Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Association between dysglycemia and the Charlson Comorbidity Index among hospitalized patients with diabetes

AimInpatient dysglycemia has been linked to short-term mortality, but longer-term mortality data are lacking. Our aim was to evaluate the association between inpatient dysglycemia and one-year mortality risk.MethodsRetrospective chart review of adults with diabetes hospitalized between 2015 and 2019. The Charlson Comorbidity Index (CCI) was used to estimate 1-year mortality risk, stratified into low (CCI ≤ 5) and high risk (CCI ≥6). Simple and multivariable logistic regression was used to evaluate the association between dysglycemic measures and high mortality risk.ResultsAmong 22,639 unique admissions, BG ≥ 180, ≥300, ≤70, <54 and <40 mg/dL were associated with adjusted odds of 1.43 (95 % CI, 1.33, 1.54), 1.58 (95 % CI, 1.48, 1.68), 2.16 (95 % CI, 2.01, 2.32), 2.58 (95 % CI, 2.32, 2.86), and 2.56 (95 % CI, 2.19, 2.99) for high mortality risk, respectively. Older age and Black race were positively associated with hyperglycemia and hypoglycemia. Myocardial infarction, congestive heart failure (CHF), and moderate to severe liver disease were most strongly associated with hyperglycemia, while renal disease, CHF, peripheral vascular disease, and peptic ulcer disease were most strongly associated with hypoglycemia.ConclusionsInpatient hypoglycemia and hyperglycemia were both positively associated with higher one-year mortality risk, with stronger magnitude of association observed for hypoglycemia. The association appears to be mediated mainly by presence of diabetes-related complications.     

Non invasive assessment of human oocytes and embryos in assisted reproduction: Review on present practices and future trends

Oocyte and embryo grading is one of the most important steps in assisted reproductive technology to identify the best among cultured embryos for transfer or vitrification. The most commonly used non-invasive method is morphological assessment of gametes and embryos using a microscope. This method despite being simple and cost-effective has interobserver and intraobserver variability and subjectivity and has little to offer about the physiological state of embryos. This review sourced research articles and reviews pertaining to other non-invasive assessment methodologies from Medline and PubMed to collate latest technologies in vogue and identify novel methodologies of the future. The review assesses the current understanding in oocyte and embryo grading and touches upon novel non-invasive techniques and potential biomarkers to identify the best embryo. The latest available literature on time-lapse imaging, hierarchical algorithms, omics (consisting of proteomics and secretomes), miRNAs, mitochondrial RNAs and artificial intelligence has been accessed to summarize the enormous information available, to identify gaps in current interpretations, to identify emerging technologies and to provide direction for future research. This review will greatly benefit anyone practicing assisted reproduction and clinical embryology.     

Using Big Data for Cardiovascular Health Surveillance: Insights From 10.3 Million Individuals in the CANHEART Cohort

BackgroundThe increasing availability of large electronic population-based databases offers unique opportunities to conduct cardiovascular health surveillance traditionally done using surveys. We aimed to examine cardiovascular risk-factor burden, preventive care, and disease incidence among adults in Ontario, Canada—using routinely collected data—and compare estimates with health survey data.MethodsIn the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) initiative, multiple health administrative databases were linked to create a population-based cohort of 10.3 million adults without histories of cardiovascular disease. We examined cardiovascular risk-factor burden and screening and outcomes between 2016 and 2020. Risk- factor burden was also compared with cycles 3 to 5 (2012 to 2017) of the Canadian Health Measures Survey (CMHS), which included 9473 participants across Canada.ResultsMean age of our study cohort was 47.9 ± 17.0 years, and 52.0% were women. Lipid and diabetes assessment rates among individuals 40 to 79 years were 76.6% and 78.2%, respectively, and lowest among men 40 to 49 years of age. Total cholesterol levels and diabetes and hypertension rates among men and women 20 to 79 years were similar to Canadian Health Measures Survey (CHMS) findings (total cholesterol: 4.80/4.98 vs 4.94/5.25 mmol/L; diabetes: 8.2%/7.1% vs 8.1%/6.0%; hypertension: 21.4%/21.6% vs 23.9%/23.1%, respectively); however, patients in the CANHEART study had slightly higher mean glucose (men: 5.79 vs 5.44; women: 5.39 vs 5.09 mmol/L) and systolic blood pressures (men: 126.2 vs 118.3; women: 120.6 vs 115.7 mm Hg).ConclusionsCardiovascular health surveillance is possible through linkage of routinely collected electronic population-based datasets. However, further investigation is needed to understand differences between health administrative and survey measures cross-sectionally and over time.     

Prevention of alloimmune rejection using XBP1-deleted bone marrow-derived dendritic cells in heart transplantation

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Diagnostic significance of the histopathology of bone marrow macrophages in forensic autopsies

Forensic pathologists often encounter autopsies that require an assessment of antemortem general conditions (e.g., infection, metabolic disorders). To establish evaluation clues for such cases, we quantitatively examined macrophages and the general pathology of bone marrow in samples from 180 forensic autopsy cases of decedents with various conditions. Hematoxylin-eosin staining, Berlin blue staining, and immunostainings for CD163, CD138, and CD61 were performed. We determined the numbers per field (density) of total macrophages, swollen macrophages, macrophages with hemophagocytosis, and hemosiderin-laden macrophages. Each density was standardized by identifying its ratio to the total number of macrophages. The decedents' background data (cause of death, other pathological findings, postmortem interval, antemortem symptoms, and presence of resuscitation) were extracted. No correlations were found between the postmortem interval and the other decedent data, indicating that these data are not affected by postmortem changes. In the group in which inflammatory disease was the cause of death, there were significant elevations in the ratio of the swollen macrophage density to total macrophages. Significantly higher ratios of the density of swollen and hemophagocytic macrophages were observed in the group in which conditions with a prolonged agonal period were the cause of death. The group with a return of spontaneous circulation to resuscitation showed a significantly higher ratio of macrophage density with hemophagocytosis. This study provides the first statistical analysis focused on bone marrow histopathology in forensic autopsies. The results will be useful for elucidating causes of death and agonal-period conditions.