Rivaroxaban Plus Aspirin Shows Favorable Benefit-Risk Profile in PAD Patients after revascularization, suggests study

The VOYAGER PAD trial evaluated the efficacy and safety of rivaroxaban plus aspirin compared to aspirin alone in patients with symptomatic peripheral artery disease (PAD) undergoing lower extremity revascularization procedures. Recently, the US Food and Drug Administration requested additional quantitative benefit-risk analyses to inform decision-making.

The researchers have found in a new study that in patients with PAD who had undergone lower‐extremity revascularization receiving antiplatelet therapy, rivaroxaban 2.5 mg twice daily demonstrated a favorable benefit-risk profile compared with placebo. Further the findings were more pronounced with the on‐treatment analysis and generally consistent between unweighted assessment and weighted MCDA analyses.

The study published in the Journal Of The American Heart Association was conducted by Zhong Y. and colleagues.

Peripheral artery disease is a common condition associated with significant morbidity and mortality due to thrombotic vascular events. Antithrombotic therapy, such as rivaroxaban and aspirin, has been studied to reduce the risk of these events in PAD patients undergoing revascularization procedures. However, balancing the benefits and risks of such therapy is crucial for clinical decision-making.

The analysis assessed benefits and risks using rate differences between treatment groups and conducted a multi-criteria decision analysis incorporating health state utility values as weights. Monte Carlo simulations were used to incorporate statistical uncertainties. Intent-to-treat and on-treatment analyses were performed.

The key findings of the study were as follows:

  • Rivaroxaban plus aspirin resulted in 120 fewer events of the primary composite endpoint per 10,000 patient-years compared to aspirin alone.

  • However, rivaroxaban was associated with an excess of 40 Thrombolysis in Myocardial Infarction major bleeding events.

  • When incorporating health state utility values as weights, rivaroxaban therapy showed a utility equivalent of 13.7 and 68.1 fewer deaths per 10,000 patient-years in intent-to-treat and on-treatment analyses, respectively.

  • Monte Carlo simulation indicated probabilities of 64.4% and 98.7% favoring rivaroxaban in terms of benefits outweighing risks.

The analyses from the VOYAGER PAD trial demonstrate a favorable benefit-risk profile of rivaroxaban plus aspirin therapy in patients with symptomatic PAD undergoing lower extremity revascularization procedures. The findings support the use of rivaroxaban as an effective treatment option for reducing thrombotic vascular events in this patient population, with a generally consistent outcome between unweighted and weighted approaches. These results provide valuable insights for clinicians in making informed treatment decisions for PAD patients.

Reference:

Yuan, Z., Levitan, B., Deng, H., Szarek, M., Bauersachs, R. M., Berkowitz, S. D., Haskell, L., Barnathan, E. S., & Bonaca, M. P. (2024). Quantitative benefit–risk evaluation of rivaroxaban in patients after peripheral arterial revascularization: The VOYAGER PAD trial. Journal of the American Heart Association. https://doi.org/10.1161/jaha.123.032782

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New urine test has higher diagnostic accuracy for prostate cancer: JAMA

A new urine test that measures 18 genes associated with prostate cancer provides higher accuracy for detecting clinically significant cancers than PSA and other existing biomarker tests, according to a study published in JAMA Oncology. The urine test, MyProstateScore 2.0 (MPS2), was shown to meaningfully reduce unnecessary prostate biopsies while providing highly accurate detection of worrisome prostate cancers, the researchers concluded.

“In nearly 800 patients with an elevated PSA level, the new test was capable of ruling out the presence of clinically significant prostate cancer with remarkable accuracy. This allows patients to avoid more burdensome and invasive tests, like MRI and prostate biopsy, with great confidence that we are not missing something,” said Jeffrey Tosoian, MD, assistant professor of Urology and director of Translational Cancer Research at Vanderbilt University Medical Center, who is first author of the study.

Prostate cancer is the most common cancer and the second leading cause of cancer death among men in the U.S. The PSA blood test has been widely used as the initial step in prostate cancer screening. Although PSA is elevated in the vast majority of men with prostate cancer, it is also elevated in a significant proportion of men without cancer.

As a result, the use of elevated PSA alone to prompt a prostate biopsy results in numerous unnecessary biopsies. Although generally safe, prostate biopsies are invasive, uncomfortable, and carry some risk of worrisome complications. Therefore, for patients with an elevated PSA, there is a great need for a second-line test to better identify which men truly need a biopsy and which do not.

