The Upstate New York Surgical Quality Improvement Opioid Reduction Project.

Over 5 million Americans currently abuse prescription opioids. Patients' first exposure to opioids is often after surgery. Few opioid guidelines account for the challenges to health care institutions that serve wide catchment areas. We standardized postoperative opioid prescribing recommendations amongst surgical providers at our institutions and analyzed postoperative prescribing habits. The Upstate New York Surgical Quality Improvement (UNYSQI) collaborative met with surgical champions from 16 hospitals to standardize opioid prescribing for 21 surgical procedures. The guidelines were distributed to all surgical care providers at participating institutions. 581,465 pills were dispensed for 12,672 surgeries (average of 45.9 pills per procedure) before implementation. Post-implementation, 1,097,849 pills were dispensed for 28,772 surgeries (average of 38.2 pills per surgery) with over 222,000 fewer pills being prescribed. Our project suggests opioid prescribing guidelines for institutions that serve diverse communities.

Energy-restricted interventions are effective for the remission of newly diagnosed type 2 diabetes: A systematic review of the evidence base.

BACKGROUND: Type 2 diabetes (T2D) is a chronic, progressive disease. Caloric restriction and subsequent weight loss have been associated with both improvements and, in some cases, remission of T2D. AIM: To systematically review the safety and effectiveness of calorie-restricted diets on weight change and the remission of T2D. METHODS: Electronic databases were searched. Intervention trials including a calorie restriction, published between 2010 and 2020, evaluating the remission of T2D (HbA1c <6.5% without diabetes medication) were selected. Risk of bias was assessed. RESULTS: Eight trials met inclusion criteria including four randomized controlled and four single-arm trials. Three controlled trials found greater remission in the calorie-restricted arm (p < 0.05). A recent diagnosis of diabetes was associated with higher remission rates (75%-80%) with an inverse association between duration of diabetes and rate of remission (r = -0.94). A higher level of remission was observed with greater calorie restriction in non-new diagnosis studies. Greater weight loss was associated with increasing rates of remission (r = 0.83). No reported adverse events led to withdrawal from trials. There was great heterogeneity in study design. CONCLUSION: Remission rate of T2D achieved through calorie restriction is high and similar to that reported in the bariatric surgery literature. Remission should be the aim at diagnosis and calorie restriction could be used to achieve this. The target weight loss should be >10% body weight in people with obesity. More research is needed into the optimum level of calorie restriction and the support required for long-term remission. National guidelines should be updated to reflect recent evidence.

Isolated brachioradialis metastasis of gastric adenocarcinoma after R0 resection.

BACKGROUND: Gastric cancer is the fifth most common cancer worldwide, with an incidence of 6.72 per 100,000 people. Thirty-two percent of gastric cancer patients will live 5 years after diagnosis. Single-site metastasis is noted in 26% of patients with gastric cancer, most commonly in the liver (48%), peritoneum (32%), lung (15%), and bone (12%). Here, a case is presented in which a single skeletal muscle metastasis appeared after appropriate resection and treatment. CASE PRESENTATION: A 63-year-old man underwent neoadjuvant chemotherapy and a multivisceral en bloc R0 resection. Final pathology showed no evidence of lymph node metastasis with 31 negative lymph nodes. Four months postoperatively, the patient was found to have a rapidly growing biopsy-proven extremity soft tissue gastric metastasis within the brachioradialis muscle. He subsequently underwent metastasectomy and immunotherapy. CONCLUSION: This case is a rare example of an isolated extremity metastasis of gastric adenocarcinoma in the setting of an R0 resection of the primary tumor and negative nodal disease on final pathology, suggestive of hematogenous spread. We review the biology, workup, and management of gastric cancer and highlight new advancements in the treatment of this aggressive cancer.

Anal Cancer.

Anal cancer is a rare cancer, comprising less than 5% of gastrointestinal tract malignancies. Diagnosis of anal canal cancer can be difficult given that presenting symptoms are similar to those of benign anorectal diseases. General surgeons who encounter suspected anal canal cancer need to have a good understanding of the anatomy of the anal canal, high index of suspicion for malignancy, and low threshold to biopsy lesions when indicated. This article discusses the most commonly encountered anal canal tumors, the evaluation of these tumors, and their management. The foundation for successful therapy includes timely diagnosis, accurate staging, and routine surveillance.

Multiple roles of Adenomatous Polyposis Coli gene in Wnt Signalling - a Computational Model.

The Adenomatous Polyposis Coli (APC) gene is a multifunctional gene that plays a major role in regulating the Wnt signalling pathway. The Wnt pathway, when activated by Wnt signalling molecules, initiates cell division. Mutation of APC disrupts the regulation and causes continuous activation of the Wnt pathway even in the absence of Wnt signals, thus causing uncontrolled cell proliferation. APC regulates the Wnt pathway by controlling the formation of the nuclear complex ß-catenin/TCF that initiates the transcription of the Wnt target genes. There are at least five mechanisms by which APC can regulate the formation of the ß-catenin/TCF complex: This paper presents a computational model for the Wnt pathway that explicitly includes the above five roles of APC in regulating ß-catenin/TCF formation. We use this computational model to perform in-silico experiments to study the effect of different functional losses of APC on the level of ß-catenin/TCF complex. The simulations also demonstrate the different outcomes that could be expected when the system is governed by different hypotheses.

In silico prediction of ErbB signal activation from receptor expression profiles through a data analytics pipeline.

