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The aim of this study was to determine if hypophosphatemia is more common in patients with severe alcohol-induced acute pancreatitis (AAP).This is a retrospective, single institution, cohort study that analyzed 147 patients admitted to the hospital for AAP. Multivariate logistic regression was used to determine if hypophosphatemia would be related to clinical outcomes of disease severity.Hypophosphatemia was more common in patients with severe AAP at admission; in addition, all patients with severe AAP (100%) eventually developed hypophosphatemia during admission, relative to those with mild (43%) and moderately severe (54%) AAP. The magnitude of the lowest phosphate measurement obtained during admission was lower in patients with severe AAP (mean, 1.5 mg/dL, standard deviation [SD], 0.5 mg/dL) relative to those with mild (mean, 2.6 mg/dL; SD, 0.9 mg/dL) and moderately severe (mean, 2.3 mg/dL; SD, 0.9 mg/dL) AAP (P0.001). Finally, patients who developed hypophosphatemia during admission were more likely to require intensive care unit admission (P0.001), vasopressors (P = 0.01), or intubation (P = 0.003).Hypophosphatemia is more common and of greater magnitude in patients admitted to the hospital with severe AAP. In addition, patients with severe AAP who develop hypophosphatemia during admission are more likely to have poorer clinical outcomes.

The aim of this study was to determine if the quick Sepsis-Related Organ Failure Assessment (qSOFA) score assessed at and 48 hours after admission is prognostic for alcohol-induced acute pancreatitis (AAP) severity.This is a retrospective cohort review study of 161 patients admitted to a single academic hospital in Houston, TX, with the diagnosis of AAP. Receiver operator characteristics analysis and logistic regression were used to assess the diagnostic accuracy and prognostic ability of the qSOFA score.A qSOFA score of 2 or higher at and 48 hours after admission had a specificity of 94% or greater and sensitivity of 33% or higher for pancreatitis severity and need for intensive care admission, intubation, or vasopressors. The qSOFA score at and 48 hours after admission was prognostic of intensive care unit admission by an adjusted odds ratio of 48.5 (95% confidence interval [CI], 6.4-1013.3; Plt; 0.001) and 18.8 (95% CI, 2.2-467.3; Plt; 0.05), respectively. The qSOFA score at admission was prognostic of severe pancreatitis by an adjusted odds ratio of 35.3 (95% CI, 7.2-224.3; Plt; 0.001).A qSOFA score of 2 or higher is highly specific and prognostic of multiple clinical outcomes both at and 48 hours after admission in patients with AAP.

Introduction Prognostic factors are needed to aid clinicians in managing Covid‐19, a respiratory illness. Lymphocytopenia has emerged as a simply obtained laboratory value that may correlate with prognosis. Methods In this article, we perform a retrospective cohort review study on patients admitted to one academic hospital for Covid‐19 illness. We analyzed basic demographic, clinical, and laboratory data to understand the relationship between lymphocytopenia at the time of hospital admission and clinical outcomes. Results We discovered that lymphocyte count is lower (P = .01) and lymphocytopenia more frequent by an odds ratio of 3.40 (95% CI: 1.06‐10.96; P = .04) in patients admitted to the Intensive Care Unit (ICU), a marker of disease severity, relative to those who were not. We additionally find that patients with lymphocytopenia were more likely to develop an acute kidney injury (AKI), a marker of organ failure, during admission by an odds ratio of 4.29 (95% CI: 1.35‐13.57; P = .01). Conclusion This evidence supports the hypothesis that lymphocytopenia can be an early, useful, and easily obtained, prognostic factor in determining the clinical course and disease severity of a patient admitted to the hospital for Covid‐19.

