Single-wavelength bidirectional 4-core MCF self-homodyne coherent link.

In this paper, we propose and demonstrate a single-wavelength bidirectional self-homodyne coherent (SHC) link over a 125 µm cladding diameter based multicore fiber (MCF). The 4-core MCF based link efficiently uses two cores for each direction of propagation. In either direction, one of the cores carries a dual-polarized 40 Gbaud 16-QAM signal, and the second core carries a 40 Gbaud 16-QAM signal in one of the polarizations with the carrier multiplexed in its orthogonal polarization. Thus, a 480 Gbps data transmission rate is achieved in either direction of propagation over the 12.8 km long 4-core MCF. The SHC link operates at the same wavelength for each of the directions and eliminates the need for reconfigurable transceivers. A low-cost DFB laser (linewidth = 1 MHz) is used to demonstrate the bidirectional link, and the bit error rates (BERs) of the received signals are <5.5×10-4. With higher baud rates, this approach can meet the capacity requirements of future short-reach data center interconnects (DCIs).

Clinical significance of SPOP and APC gene alterations in colorectal cancer in Indian population.

Speckle-Type Poz Protein (SPOP) involved in the regulation of proteasome-mediated degradation of several oncoproteins, resulting in cancer initiation and progression. Mutations in Adenomatous Polyposis Coli (APC) gene is reported in most sporadic and hereditary colorectal cancer (CRC). Identifying the cellular changes involved in carcinogenesis when APC is mutated is an important issue that needs attention. The tumor suppressive function of SPOP and APC has long been a major focus in the research field of colorectal cancer. However, the clinical significance of SPOP and APC gene alteration in CRC has not been established to date. Mutational analysis was performed by single-strand conformational polymorphism followed by Sanger sequencing, methylation status by methylation-specific PCR, and protein expression by immunohistochemistry on 142 tumor tissues along with their adjacent non-cancerous specimens. The overall survival (OS) and recurrence free survival (RFS) were estimated by Kaplan-Meier Curve. Mutation rates of APC and SPOP gene were 2.8% and 11.9% while that of promoter hypermethylation were 37% and 47%, respectively. The grade of differentiation and Lymph node metastasis were significantly correlated with APC methylation pattern (p ≤ 0.05). The down regulation of APC was more often seen in colonic cancer compared to rectal cancer (p = 0.07) and more commonly in T3-4 depth of invasion (p = 0.07) and in patients without lymphovascular and perineural invasion (p = 0.007, p = 0.08 respectively). The median overall survival and recurrence free survival (RFS) was 67 & 36 months while 3-yr and 5-yr OS and RFS were 61.1% & 56.4% and 49.2% & 44.8%, respectively. APC promoter methylation had a better overall survival (p = 0.035) while loss of SPOP expression had a worse survival (p = 0.09). Our findings reveal high percentage of SPOP gene mutations in CRC. A significant link is found between promoter hyper methylation and protein expression in all mutant cases of APC and SPOP, suggesting that both genes may be associated in the development of colorectal cancer in people of Indian decent. Hypermethylation of APC gene and loss of SPOP expression have shown an association with disease prognosis and could be further studied looking at its potential role in planning adjuvant treatment in CRC patients.

Covid-MANet: Multi-task attention network for explainable diagnosis and severity assessment of COVID-19 from CXR images.

