Prospective Analysis Research Articles

The role of radiation therapy in the treatment of early-stage skin cancer

Introduction. Radiation therapy remains one of the main methods of radical treatment of early-stage skin cancer. Its position in combination and comprehensive treatment has changed significantly as improvements of radiotherapy techniques and introduction of modern technologies led to increased effectiveness and comfort of the method and allowed to achieve better prognostic outcomes.Aim. To evaluate the role of radiotherapy in treatment of patients with early-stage skin cancer (T1–2N0M0).Materials and methods. A retrospective and prospective analyses of data from 1049 patients with early-stage skin cancer were performed. In 527 (50.23 %) cases, the tumor was localized mainly on the head and neck: 48 % of patients had nonkeratinizing squamous cell carcinoma of the skin, 7.59 % of patients had keratinizing squamous cell carcinoma, 44.41 % of patients had basal cell carcinoma.Results. Data from 527 patients (51.04 % man and 48.96 % women) with early-stage skin cancer (T1–2N0M0) who received treatment and are registered at the Republican Oncological Scientific Center of the Ministry of Health and Social Protection of the Tajikistan Republic were analyzed. The disease was more common in patients aged between 60 and 90 years. The main factor in stage determination was tumor size in accordance with the Tumor, Nodus and Metastasis (TNM) classification. In 240 (46.54 %) patients, the size of primary tumor was less than 2 cm in the largest diameter (T1N0M0), in 287 (54.46 %) patients its maximal size was between 2 and 4 cm (T2N0M0). Selection of treatment method was mainly based on morphological characteristics and location of the tumor. In 121 (50.42 %) patients with skin cancer T1N0M0, radiation therapy was performed as monotherapy in a radical program; in 88 (36.37 %) patients in combination with cobalt therapy and surgery; in 23 (9.59%) patients in combination with cobalt therapy, polychemotherapy and surgery; in 8 (3.41%) patients in combination with cobalt therapy and polychemotherapy.The capabilities of radiation therapy both as monotherapy and in combination with other treatment methods before and after surgical treatment present ample opportunities for clinicians to achieve good outcomes. The use of radiation therapy as monotherapy in a radical program in patients with T1N0M0 stage skin cancer is effective in 96.4 % of cases, in patients with stage T2N0M0 the effectiveness can reach 91.2 %.Conclusion. Radiation therapy can be successfully used in treatment of early-stage skin cancer along with other methods. Its use both independently and as part of combination and comprehensive therapy allows to achieve reliable treatment outcomes. Adequate selection of radiation therapy option in treatment of early-stage skin cancer is the key to longterm clinical remission and improvement of patients’ quality life.

The Functional Outcome of Limb Salvage of Proximal Femur Tumors With Modular Endoprosthesis: A Prospective Study.

Introduction The proximal femur is a common siteforprimary bone sarcomas, includingEwing's sarcoma, chondrosarcoma, osteosarcoma, and giant celltumors (GCT). Extensive resections arechallengingto reconstruct because the size of the tumormay necessitate an extensive resection ofthefemur to achieve adequate oncologic clearance. The resection of the proximal femur can result inhip jointinstabilitydue totheloss of the strong native hipcapsule orhip abductor strength. With a wide range of reconstruction options,such asresection arthrodesis, allograft-prosthetic composite (APC),andendoprosthesis,we can achieve limb salvage with good functionaloutcomes. Objective The objective of this case series isto evaluate the clinical outcomes and complications associatedwith endoprosthesis replacement in patients with proximal femur tumors. Methods A prospective analysis was conducted with 32 patients who underwent modular endoprosthesis replacement for proximal femoral tumors at our institution. Patient data, tumor characteristics, surgicaldetails, and postoperative outcomes were collected and analyzed. Results The study involved 32 patientswho met theinclusion criteria.Theywere assessed usingthe MusculoskeletalTumor Society Score (MSTS), which showedgoodfunctional outcomesin72.84%of the patients. The study highlights the functionaloutcomes and potential complications associated with the use of modular prostheses. Conclusion Endoprosthesis replacement in proximal femur tumors is a viable treatment option, providinggood functional outcomes and an acceptable method for limb salvage, which enhances the quality of life.