Prognostic markers are needed to understand the disease course and severity in patients with Covid-19. There is evidence that Covid-19 causes gastrointestinal symptoms and abnormalities in liver enzymes. We aimed to determine if hepatobiliary laboratory data could predict disease severity in patients with Covid-19. In this retrospective, single institution, cohort study that analyzed patients admitted to a community academic hospital with the diagnosis of Covid-19, we found that elevations of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) at any time during hospital admission increased the odds of ICU admission by 5.12 (95% CI: 1.55–16.89; p = 0.007), 4.71 (95% CI: 1.51–14.69; p = 0.01) and 4.12 (95% CI: 1.21–14.06, p = 0.02), respectively. Hypoalbuminemia found at the time of admission to the hospital was associated with increased mortality (p = 0.02), hypotension (p = 0.03), and need for vasopressors (p = 0.02), intubation (p = 0.01) and hemodialysis (p = 0.002). Additionally, there was evidence of liver injury: AST was significantly elevated above baseline in patients admitted to the ICU (54.2 ± 15.70 U/L) relative to those who were not (9.2 ± 4.89 U/L; p = 0.01). Taken together, this study found that hypoalbuminemia and abnormalities in hepatobiliary laboratory data may be prognostic factors for disease severity in patients admitted to the hospital with Covid-19.

Only a single study investigated erectile dysfunction (ED) among patients with chronic brucellosis without including a control group. Our study objective was to determine the prevalence of ED among patients with chronic brucellosis compared to normal subjects, and to explore the predictors of ED. We included 93 chronic brucellosis patients and 92 subjects as a control, from June 2013 to August 2017. Chronic brucellosis was diagnosed based on persistent symptoms for ≥1 year with positive immunoglobulin G antibody titer (≥1:160) by standard tube agglutination test; the mean duration was 21 ± 6.2 months. Clinical evaluation (including an Arabic validated version of the five-item International Index of Erectile Function to diagnose ED; score of 5–21 was diagnostic), imaging studies (including scrotal ultrasonography) and laboratory investigations (including estimation of fasting serum level of glucose (after fasting for 8 h), lipids profile (after fasting for 14 h), and serum level of testosterone) were conducted. A fasting serum glucose level of ≥ 7 mmol/L defined diabetes mellitus (DM). Predictors of ED were identified using multivariate analysis (binary logistic regression). The mean age of patients was 35.4 ± 13.7 years; 24.7% of them had DM, while low serum level of testosterone was detected among 54.8%. Among the patients, ED was significantly more frequent compared to the control subjects (69.9% vs. 19.6%, p

Maslinic acid (MA), a natural pentacyclictriterpene, displays cytotoxic activity on various types of cancer cells. However, its underlying mechanism is unclear. In this study, we assessed the effect of MA on autophagy of human pancreatic cancer cells, and the potential autophagic pathway was presented. MA inhibited the proliferation and induced autophagy of Panc-28 cells by altering the expressions of autophagy related proteins. SDS-PAGE analysis revealed that one protein band was significantly down-regulated in cells treated with MA, and the band was identified as heat shock protein HSPA8 as analyzed using Western blot and MS, MS/MS approaches. HSPA8 knockdown could significantly inhibit cell viability and enhance the cytotoxic effects of MA, whereas HSPA8 overexpression was able to enhance cell viability, diminishing the effects of MA. Western blot analysis indicated that the effect of MA on the expression of autophagy related genes was increased significantly in cells treated with HSPA8 inhibitor VER-155008, whereas HSPA8 inducer geranylgeranylacetone antagonized the effects of MA. Our study provides evidence that MA is able to induce of autophagy via down-regulation of HSPA8 in Panc-28 cells.

