Precision in stereochemistry: the integral role of catalytic asymmetric Biginelli reaction in crafting enantiomerically pure dihydropyrimidinones.

One well-known multicomponent reaction that is helpful in the synthesis of dihydropyrimidinones (DHPMs), important molecules in organic synthesis and medicinal chemistry, is the Biginelli reaction. Because of their wide range of biological activities, DHPMs are regarded as essential chemicals. A great deal of research has been done in the last few decades to find ways to produce enantiomerically pure DHPMs because of their notable and focused target-oriented biological activities. In this reaction, numerous structural variants and catalysts have been employed in a range of solvents to yield an enormous number of Biginelli-type compounds. In the present review, the available catalysts in the literature including ionic liquids, Lewis acids, and organocatalysts for the Biginelli reaction and synthesis of a large number of asymmetric compounds since 2003 are summarized.

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.

Technical performance and diagnostic yield of motorised spiral enteroscopy compared with single-balloon enteroscopy in suspected Crohn's disease: a randomised controlled, open-label study (the MOTOR-CD trial).

OBJECTIVE: Recent studies have shown that motorised spiral enteroscopy (MSE) enables deeper and total small bowel evaluation compared with single-balloon enteroscopy (SBE) in suspected Crohn's disease (CD) when analysed per procedure. However, no randomised controlled study has compared bidirectional MSE with bidirectional SBE in suspected CD. DESIGN: Patients with suspected CD requiring small bowel enteroscopy were randomly assigned to either SBE or MSE between May 2022 and September 2022 in a high volume tertiary centre. Bidirectional enteroscopy was done if intended lesion could not be reached on unidirectional study. Comparison was made with regard to technical success (ability to reach lesion), diagnostic yield, depth of maximal insertion (DMI), procedure time and total enteroscopy rates. Depth:time ratio was calculated to avoid confounding for the location of lesion. RESULTS: Among 125 suspected patients with CD (28% female, 18-65 years, median 41 years), 62 and 63 underwent MSE and SBE, respectively. The overall technical success (98.4 %: MSE, 90.5 %: SBE; p=0.11), diagnostic yield (95.2%: MSE; 87.3%: SBE, p=0.2) and procedure time were not significantly different. However, MSE appeared to have higher technical success (96.8% vs 80.7%, p=0.08) in deeper small bowel (distal jejunum/proximal ileum) with higher DMI, higher depth:time ratio and total enteroscopy rates when attempted (77.8% vs 11.1%, p=0.0007). Both the modalities were safe although minor adverse events were more common with MSE. CONCLUSION: MSE and SBE have comparable technical success and diagnostic yield for small bowel evaluation in suspected CD. MSE scores over SBE with regard to deeper small bowel evaluation with complete small bowel coverage and higher depth of insertion in a shorter time. TRIAL REGISTRATION NUMBER: NCT05363930.

QbD driven targeted pulmonary delivery of dexamethasone-loaded chitosan microspheres: Biodistribution and pharmacokinetic study.

Inhaling drugs, on the other hand, is limited mainly by the natural mechanisms of the respiratory system, which push drug particles out of the lungs or make them inefficient once they are there. Because of this, many ways have been found to work around the problems with drug transport through the lungs. Researchers have made polymeric microparticles (MP) and nanoparticles as a possible way to get drugs into the lungs. They showed that the drug could be trapped in large amounts and retained in the lungs for a long time, with as little contact as possible with the bloodstream. MP were formulated in this study to get dexamethasone (DMC) into the pulmonary area. The Box-Behnken design optimized microspheres preparation to meet the pulmonary delivery prerequisites. Optimized formulation was figured out based on the desirability approach. The mass median aerodynamic diameter (MMAD) of the optimized formula (O-DMC-MP) was 8.46 ± 1.45 µm, and the fine particle fraction (FPF) was 77.69 ± 1.26%. This showed that it made suitable drug delivery system, which could make it possible for MP to settle deeply in the lung space after being breathed in. With the first burst of drug release, it was seen that drug release could last up to 16 h. Also, there was no clear sign that the optimized formulation was toxic to the alveoli basal epithelial cells in the lungs, as supported by cytotoxic studies in HUVEC, A549, and H1299 cell lines. Most importantly, loading DMC inside MP cuts the amount of drug into the bloodstream compared to plain DMC, as evident from biodistribution studies. Stability tests have shown that the product can stay the same over time at both the storage conditions. Using chitosan DMC-MP can be a better therapeutic formulation to treat acute respiratory distress syndrome (ARDS).

