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Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients, the disease progresses to critical limb ischaemia (CLI), also known as critical limb-threatening ischaemia. In a substantial number of individuals with CLI, no effective treatment options other than amputation are available, with around a quarter of these patients requiring a major amputation during the following year. This is the second update of a review first published in 2011.To evaluate the benefits and harms of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for CLI.We used standard, extensive Cochrane search methods. The latest search date was 8 November 2021.We included all randomised controlled trials (RCTs) of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention, conventional conservative therapy, or placebo).We used standard Cochrane methods. Our primary outcomes of interest were all-cause mortality, pain, and amputation. Our secondary outcomes were angiographic analysis, ankle-brachial index (ABI), pain-free walking distance, side effects and complications. We assessed the certainty of the evidence using the GRADE approach.We included four RCTs involving a total of 176 participants with a clinical diagnosis of CLI. Participants were randomised to receive either intramuscular cell implantation of BMMNCs or control. The control arms varied between studies, and included conventional therapy, diluted autologous peripheral blood, and saline. There was no clear evidence of an effect on mortality related to the administration of BMMNCs compared to control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.15 to 6.63; 3 studies, 123 participants; very low-certainty evidence). All trials assessed changes in pain severity, but the trials used different forms of pain assessment tools, so we were unable to pool data. Three studies individually reported that no differences in pain reduction were observed between the BMMNC and control groups. One study reported that reduction in rest pain was greater in the BMMNC group compared to the control group (very low-certainty evidence). All four trials reported the rate of amputation at the end of the study period. We are uncertain if amputations were reduced in the BMMNC group compared to the control group, as a possible small effect (RR 0.52, 95% CI 0.27 to 0.99; 4 studies, 176 participants; very low-certainty evidence) was lost after undertaking sensitivity analysis (RR 0.52, 95% CI 0.19 to 1.39; 2 studies, 89 participants). None of the included studies reported any angiographic analysis. Ankle-brachial index was reported differently by each study, so we were not able to pool the data. Three studies reported no changes between groups, and one study reported greater improvement in ABI (as haemodynamic improvement) in the BMMNC group compared to the control group (very low-certainty evidence). One study reported pain-free walking distance, finding no clear difference between BMMNC and control groups (low-certainty evidence). We pooled the data for side effects reported during the follow-up, and this did not show any clear difference between BMMNC and control groups (RR 2.13, 95% CI 0.50 to 8.97; 4 studies, 176 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the concerns about risk of bias, imprecision, and inconsistency.We identified a small number of studies that met our inclusion criteria, and these differed in the controls they used and how they measured important outcomes. Limited data from these trials provide very low- to low-certainty evidence, and we are unable to draw conclusions to support the use of local intramuscular transplantation of BMMNC for improving clinical outcomes in people with CLI. Evidence from larger RCTs is needed in order to provide adequate statistical power to assess the role of this procedure.

IDegLira-HIGH trial was a non-inferiority, prospective, randomized clinical trial, comparing the efficacy and safety of insulin degludec/liraglutide combination (IDegLira) and a regimen of multiple daily injections (MDI) with basal-bolus insulin (BB) in adults (>18-80 years of age) , with type 2 diabetes (T2D) , and very high HbA1c (>9%-15%) , previously treated with basal insulin or multiple oral agents. Primary endpoint was change in HbA1c from baseline to week 26. Secondary endpoints included incidence of hypoglycemia, changes on weight and glycemic variability (% coefficient of variation [%CV]) . Treatment with IDegLira and BB insulin resulted in similar improvement in glycemic control: 7.7±1.7% and 7.7±1.5%, (p=0.76) , with a reduction from baseline of -3.2±2.3% and -3.0±1.8%, (p=0.39) at 26-weeks. IDegLira resulted in lower rates of hypoglycemia Disclosure R.J.Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. B.Moazzami: None. M.F.Scioscia: None. P.Vellanki: n/a. G.M.Davis: Consultant; Medscape, Research Support; Insulet Corporation. F.J.Pasquel: Consultant; AI Health LLC, Boehringer Ingelheim International GmbH, Dexcom, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Merck & Co., Inc. M.Fayfman: None. A.L.Migdal: None. J.Saling: None. Funding Investigator-initiated study to Emory University (PI. Dr. Rodolfo J. Galindo) from Novo Nordisk.

