Alirocumab addition to statins fails to improve endothelial function in acute MI patients: PACMAN-AMI trial substudy

Switzerland: In a significant development in cardiovascular medicine, findings from a substudy of the PACMAN-AMI randomized clinical trial shed light on the potential benefits of alirocumab in improving endothelial function and reducing coronary atherosclerosis, in patients who have experienced myocardial infarction (MI). This substudy, conducted within the larger PACMAN-AMI trial framework, represents a crucial step forward in understanding the therapeutic potential of alirocumab in post-MI care.

The research, published in the Atherosclerosis journal, found no further improvement of flow-mediated dilation (FMD) with the addition of alirocumab among patients with acute myocardial infarction (AMI) than 52 weeks of secondary preventative medical therapy, including high-intensity statin therapy. FMD was significantly associated with baseline coronary plaque burden, but not lipid pool or fibrous cap thickness.

Myocardial infarction, commonly known as a heart attack, is a life-threatening condition characterized by the interruption of blood flow to the heart muscle, usually due to the obstruction of a coronary artery by a blood clot. Following a heart attack, patients are at increased risk of recurrent cardiovascular events, including further heart attacks and stroke, making effective secondary prevention strategies imperative.

Alirocumab, a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), has garnered attention as a potential therapeutic agent for reducing low-density lipoprotein cholesterol (LDL-C) levels and lowering the risk of cardiovascular events.

Emrush Rexhaj, Department of Cardiology, Bern University Hospital Inselspital, Freiburgstrasse, Bern, Switzerland, and colleagues aimed to examine the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD. They also investigated its association with coronary atherosclerosis in non-infarct-related arteries using near-infrared spectroscopy (NIRS), intracoronary intravascular ultrasound (IVUS), and optical coherence tomography (OCT).

For this purpose, the researchers conducted a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial that compared the effects of biweekly alirocumab 150 mg versus placebo added to rosuvastatin. At 4 and 52 weeks, brachial artery FMD was measured, and intracoronary imaging at baseline and 52 weeks.

The researchers reported the following findings:

  • 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = −0.21%).
  • FMD improved throughout 52 weeks in both groups similarly.
  • There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = −1.00), but not with lipid pool (NIRS) (n = 139, slope = −7.36), or fibrous cap thickness (OCT) (n = 81, slope = −1.57).

The study revealed improvement in endothelial function as evaluated by brachial artery FMD achieved throughout one year with guideline-based secondary preventative medical therapy, including a high-intensity statin in patients with AMI. However, adding PCSK9 inhibitor alirocumab did not further improve endothelial function.

FMD was significantly inversely related to non-infarct related arteries (non-IRA) intracoronary plaque burden before treatment initiation, but not to lipid pool or fibrous cap thickness.

Reference:

Rexhaj E, Bär S, Soria R, Ueki Y, Häner JD, Otsuka T, Kavaliauskaite R, Siontis GC, Stortecky S, Shibutani H, Spirk D, Engstrøm T, Lang I, Morf L, Ambühl M, Windecker S, Losdat S, Koskinas KC, Räber L; PACMAN-AMI Investigators. Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy. Atherosclerosis. 2024 May;392:117504. doi: 10.1016/j.atherosclerosis.2024.117504. Epub 2024 Mar 6. PMID: 38513436.

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Semaglutide tied to meaningful weight loss, waist size reduction and CV benefits in non diabetic overweight adults: Study

Researchers have found in latest  research  that Semaglutide can produce clinically meaningful weight loss and reduce waist size for at least 4 years in adults with overweight or obesity who don’t have diabetes, and delivers cardiovascular benefits irrespective of weight lost. 

Two important studies based on the largest and longest clinical trial of the effects of semaglutide on weight in over 17,000 adults with overweight and obesity but not diabetes find patients lost on average 10% of their body weight and over 7cm from their waistline after 4 years.

Clinically meaningful weight loss was achieved by men and women of all races, ages, and body sizes, across all regions, with a lower rate of serious adverse events compared with placebo.

