseness and hypoparathyroidism in a small percentage of patients, whereas, MWA showed a relatively safe profile with low postoperative complications.

The conclusion of this extensive comparison highlights the potential of MWA as a critical treatment option for selected patients with multifocal T1N0M0 PTC. Overall, this study offers a less invasive treatment pathway that paves the way for improved quality of life and disease management strategies. Further research and comparative analyses is imperative which will solidify the role of MWA in the comprehensive management of thyroid cancer for the patients who face the bad prospect of thyroid surgery.

Source:

Zhao, Z.-L., Wang, S.-R., Dong, G., Liu, Y., He, J.-F., Shi, L.-L., Guo, J.-Q., Wang, Z.-H., Cong, Z.-B., Liu, L.-H., Yang, B.-B., Qu, C.-P., Niu, W.-Q., Wei, Y., Peng, L.-L., Li, Y., Lu, N.-C., Wu, J., & Yu, M.-A. (2024). Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study. In Radiology (Vol. 311, Issue 1). Radiological Society of North America (RSNA). https://doi.org/10.1148/radiol.230459

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Preventive PCI shows clinical benefit for Vulnerable non-flow-limiting Coronary Plaque in PREVENT trial

South Korea: Preventive percutaneous coronary intervention (PCI) reduces major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone in patients with non-flow-limiting vulnerable coronary plaques, PREVENT trial has shown.

“Focal preventive PCI resulted in a large reduction in target vessel failure at two years (0.4% vs 3.4%; HR 0.11) — the benefit persisting out to 7 years (6.5% vs 9.4%; HR 0.54), compared with standard therapy alone,” the researchers reported that the American College of Cardiology (ACC) meeting. The findings were subsequently published in The Lancet.

Target vessel failure was defined as a composite of target vessel myocardial infarction (MI), cardiac death, ischemia-driven target vessel revascularization, and hospitalization for unstable or progressive angina — the benefit of PCI was driven by the latter two endpoint components.

The study stated, “Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for PCI to include non-flow-limiting, high-risk vulnerable plaques.”

Sudden cardiac death and acute coronary syndrome are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The effectiveness and safety of focal preventive therapy with PCI of vulnerable plaques in reducing adverse cardiac events are unknown.

To fill this knowledge gap, Prof Seung-Jung Park, University of Ulsan College of Medicine, Seoul, South Korea, and colleagues aimed to assess whether preventive PCI of non-flow-limiting vulnerable plaques improves clinical outcomes versus optimal medical therapy alone.

For this purpose, the researchers conducted a PREVENT trial at 15 research hospitals in four countries. Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were included. They were randomly assigned in a 1:1 ratio to either PCI plus optimal medical therapy or optimal medical therapy alone. In all enrolled patients, follow-up continued annually until the last enrolled patient reached two years after randomization.

The study’s primary outcome was a composite of death from cardiac causes, ischemia-driven target-vessel revascularization, target-vessel myocardial infarction, or hospitalization for unstable or progressive angina.

The study led to the following findings:

· 5627 patients were screened for eligibility between 2015 and 2021, 1606 of whom were enrolled and randomly assigned to PCI (n=803) or optimal medical therapy alone (n=803). 73% of patients were men.

· Two-year follow-up for the primary outcome assessment was completed in 97% of patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776).

· At 2 years, the primary outcome occurred in 0·4% of patients in the percutaneous coronary intervention group and 3·4% of patients in the medical therapy group.

· The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome.

· Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at two years, 0·5% versus 1·3% patients died, and 1·1% versus 1·7% patients had a myocardial infarction.

The researchers of the PREVENT trial acknowledged that their open-label study design left room for a placebo effect and ascertainment bias. Lower-than-expected event rates also limited them.

They pointed to multiple ongoing randomized trials — INTERCLIMA, COMBINE-INTERVENE, FAVOR V AMI, and VULNERABLE– for more answers about preventive PCI on vulnerable plaques.

