Mutation of BAX occurs infrequently in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas

Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHLs) consistently derive from B cells, are histologically heterogeneous, and are associated with distinct molecular pathways depending upon histology. Recently, it has been proposed that inactivating mutations of the bax death agonist may contribute to the pathogenesis of human tumors. In particular, among B-cell malignancies, BAX mutations have been detected at a certain frequency in Burkitt lymphomas. This study is aimed at defining the status of the BAX gene throughout the clinicopathologic spectrum of AIDS-NHL (n = 54), including AIDS-related Burkitt lymphoma (n = 14), AIDS-related Burkitt-like lymphoma (n = 8), AIDS-related diffuse large cell lymphoma (n = 15), AIDS-related primary central nervous system lymphoma (n = 6), and AIDS-related primary effusion lymphoma (n = 11). All 6 BAX exons and flanking sequences were subjected to mutational analysis by polymerase chain reaction-single strand conformation polymorphism followed by DNA direct sequencing of positive cases. Mutations of BAX among AIDS-NHL were restricted to a cell line of AIDS-related primary effusion lymphoma, which harbored a frameshift mutation causing the introduction of a proximal stop codon. All other AIDS-NHL displayed wild-type BAX alleles. In order to investigate whether BAX inactivation in AIDS-NHL may occur through mechanisms other than gene mutation, bax protein expression was investigated by Western blot analysis or immunohistochemistry in selected cases. All AIDS-NHL analyzed expressed normal bax proteins. Overall, this study indicates that deregulation of apoptotic control in AIDS-NHL is not caused by BAX alterations. Genes Chromosomes Cancer 27:177-182, 2000.     

The genetic basis of Turner syndrome aortopathy

Our goal is to identify the genetic underpinnings of bicuspid aortic valve and aortopathy in Turner syndrome. We performed whole exome sequencing on 188 Turner syndrome study subjects from the GenTAC registry. A gene‐based burden test, SKAT‐O, was used to evaluate the data using bicuspid aortic valve (BAV) and aortic dimension z‐scores as covariates. This revealed that TIMP3 was associated with BAV and increased aortic dimensions at exome‐wide significance. It had been previously shown that genes on chromosome Xp contribute to aortopathy when hemizygous. Our analysis of Xp genes revealed that hemizygosity for TIMP1, a functionally redundant paralogue of TIMP3, increased the odds of having BAV aortopathy compared to individuals with more than one TIMP1 copy. The combinatorial effect of a single copy of TIMP1 and TIMP3 risk alleles synergistically increased the risk for BAV aortopathy to nearly 13‐fold. TIMP1 and TIMP3 are tissue inhibitors of matrix metalloproteinases (TIMPs) which are involved in development of the aortic valve and protection from thoracic aneurysms. We propose that the combination of TIMP1 haploinsufficiency and deleterious variants in TIMP3 significantly increases the risk of BAV aortopathy in Turner syndrome, and suggest that TIMP1 hemizygosity may play a role in euploid male aortic disease.     

Evaluation of Urea-motility-indole medium for recognition and differentiation of Salmonella and Shigella species in stool cultures.

A semisolid urea-motility-indole medium designed for detection in Enterobacteriaceae of urease activity, motility, and indole production in one tube was prepared and evaluated. The formulation of the medium was similar to that of Christensen urea agar, but the agar concentration was 0.2%, and 1% tryptone was added. Results with 687 strains of Enterobacteriaceae were the same as those obtained with standard test media (98% overall agreement). The urea-motility-indole medium was also used in combination with Kligler iron agar for the recognition and differentiation of Salmonella and Shigella species from colonies picked from plating media in fecal cultures. This combination was compared with the combination of Kligler iron agar and lysine iron agar with 507 strains of non-lactose-fermenting Enterobacteriaceae. Although both combinations enabled the presumptive recognition and differentiation of Salmonella and Shigella species, an analysis of data indicated that the combination of Kligler iron agar and urea-motility-indole medium performed better than the combination of Kligler iron agar and lysine iron agar in detecting Salmonella and Shigella species.     

Proposals for person‐centred care in the COVID‐19 era. Delphi study

BackgroundIn this COVID‐19 era, we need to rethink the criteria used to measure the results of person‐centred care strategies.ObjectiveTo identify priorities, and criteria that health services can use to pursue actually the goal of achieving person‐centred care.DesignThree‐phase online qualitative study performed during May–July of 2020 using the Delphi technique.Setting and ParticipantsAn online platform was used for a consensus meeting of 114 participants, including health planning experts, health‐care institution managers, clinicians and patients.Main Outcome MeasuresCriteria and indicators for the achievement of person‐centred care.Main ResultsThe first round began with 125 proposals and 11 dimensions. After the second round, 28 ideas reached a high level of consensus among the participants. Ultimately, the workgroup agreed on 20 criteria for goals in the implementation of person‐centred care during the COVID‐19 era and 21 related indicators to measure goal achievement.DiscussionNine dimensions and 28 priorities were identified. These priorities are also in accordance with the quadruple aim approach, which emphasizes the need for care for health‐care professionals, without whom it is impossible to achieve a better quality of care.ConclusionsPerson‐centred care continues to be a key objective. However, new metrics are needed to ensure its continued development during the restoration of public health services beyond the control of COVID‐19.Patient or Public ContributionTwelve professionals and patient representatives participated voluntarily in the construction of the baseline questionnaire and in the selection of the criteria and indicators using an online platform for consensus meetings.     