Over half of adults taking semaglutide moved down at least one BMI category after 2 years compared to 16% receiving placebo; and 12% reached a healthy BMI (25 kg/m² or less) compared with 1% in the placebo group.

Importantly, the findings also indicate that semaglutide delivers cardiovascular benefits irrespective of starting weight and the amount of weight lost-suggesting that even patients with mild obesity or those not losing weight are likely to gain some advantage.

Two important studies are being presented at this year’s European Congress on Obesity (ECO) in Venice, Italy (12-15 May), based on the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial from the same international author group. The first new study, led by Professor Donna Ryan from Pennington Biomedical Research Centre, New Orleans, USA, and being published simultaneously in Nature Medicine, examines the long-term weight effects of semaglutide. The second study led by led by Professor John Deanfield from University College London, UK, investigates whether the cardiovascular benefits are related to starting weight or the amount of weight lost.

Semaglutide is a GLP-1 medication primarily prescribed for adults with type 2 diabetes but is also approved for weight loss in people with obesity or overweight who have at least one other health issue. This class of medications simulate the functions of the body’s natural incretin hormones, which help to lower blood sugar levels after a meal. Adjusting these hormone levels can also make people feel full, and in doing so, helps lower their daily calorie intake.

In 2023, the SELECT trial reported that adults with overweight or obesity but not diabetes taking semaglutide for more than 3 years had a 20% lower risk of heart attack, stroke, or death due to cardiovascular disease, and lost an average 9.4% of their bodyweight [1].

Between October 2018 and June 2023, 17,604 adults (aged 45 or older; 72% male) from 804 sites in 41 countries with overweight or obesity (BMI of 27 kg/m² or higher) were enrolled and treated with Semaglutide (2.4mg) or placebo for an average of 40 months. They had previously experienced a heart attack, stroke and/or had peripheral artery disease, but did not have type 1 or type 2 diabetes when they joined the study.

The researchers examined markers of obesity that include body composition and fat distribution (waist circumference and waist circumference-to-height ratio [WHtR]), rather than just BMI alone, to help clarify the effect of semaglutide on central abdominal fat which has been proven to cause greater cardiovascular risk than general obesity.

Clinically meaningful weight loss in all sexes, races, body sizes, and regions

The first new study shows that once-weekly treatment with semaglutide can produce clinically meaningful and sustained weight loss and decrease waist size for at least 4 years in adults with overweight or obesity who do not have diabetes, with a lower rate of serious adverse events compared with placebo.

Importantly, men and women of all races, ages, and body sizes, across all geographical regions were able to achieve sustained, clinically meaningful weight loss.

“Our long-term analysis of semaglutide establishes that clinically relevant weight loss can be sustained for up to 4 years in a geographically and racially diverse population of adults with overweight and obesity but not diabetes,” says Professor Ryan. “This degree of weight loss in such a large and diverse population suggests that it may be possible to impact the public health burden of multiple obesity-related illnesses. While our trial focused on cardiovascular events, many other chronic diseases including several types of cancer, osteoarthritis, and anxiety and depression would benefit from effective weight management.”

In the semaglutide group, weight loss continued to week 65 and was sustained for 4 years, with participants’ losing on average 10.2% of their body weight and 7.7cm from their waistline, compared with 1.5% and 1.3cm respectively in the placebo group.

Similarly, in the semaglutide group, average WHtR fell by 6.9% compared with 1% in the placebo group.

These improvements were seen across both sexes and all categories of race and age, irrespective of starting blood sugar (glycaemic) status or metabolically unhealthy body fat. However, women taking semaglutide tended to lose more weight on average than men, and Asian patients lost less weight on average than other races.