Background Our objective in this study was to evaluate the role and benefits in terms of local toxicity and biochemical disease-free survival (bDFS) following escalated-dose conformal radiation therapy in prostate adenocarcinoma. Methods The study population was composed of 53 patients with histologically proven T1b-T4, NO, MO prostate adenocarcinoma, having any Gleason score with prostate-specific antigen (PSA) of less than 50 ng/mL at diagnosis, given escalated dose EBRT (74 Gy) during the period between January 2011 and December 2013, retrospectively and evaluated for a period of 2 years post-radiation. Patients were followed up for a period of 2 years, beginning after completion of escalated dose external beam radiotherapy (EBRT) for biochemical failure as defined in ASTRO consensus committee guidelines 1996 and investigated for gastrointestinal, genitourinary skin toxicity. Results Out of 53 patients, 35 showed no biochemical failure at the end of 2 years following the completion of definitive escalated dose conformal radiotherapy while 18 were observed to have biochemical relapse. Acute gastrointestinal grade 1 toxicity was found in 26 patients, grade 2 in 24, and grade 3 only in 3 patients. Late gastrointestinal grade 0 toxicity was found in 16 patients, grade 1 in 28, grade 2 in 7 and grade 3 only in 2 patients. Grade 1 acute genitourinary toxicity was the highest in frequency observed in 28 of the total population followed by grade 2 in 21, grade 0 and grade 3 each, only in 2 patients. Late genitourinary Grade 0 toxicity was observed in 32 patients, grade 1 in 19, grade 2 and 3 only in 1 patient of the total population, respectively. Conclusion Our data were comparable to international studies of dose escalation using 3D and beneficial as compared to conventional radiation therapy delivered by 2D in terms of biochemical failure rate and treatment related toxicity.

Background and study aims There is a lack of studies on erectile dysfunction (ED) in patients diagnosed with nonalcoholic fatty liver disease (NAFLD). The present study aimed to estimate the prevalence of ED in patients with NAFLD and to determine the independent predictors of ED in these patients. Patients and methods We conducted a prospective, hospital-based study of 192 consecutive male patients with NAFLD. All patients underwent clinical evaluation; abdominal ultrasonography; test for viral hepatitis markers; and estimation of liver chemistry panel, complete blood count, prothrombin time, serum lipids panel, serum testosterone, and fasting serum levels of glucose, insulin, and C-peptide. Results The mean age of the study population was 42.4 ± 7.7 years (79.1% ≥ 40 years). Of the 192 patients with NAFLD, 88 (45.8%) had ED, 28 (14.6%) had metabolic syndrome, 25 (13%) had type-2 diabetes mellitus (DM), and 131 (68.2%) had insulin resistance (IR). The mean level of serum testosterone was 3.17 ± 2.94 ng/mL, while the mean insulin resistance index was 2.9 ± 1.7. Mild ED (38.6%) was the most frequent grade of ED. Age ≥ 40 years (odds ratio [OR] 6.4; 95% confidence interval [CI] 1.7–24.1; p- 0.006), IR (OR 5.9; 95% CI 1.7–20.6; p- 0.005), and low serum testosterone (OR 5.1; 95% CI 1.5–17.1; p- 0.009) were the predictors of ED. Conclusions ED is a common disorder in male patients with NAFLD; both IR and low serum testosterone contribute to its development. Treatment of IR may carry a dual benefit of improving erectile function and decreasing the grade of hepatic steatosis.

Background: Patients in countries endemic for chronic viral hepatitis are more vulnerable to antituberculosis therapy-induced liver disorders (ATT-LDs). The aim of this study was to explore the role of cholecalciferol in prophylaxis against ATT-LD among patients with pulmonary tuberculosis (TB) receiving ATT. Material and Methods: We conducted a hospital-based, prospective, randomized, comparative study which included 300 consecutive, naive patients with pulmonary TB eligible for ATT. The patients were randomly allocated to Group A (150 patients who received ATT) and Group B (150 patients who received ATT with cholecalciferol) who had clinical evaluation, laboratory investigations, and imaging studies. Statistical analysis used student's t-test and Chi-square test were used as appropriate to compare the variables between the study groups. Results: The study population mean age was 35.6 ± 15.3 years. The overall incidence rate of ATT-LD among the study population was 9.3%; the incidence rate was significantly higher among Group A patients compared to those of Group B (13.3 vs. 5.3%;P = 0.001). The onset of ATT-LD was significantly earlier among patients of Group A compared to those of Group B (31.4 vs. 58.7 days,P = 0.027), while the duration of ATT-LD was significantly longer among patients of Group A compared to those of Group B (34.8 vs. 16.9 days,P = 0.009). No adverse effects related to cholecalciferol use were observed. Conclusions: Adjuvant cholecalciferol supplementation may be protective against ATT-LD without extra adverse effects. Before recommending the routine use of cholecalciferol supplementation for prevention of ATT-LD, larger scale studies are recommended.