Background and Methods: This cross-sectional study determined the prevalence of diabetic retinopathy (DR) in non-Hispanic African Americans (AA) with end-stage-kidney disease (ESKD) and their impact on quality of life. A total of 95 adults with type 1 (n= 10) and type 2 (n= 85) on dialysis diabetes were assessed for DR using portable hand-held (Optomed Aurora) with artificial intelligence report with AEYE Diagnostic System (AEYE-DS) , visual acuity using a Snellen chart, and social determents of health, and standardized questionnaires (Kidney Disease Quality of Life (KDQoL) , depression screening (Patient health Questionaire-9) and food insecurity. Results: Among the 95 participants (female 51%, mean age 59.5 ±12.3 years, duration of diabetes (DM) 18.2 ± 12.0 years and duration of dialysis 4.5±3.6 years) . A total of 55% of patients had a diagnosis of (DR+) , who had a longer duration of DM (18.8±9.5 vs. 15.8±12.2 years, p=0.20 and shorter duration of dialysis (3.6±2.7 vs. 5.9±5.0 years compared to DR negative (DR-) , p=0.09. Kidney Disease Quality of Life score on symptoms/problems related to ESKD and greater effect of kidney disease in daily life were lower compared to the general US, AA population with ESKD, p Disclosure M. Egeolu: None. G. E. Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. E. Manishimwe: None. Z. E. Zabala: None. B. Moazzami: None. R. L. Caleon: None. R. J. Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. J. E. Navarrete: None. A. Y. G. Gerges: None. L. Peng: None.

Background: Prescribing insulin pens without needles during hospital discharge was common in our hospital system. We assessed the impact of quality initiatives and prescribing guidance on the prevalence of patients discharged on insulin pens with and without an associated prescription for pen needles. Methods: We retrospectively collected data from Emory-healthcare hospitals, from January 2015-May 2018 (pre-intervention period) , then up to October 2021 (post-intervention period) . Adults (>18 years) with at least one prescription for insulin pens were included. As part of an updated discharge plan, an automated EMR alert was linked to orders for insulin pens without needles, aiming to reduce prescription errors at discharge. We compared the proportion of patients discharged on insulin pens with/without an associated pen needles prescription during the pre and post-intervention periods. We used interrupted time-series analysis (ITS) to examine the intervention impact on 30- and 90-day hospital readmissions. Result: Among 7654 patients discharged with insulin pens (median age 56 years, IQR 45-66) , 50.4% were Females, 65.5% were African-Americans, and mean HbA1c was 10.9±2.9%. After the intervention, the proportion of patients without an associated prescription for pen needles decreased compared to the pre-intervention (mean decrease 31.3%, 95% CI: 31.2%, 31.3%) . Inpatient diabetes education consult was more common among those with an associated pen needles prescription during the pre- (61.4% vs. 33.7%) and post-intervention period (64.7% vs. 33%) , compared to those without it, p Conclusion: Our initiative significantly decreased the prevalence of missing pen needles prescriptions by ∼30%, and was associated with less 90-days hospital readmission rates. Disclosure B. Moazzami: None. M. Wald: None. R. Jagannathan: None. R. J. Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. P. Hwang: None. S. Ashraf: None. A. Van prooyen: None. H. F. Shabbir: None. M. Klimenko: None. E. Brechtelsbauer: None. E. Molitch-hou: None. M. A. Hinds: None.

BACKGROUND: Decision-making on allocating scarce medical resources is crucial in the context of a strong health system reaction to the coronavirus disease 2019 (COVID-19) pandemic. Therefore, understanding the risk factors related to a high mortality rate can enable the physicians for a better decision-making process. METHODS: Information was collected regarding clinical, demographic, and epidemiological features of the definite COVID-19 cases. Through Cox regression and statistical analysis, the risk factors related to mortality were determined. The Kaplan-Meier curve was used to estimate survival function and measure the mean length of living time in the patients. RESULTS: Among about 3000 patients admitted in the Taleghani hospital as outpatients with suspicious signs and symptoms of COVID-19 in 2 months, 214 people were confirmed positive for this virus using the polymerase chain reaction (PCR) technique. Median time to death was 30 days. In this population, 24.29% of the patients died and 24.76% of them were admitted to the ICU (intensive care unit) during hospitalization. The results of Multivariate Cox regression Analysis showed that factors including age (HR, 1.031; 95% CI, 1.001-1.062; P value=0.04), and C-reactive protein (CRP) (HR, 1.007; 95% CI, 1.000-1.015; P value=0.04) could independently predict mortality. Furthermore, the results showed that age above 59 years directly increased mortality rate and decreased survival among our study population. CONCLUSION: Predictor factors play an important role in decisions on public health policy-making. Our findings suggested that advanced age and CRP were independent mortality rate predictors in the admitted patients.