Because some low-grade, prostate cancers do not require treatment and can be safely monitored with an approach termed active surveillance, the MPS2 test was developed to detect more specifically the higher-grade, “clinically significant” cancers in need of early detection and treatment. To do this, the research team analyzed prostate tumors from across the U.S. to identify novel genes more often detected in the presence of significant cancers. The most informative 18 genes were combined into the MPS2 test, which was then tested in a National Cancer Institute trial of men with an elevated PSA level. Uniquely, the authors were able to compare the novel test to other prostate cancer tests, including the original, two-gene MPS test.

The study involved 743 men with a median age of 62 years and a median PSA level of 5.6. While existing biomarker tests could have avoided 15% to 30% of unnecessary biopsies (i.e. biopsies that were negative or found low-grade cancers not requiring treatment), use of MPS2 would have avoided 35% to 42% of unnecessary biopsies without missing any additional diagnoses of clinically significant cancer. The improvement was even more pronounced in men with a history of a previous negative biopsy, reducing the rate of unnecessary biopsies from 46% to 51% with use of MPS2, as compared to 9% to 21% for existing tests.

Multiparametric magnetic resonance imaging (mpMRI) is another second-line test that has been utilized, but while it can improve detection of clinically significant prostate cancer, interpretation of the results can be subjective and vary significantly. The authors also noted that mpMRI is not available in some community settings and is not an option for some patients. The current study was not designed to compare biomarkers to mpMRI, but the researchers are currently conducting a prospective, multicenter trial for that purpose.

In patients shown to be without clinically significant prostate cancer by the new test, the authors concluded that the “externally validated performance of MPS2 supports its effectiveness in accurately ruling out the need for mpMRI and biopsy altogether.” They noted a limitation of the study was that only 13% of participants were African American. Because prostate cancer is more prevalent among African American men, the research team is currently pursuing further analyses in more racially diverse populations.

Reference:

Tosoian JJ, Zhang Y, Xiao L, et al. Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer. JAMA Oncol. Published online April 18, 2024. doi:10.1001/jamaoncol.2024.0455.

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Bariatric surgery cuts use of medications for hypertension, diabetes and dyslipidemia, suggests study

Bariatric surgery cuts use of medications for hypertension, diabetes and dyslipidemia, suggests study published in the Surgery for Obesity and Related Diseases.

Limited evidence exists on the patterns of medication use for hypertension, diabetes mellitus (DM), and dyslipidemia after bariatric surgery among Asian patients. A study was done to investigate the patterns in the use of blood pressure-lowering, glucose-lowering, and lipid-lowering medications following Bariatric surgery in Korean patients with morbid obesity. This study is a retrospective cohort study using the Health Insurance Review and Assignment claims database of South Korea (from 2019 to 2021). They included patients who underwent Bariatric surgery between 2019 and 2020 in South Korea. We evaluated the treatment patterns of blood pressure-lowering, glucose-lowering, and lipid-lowering medications at 3-month intervals for 1-year following BS, including medication use, individual medication classes, and the number of medications prescribed. Furthermore, we estimated remission rates for each disorder based on patient characteristics by defining patients who discontinued their medications for at least 2 consecutive quarters as remission. RESULTS: A total of 3810 patients were included in this study. For 1-year following Bariatric surgery, a marked decrease in the number of patients using blood pressure-lowering, glucose-lowering, and lipid-lowering medications was observed. The most remarkable decrease occurred in glucose-lowering medications, which decreased by approximately -75.1% compared with that at baseline. This tendency was consistently observed when analyzing both the number of medications prescribed and the specific medication classes. Regarding remission rates, patients who were female, younger, and received the biliopancreatic diversion-duodenal switch as their Bariatric surgery showed a relatively higher incidence of remission than other groups. Bariatric surgerywas associated with a decrease in the use of medications for hypertension, diabetes mellitus (DM), and dyslipidemia.

Reference:

Jeon, Soo Min, et al. “Discontinuation of Blood Pressure-lowering, Glucose-lowering, and Lipid-lowering Medications After Bariatric Surgery in Patients With Morbid Obesity: a Nationwide Cohort Study in South Korea.” Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery, 2024.