Prenatal Phenol and Paraben Exposures and Adverse Birth Outcomes: A Prospective Analysis of U.S. Births

BackgroundSynthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1–2 spot samples during pregnancy and limited diversity of populations. ObjectiveTo study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program. ResultsWhile many associations were modest and statistically imprecise, a 1-unit increase in log10 pregnancy averaged concentration of benzophenone-3 and methylparaben were associated with decreases in birthweight, birthweight adjusted for gestational age and SGA. Increases in the odds of being SGA were 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%), respectively. Bisphenol S in third trimester was also associated with SGA (OR 1.52, 95% CI 1.08, 2.13). Associations of benzophenone-3 and methylparaben with PTB and LBW were null. In addition, a 1-unit increase in log10 pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: −67%, −2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: −53%, 8%). DiscussionIn a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life.

Usage of antimicrobials in patients having intricate clean-contaminated head and neck surgeries.

Objective: The goal of this study is to characterize, the infectious complications and to identify the risk variables most frequently linked, after head and neck surgeries.Methodology: 47 patients who underwent major clean-contaminated head and neck surgery between 2019 and 2022 at the cervicomaxillofacial Surgery Department (Saint-Pierre Hospital) were the subject of a prospective cohort analysis. Two groups of patients were created: group I received a postoperative antibiotic regimen for just 24 hours; group II re-ceived a longer postoperative antibiotic course lasting more than 24 hours. Amoxicillin and clavulanate were given intra-venously 30 to 60 minutes before making the incision as antibacterial precautions. Following surgery, the antibiotic course was maintained. Univariate analysis was used to assess the predictive importance of the antibiotic regimen on postoperative outcomes, including clinical symptoms of infection and biological indicators like the white blood cell count and C-reactive protein levels was evaluated using univariate analysis.Results: 18 patients experienced SSIs. Antibiotics were used to treat each of these grade 2 illnesses. Only a history of hypothyroidism appears to be a predictor of SSI after univariate analysis (P = 0.038). When we compared the patients who received antibiotics for 24 h or more, there was no discernible difference in terms of onset and hospital stay. Addi-tionally, neither group had a different rate of germs that were multidrug resistant.Conclusion: Our findings imply that using postoperative antibiotics for more than 24 hours has no positive effects on SSI.
 Key words: Cervico-maxillofacial Surgery, clean contaminated surgery, antimicrobials, Surgical Site Infection.

Didactical Analysis of Mathematical Literacy Skills to Identify Learning Obstacles on Space and Shape Content

Mathematical literacy can be defined as the ability to understand and use mathematics in various contexts to solve problems, geometry is a lesson that can still make students experience learning obstacles or called learning obstacles. The purpose of the study was to identify learning obstacles and didactically analyze students' mathematical literacy on space and shape content. This research uses a qualitative method, incorporating the dedactical design model (Didactical Design Research). The qualitative method consists of interviews, observations, and documentation studies. The instruments used were interview guidelines and observation guidelines. Meanwhile, the dedactical design consists of: 1) prospective analysis (before learning) 2) metapedactic analysis and 3) retrospective analysis (combined results of prospective and metapedactic analysis). The research subjects were 6 students who were selected by purposive sampling. Based on the dedactical design, the researcher only reached the prospective stage. Based on the results of research on students' mathematical literacy skills in solving PISA questions on space and shape content, namely on the three subjects showing different results. Based on the written test results, AD and AL subjects have high mathematical literacy skills. then JU subjects have moderate literacy skills. And subjects NF, RI and MA have low mathematical literacy skills. So that from these three subjects it can be said that the students' mathematical literacy skills are still low. Efforts that can be made based on learning obstacles are that students are guided and familiarized when given problems to solve by starting to write what is known and what is asked in the given problem, linking to real-world concepts, expressing arguments in solving problems, developing strategies, using symbols, mathematical tools, and making conclusions of mathematical solutions.