Both the innate and adaptive arms of the immune system are involved in the development of autoimmune diseases. The main mechanism of disease is due to adaptive immune cells that are active against self-antigens. These cells can cause major damage to body tissues. Innate lymphoid cells (ILCs) are an important type of innate immune cell, whose role has been highlighted in recent years. ILCs are responsible for some of the inflammation in the pathogenesis of autoimmune diseases. In this review, we discuss the role of ILCs in the immune response, as well as their involvement in various autoimmune diseases.

Introduction The prevalence of undiagnosed primary immunodeficiency diseases is remarkably high and contributes to increasing the rate of morbidity and mortality among this group of patients. Objective To examine the 10 warning sign scoring system in patients suspected of primary immune deficiency and also estimate the diagnostic delay in patients with proven disease. Methods This descriptive cross-sectional study was carried out during the years 2015–2016 in Ali Asghar (AS) Clinic and Hospital. Two hundred patients with suspected primary immune deficiency disease were eligible for inclusion in the study. Multivariable logistic regression analysis was used to determine the relation between findings. Results In this study, the majority of suspected cases of immunodeficiency were males (57%) with a mean age of 3.33 ± 2.89 years. Twenty-one (10.5%) patients were diagnosed with immunodeficiency disease. The mean diagnostic delay among primary immune deficient patients was 2.05 ± 1.7 years. There was a significant relationship between having parental consanguinity (OR = 2.68, 95% CI: 1.07–6.70), allergies (OR = 5.03, 95% CI: 1.13–22.31), vaccine adverse effects (OR = 9.31, 95% CI: 1.24–69.96) and primary immune deficiency diagnosis. No association was observed between age (OR = 0.98, 95% CI: 0.84–1.14), gender (OR = 0.99, 95% CI: 0.39–2.47), immune deficiency scoring (OR = 0.68, 95% CI: 0.31–1.45) and primary immune deficiency diagnosis. Conclusion Ten warning sign scoring system is of less value to consider a patient suspected of having primary immune deficiency. There is a meaningful delay in diagnosis of primary immune deficiencies especially in antibody deficiency defects which seeks further upgrading of knowledge in physicians.

The liver plays a pivotal role in maintaining the homeostasis of various organ systems. Also, end-stage liver disease and its complications are major causes of morbidity and mortality among adults. Individuals who develop a chronic liver disease are at increased risk of progression to multi-organ dysfunction, including the pulmonary system. The clinical complications of pulmonary problems related to the presence of liver disease range from mild (such as hypoxemia) to life-threatening diseases (such as portopulmonary hypertension and hepatopulmonary syndrome). Herein, the major pulmonary complications related to liver cirrhosis and considerations for performing liver transplantation are reviewed.

Since the rapidly evolving outbreak of COVID-19, several empirical therapeutic options have been recommended including the use of antivirals, steroids, and vaccines. According to recent observations about different modalities in treatment of patients infected with COVID-19, plasmapheresis and intravenous immunoglobulin (IVIg) have been reported to be an effective empirical therapeutic option to control the infection. In this review, we aimed to provide an overview on the possible application of plasmapheresis and intravenous immunoglobulin in patients with COVID-19.

OBJECTIVES Length of stay is considered an important surrogate for transplant survival rate and resource utilization. Therefore, in the present study, our aim was to determine factors affecting length of hospital stay. MATERIALS AND METHODS We retrospectively analyzed records of patients who underwent liver transplant at the Tehran University of Medical Sciences Liver Transplantation Center from March 2014 to March 2016. RESULTS For our final analyses, there were 161 adult recipients, including 106 males (65.8%) and 55 females (34.1%). Univariate analyses showed that body mass index, Modelfor End-Stage Liver Disease score, duration of surgery, number of administered packed red blood cells and fibrinogen during surgery, reoperation, retransplant, bacterial infection, pleural effusion, ascites, renal failure that required dialysis, and wound infection were risk factors for length of hospital stay. After multivariate linear regression analysis, only body mass index (β = 0.016; P = .028), Model for End-Stage Liver Disease score (β = 0.017; P = .002), surgical duration (β = 0.002; P = .001), reoperation (β = 0.016; P < .001), presence of pleural effusion (β = 0.212; P = .042), and management of bacterial infection (β = 0.21; P = .03) and psychiatric problems after liver transplant (β = 0.213; P = .025) were independent risk factors for length of hospital stay. CONCLUSIONS The present study showed that multiple preoperative, intraoperative, and postoperative variables could have an impact on length of hospitalization. Therefore, methods for assessing these factors could improve patient outcomes and resource savings in liver transplant centers.

