Cramerlundberg5594
The biology of CNS remyelination has attracted considerable interest in recent years because of its translational potential to yield regenerative therapies for the treatment of chronic and progressive demyelinating diseases such as multiple sclerosis (MS). Critical to devising myelin regenerative therapies is a detailed understanding of how remyelination occurs. The accepted dogma, based on animal studies, has been that the myelin sheaths of remyelination are made by oligodendrocytes newly generated from adult oligodendrocyte progenitor cells in a classical regenerative process of progenitor migration, proliferation and differentiation. However, recent human and a growing number of animal studies have revealed a second mode of remyelination in which mature oligodendrocytes surviving within an area of demyelination are able to regenerate new myelin sheaths. This discovery, while opening up new opportunities for therapeutic remyelination, has also raised the question of whether there are fundamental differences in myelin regeneration between humans and some of the species in which experimental remyelination studies are conducted. Here we review how this second mode of remyelination can be integrated into a wider and revised framework for understanding remyelination in which apparent species differences can be reconciled but that also raises important questions for future research.
This study compared the epidemiology of carbapenem-resistant (CRKP) and carbapenem-sensitive (CSKP) K. pneumoniae bloodstream infections (BSIs), and assessed risk factors for 28-day mortality of patients with K. pneumoniae BSIs.
A retrospective cohort study was conducted in a 2000-bed tertiary teaching hospital of Beijing between Jan 1st 2013 to Dec 31st, 2019. All patients with K. pneumoniae BSI were identified through the Hospital Information System. The endpoints included incidence rate, mortality and risk factors for mortality of patients with K. pneumoniae BSIs.
496 patients with K. pneumoniae BSIs were included in the analysis, with 108 CRKP BSIs. The incidence rate of K. pneumoniae BSI was 10.6 (CI 9.7, 11.6) per 100 000 patient-days, with the rate for CRKP BSI was 2.3 (95% CI 1.9, 2.8). The 28-day mortality was 38.0% for CRKP BSI and 8.8% for CSKP BSI, respectively. Logistic analysis showed, higher Charlson Comorbidity Index score (OR = 1.26, 95%CI 1.12-1.43, p < 0.001), respiratory failure (ck), and healthcare factors (mechanical ventilation and CRKP infection) were independently associated with 28-day mortality. Understanding these risks helps better establishment of infection control strategies.
The COVID-19 pandemic necessitated a rapid shift to remote instruction. This may have caused particular challenges for students with disabilities.
We aimed to describe the availability of remote instruction and counseling resources on the disability/accessibility websites of colleges and universities in the greater New York City area. At the time this study was conducted, this region was the global COVID-19 epicenter.
All colleges/universities in the New York City metropolitan area were identified using Petersen's online search guide. Descriptive information (institution's name, size, and location) was recorded. The disability/accessibility pages of websites were located and examined for remote instructional resources for both educators and for students, a way to make an appointment with the counseling center (phone number and/or email address), and a link to the counseling center. Descriptive statistics were recorded (percentages of small, medium, large size institutions, mean, median, range and standacessibility in higher education. Doing so is all the more necessary given the challenges wrought by the COVID-19 pandemic, challenges which are likely to continue for years to come.Recommendations from international guidelines on optimal thromboprophylaxis after mitral repair are controversial and based on underpowered observational studies. This study aimed to evaluate the prophylactic use of warfarin after isolated mitral valve repair (MVr). Selleck Polyinosinic acid-polycytidylic acid A PubMed, EMBASE and Scopus search for studies in English on postoperative thromboprophylaxis for isolated MVr published to February 2020 was performed. The analysis excluded all studies with combined operations, mitral valve replacement and preoperative or postoperative atrial fibrillation. Clinical endpoints that were studied were thromboembolic events, bleeding complications and mortality. Random effects meta-analyses of the effect of postoperative warfarin use as compared with no warfarin use across all clinical endpoints was conducted. Warfarin use did not confer benefit in terms of thromboembolic prophylaxis after isolated MVr in patients without atrial fibrillation (OR, 0.97; 95% CI, 0.72-1.31). At the same time, it did not increase the risk of bleeding complications (OR, 1.10; 95% CI, 0.53-2.30) or affect overall survival during the follow-up period of the included studies (OR, 1.06; 95% CI, 0.28-4.05). To conclude, warfarin use is not necessary for patients after isolated MVr who remain in sinus rhythm. Recommendations from international guidelines may need to be revisited for this group of patients.
Ischaemic mitral regurgitation (IMR) is associated with an increase in both mortality and congestive heart failure in patients undergoing coronary artery bypass grafting (CABG). Intervention for moderate to severe IMR involves either valve repair or replacement. The ideal option is yet to be fully defined with relatively poor long-term survival being noted in the literature.
A retrospective observational study was conducted to review the outcomes of patients undergoing CABG in combination with either mitral valve repair (MVr) or mitral valve replacement (MVR) for concurrent coronary artery disease with moderate to severe IMR at The Prince Charles Hospital in Brisbane between the years 2002 to2015.
One hundred and five (105) patients were included, 81 patients (77%) undergoing CABG and MVr and 24 patients (23%) undergoing CABG and MVR. There was no difference in 30-day mortality between the two groups (1% in MVr and 0% in MVR, p=0.589), however patients in the MVr group were significantly more likely, in univariate and multivariate analysis, to develop at least moderate MR (40% v. 8%, p=0.006). The 5-year survival was 87% and 55% at 10 years.