The devastating outbreak of Coronavirus Disease (COVID-19) cases in early 2020 led the world to face health crises. Subsequently, the exponential reproduction rate of COVID-19 disease can only be reduced by early diagnosis of COVID-19 infection cases correctly. The initial research findings reported that radiological examinations using CT and CXR modality have successfully reduced false negatives by RT-PCR test. This research study aims to develop an explainable diagnosis system for the detection and infection region quantification of COVID-19 disease. The existing research studies successfully explored deep learning approaches with higher performance measures but lacked generalization and interpretability for COVID-19 diagnosis. In this study, we address these issues by the Covid-MANet network, an automated end-to-end multi-task attention network that works for 5 classes in three stages for COVID-19 infection screening. The first stage of the Covid-MANet network localizes attention of the model to the relevant lungs region for disease recognition. The second stage of the Covid-MANet network differentiates COVID-19 cases from bacterial pneumonia, viral pneumonia, normal and tuberculosis cases, respectively. To improve the interpretation and explainability, three experiments have been conducted in exploration of the most coherent and appropriate classification approach. Moreover, the multi-scale attention model MA-DenseNet201 proposed for the classification of COVID-19 cases. The final stage of the Covid-MANet network quantifies the proportion of infection and severity of COVID-19 in the lungs. The COVID-19 cases are graded into more specific severity levels such as mild, moderate, severe, and critical as per the score assigned by the RALE scoring system. The MA-DenseNet201 classification model outperforms eight state-of-the-art CNN models, in terms of sensitivity and interpretation with lung localization network. The COVID-19 infection segmentation by UNet with DenseNet121 encoder achieves dice score of 86.15% outperforming UNet, UNet++, AttentionUNet, R2UNet, with VGG16, ResNet50 and DenseNet201 encoder. The proposed network not only classifies images based on the predicted label but also highlights the infection by segmentation/localization of model-focused regions to support explainable decisions. MA-DenseNet201 model with a segmentation-based cropping approach achieves maximum interpretation of 96% with COVID-19 sensitivity of 97.75%. Finally, based on class-varied sensitivity analysis Covid-MANet ensemble network of MA-DenseNet201, ResNet50 and MobileNet achieve 95.05% accuracy and 98.75% COVID-19 sensitivity. The proposed model is externally validated on an unseen dataset, yields 98.17% COVID-19 sensitivity.

Management of Obscurely Dilated Common Bile Duct with Normal Liver Function Tests: A Pragmatic Approach.

OBJECTIVE: Dilated common bile duct (CBD) (8-15 mm) with normal liver function tests is seen not infrequently, while management of such patients is ambiguous. We propose a treatment algorithm for this cohort of patients after observing them over a period of 8 years. METHODS: Seventy-eight such patients were managed from 2009 to 2017 and categorized as: Group A-dilated CBD with post-cholecystectomy status (n = 15); B-dilated CBD with cholelithiasis (n = 34); C-dilated CBD without cholelithiasis (n = 16); D-dilated CBD with no cause identified and underwent CBD excision (n = 13). Causes for CBD dilatation were evaluated. The outcome of patients in Group B + C without any cause (n = 33) was compared with Group D. RESULT: Median age, CBD diameter, bilirubin and alkaline phosphatase were 51 years (13-79), 10 mm (8-20), 0.6 mg/dl (0.2-2.5) and 126 IU (60-214), respectively. Group-A patients who did not manifest any cause of CBD dilatation were managed conservatively. The aetiology was identified in 17/50 patients in Group B & C [acute pancreatitis (n = 6), passed CBD calculi (n = 3), perivaterian diverticulum (n = 3), viral aetiology (n = 4) and tumour (n-1)]. In Group-C, 7 patients with no obvious cause underwent endoscopic sphincterotomy, pancreatoduodenectomy (n = 1), and the rest were managed conservatively (n = 8). There was no significant difference in the complication between Group B + C (without any cause) and Group D (3/33 vs. 1/13; p = 0.58) at a median follow-up of 72 months (30-90). CONCLUSION: Dilated CBD with normal LFT's without apparent cause is mostly benign and of no consequence. Excision of the CBD is not required for most of these patients.

Enhanced Gaussian process regression-based forecasting model for COVID-19 outbreak and significance of IoT for its detection.