Cholangiocarcinoma (CCA) is the second most frequent primary liver tumor and defined as the heterogeneous group of tumors derived from cells in the biliary tree. Based on the anatomical locations (intrahepatic, perihilar, and distal), there are various approaches to the diagnosis and treatment of CCA. Imaging modalities, staging classifications, understandings around natural behavior of CCA, and therapeutic strategies have had remarkable progress in recent years. This article reviews and discusses the epidemiology, clinical presentation, diagnosis, and treatment modalities of CCA; determines the appropriate inclusion and exclusion criteria for liver transplantation (LT); and defines the risk of disease progression for patients in the waiting list of LT.

Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a negative impact on patient quality of life and potentially resulting in early liver transplants. Given the main role of the autotaxin enzyme in pruritus induced by CLD and the suppressive effects of melatonin on the expression of the autotaxin gene, this study was designed to evaluate the antipruritic effect of melatonin in patients with CLD. A double-blind, cross-over, randomized, placebo-controlled pilot trial was conducted on patients with CLD -induced pruritis. Patients were randomly assigned to two groups where they received melatonin 10-mg at night or placebo for 2 weeks. After a 2-week washout period, patients were then crossed over to the other group. The Visual Analog Scale (VAS) and the 12-Item Pruritus Severity Score (12-PSS) were used to assess patient response to therapy as the co-primary outcomes, while liver function tests were assayed too. Forty patients completed the study. The VAS score showed alleviation of 3.21 ± 2.24 (in pruritus) with melatonin (

Hyper Immunoglobulin M (HIgM) syndrome is a heterogeneous group of primary immunodeficiency disorders, characterized by recurrent infections and associated with decreased serum IgG and IgA, but normal or increased IgM. The aim of the present study was to evaluate respiratory manifestations in patients with HIgM syndrome. A total number of 62 patients, including 46 males and 16 females were included in the present study. To investigate the respiratory complications among HIgM patients, we evaluated the clinical hospital records, immunologic and molecular diagnostic assays, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans. Pneumonia was the most common respiratory manifestation (n = 35, 56.4%), followed by otitis media (45.1%), sinusitis (33.8%), and bronchiectasis (14.5%). 52.1% of the patients had abnormal PFT results, with a predominant restrictive pattern of changes. HRCT scans demonstrated abnormal findings in 85.7% of patients with found mutations. Ten cases had hilar lymphadenopathy and para-hilar infiltrates in their HRCT findings. Genetic diagnosis was confirmed in 29 HIgM patients (72.4% CD40 ligand (CD40L) and 24.1% activation-induced cytidine deaminase (AICDA/AID) deficiencies). Majority of patients with CD40L (71.4%) and AID (57.1%) deficiencies had missense mutations. Pneumonia and abnormal high-resolution computed tomography (HRCT) findings were more frequent among patients with CD40L mutation. Respiratory failure constituted the major cause of mortality (37.5%) with majority of cases occurring in CD40L-deficient patients (50%). Respiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients.

OBJECTIVES Protein tyrosine phosphatase non-receptor type 22 gene (PTPN22) single-nucleotide polymorphisms (SNP) have been associated with a number of different autoimmune diseases. This study aimed to investigate the association of five polymorphisms of PTPN22 gene with susceptibility to ulcerative colitis (UC) in Iran. MATERIALS AND METHODS A total of 67 patients diagnosed with UC (35 female and 32 male all under 18 years) and 93 healthy subjects were selected. The samples were genotyped for the, rs12760457, rs2476601, rs1310182, rs1217414, and rs33996649 in PTPN22 gene using real-time polymerase chain reaction (PCR) allelic discrimination TaqMan genotyping assays. RESULTS The frequencies of the rs1310182 A and G alleles, and also the AA and GG genotypes were significantly different between the patient and the control groups (p

