Assessing the Efficacy of a Novel Massive Open Online Soft Skills Course for South Asian Healthcare Professionals.

In healthcare professions, soft skills contribute to critical thinking, decision-making, and patient-centered care. While important to the delivery of high-quality medical care, soft skills are often underemphasized during healthcare training in low-and-middle-income countries. Despite South Asia's large population, the efficacy and viability of a digital soft skills curriculum for South Asian healthcare practitioners has not been studied to date. We hypothesized that a web-based, multilingual, soft skills course could aid the understanding and application of soft skills to improve healthcare practitioner knowledge, confidence, attitudes, and intent-to-change clinical practice.In September 2019 a needs assessment observing soft skills practices was conducted in several Indian states. We developed a communication-focused soft skills curriculum that comprised seven 10-minute video lectures, recorded in spoken English and Hindi. Participants consisted of any practicing healthcare professionals and trainees in select South Asian countries age 18 and over. Participant knowledge, confidence, attitudes, and intent-to-change clinical practice were evaluated using pre- and post-course tests and surveys. Statistical analyses were performed using STATA and SPSS.From July 26, 2021 to September 26, 2021, 5750 registered and attempted the course, 2628 unique participants completed the pre-test, and 1566 unique participants completed the post-test. Participants demonstrated small but statistically significant gains in confidence (𝑝<0.001), attitudes toward course topics relevance (𝑝<0.001), and intent-to-change clinical practice (𝑝<0.001). There was no statistically significant gain in knowledge. A digital soft-skills massive open online course for healthcare practitioners in South Asia could serve as a viable approach to improve the quality of soft skills training in low-to-middle income countries.

Adjuvant therapy may improve overall survival in high-risk periampullary adenocarcinomas patients - A match-pair analysis from a multi-institutional cohort study (The MIPPAP study).

BACKGROUND: The role of adjuvant therapy in resected periampullary adenocarcinomas is equivocal due to contrasting data and limited prospective trials. METHODS: The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP), included data from 8 institutions across India. Of the 1679 pancreatic resections, 736 patients with T3/T4 and/or Node positive adenocarcinomas (considered as high risk for recurrence) were included for analysis. Three (adjuvant): one (observation) matching, using T3/T4 T staging, nodal positivity and ampullary subtype was performed by using the nearest neighbour matching method. RESULTS: Of 736 patients eligible for inclusion, 621 patients were matched of which 458 patients received adjuvant therapy (AT) (predominantly gemcitabine-based) and 163 patients were observed (O). With a median follow-up of 42 months, there was a statistical difference in overall survival in favour of patients receiving AT as compared to those on observation [68.7 months vs. 61.1 months, Hazard ratio: 0.73 (95% CI: 0.54-0.97); p = 0.03]. Besides AT, presence of nodal involvement (median OS: 65.4 months vs not reached; p = 0.04) predicted for inferior OS. CONCLUSIONS: The results of the match-pair analysis suggest that adjuvant therapy improves overall survival in periampullary adenocarcinomas at high risk of recurrence with a greater benefit in T3/T4, node-positive and ampullary subtypes.

Integration of metabolites from meta-analysis with transcriptome reveals enhanced SPHK1 in PDAC with a background of pancreatitis.

BACKGROUND: Pathophysiology of transformation of inflammatory lesions in chronic pancreatitis (CP) to pancreatic ductal adenocarcinoma (PDAC) is not clear. METHODS: We conducted a systematic review, meta-analysis of circulating metabolites, integrated this data with transcriptome analysis of human pancreatic tissues and validated using immunohistochemistry. Our aim was to establish biomarker signatures for early malignant transformation in patients with underlying CP and identify therapeutic targets. RESULTS: Analysis of 19 studies revealed AUC of 0.86 (95% CI 0.81-0.91, P < 0.0001) for all the altered metabolites (n = 88). Among them, lipids showed higher differentiating efficacy between PDAC and CP; P-value (< 0.0001). Pathway enrichment analysis identified sphingomyelin metabolism (impact value-0.29, FDR of 0.45) and TCA cycle (impact value-0.18, FDR of 0.06) to be prominent pathways in differentiating PDAC from CP. Mapping circulating metabolites to corresponding genes revealed 517 altered genes. Integration of these genes with transcriptome data of CP and PDAC with a background of CP (PDAC-CP) identified three upregulated genes; PIGC, PPIB, PKM and three downregulated genes; AZGP1, EGLN1, GNMT. Comparison of CP to PDAC-CP and PDAC-CP to PDAC identified upregulation of SPHK1, a known oncogene. CONCLUSIONS: Our analysis suggests plausible role for SPHK1 in development of pancreatic adenocarcinoma in long standing CP patients. SPHK1 could be further explored as diagnostic and potential therapeutic target.