Interestingly, after 2 years over half (52%) of participants treated with semaglutide had transitioned to a lower BMI category compared with 16% of those given placebo. For example, the proportion of participants with obesity (BMI 30kg/m² or higher) declined from 71% to 43% in the semaglutide group, and from 72% to 68% in the placebo group. Moreover, 12% of adults in the semaglutide group achieved a healthy weight (BMI 25kg/m² or less) compared with 1.2% in the placebo group

For each BMI category (<30, ≤30-<35, ≤35-<40, and ≥40 kg/m2) there were lower rates (events per 100 years of observation) of SAEs with semaglutide (43.23, 43.54, 51.0, 47.06) than with placebo (50.48, 49.66, 52.73, 60.85) respectively.

There were no unexpected safety issues with semaglutide in the SELECT trial. The proportion of participants with serious adverse events (SAEs) was lower in the semaglutide group than the placebo group (33% vs 36%), mainly driven by differences in cardiac disorders (11.5% vs 13.5%). More patients receiving semaglutide discontinued the trial due to gastrointestinal symptoms, including nausea and diarrhoea, mainly during the 20-week dose escalation phase. Importantly, semaglutide did not lead to an increased rate of pancreatitis, but rates of cholelithiasis (stones in gallbladder) were higher in the semaglutide group.

Cardiovascular benefits irrespective of weight loss

The second study examined the relationship between weight measures at baseline, and change in weight during the study with cardiovascular outcomes. These included time to first major adverse cardiovascular event (MACE) and heart failure measures.

The findings showed that treatment with semaglutide delivered cardiovascular benefits, irrespective of the starting weight and the amount of weight lost. This suggests that even patients with relatively mild levels of obesity, or those who only lose modest amount of weight, may have improved cardiovascular outcome.

“These findings have important clinical implications”, says Professor Deanfield. “Around half of the patients that I see in my cardiovascular practice have levels of weight equivalent to those in the SELECT trial and are likely to derive benefit from taking Semaglutide on top of their usual level of guideline directed care.”

He adds, “Our findings show that the magnitude of this treatment effect with semaglutide is independent of the amount of weight lost, suggesting that the drug has other actions which lower cardiovascular risk beyond reducing unhealthy body fat. These alternative mechanisms may include positive impacts on blood sugar, blood pressure, or inflammation, as well as direct effects on the heart muscle and blood vessels, or a combination of one or more of these.”

Despite these important findings, the authors caution that SELECT is not a primary prevention trial so that the data cannot be extrapolated to all adults with overweight and obesity to prevent MACE; and despite being large and diverse, it does not include enough individuals from different racial groups to understand different potential effects.

References:

1. Ryan, D.H., Lingvay, I., Deanfield, J. et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med (2024). https://doi.org/10.1038/s41591-024-02996-7

2. Semaglutide can produce clinically meaningful weight loss and reduce waist size for at least 4 years in adults with overweight or obesity who don’t have diabetes, and delivers cardiovascular benefits irrespective of weight lost, European Association for the Study of Obesity, Meeting: European Congress on Obesity (ECO2024).

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Meta-analysis reveals insights into mRNA vaccine-induced thyroid diseases

USA: In a groundbreaking meta-analysis presented at the American Association of Clinical Endocrinology (AACE) conference of 2024, researchers shed light on the rare phenomenon of mRNA vaccine-induced hyperthyroidism, particularly in the context of the SARS-CoV-2 vaccines. This comprehensive study delved into the incidence, risk factors, and outcomes linked to this condition, offering crucial insights for healthcare providers and vaccine recipients.

The meta-analysis revealed that the chance of new-onset thyroid disease following mRNA COVID-19 vaccine administration was rare but still noteworthy.

The researchers found that there were 77 cases of thyroid-related autoimmune diseases among people with no history of autoimmune disease before receiving the COVID-19 vaccine, with 39 cases of subacute thyroiditis (SAT), and 38 cases of Graves’ disease (GD).

Additionally, these autoimmune diseases occurred more frequently in women than in men, “about a 2-1 breakdown, which is what we would expect as women tend to have more autoimmune disease overall than men,” Vikram Gill, MBBS, of St. Peter’s University Hospital/Rutgers University in New Brunswick, New Jersey, said at the poster presentation.