Background Dietary modification is considered as one of the main strategies in the management of nonalcoholic fatty liver disease (NAFLD). The objective of this study was to systematically investigate the effect of dietary interventions on the cardio-metabolic risk factors, including lipid profile and insulin resistance in this population. Methods We searched electronic databases of PubMed and Scopus until January 2020 and included randomized controlled trials that compared the effect of dietary modifications vs. control on lipid profile and insulin resistance in patients with NAFLD. The random-effect analysis was performed to calculate pooled weighted mean differences (WMD). Results Our finding showed that serum triglycerides (TG) (n=5, WMD -38.50 mg/dL, 95% confidence interval [CI] -61.68 to -15.31; P=0.001) and total cholesterol (TC) (n=4, WMD -18.70 mg/dL, 95%CI -34.85 to -2.53; P=0.023) decrease following diet intervention along with marginally significant weight reduction (n=5, WMD -3.61 mg/dL, 95%CI -7.25 to 0.04; P=0.053). There was no change in the homeostatic model assessment for insulin resistance, high- and low-density lipoprotein (LDL) levels (P>0.05). Subgroup analysis revealed that Mediterranean diet reduced TG (n=2, WMD -57.52 mg/dL, 95%CI -75.73 to -39.31; P

Primary sclerosing cholangitis is a chronic cholestatic liver disease defined by strictures of the biliary tree which could ultimately lead to liver cirrhosis and cholangiocarcinoma. Although the exact underlying etiology of this disorder is not fully understood, the pathology is believed to be caused by immune mediated mechanisms. Growing body of evidence suggests several treatment modalities mainly focusing on the inflammation aspect of this disorder. However, there is still no consensus regarding the best treatment option for these patients. Thus, the present study aimed to review the current treatment options for patients with primary sclerosing cholangitis.

The well-being of the health care workforce is the cornerstone of every well-functioning health system. As a result of the pandemic, medical healthcare providers are under an enormous amount of workload pressure along with increased total health expenditures. The overwhelming burden of COVID-19 illness could lead to caregiver burnout. Direct-to-consumer telemedicine can enable patients to connect with their healthcare provider at a distance. This virtual platform could be used by smartphones or webcam-enabled computers and allows physicians to effectively screen patients with early signs of COVID-19 before they reach to hospital.

Moazzami B, Moazzami K, Rezaei N. Early onset inflammatory bowel disease: manifestations, genetics and diagnosis. Turk J Pediatr 2019; 61: 637-647. Crohn`s disease and ulcerative colitis are immunologically mediated chronic inflammatory conditions, collectively referred to as inflammatory bowel diseases (IBD). While most studies have described the condition in the adult population, recent evidences suggest that IBD in children may represent an etiologically distinct disease from the adult onset IBD. Since a significant proportion of patients diagnosed with IBD demonstrate their clinical manifestations during childhood, knowledge about the disease progression, severity and diagnosis in this particular patient population is crucial. Therefore, in the present study, the clinical manifestations, recent advancements in the genetics of early onset IBD and the clinical approach to diagnoses of IBD in children are described.

The prevalence and mortality rate of colorectal cancer have been dramatically rising globally. Currently, colorectal cancer is emerging as the fourth leading cause of death and the third most common malignancy worldwide. The major drawback in colorectal cancer treatment is related to severe adverse events of both chemotherapy and radiation therapy that lead to toxicity and inflammation. Recently, melatonin as an antioxidant, immune-stimulant, and antimutagenic agent has been noticed. Different studies worked on the molecular role of melatonin on carcinogenesis progression. Overall, the anticancer activity of melatonin, combined with its actions via multiple signaling pathways, is considered hugely exciting to use this drug as a possible treatment strategy to cure cancer. Apart from its anticancer potential, this drug has shown to induce modulation of chemotherapy toxicity and improving its therapeutic efficacy. The present review aimed to discuss the possible role of melatonin usage in management of colorectal cancer.

