Atlantic Health System

About: Atlantic Health System is a healthcare organization based out in Morristown, New Jersey, United States. It is known for research contribution in the topics: Health care & Medicine. The organization has 277 authors who have published 299 publications receiving 6594 citations.

Risk Markers for Significant Bleeding and Thrombosis in Pediatric Acute Promyelocytic Leukemia; Report From the Children's Oncology Group Study AAML0631.

Abstract: Acute promyelocytic leukemia (APL) is characterized by a heightened risk of coagulopathy with significant morbidity and mortality. Here we report our evaluation of presenting white blood cell (WBC) and the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scoring system as markers for early death and nonlethal coagulopathy in pediatric APL. We evaluated 79 pediatric patients treated on a Children's Oncology Group phase III clinical trial. There were 4 early deaths and 13 nonlethal, clinically significant (grade III to IV) coagulopathy events during induction. Elevated presenting WBC was significantly associated with early death but not with both lethal and nonlethal coagulopathy events. An ISTH DIC score of ≥5 (the original ISTH criteria for overt DIC) was not associated with either early deaths or coagulopathy events. An ISTH DIC score threshold of 6, however, was significantly associated with early death (12% score ≥6 vs. 0% score <6) and with both lethal and nonlethal coagulopathy events (35% score ≥6 vs. 11% score <6). In pediatric APL patients, the presenting WBC is a marker for risk of early death. Although the ISTH score using a cutoff of ≥6 showed improved correlation with adverse coagulation events during induction, the sensitivity was only 70.6% (95% confidence interval, 44.0%-89.7%) and the specificity was 64.5% (95% confidence interval, 51.3%-76.3%). Thus, there is a strong need to identify other biomarkers that can predict APL-associated coagulopathy.

Reducing Hospital-Acquired Infections Among the Neurologically Critically Ill

Abstract: Hospital-acquired infections (HAIs) result in excess morbidity, mortality, and resource consumption. Immobilized, ventilator-dependent ICU patients are at the highest risk of HAI. Despite broad implementation of relevant bundles, HAI incidence in our neuro ICU remained high, particularly catheter-associated urinary tract infections (CAUTIs) and ventilator-associated events (VAEs). We reviewed the administrative data and nosocomial infection markers (NIMs) for all neurology and cranial neurosurgery patients admitted to our neuro ICU between January 2011 and May 2014, identified and implemented interventions, and measured effects using National Healthcare Safety Network (NHSN)-defined CAUTIs and VAEs. Interventions included (1) reviewing Foley catheter use, including indications and alternatives, and instituting daily rounds, continuously questioning the ongoing need for a catheter; (2) re-educating neuro ICU personnel in insertion and maintenance technique, introducing a new kit that simplified and standardized sterile insertion; and (3) placing a mobile CT in the neuro ICU since our patients required repeated transports for brain imaging and since we found correlations between frequencies of these transports, and both respiratory and urinary NIMS. VAEs decreased 48 %, Foley use decreased 46 %, CAUTIs decreased from 11/1000 catheter days to 6.2. Overall complication rate decreased 55 %, ICU length of stay 1.5 days, and risk-adjusted mortality 11 %. Combining a multidisciplinary approach with rigorous analysis of objective data, we decreased total HAIs by 53 % over 18 months. Key drivers were decreased urinary catheter use and decreased patient transport from the ICU for imaging.

Diffuse midline gliomas with subclonal H3F3A K27M mutation and mosaic H3.3 K27M mutant protein expression

Abstract: mutant protein, and discuss the implications with regard to classification and grading. The first patient is a 30-year-old woman who presented with headaches and symptoms of increased intracranial pressure. Imaging demonstrated a heterogeneously enhancing mass centered in the right thalamus (Fig. 1a and Supplemental Fig. 1), and subtotal resection was performed. Sections demonstrated a highly cellular infiltrative astrocytic neoplasm with WHO grade IV histologic features including frequent mitoses, marked nuclear pleomorphism, palisading necrosis, and microvascular proliferation (Fig. 1c and Supplemental Fig. 2a, b). The tumor was negative for IDH1 R132H mutant protein immunostaining and showed somatic loss of ATRX expression diffusely in all tumor nuclei (Supplemental Fig. 2c). Immunohistochemistry for histone H3 K27M mutant protein revealed a mosaic staining pattern with expression seen in some but not all tumor cells (Fig. 1e and Supplemental Fig. 2d). While the majority of tumor cells lacked H3 K27M mutant protein expression, there were scattered large groups, small clusters, and admixed single cells that were positive. Immunohistochemistry for trimethylation of lysine-27 of histone H3 (H3K27me3) revealed an Diffuse midline gliomas are aggressive tumors centered in midline structures of the brain that most commonly occur in children and young adults [6]. They are genetically defined by the presence of K27M mutation in either the H3F3A or HIST1H3B genes, which encode the histone H3 variants H3.3 and H3.1, respectively [1]. Given their poor prognosis, the 2016 WHO Classification includes “Diffuse midline glioma, H3 K27M-mutant” as a WHO grade IV entity, even in cases where only lower-grade histologic features are present [4]. In all cases reported to date, H3 K27M mutation has been a clonal alteration in all regions of tumors assessed by sequencing, and immunostaining with antibodies against H3 K27M mutant protein has revealed uniform expression in all tumor cells [2, 5, 6]. Thus, it has been hypothesized that H3 K27M mutation is the earliest or initiating genetic alteration during gliomagenesis in these tumors. Here we describe two cases of diffuse midline glioma with subclonal H3F3A K27M mutation and mosaic expression of H3.3 K27M