10 men and 28 women were diagnosed with Graves’ disease, while 13 and 26, respectively, were diagnosed with SAT. The average ages of women and men who developed post-vaccination autoimmune diseases were around 44 and 41, respectively.

The emergence of mRNA vaccines, such as those developed against COVID-19, has revolutionized the field of immunization, providing potent protection against infectious diseases. However, as with any medical intervention, rare adverse events can occur. One such complication that has garnered attention is hyperthyroidism, an overactive thyroid gland, which has been reported following mRNA vaccination.

Previous research has revealed links between COVID-19 vaccination and autoimmune disorders, although other research has indicated that having a COVID-19 diagnosis raises the risk for these same disorders, but that vaccination can mitigate that risk.

The researchers searched for articles reporting GD and SAT following COVID-19 mRNA vaccinations from 2019 to November 2023.

The following were the key findings of the study:

  • A GD diagnosis happened about 40 days after the first dose, with SAT emerging sooner, at about 11 days after the first jab.
  • In the group with GD, over half developed hyperthyroidism symptoms after the first dose of the mRNA vaccine, while around 45% showed symptoms after dose 2. Roughly 5% showed signs after the third dose.
  • In the SAT group, almost 54% showed hyperthyroidism symptoms after dose 1, as did about 44% after dose 2, and around 5% after dose 3.
  • Positive anti-TPO [anti-thyroid peroxidase] was only seen in five out of 32 patients who were tested (15.6%), and 32 patients (74.4%) were negative for anti-TPO.
  • Eleven out of 33 patients who were tested (33.3%) were positive for anti-Tg [antithyroglobulin], 22 patients (66.6 %) were negative,

Moving forward, the findings of this meta-analysis will inform clinical practice and public health strategies surrounding mRNA vaccination. Enhanced awareness, coupled with tailored monitoring protocols, will ensure the continued safety and efficacy of these groundbreaking vaccines in combating infectious diseases like COVID-19. As the global vaccination effort progresses, studies like this serve as invaluable tools in optimizing healthcare delivery and promoting vaccine confidence.

Reference:

Gill V and Luo H “mRNA (SARS-CoV-2) vaccine-induced hyperthyroidism — Learnings based on the meta-analysis” AACE 2024.

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Seralutinib effective in managing pulmonary arterial hypertension: Lancet

In the field of pulmonary arterial hypertension (PAH), where morbidity and mortality rates remain alarmingly high, a new inhaled drug can greatly enhance the outcomes in patients. A recent study called as the TORREY trial unveiled promising results regarding the efficacy and safety of a new inhaled drug, the Seralutinib, in managing this life-threatening condition. The findings were published in The Lancet Respiratory Medicine. 

The TORREY trial revealed that Seralutinib, an inhaled kinase inhibitor, targets the crucial pathways involved in PAH progression. Seralutinib disrupts inflammatory, proliferative and fibrotic pathways driving pulmonary vascular remodeling in PAH by inhibiting platelet-derived growth factor receptor, the colony stimulating factor 1 receptor and mast or stem cell growth factor receptor kinases.

This phase 2, randomized, multicenter, double-blind, placebo-controlled study enrolled a total of 86 adult patients with PAH from various hospital and community sites. The participants were randomly assigned to receive either Seralutinib or a placebo via dry powder inhaler over a span of 24 weeks. The patients were already receiving standard background therapy for PAH. The primary endpoint of the trial was the change in pulmonary vascular resistance (PVR) from baseline to 24 weeks.

The results observed that patients treated with Seralutinib expressed a significant reduction in PVR when compared to the patients receiving the placebo. Also, the least squares mean difference in PVR change between the Seralutinib and placebo groups was clinically significant at -96.1 dyne·s/cm5 (p=0.03). While generally well-tolerated, the most common treatment-emergent adverse event in both groups was cough which was reported in 38% of the placebo group and 43% of the Seralutinib group.

