Risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) abdominal pain in patients without post-ERCP pancreatitis.

BACKGROUND: Abdominal pain is often observed after endoscopic retrograde cholangiopancreatography (ERCP). Few studies have focused on the risk factors of post-ERCP abdominal pain without post-ERCP pancreatitis (PEP). This study aimed to identify risk factors of post-ERCP abdominal pain without PEP and investigate characteristics of the abdominal pain in non-PEP patients. METHODS: Data from patients who underwent ERCP from August 2019 to January 2020 were retrospectively collected. Characteristics of the abdominal pain after ERCP were recorded and compared between PEP and non-PEP patients. Multivariate analysis was conducted to identify risk factors of non-PEP abdominal pain. RESULTS: A total of 1295 ERCP procedures were investigated in this study, among which 100 (7.72%) patients presented post-ERCP abdominal pain without PEP and 63 (4.86%) patients with PEP. Multivariate analysis found 9 risk factors of non-PEP abdominal pain: age ≤ 65 years [odds ratio (OR): 1.971], primary ERCP (OR: 2.442), dilated extrahepatic bile duct (OR: 1.803), no papilla opening (OR: 2.095), pancreatic guidewire passages (OR: 2.258), white blood cells (WBC) ≤ 6.0 × 109/L (OR: 1.689), platelet (PLT) ≤ 250 × 109/L (OR: 2.505), serum γ-glutamyl transferase (γ - GT) ≤ 35 U/L (OR: 2.190), and albumin ≥ 40 g/L (OR: 1.762). The PEP group had later pain onset, higher pain frequency and longer hospital stay than those of the non-PEP pain group (P < 0.05). There were no significant differences in the pain duration, visual analogue scale score and mortality between the PEP group and non-PEP pain group (P > 0.05). CONCLUSIONS: This study indicated that age ≤ 65 years, primary ERCP, dilated extrahepatic bile duct, no papilla opening, pancreatic guidewire passages, lower WBC, lower PLT, normal γ - GT and elevated albumin were independent risk factors for post-ERCP abdominal pain without PEP. The pain occurred earlier in non-PEP patients than in PEP patients.

Assessment of Excess Mortality and Household Income in Rural Bangladesh During the COVID-19 Pandemic in 2020.

Importance: A slow or incomplete civil registry makes it impossible to determine excess mortality due to COVID-19 and difficult to inform policy. Objective: To quantify the association of the COVID-19 pandemic with excess mortality and household income in rural Bangladesh in 2020. Design, Setting, and Participants: This repeated survey study is based on an in-person census followed by 2 rounds of telephone calls. Data were collected from a sample of 135 villages within a densely populated 350-km2 rural area of Bangladesh. Household data were obtained first in person and subsequently over the telephone. For the analysis, mortality data were stratified by month, age, sex, and household education. Mortality rates were modeled by bayesian multilevel regression, and the strata were aggregated to the population by poststratification. Data analysis was performed from February to April 2021. Exposures: Date and cause of any changes in household composition, as well as changes in income and food availability. Main Outcomes and Measures: Mortality rates were compared for 2019 and 2020, both without adjustment and after adjustment for nonresponse and differences in demographic variables between surveys. Income and food availability reported for January, May, and November 2020 were also compared. Results: Enumerators collected data from an initial 16 054 households in January 2020; 14 551 households (91%) responded when contacted again by telephone in May 2020, and 11 933 households (74%)responded when reached again over the telephone in November 2020, for a total of 58 806 individuals (29 726 female participants [50.5%]; mean [SD] age, 26.4 [19.8] years). A total of 276 deaths were reported between February and the end of October 2020 for the subset of the population that could be contacted twice over the telephone, slightly below the 289 deaths reported for the same population over the same period in 2019. After adjustment for survey nonresponse and poststratification, 2020 mortality changed by -8% (95% CI, -21% to 7%) compared with an annualized mortality of 6.1 deaths per 1000 individuals in 2019. However, in May 2020, salaried primary income earners reported a 40% decrease in monthly income (from 17 485 to 10 835 Bangladeshi Taka), and self-employed earners reported a 60% decrease in monthly income (23 083 to 8521 Bangladeshi Taka), with only a small recovery observed by November 2020. Conclusions and Relevance: In this study of households in rural Bangladesh, all-cause mortality was lower in 2020 compared with 2019. Restrictions imposed by the government may have limited the scale of the COVID-19 pandemic in rural areas, although economic data suggest that these restrictions need to be accompanied by expanded welfare programs.

