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Introduction The COVID-19 pandemic resulted in the suspension of nonemergent surgeries throughout New York. Our tertiary care children’s hospital pivoted towards a brief trial of intravenous (IV) antibiotic therapy in all patients in order to limit operating room (OR) utilization and avoid prolonged hospital stays. We describe our pandemic-based strategy for non-operative management (NOM) of appendicitis but with a limited duration of IV antibiotics. Methods We performed a retrospective study of children treated for acute appendicitis at our center from 3/31/2020 to 5/3/2020 during the peak of the New York pandemic. We compared appendicitis volume to similar months in prior years. We evaluated failure of NOM, length of stay, and compared characteristics of children we successfully treated with our expanded NOM protocol to previously published inclusion criteria for NOM. Results 45.5% of children (25/55) with acute appendicitis underwent NOM. Of the 30 who underwent surgery, 13 had complicated appendicitis while 17 had simple appendicitis. Three patients were COVID-positive, although none had respiratory symptoms. The majority of patients presenting with acute appendicitis (78.2%) did not meet previously published criteria for NOM. Conclusions We treated a similar volume of children with acute appendicitis during the pandemic compared to prior years. We applied non-operative management to nearly half our patients, even as we expanded inclusion criteria for NOM to reduce OR utilization, but limited the duration of the antibiotic trial to avoid prolonged hospital stays. Type of study Retrospective study. Level of evidence IV.

Background: The development of beta-site amyloid-beta precursor protein cleaving enzyme (BACE) 1 inhibitors for the treatment of Alzheimer’s disease requires optimization of inhibitor potency, selectivity, and brain penetration. Moreover, there is a need for low-dose compounds since liver toxicity was found with some BACE inhibitors. Objective: To determine whether the high in vitro potency and robust pharmacodynamic effect of the BACE inhibitor LY3202626 observed in nonclinical species translated to humans. Methods: The effect of LY3202626 versus vehicle on amyloid-β (Aβ) levels was evaluated in a series of in vitro assays, as well as in in vivo and multi-part clinical pharmacology studies. Aβ levels were measured using analytical biochemistry assays in brain, plasma, and cerebrospinal fluid (CSF) of mice, dogs and humans. Nonclinical data were analyzed using an ANOVA followed by Tukey’s post hoc test and clinical data used summary statistics. Results: LY3202626 exhibited significant human BACE1 inhibition, with an IC50 of 0.615±0.101 nM in a fluorescence resonance energy transfer assay and an EC50 of 0.275±0.176 nM for lowering Aβ1–40 and 0.228±0.244 nM for Aβ1–42 in PDAPP neuronal cultures. In dogs, CSF Aβ1hboxx concentrations were significantly reduced by ∼80% at 9 hours following a 1.5 mg/kg dose. In humans, CSF Aβ1–42 was reduced by 73.1±7.96 % following administration of 6 mg QD. LY3202626 was found to freely cross the blood-brain barrier in dogs and humans. Conclusion: LY3202626 is a potent BACE1 inhibitor with high blood-brain barrier permeability. The favorable safety and pharmacokinetic/pharmacodynamic profile of LY3202626 supports further clinical development.

Background A longitudinal vaginal septum is a rare congenital anomaly that can cause dyspareunia, difficulty with tampon insertion, persistent vaginal bleeding, and dysmenorrhea. Various surgical techniques have been described. Case We present the case of a 14-year-old girl with obesity and diabetes mellitus with uterine didelphys and double vagina with a longitudinal vaginal septum. The patient presented with dysmenorrhea. Resection of the longitudinal vaginal septum using a GIA and EndoGIA (Medtronic, Inc, Doral Fl) stapler device was performed. Summary and Conclusion We introduce a safe and effective technique for resecting a longitudinal vaginal septum using stapler technology. This technique eliminates the potential risk of thermal injury to nearby structures from currently described methods.

During granulomatous inflammatory reactions, myeloid cells can differentiate into activated phagocytic macrophages, wound-healing macrophages, foreign body giant cells, and bone-resorbing osteoclasts. Although it is appreciated that a variety of stimuli, including cytokines, cell–matrix interactions, and challenge with foreign materials can influence myeloid cell fate, little is known of how these signals integrate during this process. In this study, we have investigated the cross talk between receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and particle phagocytosis-induced activation of human monocytes. Understanding interconnected signals is of particular importance to disorders, such as periprosthetic osteolysis, in which granulomatous inflammation is initiated by particle phagocytosis in proximity to bone and leads to inflammatory bone loss. Using cell-based osteoclastogenesis and phagocytosis assays together with expression analysis of key regulators of osteoclastogenesis, we show in this study that phagocytosis of disease-relevant particles inhibits RANKL-mediated osteoclastogenesis of human monocytes. Mechanistically, phagocytosis mediates this effect by downregulation of RANK and c-Fms, the receptors for the essential osteoclastogenic cytokines RANKL and M-CSF. RANKL pretreatment of monocytes generates preosteoclasts that are resistant to RANK downregulation and committed to osteoclast formation, even though they retain phagocytic activity. Thus, the relative timing of exposure to phagocytosable particulates and to osteoclastogenic cytokines is critically important in the determination of myeloid cell fate.

BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia and industry. Herein, we report the nonclinical and early clinical development of LY2886721, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD. LY2886721 has high selectivity against key off-target proteases, which efficiently translatesin vitroactivity into robustin vivoamyloid β lowering in nonclinical animal models. Similar potent and persistent amyloid β lowering was observed in plasma and lumbar CSF when single and multiple doses of LY2886721 were administered to healthy human subjects. Collectively, these data add support for BACE1 inhibition as an effective means of amyloid lowering and as an attractive target for potential disease modification therapy in AD.

Congenital mesoblastic nephroma (CMN) is a rare renal tumor of infancy. Here, we present a case of CMN presenting in a 29 week premature male in a twin gestation. An abdominal mass had been noted on prenatal ultrasound. He was initially treated with right radical nephrectomy. Pathology was consistent with cellular type CMN. Three months postoperatively, the patient developed pulmonary metastasis and underwent wedge resection of the right lung lesion. He subsequently underwent adjuvant chemotherapy, to which he has responded well. We discuss the presentation and management of patients with CMN and address the indications for postoperative chemotherapy.