Keywords:

Bariatric surgery, cuts use, medications, hypertension, diabetes and dyslipidemia,study, Jeon, Soo Mi, Surgery for Obesity and Related Diseases

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Scientists discover potential treatment approaches for polycystic kidney disease

Researchers have shown that dangerous cysts, which form over time in polycystic kidney disease (PKD), can be prevented by a single normal copy of a defective gene. This means the potential exists that scientists could one day tailor a gene therapy to treat the disease. They also discovered that a type of drug, known as a glycoside, can sidestep the effects of the defective gene in PKD. The discoveries could set the stage for new therapeutic approaches to treating PKD, which affects millions worldwide. The study, partially funded by the National Institutes of Health (NIH), is published in Cell Stem Cell.

Scientists used gene editing and 3-D human cell models known as organoids to study the genetics of PKD, which is a life-threatening, inherited kidney disorder in which a gene defect causes microscopic tubes in the kidneys to expand like water balloons, forming cysts over decades. The cysts can crowd out healthy tissue, leading to kidney function problems and kidney failure. Most people with PKD are born with one healthy gene copy and one defective gene copy in their cells.

“Human PKD has been so difficult to study because cysts take years and decades to form,” said senior study author Benjamin Freedman, Ph.D., at the University of Washington, Seattle. “This new platform finally gives us a model to study the genetics of the disease and hopefully start to provide answers to the millions affected by this disease.”

To better understand the genetic reasons cysts form in PKD, Freedman and his colleagues sought to determine if 3-D human mini-kidney organoids with one normal gene copy and one defective copy would form cysts. They grew organoids, which can mimic features of an organ’s structure and function, from induced pluripotent stem cells, which can become any kind of cell in the body.

To generate organoids containing clinically relevant mutations, the researchers used a gene editing technique called base editing to create mutations in certain locations on the PKD1 and PKD2 genes in human stem cells. They focused on four types of mutations in these genes that are known to cause PKD by disrupting the production of polycystin protein. Disruptions in two types of the protein – polycystin-1 and polycystin-2 – are associated with the most severe forms of PKD.

They then compared cells with two gene copy mutations in organoids to cells with only one gene copy mutation. In some cases, they also used gene editing to correct mutations in one of the two gene copies to see how this affected cyst formation. They found organoids with two defective gene copies always produced cysts and those that carried one good gene copy and one bad copy did not form cysts.

“We didn’t know if having a gene mutation in only one gene copy is enough to cause PKD, or if a second factor, such as another mutation or acute kidney injury was necessary,” Freedman said. “It’s unclear what such a trigger would look like, and until now, we haven’t had a good experimental model for human PKD.”

According to Freedman, the cells with one healthy gene copy make only half the normal amount of polycystin-1 or polycystin-2, but that was sufficient to prevent cysts from developing. He added that the results suggest the need for a second trigger and that preventing that second hit might be able to prevent the disease.

The organoid models also provided the first opportunity to study the effectiveness of a class of drugs known as eukaryotic ribosomal selective glycoside on PKD cyst formation.

“These compounds will only work on single base pair mutations, which are commonly seen in PKD patients,” explained Freedman. “They wouldn’t be expected to work on any mouse models and didn’t work in our previous organoid models of PKD. We needed to create that type of mutation in an experimental model to test the drugs.”

Freedman’s team found that the drugs could restore the ability of genes to make polycystin, increasing the levels of polycystin-1 to 50% and preventing cysts from forming. Even after cysts had formed, adding the drugs slowed their growth.

Freedman suggested that a next step would be to test existing glycoside drugs in patients. Researchers also could explore the use of gene therapy as a treatment for PKD.

Reference:

 Courtney E. Vishy, Chardai Thomas, Thomas Vincent, Daniel K. Crawford, Matthew M. Goddeeris, Benjamin S. Freedman, Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease, Cell Stem Cell, DOI:https://doi.org/10.1016/j.stem.2024.03.005.

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Immediate impression method in digital workflow as good as staged impression method for single-unit implants in posterior area: Study

Immediate impression method in the digital workflow as good as the staged impression method for single-unit implants in the posterior area suggests a new study published in the Journal of Prosthodontics.