These findings hold profound benefits for the management and treatment of PAH. This trial offers hope for patients with this debilitating condition by demonstrating the efficacy of inhaled Seralutinib in reducing PVR. The safety profile of the drug suggests its potential as a valuable addition to existing PAH therapies. Further investigation and development will guide forward this innovative therapy against pulmonary arterial hypertension by offering renewed prospects for patients throughout the globe.

Source:

Frantz, R. P., McLaughlin, V. V., Sahay, S., Escribano Subías, P., Zolty, R. L., Benza, R. L., Channick, R. N., Chin, K. M., Hemnes, A. R., Howard, L. S., Sitbon, O., Vachiéry, J.-L., Zamanian, R. T., Cravets, M., Roscigno, R. F., Mottola, D., Osterhout, R., Bruey, J.-M., Elman, E., … Ghofrani, H.-A. (2024). Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial. In The Lancet Respiratory Medicine. Elsevier BV. https://doi.org/10.1016/s2213-2600(24)00072-9

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Staged bilateral FUS-STN safely improves motor features in Parkinsonism: JAMA

Staged bilateral FUS-STN safely improves motor features in Parkinsonism suggests a study published in the JAMA Neurology.

Unilateral magnetic resonance imaging (MRI)–guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson’s disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. A study was done to assess the safety and effectiveness of staged bilateral FUS-STN to treat Parkinson’s disease. This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with Parkinson’s disease who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication.

Primary outcomes were assessed 6 months after the second treatment and included safety (incidence and severity of adverse events after the second treatment) and effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation). Secondary outcomes included motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake), motor complications (measured with the MDS-UPDRS IV), daily living activities (measured with the MDS-UPDRS I-II), quality of life (measured with the 39-item Parkinson’s Disease Questionnaire), change in dopaminergic treatment, patient’s global impression of change (measured with the Global Impression of Change [PGI-C] scale), and long-term (24-month) follow-up. Results: Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients’ median duration of disease was 5.7 years (IQR, 4.7-7.3 years).

The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioural or cognitive disturbances were found on neuropsychological testing. For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive. Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

Reference:

Martínez-Fernández R, Natera-Villalba E, Rodríguez-Rojas R, et al. Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease. JAMA Neurol. Published online May 13, 2024. doi:10.1001/jamaneurol.2024.1220

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Use of restorations on vertically prepared teeth suitable option to classical horizontal preparations: Study

The use of restorations on vertically prepared teeth suitable for classical horizontal preparations suggests a study published in the Journal of Dentistry.

A study was done to evaluate the clinical conditions of single-unit posterior restorations on teeth prepared without a finishing line, after 5.6 years of clinical service. 50 crowns (25 zirconia-based (Zr) and 25 porcelain-fused-to-metal (PFM)) were selected from 34 patients. The restorations were evaluated according to the California Dental Association (CDA) Quality Criteria, and periodontal variables were studied in the abutment teeth compared with the unrestored contralateral teeth. Variables were examined using Mann-Whitney and Pearson´s Chi-Square tests (α = 0.05). The success of the prosthesis was calculated using the Kaplan-Meier test. Results: CDA Quality Criteria was considered satisfactory- excellent in all restorations except for one of them, due to chipping on a PFM crown. At, 66 months, the success rates for PFM and Zr crowns were 85.7% and 100%, respectively. The plaque index (PI) showed that the restored abutment teeth accumulated significantly less plaque than the control teeth, but the gingival index (GI) was statistically higher in the abutment teeth. In 80% of cases, the probing depth (PB) was ≤ 3mm. In addition, in 21% of the cases, gingival recession was less than 2mm. The restoration material had a statistically significant effect on GI and PB, with Zr crowns showing less inflammation and fewer deep pockets than PFM restorations. On the contrary, greater gingival recession was found at the margins of the Zr crowns when compared to the PFM. No statistical differences were found between the two materials in the GI. Cemented crowns on vertical preparations show good clinical behavior after 5 years. The periodontal parameters (PI, GI, PD) of the Zr restorations are significantly better than those of PFM, with the exception of gingival recession. The use of restorations on vertically prepared teeth is a suitable alternative to classical horizontal preparations.

