Donn Spight

Psychiatric illness delays diagnosis of esophageal cancer

Evidence suggests that patients with psychiatric illnesses may be more likely to experience a delay in diagnosis of coexisting cancer. The association between psychiatric illness and timely diagnosis and survival in patients with esophageal cancer has not been studied. The specific aim of this retrospective cohort study was to determine the impact of coexisting psychiatric illness on time to diagnosis, disease stage and survival in patients with esophageal cancer. All patients with a diagnosis of esophageal cancer between 1989 and 2003 at the Portland Veterans Administration hospital were identified by ICD-9 code. One hundred and sixty patients were identified: 52 patients had one or more DSM-IV diagnoses, and 108 patients had no DSM-IV diagnosis. Electronic charts were reviewed beginning from the first recorded encounter for all patients and clinical and demographic data were collected. The association between psychiatric illness and time to diagnosis of esophageal cancer and survival was studied using Cox proportional hazard models. Groups were similar in age, ethnicity, body mass index, and history of tobacco and alcohol use. Psychiatric illness was associated with delayed diagnosis (median time from alarm symptoms to diagnosis 90 days vs. 35 days in patients with and without psychiatric illness, respectively, P < 0.001) and the presence of advanced disease at the time of diagnosis (37% vs. 18% of patients with and without psychiatric illness, respectively, P= 0.009). In multivariate analysis, psychiatric illness and depression were independent predictors for delayed diagnosis (hazard ratios 0.605 and 0.622, respectively, hazard ratio < 1 indicating longer time to diagnosis). Dementia was an independent risk factor for worse survival (hazard ratio 2.984). Finally, psychiatric illness was associated with a decreased likelihood of receiving surgical therapy. Psychiatric illness is a risk factor for delayed diagnosis, a diagnosis of advanced cancer, and a lower likelihood of receiving surgical therapy in patients with esophageal cancer. Dementia is associated with worse survival in these patients. These findings emphasize the importance of prompt evaluation of foregut symptoms in patients with psychiatric illness.

Granulocyte-macrophage-colony-stimulating factor-dependent peritoneal macrophage responses determine survival in experimentally induced peritonitis and sepsis in mice

Granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays a critical role in innate immunity by stimulating the differentiation of tissue macrophages via the transcription factor PU.1. Previous studies showed that GM-CSF-deficient (GM-CSF−/−) mice had susceptibility to and impaired clearance of group B streptococcal bacteria by macrophages. For these studies, we hypothesized that GM-CSF−/− mice have increased susceptibility to peritonitis caused by immune dysfunction of peritoneal macrophages. We examined the role of peritoneal macrophages in pathogen clearance, cytokine responses, and survival in a murine cecal ligation and puncture (CLP) model of peritonitis/sepsis. Surprisingly, CLP minimally affected survival in GM-CSF−/− mice while markedly reducing survival in wild-type mice. This was not explained by differences in the composition of microbial flora, rates of bacterial peritonitis, or sepsis, all of which were similar in GM-CSF−/− and wild-type mice. However, survival correlated with peritoneal and serum TNF-&agr; and IL-6 levels that were significantly lower in GM-CSF−/− than in control mice. After peritoneal LPS instillation, GM-CSF−/− mice also had improved survival and reduced TNF-&agr; and IL-6 responses. In vitro studies demonstrated reduced secretion of TNF-&agr; and IL-6 by peritoneal macrophages isolated from sham GM-CSF−/− mice as compared with macrophages from sham control mice. Peritoneal instillation of GM-CSF−/−/PU.1+ macrophages, but not GM-CSF−/−/PU.1− macrophages into GM-CSF−/− mice conferred susceptibility to death after CLP or peritoneal LPS exposure. These results demonstrate that GM-CSF-/PU.1-dependent peritoneal macrophage responses are a critical determinant of survival after experimentally induced peritonitis/sepsis or exposure to LPS and have implications for therapies to treat such infections.

Heat shock inhibition of lipopolysaccharide-mediated tumor necrosis factor expression is associated with nuclear induction of MKP-1 and inhibition of mitogen-activated protein kinase activation