Is AVPU comparable to GCS in critical prehospital decisions? - A cross-sectional study.

BACKGROUND: Advanced Trauma Life Support field triage utilizes the Glasgow Coma Scale (GCS) to assess the level of consciousness. However, prehospital care providers in low- and middle-income countries (LMICs) often use the Alert, Verbal, Pain, and Unresponsive (AVPU) scale to assess the level of consciousness. This study aimed to determine whether prehospital AVPU categorization correlates with mortality rates in trauma victims, similarly to GCS. METHODS: In this cross-sectional study conducted between November 2015 and January 2016, we enrolled a convenience sample of prehospital trauma-related field activations. The primary outcome measure was the probability of death within 48 h for each category of AVPU. RESULTS: In a convenience sample of 4514 activations, 1606 (35.6%) met exclusion criteria, four did not have AVPU, and four did not have GCS, leaving 2900 (64.2%) trauma activations with both AVPU and GCS available for analysis. Forty-eight-hour follow-up data were available for 2184 (75.3%) activations out of these 2900. The 48-h mortality rates for each category of AVPU were 1.1% (Alert), 4.3% (Verbal), 17.9% (Pain), 53.2% (Unresponsive); and, for each GCS-based injury severity category, they were 0.9% (Mild, GCS 13-15), 8.1% (Moderate, GCS 9-12), 43.5% (Severe, GCS ≤ 8). Overall, there was a statistically significant difference in GCS for each category of AVPU (p < 0.001) except between patients responding to verbal commands and those responding to pain (p = 0.18). The discriminative ability of AVPU (AUC 79.7% (95% CI 73.4-86.1)) and GCS (AUC 81.5% (95% CI 74.8-88.2)) for death within 48-h following hospital drop-off were comparable. CONCLUSION: EMT assessments of AVPU and GCS relate to each other, and AVPU predicts mortality at 48 h. Future studies using AVPU to assess the level of consciousness in prehospital trauma protocols may simplify their global application without impacting the overall quality of care.

Non-compliance to practice guidelines still exist in the early management of acute pancreatitis: Time for reappraisal?

INTRODUCTION: Earlier national surveys on the management of acute pancreatitis (AP) had reported non-compliance to practice guidelines. In the past decade, several guidelines were revised based on new evidence. In this multicenter international survey, we aimed to evaluate the practice patterns of early management of AP and compliance to the revised treatment guidelines across different disciplines and practice environments. METHODS: A structured questionnaire was sent via email to a target population of 654 that constituted of medical and surgical gastroenterologists, physicians and general surgeons, paediatricians from academic and non-academic centres across 30 countries. Other than demographic variables, the questionnaire contained items pertaining to early management of AP, such as, assessment at admissions and within first 72 h s, details regarding analgesics, IV hydration, oral/enteral feeding and antibiotic use. RESULTS: The response rate was 46.2% and after exclusions, a total of 297 participant's responses were analysed. Majority of the participants were from Asia, followed by Europe and the Americas. 181 (60.9%) claimed to follow practice guidelines, out of which 59 (32.6%) followed more than one. On further probing, only 41.9% were actually compliant to feeding and 59.7% to antibiotic guidelines. Even though participants opted for aggressive hydration, early feeding and avoidance of prophylactic antibiotics, there were non-compliance and discrepancies in titration of fluid therapy, indications of feeding and antibiotic use. DISCUSSION: Discrepancies and non-compliance still appear to exist in the early management of AP due to lack of strong evidence. We discuss ways that could improve compliance to the existing guidelines until stronger evidence comes to the fore.

Hemosuccus Pancreaticus: A systematic approach.