OBJECTIVE To determine the frequency of therapeutic failure among patients with acute and subacute brucellosis and to explore the predictors of failure. METHODS The study included 213 consecutive, naive patients with acute and subacute brucellosis. All participants underwent clinical evaluation, chest radiography, stool microscopic examination and interferon-gamma release assay. Patients received the WHO-recommended therapy of doxycycline 200 mg/day and rifampin 900 mg/day, for 6 weeks. RESULTS Mean age of the study population was 39.8 ± 12.2 years; 64.8% of them were males. The therapeutic failure rate was 16.4%. Adverse effects were reported by 13.1%. Multivariate analysis of factors associated with therapeutic failure revealed latent tuberculosis infection (LTBI) (OR 3.1, 95% CI, 1.9-24.6, P: 0.009), ascariasis (OR 2.6, 95% CI 1.5-17.9, P: 0.012), and the use of acid suppressive therapy (OR 2.1, 95% CI 1.2-19.5, P: 0.037) as the predictors of therapeutic failure. CONCLUSIONS The prevalence of therapeutic failure among the Egyptian patients with acute/subacute brucellosis is increasing. Predictors of therapeutic failure are LTBI, ascariasis, and the use of acid suppressive therapy.

Background Aging population, is a reality in many countries because of improvement in the health care, patient safety and other supplemental factors. Pharmacotherapy in this population must be evaluated due to their higher susceptibility to adverse drug outcomes, like potential drug-drug interactions (PDDIs). Research in this regard is limited particularly in developing countries. The aim of the study was to evaluate the prevalence and associated factors in this population. Methods The multicentered study evaluated the prevalence of potential drug-drug interactions and associated factors in elderly population at critical care units in Peshawar, Pakistan. Potential drug-drug interactions were evaluated using Micromedex DrugReax, while statistical analysis was performed using SPSS. Results A total of 70.17% elderly patients were observed to have at least one PDDI. A significant association was observed between presence of PDDIs and number of prescribed drugs, duration of stay and age (p

To explore the role of cholecalciferol for the prophylaxis against recurrent urinary tract infection (UTI) in patients with benign prostatic hyperplasia (BPH). Our randomized, uncontrolled prospective study included 389 naive BPH patients with moderate/severe symptoms, consecutively. The patients were randomly allocated to two groups; group-A included 193 patients who received tamsulosin, while group-B included another 196 patients who received tamsulosin with cholecalciferol. The study population was followed up for 2 years after the start of the treatment. For all the patients enrolled, clinical evaluation, imaging studies (abdominal and trans-rectal ultrasonography), and laboratory investigations [including urinalysis, urine culture with antibiotic susceptibility testing for positive cultures and estimation of prostate-specific antigen (PSA) level] were provided. The incidence rate of recurrent UTI was 9% among the study population; it was significantly higher among group-A patients compared to those of group-B (13.5% vs. 4.6%, p 0.003, OR 2.7, 95% CI 1.5–4.3). Compared to patients of group-A, those of group-B developed a significantly lower level of PSA at the end of treatment period (0.16 ± 0.03 ng/mL vs. 0.27 ± 0.08 ng/mL, p 0.043, OR 1.9, 95% CI 1.2–6.8). Adjuvant cholecalciferol supplementation may be protective against recurrent UTI among patients with BPH receiving tamsulosin therapy without extra adverse effects.