This clinical study compares immediate and staged impression methods in a complete digital workflow for single-unit implants in the posterior area. Sixty patients requiring single-unit implant crowns were enrolled. Forty patients were assigned to the test group, immediate digital impression after implant surgery with crown delivery 4 months later. The remaining 20 patients were assigned to the control group, staged digital impressions 4 months after implant surgery, and crown delivery 1 month later. Both workflows involved free-model CAD-CAM crown fabrications. The crowns were scanned before and after clinical adjustment using an intraoral scanner (TRIOS Color; 3Shape). Two 3D digital models were trimmed and superimposed to evaluate the dimensional changes using Geomagic Control software. Chairside times for the entire workflow were recorded. Kruskal–Wallis was performed to compare crown adjustments between two groups, while one-way ANOVA was used to compare chairside time durations between the test and control groups. Results: All crowns were delivered without refabrication. The average maximum occlusion adjustment of crowns was−353.2±207.1μm in the test group and−212.7±150.5μm in the control group (p=0.02). The average area of occlusal adjustment, measured as an area of deviation larger than 100μm, was 14.8±15.3 and8.4±8.1 mm2in the test and control groups, respectively (p=0.056). There were no significant differences in the mesial and distal contact adjustment amounts, or the maximum deviations of the proximal area, between the two groups. The mean chair-side time was 50.25±13.48 and 51.20±5.34 min in the test and control groups, respectively (p=0.763). The immediate impression method in the digital workflow for single-unit implants required more occlusal adjustments of crowns but showed similar chairside-times compared to the staged impression method.

Reference:

Ren S, Jiang X, Lin Y, Di P.Crown adjustment and chairside efficiency ofsingle-unit restorations fabricated from immediate andstaged impressions using a digital workflow forposterior implants. J Prosthodont. 2024;1–8.https://doi.org/10.1111/jopr.13851

Keywords:

Immediate, impression method, digital workflow, good, staged impression, method, single-unit, implants, posterior area, study, Scrown accuracy, digital workflow, immediate digital impression

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Antipsychotics for dementia linked to more harms than previously acknowledged: BMJ

Antipsychotic use in people with dementia is associated with elevated risks of a wide range of serious adverse outcomes including stroke, blood clots, heart attack, heart failure, fracture, pneumonia, and acute kidney injury, compared with non-use, finds a study published by The BMJ today.

These findings show a considerably wider range of harms associated with antipsychotic use in people with dementia than previously acknowledged in regulatory alerts, with risks highest soon after starting the drugs, underscoring the need for increased caution in the early stages of treatment.

Despite safety concerns, antipsychotics continue to be widely prescribed for behavioural and psychological symptoms of dementia such as apathy, depression, aggression, anxiety, irritability, delirium, and psychosis.

Previous regulatory warnings when prescribing antipsychotics for these symptoms are based on evidence of increased risks for stroke and death, but evidence of other adverse outcomes is less conclusive amongst people with dementia.

To address this uncertainty, researchers set out to investigate the risks of several adverse outcomes potentially associated with antipsychotic use in people with dementia.

The outcomes of interest were stroke, major blood clots (venous thromboembolism), heart attack (myocardial infarction), heart failure, irregular heart rhythm (ventricular arrhythmia), fractures, pneumonia, and acute kidney injury.

Using linked primary care, hospital, and mortality data in England, they identified 173,910 people (63% women) diagnosed with dementia at an average age of 82 between January 1998 and May 2018 who had not been prescribed an antipsychotic in the year before their diagnosis.

Each of the 35,339 patients prescribed an antipsychotic on or after the date of their dementia diagnosis was then matched with up to 15 randomly selected patients who had not used antipsychotics.

Patients with a history of the specific outcome under investigation before their diagnosis were excluded from the analysis of that outcome.

The most commonly prescribed antipsychotics were risperidone, quetiapine, haloperidol, and olanzapine, which together accounted for almost 80% of all prescriptions.

Potentially influential factors including personal patient characteristics, lifestyle, pre-existing medical conditions, and prescribed drugs were also taken into account.

Compared with non-use, antipsychotic use was associated with increased risks for all outcomes, except ventricular arrhythmia. For example, in the first three months of treatment, rates of pneumonia among antipsychotic users were 4.48% vs 1.49% for non-users. At one year, this rose to 10.41% for antipsychotic users vs 5.63% for non-users.

Risks were also high among antipsychotic users for acute kidney injury (1.7-fold increased risk), as well as stroke and venous thromboembolism (1.6-fold increased risk) compared with non-users.

For almost all outcomes, risks were highest during the first week of antipsychotic treatment, particularly for pneumonia.

