A 44-year-old male patient was referred to our department with unremarkable physical examination and laboratory data due to a mass which was incidentally found in the right atrial during a routine examination. Transthoracic and transesophageal echocardiography revealed a 46 × 30 mm, well-delimited, nonmobile mass in the superior portion of the right atrium. Besides the intracardiac mass, another low density was detected in adjacent pericardial cavity at cardiac computed tomography; he extracardiac mass appeared to be caused by invasive growth from the intracardiac mass. An operation was performed through right anterolateral minithoracotomy with the patient under hypothermic cardiopulmonary bypass. During operation, it was found that the surface of the right atrium was covered by an adipose mass (30 × 40 mm; Figure 2A). Intracardiac mass also showed yellow adipose tissue (40 × 50 mm; Figure 2B). Both parts of the mass infiltrated the myocardium. The mass was resected completely; and right atrium was reconstructed by using bovine pericardium pad. After the operation, the pathology confirmed the both intracardiac and extracardiac tissues as lipoma; transthoracic echocardiogram showed the atrial mass was removed completely and the left ventricular ejection fraction was normal. The patient's postoperative course was uneventful and he was discharged home after 7 days.The wide variability of isoniazid (INH) pharmacokinetics is mainly attributed to the trimodal N-acetyltransferase 2 (NAT2) acetylator phenotype, that is, rapid, intermediate, and slow. Consequently, a uniform INH dose in current clinical practice may lead to treatment failure and emergence of drug resistance. There is a lack of studies on specific doses of INH for different NAT2 acetylator phenotypes among tuberculosis (TB) patients. Therefore, we aimed to provide insight into the optimal dosing of INH for each NAT2 acetylator phenotype with respect to the probability of achieving a pharmacokinetic (PK)/pharmacodynamic target. Sodium Monensin Antineoplastic and I chemical PK, the NAT2 genotype, and clinical data were collected in a multicenter prospective cohort study conducted at 13 clinical centers in Korea. Population PK modeling and simulation were carried out. Data from 454 TB patients were divided into a training data set and a test data set at a ratio of 4 to 1. The PK of the training data were best described by a 2-compartment model with allometric scaling for body size effect. Importantly, NAT2 acetylator phenotypes significantly affected the apparent clearance. Our model, which provided better predictive performance compared with previously published models, was evaluated by external validation using the test set. The simulation for assessing target efficacy and toxicity indicated that the best INH dosing regimens for Korean tuberculosis patients were once-daily doses of 400, 300, and 200 mg for rapid, intermediate, and slow acetylators, respectively. In conclusion, our study provides a step forward in precision dosing for antituberculosis management.
Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR.
Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19-related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed.
IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8
T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features.
A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8
T cells in severe COVID-19 patients, which in turn may impact the development of MDR.
A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8+ T cells in severe COVID-19 patients, which in turn may impact the development of MDR.An excess risk of thyroid cancer has been reported in different World Trade Center (WTC)-dust exposed cohorts. Increased surveillance of these cohorts has been suggested as a potential explanation of this reported excess thyroid cancer risk leading to an increased diagnosis of earlier-stage thyroid cancers. However, the uncertainty to what extent surveillance or physician bias may be contributing to the reported incidence of thyroid cancer in WTC-dust exposed populations remains, highlighting the need to investigate a potential causal link between WTC dust exposure and thyroid cancer. Future studies are therefore indicated to investigate potential consequences of WTC dust exposure on the thyroid gland. Studies of the heavily exposed populations offer the possibility to better understand the mechanisms behind the exposure to a variety of environmental contaminants, and may provide useful insights into exposures harmful to the thyroid. These can be used in risk stratification when implementing screening in high-risk populations and may inform shared decision-making regarding the extent of thyroid cancer treatment.This study analyzed the impact of the COVID-19 pandemic on the detection of new cases of leprosy in the state of Bahia, Brazil. The periods January-September 2019 and January-September 2020 were compared. There was a 44.40% reduction in the diagnosis of leprosy when comparing the two periods (1,705 in 2019 and 948 in 2020). There was a reduction in the number of municipalities with reported cases 251 municipalities in 2019 and 202 in 2020, expressing a reduction of 24.25%. Considering only the months following the arrival of the virus (April-September), the reduction was 51.10%. An inverse correlation was observed between the number of new cases of leprosy and the cumulative number of cases of COVID-19 (Spearman's correlation coefficient = -0.840; P less then 0.001) and the number of new monthly cases of COVID-19 (Spearman's correlation coefficient = -0.817; P less then 0.001). A slight increase was also observed in the proportion of multibacillary cases in the state (70.38% in 2019 and 72.69% in 2020) as well as in the proportion of individuals with the degree of physical disability not assessed at diagnosis, whose proportion rose from 16.Sodium Monensin Antineoplastic and I chemical
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