The ErbB signalling pathway has been studied extensively owing to its role in normal physiology and its dysregulation in cancer. Reverse engineering by mathematical models use the reductionist approach to characterize the network components. For an emergent, system-level view of the network, we propose a data analytics pipeline that can learn from the data generated by reverse engineering and use it to re-engineer the system with an agent-based approach. Data from a kinetic model that estimates the parameters by fitting to experiments on cell lines, were encoded into rules, for the interactions of the molecular species (agents) involved in biochemical reactions. The agent model, a digital representation of the cell line system, tracks the activation of ErbB1-3 receptors on binding with ligands, resulting in their dimerization, phosphorylation, trafficking and stimulation of downstream signalling through P13-Akt and Erk pathways. The analytics pipeline has been used to mechanistically link HER expression profile to receptor dimerization and activation of downstream signalling pathways. When applied to drug studies, the efficacy of a drug can be investigated in silico. The anti-tumour activity of Pertuzumab, a monoclonal antibody that inhibits HER2 dimerization, was simulated by blocking 80% of the cellular HER2 available, to observe the effect on signal activation.

Agent-based re-engineering of ErbB signaling: a modeling pipeline for integrative systems biology.

Motivation: Experiments in systems biology are generally supported by a computational model which quantitatively estimates the parameters of the system by finding the best fit to the experiment. Mathematical models have proved to be successful in reverse engineering the system. The data generated is interpreted to understand the dynamics of the underlying phenomena. The question we have sought to answer is that - is it possible to use an agent-based approach to re-engineer a biological process, making use of the available knowledge from experimental and modelling efforts? Can the bottom-up approach benefit from the top-down exercise so as to create an integrated modelling formalism for systems biology? We propose a modelling pipeline that learns from the data given by reverse engineering, and uses it for re-engineering the system, to carry out in-silico experiments. Results: A mathematical model that quantitatively predicts co-expression of EGFR-HER2 receptors in activation and trafficking has been taken for this study. The pipeline architecture takes cues from the population model that gives the rates of biochemical reactions, to formulate knowledge-based rules for the particle model. Agent-based simulations using these rules, support the existing facts on EGFR-HER2 dynamics. We conclude that, re-engineering models, built using the results of reverse engineering, opens up the possibility of harnessing the power pack of data which now lies scattered in literature. Virtual experiments could then become more realistic when empowered with the findings of empirical cell biology and modelling studies. Availability and Implementation: Implemented on the Agent Modelling Framework developed in-house. C ++ code templates available in Supplementary material . Contact: liz.csir@gmail.com. Supplementary information: Supplementary data are available at Bioinformatics online.

A Study on the Cardiac Manifestations of Dengue.

OBJECTIVE: This study was done to study the prevalence of cardiac manifestations of dengue fever in patients presenting to our hospital and to find out the correlation of cardiac manifestations to warning signs of dengue and severe dengue. METHODS: The study was conducted at Sree Gokulam Medical College and Research Foundation, which is a tertiary care hospital, in the Department of Medicine in the month of July 2013. One hundred consecutive patients aged 13 years or more with positive dengue serology were interviewed and examined. ECG was done for all patients and selected patients underwent echo evaluation and troponin testing. The data was analyzed using statistical significance tests. RESULTS: Thirty-three patients had no warning signs, 58 patients had one warning sign or the other. Nine patients had severe dengue. The minimum pulse rate was 34/ minute. The most common cardiac abnormalities noted were rhythm abnormalities of which the commonest was sinus bradycardia, found in 32 percent. There was statistically significant correlation between cardiac manifestations and all the warning signs except persistent vomiting. Among severe dengue, fluid accumulation causing respiratory distress was found to have a significant correlation with the cardiac manifestations. CONCLUSIONS: The most common cardiac manifestations noted were transient rhythm abnormalities, of which sinus bradycardia was the commonest. There was no evidence of myocarditis in any of the patients. There was statistically significant correlation between cardiac manifestations and all the warning signs except persistent vomiting.Among severe dengue, fluid accumulation causing respiratory distress was found to have a significant correlation with the cardiac manifestations.

The Association of Vitamin D Status and Pre-operative Physical Activity in Patients with Hip or Knee Osteoarthritis.

BACKGROUND: Vitamin D is important for musculoskeletal health and may have significant implications for maintaining physical activity in elderly patients. Our goal was to investigate whether serum 25-hydroxyvitamin D (25OHD) levels are associated with pre-operative physical activity in patients who are offered elective knee or hip joint replacement surgery. METHODS: We performed a single-center, retrospective analysis of patients who had elective knee or hip replacement surgery from 2002 to 2012. To investigate the association of serum 25OHD levels with pre-operative physical activity, as assessed by the University of California, Los Angeles (UCLA) activity scale, we performed a multivariable logistic regression analysis while controlling for age, sex, race, body mass index, American Society of Anesthesiologists physical status score, and season. RESULTS: We identified 182 patients who met inclusion criteria. Mean (± standard deviation) 25OHD level and UCLA activity scale score were 29±13 ng/mL and 4±2, respectively. Patients with 25OHD levels <20 ng/mL were almost three times more likely to have UCLA activity scale scores ≤3 [adjusted odds ratio 2.78; 95% confidence interval 1.72-9.17]. Further adjusting for "type of 25OHD assay" or "type of joint surgery" did not materially change this result. CONCLUSION: In our cohort of knee or hip joint replacement surgery patients, 25OHD levels were associated with pre-operative physical activity scores. Prospective, randomized, clinical trials are needed to verify whether optimizing pre-operative vitamin D status may improve physical activity and influence clinical decision-making in knee or hip joint replacement surgery candidates.