The researchers estimate that over the first six months of treatment, antipsychotic use might be associated with one additional case of pneumonia for every 9 patients treated, and one additional heart attack for every 167 patients treated. At two years, there might be one additional case of pneumonia for every 15 patients treated, and one additional heart attack for every 254 patients treated.

This is an observational study so no firm conclusions can be drawn about cause and effect, and the researchers cautioned that some misclassification of antipsychotic use may have occurred. And although they adjusted for a range of factors, they can’t rule out the possibility that other unmeasured variables may have affected their results.

However, this was a large analysis based on reliable health data that investigated a wide range of adverse events and reported both relative and absolute risks over several periods.

As such, the researchers say antipsychotics are associated with a considerably wider range of serious adverse outcomes than previously highlighted in regulatory alerts, with the highest risks soon after starting treatment, and are therefore of direct relevance to guideline developers, regulators, clinicians, patients and their carers.

Any potential benefits of antipsychotic treatment need to be weighed against risk of serious harm and treatment plans should be reviewed regularly, they add.

The findings of this study will equip healthcare professionals with more nuanced data to help guide personalised treatment decisions, say US researchers in a linked editorial.

They explain that international guidelines advise restricting use to adults with severe behavioural and psychological symptoms of dementia, but the rate of prescribing has risen in recent years, partly due to the relative scarcity of effective non-drug alternatives and the substantial resources needed to implement them.

“Increased priority on more patient centric care, tailored care plans, regular reassessment of management options, and a move away from the overprescription of antipsychotics is overdue,” they conclude.

Reference:

https://www.bmj.com/content/385/bmj-2023-076268

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FAPI-PET imaging may enhance detection of lepidic subtype lung cancer, reveals study

A recent study introduced a new diagnostic imaging technique that could significantly improve the detection of certain lung cancer subtypes traditionally elusive to standard PET scans. This resaerch focused on the diagnostic capabilities of a novel PET imaging method using 68Ga-labeled fibroblast activation protein inhibitors (FAPIs) that could revolutionize how oncologists identify and treat lung cancers, particularly the lepidic subtype that often does not show up on conventional 18F-FDG PET scans. The key findings of the study were published in the Journal of Nuclear Medicine.

Lung cancer remains one of the most challenging malignancies to diagnose and treat, primarily because of its varied subtypes and the limitations of current imaging technologies. 18F-FDG PET often fails to detect lepidic lung cancer and to address this, Manuel Röhrich and team evaluated the effectiveness of 68Ga-FAPI-46 PET in detecting 18F-FDG–negative pulmonary lesions.

The study included 19 patients with suspected lung cancer and who underwent surgery or biopsy for a definitive histologic diagnosis after their PET scans. The research utilized FAP immunohistochemistry on tissue samples to corroborate the PET findings and to confirm the presence of FAP-positive cancer-associated fibroblasts predominantly in lepidic lung cancer.

During the clinical trials, both static and dynamic 68Ga-FAPI-46 PET scans were performed along with the standard 18F-FDG PET. The results showed that lung cancer lesions expressed significantly higher uptake of 68Ga-FAPI-46 which reflected in increased maximum and mean standardized uptake values (SUVmax and SUVmean) and tumor-to-background ratios (TBR) when compared to benign lesions. The dynamic imaging results differentiated lung cancer from non-cancerous lesions through distinct time-activity curve patterns. These patterns included an initial increase in activity typical of lung cancer that contrasted with the decreasing curves which were indicative of benign conditions.

The findings underline the superior sensitivity and specificity of 68Ga-FAPI-46 PET in distinguishing between malignant and benign pulmonary lesions in cases where 18F-FDG PET falls short. The introduction of 68Ga-FAPI-46 PET could thus lead to better patient stratification and more patient-specific treatment approaches by improving outcomes for the individuals with hard-to-diagnose subtypes of lung cancer.