Reference:

M Gonzalez-Bonilla, S Berrendero, B Moron-Conejo, F Martinez-Rus, MP Salido,

Clinical evaluation of posterior zirconia-based and porcelain-fused-to-metal crowns with a vertical preparation technique: an up to 5-year retrospective cohort study.,

Journal of Dentistry, 2024, 104953, ISSN 0300-5712, https://doi.org/10.1016/j.jdent.2024.104953.

(https://www.sciencedirect.com/science/article/pii/S0300571224001234)

Keywords:

Use, restorations, vertically, prepared, teeth, suitable, option, classical, horizontal, preparations, study, Journal of Dentistry, M Gonzalez-Bonilla, S Berrendero, B Moron-Conejo, F Martinez-Rus, MP Salido,Vertical preparation; Crown; Zirconia; Porcelain-fused-to-metal; Periodontal parameters

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Chronic stress during adolescence may reduce fertility in adulthood, suggests

Male rats exposed to moderate and repeated stress during adolescence may have reduced fertility, according to research presented at the 26th European Congress of Endocrinology in Stockholm. This study sheds light on the harmful effects that early-life stress has on health and could help to uncover future prevention strategies for children and adolescents.

While hormone levels fluctuate pathologically-especially during life stages such as puberty-stress can cause too much or too little of a hormone in the bloodstream. This hormonal imbalance negatively impacts puberty and the reproduction system, with effects on libido, ovulation function and sperm cell production. However, the long-term reproductive effects of chronic stress in adolescents are largely unknown.

In this study, researchers from the V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Science of Ukraine, examined male and female rats, aged 6 months, after individually placing about half of them in enclosed spaces for one hour every morning for two weeks during adolescence (30–45 days old). They compared the rats who had been exposed to these stressful conditions to the control group and found that chronic stress during puberty delayed sexual maturity in females, and males gained weight more slowly. In adult males, sperm count fell by 25.9%, some sperm were abnormally shaped and sluggish or became immobile, and the breathing process by which sperm cells derive energy slowed down. Additionally, males had almost two times lower levels of corticosterone – the main stress hormone in rats, equivalent to cortisol in humans.

“Our work is the first to report to show that even moderate and repetitive stress in adolescence has a long-lasting negative impact on the endocrine system of reproduction and adaptation of the body to changing living conditions,” said lead investigator, Professor Aleksander Reznikov.

“Our results make it possible to predict the development of anomalies in reproduction and bodily adaptation systems and are the basis for finding methods for their prevention.”

Professor Reznikov added: “We discovered for the first time that lipid peroxidation (a process in which oxidants like free radicals attack lipid membranes of cells and eventually damage them) in the ovaries and testes was significantly increased. This, however, needs further investigation.”

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Study Reveals Relationship Between Peak Expiratory Flow Changes and Asthma Exacerbations in Children

China: A recent study published in BMC Pediatrics has unveiled crucial insights into the relationship between changes in peak expiratory flow (PEF) and asthma exacerbations in pediatric patients. Conducted with a focus on asthmatic children, the research underscores the significance of PEF monitoring as a valuable tool in predicting and preventing asthma exacerbations.

Researchers uncovered a crucial early warning sign for pediatric asthma exacerbations: children with asthma exhibited a decline in PEF approximately 1.34 days before the onset of symptoms. Upper respiratory tract infections emerged as the primary trigger for acute asthma exacerbations, and air pollution exhibited a significantly higher impact on PEF variation versus other factors.

Asthma, a chronic respiratory condition characterized by airway inflammation and hyperresponsiveness, affects millions of children worldwide, posing a significant burden on both patients and healthcare systems. Asthma exacerbations, marked by sudden worsening of symptoms, represent a major concern due to their potential to escalate into severe respiratory distress and hospitalization.