BACKGROUND: Pediatric-onset systemic lupus erythematosus (pSLE) accounts for about 10%-20% of all patients with SLE. Deficiencies in early complement components of the classical pathway are the strong genetic risk factor for the development of SLE. In this study, clinical and laboratory manifestations of both complement-deficient and normal complement pSLE patients were compared. MATERIALS AND METHODS: To investigate clinical and immunological manifestations of pSLE in Iran, 36 consecutive pSLE patients (onset before 18 years) who were followed up over a period of 2 years, were studied. Complement C1q and C2 levels were measured using radial immunodifusion assay and complement C3 and C4 levels were measured using nephelometry. Medical records were retrospectively evaluated from patient database of Children Medical Center Hospital. Data were assessed through descriptive analysis (confidence interval = 95%), paired t-test, and Pearson correlation test. RESULTS: Twenty-one patients (58%) had at least one component of complement deficiency. Ten patients (27%) had low C1q level, 11 patients (30.5%) had low C2, nine patients (25%) had low C3, and four patients (11%) had low C4 level. Serum level of complement in pSLE was significantly lower than the control group, except C4 (P = 0.005). The low C1q patients had an earlier age of onset of disease (P < 0.0001). The cutaneous manifestations were more frequent and much more severe in pSLE with low complement (100% vs. 73%). The frequency of renal and musculoskeletal symptoms was equal, but renal morbidity was more common in pSLE with low complement. Positivity for anti-ds-DNA was less common in pSLE with low complement (71% vs. 86%). CONCLUSION: In pSLE patients with early disease onset and more aggressive SLE manifestations and negative anti-ds-DNA test, complement deficiency should be considered.

Background: We conducted a meta-analysis to investigate the possible effects of vitamin D deficiency on clinical outcomes of critically-ill children.Methods: We searched Scopus-Embase and PubMed-Medline databases to find eligible observational articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations.Results: Seventeen articles (eighteen studies) involving 2987 critically ill patients met our inclusion criteria. Vitamin D deficiency was not associated with increased mortality. A significant association was only observed in very high developed countries between vitamin D deficiency and risk of sepsis [OR (95%CIs): 2.65 (1.30, 5.41)] and ventilation support requirement [OR (95%CIs): 1.35 (1.03, 1.77)].Conclusion: Our findings suggest that vitamin D deficiency is not associated with higher mortality among critically ill children but increases susceptibility to sepsis and the need for ventilator support in critical care settings.

Background:Thrombocytopenia is the most well-known hematological abnormality occurring in patients with liver cirrhosis. However, the rate of platelet count reduction is not the same across different chronic liver disease etiologies. Therefore, the aim of the present study was to compare the differences in the platelet count levels between primary sclerosing cholangitis-related cirrhosis (PSC-C) and other causes of liver disease. Methods:In this cohort study, the association between PSC-C and risk of platelet count reduction was investigated. The platelet counts were repeatedly measured among 242 consecutive cirrhotic patients (144 males and 98 females) including 67 patients with PSC-C and 175 patients with non-PSC-C who were on the waiting list for liver transplantation. The Poisson regression analysis was used to assess the relationship between platelet count reduction and PSC-C, after adjusting for potential confounding factors. Results: During the five years of follow-up, comparison between the two groups revealed that significantly higher levels of platelet were found in PSC-C patients when compared to the non-PSC-C group [148 (106–280) (×103 /µL) vs. 79 (50–110) (×103 /µL), respectively, P < 0.001]. After adjusting for confounding factors, a significant association was observed between non-PSC-C and the risk of platelet count reduction (relative risk, RR: 14.81, 95% CI: 1.21–160.42; P= 0.03). Conclusion: The findings indicate that PSC-C patients present with mild degrees of thrombocytopenia compared to other causes of chronic liver disease.

Background: Procalcitonin (PCT) has been shown as a reliable diagnostic biomarker for identifying sepsis and bacterial infection. Objectives: The present study examined the sensitivity and specificity of PCT evaluation in the diagnosis of infectious diseases after liver transplantation. Methods: The present prospective cohort study was conducted on postoperative liver transplant (LT) patients in the liver transplant ward of Imam Khomeini Hospital Complex affiliated to Tehran University of Medical Sciences between January 2014 and March 2015. Serum PCT levels were evaluated before transplantation and one, two, and six or seven days post-operation by semi-quantitative kits with a 30 seconds response. Results: A total number of 28 LT patients were enrolled in this study. The mean patients’ ages were 48.6 ± 10.9 (range 26 - 66) years old. Serum PCT levels in all patients were < 0.5 ng/mL prior to the operation. At first and second days post-operation, PCT levels were more than 2 ng/mL in all patients and decreased to 0.5 ng/mL after 6 or 7 days in 23 patients. Serum PCT level of higher than 5 ng/mL on the first and second days post-surgery with a sensitivity of 77.8% and specificity of 79% had the most accuracy for the infection diagnosis. The PCT level more than 5 ng/mL in the sixth and seventh days had a 100% positive predictive value in the infection prediction. Conclusions: Serial evaluations of serum PCT after liver transplantation had good sensitivity and specificity to predict postoperative infection. Increased serum PCT level within the first days after transplantation and/or failure to decrease after one week, predicts infectious complications and undesirable outcome.