Background/objective Vitamin D deficiency may contribute to the therapeutic failure of antituberculosis therapy (ATT). The aim of this study is to explore the role of adding cholecalciferol to the standard ATT in improving the therapeutic outcome among the naive patients with pulmonary tuberculosis (TB). Methods A randomized, controlled, clinical study, which included 496 naive patients with pulmonary TB, was carried out. The patients were randomly allocated to two groups. Group-A included 247 patients who received ATT, while group-B included 249 patients who received ATT with cholecalciferol. Results The rate of therapeutic failure among the study population was 29.4%; it was significantly lower among patients of group-B compared to those of group-A (22.1% (95% CI 14.7–26.2) vs 38.1% (95% CI 31.5–46.1), p 0.036). In addition, the rate of early therapeutic response was significantly higher among patients of group-B compared to those of group-A (35.3% (95% CI 29.6–42.3) vs 19.4% (95% CI 15.1–24.6), p 0.041). Incidence rate of adverse effects was 19.3%; it was higher (although not statistically significant) among patients of group-A compared to those of group-B (21.9% vs 16.9%). Conclusions In conclusion, cholecalciferol-augmented ATT can be more efficacious in treating naive patients with pulmonary TB compared to the standard ATT. In addition, adding vitamin D3 to ATT provides extra protection against the hepatic and muscular adverse effects of ATT.

Background Infection with the Hepatitis B virus (HBV) continues to be one of the leading healthcare issues in Pakistan, affecting over 6 million people. The existence of HBsAg mutants is well documented in many countries. In Pakistan, HBV screening in the majority of the blood banks is performed by Rapid Detection Devices or ELISA tests. These tests are designed to detect HBsAg, but may not detect the mutant HBsAg. Failure to detect the HBsAg mutant may result in the transmission of HBV infection from donor to recipient. Hence, there is a need to identify a HBsAg assay which can detect mutants in a country where simple and conventional HBsAg assays with varying sensitivity and specificity are used to detect HBV infections. Material and methods Three routinely used diagnostic tests (Rapid Detection Devices, ELISA and CLIA) for HBsAg were compared with the LIAISON® XL Murex HBsAg Quant Assay to determine the prevalence of HBV mutants in the Pakistani blood donor population. The samples of blood donors from different cities of Pakistan were collected. The testing was performed using SD Bioline rapid assay (n = 1500), ELISA (n = 1500), and Abbott ARCHITECT®CLIA system (n = 1500) at the centers where the donations were collected. All samples (n = 4500) were re-tested for comparative analysis on the LIAISON® XL Murex HBsAg Quant assay (DiaSorin S.p.A.). PCR testing was performed as a gold standard on all discordant samples. Results 119/4500 (2.64%) of the samples were positive for antibodies against HBsAg. The sensitivity of SD Bioline Rapid, GB HBsAg ELISA, Abbott ARCHITECT® and LIAISON® XL Murex HBsAg Quant assay was 17.24%, 43.75%, 90.91%and 100% respectively. The specificity of SD Bioline Rapid, GB HBsAg ELISA, Abbott ARCHITECT® and LIAISON® XL Murex HBsAg Quant Assay was 98.82%, 99.59%, 100% and 100%, respectively. Conclusion LIAISON® XL Murex HBsAg Quant assay is a highly sensitive, specific and accurate screening assay for detecting wild type as well as mutant HBsAg.