Analysis of Students' Learning Obstacles on PISA-based Uncertainty and Data Content

Mathematical literacy ability is an ability that can be measured in PISA (Programme for International Student Assesment), one of the contents studied is uncertainty and data (Uncertainly and data). This study aims to describe the learning obstacles experienced by students in uncertainty material content and PISA-based data. This research is a type of descriptive research with a qualitative approach using didactical design (Didactical Design Research) didactic situation analysis stage before learning (prospective analysis). This research was conducted at SMP Pesantren Guppi Samata class VIII with a sample of 16 students using a test instrument in the form of 5 points of description questions and non-tests in the form of observation guidelines. Mathematical literacy indicators used in this study are Communication, Mathematising, Representation, Reasoning and argument, Devising strategies for solving problems, Using symbolic, formal , technical language and operations (Using symbolic, formal, technical and operating language), and Using mathematical tools. The results of this study include: 1) difficulties in understanding the problem; 2) Difficulty in formulating problems; 3) Difficulty in understanding the meaning of the problem; and 4) Difficulty in drawing conclusions. So that the obstacles faced by students are ontogenic obstacles and epistemological obstacles.

Assessing the Utility of a Machine-Learning Model to Assist With the Assignment of the American Society of Anesthesiology Physical Status Classification in Pediatric Patients

BACKGROUND: The American Society of Anesthesiologists Physical Status Classification System (ASA-PS) is used to classify patients’ health before delivering an anesthetic. Assigning an ASA-PS Classification score to pediatric patients can be challenging due to the vast array of chronic conditions present in the pediatric population. The specific aims of this study were to (1) suggest an ASA-PS score for pediatric patients undergoing elective surgical procedures using machine-learning (ML) methods; and (2) assess the impact of presenting the suggested ASA-PS score to clinicians when making their final ASA-PS assignment. The intent was not to create a new ASA-PS score but to use ML methods to generate a suggested score, along with information on how the score was generated (ie, historical information on patient comorbidities) to assist clinicians when assigning their final ASA-PS score. METHODS: A retrospective analysis of 146,784 pediatric surgical encounters from January 1, 2016, to December 31, 2019, using eXtreme Gradient Boosting (XGBoost) methods to predict ASA-PS scores using patients’ age, weight, and chronic conditions. SHapley Additive exPlanations (SHAP) were used to assess patient characteristics that contributed most to the predicted ASA-PS scores. The predicted ASA-PS model was presented to a prospective cohort study of 28,677 surgical encounters from December 1, 2021, to October 31, 2022. The predicted ASA-PS score was presented to the anesthesiology provider for review before entering the final ASA-PS score. The study focused on summarizing the available information for the anesthesiologist by using ML methods. The goal was to explore the potential for ML to provide assistance to anesthesiologists by highlighting potential areas of discordance between the variables that generated a given ML prediction and the physician’s mental model of the patient’s medical comorbidities. RESULTS: For the retrospective analysis, the distribution of predicted ASA-PS scores was 22.7% ASA-PS I, 48.5% II, 23.6% III, 5.1% IV, and 0.04% V. The distribution of clinician-assigned ASA-PS scores was 24.3% for ASA-PS I, 44.5% for ASA-PS II, 24.9% for ASA III, 6.1% for ASA-PS IV, and 0.2% for ASA-V. In the prospective analysis, the final ASA-PS score matched the initial ASA-PS 90.7% of the time and 9.3% were revised after viewing the predicted ASA-PS score. When the initial ASA-PS score and the ML ASA-PS score were discrepant, 19.5% of the cases have a final ASA-PS score which is different from the initial clinician ASA-PS score. The prevalence of multiple chronic conditions increased with ASA-PS score: 34.9% ASA-PS I, 73.2% II, 92.3% III, and 94.4% IV. CONCLUSIONS: ML derivation of predicted pediatric ASA-PS scores was successful, with a strong agreement between predicted and clinician-entered ASA-PS scores. Presentation of predicted ASA-PS scores was associated with revision in final scoring for 1-in-10 pediatric patients.