Reference:

DOI: https://doi.org/10.1016/S01406736(24)00413-6

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Preventive ablation of ventricular tachycardia may effectively prevent ICD shocks and hospitalization: Study

The first randomised trial to investigate preventive ablation of a potential arrhythmogenic substrate associated with coronary chronic total occlusion (CTO) in patients at high risk of ventricular arrhythmias (VAs) reduces the risk of appropriate implantable cardioverter-defibrillator (ICD) therapy and unplanned hospitalisation in patients with no previously recorded VAs. The late-breaking science is presented at EHRA 2024, a scientific congress of the European Society of Cardiology (ESC).

Principal investigator Dr. David Zizek of the University Medical Centre Ljubljana, Slovenia said: “In everyday clinical practice, ventricular tachycardia (VT) ablation is still often regarded as a last resort in the management of patients with ischaemic cardiomyopathy. We hypothesised that ablation early in the course of the disease, when patients have a lower burden of comorbidities, might be associated with fewer periprocedural complications and improved clinical outcomes compared to withholding the procedure until several ICD shocks have occurred. Our study shows that a primary prevention ablation strategy can be a safe and effective treatment option to prevent ICD interventions and arrhythmia-related hospitalisations.”

ICD therapy is recommended for primary prevention of sudden cardiac death in ischaemic cardiomyopathy patients with reduced ejection fraction despite optimal medical treatment. Approximately one in three ischaemic cardiomyopathy patients with previous myocardial infarction have infarct-related coronary CTO. Infarct-related CTO is a strong and independent predictor of VAs in ischaemic patients with a primary prevention ICD. Appropriate ICD shocks are live-saving, but are linked with reduced quality of life, physiological distress, pain, heart failure hospitalisation, and cardiovascular death. However, the optimal time to perform VT ablation is uncertain.

The PREVENTIVE VT trial investigated the impact of preventive VT ablation on ICD interventions in patients with ischaemic cardiomyopathy and infarct-related coronary CTO. The trial was conducted at four centres in Slovenia between September 2017 and January 2024. It enrolled patients with ischaemic cardiomyopathy, reduced ejection fraction (≤40%), angiographically proven coronary CTO associated with previous myocardial infarction, and no previously documented sustained VAs. In addition, patients were not eligible for revascularisation, were on optimal medical therapy, and had an indication for primary prevention ICD implantation.

Participants were randomly assigned 1:1 to preventive substrate ablation before ICD implantation (preventive ablation group) or ICD implantation only (standard therapy group). The purpose of ablation was to abolish abnormal ventricular electrograms within the scar and its border and achieve non-inducibility of monomorphic VT after a uniform stimulation protocol. High-density voltage mapping with a 3D electroanatomical mapping system was used to delineate the infarct-related CTO and the border zone, and scar homogenisation was performed. Primary prevention ICD settings for arrhythmia detection and therapy were recommended for both groups.

The primary outcome was a composite of appropriate ICD therapy or unplanned hospital admission for symptomatic VAs. Secondary outcomes included the incidence of appropriate ICD therapies, unplanned VA-related hospitalisation, cardiac hospitalisation (due to VA or worsening heart failure), electrical storm, and cardiovascular mortality.

A total of 60 patients were enrolled (30 in each group). The average age was 67.5 ± 8.1 years and 91.7% were male. In the preventive ablation group, total elimination of abnormal electrograms was achieved in 26 (86.7%) patients and VT was not inducible in 27 (90%) patients. There were 2 (6.6%) major complications associated with the ablation procedure.

During a mean follow-up of 44.73 months, the primary endpoint occurred in 5 (16.7%) patients undergoing ablation and 13 (43.3%) patients receiving an ICD only (multivariate hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.11-0.91; p=0.032). Univariate analyses showed that patients in the ablation group had fewer appropriate ICD therapies (17% vs. 40%; HR 0.37, 95% CI 0.13-1.05, p=0.051), unplanned VA-related hospitalisations (0% vs. 30%; p=0.001), and cardiac hospitalisations (13% vs. 53%; HR 0.21, 95% CI 0.07-0.63, p=0.002). While preventive ablation reduced the number of electrical storms (0% vs. 20%; p=0.01), it had no significant impact on cardiovascular mortality (13.3% vs. 26.7%; HR 0.41, 95% CI 0.12-1.38, p=0.139). Multivariate analyses were performed when events were recorded in both arms and yielded similar results.