Virus based epidemic is one of the speedy and widely spread infectious disease which can affect the economy of the country as well as it is life-threatening too. So, there is a need to forecast the epidemic lifespan, which can help us in taking preventive measures and remedial action on time. These preventive measures and corrective action may consist of closing schools, closing malls, closing theaters, sealing of borders, suspension of public services, and suspension of traveling. Resuming such restrictions is depends upon the outbreak momentum and its decay rate. The accurate forecasting of the epidemic lifespan is one of the enormously essential and challenging tasks. It is a challenging task because the lack of knowledge about the novel virus-based diseases and its consequences with complicated societal-governmental factors can influence the widespread of this newly born disease. At this stage, any forecasting can play a vital role, and it will be reliable too. As we know, the novel virus-based diseases are in a growing phase, and we also do not have real-time data samples. Thus, the biggest challenge is to find out the machine learning-based best forecasting model, which could offer better forecasting with the limited training samples. In this paper, the Multi-Task Gaussian Process (MTGP) regression model with enhanced predictions of novel coronavirus (COVID-19) outbreak is proposed. The purpose of the proposed MTGP regression model is to predict the COVID-19 outbreak worldwide. It will help the countries in planning their preventive measures to reduce the overall impact of the speedy and widely spread infectious disease. The result of the proposed model has been compared with the other prediction model to find out its suitability and correctness. In subsequent analysis, the significance of IoT based devices in COVID-19 detection and prevention has been discussed.

Raised CA19-9 and CEA have prognostic relevance in gallbladder carcinoma.

BACKGROUND: Role of tumor markers in gall bladder carcinoma (GBC) is not well established. We evaluated the prognostic value of carbohydrate antigen 19-9 (CA19-9) and carcinoma embryonic antigen (CEA) in patients with GBC. METHODS: Of the 225 patients of GBC enrolled,176 patients were included in the study (excluded 49 patients with jaundice). Patients were divided into 3 groups; resectable n = 92, unresectable n = 17, metastatic n = 67. The clinico-pathological characteristics, tumor markers and survival data were analysed. The cutoff values of CA19-9 & CEA for predicting metastases were computed using receiver operating characteristic curve. Kaplan Meir survival and Cox regression analysis were done for factors predicting survival and recurrence. RESULTS: The median value of Ca19-9 was significantly higher in metastatic group [resectable: 21.3, unresectable: 53.9 and metastatic: 79; p < 0.001] but not for CEA [3.5, 7.8 and 5 ng/ml (p = 0.20)]. A cutoff value of 72 IU/ml for CA19-9, 5 ng/ml for CEA had a sensitivity and specificity of 52 and 80%, 51 and 72% respectively for detection of metastatic disease. Median, 3-year & 5-year survival were significantly lower in patients with CEA > 4 (p = 0.041), Ca19.9 > 37 (p = 0.019), T3/T4 (p = 0.001), node positive (p = 0.001) and presence of perineural invasion (p = 0.001). However, on multivariate analysis, only Ca19.9 > 37 predicted recurrence (p = 0.002, HR 5.8). CONCLUSIONS: Raised CA19.9 and CEA predict metastatic disease in patients with GBC without jaundice with a high specificity and may help in prognostication of the patient. CA19-9 was better than CEA in prediction of tumor burden and in predicting recurrence.

ERCP-related perforation: an analysis of operative outcomes in a large series over 12 years.

BACKGROUND: Perforation is a rare but serious adverse event of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to determine the predictors of morbidity and mortality after surgical management of ERCP-related perforation (EP). METHODS: The records of patients with EP requiring surgical intervention at a tertiary referral center in a 12-year period (2004-2016) were retrospectively analyzed for demography, indications for ERCP, risk factors, timing and type of surgical repair, post-operative course, hospital stay, and outcome. Multiple logistic regression was used to identify the parameters predicting survival. RESULTS: Of 25,300 ERCPs, 380 (1.5%) had EP. Non-operative management was successful in 330 (86.8%) patients. 50 (13.2%) patients were operated for EP. Out of 50, the perforation was detected during ERCP (intra-procedure) in 32 patients (64%). In 30 patients (60%), the surgery was performed within 24 h of ERCP. Twenty patients underwent delayed surgery (after 24 h of ERCP) following the failure of initial non-operative management. The delayed surgery after an unsuccessful medical treatment had a detrimental effect on morbidity, mortality and hospital stay. Post-operative duodenal leak was the only independent predictor of 90-day mortality (p = 0.02, OR = 9.1, 95% CI 1.52-54.64). Addition of T-tube duodenostomy (TTD) to the primary repair for either type I or type II perforations increased post-operative duodenal leak (type I, p = 0.048 and type II; p = 0.001) and mortality (type I, p = 0.009 and type II, p = 0.045). CONCLUSION: Although EP is a rare event, it has a serious impact on morbidity and mortality. Delaying of surgery following failed non-operative management worsens the prognosis. Addition of TTD to the repair is not helpful in these patients.