Mn3O4 nano-octahedrons embedded in nitrogen-doped graphene oxide as potent anode material for lithium-ion batteries.

Mn3O4 nano-octahedrons embedded in N-doped graphene oxide (MNGO) nanosheets were synthesized using a simple, energy-efficient, and rapid microwave-digested hydrothermal route in a single step. The structural and morphological aspects of synthesized materials were evaluated by XRD, IR, Raman, FE-SEM, and HR-TEM techniques. Then, the composite MNGO was tested for its Li-ion storage properties and compared with reduced graphene oxide (rGO) and Mn3O4 materials. The MNGO composite exhibited superior reversible specific capacity, excellent cyclic stability, and outstanding structural integrity throughout the electrochemical studies. The MNGO composite showed a reversible capacity of 898 mA h g-1 after 100 cycles at 100 mA g-1 and Coulombic efficiency of 97.8%. Even at a higher current density of 500 mA g-1, it exhibits a higher specific capacity of 532 mA h g-1 (~1.5 times higher than commercial graphite anode). These results demonstrate that Mn3O4 nano-octahedrons embedded on N-doped GO are a highly durable and potent anode material for LIBs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11581-023-05035-6.

Endoscopic full-thickness plication for the treatment of PPI-dependent GERD: results from a randomised, sham controlled trial.

BACKGROUND: The majority of endoscopic antireflux procedures for GERD are cumbersome to use and randomised long-term data are sparse. We conducted such a trial to determine the efficacy and safety of a novel, easy to use endoscopic full-thickness fundoplication (EFTP) device in patients with GERD. DESIGN: Patients with proton pump inhibitor (PPI)-dependent GERD were randomised to either EFTP or a sham procedure in 1:1 ratio. The primary endpoint was ≥50% improvement in the health-related quality of life (GERD-HRQL) score at 3 months. Secondary end points included improvement in GERD-HRQL, reflux symptom scores, PPI usage, oesophageal acid exposure and reflux episodes and endoscopic findings at 3, 6 and 12 months. RESULTS: Seventy patients were randomised; 35 in each group with a median (IQR) age of 36 (29-42) years, 71.4% males. 70% had non-erosive reflux disease on endoscopy with a mean DeMeester score of 18.9 (±19.93). The mean (±SD) duration of EFTP procedure was 17.4 (±4) min. The primary end point was more frequently achieved in the EFTP group (65.7% vs 2.9%; p<0.001). Median (IQR) % improvement in GERD-HRQL was significantly higher in the EFTP group at 6 (81.4 (60.9-100.0) versus 8.0 (2.2-21.6); p<0.001) and 12 (92.3 (84.4-100.0) versus 9.1 (4.8-36.0); p<0.001) months. In the EFTP group, 62.8% patients were off-PPI at 12 months compared with 11.4% in the sham group (p<0.001). pH-metry parameters partially improved at 3 months, (n=70; total reflux episodes in EFTP arm and non-acid reflux episodes for EFTP vs sham) but not at 12 months (n=27); endoscopic oesophagitis was seen in 0% in the treatment (n=18) and 5 (29.4%) in the control group (n=17) at 12 months. No major procedure-related adverse events were encountered in either group. CONCLUSION: EFTP using a novel device is safe and effective in improving quality of life in patients with PPI dependent mostly non-erosive reflux disease at short and long terms; objective parameters showed a limited response rate. TRIAL REGISTRATION NUMBER: NCT03322553.

EUS versus MRCP to perform ERCP in patients with intermediate likelihood of choledocholithiasis: a randomised controlled trial.

