医学最新文献

Background: Vascular calcification is highly prevalent and associated with mortality in hemodialysis patients. However, extreme splanchnic arterial calcification in calciphylaxis with poor prognosis raises questions regarding the reliability of previous vascular calcification scoring methods. Therefore, this study aimed to examine the distribution characteristics of abdominal aortic branch calcification and identify a more reliable predictor of mortality in hemodialysis patients.

Methods: The cohort study included 237 hemodialysis patients. The distribution characteristics of abdominal aortic branch calcification were determined by quantifying the calcification volumes. The primary and secondary outcomes were all-cause mortality and new-onset cardiovascular events, respectively. We compared the prognostic values of abdominal aortic branch calcification and constructed a predictive nomogram model.

Results: The prevalence of abdominal vascular calcification in hemodialysis patients was 95.36%, with the highest prevalence in the abdominal aorta (88.61%) and internal iliac artery (85.65%). During a median follow-up period of 3.92 years, 137 patients died. Internal iliac artery and mesenteric artery calcification showed the greatest predictive values for mortality. Internal iliac artery calcification and serum albumin level were independently associated with mortality in hemodialysis patients (p < .001). The nomogram model constructed with internal iliac artery calcification, serum albumin level, age, and comorbid cardiovascular disease was well discriminative, calibrated, and clinically applicable for predicting 3-year survival.

Conclusion: Abdominal aortic branch calcification, particularly internal iliac artery calcification, is a preferable prognostic predictor than abdominal aorta or coronary artery calcification in hemodialysis patients.

The incidence for congenital heart block is estimated as high as 1 in 15,000 live births. Up to 90% of cases of congenital heart block, in which there is no anatomical abnormalities, are attributed to maternal systemic lupus erythematous or Sjögren's disease. 50% of these mothers are asymptomatic at time of diagnosis. The post-natal cardiac manifestations have been felt to be irreversible. In this article we present, to our knowledge, the first case of spontaneous conversion of immune mediate 3^rd degree heart block to sinus rhythm postnatally.

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the mainstay of treatment for adults with high-risk acute lymphoblastic leukemia (ALL). Due to the crucial role of measurable residual disease (MRD) before Allo-HSCT in predicting relapse and the promising anti-leukemia effect of blinatumomab, we documented a short-course, low-dose conditioning regimen incorporating blinatumomab for Allo-HSCT in three ALL patients with positive MRD. Following the administration of the blinatumomab-containing conditioning regimen, all patients attained complete remission (CR) with negative MRD status, and no severe adverse events were observed. After a 2-year follow-up, 2/3 of patients remained disease-free and attained long-term survival following transplantation. These cases indicated a short-term blinatumomab conditioning regimen may effectively prolong patient survival, improve prognosis, and offer a safe and cost-effective treatment for high-risk ALL patients with positive MRD. The addition of blinatumomab to the conditioning regimen of Allo-HSCT is feasible for high-risk ALL patients with positive MRD.

In-silico prediction of protein biophysical traits is often hindered by the limited availability of experimental data and their heterogeneity. Training on limited data can lead to overfitting and poor generalizability to sequences distant from those in the training set. Additionally, inadequate use of scarce and disparate data can introduce biases during evaluation, leading to unreliable model performances being reported. Here, we present a comprehensive study exploring various approaches for protein fitness prediction from limited data, leveraging pre-trained embeddings, repeated stratified nested cross-validation, and ensemble learning to ensure an unbiased assessment of the performances. We applied our framework to introduce NanoMelt, a predictor of nanobody thermostability trained with a dataset of 640 measurements of apparent melting temperature, obtained by integrating data from the literature with 129 new measurements from this study. We find that an ensemble model stacking multiple regression using diverse sequence embeddings achieves state-of-the-art accuracy in predicting nanobody thermostability. We further demonstrate NanoMelt's potential to streamline nanobody development by guiding the selection of highly stable nanobodies. We make the curated dataset of nanobody thermostability freely available and NanoMelt accessible as a downloadable software and webserver.

Background: Patients with end-stage kidney disease undergoing chronic hemodialysis (HD) have an unparalleled risk of vascular calcification (VC) and high alkaline phosphatase (Alk-P) levels. However, whether VC contributed to the cardiovascular risk modified by serum Alk-P levels was not addressed in the population.

Methods: A retrospective cohort study was conducted on chronic HD patients, between October 1 and December 31, 2018, with aortic arch calcification (AoAC) scores and serum Alk-P levels. Patients were categorized into four groups: non-to-mild AoAC/low Alk-P, non-to-mild AoAC/high Alk-P, moderate-to-severe AoAC/low Alk-P, and moderate-to-severe AoAC/high Alk-P. The Cox proportional hazard model and Kaplan-Meier analysis were used to evaluate the risks of major adverse cardiovascular effects (MACEs) and cardiovascular and all-cause mortality after multivariate adjustment.

Results: Among 376 chronic HD patients recruited, 125 (33%) had non-to-mild AoAC/low Alk-P, 76 (20%) had non-to-mild AoAC/high Alk-P, 89 (24%) had moderate-to-severe AoAC/low Alk-P, and 86 (23%) had moderate-to-severe AoAC/high Alk-P. After 3 years of follow-up, patients with coexisting moderate-to-severe AoAC and high Alk-P had a higher risk of MACEs (aHR 1.76; 95% CI 1.06-2.92), and cardiovascular (aHR 2.49; 95% CI 1.21-5.11) and all-cause mortality (aHR 2.67; 95% CI 1.39-5.13) compared to those with non-to-mild AoAC/low Alk-P even after adjustments for significant clinical variables.