BACKGROUND AND AIM: Hemosuccus pancreaticus is considered as one of the rare cause of upper gastrointestinal bleeding. Intermittent nature of bleeding and lack of standardized approach for diagnosis has resulted in significant delay in definitive management. METHODS: We retrospectively analyzed prospectively maintained data of patients with suspected hemosuccus pancreaticus between January 2010 and December 2019. RESULTS: Out of 114 patients, 87 patients were diagnosed with hemosuccus pancreaticus. Mean age was 35.7 ± 11.7 years with 89.7% men. Median duration of bleeding before diagnosis was 10 days, with 40.2%, 10.3%, and 5.7% patients had symptoms beyond 1, 6, and 12 months, respectively. Visceral artery aneurysm was noted in 62% of cases with splenic artery aneurysm (37.9%) being the common source of bleed. Rarer causes noted were superior mesenteric artery aneurysm, pancreatic adenocarcinoma, gastrointestinal stromal tumor, and post-endoscopic retrograde cholangiopancreatography (2.3% each). Santorinirrhage was seen in 3.4% patients. Endoscopic diagnosis was possible in 64.4% of patients, and angiogram localization of bleeding source was noted in 94.2%. A 56.3% of patients underwent conventional angioembolization with 95.9% success and 28.7% underwent surgery, with overall rebleeding rate of 11.5%. CONCLUSIONS: Early diagnosis of hemosuccus pancreaticus avoids prolonged suffering, multiple hospital admissions, and multiple blood transfusions. It is not uncommon in the absence of aneurysm. In cases of high suspicion, repeating the endoscopy with proper technique and proper timing increases the yield. Angioembolization remains the most preferred first line therapeutic approach in majority of cases.

Is intraoperative enteroscopy still relevant in small bowel disorders in the era of capsule endoscopy and device-assisted enteroscopy? Real-world experience from a tertiary care hospital.

BACKGROUND AND AIM: With the advent of video capsule endoscopy (VCE) and device-assisted enteroscopy (DAE), the indication of intraoperative enteroscopy (IOE) has become limited due to reported high morbidity/mortality. Most of the earlier studies on IOE were small/from pre-VCE/DAE era. We aimed to evaluate the impact of IOE in management of small bowel disorders (SBD) in post-VCE/DAE era. METHODS: Patients with SBD undergoing IOE over last 15 years were evaluated retrospectively. Overall diagnostic/therapeutic yield, incremental diagnostic yield over preoperative investigations, and adverse events were noted. We also evaluated the number of cases in which IOE changed the management or guided surgical or endoscopic therapy. Rebleeding and recurrence were evaluated in patients with available follow-up data. RESULTS: A total of 89 patients (59 male, 9-82 years) were included in the study. Overall diagnostic and therapeutic yield were 92.1% and 85.4%, respectively. Common findings of IOE were benign ulcers/strictures (30.1%), vascular lesions (26%), diverticula (15.1%), and tumors (13.7%). A total of 49.4% (44/89), 36% (32/89), and 20.2% (18/89) underwent VCE, DAE, or both, respectively, before IOE. Incremental diagnostic yield over preoperative work-up was 31.5% (28/89), and IOE changed the management in 37.1% (33/89) patients. IOE was used to guide surgery/endotherapy in 39.3% (35/89) patients. Recurrent gastrointestinal bleed occurred in 21.2% (14/66) patients. Morbidity and mortality rates were 20.2% (18/89) and 3.4% (3/89), respectively. CONCLUSIONS: Intraoperative enteroscopy remains an essential technique to evaluate SBD and can detect new and additional lesions even after extensive preoperative evaluation. IOE is useful in guiding therapy in preoperatively identified lesions and can change management in a substantial proportion of patients. Hence, IOE has a definitive role in post-VCE/DAE era in carefully selected patients with SBD.

Emergency medical dispatch services across Pan-Asian countries: a web-based survey.

BACKGROUND: Dispatch services (DS's) form an integral part of emergency medical service (EMS) systems. The role of a dispatcher has also evolved into a crucial link in patient care delivery, particularly in dispatcher assisted cardio-pulmonary resuscitation (DACPR) during out-of-hospital cardiac arrest (OHCA). Yet, there has been a paucity of research into the emerging area of dispatch science in Asia. This paper compares the characteristics of DS's, and state of implementation of DACPR within the Pan-Asian Resuscitation Outcomes (PAROS) network. METHODS: A cross-sectional descriptive survey addressing population characteristics, DS structures and levels of service, state of DACPR implementation (including protocols and quality improvement programs) among PAROS DS's. RESULTS: 9 DS's responded, representing a total of 23 dispatch centres from 9 countries that serve over 80 million people. Most PAROS DS's operate a tiered dispatch response, have implemented medical oversight, and tend to be staffed by dispatchers with a predominantly medical background. Almost all PAROS DS's have begun tracking key EMS indicators. 77.8% (n = 7) of PAROS DS's have introduced DACPR. Of the DS's that have rolled out DACPR, 71.4% (n = 5) provided instructions in over one language. All DS's that implemented DACPR and provided feedback to dispatchers offered feedback on missed OHCA recognition. The majority of DS's (83.3%; n = 5) that offered DACPR and provided feedback to dispatchers also implemented corrective feedback, while 66.7% (n = 4) offered positive feedback. Compression-only CPR was the standard instruction for PAROS DS's. OHCA recognition sensitivity varied widely in PAROS DS's, ranging from 32.6% (95% CI: 29.9-35.5%) to 79.2% (95% CI: 72.9-84.4%). Median time to first compression ranged from 120 s to 220 s. CONCLUSIONS: We found notable variations in characteristics and state of DACPR implementation between PAROS DS's. These findings will lay the groundwork for future DS and DACPR studies in the PAROS network.