Reference:

Röhrich, M., Daum, J., Gutjahr, E., Spektor, A.-M., Glatting, F. M., Sahin, Y. A., Buchholz, H. G., Hoppner, J., Schroeter, C., Mavriopoulou, E., Schlamp, K., Grott, M., Eichhorn, F., Heußel, C. P., Kauczor, H. U., Kreuter, M., Giesel, F., Schreckenberger, M., Winter, H., & Haberkorn, U. (2024). Diagnostic Potential of Supplemental Static and Dynamic68Ga-FAPI-46 PET for Primary18F-FDG–Negative Pulmonary Lesions. In Journal of Nuclear Medicine (p. jnumed.123.267103). Society of Nuclear Medicine. https://doi.org/10.2967/jnumed.123.267103

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Remdesivir may lower risk of in hospital death among COVID-19 patients not requiring oxygen: Study

Remdesivir may lower the risk of in-hospital death among COVID-19 patients not requiring oxygen suggests a new study published in the Open Forum Infectious Diseases.

Use of Remdesivir was linked to a significant decline in in-hospital death at both 14 and 28 days, regardless of variant of concern. Remdesivir has demonstrated benefit in some hospitalized patients with COVID-19 on supplemental oxygen and in non-hospitalized patients at room air. The durability of this benefit across time periods with different circulating SARS-CoV-2 variants of concern (VOC) is unknown. This comparative effectiveness study compares inpatient mortality among patients hospitalized for COVID-19 not receiving supplemental oxygen at admission initiating remdesivir treatment in the first two days of admission vs. no remdesivir during the hospitalization across different VOC periods. Using a large, multicenter US hospital database, in-hospital mortality was compared among patients hospitalized for COVID-19 not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir upon hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality or discharge to hospice. Results: Among the 121,336 eligible patients, 58,188 remdesivir-treated patients were matched to 17,574 unique non-remdesivir patients. Overall, 5.4% of remdesivir-treated and 7.3% of non-remdesivir patients died within 14 days, while 8.0% of remdesivir-treated and 9.8% of non-remdesivir patients died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in in-hospital mortality compared to non-remdesivir treatment (14-day adjusted hazard ratio (aHR): 0.75, 95% confidence interval (CI): 0.68-0.83; 28-day aHR: 0.83, 0.76-0.90). This significant mortality benefit endured across the different VOC periods. Remdesivir initiation in patients hospitalized for COVID-19, not requiring supplemental oxygen at admission, was associated with a statistically significant reduction in in-hospital mortality. These findings highlight a potential survival benefit when clinicians initiated remdesivir upon admission across the dominant variant eras of the evolving pandemic.

Reference:

Essy Mozaffari, Aastha Chandak, Chidinma Chima-Melton, Andre C Kalil, Heng Jiang, EunYoung Lee, Celine Der-Torossian, Mark Thrun, Mark Berry, Richard Haubrich, Robert L Gottlieb, Remdesivir is associated with reduced mortality in patients hospitalized for COVID-19 not requiring supplemental oxygen, Open Forum Infectious Diseases, 2024;, ofae202, https://doi.org/10.1093/ofid/ofae202

Keywords:

Remdesivir, lower risk, hospital, death, among, COVID-19 patients, oxygen, study, Open Forum Infectious Diseases, Essy Mozaffari, Aastha Chandak, Chidinma Chima-Melton, Andre C Kalil, Heng Jiang, EunYoung Lee, Celine Der-Torossian, Mark Thrun, Mark Berry, Richard Haubrich, Robert L Gottlieb, COVID-19, comparative effectiveness research, hospitalization, mortality, remdesivir

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Non-thermal atmospheric-pressure plasma novel approach to treatment of bone fractures: Study

“Break a leg!” is a welcome blessing of good luck, but who wants to hear that they have actually broken a bone? What’s worse, fractures that are displaced or complex require surgery and possibly lengthy recovery times while the patient remains partly or wholly immobilized.

Aiming to shorten recovery times, an Osaka Metropolitan University-led research group is focusing on plasma irradiation as a treatment method to speed up bone healing.

The Department of Orthopedic Surgery’s Kosuke Saito, a graduate student in the Graduate School of Medicine, Associate Professor Hiromitsu Toyoda, and Professor Hiroaki Nakamura, and Graduate School of Engineering Professor Jun-Seok Oh were among the researchers who used laboratory rats for their experiment.

The researchers broke the legs of the rats in two ways. One group of 24 rats had normal fractures that are generally easy to heal. The other group of 20 rats had fractures known as non-union ones where healing is usually prolonged or does not happen. Some were then irradiated with non-thermal atmospheric-pressure plasma, which didn’t offer the normal fracture group any significant advantages but boosted the healing and recovery time of the rats with non-union fractures. The strength of the healed areas of the irradiated non-union rats was also about 3.5 times stronger than that of the nonirradiated ones.