A Multicentric Observational Study to Determine Myocardial Injury in Severe Community-Acquired Pneumonia (sCAP).

Background: Severe community-acquired pneumonia (sCAP) is the most frequent admission for acute respiratory failure in intensive care medicine. Observational studies have found a correlation between patients who were admitted with CAP and the development of cardiovascular events. The risk of acute myocardial damage in patients with CAP is particularly high within the first 30 days of hospitalization. Research design and methods: Multicenter prospective cohort analysis conducted in consecutive patients admitted to an ICU with microbiologically confirmed diagnoses of sCAP. The aim was to determine any structural cardiac damage detected by advanced imagining techniques (cardiac MRI) and cardiac biomarkers in patients with sCAP. The patients were stratified, according to their etiology, into pneumococcal or not-pneumococcal sCAP. The primary outcome was cardiac damage at day 5 and 7 of clinical presentation. Results: A total of 23 patients were consecutively and prospectively enrolled for two winter periods. No significant differences were observed between the median troponin when comparing the pneumococcal vs. non-pneumococcal. The incidence of myocardial damage was numerically higher in the pneumococcal subgroup (70% vs. 50%, p = 0.61) on day 5 and on day 7 (53% vs. 40%, p = 0.81) but did not achieve significance. Confirming a correlation between the biomarkers of cell damage and the biomarkers of myocardial damage, only a positive and significant correlation was observed between h-FABP and DNA on day 1 (r = 0.74; p < 0.01) and day 3 (r = 0.83; p < 0.010). Twenty cardiac MRIs were performed on the 23 patients (87%). No presence of fibrosis was observed in any of the studies carried out within the first 15 days of admission. Conclusions: No significant myocardial damage was found in patients with sCAP independent of the bacterial etiology in accordance with biomarker alterations (Troponin and/or h-FABP) or cardiac MRI. Using cardiac MRI, we could not find any presence of myocardial fibrosis within the first 15 days of admission.

Prevalence of transthyretin amyloidosis in patients undergoing carpal tunnel surgery: a prospective cohort study and risk factor analysis.

Transthyretin amyloidosis is a frequent cause of heart failure, resulting from an accumulation of abnormal proteins in the myocardium. Recent research has highlighted the importance of early diagnosis to enhance the effectiveness of specific treatments. Extra-cardiac symptoms may precede several years before cardiac complications, with carpal tunnel syndrome often considered a red flag. The aim of this prospective, observational cohort study was to determine the incidence rate of positive synovial biopsies for transthyretin amyloidosis in patients aged 60-80 years undergoing carpal tunnel decompression, and to identify risk factors. The diagnosis of transthyretin amyloidosis was confirmed through the analysis of synovial tissue biopsies using Congo Red and immunohistochemical staining. The study included 254 patients, with an 18.5% prevalence of transthyretin amyloidosis. Risk factors for positive test results were identified as male sex, trigger finger, hearing disorders and valve disease. A predictive analysis using logistic regression yielded a probability model for individuals belonging to the positive group.Level of evidence III.

Improving outcomes in single chamber leadless pacemakers: strategies for minimizing vascular complications

BackgroundLeadless pacemaker therapy is associated with a significant reduction in lead-related complication rate compared to conventional transvenous single chamber pacemaker therapy. However, a significant complication rate of 1.2% was observed in vascular access due to the use of large delivery femoral sheath (27Fr). The aim of this study was to evaluate the effectiveness of real-time ultrasound guidance and Z suture technique in reducing total and major vascular complications in leadless pacemaker therapy.MethodIn this study, we performed a retrospective and prospective analysis of all adverse events associated with leadless pacemaker (Micra) implantation by two operators at a single tertiary center from December 2016 to December 2018. To mitigate the risk of vascular complications, all patients underwent real-time ultrasound-guided venipuncture for vascular access, as well as the application of a Z-suture technique for hemostasis at the end of the procedure. Data were collected on implant indications, implant procedure details, complications, and follow-up information.ResultsIn this study, 45 patients with an age range of 24 to 94 years (mean 76 ± 14 years) were recruited, with 21 (46.6%) being female. The pacing indications for the patients included atrial fibrillation (24, 53.3%), vascular (7, 15.5%), infection (9, 20%), cognitive/frailty (3, 6.6%), and occupational (2, 4.4%). The implant procedures were performed under general anesthesia in 6 (13.3%) of the cases, and under local anesthesia and sedation in 39 (86.6%) of the cases. A single deployment was achieved in 43 (95.5%) of the patients, while 2 deployments were required in 2 (4.4%) of the patients. Notably, no vascular or major complications were reported in our cohort of patients.ConclusionsThe results of this observational study indicate that incorporating real-time ultrasound guidance during venipuncture and the use of a Z-suture technique significantly reduce the occurrence of both total and major vascular complications associated with the implantation of leadless pacemaker. However, more robust and larger studies are required in order to confirm these results and implications for clinical practice.