ESWL for large pancreatic calculi: Report of over 5000 patients.

INTRODUCTION: The primary aim of this study was to evaluate efficacy, safety and short-term pain relief after ESWL for large pancreatic calculi in over 5000 patients at a single center. METHODS: This is a retrospective analysis of prospectively collected data. Patients with painful calculi >5 mm, located in the head, neck and body region in the MPD, who were not amenable for extraction by the standard procedure of endoscopic pancreatic sphincterotomy were subjected to ESWL using a third generation dual focus lithotripter. Patients were followed up at 6 months for outcome evaluation. RESULTS: A total of 5124 patients (66% males) were subjected to ESWL. Majority of stones (79.2%) were radiopaque. Single calculi were seen in 3851 (75.1%).The majority of stones were located in head region of MPD in 2824 (55.1%) patients. 4386 (85.5%) patients required 3 or less sessions for fragmentation and complete stone clearance was achieved in 3722 (72.6%). EPS was performed in 5022 (98%) while PD stenting was required in 3536 (69%) patients. Of the 4280 patients followed up for 6 months, 3529 (82.6%) patients were pain free. Another 512 (11.9%) patients had significant reduction in VAS score. In 229 (5.3%) there was no decrease in pain intensity. Minor and self-limiting complications were reported in 1153 (22.5%). DISCUSSION: Our study confirms the safety and efficacy and short-term pain relief of ESWL for large calculi in the MPD. In properly selected patients, this should be offered as the first line of therapy for all large MPD calculi not amenable to the standard techniques of stone extraction.

Plasma microRNA192 in combination with serum CA19-9 as non-invasive prognostic biomarker in periampullary carcinoma.

In this study, circulating microRNAs (miRNAs) are being investigated as non-invasive biomarkers for early diagnosis and prognosis of human cancers. Since the prognosis for pancreatobiliary subtype of periampullary carcinoma is poor, we assessed the prognostic relevance of miRNAs in combination with CA19-9 as noninvasive biomarker in periampullary carcinoma. Circulating miRNAs in plasma and serum CA19-9 were evaluated in periampullary carcinoma patients (n = 109) undergoing Whipple's pancreaticoduodenectomy and in healthy volunteers (n = 92). Tumour tissues were subjected to staging and subtyping prior to determining differentially expressed miRNAs in them by quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis involved correlation, receiver operating characteristic, logistic regression, survival analyses and Cox-proportional regression. Of the three differentially expressed circulating miRNA, miRNA192 was significantly increased both in circulation and in tumour tissue and correlated with tumour stage and aggressiveness (r = 0.96, P < 0.0001). Area under the curve of circulating miRNA192 + CA19-9 combination was 0.877 (95% confidence interval, 0.72 to 0.96) for stage III and 0.92 (95% confidence interval, 0.77 to 0.88) for tumour aggressiveness. The combination was associated with poor survival (median: 22 months, P = 0.0008) in stage III patients. Cox-proportional regression analysis revealed prognostic importance of combination of circulating miR192 and CA19-9 (HR = 1.005, P = 0.0001) in periampullary carcinoma. In conclusion, combination of circulating miRNA192 with serum CA19-9 is a better prognostic biomarker than CA19-9 alone.

Endoscopic "step-up approach" using a dedicated biflanged metal stent reduces the need for direct necrosectomy in walled-off necrosis (with videos).