In patients with poor perception, identifying acute asthma exacerbations by clinical asthma score, asthma control test, or asthma control questionnaire is difficult. Considering this, Kunling Shen, Department of Respiratory, Shenzhen Children Hospital, Shenzhen, China, and colleagues aimed to analyze whether children with asthma have changes in peak expiratory flow before an acute asthma exacerbation. They also evaluated the relationship between PEF and asthma exacerbation.

For this purpose, the researchers collected basic information (including age, sex, atopy, etc.) and clinical information of asthmatic children who registered in the Electronic China Children’s Asthma Action Plan (e-CCAAP) from 2017 to 2021. Subjects with fourteen consecutive days of PEF measurements were eligible. The study subjects were categorized into an exacerbation group and a control group. They analyzed the relationship between changes in PEF% pred and asthma symptoms.

The study included 194 children with asthma who met the inclusion criteria, including 74.2% males and 25.8% females, with a male-to-female ratio of 2.88:1. The subjects’ mean age was 9.51 ± 2.5 years.

The researchers reported the following findings:

  • There were no significant differences in sex, age, allergy history, or baseline PEF between the two groups.
  • There was no significant difference between the variation in PEF at 14 days in children with and without a history of allergy.
  • Patients who only had a reduction in PEF but no symptoms of asthma exacerbation had the greatest decrease in PEF compared to the other groups.
  • The most common cause of acute exacerbations of asthma is upper respiratory tract infection.
  • Among the causes of acute exacerbations of asthma, the variation in PEF caused by air pollution was significantly higher than that of other causes.
  • In acute exacerbations, the decrease in PEF was significantly greater in the exacerbation group than in the control group.
  • In children with asthma symptoms, there was a decrease in PEF approximately 1.34 days before the onset of the symptoms.

The findings revealed that children with asthma show a decrease in PEF 1.34 days before the onset of asthma symptoms.

“We recommend that asthmatic children who show PEF reduction should step up asthma therapy,” the researchers wrote. “The most common cause of asthma’ acute exacerbations was upper respiratory tract infections, and PEF variation caused by air pollution was significantly higher than that caused by other factors.”

Reference:

Chen, X., Han, P., Kong, Y. et al. The relationship between changes in peak expiratory flow and asthma exacerbations in asthmatic children. BMC Pediatr 24, 284 (2024). https://doi.org/10.1186/s12887-024-04754-7

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Gabapentinoid prescriptions in Isolated Low Back Pain patients by primary care physicians not useful: Study

Gabapentinoids have been increasingly studied as a non-narcotic option for neuropathic and postoperative pain. However, there is evidence suggesting that off-label use of these medications for the treatment of isolated LBP is not effective.

Low back pain (LBP) remains one of the leading causes of disability worldwide. In wake of the ongoing opioid epidemic, reducing narcotic use is a high priority for patients, physicians, and systems. For some indications, non narcotic analgesic alternatives exist – such as gabapentinoids – however, evidence does not support their use for axial LBP.

Maloy et al conducted a study to evaluate prescription patterns for gabapentinoids among patients with isolated low back pain. The study has been published in ‘Global Spine Journal.’

Adult patients with LBP were abstracted from the dataset using International Classification of Diseases (ICD-10) code M54.5. Patients were excluded if they had a diagnosis of neurologic symptoms, history of spinal surgery, spinal fracture, or conditions for which gabapentinoids are FDA approved. Gabapentinoid and narcotic prescriptions within one year of LBP diagnosis were identified. Patient characteristics and prescriber specialty were extracted from the dataset and predictors of gabapentinoid prescriptions were determined using univariate and multivariate analyses.

Key findings of the study:

• Among the 1,158,875 isolated LBP patients, gabapentinoids were prescribed for 11% (gabapentin for 85%, pregabalin for 12% pregabalin, and both for 3%), narcotics for 8%, and both for 3%.

