Citations

ABSTRACT MICs of 25 Abiotrophia defectiva and 109 Granulicatella adiacens isolates were determined by broth microdilution. Using CLSI breakpoints, the susceptibilities of A. defectiva and G. adiacens isolates were, respectively, 24% and 34% to penicillin, 92% and 22% to ceftriaxone, 48% and 3% to cefepime, 72% and 87% to meropenem, 92% and 10% to cefotaxime, 100% and 97% to levofloxacin, 92% and 80% to clindamycin, and 24% and 50% to erythromycin. All isolates were susceptible to vancomycin. In the penicillin-susceptible subgroup, all A. defectiva isolates were susceptible to ceftriaxone; however, 62% of G. adiacens isolates were ceftriaxone nonsusceptible.

Significance Nucleosome assembly is regulated at multiple levels to impact distinct cellular processes. Mutations in factors involved in nucleosome assembly, such as histone chaperones and histone variants, result in genome instability and gene expression defects that, in turn, promote the development of human disease including cancer and aging. Therefore, it is important to determine how nucleosome assembly of H3.3 is regulated. Our findings demonstrate a role for O-linked N -acetylglucosamine (GlcNAc) transferase in regulating H3.3 deposition/exchange and establish the O-GlcNAc modification of HIRA as a previously unidentified mechanism regulating nucleosome assembly of H3.3 and cellular senescence.

ABSTRACTIntroduction: Apart from a case series of 100 subjects in 1996 and several small cohorts, there have been no large retrospective series of cranial nerve XII (CN XII) palsy. Methods: From 1984 to 2014, 245 cases of CN XII palsy were identified via retrospective chart review using historical and exam findings that confirmed the diagnosis. In addition to clinical characteristics, univariate and multivariate models were investigated to predict neoplastic CN XII palsy. Results: Major etiologic categories included: postoperative (29.3%), idiopathic (15.1%), primary neoplastic (14.2%), metastatic malignancy (13.0%), inflammatory (7.3%), radiation (6.1%), and traumatic (4.1%). A multivariate model revealed male gender and a personal history of cancer as predictive of neoplastic CN XII palsy. Conclusions: The most frequent etiologies and disease categories of CN XII palsy were identified, and male gender and personal history of cancer were found to be predictive of a neoplastic cause of CN XII palsy. Muscle Nerve 54: 1050–1054, 2016

In routine practice, the World Health Organization classification of systemic mastocytosis (SM) is also the de facto prognostic system; a core value is distinguishing indolent (ISM) from advanced SM (includes aggressive SM [ASM], SM with associated hematological neoplasm [SM‐AHN] and mast cell leukemia [MCL]). We sequenced 27 genes in 150 SM patients to identify mutations that could be integrated into a clinical‐molecular prognostic model for survival. Forty four patients (29%) had ISM, 25 (17%) ASM, 80 (53%) SM‐AHN and 1 (0.7%) MCL; overall KITD816V prevalence was 75%. In 87 patients, 148 non‐KIT mutations were detected; the most frequently mutated genes were TET2 (29%), ASXL1 (17%), and CBL (11%), with significantly higher mutation frequency in SM‐AHN > ASM > ISM (P < 0.0001). In advanced SM, ASXL1 and RUNX1 mutations were associated with inferior survival. In multivariate analysis, age > 60 years (HR = 2.4), hemoglobin < 10 g/dL or transfusion‐dependence (HR = 1.7), platelet count < 150 × 109/L (HR = 3.2), serum albumin < 3.5 g/dL (HR = 2.6), and ASXL1 mutation (HR = 2.3) were associated with inferior survival. A mutation‐augmented prognostic scoring system (MAPSS) based on these parameters stratified advanced SM patients into high‐, intermediate‐, and low‐risk groups with median survival of 5, 21 and 86 months, respectively (P < 0.0001). These data should optimize risk‐stratification and treatment selection for advanced SM patients. Am. J. Hematol. 91:888–893, 2016. © 2016 Wiley Periodicals, Inc.

ABSTRACT Background The clinical course of dementia with Lewy bodies patients is heterogeneous. The ability to more accurately prognosticate survival is important. Objective The objective of this study was to investigate hippocampal volume as a predictor of survival in dementia with Lewy bodies patients. Methods Survival analysis for time from onset of cognitive symptoms to death was carried out using Cox proportional hazards models. Given their age and total intracranial volume, patients were dichotomized into low/medium (0%‐66.7%) and high (66. 7%‐100%) hippocampal volume categories. The models using these categories to predict survival were adjusted for field strength, APOE ε4 status, and estimated onset age of cognitive problems. Results We investigated 167 consecutive patients with dementia with Lewy bodies. The median age at MRI was 72 years (interquartile range 67‐76), and 80% were male. The median time from estimated first cognitive symptom to death was 7.4 years (interquartile range:5.7‐10.2). Lower hippocampal volumes were significantly associated with higher risk of death (hazard ratio 1.28; 95% confidence interval 1.04‐1.58; P = .024). The predicted median survival for participants with onset of cognitive symptoms at age 68 was 10.63 years (95% confidence interval 8.66‐14.54) for APOE ε4 negative, high hippocampal volume participants; 8.89 years (95% confidence interval 7.56‐12.36) for APOE ε4 positive, high hippocampal volume participants; 8.10 years (95% confidence interval 7.34‐11.08) for APOE ε4 negative, low/medium hippocampal volume participants; and 7.38 (95% confidence interval 6.74‐9.29) years for APOE ε4 positive, low/medium hippocampal volume participants. Conclusions Among patients with clinically diagnosed dementia with Lewy bodies, those with neuroimaging evidence of hippocampal atrophy have shorter survival times. © 2016 International Parkinson and Movement Disorder Society

