Explore the vast range of titles available.

Pancreatic cancer is a highly aggressive and lethal cancer characterized by high invasiveness, local and extensive dissemination at time of diagnosis and resistance to treatment. Few therapies have shown efficacy in the past and even standard of care therapies yield only modest improvements in the mortality of patients with advanced or metastatic disease. Efforts have been undertaken to study the pancreatic tumor microenvironment and have established its complex and immunosuppressive nature which could explain the high resistance to chemotherapy. Novel therapies targeting the tumor microenvironment with an aim to decrease this resistance, improve immune tolerance and increase the efficacy of the current treatment have shown some promising preliminary results in preclinical and clinical trials. We review the current advances in the field of immunotherapy and their effectiveness as a potential treatment strategy in the pancreatic cancer.

Timely and accurate diagnosis of influenza remains a challenge but is critical for patients who may benefit from antiviral therapy. This study determined the test characteristics of provider diagnosis of influenza, final ED electronic medical record (EMR) diagnosis of influenza, and influenza-like illness (ILI) in patients recommended to receive antiviral treatment according to Centers for Disease Control and Prevention (CDC) guidelines. In addition, we evaluated the compliance with CDC antiviral guidelines. A prospective cohort of adults presenting to a tertiary care ED with an acute respiratory illness who met CDC criteria for recommended antiviral treatment were enrolled and tested for influenza. A clinical diagnosis of influenza was assessed by asking the clinician: “Do you think this patient has influenza?” Influenza-like illness was defined according to current CDC criteria. In this cohort of 270 subjects, 42 (16%; 95% confidence interval [CI], 11%-20%) had influenza. Clinician diagnosis had a sensitivity of 36% (95% CI, 22%-52%) and specificity of 78% (95% CI, 72%-83%); EMR final ED diagnosis had a sensitivity of 26% (95% CI, 14%-42%) and specificity of 97% (95% CI, 94%-99%); ILI had a sensitivity of 31% (95% CI, 18%-47%) and specificity of 88% (95% CI, 83%-92%). Only 15 influenza-positive patients (36%) received antiviral treatment. Clinician diagnosis, final ED EMR diagnosis, and ILI have low sensitivity for diagnosing influenza, and there is overall poor compliance with CDC antiviral treatment recommendations. Improved methods of influenza diagnosis are needed to help guide management in the clinical setting.

Pouchitis is a common complication found in patients with refractory ulcerative colitis (UC) who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Failure to response to antibiotics has been noted which lead to difficult to manage entity Chronic Antibiotic-Refractory Pouchitis (CARP). Primary sclerosing cholangitis (PSC) has consistently been shown to be a risk factor, namely PSC-associated pouchitis/enteritis. Vancomycin has been explored in the treatment of PSC. We hypothesized that oral vancomycin therapy may benefit patients with PSC-associated pouchitis. The objective of this report is to describe an effective approach for management of CARP with vancomycin. A 48-year-old male with history of primary sclerosing cholangitis (PSC) and UC status post total proctocolectomy with IPAA presented with complains of worsening symptoms of his long standing diarrhea of 10 years. This is associated with abdominal pain and weight loss of 15 lbs. He is an active smoker but denies any alcohol or NSAIDs use. Patient was diagnosed with pouchitis on colonoscopy and biopsy. Past treatment included mesalamine, hydrocortisone enema, budenoside, probiotics with no relief of symptoms. Current treatment included metronidazole, ciprofloxacin and steroids for acute flare but with minimal relief. Pouchoscopy showed diffuse inflammation of pouch body. Biopsy findings confirmed chronic active enteritis. Clostridium difficile test was negative. He was started on oral vancomycin 125 mg four times a day for CARP. Patient responded well symptomatically. Repeat pouchoscopy and biopsies a year later showed mucosal healing with no active disease in pouch body and rectal cuff. Management of CARP is complicated by non-responsiveness to standard antibiotic regimen. Immunologic agents have shown efficacy against CARP suggesting role of dysregulation of immune related markers with IgG4 or immune related pouchitis. Evidence is quite variable in their results. Through our case here we report use of vancomycin to successfully treat and maintain remission in otherwise resistant chronic PSC associated pouchitis. Complete resolution of symptoms and endoscopic clearance is noted. This may point towards emerging resistance towards conventional antibiotics and or delayed identification of immune mediated pouchitis. That said a case to case basis approach is recommended and more evidence towards treatment of pouchitis with newer antibiotics including vancomycin is warranted.