Development and validation of a risk prediction model and scoring system for post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND: A few models have been proposed for the prediction of the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), but many include factors that are not assessed routinely. Herein, we intend to develop and validate a predictive model for the occurrence of PEP. METHODS: Data of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) from January 01, 2016 to May 16, 2019 (training set and internal test set) and from May 17, 2019 to December 25, 2019 (external test set) were retrospectively collected. The performance of the model was validated in the two validation cohorts. RESULTS: A total of 342 patients were included for the external test set, and 47 (13.7%) developed PEP. The variables included in the scoring system were gastrectomy history, high direct bilirubin (DBIL), high albumin (ALB), villous type of papillary orifice, nodular type of papillary orifice, pancreatic guidewire passages, precut sphincterotomy, and high operator experience. A total score >5 indicated high risk. In the external test set, the area under the curve (AUC) was 0.718, the sensitivity was 0.723, and the specificity was 0.676. In the external test set, the probability of PEP was 6.1%, 17.0%, and 37.5% in patients with low (<0), moderate (0-5), and high (>5) risk scores, respectively. CONCLUSIONS: This study established a scoring system for predicting the risk of PEP using routinely measured clinical variables. Its application in routine work warrants further investigation.

Endoscopic ultrasound-guided cholecystostomy for resection of gallbladder polyps with lumen-apposing metal stent.

Laparoscopic cholecystectomy is the routine method to treat gallbladder polyps. Nowadays, endoscopic ultrasound (EUS)-guided cholecystostomy as a bridge for per-oral transmural endoscopic resection of gallbladder polyps is introduced because preservation of gallbladder is increasingly getting attention. The aim of our study was to evaluate the approach in the treatment of patients with gallbladder polyps and symptomatic gallstones.EUS-guided cholecystostomy with the placement of a lumen-apposing metal stent (LAMS) was performed for those patients with accompanying gallbladder polyps and symptomatic gallstones. Several days after the cholecystostomy with LAMS, a gastroscope was introduced into the gallbladder to remove gallbladder polyps.All patients were successfully performed with the procedures of EUS-guided cholecystoduodenostomy (n = 3) or cholecystogastrostomy (n = 1) and endoscopic resection of gallbladder polyps. One patient experienced severe peritonitis. During the follow-up at 3 months, 1 patient was performed with laparoscopic cholecystectomy because ultrasonography examination showed the reappeared gallstones. No stone recurrence was found in other patients. During the follow-up of 3 to 15 months, no polyp recurrence was found in all the patients.The approach is novel for performing EUS-guided gallbladder fistulization, which can subsequently allow procedures of per-oral transmural endoscopic resection of gallbladder polyps to avoid cholecystectomy in the patients with gallbladder polyps and gallstones. However, further studies are needed before clinical recommendation because of the complications and stone recurrence.

Thromboelastography in Patients with Inflammatory Bowel Disease.

PURPOSE: Patients with inflammatory bowel disease (IBD) frequently suffer from venous thromboembolic events, and the risk of thromboembolism increases along with disease activity. This study was conducted to discover novel thrombophilic markers using thromboelastography (TEG) and to evaluate the relation between the predisposing factors and the activity of disease in Chinese patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Thirty-four patients with CD, 29 patients with UC, and 53 healthy volunteers were enrolled into this study. Blood levels of R, K, α Angle, G, maximal amplitude (MA), and LY30 with TEG were determined. RESULTS: Mean values of R, K, α Angle, G, and MA were significantly different in patients with CD and UC compared with the healthy individuals. Patients with active CD had different K, α Angle, G, and MA levels compared with patients in remission (P < 0.05, P < 0.001, P < 0.001, and P < 0.001). Levels of R, α Angle, G, and MA were also significantly different in active UC patients compared with those in remission (P < 0.01, P < 0.001, P < 0.001, and P < 0.001). Except for the G level in the CD group, differences in all TEG levels between healthy individuals and IBD patients in remission were not statistically significant. No statistical differences were observed in LY30 among patients with active phase, patients in remission, and the healthy individuals. CONCLUSION: Thrombophilic defects are common in Chinese patients with IBD, and TEG can be considered a new direction to anticoagulant thromboprophylaxis in IBD.