No previous studies have investigated the prevalence of latent tuberculosis infection (LTBI) among patients with erectile dysfunction (ED) or its contribution to the development of high-grade ED through a process of chronic inflammation-induced atherosclerosis. The aim of this study was to determine the frequency of LTBI among patients with erectile dysfunction and to explore the contribution of LTBI to high-grade ED. For all the study sample, clinical evaluation, imaging studies, and laboratory investigations were provided. Evaluation included, but was not confined to, scrotal ultrasonography, tuberculin skin test, and QuantiFERON-TB Gold test. The study sample mean ± SD age was 47.9 ± 13.6 years. Approximately 30% of the patients had LTBI and 43% had high-grade ED. After a multivariate analysis, it was found that older age (≥40 years) (OR, 5.2; 95% CI, 1.9–54.6; p 0.004), metabolic syndrome (MS) (OR, 3.4; 95% CI, 1.3–48.2; p 0.016), and LTBI (OR, 4.1; 95% CI, 1.7–61.3; p 0.021) were significantly, independently associated with high-grade ED as opposed to low-grade ED. In conclusion, the prevalence of LTBI among patients with high-grade ED is higher than among those with low-grade ED. In addition to LTBI, older age and MS are associated with high-grade ED as opposed to low-grade ED.

Background & Aims The NACHT, LRR, and pyrin domain–containing protein 3 (NLRP3) inflammasome induces inflammation in response to organ injury, but little is known about its regulation. Toll-like receptors (TLRs) provide the first signal required for activation of the inflammasome and stimulate aerobic glycolysis to generate lactate. We examined whether lactate and the lactate receptor, G i -protein–coupled receptor 81 (GPR81), regulate TLR induction of signal 1 and limit inflammasome activation and organ injury. Methods Primary mouse macrophages and human monocytes were incubated with TLR4 agonists and lactate and assayed for levels of pro-interleukin (IL)1β, NLRP3, and caspase-1 (CASP1); release of IL1β; and activation of nuclear factor-κB (NF-κB) and caspase-1. Small interfering RNAs were used to reduce levels of GPR81 and arrestin β-2 (ARRB2), and an NF-κB luciferase reporter transgene was transfected in RAW 264.7 cells. Cell lysates were analyzed by immunoprecipitation with an antibody against GPR81. Acute hepatitis was induced in C56BL/6N mice by administration of lipopolysaccharide and D-galactosamine. Acute pancreatitis was induced by administration of lipopolysaccharide and cerulein. Some mice were given intraperitoneal injections of sodium lactate or small interfering RNA against Gpr81. Activation of NF-κB in tissue macrophages was assessed in mice that expressed a reporter transgene. Results In macrophages and monocytes, increasing concentrations of lactate reduced TLR4-mediated induction of Il1B , Nlrp3 , and Casp1 ; activation of NF-κB; release of IL1β; and cleavage of CASP1. GPR81 and ARRB2 physically interacted and were required for these effects. The administration of lactate reduced inflammation and organ injury in mice with immune hepatitis; this reduction required Gpr81 dependence in vivo. Lactate also prevented activation of NF-κB in macrophages of mice, and, when given after injury, reduced the severity of acute pancreatitis and acute liver injury. Conclusions Lactate negatively regulates TLR induction of the NLRP3 inflammasome and production of IL1β, via ARRB2 and GPR81. Lactate could be a promising immunomodulatory therapy for patients with acute organ injury.

Question: A 60-yearold obese (body mass index of 50 kg/m2) woman was admitted through the emergency department with a history of severe colicky abdominal pain, abdominal distension, and constipation. She was known to have diverticular disease of sigmoid colon, hypertension, diabetes, and chronic obstructive pulmonary disease. here was no history of any previous abdominal operations. On examination, she was found to have distended abdomen with severe enderness and guarding in the left iliac fossa. Her bowel sounds were increased. She had an elevated white cell count (18,000/mm3) and normal liver function tests. Her plain abdominal film showed large bowel dilatation with cutoff in the sigmoid colon. With the clinical impression of large bowel obstruction with possible acute diverticulitis she underwent an emergency abdominal (Figure A) and pelvic (Figure B) computed tomography (CT). What is the complete diagnosis? Look on page 2279 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information n submitting your favorite image to Clinical Challenges and Images in GI. Conflicts of interest: The authors disclose no conflicts. © 2011 by the AGA Institute 0016-5085/$36.00 doi:10.1053/j.gastro.2010.11.042