BACKGROUND AND AIMS: EUS-guided drainage using plastic stents may be inadequate for treatment of walled-off necrosis (WON). Recent studies report variable outcomes even when using covered metal stents. The aim of this study was to evaluate the efficacy of a dedicated covered biflanged metal stent (BFMS) when adopting an endoscopic "step-up approach" for drainage of symptomatic WON. METHODS: We retrospectively evaluated consecutive patients with symptomatic WON who underwent EUS-guided drainage using BFMSs over a 3-year period. Reassessment was done between 48 and 72 hours for resolution. Endoscopic reinterventions were tailored in nonresponders in a stepwise manner. Step 1 encompassed declogging the blocked lumen of the BFMS. In step 2, a nasocystic tube was placed via BFMSs with intermittent irrigation. Step 3 involved direct endoscopic necrosectomy (DEN). BFMSs were removed between 4 and 8 weeks of follow-up. The main outcome measures were technical success, clinical success, adverse events, and need for DEN. RESULTS: Two hundred five WON patients underwent EUS-guided drainage using BFMSs. Technical success was achieved in 203 patients (99%). Periprocedure adverse events occurred in 8 patients (bleeding in 6, perforation in 2). Clinical success with BFMSs alone was seen in 153 patients (74.6%). Reintervention adopting the step-up approach was required in 49 patients (23.9%). Incremental success was achieved in 10 patients with step 1, 16 patients with step 2, and 19 patients with step 3. Overall clinical success was achieved in 198 patients (96.5%), with DEN required in 9.2%. Four patients failed treatment and required surgery (2) or percutaneous drainage (2). CONCLUSIONS: The endoscopic step-up approach using BFMSs was safe, effective, and yielded successful outcomes in most patients, reducing the need for DEN.

Transport of pregnant women and obstetric emergencies in India: an analysis of the '108' ambulance service system data.

BACKGROUND: The transport of pregnant women to an appropriate health facility plays a pivotal role in preventing maternal deaths. In India, state-run call-centre based ambulance systems ('108' and '102'), along with district-level Janani Express and local community-based innovations, provide transport services for pregnant women. We studied the role of '108' ambulance services in transporting pregnant women routinely and obstetric emergencies in India. METHODS: This study was an analysis of '108' ambulance call-centre data from six states for the year 2013-14. We estimated the number of expected pregnancies and obstetric complications for each state and calculated the proportions of these transported using '108'. The characteristics of the pregnant women transported, their obstetric complications, and the distance and travel-time for journeys made, are described for each state. RESULTS: The estimated proportion of pregnant women transported by '108' ambulance services ranged from 9.0 % in Chhattisgarh to 20.5 % in Himachal Pradesh. The '108' service transported an estimated 12.7 % of obstetric emergencies in Himachal Pradesh, 7.2 % in Gujarat and less than 3.5 % in other states. Women who used the service were more likely to be from rural backgrounds and from lower socio-economic strata of the population. Across states, the ambulance journeys traversed less than 10-11 km to reach 50 % of obstetric emergencies and less than 10-21 km to reach hospitals from the pick-up site. The overall time from the call to reaching the hospital was less than 2 h for 89 % to 98 % of obstetric emergencies in 5 states, although this percentage was 61 % in Himachal Pradesh. Inter-facility transfers ranged between 2.4 % -11.3 % of all '108' transports. CONCLUSION: A small proportion of pregnant women and obstetric emergencies made use of '108' services. Community-based studies are required to study knowledge and preferences, and to assess the potential for increasing or rationalising the use of '108' services.

Peroral endoscopic myotomy for achalasia cardia: Treatment analysis and follow up of over 200 consecutive patients at a single center.

BACKGROUND AND AIM: Peroral endoscopic myotomy (POEM) is a recently introduced technique for the treatment of achalasia cardia (AC). Data regarding safety and efficacy are still emerging. We report our experience of POEM emphasizing its safety, efficacy and follow-up data. METHODS: Patients with AC (220; mean age 39 years, range 9-74 years) underwent POEM from January 2013 to August 2014 for AC. Retrospective analysis of prospectively collected data was done. POEM was carried out by the standard technique of mucosal incision, submucosal tunneling, and myotomy of the esophageal and gastric muscle bundles followed by closure of the mucosal incision by hemoclips. Eckardt score, high-resolution manometry (HRM) and timed barium esophagogram (TBE) were used to evaluate the results. Post-procedure patients were followed up. RESULTS: Technical success rate of POEM was 96%. At 1 year, clinical success rate was 92%. Mean Eckardt score was 7.2 ± 1.55 prior to POEM and 1.18 ± 0.74 after POEM (P = 0.001). There was significant improvement of esophageal emptying on TBE (38.4 ± 14.0 % vs 71.5 ± 16.1 % (P = 0.001). Pre-procedure and post-procedure mean lower esophageal sphincter pressure was 37.5 ± 14.5 mmHg and 15.2 ± 6.3 mmHg, respectively. (P = 0.001) Erosive esophagitis was seen in 16% of patients who underwent POEM. There were no major adverse events. CONCLUSIONS: Study demonstrates excellent safety profile of POEM with significant relief of symptoms, reduced pressure at HRM and improved emptying at TBE. Further prospective studies are required to compare with other treatment modalities.