Fallout of Lead Over Paris From the 2019 Notre-Dame Cathedral Fire.

The roof and spire of Notre-Dame cathedral in Paris that caught fire and collapsed on 15 April 2019 were covered with 460 t of lead (Pb). Government reports documented Pb deposition immediately downwind of the cathedral and a twentyfold increase in airborne Pb concentrations at a distance of 50 km in the aftermath. For this study, we collected 100 samples of surface soil from tree pits, parks, and other sites in all directions within 1 km of the cathedral. Concentrations of Pb measured by X-ray fluorescence range from 30 to 9,000 mg/kg across the area, with a higher proportion of elevated concentrations to the northwest of the cathedral, in the direction of the wind prevailing during the fire. By integrating these observations with a Gaussian process regression model, we estimate that the average concentration of Pb in surface soil downwind of the cathedral is 430 (95% interval, 300-590) mg/kg, nearly double the average Pb concentration in the other directions of 240 (95% interval, 170-320) mg/kg. The difference corresponds to an integrated excess Pb inventory within a 1 km radius of 1.0 (95% interval, 0.5-1.5) t, about 0.2% of all the Pb covering the roof and spire. This is over 6 times the estimated amount of Pb deposited downwind 1-50 km from the cathedral. To what extent the concentrated fallout within 1 km documented here temporarily exposed the downwind population to Pb is difficult to confirm independently because too few soil, dust, and blood samples were collected immediately after the fire.

Seminal vesicle metastasis after liver transplantation for hepatocellular carcinoma: A case report.

RATIONALE: Cancer recurrence and metastasis after liver transplantation (LT) is common in some hepatocellular carcinoma (HCC) patients. The most common sites of extrahepatic metastases are lung, regional lymph node, adrenal gland, and bone. To our knowledge, HCC metastasis to the seminal vesicle after LT has not been reported in the literature. PATIENT CONCERNS: A 56-year-old Asian man presented at hospital with a 9-year history of orthotopic LT because of HCC. The patient underwent surgery and radiotherapy for HCC metastasis to adrenal gland and 1 year later, chemotherapy for peritoneal metastasis. A few months later, the patient presented with computed tomography (CT) image showing masses in right lobe of liver, seminal vesicle, and space occupying mass between the spleen and stomach. DIAGNOSES: Combination of clinical and pathological features revealed the seminal vesicle mass as metastasis from HCC. INTERVENTIONS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for liver and seminal vesicle lesions was performed and the postoperative pathology revealed malignancy. Thus, the patient underwent surgery and the diagnosis of seminal vesicle metastasis of HCC was confirmed by pathology and immunohistochemical analysis. OUTCOMES: The patient died due to systemic failure. LESSONS: Seminal vesicle metastasis from HCC after LT is rare and there is no consensus on its treatment. Further research into the pathogenesis and therapy of seminal vesicle from HCC after LT is needed to improve outcomes in the rare disease.

Crosstalk of mTOR/PKM2 and STAT3/c-Myc signaling pathways regulate the energy metabolism and acidic microenvironment of gastric cancer.