Dr. Zizek said: “Our study also highlights the importance of identifying ischaemic cardiomyopathy patients with a high risk of VAs in whom substrate ablation might prevent arrhythmias and consequent debilitating ICD shocks, while outweighing the potential for procedural complications.”

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Vitamin D concentration above 30 ng/mL may protect against gestational diabetes in twin pregnancy: Study

China: A recent study revealed a significantly lowered risk of gestational diabetes mellitus (GDM) in twin pregnant women with vitamin D concentrations ≥ 30 ng/mL in the second trimester. The findings were published online in Nutrition Journal on April 10, 2024.

Gestational diabetes is a common complication of pregnancy, with significant short-term and long-term effects for both mothers and their offspring. Previous studies have shown the potential benefits of vitamin D in reducing GDM risk, yet not much is known about this association in twin pregnancies. To fill this knowledge gap, Li Wen, Chongqing Health Center for Women and Children, Chongqing, China, and colleagues aimed to investigate maternal vitamin D status in the second trimester and determine its association with the risk of GDM in twin pregnancies.

For this purpose, they conducted a prospective cohort study based on Chongqing Longitudinal Twin Study (LoTiS) data. To measure 25(OH)D concentrations, peripheral blood serum was collected from the mothers in the second trimester. Gestational diabetes was diagnosed at 23–26 weeks of gestation using a 75-g 2-h oral glucose tolerance test. The correlations between vitamin D status and GD risk were also examined.

The study revealed the following findings:

· Of the total participants, 29.9% of women were diagnosed with GDM.

· The mean serum 25(OH)D concentration in the second trimester was 31.1 ± 11.2 ng/mL, and the rate of vitamin D insufficiency and deficiency were 23.5% and 18.7%, respectively.

· Compared to women with a 25(OH)D concentration < 30 ng/mL, those with a 25(OH)D concentration ≥ 30 ng/mL had a significantly lower risk of GDM (RR 0.61), especially those who were overweight before pregnancy (RR 0.32).

· The restricted cubic splines model showed an inverted J-shaped relationship between vitamin D concentrations and GDM risk.

In conclusion, the risk of GDM was significantly reduced in those with vitamin D levels ≥ 30 ng/mL in the second trimester in twin pregnant women with vitamin D concentrations < 30 ng/mL in the second trimester. The researchers found a nonlinear association between vitamin D concentrations and GDM incidence, with 30 ng/mL considered as the cutoff for the vitamin D concentration that could significantly reduce GDM risk in twin pregnancies.

“There is a need for further multicenter research to provide more evidence elucidating the relationship between vitamin D and GDM in twin pregnancies,” the researchers concluded.

One limitation was the study’s single-center design, which limits the findings generalizability of the findings. Another limitation was the lack of accurate data on vitamin D supplementation during the second trimester.

Reference:

Li, Dy., Wang, L., Li, L. et al. Maternal vitamin D status and risk of gestational diabetes mellitus in twin pregnancies: a longitudinal twin pregnancies birth cohort study. Nutr J 23, 41 (2024). https://doi.org/10.1186/s12937-024-00944-2

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Vaccinations Do Not Increase Graft Rejection Risk in Corneal Transplant Recipients: Study

A comprehensive study published in the American Journal of Ophthalmology suggest that vaccinations do not significantly increase the risk of corneal graft rejection among transplant recipients. This research from Kaiser Permanente Southern California spanned from January 2008 to August 2022. This study by Jennifer H. Ku involved the examination of the health records of a total of 601 corneal transplant recipients who experienced graft rejection and matched them with 1,803 controls.

Corneal transplantation (also known as keratoplasty) is a surgical procedure that replaces a damaged or diseased cornea with healthy donor tissue. One of the main complications following this surgery is the graft rejection. And so this study evaluated whether receiving vaccinations within 12 weeks prior to the index date of graft rejection could be a contributing factor to this major complication.

The key findings of the study were;

Approximately 23% of the cases and 22% of the controls received one or more vaccinations within the 12-week period leading up to the index date. The adjusted odds ratios (aORs) were calculated to measure the association between receiving vaccinations and experiencing a graft rejection. The results showed that the overall risk did not increase significantly after vaccination, with an aOR of 1.17 (95% CI: 0.91, 1.50).