Background: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM. Methods: Clinical and immunological data were collected from the 75 patients’ medical records diagnosed in Children’s Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing. Results: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients. Conclusion: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.

Background: Little is known about the prognostic ability of post-liver transplantation (LT) model for end-stage liver disease (MELD) score measurement in assessing long-term outcomes. The aim of the present study was to investigate this possible relationship. Methods: In this retrospective cohort study, the medical records of LT recipients operated under a LT program were reviewed. The accuracy of post-operation MELD score for predicting mortality was evaluated based on receiver operating characteristic (ROC) curves. Univariate and Cox proportional hazard regression models were used to assess the risk factors associated with mortality. Results: Eight hundred twenty-six consecutive LT recipients were included in the study. The areas under the ROC curve on postoperative days (POD) 5 and 9 for predicting 1-year mortality were 0.712 (95% confidence interval [CI] 0.614-0.811) and 0.682 (95%CI 0.571-0.798), respectively. A cutoff point of 14.5 was obtained for MELD score on POD5 that significantly differentiated between survivors and non-survivors with a sensitivity of 69.8% (95%CI 50.7-83.1) and a specificity of 57.2% (95%CI 50.6-63.6). In the Cox multivariate analysis, factors including MELD score on POD5 (hazard ratio [HR] 1.83, 95%CI 1.07-3.12; P=0.026), pre-transplant MELD (HR 1.064, 95%CI 1.025-1.104; P=0.001) and operation duration (min) (HR 1.004, 95%CI 1.003-1.006; P=0.013) were identified as independent risk factors for predicting overall survival. Conclusion: The immediate postoperative MELD scores after LT may be of value in predicting mortality and could be used as a tool for postoperative risk assessment of patients.

Defects in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) are closely related to very early onset (infantile) inflammatory bowel disease (VEO-IBD). In the present study, we report a novel homozygous null mutation within interleukin-10 receptor B (IL10RB) gene in a child presenting with severe VEO-IBD. In accordance with previous reports, our patient manifested with chronic diarrhea, failure to thrive, intermittent fever and multiple anal ulcers associated with Candidiasis. Homozygous null mutation within IL10RB gene (c.92C > T, p.S31P) affecting the extracellular domain of protein was discovered in this patient. In conclusion, the diagnosis of IL-10R gene mutations should always be considered as a possible cause of refractory diarrhea and failure to thrive. Mutation analysis could help detect the genetic defects associated with these clinical manifestations and to determine the most appropriate treatment option for patients affected by this disease.

Background: Plastic biliary stent placement has been widely used as a safe approach for the management of hilar neoplasms or the dilation of benign biliary obstruction. Despite the complexity of this procedure, this approach is followed by a few complications. The incidence rate of stent migration is about 10%. In a majority of cases, the migrated stents are retained within the gastrointestinal tract and pass through the intestine with no complication or need for medical intervention. Case Report: In this paper, we described the case of the migrated biliary stent with prolonged abdominal pain, which was removed successfully by using double-balloon. Conclusion: In the case of patient with prolonged abdominal pain and previous history of biliary stent placement, migration of stent should be considered as differential diagnosis and Double-Balloon Enteroscopy can be a safe approach in those cases.[GMJ.2020;9:e1809]

[Background] Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by recurrent upper and lower respiratory tract infections and some noninfectious clinical complications., [Objective] To provide a detailed evaluation of respiratory presentations and complications in a cohort of Iranian patients with CVID., [Methods] A retrospective cohort study was conducted on 245 CVID patients who were recorded in the Iranian primary immunodeficiency disorders registry network. Respiratory manifestations were evaluated by reviewing clinical hospital records, immunologic findings, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans., [Results] Most of the patients (n = 208, 85.2%) had experienced at least 1 episode of acute respiratory manifestation, and pneumonia was observed in 31.6 % (n = 77) of cases as a first disease manifestation. During the follow-up, pneumonia, sinusitis, and otitis media were documented in 166 (68.6%), 125 (51.2%), and 103 (42.6%) cases, respectively. Abnormal PFT measurements were documented in 53.8% of patients. Among these patients, 21.5% showed restrictive changes, whereas 18.4% of patients showed an obstructive pattern. Bronchiectasis was the most frequent radiological finding, confirmed in 27.2% of patients. Patients with bronchiectasis were older at the time of immunodeficiency diagnosis (P < .001) and had longer diagnosis delay (P < .001) when compared with patients without bronchiectasis., [Conclusion] This study highlights the importance of monitoring the respiratory tract system even in asymptomatic patients. Pulmonary function tests and CT scans are the most commonly used techniques aiming to identify these patients early, aiming to reduce the rate of long-term respiratory complications., Funding Sources: This research was supported by the Tehran University of Medical Sciences, Tehran, Iran (grant no. 35741).