AbstractIntroductionDespite advances in trauma care, hemorrhage continues to be the leading cause of preventable mortality in trauma. The evidence to support its use in non‐trauma patients is limited. We aim to report our experience with prehospital blood product transfusion. We hypothesize that it is safe, appropriately utilized, and that our protocol, which was designed for trauma patients, is adaptable to fit the needs of non‐trauma patients.MethodsPatients transfused with blood products, packed red blood cells (pRBCs) or plasma, in the prehospital environment between 2002 and 2014 were included. Trauma patients were compared to non‐trauma patients using descriptive statistics.ResultsA total of 857 patients (n = 549 trauma and n = 308 non‐trauma) were transfused with pRBCs (76 %, n = 654, mean 1.6 ± 1.1 units en route), plasma (53 %, n = 455, mean 1.7 ± 0.7 unit), or both (29 %, n = 252) during ground (12 %) or air (84 %) critical care transport. Mean age was 60.8 ± 21.6 years with 60.1 % (n = 515) males. Subsequently, in‐hospital blood transfusions were performed in 80 % of patients, operations in 44 %, and endoscopy in 31 %. Five percent (n = 41) of patients did not require any of these interventions. Thirty‐day mortality rate was 18 %, and one patient (<0.01 %) had a transfusion reaction. The majority of patients were non‐trauma (n = 549, 64 %). Of the non‐trauma patients, 219 (40 %) were surgical, 193 (35 %) gastrointestinal bleeds, and 137 (25 %) medical.ConclusionBoth non‐trauma and trauma patients require blood products for life threatening hemorrhage and the majority required further interventions. Further research on the benefits of transfusion among non‐trauma patients is warranted.

ABSTRACT We describe a 16-year-old neutropenic patient from the Middle East with bloodstream infection caused by two carbapenemase-producing Escherichia coli isolates that we characterized by whole-genome sequencing. While one displayed meropenem resistance and was bla NDM positive, the other demonstrated meropenem susceptibility yet harbored bla OXA181 (which encodes a bla OXA48 -like enzyme). This report highlights the challenge of laboratory detection of bla OXA48 -like enzymes and the clinical implications of genotypic resistance detection in carbapenemase-producing Enterobacteriaceae .

Objective To investigate the risk of malignancy in patients with sarcoidosis in a population‐based cohort. Methods A cohort of Olmsted County, Minnesota, residents diagnosed with sarcoidosis between January 1, 1976 and December 31, 2013 was identified based on individual medical record review. For each sarcoidosis subject, 2 sex‐ and age‐matched comparator subjects without sarcoidosis were randomly selected. Cases and comparators were then cross‐indexed with the Mayo Clinic Cancer Registry, which collected data on every type of malignancy except for nonmelanoma skin cancer, for malignancy ascertainment. Results A total of 345 incident cases of sarcoidosis and 690 comparators were identified. There was no difference in the prevalence of malignancy at the index date between the 2 groups (4.3% among cases and 4.3% among comparators; P = 1.0). During followup, 36 patients with sarcoidosis and 91 subjects without sarcoidosis developed malignancy, with a cumulative incidence at 10 years of 3.8% and 7.1%, respectively. The difference corresponded to a hazard ratio (HR) of 0.72 (95% confidence interval [95% CI] 0.49–1.06). The cumulative incidences at 10 years for individual types of malignancy were also similar between the 2 groups, with nonsignificant HRs. However, subgroup analysis found that cases with extrathoracic involvement were at higher risk of incident hematologic malignancy compared with cases without extrathoracic involvement (HR 1.87 [95% CI 1.09–3.22]). Conclusion Risk of malignancy was similar among patients with sarcoidosis compared to nonsarcoidosis subjects. However, the risk of incident hematologic malignancy was significantly higher among patients with sarcoidosis with extrathoracic involvement compared to patients without extrathoracic disease.

One of the most controversial health decisions facing women is deciding upon the use of hormonal treatments for symptoms of menopause. This brief review focuses on the historical context of use of menopausal hormone treatments (MHT), summarizes results of major observational, primary and secondary prevention studies of MHT and cardiovascular (CV) outcomes, provides evidence for how sex steroids modulate CV function and identifies challenges for future research. As medicine enters an era of personalization of treatment options, additional research into sex differences in the aetiology of CV diseases will lead to better risk identification for CV disease in women and identify whether a woman might receive CV benefit from specific formulations and doses of MHT.