Cholecystectomy is associated with a higher risk of irritable bowel syndrome in the UK Biobank: a prospective cohort study.

Background: Recent studies have shown that bile acids are essential in irritable bowel syndrome (IBS) pathology, and cholecystectomy has direct effects on bile acid metabolism. However, whether cholecystectomy increases the risk of IBS remains unclear. We aimed to investigate the association between cholecystectomy and IBS risk in the UK Biobank (UKB). Methods: This study is a prospective analysis of 413,472 participants who were free of IBS, inflammatory bowel disease, cancer, or common benign digestive tract diseases. We identified incidents of IBS through self-reporting or links to primary healthcare and hospitalization data. We evaluated hazard ratios (HRs) adjusted for sociodemographic characteristics, health behaviours, comorbidities, and medications. Results: During a median follow-up period of 12.7years, we observed 15,503 new cases of IBS. Participants with a history of cholecystectomy had a 46% higher risk of IBS than those without (HR = 1.46, 95% CI: 1.32-1.60), and further subtype analysis showed that the risk of IBS with diarrhoea was significantly higher than the risk of IBS without diarrhoea (HR = 1.71, 95% CI: 1.30-2.25 vs. HR = 1.42, 95% CI: 1.28-1.58). The overall covariate-adjusted HRs for IBS were similar between the group with both cholecystectomy and gallstones (HR = 1.45, 95% CI: 1.32-1.58) and the group with cholecystectomy without gallstones (HR = 1.50, 95% CI: 1.36-1.67) when the group without both cholecystectomy and gallstones was used as a reference. The overall covariate-adjusted HR was not significantly different in the group without cholecystectomy with gallstones (HR = 1.18, 95% CI: 0.95-1.47). The positive association of cholecystectomy with IBS risk did not change when stratifying the data based on age, sex, BMI, smoking, alcohol consumption, healthy diet, quality sleep, physical activity, type 2 diabetes, hypertension, hyperlipidaemia, mental illness, NSAID intake, or acid inhibitor intake. Sensitivity analyses, including propensity score matching analysis and lagging the exposure for two or fouryears, indicated that the effects were robust. Conclusion: Cholecystectomy was associated with a higher risk of IBS, especially IBS with diarrhoea. Additional prospective randomized controlled and experimental studies are warranted to further validate the association and to explore the relevant biological mechanisms.

Spatiotemporal variations of “triple-demic” outbreaks of respiratory infections in the United States in the post-COVID-19 era

BackgroundThe US confronted a “triple-demic” of influenza, respiratory syncytial virus (RSV), and COVID-19 in the winter of 2022, leading to increased respiratory infections and a higher demand for medical supplies. It is urgent to analyze these epidemics and their spatial-temporal co-occurrence, identifying hotspots and informing public health strategies.MethodsWe employed retrospective and prospective space-time scan statistics to assess the situations of COVID-19, influenza, and RSV in 51 US states from October 2021 to February 2022, and from October 2022 to February 2023, respectively. This enabled monitoring of spatiotemporal variations for each epidemic individually and collectively.ResultsCompared to winter 2021, COVID-19 cases decreased while influenza and RSV infections significantly increased in winter 2022. We found a high-risk cluster of influenza and COVID-19 (not all three) in winter 2021. In late November 2022, a large high-risk cluster of triple-demic emerged in the central US. The number of states at high risk for multiple epidemics increased from 15 in October 2022 to 21 in January 2023.ConclusionsOur study offers a novel spatiotemporal approach that combines both univariate and multivariate surveillance, as well as retrospective and prospective analyses. This approach offers a more comprehensive and timely understanding of how the co-occurrence of COVID-19, influenza, and RSV impacts various regions within the United States. Our findings assist in tailor-made strategies to mitigate the effects of these respiratory infections.