Cancer cells consume large amounts of glucose to produce lactate, even in the presence of ample oxygen. This phenomenon is called the Warburg effect. c-Myc is an important member of the Myc gene family and is involved in the development of various tumors. It plays an important role in the regulation of tumor energy metabolism, which can regulate glycolysis to promote the Warburg effect in a tumor. Our study aimed to improve the malignant biological behavior by controlling the energy metabolism of gastric cancer through the mTOR/PKM2 and signal transduction and activator 3 (STAT3)/c-Myc signaling pathways through a series of in vitro experiments. Human gastric cancer AGS and HGC-27 cells were treated with PKM2 and c-Myc lentivirus, and the effects of the knockdown of PKM2 and/or c-Myc were analyzed on cell proliferation, cell apoptosis, the ability of cell migration, and the growth signaling pathway in vitro. The expressions of PKM2, c-Myc, LDHA, STAT3, P-STAT3, GLUT-1 gene were identified by the quantitative real-time polymerase chain reaction and Western blot analysis. Lactate and glucose levels were tested by the corresponding kit. Our findings showed that PKM2 and c-Myc were upregulated in human gastric cancer. Knockdown of c-Myc in gastric cancer cells suppressed cell proliferation capacity and glycolysis level, and the inhibitory effects on gastric cancer cells upon co-knockdown of PKM2 and c-Myc were more obvious compared with knockout of PKM2 or c-Myc alone. And there was a correlation between the mTOR/PKM2 and the STAT3/c-Myc signaling pathways. Our results suggested that c-Myc might be considered a potential therapeutic target for gastric cancer and PKM2 combined with c-Myc could better inhibit the malignant biological behaviors of gastric cancer.

Effects of proton pump inhibitors on reversing multidrug resistance via downregulating V-ATPases/PI3K/Akt/mTOR/HIF-1α signaling pathway through TSC1/2 complex and Rheb in human gastric adenocarcinoma cells in vitro and in vivo.

BACKGROUND: Our study aimed to explore the effects of PPIs on reversing multidrug resistance (MDR) to chemotherapy in gastric cancer by inhibiting the expression of V-ATPases and the PI3K/Akt/mTOR/HIF-1α signal pathway. METHODS: The gastric cancer cell lines SGC7901 and the multidrug resistance cell lines SGC7901/MDR were pretreated by the pantoprazole or the esomeprazole, respectively. Real-time PCR was used to determine mRNA levels, and western blotting and immunofluorescent staining analyses were employed to determine the protein expressions and intracellular distributions of the V-ATPases, PI3K, Akt, mTOR, HIF-1α, P-gp and MRP1 before and after PPIs pretreatment. SGC7901/MDR cells were planted on the athymic nude mice. Then the effects of PPZ pretreatment and/or ADR were compared by determining the tumor size, tumor weight and nude mice weight. RESULTS: PPIs pretreatment could inhibit mRNA levels of V-ATPases, MDR1 and MRP1, PI3K, Akt, mTOR and HIF-1α. PPIs inhibited V-ATPases and down-regulated the expressions of P-gp and MRP1. And further to block the expression of mTOR by Rapamycin could obviously inhibit the expressions of HIF-1α, P-gp and MRP1 in a dose-dependent manner. Therefore, PPIs inhibited the expressions of V-ATPases and then reversed MDR of the chemotherapy in gastric cancer by inhibiting P-gp and MRP1, and it could be speculated that the mechanism might be closely related to down-regulating the PI3K/Akt/mTOR/HIF-1α signaling pathway. Meanwhile, PPIs also could inhibit the expressions of TSC1/TSC2 complex and Rheb which might be involved into regulating the signaling pathway intermediately. The weight growth rate of the mice bearing tumor in the treatment group was lower than that of the nude mice in the normal group, while the weight growth rate of the mice in control group was significantly lower than that of the normal group and the treatment group, presenting a downward trend. CONCLUSION: Therefore, PPIs inhibited the expressions of V-ATPases and then reversed MDR of the chemotherapy in gastric cancer by inhibiting P-gp and MRP1, and it could be speculated that the mechanism might be closely related to down-regulating the PI3K/Akt/mTOR/HIF-1α signaling pathway, and also to inhibiting the expressions of TSC1/TSC2 complex and Rheb which might be involved into regulating the signaling pathway intermediately.

Biomimetic Silk Scaffolds with an Amorphous Structure for Soft Tissue Engineering.

Fine tuning physical cues of silk fibroin (SF) biomaterials to match specific requirements for different soft tissues would be advantageous. Here, amorphous SF nanofibers were used to fabricate scaffolds with better hierarchical extracellular matrix (ECM) mimetic microstructures than previous silk scaffolds. Kinetic control was introduced into the scaffold forming process, resulting in the direct production of water-stable scaffolds with tunable secondary structures and thus mechanical properties. These biomaterials remained with amorphous structures, offering softer properties than prior scaffolds. The fine mechanical tunability of these systems provides a feasible way to optimize physical cues for improved cell proliferation and enhanced neovascularization in vivo. Multiple physical cues, such as partly ECM mimetic structures and optimized stiffness, provided suitable microenvironments for tissue ingrowth, suggesting the possibility of actively designing bioactive SF biomaterials. These systems suggest a promising strategy to develop novel SF biomaterials for soft tissue repair and regenerative medicine.