Validation of low-cost models for minimal invasive surgery training of congenital diaphragmatic hernia and esophageal atresia

BackgroundMinimal invasive surgery (MIS) is increasingly used for the correction of congenital diaphragmatic hernia (CDH) and esophageal atresia (EA). It is important to master these complex procedures, preferably preclinically, to avoid complications. The aim of this study was to validate recently developed models to train these MIS procedures preclinically.MethodsTwo low cost, reproducible models (one for CDH and one for EA) were validated during several pediatric surgical conferences and training sessions (January 2017–December 2018), used in either the LaparoscopyBoxx or EoSim simulator. Participants used one or both models and completed a questionnaire regarding their opinion on realism (face validity) and didactic value (content validity), rated on a five-point-Likert scale.ResultsOf all 60 participants enrolled, 44 evaluated the EA model. All items were evaluated as significantly better than neutral, with means ranging from 3.7 to 4.1 (p < 0.001). The CDH model was evaluated by 48 participants. All items scored significantly better than neutral (means 3.5–3.9, p < 0.001), with exception of the haptics of the simulated diaphragm (mean 3.3, p = 0.054). Both models were considered a potent training tool (means 3.9).ConclusionThese readily available and low budget models are considered a valid and potent training tool by both experts and target group participants.Type of studyProspective study.Level of evidenceLevel II.     

Short-term multiorgan metabolic benefits of rapid weight loss after sleeve gastrectomy in severely obese patients

BackgroundSleeve gastrectomy (SG) has become the most prevalent bariatric-metabolic surgical approach in the United States. Its popularity among surgeons and patients is mainly due to a better safety profile and less overall morbidity, with broad benefits from a systemic and metabolic perspective.ObjectiveComprehensively describe the short-term multiorgan metabolic effects of rapid weight loss after SG.SettingAcademic hospital, United States.MethodsWe retrospectively reviewed the charts of patients that underwent SG at our institution between 2012 and 2016. We analyzed the required variables to calculate multiple risk scores, such as cardiovascular, hypertension, and diabetes risk scores. Furthermore, the renal and hepatic functions and the metabolic and hematologic profiles were assessed at 12 months of follow-up.ResultsA total of 1002 patients were included in the analysis. The percentage of excess body mass index loss was, on average, 65% at 12 months of follow-up. We observed a positive cardio-renal-hepatic improvement, demonstrated by a substantial reduction of the 10-year cardiovascular risk. We noticed an improvement of renal function, which was more significant in chronic kidney disease (stage ≥2), and a significant improvement on liver function tests (measured by decreased aspartate aminotransferase and alanine transaminase) at 12 months of follow-up. Our data also show a positive impact on decreasing the risk of developing hypertension and type 2 diabetes. There was a positive impact on the lipid profile, with the exception of low-density lipoprotein.ConclusionThere are significant short-term benefits on multiorgan metabolic parameters after rapid weight loss in severely obese patients undergoing sleeve gastrectomy.     

Left ventricular mass index and ventricular contractility improvement in patients with severe obesity following rapid weight loss after bariatric surgery

BackgroundObesity is a well-known risk factor for heart disease, resulting in a broad spectrum of cardiovascular changes. Left ventricular mass (LVM) and contractility are recognized markers of cardiac function.ObjectivesTo determine the changes of LVM and contractility after bariatric surgery (BaS).SettingUniversity hospital, United StatesMethodsTo determine the cardiac changes in ventricular mass, ventricular contractility, and left ventricular shortening fraction (LVSF), we retrospectively reviewed the 2-dimensional echocardiographic parameters of patients with obesity who underwent BaS at our institution. We compared these results before and after BaS.ResultsA total of 40 patients met the inclusion criteria. The majority were females (57.5%; n = 23), with an average age of 63.5 ± 12.1. The excess body mass index (BMI) lost at 12 months was 48.9 ± 28.9%. The percent total weight loss after BaS was 16.46 ± 9.9%. The left ventricular mass was 234.9 ± 88.1 grams before and 181.5 ± 52.7 grams after BaS (P = .002). The LVM index was 101.3 ± 38.3 g/m² before versus 86.7 ± 26.6 g/m² after BaS (P = .005). The LVSF was 31% ± 8.8% before and 36.3% ± 8.2% after BaS (P = .007). We found a good correlation between the decrease in LVM index and the BMI after BaS (P = .03).ConclusionRapid weight loss results in a decrease of the LVM index, as well as improvement in the left ventricular muscle contractility. Our results suggest that there is left ventricular remodeling and an improvement of heart dynamics following bariatric surgery. Further studies are needed to better assess these findings.