Evidence of a novel mechanism for partial γ-secretase inhibition induced paradoxical increase in secreted amyloid β protein.

Abstract: BACE1 (β-secretase) and α-secretase cleave the Alzheimer's amyloid β protein (Aβ) precursor (APP) to C-terminal fragments of 99 aa (CTFβ) and 83 aa (CTFα), respectively, which are further cleaved by γ-secretase to eventually secrete Aβ and Aα (a.k.a. P3) that terminate predominantly at residues 40 and 42. A number of γ-secretase inhibitors (GSIs), such as N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), have been developed with the goal of reducing Aβ to treat Alzheimer's disease (AD). Although most studies show that DAPT inhibits Aβ in a dose-dependent manner several studies have also detected a biphasic effect with an unexpected increase at low doses of DAPT in cell cultures, animal models and clinical trials. In this article, we confirm the increase in Aβ40 and Aβ42 in SH-SY5Y human neuroblastoma cells treated with low doses of DAPT and identify one of the mechanisms for this paradox. We studied the pathway by first demonstrating that stimulation of Aβ, a product of γ-secretase, was accompanied by a parallel increase of its substrate CTFβ, thereby demonstrating that the inhibitor was not anomalously stimulating enzyme activity at low levels. Secondly, we have demonstrated that inhibition of an Aβ degrading activity, endothelin converting enzyme (ECE), yielded more Aβ, but abolished the DAPT-induced stimulation. Finally, we have demonstrated that Aα, which is generated in the secretory pathway before endocytosis, is not subject to the DAPT-mediated stimulation. We therefore conclude that impairment of γ-secretase can paradoxically increase Aβ by transiently skirting Aβ degradation in the endosome. This study adds to the growing body of literature suggesting that preserving γ-secretase activity, rather than inhibiting it, is important for prevention of neurodegeneration.

Sexual function before and 1 year after laparoscopic sacrocolpopexy.

Abstract: Objective: This study aimed to compare sexual function before and 1 year after laparoscopic sacrocolpopexy using a porcine dermis or a polypropylene mesh material. Methods: This was a secondary analysis of sexual function measured before and 1 year after laparoscopic sacrocolpopexy in a group of 81 sexually active women participating in a randomized controlled trial comparing porcine dermis and polypropylene mesh. Sexual function was assessed using the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Responses to individual questions from the physical domain of the PISQ-12 were also analyzed. Additional information included the type of mesh material used and whether a concomitant suburethral sling or perineorrhaphy was performed. Results: There was a significant postoperative improvement in total PISQ-12 scores for the entire cohort (33.2 vs 38.3, P G 0.01). Similarly, PISQ-12 scores were significantly improved in both groups (33.2 preoperative vs 37.4 one year postoperative in the porcine dermis, P G 0.01 and 33.2 vs 39.2 in the polypropylene mesh, P G 0.01). There were no differences between the 2 graft material groups. Preoperatively, 63.0% (48/76) of women reported avoiding sexual intercourse because of bulging in vagina (PISQ12-question #8), at 1 year postoperatively only 4% (3/76) had a positive response (P G 0.01). We observed a significant decrease in the number of women who reported pain during intercourse at 12 months as evidenced by the responses to the PISQ12-question #5, 47.4% (36/76) versus 26.3% (20/76) (P G 0.01). The addition of a suburethral sling or a perineorrhaphy did not negatively impact sexual function at 1 year. Conclusions: Laparoscopic sacrocolpopexy had a positive impact on sexual function at 1 year regardless of whether a porcine dermis or a polypropylene mesh material was used.