Index CT-Based Scoring Systems in Operative Blunt Bowel and Mesenteric Injury Identification.

INTRODUCTION: Determining the need for surgical management of blunt bowel and mesenteric injury (BBMI) remains a clinical challenge. The Faget score and Bowel Injury Prediction Score (BIPS) have been suggested to address this issue. Their efficacy in determining the need for surgery was examined. METHODS: A retrospective review of all adult blunt trauma patients hospitalized at a level 1 trauma center between January 2009 and August 2019 who had small bowel, colon, and/or mesenteric injury was conducted. We further analyzed those who underwent preoperative computed tomography (CT) scanning at our institution. Final index CT reports were retrospectively reviewed to calculate the Faget and BIPS CT scores. All images were also independently reviewed by an attending radiologist to determine the BIPS CT score. RESULTS: During the study period, 14,897 blunt trauma patients were hospitalized, of which 91 had BBMI. Of these, 62 met inclusion criteria. Among patients previously identified as having BBMI in the registry, the retrospectively applied Faget score had a sensitivity of 39.1%, specificity of 81.2%, positive predictive value (PPV) of 85.7%, and negative predictive value (NPV) of 31.7% in identifying patients with operative BBMI. The retrospectively applied BIPS score had a sensitivity of 47.8%, specificity of 87.5%, PPV of 91.7%, and NPV of 36.8% in this cohort. When CT images were reviewed by an attending radiologist using the BIPS criteria, sensitivity was 56.5%, specificity 93.7%, PPV 96.3%, and NPV 42.8%. CONCLUSIONS: Existing BBMI scoring systems had limited sensitivity but excellent PPV in predicting the need for operative intervention for BBMI. Attending radiologist review of CT images using the BIPS scoring system demonstrated improved accuracy as opposed to retrospective application of the BIPS score to radiology reports.

Postoperative outcomes for sleeve gastrectomy patients with positive pH-defined GERD.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a possible side effect of sleeve gastrectomy (SG). However, procedure selection for patients with GERD and risk factors for morbidity after bypass surgeries is complex. For patients with a preoperative GERD diagnosis, literature related to worsening postoperative symptoms is discordant. OBJECTIVE: This study evaluated the effects of SG on patients with pre-operative GERD confirmed through pH testing. SETTING: University Hospital, United States. METHODS: This was a single-center case-series. SG patients with preoperative pH testing were compared based on DeMeester scoring. Preoperative demographics, endoscopy results, need for conversion surgery, and changes in gastrointestinal quality of life (GIQLI) scores were compared. Two-sample independent t-tests assuming unequal variances were used for statistical analysis. RESULTS: Twenty SG patients had preoperative pH testing. Nine patients were GERD positive; median DeMeester score 26.7 (22.1-31.15). Eleven patients were GERD negative, with a median DeMeester score of 9.0 (4.5-13.1). The two groups had similar median BMI, preoperative endoscopic findings and use of GERD medications. Concurrent hiatal hernia repair was performed in 22% of GERD positive vs. 36% of GERD negative patients, (p = 0.512). Two patients in the GERD positive cohort required conversion to gastric bypass (22%), while none in the GERD negative cohort did. No significant postoperative differences were noted in GIQLI, heartburn, or regurgitation symptoms. CONCLUSION: Objective pH testing may allow the differentiation of patients who would be higher risk for need for conversion to gastric bypass. For patients with mild symptoms, but negative pH testing, SG may represent a durable option.

Reduced synaptic activity and dysregulated extracellular matrix pathways in midbrain neurons from Parkinson's disease patients.

Several mutations that cause Parkinson's disease (PD) have been identified over the past decade. These account for 15-25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from the induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, show changes that are central and convergent to PD and suggest a strong involvement of the tetra-partite synapse in PD pathophysiology.

Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

Mitochondrial DNA (mtDNA), the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD) patients who had developed L-DOPA Induced Dyskinesia (LID), compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr) treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.