Endoscopic cystogastrostomy versus surgical cystogastrostomy in the management of acute pancreatic pseudocysts.

Background: Studies comparing surgical versus endoscopic drainage of pseudocyst customarily include patients with both acute and chronic pseudocysts and the endoscopic modalities used for drainage are protean. We compared the outcomes following endoscopic cystogastrostomy (ECG) and surgical cystogastrostomy (SCG) in patients with acute pseudocyst. Methods: Seventy-three patients with acute pseudocyst requiring drainage from 2011 to 2014 were analysed (18 patients excluded: transpapillary drainage n = 15; cystojejunostomy n = 3). The remaining 55 patients were divided into two groups, ECG n = 35 and SCG n = 20, and their outcomes (technical success, successful drainage, complication rate and hospital stay) were compared. Results: The technical success (31/35 [89%] vs. 20/20 [100%] P = 0.28), complication rate (10/35 [28.6%] vs. 2/20 [10%]; P = 0.17) and median hospital stay (6.5 days [range 2-12] vs. 5 days [range 3-12]; P = 0.22) were comparable in both the groups, except successful drainage which was higher in surgical group (27/35 [78%] vs. 20/20 [100%] P = 0.04). The conversion rate to surgical procedure was 17%. The location of cyst towards tail of pancreas and presence of necrosis were the main causes of technical failure and failure of successful endoscopic drainage, respectively. Conclusion: Surgical drainage albeit remains the gold standard for management of pseudocyst drainage; endoscopic drainage should be considered a first-line treatment in patients with acute pseudocyst considering the reasonably good success rate.

Early recurrence after laparoscopic radical cholecystectomy in a patient with gallbladder cancer.

Laparoscopic radical cholecystectomy for gallbladder cancer (GBC) has been performed at various oncology centres reporting its technical feasibility. Considering GBC an aggressive malignancy, laparoscopic radical cholecystectomy should be dealt with caution. We recently encountered a case of carcinoma gallbladder who underwent laparoscopic radical cholecystectomy elsewhere and presented with early recurrence. The patient's records were evaluated and he underwent re-resection. Hereby, we discuss the factors that could lead to early recurrence after laparoscopic radical cholecystectomy and measures that can be taken to prevent it.

Utilization of Gastric Conduit in the Management of Combined Corrosive Esophageal and Stomach Stricture.

BACKGROUND: Corrosive stricture of esophagus may be associated with variable involvement of stomach. We analyzed the outcome of gastric conduit used in the management of corrosive esophageal stricture with concomitant antro-pyloric stricture. STUDY DESIGN: Among 101 esophageal replacements performed, 53 patients had combined esophagus and stomach strictures. Colon was used as a conduit in 43 patients, while stomach was used in ten patients. Indications, perioperative complications and early/late outcomes of patients with gastric pull-up were reviewed and compared with those undergone colon pull-up. RESULTS: The indications of using gastric conduit were impromptu in four patients [colonic conduit ischemia (n = 2) and an oversight of antro-pyloric stricture after forming the gastric conduit (n = 2)]. Six patients had preconceived gastric conduit (distal antro-pyloric stricture with distended stomach). The median age was 29 years (range 16-50), and median BMI was 15.4 kg/m2 (range 14.5-20.1). The stomach was drained using loop gastrojejunostomy (n = 7) or Roux-en-Y gastrojejunostomy (n = 3). One patient died due to sepsis secondary to anastomotic leak. Median hospital stay was 9 days (range 7-22). At median follow-up of 25 months (range 14-80), the remaining nine patients are able to have solid diet and have gained weight. The level of esophageal stricture was low (p = 0.01), and duration of surgery (p = 0.02) and median hospital stay (p = 0.04) were significantly less in patients with gastric conduit plus drainage as compared to patients undergone colonic pull-up. CONCLUSION: Gastric conduit in a subject with distal antro-pyloric stricture can be used safely along with gastrojejunostomy in selected patients of corrosive esophageal stricture.