A more detailed analysis revealed that the aOR was 1.09 for individuals who received one vaccination, 1.53 for those who received two vaccinations, and 1.79 for those who received three or more. Additionally, the study evaluated the impact of different types of vaccines, including mRNA vaccines and adjuvanted or high-dose vaccines. The aOR for mRNA vaccines was 1.60, while for adjuvanted or high-dose vaccines the aOR was 1.19.

These findings are crucial as they suggest that completing recommended vaccinations poses no significant risk to corneal graft viability. This research supports the ongoing vaccination of corneal transplant recipients. We believe that maintaining vaccination schedules is crucial for this population, without increasing the risk of corneal graft rejection. The outcomes of this study provide critical data that can help guide clinical decisions regarding the vaccination of corneal transplant recipients. Overall, these results reassure that adhering to recommended vaccination schedules is a safe practice which should not be deferred.

Reference:

KU, J. H., NANJI, A. A., TUBERT, J. E., JOE, C., SRIKUMARAN, D., WINTHROP, K. L., BRUNTON, A. E., FLOREA, A., FRAUNFELDER, F., TSENG, T., & LUO, Y. (2024). Risk of Corneal Graft Rejection and Vaccination: A Matched Case-Control Study From a United States Integrated Health Care System. In American Journal of Ophthalmology (Vol. 263, pp. 133–140). Elsevier BV. https://doi.org/10.1016/j.ajo.2024.02.015

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Submit global regulatory status of Atezolizumab for IV, SC route: CDSCO Panel Tells Roche Products India

New Delhi: In response to the proposal presented by the drug major Roche Products India for granting permission to import and market Atezolizumab injection (1875mg/15ml vial) (Tecentriq) by new route of administration i.e., subcutaneous route, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the firm to submit the global regulatory status of the drug Atezolizumab for IV and SC route of administration along with indication.

This came after the proposal of the firm has been re-deliberated for the grant of permission to import and market Atezolizumab injection (1875mg/15ml vial) (Tecentriq) by new route of administration i.e., subcutaneous route for indications of Atezolizumab injection approved for Intravenous (IV) route for sale or for distribution in India with local Phase III clinical trial waiver under unmet need in India and commitment to conduct Phase IV study.

Atezolizumab is a monoclonal antibody used to treat advanced or metastatic urothelial carcinoma with disease progression during or up to 12 months after platinum-containing chemotherapy. Atezolizumab injection is used alone to help prevent non-small cell lung cancer (NSCLC) from coming back in patients whose tumors have been removed by surgery and who have received other cancer medicines (eg, platinum). It is given to patients who have stage 2 to stage 3A NSCLC and whose tumors express PD-L1.

Inhibition of PD-L1 by atezolizumab can remove this inhibitor effect and thereby engender an anti-tumor response. It is one of several ways to block inhibitory signals related to T-cell activation, a more general strategy known as “immune checkpoint inhibition.”

At an earlier SEC meeting dated 09.01.2024, the drug major Roche Products India presented a proposal for granting permission to import and market Atezolizumab Injection (1875mg/15ml vial) (Tecentriq) by new route of administration i.e., Subcutaneous route for indications of Atezolizumab injection approved for Intravenous (IV) route for sale or distribution in India with local Phase III and Phase IV clinical trial waiver for under unmet need in India.

The committee noted that the i.v formulation of Atezolizumab was already available in the market and the formulation and dose of the proposed s.c route was different from the i.v route. Furthermore, the committee found that India was not part of the global clinical study conducted to establish safety and efficacy data for the new route of administration i.e. s.c route.

In line with the above observation, the expert panel opined the firm to conduct a Phase III study to establish the safety and efficacy of the product for the proposed SC route.

Now, in continuation with the above, at the recent SEC meeting dated 19.03.2024 and 20.03.2024, the proposal of the firm has been redeliberated.

After detailed deliberation, the committee recommended the following:

1. The firm should submit the global regulatory status of the drug for IV and SC route of administration along with indication.

2. The firm should clarify the reason for the withdrawal of indications by USFDA along with its current status.

Accordingly, the expert panel suggested that the firm should submit the above clarifications to CDSCO for further evaluation by the committee.

Also Read: Eli Lilly Gets CDSCO Panel Nod To Import, Market Anti-cancer Drug Selpercatinib

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