OBJECTIVE: In patients with an intermediate likelihood of choledocholithiasis, European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP) to diagnose choledocholithiasis to make the indication for endoscopic retrograde cholangiopancreatography (ERCP) treatment; there is no randomised control trial to compare both in this setting. DESIGN: Patients with suspected choledocholithiasis satisfying ESGE guideline's intermediate likelihood were screened for this single-centre randomised controlled trial between November 2019 and May 2020. The enrolled patients were randomised to either EUS or MRCP. ERCP was performed in stone positive cases or if clinical suspicion persisted during follow-up. Negative cases underwent a further 6-month clinical follow-up. Main outcome was accuracy (sensitivity/specificity) of both tests to diagnose choledocholithiasis, with ERCP or follow-up as a gold standard. RESULTS: Of 266 patients, 224 patients (mean age: 46.77±14.57 years; 50.9 % female) were enrolled; overall prevalence of choledocholithiasis was 49.6%, with a higher frequency in the MRCP group (63/112 vs 46/112 for EUS). Both sensitivity of EUS and MRCP were similarly high (92%-98%), without significant differences between the two groups. The negative predictive value and likelihood ratio + were significantly higher in EUS arm (p<0.05). The percentage of ERCPs either incorrectly halted back (false negatives: EUS: 2 vs MRCP: 5) or performed unnecessarily (false positives: EUS: 1 vs MRCP: 2) was low in both groups. CONCLUSION: The performance parameters of both EUS and MRCP are comparable for detecting choledocholithiasis in the intermediate-risk group of choledocholithiasis and the choice of a test should be based on local expertise, availability of resources and patient preference. TRIAL REGISTRATION NUMBER: NCT04173624.

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.

Design of ZIF-67 nanoflake derived NiCo-LDH/rGO hybrid nanostructures for aqueous symmetric supercapattery application under alkaline condition.

Well-defined polyhedral ZIF-67 metal-organic frameworks (MOFs) are usually synthesized using methanol as solvent. In this work, methanol is replaced with deionized water as a solvent to synthesize ZIF-67 MOFs with unique nanoflake morphology. The ZIF-67 nanoflakes are synthesized directly byin situmethod on reduced graphene oxide (rGO) to obtain ZIF-67/rGO-xprecursors which are further transformed into NiCo-layered double hydroxide nanocomposites (NiCo-LDH/rGO-x,x = 10, 30, 50 and 90 mg of rGO). The NiCo-LDH/rGO-xnanostructured composites are found to be excellent materials for battery type supercapacitor (supercapattery) applications. Among these samples, the NiCo-LDH/rGO-30 composite gives maximum specific capacity of 829 C g-1(1658 F g-1) at a current density of 1 A g-1and high rate capability. The as fabricated 2-electrode symmetric Swagelok deviceNiCo-LDH/rGO-30NiCo-LDH/rGO-30delivered a high energy density of 49.2 Wh kg-1and a power density of 4511 W kg-1, and enabled us to glow red, blue and white LED bulbs using three coin cells. The device can show good capacity retention even after 3000 continuous charge-discharge cycles. The NiCo-LDH/rGO-30 composite,in situderived from ZIF-67 MOF in combination with optimal amount of rGO, is an excellent material to deliver both high energy density and high power density in supercapattery devices.

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.

Development of multiplex RT-PCR assay for simultaneous detection of four viruses infecting apple (Malus domestica).

The major viruses infecting apple cultivars throughout the world including India are apple mosaic virus (ApMV), apple stem pitting virus (ASPV), apple stem grooving virus (ASGV), apple chlorotic leaf spot virus (ACLSV), and recently, a new virus, apple necrotic mosaic virus (ApNMV), was reported from mosaic-infected apple cultivars in India. The aim of this study was to detect the ApNMV virus along with the other three viruses (ApMV, ASPV and ASGV) simultaneously by multiplex RT-PCR. Four primer-pair-produced amplicons of 670, 550, 350 and 210 bp corresponding to ApNMV, ApMV, ASPV and ASGV, respectively, were found to be specific for these viruses when tested individually. The annealing temperature (55°C), primer concentration (0·8 µl) and other components of the master mix were standardized for the development of one-step m-RT-PCR assay. The m-RT-PCR protocol developed was further validated with 30 samples from seven symptomatic or asymptomatic apple cultivars, which revealed the presence of more than one virus in these cultivars. Most of the viruses were found to be present either alone or in mixed infection; however, ASPV was more common in tested cultivars. An easy, cost-effective and rapid multiplex RT-RCR protocol was developed to detect the four viruses, which infect apple plants either in individually or together in the field. This assay will help in the surveying and indexing of apple germplasm and the distribution of all four viruses in the apple growing regions of India.

Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature.

Literature on COVID-19-associated pulmonary mucormycosis (CAPM) is sparse. Pulmonary artery pseudoaneurysm (PAP) is an uncommon complication of pulmonary mucormycosis (PM), and rarely reported in CAPM. Herein, we report five cases of CAPM with PAP managed at our center and perform a systematic review of the literature. We diagnosed PM in those with clinico-radiological suspicion and confirmed it by microbiology or histopathology. We encountered five cases of CAPM with PAP (size ranged from 1 × 0.8 cm to ~ 4.9 × 4.8 cm). All subjects had diabetes and were aged 55-62 years (75% men). In two cases, COVID-19 and mucormycosis were diagnosed simultaneously, while in three others, COVID-19 preceded PM. One subject who underwent surgery survived, while all others died (80% mortality). From our systematic review, we identified one additional case of CAPM with PAP in a transplant recipient. CAPM with PAP is rare with high mortality. Early diagnosis and multimodality management are imperative to improve outcomes.

Value Addition and Fortification in Non-Centrifugal Sugar (Jaggery): A Potential Source of Functional and Nutraceutical Foods.

Nutraceutical, functional or fortified food not only supplements the diet but also assists in developing immunity and preventing diseases. Therefore, it also provides medical benefits apart from nutrition. Individual health and diet are receiving a lot of attention these days. Food products that are healthy, safe, and easy to use are in high demand. A lot of emphases has been directed toward food products with added health benefits. Jaggery (non-centrifugal sugar), made from sugarcane juice, is one of them. It is known to mankind for the last 3000 years and is an essential part of the diet in the rural part of many countries. Jaggery is recognized as a nutraceutical due to the presence of a variety of essential amino acids, antioxidants, phenolics, minerals like calcium, phosphorus, iron, and vitamins. Jaggery has a better natural source and nutrients for health benefits and could be used as a healthier dietary substitute to white sugar. The nutraceutical value of jaggery can be enhanced with value addition and fortification of medicinally important herbs and spices. This would not only enhance the quality of nutritive jaggery but will also offer value-added products with exciting flavors for daily use sweeteners with several nutritional health benefits.

Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia.

A recent study showed the association of minor alleles of rs2228611 (T allele) and rs2114724 (T allele) of DNMT1 with schizophrenia (SZ) and suggested their effects on splicing of the transcripts. We performed a replication study using 310 controls and 304 SZ patients and confirmed the association of the homozygous minor allele genotypes with SZ (P = 0.04 for rs2114724 and P = 0.007 for rs2228611). This significant association persisted after Bonferroni correction when the previously published data of 301 controls and 325 patients were also considered (P ≤ 0.0002). In addition, we found that the proportion of male patients with homozygous minor alleles at rs2114724 was significantly higher than that of females (P = 0.002). When haplotype analysis of both loci was performed, we observed a significant association of T/T-T/T and T/T-C/T (P = 0.04) haplotypes with SZ. To gain insights into the functional effects of the two SNPs on the levels of DNMT1 transcripts, quantitative real-time PCR experiments were performed using peripheral blood monocytes from 10 individuals each with T/T-T/T (homozygous minor allele), C/T-C/T (heterozygous), and C/C-C/C (homozygous major allele) haplotypes. Independently, the levels of DNMT1 protein were also compared in three individuals each by immunofluorescence. These results suggest that neither DNMT1 transcript nor the protein levels were significantly different in the peripheral blood monocytes among the individuals studied for the three groups. Taken together, our results confirm that the two minor alleles in homozygosity are associated with SZ but with no discernible effects on transcript or protein levels of DNMT1 in the peripheral blood monocytes of the small number of samples tested.

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.

Inspection plan for COVID-19 patients for Weibull distribution using repetitive sampling under indeterminacy.