Association between a lifestyle score and all-cause mortality: a prospective analysis of the Chilean National Health Survey 2009-2010.

To investigate the association between a lifestyle score and all-cause mortality in the Chilean population. Prospective study. The score was based on seven modifiable behaviours: salt intake, fruit and vegetable intake, alcohol consumption, sleep duration, smoking, physical activity and sedentary behaviours. 1-point was assigned for each healthy recommendation. Points were summed to create an unweighted score from 0 (less healthy) to 7 (healthiest). According to their score, participants were then classified into: less healthy (0-2 points), moderately healthy (3-4 points) and the healthiest (5-7 points). Associations between the categories of lifestyle score and all-cause mortality were investigated using Cox proportional hazard models adjusted for confounders. Nonlinear associations were also investigated. 2706 participants from the Chilean National Health Survey 2009-2010. After a median follow-up of 10·9 years, 286 (10·6 %) participants died. In the maximally adjusted model, and compared with the healthiest participants, those less healthy had 2·55 (95 % CI 1·75, 3·71) times higher mortality risk due to any cause. Similar trends were identified for the moderately healthy group. Moreover, there was a significant trend towards increasing the mortality risk when increasing unhealthy behaviours (hazard ratio model 3: 1·61 (95 % CI 1·34, 1·94)). There was no evidence of nonlinearity between the lifestyle score and all-cause mortality. Individuals in the less healthy lifestyle category had higher mortality risk than the healthiest group. Therefore, public health strategies should be implemented to promote adherence to a healthy lifestyle across the Chilean population.

Fungi in Egypt: A bibliometric analysis of current research and future prospects

Fungi in Egypt: A bibliometric analysis of current research and future prospects

An analysis of the application prospects of nano-targeted drug delivery systems in cancer therapy

Cancer is an important cause of human death in the world today. Traditional cancer treatment methods have many defects, such as high damage to normal cells and the inability to efficiently remove tumor cells. In recent years, due to the EPR effect of nano-targeted drugs can stay in the tumor site for a long time, as well as their high specificity to cancer cells and better therapeutic ability than traditional drugs, more and more scholars believe that nano-targeted drug delivery system is a very promising research direction for cancer treatment. This article focuses on recent research in this field, focuses on targeting the tumor itself and various pathways by which T cells kill tumor cells, including promoting apoptosis, reversing polarization TAMs, Inducing iron death in cancer cells, Remodeling the tumor microenvironment and reprogramming metabolism. Through analysis of recent research, it was found that these methods have their own advantages and can be combined to improve the therapeutic effect of drugs. However, the more basic mechanism is still a blank, and more exploration is needed.

Transesophageal echocardiography and computerized tomography angiography mismatch in left atrial appendage thrombus evaluation.