Decreased expression of MGMT in correlation with aberrant DNA methylation in esophageal cancer patients from North India.

O-6-methylguanine-DNA methyltransferase, DNA repair gene, has been found to be involved with the pathogenesis of the esophageal cancer. DNA hypermethylation and other factors have been suggested to downregulate O-6-methylguanine-DNA methyltransferase. In this communication, the methylation status of O-6-methylguanine-DNA methyltransferase gene and the corresponding O-6-methylguanine-DNA methyltransferase protein expression in esophageal cancer from North India has been studied. In all, 80 samples of tumor tissue along with adjacent normal tissue as controls were analyzed for messenger RNA level of O-6-methylguanine-DNA methyltransferase gene, protein expression, and subcellular localization. The messenger RNA expression was studied using real-time quantitative polymerase chain reaction, protein expression, and its subcellular localization by Western blotting and immunohistochemistry. DNA methylation was assessed through methylation-specific polymerase chain reaction. Clinicopathological parameters were recorded and correlated with the O-6-methylguanine-DNA methyltransferase expression. O-6-methylguanine-DNA methyltransferase messenger RNA expression was found to be downregulated in 65% cases (52/80). The expression of O-6-methylguanine-DNA methyltransferase at the protein level was also found to be absent in 65% (52/80) cases. In all, 52 cases had low or no expression of the protein, whereas out of those 28 remaining cases, 11.25% (09/80) cases had high O-6-methylguanine-DNA methyltransferase protein expression. The absence of O-6-methylguanine-DNA methyltransferase protein coincided with the methylated cases in 84% (38/45), whereas in 07 cases, out of the 45 methylated, O-6-methylguanine-DNA methyltransferase protein was present. The aggressive esophageal cancer patients having methylated O-6-methylguanine-DNA methyltransferase had more than 50% cases with no/mild expression of the O-6-methylguanine-DNA methyltransferase protein ( p > 0.001). Loss of O-6-methylguanine-DNA methyltransferase protein was very frequent in the incidence of esophageal cancer from North Indian patients, and methylation of the promoter region of O-6-methylguanine-DNA methyltransferase was significantly associated in its downregulation.

Step-Down Approach for Pharyngoesophageal Corrosive Stricture: Outcome and Analysis.

BACKGROUND: Pharyngoesophageal stricture (PES) is an Achilles' heel in the management of corrosive injury. Advances in endoscopic techniques were utilized in its management. We classified the stricture as per its dilatability and then planned their treatment. METHODS: PES was sub-categorized based on endoscopic dilatation and availability of cervical oesophagus: group-1 stricture with available cervical oesophagus; group-2 stricture with some part of upper oesophagus made available after endoscopic dilatation and anastomosis in cervico-pharyngeal area; group-3 stricture not amenable for dilatation, anastomosis done at the pharynx. Endoscopic dilatation was performed using through-the-scope pyloric balloon. Number and duration of dilatation sessions before surgery, incidence of tracheostomy, time and incidence for re-stricture and present status of swallowing were evaluated. RESULTS: Of 226 patients managed, 46 underwent oesophageal replacement for PES. Group 1, 2 and 3 had 12, 14 and 20 patients, respectively. An average 3 (2-4) preoperative balloon dilatation sessions were performed over 6-8 weeks. Tracheostomy was required in 1, 0, 8 patients (p = 0.010), and median hospital stay was 10, 9 and 13 days (p = 0.09) in group 1, 2, 3, respectively. Re-stricture developed in 4/12, 4/14, 9/20 patients with average sessions of dilatation required in post-operative period was 4, 3.5 and 8 in group 1, 2, 3, respectively. >90% of patients are taking normal diet in each group. CONCLUSION: We attempted to avoid the high anastomosis by dilating the PES and step down the level of anastomosis in two-third patients. We thereby avoided tracheostomy, aspiration and swallowing problems related to high strictures.