BACKGROUND: This research work is elaborated investigation of COVID-19 data for Weibull distribution under indeterminacy using time truncated repetitive sampling plan. The proposed design parameters like sample size, acceptance sample number and rejection sample number are obtained for known indeterminacy parameter. METHODS: The plan parameters and corresponding tables are developed for specified indeterminacy parametric values. The conclusion from the outcome of the proposed design is that when indeterminacy values increase the average sample number (ASN) reduces. RESULTS: The proposed repetitive sampling plan methodology application is given using COVID-19 data belong to Italy. The efficiency of the proposed sampling plan is compared with the existing sampling plans. CONCLUSIONS: Using the tables and COVID-19 data illustration, it is concluded that the proposed plan required a smaller sample size as examined with the available sampling plans in the literature.

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.

Impact of ductal interventions on diabetes in patients with chronic pancreatitis.

BACKGROUND AND AIM: Even though ductal interventions in chronic pancreatitis (CP) are known to improve pain, its impact on diabetes is unclear. In this cohort study, we evaluated the impact of ductal interventions on diabetes in these patients. METHODS: Consecutive patients with CP visiting the pancreas clinic between August 1, 2011, and July 21, 2012, were enrolled and followed until December 2018. Detailed clinical, laboratory, imaging, and treatment data were recorded at enrolment and follow-up. Patients were followed up every 6 months through hospital visit and/or telephonic interview. Risk factors for diabetes were evaluated using logistic regression. The impact of ductal interventions on diabetes was evaluated using Kaplan-Meier survival analyses and Cox proportional hazards. RESULTS: A total of 644 patients were enrolled of which 137 were excluded. Of these, 326 (64.3%) patients had idiopathic CP, and 283 (55.8%) patients underwent ductal intervention. The cumulative incidence of diabetes was 57.9%. Median duration between symptom onset and ductal intervention was similar irrespective of diabetes (2.6 [0.6-6.0] vs 3.0 [1.0-5.5] years; P = 0.69). Alcohol intake and pancreatic ductal calculi were independent risk factors for diabetes (odds ratio [95% confidence interval] of 2.05 (1.18-3.55), P = 0.01, and 2.05 (1.28-3.28), P = 0.003, respectively). Kaplan-Meier analyses revealed that diabetes free interval was significantly longer in patients undergoing ductal interventions, predominantly in those with idiopathic CP with obstructive ductal calculi (hazard ratio [95% confidence interval] 0.39 [0.28-0.55]; P < 0.0001). There were no differences in glycemic status in patients with non-idiopathic CP and those with pre-existing diabetes. CONCLUSION: Early ductal intervention could delay development of diabetes in patients with idiopathic CP with obstructive ductal calculi.

Fatty acid ethyl ester (FAEE) associated acute pancreatitis: An ex-vivo study using human pancreatic acini.

BACKGROUND & AIM: Fatty acid ethyl esters (FAEEs), are produced by non-oxidative alcohol metabolism and can cause acinar cell damage and subsequent acute pancreatitis in rodent models. Even though experimental studies have elucidated the FAEE mediated early intra-acinar events, these mechanisms have not been well studied in humans. In the present study, we evaluate the early intra-acinar events and inflammatory response in human pancreatic acinar tissues and cells in an ex-vivo model. METHODS: Experiments were conducted using normal human pancreatic tissues exposed to FAEE. Subcellular fractionation was performed on tissue homogenates and trypsin and cathepsin B activities were estimated in these fractions. Acinar cell injury was evaluated by histology and immunohistochemistry. Cytokine release from exposed acinar cells was evaluated by performing Immuno-fluorescence. Serum was collected from patients with AP within the first 72 h of symptom onset for cytokine estimation using FACS. RESULTS: We observed significant trypsin activation and acinar cell injury in FAEE treated tissue. Cathepsin B was redistributed from lysosomal to zymogen compartment at 30 min of FAEE exposure. IHC results indicated the presence of apoptosis in pancreatic tissue at 1 & 2hrs of FAEE exposure. We also observed a time dependent increase in secretion of cytokines IL-6, IL-8, TNF-α from FAEE treated acinar tissue. There was also a significant elevation in plasma cytokines in patents with alcohol associated AP within 72 h of symptom onset. CONCLUSION: Our data suggest that alcohol metabolites can cause acute acinar cell damage and subsequent cytokine release which could eventually culminant in SIRS.