Objectives: Coronary artery (CA) involvement is the most well known complication of Kawasaki disease (KD). Previous studies have suggested that QT dispersion has a predictive value in diagnosing cardiac ischemia, ventricular arrhythmia, and sudden cardiac death. However, limited data exits regarding the application of QT dispersion in KD. Therefore, we sought to determine whether there is a relationship between QT dispersion and CA involvement in patients with KD. Methods: We performed a cross-sectional study of all consecutive patients with KD who were followed-up at the Pediatric Rheumatology Department (Pediatrics Center of Excellence affiliated to Tehran University of Medical Sciences, Tehran, Iran) from September 2013 to November 2015. Patients who met the criteria for KD, based on the American Heart Association guideline, were enrolled in the study. We collected data regarding patients’ demographics, clinical manifestations, laboratory, and echocardiographic findings. Results: A total of 70 KD patients were identified, including 43 males (61.4%) and 27 females (38.6%). The median age of patients was 21.0 (11.0–48.0) months. We found statistically significant differences between age, gender, and platelet count among patients with and without CA involvement (p < 0.050). Median corrected QT dispersion in patients with CA involvement calculated from 12 leads in the acute phase was significantly higher compared to the non-CA involvement group (108.0 (89.5–138.5) ms vs. 63.0 (54.0–74.5) ms, respectively (p < 0.001)). Conclusions: Prolonged QT dispersion (corrected or non-corrected) during the acute and convalescence phases in patients with KD is associated with coronary involvement.

Hyper Immunoglobulin M syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by low or absent levels of serum IgG, IgA, IgE and normal or increased levels of serum IgM. Various X-linked and autosomal recessive/dominant mutations have been reported as the underlying cause of the disease. Based on the underlying genetic defect, the affected patients present a variety of clinical manifestations including pulmonary and gastrointestinal complications, autoimmune disorders, hematologic abnormalities, lymphoproliferation and malignancies which could be controlled by multiple relevant therapeutic approaches. Herein, the epidemiology, pathogenesis, clinical manifestations, diagnosis, management, prognosis and treatment in patients with HIGM syndrome have been reviewed.

Chronic heart failure (CHF) is a complex clinical syndrome that represents the end stage of various cardiac diseases and is characterized by the inability of the heart to meet metabolic demands of the body. Many physiological systems are involved in this disease. In particular, the activation of the immune system has received considerable interest in the last decade. Evidence from both experimental and clinical trials indicates that inflammatory mediators are of importance in the pathogenesis and progression of chronic heart failure. Excessive pro-inflammatory cytokines induce contractile dysfunction, hypertrophy, and fibrosis and cell death in Cardiac myocyte. We examined the expression of IL-23 in PBMCs between CHF patients and healthy controls. In this report, we used real-time PCR assay to compare the relative expression of IL-23 in peripheral blood mononuclear cells (PBMC) from CHF patients with various heart diseases (n=42, EF

Introduction Primary immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders, characterised by recurrent severe infections, autoimmunity and lymphoproliferation. Despite impressive progress in identification of novel PID, there is an unfortunate lack of awareness among physicians in identification of patients with PID, especially in non-capital cities of countries worldwide. Result This study was performed in a single-centre paediatric hospital in Northern Iran during a 21-year period (1994–2015). Ninety-four patients were included in this study. The majority of cases had antibody deficiencies (37.23%), followed by well-defined syndromes with immunodeficiency in 16 (17.02%), phagocytic disorders in 15 patients (15.95%), complement deficiencies in 15 patients (15.95%), immunodeficiencies affecting cellular and humoral immunity in nine patients (9.57%), disease of immune dysregulation in three (3.19%), and defects in intrinsic and innate immunity in one (1.06%). Conclusion It seems that there are major variations in frequency of different types of PID in different regions of a country. Therefore, reporting local data could provide better ideas to improve the local health care system strategists and quality of care of PID patients.

Background Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011. Objectives To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI). Search methods For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1). Selection criteria We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication. Data collection and analysis Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author. Main results Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026). In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). Authors' conclusions The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.