Prognostic Significance of HER-2 and p53 Expression in Gallbladder Carcinoma in North Indian Patients.

BACKGROUND/OBJECTIVE: Proto-oncogenes (HER-2) and tumor suppressor genes (p53) are commonly deregulated in gallbladder cancer (GBC). Available literature discloses skewed data from endemic Asian countries, especially north India. This study evaluates the prognostic significance of HER-2 and p53 in GBC patients from two major hospitals. METHODS: Sixty resectable tumor and control specimens were prospectively collected from December 2012 to January 2016. Immunohistochemical staining was done using monoclonal antibodies to semiquantitatively evaluate HER-2 and p53 protein expression. The criterion for HER-2 positivity was set at >30% tumor cells showing complete, membranous staining while p53 positivity was established at <50% tumor cells showing complete nuclear staining. Clinicopathological correlations were drawn with major clinical outcomes. RESULTS: It was observed that 36.67% (22/60) tumor cases and 5% (3/60) control cases showed strong HER-2 overexpression significantly correlating with sex, T-stage, nodal spread and distant metastasis (p < 0.05), while 33.3% (20/60) positivity was observed for p53 in tumor cases and 1.7% (1/60) in control cases. Multivariate analysis showed HER-2 (p = 0.04; hazard ratio: 2.36; 95% confidence interval: 1.04-5.33) and p53 (p = 0.03; hazard ratio: 5.63; 95% confidence interval: 1.21-26.26) expression to be independent prognostic factors. CONCLUSION: Our study thus suggests the plausible role of HER-2 and p53 expression in worse prognosis of GBC in a north Indian population.

Allelic loss at PTEN locus leads to progression of colorectal carcinoma among North Indian patients.

We evaluated the loss of heterozygosity (LOH) at 10q23.3 locus of microsatellite markers; D10S198, D10S192, and D10S541 of PTEN gene in 223 North Indian colorectal cancer (CRC) specimens. DNA was isolated and microsatellite-specific markers polymerase chain reaction was performed. Out of total 223 cases 102 showed LOH for at least one of the locus. In addition, thereto a significant association was found with the clinicopathologic features like grade of differentiation, clinical stage, invasion, lymph node invasion, and the clinical outcome (p < 0.05). These data argue that the given markers to check the possible LOH of PTEN gene at locus 10q23.3 could be considered as one of the diagnostic markers in CRC.

Mutational and expressional analyses of PTEN gene in colorectal cancer from Northern India.

The PTEN is a tumor-suppressor gene located on chromosome 10q23.3 and established to play key role in the varied types of cancer. To elucidate the possible effect of mutations and inactivation of PTEN gene on the occurrence and development of colorectal cancer (CRC), 223 cancer specimens were selected to probe PTEN gene mutations through the micro dissection of the genome. Polymerase chain reaction single-strand conformation polymorphism and DNA sequencing methods were applied for mutations while protein expression was evaluated by immunohistochemistry. Mutations in exons 7 and 8 of PTEN were observed in 12.5% and PTEN loss of expression was identified in 48% in CRC. In exon 7, we found the insertion of "G" resulted into the change at codon 218 from TGC to GTC leading to change in the reading frame starting downward from Cystein to Valine. In addition, the insertion of "A" in the same exon at codon 213 resulted into the change of codon CCT to CCA, which cause silent mutation. In exon 8, however, "A" is replaced by C at codon 282, but both encodes for Glycine. Statistically significant loss of PTEN expression was observed in cancerous tissue when compared with the adjacent control (P < 0.05). Furthermore, weak PTEN expression in CRC tissues were significantly associated with tumor size, depth of invasion, lymphatic invasion, lymph node metastasis, grade of differentiation, and TNM stage (P < 0.05). Our results suggested that PTEN gene mutation and loss of PTEN expression may provide valuable prognostic information to aid treatment strategies for CRC patients.