Transesophageal echocardiography (TEE) is the gold standard test for the diagnosis of left atrial appendage (LAA) thrombus. Nonetheless, computerized tomography angiography (CTA) is readily used to exclude LAA thrombus before pulmonary vein isolation (PVI) and LAA closure procedures. We aimed to assess the comparability of LAA thrombus diagnosis using chest CTA scans in patients with atrial fibrillation who underwent TEE. Retrospective collection of consecutive patients with atrial fibrillation who underwent TEE and chest CTA within 30 days and had evidence of spontaneous echo contrast (SEC) or LAA thrombus on TEE. Clinical, demographic, and echo data were collected. Prospective analysis of the CTA for evidence of LAA thrombus in the same group of patients was performed. We compared the findings of the two modalities. Out of 1550 patients with atrial fibrillation who underwent TEE examinations in the study period, 63 patients underwent TEE within 30 days of a chest CTA scan. Twenty-three patients had LAA thrombus and 40 had some degree of SEC according to TEE. On CTA, 11 were interpreted as positive with a high level of suspicion for the presence of an LAA thrombus. Six patients (26.1%) had LAA thrombus according to both CT and TEE. Therefore, low concordance was found between test results (chi-squared continuity correction = 5.5, df = 1, and P -value = 0.01902). The discrepancy between CTA and TEE results suggests these examinations might be more suitable as complementary examinations to exclude LAA thrombus.

Association of Bone Mineral Density and Bone Turnover Markers with the Risk of Diabetes: Hong Kong Osteoporosis Study and Mendelian Randomization.

Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS). A total of 993 and 7160 participants from the HKOS were studied for the cross-sectional and prospective analyses, respectively. The cross-sectional study evaluated the association of BMD and bone biomarkers with fasting glucose and glycated hemoglobin (HbA1c ) levels, whereas the prospective study examined the associations between BMD at study sites and the risk of T2DM by following subjects a median of 16.8 years. Body mass index (BMI) was adjusted in all full models. Mendelian randomization (MR) was conducted for causal inference. In the cross-sectional analysis, lower levels of circulating bone turnover markers and higher BMD were significantly associated with increased fasting glucose and HbA1c levels. In the prospective analysis, higher BMD (0.1 g/cm2 ) at the femoral neck and total hip was associated with increased risk of T2DM with hazard ratios (HRs) of 1.10 (95% confidence interval [CI], 1.03 to 1.18) and 1.14 (95% CI, 1.08 to 1.21), respectively. The presence of osteoporosis was associated with a 30% reduction in risk of T2DM compared to those with normal BMD (HR = 0.70; 95% CI, 0.55 to 0.90). The MR results indicate a robust genetic causal association of estimated BMD (eBMD) with 2-h glucose level after an oral glucose challenge test (estimate = 0.043; 95% CI, 0.007 to 0.079) and T2DM (odds ratio = 1.064; 95% CI, 1.036 to 1.093). Higher BMD and lower levels of circulating bone biomarkers were cross-sectionally associated with poor glycemic control. Moreover, higher BMD was associated with a higher risk of incident T2DM and the association is probably causal. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The immunogenicity and the safety of the adjuvanted glycoprotein E (gE)-based recombinant vaccine against herpes zoster (RZV) in cancer patients during immunotherapy

ABSTRACT Herpes zoster (HZ) is caused by the reactivation of latent varicella zoster virus (VZV). Severe immunocompromising conditions, such as solid tumors, have been largely associated with an increased risk for HZ due to waning VZV-specific cellular immunity. With the approval of the adjuvanted glycoprotein E (gE)-based recombinant vaccine (RZV; Shingrix™, GSK) also in immunocompromised subjects, HZ is considered a vaccine-preventable disease changing perspectives in immunocompromised subjects. To date, no clinical trial has evaluated the immunogenicity in the patients with cancer undergoing immunotherapy. In this study, we describe the humoral and cell-mediated immune responses in 38 cancer patients treated with immune checkpoint inhibitors (ICIs) and receiving RZV. We used samples collected at baseline (T0), 3 weeks (T2), and 6 months (T3) after the complete RV vaccination schedule. Our data showed that a significant proportion (40,5%) of RZV recipients mounted a stronger humoral and cell-mediated immune response at 3 weeks (T2) after complete RZV vaccination schedule. Interestingly, both humoral and cell-mediated immune responses were mostly stable over 6 months (T3). Interestingly, the overall IFNγ-producing lymphocytes was mainly associated with CD4 T cell response (p = .0012). In conclusion, data from our pilot study suggest a strong and long-lasting immunogenicity of RZV in ICI-treated patients. Prospective analyses at 1 year after vaccination will be performed in order to evaluate the long-term persistence of humoral and cell-mediated response against RZV.