• The most common prescriber specialties included: primary care physicians (45%), nurse practitioners (15%), pain management physicians (5%), neurology (4%), physical medicine and rehabilitation (4%), psychiatry (3%), rheumatology (2%), orthopedic surgery (2%), unknown (11%), and other fields (9%).

• Independent predictors of gabapentinoid prescriptions included: female sex, region of the country, and insurance type (P-values <0.001).

The authors concluded – “In sum, of nearly 1.2 million isolated LBP patients identified, 14.2% were prescribed gabapentinoids within one year of their LBP diagnosis, a number greater than narcotics and prescribed most commonly be primary care physicians. Several factors were identified as independent predictors of gabapentinoid prescription, include patient sex, region of residence, and insurance plan. While clinicians are being encouraged to shift away from the use of narcotics for isolated LBP, evidence does not well support gabapentinoids for this indication and its off label use for this population may be questioned.”

Further reading:

Characterizing Gabapentinoid Use Among Patients With Isolated Low Back Pain

Gwyneth C. Maloy et al

Global Spine Journal 2024

DOI: 10.1177/21925682231224390

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Bariatric Surgery Decreases Risk of Ocular Morbidity and Mortality finds study

Researchers have found that bariatric surgery, a treatment for morbid obesity, is associated with a decreased risk of future ocular morbidity and mortality. This large retrospective cohort study examined the effects of bariatric surgery on postoperative disease incidence, highlighting the potential benefits of surgery beyond weight loss. This study was published in the journal Eye by Russell and colleagues.

Bariatric surgery is widely used to treat morbid obesity, with known short-term effects on ocular pathology. However, the long-term impact of surgery on the incidence of postoperative ocular diseases remains largely unknown. This study aims to evaluate the relationship between bariatric surgery and the risk of various ocular conditions.

The study analyzed data from the TriNetX United States Collaborative Network national database. Patients with an ICD-10 code for morbid obesity and a procedural code for bariatric surgery were matched to those with morbid obesity but without surgery, resulting in two cohorts of 42,408 patients each. The study tracked the incidence of several ocular conditions after surgery, including:

  • Diabetic retinopathy

  • Age-related macular degeneration

  • Glaucoma

  • Low vision and blindness

Outcomes were assessed using relative risk (RR) with 95% confidence intervals (CI).

The key findings of the study were:

  • Bariatric surgery was associated with a significant reduction in the future risk of diabetic retinopathy (RR: 0.283; 95% CI: 0.252-0.319).

  • Patients who underwent bariatric surgery had a lower risk of developing macular edema (RR: 0.224; 95% CI: 0.170-0.297).

  • The risk of vitreous hemorrhage was also reduced (RR: 0.459; 95% CI: 0.323-0.653).

  • Bariatric surgery was linked to lower rates of ocular hypertension (RR: 0.387; 95% CI: 0.387-0.487) and glaucoma (RR: 0.360; 95% CI: 0.326-0.399).

  • The surgery was associated with a reduced risk of age-related macular degeneration (RR: 0.628; 95% CI: 0.447-0.882).

  • The risk of low vision and blindness was lower in the surgery group (RR: 0.328; 95% CI: 0.294-0.365).

The findings suggest that bariatric surgery not only aids in weight loss but also may have substantial protective effects against future ocular diseases. This could lead to a potential shift in how bariatric surgery is viewed as a comprehensive treatment for both obesity and ocular health.

Bariatric surgery is associated with a decreased risk of future ocular morbidity and mortality, including diabetic retinopathy, age-related macular degeneration, and glaucoma, among others. These findings highlight the importance of considering bariatric surgery not just as a weight loss intervention, but also as a potential preventive measure for various ocular conditions.

Reference:

Russell, M. W., Kumar, M., Li, A., Singh, R. P., & Talcott, K. E. (2024). Incidence of ocular pathology following bariatric surgery for with morbid obesity across a large United States National Database. Eye. https://doi.org/10.1038/s41433-024-03088-z

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