Objective:Application of heat shock before an inflammatory stimulus often results in an attenuated response to that stimulus. As a result, it has become increasingly appreciated that heat shock may induce cross-tolerance to a variety of stimuli based on in vitro and in vivo models. Circulating peripheral blood monocytes are key mediators of cytokine release following endotoxin challenge. The mitogen-activated protein kinases play a key role in the transcriptional regulation of this response including expression of tumor necrosis factor. As such, counterregulatory phosphatases that target mitogen-activated protein kinase may play a role in this heat shock-mediated effect. We hypothesized that prior heat shock to monocytes would induce a phosphatase, MKP-1, that regulated mitogen-activated protein kinase activity and subsequently conferred cross-tolerance to lipopolysaccharide stimulation. Design:Experimental. Setting:University research foundation laboratory. Subjects:THP-1 human monocyte cell line. Interventions:THP-1 cells were exposed to either heat shock (43°C, 1 hr) or normothermia (37°C, 1 hr) and allowed to recover before stimulation with endotoxin (lipopolysaccharide). Measurements and Main Results:Induction of a heat shock response was determined by heat shock protein-70 expression. Tumor necrosis factor and interleukin-10 were measured by enzyme-linked immunosorbent assay to assess heat shock inhibition of lipopolysaccharide-induced gene expression. The effect of heat shock on lipopolysaccharide-mediated activation of the p38 and ERK kinases was examined by measuring phospho-specific isoforms of p38 and ERK1/2 and correlated to in vitro kinase activity. Confirmatory data were generated from experiments employing either pharmacologic inhibition or genetic deletion of MKP-1. Heat shock induced the nuclear localized phosphatase, MKP-1, that attenuated p38 and ERK kinase activity resulting in significantly diminished tumor necrosis factor expression in response to lipopolysaccharide. Conclusions:The effect of heat shock on decreasing the tumor necrosis factor response to lipopolysaccharide is conferred by induction of MKP-1, which negatively regulates p38 and ERK kinases. Modulation of phosphatase activity may be a potential strategy for attenuating acute inflammatory responses.

Risk factors for early postoperative complications after bariatric surgery

Purpose Vertical sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are currently the most common bariatric procedures. Although the safety of these operations has markedly improved, there continues to be a certain rate of complications. Such adverse events can have a significant deleterious effect on the outcome of these procedures and represent a costly burden on patients and society at large. A better understanding of these complications and their predictive factors may help ameliorate and optimize outcomes. Methods Seven hundred seventy-two consecutive patients who underwent SG or RYGB for morbid obesity between January 2011 and October 2015, in the Division of Bariatric Surgery at a tertiary institution, were included through retrospective review of the medical database. The complications were categorized and evaluated according to severity using the Clavien-Dindo classification system. Significant risk factors were evaluated by binary logistic regression to identify independent predictors and analyzed to identify their relationship with the type of complication. Results Independent predictors of severe complication after these procedures included male gender, open and revisional surgery, hypertension, and hypoalbuminemia. Hypoalbuminemia had significant associations with occurrence of deep surgical site infection and leak. Open surgery had significant associations with occurrence of superficial and deep surgical site infection and respiratory complications. Independent predictors of severe complication after laparoscopic primary RYGB included previous abdominal surgery. Previous abdominal surgery had significant associations with deep surgical site infection and leak. Conclusion Recognition and optimization of these risk factors would be valuable in operative risk prediction before bariatric surgery.

Crisis Management Simulation: Establishing a Dual Neurosurgery and Anesthesia Training Experience

Background: Simulation training has been shown to be an effective teaching tool. Learner management of an intraoperative crisis such as a major cerebrovascular bleed requires effective teamwork, communication, and implementation of key skill sets at appropriate time points. This study establishes a first of a kind simulation experience in a neurosurgery/anesthesia resident (learners) team working together to manage an intraoperative crisis. Methods: Using a cadaveric cavernous carotid injury perfusion model, 7 neurosurgery and 6 anesthesia learners, were trained on appropriate vascular injury management using an endonasal endoscopic technique. Learners were evaluated on communication skills, crisis management algorithms, and implementation of appropriate skill sets at the right time. A preanatomic and postanatomic examination and postsimulation survey was administered to neurosurgery learners. Anesthesia learners provided posttraining evaluation through a tailored realism and teaching survey. Results: Neurosurgery learners’ anatomic examination score improved from presimulation (33.89%) to postsimulation (86.11%). No significant difference between learner specialties was observed for situation awareness, decision making, communications and teamwork, or leadership evaluations. Learners reported the simulation realistic, beneficial, and highly instructive. Conclusions: Realistic, first of kind, clinical simulation scenarios were presented to a neurosurgery/anesthesia resident team who worked together to manage an intraoperative crisis. Learners were effectively trained on crisis management, the importance of communication, and how to develop algorithms for future implementation in difficult scenarios. Learners were highly satisfied with the simulation training experience and requested that it be integrated more consistently into their residency training programs.

PGY-specific benchmarks improve resident performance on Fundamentals of Laparoscopic Surgery tasks

BACKGROUND Although expert proficiency times for Fundamentals of Laparoscopic Surgery (FLS) tasks exist, these times are not always attainable for junior residents. We hypothesize that post-graduate year (PGY)-specific benchmarks will improve resident performance of FLS tasks. METHODS In 2014, PGY-specific benchmarks were developed for FLS tasks for PGY1-PGY4 general surgery residents by averaging completion times for each task from 2007 to 2013. Resident performance on each FLS task and overall performance was compared for PGY1-PGY4 residents in the 2007-2013 group and the 2014-2016 group, before and after implementation of PGY-specific benchmarks. RESULTS There was a significant improvement in FLS performance in the 2014-2016 group at the PGY1 (p = 0.01), PGY2 (p < 0.01), and PGY3 (p = 0.01) levels, but no difference at the PGY4 level (p = 0.71). CONCLUSIONS PGY-specific benchmarks may improve efficacy of laparoscopic skills training for junior residents, increasing the efficiency of skill development.