Background/Aim: Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are common in Egypt, and their coexistence is expected. There is controversy regarding the influence of NAFLD on chronic HCV disease progression. This study evaluates the effect of NAFLD on the severity of chronic hepatitis C (CHC) (necroinflammation and fibrosis) and assesses the relative contribution of insulin resistance syndrome to the occurrence of NAFLD in patients with chronic HCV infection. Patients and Methods: Untreated consecutive adults with chronic HCV infection admitted for liver biopsy were included in this study. Before liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis. Results: Our study included 92 male patients. Their mean ± SD age and aspartate aminotransferase (AST) level were 42 ± 7.7 years (range 20-56) and 68 ± 41.7 U/L (range 16-214), respectively. The mean insulin level and insulin resistance index were 15.6 ± 18.3 mIU/mL (range 5.1-137.4) and 5.9 ± 15.2 (range 0.9-136.2), respectively. Fifty four percent of patients had steatosis and 65% had fibrosis. In multivariate analyses, steatosis was associated with insulin resistance and fibrosis was associated with high AST level, age ≥40 years, and steatosis. Conclusions: Steatosis is a histopathologic feature in >50% of patients with chronic HCV infection. Insulin resistance has an important role in the pathogenesis of steatosis, which represents a significant determinant of fibrosis together with high serum AST level and older age.

Objective/background The aim of this study is to determine the rate of hookworm infection among patients with pulmonary tuberculosis (TB) and to find out if there is a relation between hookworm infection and the therapeutic failure of pulmonary TB. Methods We carried out a prospective, hospital-based study. The study included 231 naive patients with pulmonary TB, consecutively. Patients were evaluated at the 4th month of therapy for persistence of Mycobacterium tuberculosis infection. All patients had clinical evaluation, laboratory investigations (including sputum culture and stool microscopic examination), and imaging studies (abdominal ultrasonography and chest radiography). Results The study population mean age was 42.7 ± 13.9 years old with 26.8% of them 40 years old or more. Out of 231 patients, 133 (57.6%) were men. Therapeutic failure rate of pulmonary TB was 29.4%. Hookworm infection was diagnosed among 16.5% of patients and 27.7% had diabetes mellitus (DM). Using multivariate analysis, it was found that age of 40 years or more (odds ratio [OR] 8.4; 95% confidence interval [CI] 1.7–41.3; p = .009), hookworm infection (OR 7.6; 95% CI 1.2–49.9; p = .034), and DM (OR 5.9; 1.2–28; p = .027) were independently associated with therapeutic failure of pulmonary TB among the study population with pulmonary TB. Conclusion In conclusion, the rate of therapeutic failure of pulmonary TB is high. Besides older age and DM, hookworm infection can reduce the therapeutic response of pulmonary TB. Screening for and control of DM and hookworm infection among patients with pulmonary TB may improve their therapeutic response.

Activation of the cytosolic inflammasome machinery is responsible for acute and chronic liver inflammation, but little is known about its regulation. The N-methyl-d-aspartate (NMDA) receptor families are heterotetrameric ligand-gated ion channels that are activated by a range of metabolites, including aspartate, glutamate, and polyunsaturated fatty acids. In the brain NMDA receptors are present on neuronal and nonneuronal cells and regulate a diverse range of functions. We tested the role of the NMDA receptor and aspartate in inflammasome regulation in vitro and in models of acute hepatitis and pancreatitis. We demonstrate that the NMDA receptor is present on Kupffer cells, and their activation on primary mouse and human cells limits inflammasome activation by downregulating NOD-like receptor family, pyrin domain containing 3 and procaspase-1. The NMDA receptor pathway is active in vivo, limits injury in acute hepatitis, and can be therapeutically further activated by aspartate providing protection in acute inflammatory liver injury. Downregulation of inflammasome activation by NMDA occurs via a β-arrestin-2 NF-kβ and JNK pathway and not via Ca2+ mobilization. We have identified the NMDA receptor as a regulator of inflammasome activity in vitro and in vivo. This has identified a new area of immune regulation associated by metabolites that may be relevant in a diverse range of conditions, including nonalcoholic steatohepatitis and total parenteral nutrition-induced immune suppression.