Leukocyte infiltration into spinal cord of EAE mice is attenuated by removal of endothelial leptin signaling.

Leptin, a pleiotropic adipokine, crosses the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) from the periphery and facilitates experimental autoimmune encephalomyelitis (EAE). EAE induces dynamic changes of leptin receptors in enriched brain and spinal cord microvessels, leading to further questions about the potential roles of endothelial leptin signaling in EAE progression. In endothelial leptin receptor specific knockout (ELKO) mice, there were lower EAE behavioral scores in the early phase of the disorder, better preserved BSCB function shown by reduced uptake of sodium fluorescein and leukocyte infiltration into the spinal cord. Flow cytometry showed that the ELKO mutation decreased the number of CD3 and CD45 cells in the spinal cord, although immune cell profiles in peripheral organs were unchanged. Not only were CD4(+) and CD8(+) T lymphocytes reduced, there were also lower numbers of CD11b(+)Gr1(+) granulocytes in the spinal cord of ELKO mice. In enriched microvessels from the spinal cord of the ELKO mice, the decreased expression of mRNAs for a few tight junction proteins was less pronounced in ELKO than WT mice, as was the elevation of mRNA for CCL5, CXCL9, IFN-γ, and TNF-α. Altogether, ELKO mice show reduced inflammation at the level of the BSCB, less leukocyte infiltration, and better preserved tight junction protein expression and BBB function than WT mice after EAE. Although leptin concentrations were high in ELKO mice and microvascular leptin receptors show an initial elevation before inhibition during the course of EAE, removal of leptin signaling helped to reduce disease burden. We conclude that endothelial leptin signaling exacerbates BBB dysfunction to worsen EAE.

Chronic pancreatitis with benign biliary obstruction: management issues.

BACKGROUND: Benign biliary obstruction (BBO) is an important complication in patients with advanced chronic pancreatitis (CP). Its presentation varies from an incidental finding to overt jaundice. Thus it presents certain management issues. The present study was therefore performed to analyze the clinical presentation and management of biliary obstruction in patients with CP. METHODS: Retrospective analysis was performed from a prospectively collected database of 155 CP patients managed at our institute from October 2003 to June 2012. RESULTS: Among 43 (28 %) CP patients with biliary obstruction, 3 patients had evidence of malignancy on follow-up examination and were excluded from the final analysis. The various presentations include chronic nonprogressive elevation of serum alkaline phosphatase (SAP) (n = 15), a progressive increase in SAP with episodes of jaundice (n = 17), and persistent jaundice (n = 8). Of 15 patients with chronic nonprogressive elevation of SAP, 5 were managed conservatively, and the remaining 10 underwent only a pancreatic drainage procedure. During a median follow-up of 41 months (range 11-90 months), none of the 15 patients developed complications related to biliary obstruction. All patients with progressive increase in SAP levels and persistent jaundice underwent the biliary drainage procedure [choledochojejunostomy (CDJ, n = 20) and choledochoduodenostomy (CDD, n = 3)]. During a median follow-up of 30 months (range 10-89 months), two patients died of unrelated causes and two patients had an asymptomatic elevation of SAP. CONCLUSIONS: BBO is common in patients with CP; however, biliary drainage is not indicated for chronic nonprogressive elevation of SAP. In patients with a progressive increase in SAP or persistent jaundice, both CDJ and CDD provide effective biliary drainage.

Role of adjuvant therapy in resected periampullary adenocarcinoma: A propensity matched case-control study.