Risk factor analysis of post-ERCP cholangitis: A single-center experience.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) may have complications. Our study aimed to investigate the risk factors and prevention of post-ERCP cholangitis. METHODS: We retrospectively analyzed 4234 cases undergone ERCP in the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2008 to December 2013. Patient-related factors and procedure-related factors were analyzed to find the risk factors of post-ERCP cholangitis. The time point of post-ERCP cholangitis was also analyzed. Univariate and multivariate analyses were performed to define the independent risk factors of post-ERCP cholangitis. RESULTS: The success rate of ERCP was 96.8% (4099/4234). The overall complication rate was 9.4% (399/4234). Post-ERCP cholangitis occurred in 102 cases (2.4%, 102/4234). The most dangerous time of post-ERCP cholangitis was from 24 h-48 h after ERCP (45.1%, 46/102). Univariate analysis revealed that age, hypertension, diabetes, previous ERCP history, biliary stent insertion, pancreatography, endoscopic sphincterotomy, balloon dilation and hilar obstruction were risk factors of post-ERCP cholangitis (P < 0.05). Multivariate analysis indicated that age, previous ERCP history and hilar obstruction were independent risk factors (P < 0.05). While endoscopic stone extraction was the potential protective factor. CONCLUSIONS: Many risk factors are involved in post-ERCP cholangitis. Among them, old age, previous ERCP history and hilar obstruction were independently related to this post-ERCP complication.

Dilation Time in Endoscopic Papillary Balloon Dilation for Common Bile Duct Stones.

BACKGROUND: To assess the short-term outcomes after endoscopic sphincterotomy (EST) plus endoscopic papillary balloon dilation (EPBD) versus EPBD alone and appropriate balloon dilation time in EPBD alone. MATERIALS AND METHODS: A total of 413 patients with common bile duct stones (CBDSs) were included in the EST plus EPBD group and 84 were in the EPBD alone group. We retrospectively evaluated the safety and efficacy between EST plus EPBD and EPBD alone group. The patients in EPBD alone group were assigned to dilation time ≥5 minutes group (n=35) and time <5 minutes group (n=49). Further, we preliminarily discussed the influence of balloon dilation time on the procedure-related complications. RESULTS: Compared with EST plus EPBD, the patients in EPBD alone group were younger [56.6 (range: 18 to 95) vs. 65.1 (24 to 92) y; P=0.006], had smaller diameter of the largest stone [10.4 (range: 3 to 20) vs. 12.3 (5 to 30) mm; P<0.001] and were lesser frequently performed with jaundice [22 (26.2%) vs. 189 (45.8%); P=0.001]. The mean duration of postoperative hospital stay in EPBD alone group was significantly shorter than EST plus EPBD group [6.3 (range: 1 to 18) vs. 9.2 (1 to 44) d; P<0.001]. The patients in EPBD alone group had higher risk of post endoscopic retrograde cholangiopancreatography pancreatitis than EST plus EPBD group [11 (13.1%) vs. 22 (5.3%); P=0.009]. Patients in the dilation time <5 minutes group had higher risk to suffer from postoperative pancreatitis than the EST plus EPBD group [9 (18.4%) vs. 22 (5.3%); P=0.002], while patients in the dilation time ≥5 minutes group had less procedure-related hemorrhage than the EST plus EPBD group [0 vs. 36 (8.7%); P=0.047]. CONCLUSION: Long balloon dilation time in EPBD alone is safe and effective in treating CBDSs.

Histone deacetylase 3 overexpression in human cholangiocarcinoma and promotion of cell growth via apoptosis inhibition.