Epidemiology of Shortness of Breath in Prehospital Patients in Andhra Pradesh, India.

BACKGROUND: Shortness of breath is a frequent reason for patients to request prehospital emergency medical services and is a symptom of many life-threatening conditions. To date, there is limited information on the epidemiology of, and outcomes of patients seeking emergency medical services for, shortness of breath in India. OBJECTIVE: This study describes the characteristics and outcomes of patients with a chief complaint of shortness of breath transported by a public ambulance service in the state of Andhra Pradesh, India. METHODS: This prospective, observational study enrolled patients with a chief complaint of shortness of breath during twenty-eight, 12-h periods. Demographic and clinical data were collected from emergency medical technicians using a standardized questionnaire. Follow-up information was collected at 48-72 h and 30 days. RESULTS: Six hundred and fifty patients were enrolled during the study period. The majority of patients were male (63%), from rural communities (66%), and of lower socioeconomic status (78%). Prehospital interventions utilized included oxygen (76%), physician consultation (40%), i.v. placement (15%), nebulized medications (13%), cardiopulmonary resuscitation (5%), and bag-mask ventilation (4%). Mortality ratios before hospital arrival, at 48-72 h, and 30 days were 12%, 27%, and 35%, respectively. Forty-six percent of patients were confirmed to have survived to 30 days. Predictors of death before hospital arrival were symptoms of chest pain (16% vs. 12%; p < 0.05) recent symptoms of upper respiratory infection (7.5% vs. 4%; p < 0.05), history of heart disease (14% vs. 7%; p < 0.05), and prehospital hypotension, defined as systolic blood pressure <90 mm Hg (6.3% vs. 3.7%; p < 0.05). CONCLUSIONS: Among individuals seeking prehospital emergency medical services in India, the chief complaint of shortness of breath is associated with a substantial early and late mortality, which may be in part due to the underutilization of prehospital interventions.

Microsatellite instability and promoter hypermethylation in colorectal cancer in India.

Microsatellite instability (MSI) is an important factor in tumor development and is a hypermutable phenotype caused by the loss of DNA mismatch repair activity. It is important to identify tumors with microsatellite instability as the patients have a better prognosis and differ with response to chemotherapy. Limited data are available on the incidence of MSI in Indian colorectal cancers (CRCs). The objectives of this study were to identify the extent of MSI in Indian CRC patients below 50 years and to determine promoter methylation status of hMLH1 and hMSH2 in relation to MSI. A total of 450 patients were diagnosed with CRC, out of which 91 individuals were recruited as per Bethesda guidelines and were tested for instability by the NCI-recommended Bethesda panel (BAT25, BAT26, D2S123, D5S346, and D17S2720) using labeled primers. The fragments were separated and analyzed on a Beckman GeXP sequencer. Promoter methylation status was determined by restriction enzyme digestion and PCR. MSI (high and low) was seen in 48.4% (44/91) of CRC patients, out of which microsatellite instability-high (MSI-H) was detected in 13.2% (12/91) and microsatellite instability-low (MSI-L) in 35.2% (32/91) and the rest were microsatellite stable (MSS), 51.6% (47/91). Majority of the MSI-H tumors were adenocarcinomas (10/12), in the rectum (8/12), and moderately or poorly differentiated (12/12). Promoter hypermethylation was seen in 75% of the MSI-H, 56.24% of MSI-L, and only 23.4% of MSS individuals. MSI (high and low) was associated with 48.4% of CRC patients, and a significantly higher proportion of promoter hypermethylation of hMLH1 and hMSH2 genes was associated with instable tumors.

ERCP in the management of pancreatic diseases in children.