Furthermore, in vitro study of pre-osteoblastic cells irradiated with the plasma for 5 to 15 seconds showed that the activity of a protein that is an indicator of osteoblast differentiation increased, indicating that maturation of these bone-forming cells was progressing.

“Collaboration between the medical and engineering fields creates new medical technologies that have never before existed,” Professor Toyoda declared. “In the future, combining this treatment method with current fracture treatments is expected to contribute to more reliable bone fusion and shorter recovery times.”

Reference:

Kosuke Saito,Hiromitsu Toyoda ,Mitsuhiro Okada,Jun-Seok Oh,Katsumasa Nakazawa,Yoshitaka Ban,Kumi Orita,Akiyoshi Shimatani,Hana Yao,Tatsuru Shirafuji,Hiroaki Nakamura, Fracture healing on non-union fracture model promoted by non-thermal atmospheric-pressure plasma, PLoS ONE, https://doi.org/10.1371/journal.pone.0298086

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Childhood Adiposity Linked to Polycystic Ovary Syndrome Risk later on, suggests study

Researchers have found in a new study that excess adiposity and dysfunction in adipose tissue during childhood may signal a higher risk of developing Polycystic Ovary Syndrome (PCOS) later in life. The new study has been published in the journal of Pediatrics. This study offers insights into early indicators of PCOS risk, emphasizing the importance of early detection and intervention in pediatric populations. The study was conducted by Rachel C. and colleagues.

PCOS is a common endocrine disorder among females, characterized by a range of metabolic and reproductive issues. Early detection of risk factors such as adiposity and hormonal imbalances can lead to more effective interventions and preventive measures. This study investigates the development of PCOS in a pediatric cohort and identifies potential early signs of the condition.

The prospective Project Viva cohort study included 417 females and assessed cardiometabolic biomarkers and adiposity at three visits: mid childhood (mean age 7.9 years), early teen (mean age 13.1 years), and midteen (mean age 17.8 years). PCOS was defined either through self-reported diagnosis or the presence of ovulatory dysfunction with hyperandrogenism in adolescence. Researchers used multivariable logistic regression to explore associations between metabolic and adiposity markers at each visit and the risk of developing PCOS.

The key findings of the study were:

  • Adolescents with PCOS (n = 56, 13%) had higher mean BMI z-scores and truncal fat mass compared to those without PCOS at all three visits.

  • At the early teen visit, PCOS patients had lower adiponectin-to-leptin ratios (0.65 [0.69]) compared to those without PCOS (1.04 [0.97]).

  • Logistic regression analyses revealed that higher truncal fat mass at mid childhood and early teen visits was associated with increased odds of developing PCOS.

  • A lower adiponectin-to-leptin ratio at the midteen visit was associated with decreased odds of PCOS.

  • The study found that at the mid childhood visit, patients with PCOS had a mean BMI z-score of 0.66 compared to 0.30 in those without PCOS.

  • By the early teen visit, the mean BMI z-score of PCOS patients was 0.88 compared to 0.25 in those without PCOS.

  • Truncal fat mass was higher in PCOS patients at all visits, with an average of 3.5 kg at mid childhood, 9.4 kg at the early teen visit, and 11.6 kg at the midteen visit.

  • These values were notably higher than those in the non-PCOS group. Adiponectin-to-leptin ratio was found to be lower in PCOS patients compared to those without PCOS, especially at the midteen visit (0.33 vs. 0.75).

  • The adjusted models indicated an odds ratio of 1.42 for mid childhood truncal fat mass and 1.61 for early teen truncal fat mass, suggesting a significant association with PCOS risk.

  • The lower adiponectin-to-leptin ratio at the midteen visit was linked to a significantly lower odds ratio of 0.14 for developing PCOS.

Excess adiposity and adipose tissue dysfunction during childhood could serve as early indicators of future PCOS risk. By identifying these factors early, healthcare providers may be able to implement preventative measures and interventions to reduce the risk of developing PCOS in later life.

Reference:

Whooten, R. C., Rifas-Shiman, S. L., Perng, W., Chavarro, J. E., Taveras, E., Oken, E., & Hivert, M.-F. (2024). Associations of childhood adiposity and cardiometabolic biomarkers with adolescent PCOS. Pediatrics, e2023064894. https://doi.org/10.1542/peds.2023-064894

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