Background and aimsAmpullary adenomas are treated both surgically and endoscopically, however, data comparing both techniques are lacking. We aimed to compare long-term recurrence of benign sporadic adenomas after endoscopic (EA) and surgical ampullectomy (SA).MethodsA comprehensive literature search of multiple databases (until December 29, 2020) was performed to identify studies reporting outcomes of EA or SA of benign sporadic ampullary adenomas. The outcome was recurrence rate at 1 year, 2-year, 3 year and 5 years after EA and SA.ResultsA total of 39 studies with 1753 patients (1468 EA [age 61.1 ± 4.0 years, size 16.1 ± 4.0 mm], 285 SA [mean age 61.6 ± 4.48 years, size 22.7 ± 5.4 mm]) were included in the analysis. At year 1, pooled recurrence rate of EA was 13.0% (95% confidence interval [CI] 10.5—15.9], I2 = 31%) as compared to SA 14.1% (95% CI 9.5—20.3 I2 = 15.8%) (p = 0.82). Two (12.5%, [95% CI, 8.9—17.2] vs. 14.3 [95% CI, 9.1—21.6], p = 0.63), three (13.3%, [95% CI, 7.3—21.6] vs. 12.9 [95% CI, 7.3—21.6], p = 0.94) and 5 years (15.7%, [95% CI, 7.8—29.1] vs. 17.6% [95% CI, 6.2—40.8], p = 0.85) recurrence rate were comparable after EA and SA. On meta-regression, age, size of lesion or enbloc and complete resection were not significant predictors of recurrence.ConclusionEA and SA of sporadic adenomas have similar recurrence rates at 1, 2, 3 and 5 years of follow up.

Fish scales serve as a natural dermal armor with remarkable flexibility and puncture resistance. Through studying fish scales, researchers can replicate these properties and tune them by adjusting their design parameters to create biomimetic scales. Overlapping scales, as seen in elasmoid scales, can lead to complex interactions between each scale. These interactions are able to maintain the stiffness of the fish’s structure with improved flexibility. Hence, it is important to understand these interactions in order to design biomimetic fish scales. Modeling the flexibility of fish scales, when subject to shear loading across a substrate, requires accounting for nonlinear relations. Current studies focus on characterizing these kinematic linear and nonlinear regions but fall short in modeling the kinematic phase shift. Here, we propose an approach that will predict when the linear-to-nonlinear transition will occur, allowing for more control of the overall behavior of the fish scale structure. Using a geometric analysis of the interacting scales, we can model the flexibility at the transition point where the scales start to engage in a nonlinear manner. The validity of these geometric predictions is investigated through finite element analysis. This investigation will allow for efficient optimization of scale-like designs and can be applied to various applications.

Introduction: Achalasia is primarily a neurodegenerative esophageal motility disorder of unclear etiology. It is characterized by incomplete lower esophageal sphincter (LES) relaxation with proximal esophageal body dilatation and loss of peristalsis. It is an incurable disease with chronic symptoms markedly impairing the functional status and quality of life in the patients. Pneumatic dilatation, surgical myotomy and more recently peroral endoscopic myotomy (POEM) have been shown to provide symptomatic relief in patients. Here, we report a case of complete reversal of aperistalsis after POEM in a patient with type III achalasia. Case Report: A 54 year old female presented complaining of intermittent dysphagia to solids and liquids for a year. She also complained of chest tightness, food regurgitation and unintentional weight loss of 65lbs over two years. Review of systems and examination were unremarkable. Workup prior to current presentation included barium swallow, which was normal; manometry demonstrated integrated relaxation pressure (IRP) mean of 23.8mmHg with some instances of weak peristalsis; and gastroesophageal junction (GEJ) outflow obstruction. Upper endoscopy (EGD) was unremarkable and the patient had treatment with botulinum toxin twice with no relief. Repeat studies were consistent with achalasia. The patient was deemed a candidate for POEM. Post-procedure videofluoroscopy showed marked improvement in gastric emptying and normalization of the lower esophageal sphincter (LES) pressure and complete return of peristalsis was observed on manometry. Initial Eckdart score was 5, which trended down to 4 post-POEM, and eventually 1. Three years post-POEM, the patient continues to be asymptomatic with normal videofluoroscopy. Discussion: This case describes a rare event of return of normal peristalsis after POEM for severe achalasia type III. Achalasia is a chronic condition with treatment options primarily based on symptomatic cure and focus on patient comfort and quality of life. POEM is a type of natural orifice transluminal endoscopic surgery (NOTES), which is an endoscopic alternative to surgical myotomy. A few studies have reported improvement in peristalsis after POEM, but the results are inconsistent. The exact mechanism of recovery of peristalsis is unknown; however, in this case, complete recovery of peristalsis was noted. To our knowledge, this is the first such reported case.