Backgrounds/Aims: The published data had contradictory information on the role of adjuvant therapy on resected periampullary carcinomas (PACA). The study was performed to evaluate the survival benefit of adjuvant treatment. Methods: This was a propensity score matched case-control study from a prospectively maintained database from 2004-2019. The study included patients with nonpancreatic PACA who underwent curative resection. The patients (cases) who received adjuvant chemotherapy were compared with patients (controls) who were observed alone after surgery. Results: Of 510 patients with PACA, 230 patients (cases = 107, controls = 123) formed the unmatched study cohort. After propensity score matching, 140 patients (cases = 70, controls = 70) formed the matched study cohort. The median overall survival (OS) was similar in cases than controls in the unmatched population but doubled non-significantly in cases after matching (unmatched population, 54 months vs. 54 months, p-value = 0.624; matched population, 71 months vs. 36 months, p-value = 0.087). However, the median recurrence-free survival (RFS) was non significantly higher in the control group (unmatched population, 59 months vs. 38 months, p-value = 0.195; matched population, 53 months vs. 40 months, p-value = 0.797). In cox regression analysis, age < 60 years, advanced T stage, and presence of perineural invasion were independent factors for worse RFS, while tumor recurrence was an independent factor for poor OS. Conclusions: Patients with nonpancreatic PACA may have an OS benefit from adjuvant chemotherapy, and this needs to be validated with large prospective randomized studies.

Increased accumulation of regulatory granulocytic myeloid cells in mannose receptor C type 1-deficient mice correlates with protection in a mouse model of neurocysticercosis.

Neurocysticercosis (NCC) is a central nervous system (CNS) infection caused by the metacestode stage of the parasite Taenia solium. During NCC, the parasites release immunodominant glycan antigens in the CNS environment, invoking immune responses. The majority of the associated pathogenesis is attributed to the immune response against the parasites. Glycans from a number of pathogens, including helminths, act as pathogen-associated molecular pattern molecules (PAMPs), which are recognized by pattern recognition receptors (PRRs) known as C-type lectin receptors (CLRs). Using a mouse model of NCC by infection with the related parasite Mesocestoides corti, we have investigated the role of mannose receptor C type 1 (MRC1), a CLR which recognizes high-mannose-containing glycan antigens. Here we show that MRC1(-/-) mice exhibit increased survival times after infection compared with their wild-type (WT) counterparts. The decreased disease severity correlates with reduced levels of expression of markers implicated in NCC pathology, such as interleukin-1ß (IL-1ß), IL-6, CCL5, and matrix metalloproteinase 9 (MMP9), in addition to induction of an important repair marker, fibroblast growth factor 2 (FGF2). Furthermore, the immune cell subsets that infiltrate the brain of MRC1(-/-) mice are dramatically altered and characterized by reduced numbers of T cells and the accumulation of granulocytic cells with an immune phenotype resembling granulocytic myeloid-dependent suppressor cells (gMDSCs). The results suggest that MRC1 plays a critical role in myeloid plasticity, which in turn affects the adaptive immune response and immunopathogenesis during murine NCC.

Loss of astrocytic leptin signaling worsens experimental autoimmune encephalomyelitis.

Leptin is commonly thought to play a detrimental role in exacerbating experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Paradoxically, we show here that astrocytic leptin signaling has beneficial effects in reducing disease severity. In the astrocyte specific leptin receptor knockout (ALKO) mouse in which leptin signaling is absent in astrocytes, there were higher EAE scores (more locomotor deficits) than in the wildtype counterparts. The difference mainly occurred at a late stage of EAE when wildtype mice showed signs of recovery whereas ALKO mice continued to deteriorate. The more severe symptoms in ALKO mice coincided with more infiltrating cells in the spinal cord and perivascular brain parenchyma, more demyelination, more infiltrating CD4 cells, and a lower percent of neutrophils in the spinal cord 28 days after EAE induction. Cultured astrocytes from wildtype mice showed increased adenosine release in response to interleukin-6 and the hippocampus of wildtype mice had increased adenosine production 28 days after EAE induction, but the ALKO mutation abolished the increase in both conditions. This indicates a role of astrocytic leptin in normal gliotransmitter release and astrocyte functions. The worsening of EAE in the ALKO mice in the late stage suggests that astrocytic leptin signaling helps to clear infiltrating leukocytes and reduce autoimmune destruction of the CNS.