Conclusions: In chronic HD patients, moderate to severe AoAC co-existed with high Alk-P levels and enhanced the risk of MACEs and cardiovascular and all-cause mortality. Interventions to attenuate these risk factors simultaneously should be emphasized in this population.

Balance issues have been reported to be common among females with overweight or obesity with associated fall risks. Despite the increasing reports of the negative impacts of obesity on balance and cognition, there is a scarcity of research aimed at evaluating effective interventions. To examine the effects of rebound exercises on cognition and balance among females with overweight and obesity. This Quasi-experimental study used the purposive sampling method to recruit 20 female students (aged 17-35 years) with overweight and obese at the Evangel University Akaeze, Ebonyi State Nigeria. Rebound exercise intervention was administered to all participants at the gym for 30 minutes in each session, three times a week for six weeks, while their cognitive performances, stationary balance, and dynamic balance were measured pre-and post-trial using Trail Marking Test Apparatuses, Unilateral Pedal Tests, and Meter Backward Walk Test respectively. There was a significant (p < 0.001) difference in the participants' cognition values across weeks 1, 3, and 6 with a progressive improvement over time. There was also a significant (p < 0.05) difference in the participants' static and dynamic balance values across weeks 1, 3, and 6 with a progressive improvement in balance performance over time. Rebound exercise significantly improved the cognition and balance of females with overweight or obese. This finding suggests a promising intervention to improve balance and cognitive-related problems in this population. Registered retrospectively in the Pan African Clinical Trial Registry, identification number for the registry is PACTR202405746557031. Dated 2 May 2024.

To understand whether there was an association between very young oocyte donors and adverse outcomes, this was a single centre retrospective study (Lister Fertility Clinic, London) examining data collected between 1st January 2010 and 31st December 2021. A total of 1,182 oocyte donors were included in the final analysis. Data was categorised by donor age in years; ≤22, 23-25, 26-28, 29-31, 32-34. Statistical analysis was performed using SPSS. Donors aged ≤22 years showed increased live birth rates (LBR) in fresh In Vitro Fertilisation (IVF) cycles when compared to donors aged 26-28 (p < 0.0136), 29-31 (p < 0.0044), and 32-34 (p < 0.0003) years, respectively. There was also an increased positive pregnancy rate in fresh IVF cycles for donor oocytes ≤22 years when compared to all other groups. The LBR and positive pregnancy rates decreased with increasing oocyte age with fresh IVF cycles. There was no significant difference in the LBR with frozen IVF cycles compared to fresh IVF cycles. Our data showed that very young oocyte donors are in fact associated with improved IVF outcomes, especially in fresh IVF cycles.

Dietary fiber interventions to modulate the gut microbiota have largely relied on isolated fibers or specific fiber sources. We hypothesized that fibers systematically blended could promote more health-related bacterial groups. Initially, pooled in vitro fecal fermentations were used to design dietary fiber mixtures to support complementary microbial groups related to health. Then, microbial responses were compared for the designed mixtures versus their single fiber components in vitro using fecal samples from a separate cohort of 10 healthy adults. The designed fiber mixtures outperformed individual fibers in supporting bacterial taxa across donors resulting in superior alpha diversity and unexpected higher SCFA production. Moreover, unique shifts in community structure and specific taxa were observed for fiber mixtures that were not observed for single fibers, suggesting a synergistic effect when certain fibers are put together. Fiber mixture responses were remarkably more consistent than individual fibers across donors in promoting several taxa, especially butyrate producers from the Clostridium cluster XIVa. This is the first demonstration of synergistic fiber interactions for superior support of a diverse group of important beneficial microbes consistent across people, and unexpectedly high SCFA production. Overall, harnessing the synergistic potential of designed fiber mixtures represents a promising and more efficacious avenue for future prebiotic development.

Metagenomic sequencing deepened our knowledge about the role of the intestinal microbiota in human health, and several studies with various methodologies explored its dynamics during antibiotic treatments. We compared the impact of four widely used antibiotics on the gut bacterial diversity. We used plasma and fecal samples collected during and after treatment from healthy volunteers assigned to a 5-day treatment either by ceftriaxone (1 g every 24 h through IV route), ceftazidime/avibactam (2 g/500 mg every 8 h through IV route), piperacillin/tazobactam (1 g/500 mg every 8 h through IV route) or moxifloxacin (400 mg every 24 h through oral route). Antibiotic concentrations were measured in plasma and feces, and bacterial diversity was assessed by the Shannon index from 16S rRNA gene profiling. The relationship between the evolutions of antibiotic fecal exposure and bacterial diversity was modeled using non-linear mixed effects models. We compared the impact of antibiotics on gut microbiota diversity by simulation, using various reconstructed pharmacodynamic indices. Piperacillin/tazobactam was characterized by the highest impact in terms of intensity of perturbation (maximal [IQR] loss of diversity of 27.3% [1.9; 40.0]), while moxifloxacin had the longest duration of perturbation, with a time to return to 95% of baseline value after the last administration of 13.2 d [8.3; 19.1]. Overall, moxifloxacin exhibited the highest global impact, followed by piperacillin/tazobactam, ceftazidime/avibactam and ceftriaxone. Their AUC between day 0 and day 42 of the change of diversity indices from day 0 were, respectively, -13.2 Shannon unit.day [-20.4; -7.9], -10.9 Shannon unit.day [-20.4; -0.6] and -10.1 Shannon unit.day [-18.3; -4.6]. We conclude that antibiotics alter the intestinal diversity to varying degrees, both within and between antibiotics families. Such studies are needed to help antibiotic stewardship in using the antibiotics with the lowest impact on the intestinal microbiota.