Introduction: Pyoderma Gangrenosum (PG) is a rare, extra-intestinal manifestation of inflammatory bowel disease (IBD). Due to its rarity, very few studies have analyzed factors associated with remission and recurrence of PG lesions. We conducted this study to determine the underlying disease characteristics and factors predicting remission of PG lesions. Methods: We conducted a retrospective cohort study of IBD patients with PG from 2010 to 2016. PG lesions were followed longitudinally for 12 months from the point of diagnosis. Details of the PG lesions including the number, size, site, treatments, qualitative change in lesions and concurrent clinical and endoscopic severity of IBD and treatments were recorded at each follow-up. A time-to-event analysis was performed to evaluate PG remission. Kaplan-Meier plots were constructed and unadjusted Cox regression analysis was performed to assess associations between baseline factors and remission. Results: Of 46 IBD (Crohn's disease [CD]=29; Ulcerative colitis [UC] = 17) patients with PG, majority were females (70%), Caucasian (80%) and mean age at PG diagnosis was 53.1± 13 years (table 1). Average IBD duration at the time of PG diagnosis was 18.6±12.5 years. PG lesions were most common in Peri-stomal region (50%) and lower extremity (46%). Median area of PG lesions was 3cm2and median number of PG lesions was 2. Intra-lesional steroids (44.4%) and systemic steroids (39.1%) were the most commonly used treatment for PG. There was a significant improvement in the lesion status, area of the lesion and number of lesions across the study period (figure 1). Overall 78.2% patients achieved remission (n=36/46) and 72.2% patients were in remission from PG at 12-month follow-up (figure 2). There was no significant difference in healing of PG lesions between CD and IBD patients (p=0.63). Of 26 patients who followed up after remission, recurrence rate was 24% patients at 6-month follow up. Majority of the patients were in clinical (43.5%) and endoscopic remission (55.3%) at PG diagnosis. Incidence of any IBD related surgery (p=0.014) and Ileostomy (0.005) prior to PG diagnosis was higher in CD as compared to UC. Conclusion: Approximately three out of four patients achieved healing of PG lesions at one year follow up period. Use of systemic steroids increased the chances of healing, whereas patients with hypertension and hyperlipidemia were less likely to achieve remission. Further prospective studies are required to substantiate these results.

Introduction: Without prompt management, acute cholangitis (AC) can be associated with significant morbidity, high risk of readmissions and economic burden. A subgroup of these patients contributes disproportionately to the amount of healthcare spending. We used national readmission database (NRD) to identify the clinical predictors of high utilizers among AC patients. Methods: We conducted a retrospective cohort study of adult patients admitted with AC from 2010-2014 and Q1-Q3 of 2015 by extracting data from NRD. First admission with a primary diagnosis of acute cholangitis (ICD-9 code: 576.1) was considered as the index admission and any admission after index admission was considered a readmission regardless of the primary diagnosis. A high utilizer was defined as a patient who had >2 readmissions within 90 days (figure-1) and was only defined in patients who were discharged between lanuary and September of each year. The temporal trends in readmission rates and associated characteristics were assessed by linear and polynomial linear regression. Multivariable logistic regression analyses were performed to assess the association between index characteristics and high utilizer rates. Results: From 52,906 index admissions for AC, the overall high utilizer rate is 4.6%. The rate of high utilizers (p=0.73) and inflation adjusted hospital charges (p=0.11) did not change significantly across the study period (table-1). On multivariate analysis (table-2), CCI 4-6 vs CCI 0-3 (OR=1.5; CI: 1.082.0), admission to metropolitan teaching vs. non-teaching hospital (OR=1.3; 1.09-1.6) and disposition as home health care vs. routine discharge (OR=1.5; CI: 1.1-1.9) were associated with high healthcare utilization. Patients with morbid obesity (OR=0.52; CI: 0.30-0.90) and those with cholelithiasis/ choledocholithiasis (OR=0.47; CI: 0.37-0.61) were less likely to be high utilizers. Conclusion: About one in twenty patients with AC are high healthcare utilizers. CCI of 4-6, admission to a metropolitan teaching hospital and disposition as home health care were associated with high health care utilization. Further studies are needed to understand the reasons and develop strategies to help reduce the costs and improve outcomes in these subgroup of patients.