Betapapillomavirus natural history and co-detection with alphapapillomavirus in cervical samples of adult women.

Human papillomaviruses (HPV) of the genus Betapapillomavirus can infect both cutaneous and mucosal sites, but research on their natural history at mucosal sites remains scarce. We examined the risk factors and co-detection patterns of HPVs of the Betapapillomavirus and Alphapapillomavirus genera in cervical samples of the Ludwig-McGill cohort study. We assessed a subset of 505 women from the Ludwig-McGill cohort study from São Paulo, Brazil. Cervical samples over the first year of follow-up were tested for DNA of over 40 alphapapillomavirus types and 43 betapapillomavirus types using a type-specific multiplex genotyping polymerase chain reaction assay. We assessed the risk factors for prevalent and incident betapapillomavirus type detection, and whether types were detected more frequently together than expected assuming independence using permutation tests, logistic regression, and Cox regression. We observed significant within-genus clustering but not cross-genus clustering. Multiple betapapillomavirus types were co-detected in the same sample 2.24 (95% confidence interval [CI]: 1.65-3.29) times more frequently than expected. Conversely, co-detections of alphapapillomavirus and betapapillomavirus types in the same sample occurred only 0.64 (95% CI: 0.51-0.83) times as often as expected under independence. In prospective analyses, positivity to one HPV genus was associated with a nonsignificant lower incidence of detection of types in the other genus. Lifetime number of sex partners and new sex partner acquisition were associated with lower risks of prevalent and incident betapapillomavirus detection. Betapapillomaviruses are commonly found in the cervicovaginal tract. Results suggest potentially different mechanisms of transmission for betapapillomavirus genital infections other than vaginal sex.

Xanamem shows pro‐cognitive activity with clinically meaningful effect sizes across 3 independent, placebo‐controlled clinical trials

AbstractBackgroundXanamem® is a brain‐penetrant inhibitor of 11‐beta hydroxysteroid dehydrogenase type 1, which converts intracellular cortisone to cortisol and is highly expressed in brain regions such as the hippocampus. Elevated plasma and CSF cortisol is strongly associated with cognitive decline.MethodEffects of Xanamem on cognition were assessed in 3 independent, placebo‐controlled, double‐blind trials. The XanaHES (n = 42, 20 mg) and XanaMIA (n = 105, 5 &amp; 10 mg) Phase 1b trials used the computerised Cogstate system to assess cognition in normal, older volunteers. The XanADu‐X biomarker extension study (n = 72, 10 mg) explored clinical and cognitive outcomes in subgroups (n = 34 each) of the XanADu Phase 2a AD trial with higher (H) or lower (L) plasma p‐Tau181 in a new prospective analysis. To compare the results across trials, we focus on the cognitive effect sizes measured by the Cohen’s statistic (treatment effect vs. placebo / pooled baseline standard deviation).ResultXanamem was safe and well‐tolerated with no treatment‐related SAEs and the predominantly mild AEs were generally equally distributed between Xanamem and placebo. In XanaHES and XanaMIA, a pattern of clinically significant improvements was observed in attention and working memory compared to placebo in the Xanamem groups, with Cohen’s d ranging up to 1.27. Improvements from baseline were observed in both Xanamem and placebo in domains of episodic memory and executive function without a treatment difference. In XanADu, Xanamem demonstrated clinically significant benefit with a Cohen’s d of 0.41 on the CDR‐SB compared to placebo in the H group but not in the L group. In both L and H groups improvements in executive function were seen favouring Xanamem (Cohen’s d = 0.34 and 0.26, respectively) and the MMSE (Cohen’s d = 0.32 and 0.16, respectively). There were no improvements observed on original XanADu primary outcome measures of ADAS‐Cog14 and ADCOMs.ConclusionXanamem displays activity in multiple domains of cognition including attention, working memory, and executive function with clinically meaningful effects in normal subjects and in patients with p‐Tau‐elevated mild AD. These data suggest Xanamem may be both a pro‐cognitive drug and disease‐modifying agent and guide design of future trials.