BACKGROUND: ERCP experience in pancreatic disorders in children is limited. OBJECTIVE: This study evaluated the utility and efficacy of ERCP in children with pancreatic diseases at a tertiary care referral center. PATIENTS AND SETTINGS: Consecutive patients 18 years of age and younger who underwent ERCP for pancreatic diseases from January 2010 to June 2011 were identified. Indications, findings, interventions, adverse events, and outcomes were recorded. RESULTS: A total of 221 ERCPs were performed in 172 children (102 boys, mean ± standard deviation age 13.8 ± 3.2 years, 157 therapeutic). A total of 143 children (83.1%) had chronic pancreatitis (CP), 19 (11%) had recurrent acute pancreatitis (RAP), and 10 (5.8%) had acute pancreatitis (AP). Indications included pain (153, 89.4%), pancreatic fistula (11, 6.3%), symptomatic pseudocyst (4, 2.3%), and jaundice (3, 1.7%). In chronic pancreatitis patients, findings included a dilated and irregular main pancreatic duct (92, 64.3%), pancreatic duct (PD) calculi (76, 53%), dominant PD stricture (23, 16%), PD leak (7, 4.9%), pancreas divisum (35, 24.5%), and common bile duct (CBD) stricture (3, 2%). Therapeutic procedures included major papilla sphincterotomy (93, 65%), minor papilla sphincterotomy (32, 22.3%), PD stenting (77, 53.8%), and CBD stenting (3, 2.2%). PD stones larger than 5 mm were retrieved endoscopically after 57 extracorporeal shock wave lithotripsy sessions in 50 patients (34.9%). In patients with RAP, 6 (31.5%) had complete and 1 partial pancreas divisum. All underwent minor papillotomy. In patients with AP, 4 (40%) had stenting for PD leak, 2 (20%) underwent CBD clearance for biliary pancreatitis, and 4 (40%) had transpapillary pseudocyst drainage. During 13 ± 4.7 months (range 6-22 months) of follow-up, improvement of symptoms was seen in 143 of 172 (83%) patients. Procedure-related adverse events were seen in 8 (4.7%) patients. LIMITATIONS: Retrospective study. CONCLUSION: ERCP is a safe therapeutic option for pancreatic disorders in children.

Modulation of nuclear receptor 4A1 expression improves insulin secretion in a mouse model of chronic pancreatitis.

OBJECTIVES: Diabetes secondary to chronic pancreatitis (CP) presents clinical challenges due to insulin secretory defects and associated metabolic alterations. Owing to lack of molecular understanding, no pharmacotherapies to treat insulin secretory defects have been approved to date. We aimed to delineate the molecular mechanism of ß-cell dysfunction in CP. METHODS: Transcriptomic analysis was conducted to identify endocrine specific receptor expression in mice and human CP on microarray. The identified receptor (NR4A1) was overexpressed in MIN6 cells using PEI linear transfection. RNA-Seq analysis on NovaSeq 6000 of NR4A1 overexpressed (OE) MIN6 cells was performed to identify aberrant metabolic pathways. Upstream trigger for NR4A1OE was studied by InBio Discover and cytokine exposure. Downstream effect of NR4A1OE was examined by Fura2 AM based fluorometric and imaging studies of intracellular calcium. Mice with CP were treated with IFN-γ neutralizing monoclonal antibodies to assess NR4A1 expression and insulin secretion. RESULTS: Increased expression of NR4A1 associated with decreased insulin secretion in islets (humans: controls 9 ± 0.2, CP 3.7 ± 0.2, mice: controls 8.5 ± 0.2, CP 2.1 ± 0.1 µg/L). NR4A1OE in MIN6 cells (13.2 ± 0.1) showed reduction in insulin secretion (13 ± 5 to 0.2 ± 0.1 µg/mg protein/minute, p = 0.001) and downregulation of calcium and cAMP signaling pathways. IFN-γ was identified as upstream signal for NR4A1OE in MIN6. Mice treated with IFN-γ neutralizing antibodies showed decreased NR4A1 expression 3.4 ± 0.11-fold (p = 0.03), improved insulin secretion (4.4 ± 0.2-fold, p = 0.01), associated with increased Ca2+ levels (2.39 ± 0.06-fold, p = 0.009). CONCLUSIONS: Modulating NR4A1 expression can be a promising therapeutic strategy to improve insulin secretion in CP.

Tofacitinib use in ulcerative colitis: An expert consensus for day-to-day clinical practice.

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.