Histone deacetylase 3 (HDAC3) has an oncogenic role in apoptosis and contributes to the proliferation of cancer cells. MI192 is a novel HDAC3-specific inhibitor that displays antitumor activity in many cancer cell lines. However, the role of HDAC3 and the antitumor activity of its inhibitor MI192 are not known in cholangiocarcinoma (CCA). The present study aims to identify the target of MI192 in CCA as well as evaluate its therapeutic efficacy. CCK8 and colony formation assays showed that HDAC3 overexpression promotes proliferation in CCA cell lines. HDAC3 knockdown or treatment with MI192 decreased CCA cell growth and increased caspase-dependent apoptosis, while apoptosis was partially rescued by HDAC3 overexpression. We demonstrated that MI192 can inhibit the deacetylation activity of HDAC3 and its downstream targets in vitro, and MI192 inhibited xenograft tumor growth in vivo. Immunochemistry showed that HDAC3 was upregulated in CCA tissues compared with adjacent normal tissues, and this was correlated with reduced patient survival. Taken together, these results demonstrate for the first time that MI192 targets HDAC3 and induces apoptosis in human CCA cells. MI192 therefore shows the potential as a new drug candidate for CCA therapy.

Nanoscale Silk-Hydroxyapatite Hydrogels for Injectable Bone Biomaterials.

Injectable hydrogel systems are important bone substitutes for regeneration because of their handling properties and the ability to fill irregular defects. Silk-hydroxyapatite composite materials with silk nanofibers in hydrogels were prepared and used as biomaterials for osteogenesis. These thixotropic silk nanofiber hydrogels and water-dispersible silk-HA nanoparticles were blended to form injectable nanoscale systems with a homogeneous distribution of a high HA content [60% (w/w)] to imitate bone niche. A modulus of ∼21 kPa was also achieved following the addition of HA in the systems, providing physical cues to induce osteodifferentiation. The composite hydrogels supported improved osteogenesis compared to that with silk nanofiber hydrogels. The newly formed bone tissue and bone defect healing were detected after implantation of the silk-HA composite hydrogels, suggesting utility for the regeneration of irregular bone defects.

Correction to 'A Bayesian bird's eye view of 'Replications of important results in social psychology'.

[This corrects the article DOI: 10.1098/rsos.160426.].

A Bayesian bird's eye view of 'Replications of important results in social psychology'.

We applied three Bayesian methods to reanalyse the preregistered contributions to the Social Psychology special issue 'Replications of Important Results in Social Psychology' (Nosek & Lakens. 2014 Registered reports: a method to increase the credibility of published results. Soc. Psychol.45, 137-141. (doi:10.1027/1864-9335/a000192)). First, individual-experiment Bayesian parameter estimation revealed that for directed effect size measures, only three out of 44 central 95% credible intervals did not overlap with zero and fell in the expected direction. For undirected effect size measures, only four out of 59 credible intervals contained values greater than [Formula: see text] (10% of variance explained) and only 19 intervals contained values larger than [Formula: see text]. Second, a Bayesian random-effects meta-analysis for all 38 t-tests showed that only one out of the 38 hierarchically estimated credible intervals did not overlap with zero and fell in the expected direction. Third, a Bayes factor hypothesis test was used to quantify the evidence for the null hypothesis against a default one-sided alternative. Only seven out of 60 Bayes factors indicated non-anecdotal support in favour of the alternative hypothesis ([Formula: see text]), whereas 51 Bayes factors indicated at least some support for the null hypothesis. We hope that future analyses of replication success will embrace a more inclusive statistical approach by adopting a wider range of complementary techniques.

Lymphoepithelioma-like gastric carcinoma in a patient with rectal laterally spreading tumor: A case report.

Lymphoepithelioma-like gastric carcinoma (LELGC) is a rare neoplasm of the stomach that accounts for 1-4% of all gastric cancer cases. It is characterized by the presence of a lymphoid stroma with cells arranged primarily in micro alveolar, thin trabecular and primitive tubular patterns or isolated cells. In the present study, the case of a 50-year-old male patient with LELGC and rectal laterally spreading tumor is presented. Following endoscopic submucosal dissection, a diagnosis of carcinoma was reached and the patient underwent total radical gastrectomy. The postoperative pathological stage was IA T1bN0cM0 according to the Tumor-Node-Metastasis classification of gastric carcinoma, and the patient recovered well. The present case is reported to summarize the endoscopic and pathological characteristics of LELGC.