TLR9 is a key determinant of the innate immune responses in both infectious and sterile injury. Specific antagonism of TLR9 is of great clinical interest to reduce tissue damage in a wide range of pathologies, and has been approached by modification of nucleic acids, the recognized ligand for TLR9. Such oligonucleotide-derived pharmacotherapeutics have limitations in specificity for nucleic acid receptors, significant potential for immunologic recognition with generation of innate and adaptive immune responses, and limited bioavailability. We have identified enantiomeric analogues of traditional (−)-morphinans as having TLR9 antagonist properties on reporter cell lines. One of these analogues (COV08-0064) is demonstrated to be a novel small-molecule antagonist of TLR9 with greater specificity for TLR9 than oligo-based antagonists. COV08-0064 has wide bioavailability, including the s.c. and oral routes. It specifically inhibits the action of TLR9 antagonists on reporter cells lines and the production of cytokines by TLR9 agonists from primary cells. It also has efficacy in limiting TLR9-mediated sterile inflammation in in vivo models of acute liver injury and acute pancreatitis. The identification of a morphinan-based novel small-molecule structure with TLR9 antagonism is a significant step in expanding therapeutic strategies in the field of sterile inflammatory injury.

Background and study aims Association of ulcerative colitis (UC) with hepatobiliary disorders is well recognised. The most common hepatobiliary complications of inflammatory bowel disease (IBD) are fatty liver infiltration and cholelithiasis. The prevalence of liver dysfunction in IBD remains unclear. The aim of the study is to try to identify the frequency and risk factors of hepatobiliary disorders among patients with UC in Upper Egypt. Patients and methods We prospectively analysed 33 patients with newly diagnosed UC of Tropical Medicine and Gastroenterology Department, Assiut University Hospital. For all participants, the following were conducted: clinical evaluation, abdominal ultrasonography (US) examination and laboratory investigations. Risk factors of hepatobiliary disorders were identified using univariate, then multivariate analysis. Results The frequency of hepatic disorders (fatty liver and elevated liver chemistry) was 75.8% in study patients while the frequency of biliary disorders (gallbladder stones and gallbladder wall thickening) was 54.5%. A higher risk of hepatic disorders was observed with older age (odds ratio (OR) 14, 95% confidence interval (CI) 2–124). A higher risk of biliary disorders was observed with UC severe activity index (OR 27, 95% CI 3–292). Conclusions The frequency of hepatobiliary disorders in patients with UC exceeded what was previously reported. High frequency of hepatic disorders was related to older age, while that of biliary disorders was related to UC activity.

Accurate open reduction and internal fixation for metacarpal and phalangeal fractures of the hand is required in less than 5% of the patients; otherwise, closed treatment techniques offer satisfactory results in most of these cases as these fractures are stable either before or after closed reduction. AO mini-fragment screws and plates, when used in properly selected cases, can provide rigid fixation, allowing early mobilization of joints and hence good functional results while avoiding problems associated with protruding K-wires and immobilization. The advantages of such internal fixation urged us to undertake such a study in our state where such hand injuries are commonly seen.Forty patients with 42 unstable metacarpal and phalangeal fractures were treated with open reduction and internal fixation using AO mini-fragment screws and plates over a period of three years in a prospective manner.The overall results were good in 78.5% of cases, fair in 19% of cases and poor in 2.5% of cases, as judged according to the criteria of the American Society for Surgery of the Hand.This technique is a reasonable option for treating unstable metacarpal and phalangeal fractures as it provides a highly rigid fixation, which is sufficient to allow early mobilization of the adjacent joints, thus helping to achieve good functional results.