In patients undergoing CABG and mitral valve intervention for IMR, long-term mortality remains high. There was no difference in short- or long-term mortality between repair and replacement although recurrence of at least moderate mitral regurgitation was significantly higher with mitral valve repair.
In patients undergoing CABG and mitral valve intervention for IMR, long-term mortality remains high. There was no difference in short- or long-term mortality between repair and replacement although recurrence of at least moderate mitral regurgitation was significantly higher with mitral valve repair.
Spontaneous pregnancy loss affects 10-15% of couples, with 1-2% suffering recurrent pregnancy loss and 50% of miscarriages remaining unexplained. Male genomic integrity is essential for healthy offspring, meaning sperm DNA quality may be important in maintaining a pregnancy. Does sperm DNA fragmentation measured by alkaline Comet assay act as a biomarker for early pregnancy loss?
Sperm DNA fragmentation was measured by alkaline Comet test in 76 fertile donors and 217 men whose partners had recently experienced miscarriage. Couples were divided into five groups for analysis one miscarriage after spontaneous conception; two or more miscarriages after spontaneous conception; one miscarriage after fertility treatment; two or more miscarriages after fertility treatment and biochemical pregnancy.
Receiver operator characteristic curve analysis was used to determine ability of the average Comet score (ACS), low Comet score (LCS) and high Comet score (HCS) to diagnose miscarriage and develop clinical thresholds comparing men whose partners have miscarried with men with recently proven fertility. Male partners of women who had miscarried had higher sperm DNA damage (ACS 33.32 ± 0.57%) than fertile men (ACS 14.87 ± 0.66%; P < 0.001). Average Comet score, HCS and LCS all have promise as being highly predictive of sporadic and recurrent miscarriage using clinical thresholds from comparisons with fertile men's spermatozoa receiver operating characteristic curve AUC for ACS ≥26%, 0.965; LCS ≤70%, 0.969; HCS ≥2%, 0.883; P <0.0001.
Sperm DNA damage measured by the alkaline Comet has promise as a robust biomarker for sporadic and recurrent miscarriage after spontaneous or assisted conception, and may provide novel diagnoses and guidance for future fertility pathways.
Sperm DNA damage measured by the alkaline Comet has promise as a robust biomarker for sporadic and recurrent miscarriage after spontaneous or assisted conception, and may provide novel diagnoses and guidance for future fertility pathways.
Despite recent advances, patients with pancreaticobiliary cancers have a poor prognosis. We previously demonstrated the efficacy of endoscopic ultrasound (EUS) guided acquisition of portal vein (PV) blood for enumeration of circulating tumor cells (CTCs). The aim of this study was to assess PV-CTCs as potential biomarkers for the assessment of progression-free (PFS) and overall survival (OS) in patients with pancreaticobiliary cancers.
17 patients with biopsy-proven pancreaticobiliary malignancy were enrolled. CTCs were enumerated from both peripheral and PV blood. All patients were followed until death. PFS and OS were evaluated with the log-rank test and summarized with the use of Kaplan-Meier methods. Unadjusted and adjusted Cox-proportional hazards models were fitted to study the relationship between PV-CTCs and PFS and OS.
After 3.5 years of follow-up, all patients had expired. PV-CTCs were detected in all patients (median PV-CTCs 62.0/7.5mL (interquartile range [IQR] 17-132). The mean PFS in patients with PV-CTCs <185/7.5mL was significantly longer than patients with PV-CTCs ≥185/7.5mL (43.3 weeks vs. 12.8 weeks, log-rank p=0.002). The mean OS in patients with PV-CTCs <185/7.5mL was significantly longer than patients with PV-CTCs ≥185/7.5mL (75.8 weeks vs. 29.5 weeks, log-rank p=0.021). In an adjusted Cox-proportional hazards model, PV-CTCs were significant predictors of both PFS and OS (HR 1.004, p=0.037; HR 1.004, p=0.044 respectively).
In this pilot and feasibility study, EUS-acquired PV-CTCs predicted PFS and OS. Our findings suggest that PV-CTCs can help provide important prognostic data for both providers and patients.
In this pilot and feasibility study, EUS-acquired PV-CTCs predicted PFS and OS. Our findings suggest that PV-CTCs can help provide important prognostic data for both providers and patients.
It has been shown that sexual dysfunction (SD) is highly prevalent among patients with chronic renal failure (CRF), and starting renal replacement therapy may even increase it. However, SD is an infrequently reported problem in these treated patients.
To investigate the prevalence of SD among patients with CRF undergoing renal replacement therapy, by a meta-analysis method.
PubMed, Embase, and the Cochrane Library were systematically searched for all studies assessing sexual function in patients with CRF receiving renal replacement therapy from January 2000 to April 2020. Relative risk (RR) with 95% CIs was used for analysis to assess the risk of SD in patients with CRF receiving renal replacement therapy. The cross-sectional study quality methodology checklist was used for the cross-sectional study. The methodologic quality of the case-control and cohort studies was assessed with the Newcastle-Ottawa Scale. Data were pooled for the random-effect model. Sensitivity analyses were conducted to assess potential bias.