Causes of Colectomy in Patients with Ulcerative Colitis: Findings from an Iranian National Registry.

BACKGROUND: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) marked by rectal and colon inflammation, leading to relapsing symptoms. Its prevalence is increasing, particularly in developed nations, impacting patients' health. While its exact cause remains unclear, genetic and environmental factors are implicated, elevating the risk of colorectal cancer (CRC). Colectomy, though declining, is still performed in select UC cases, necessitating further study. METHODS: We analyzed data from the Iranian Registry of Crohn's and Colitis (IRCC) to examine UC patients undergoing colectomy. We collected demographic and clinical data from 91 patients, focusing on dysplasia. Statistical analyses assessed dysplasia risk factors. RESULTS: Patients with dysplasia were older at diagnosis and surgery compared to those without dysplasia. Age emerged as a significant risk factor for dysplasia in UC patients undergoing colectomy. No significant associations were found between dysplasia and other factors. CONCLUSION: Age plays a crucial role in dysplasia risk among UC patients undergoing colectomy. Older age at diagnosis and surgery may indicate a higher risk of dysplasia and CRC. Clinicians should consider age when managing UC patients and implementing screening protocols. Further research with larger samples is needed to confirm these findings.

Genetic and Lifestyle Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Relationship with Premature Coronary Artery Disease: A Study on the Pars Cohort.

BACKGROUND: The main objective of this study is to identify the risk factors of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronary artery disease (CAD) patients. METHODS: The present retrospective cohort study is part of the Pars Cohort Study (PCS). The participants were categorized as having MAFLD or not. The pattern of independent variables in patients was compared with those who did not have MAFLD. All variables were retained in the multivariable logistic regression model. RESULTS: Totally, 1862 participants with CAD were enrolled in this study. MAFLD was diagnosed in 647 (40.1%) participants. Gender, diabetes, hypertension, tobacco, opium, alcohol, age, weight, waist circumference, cholesterol, HDL, triglyceride, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly different in MAFLD and non-MAFLD patients. Also, the results of multivariable logistic regression show male gender (OR=0.651, 95% CI: 0.470‒0.902, P value=0.01) and opium consumption (OR=0.563, 95% CI: 0.328‒0.968, P value<0.001) to be negative risk factors of MAFLD occurrence in CAD patients. Having diabetes (OR=2.414, 95% CI: 1.740-3.349, P value<0.001), high waist circumference (OR=1.078, 95% CI: 1.055‒1.102, P value<0.01), high triglyceride (OR=1.005, 95% CI: 1.001‒1.008, P value=0.006), and high ALT (OR=1.039, 95% CI: 1.026‒1.051, P value<0.01) were positive risk factors of MAFLD in CAD patients. CONCLUSION: Our study found that consuming opium decreases the likelihood of MAFLD in CAD patients, since these patients have decreased appetite and lower body mass index (BMI). On the other hand, female gender, having diabetes, high waist circumference, high triglyceride levels, and high ALT levels increase the probability of MAFLD in CAD patients.

Clinical Phenotype and Disease Course of Inflammatory Bowel Disease in Iran: Results of the Iranian Registry of Crohn's and Colitis (IRCC).

BACKGROUND: Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East. METHODS: We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries. RESULTS: In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn's disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF). CONCLUSION: In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations.

Liver fibrosis in pars cohort study: A large-scale study on the prevalence and correlated factors.

BACKGROUNDS AND STUDY AIMS: The fibrosis-4 (FIB-4) is a non-invasive scoring system for estimating liver fibrosis severity as a biomarker of chronic liver disease. We aimed to estimate the prevalence and severity of chronic liver disease at the community level using FIB-4. PATIENTS AND METHODS: This cross-sectional study was conducted using the Pars Cohort database collected in Valashar, Fars province, Iran. Participants were divided into three groups based on their FIB-4 scores: low risk of liver fibrosis (FIB < 1.45), intermediate cases (1.45 ≤ FIB-4 ≤ 3.25), and high risk of liver fibrosis (FIB-4 > 3.25). RESULTS: In total, 9269 individuals with a mean age of 52.65 years were enrolled in the study, of which 4278 (46.2 %) were male. Among all participants, 7853 (84.7 %) were in the low-risk, and 65 (0.7 %) were in the high-risk groups. In the final ordinal regression model, male gender, being a farmer or rancher, living in rural areas, history of opioid use, history of jaundice, no history of diabetes, history of depression, and positive HBs Ag were independently associated with higher FIB-4 scores. CONCLUSION: Our study revealed that males, individuals residing in rural areas, and those engaged in farming and ranching occupations face a heightened risk of liver fibrosis. These findings emphasize the need for future programs for early detection and effective management of liver fibrosis in these at-risk populations.

Multicenter validation of FIB-6 as a novel machine learning non-invasive score to rule out liver cirrhosis in biopsy-proven MAFLD.

BACKGROUND AND AIMS: We previously developed and validated a non-invasive diagnostic index based on routine laboratory parameters for predicting the stage of hepatic fibrosis in patients with chronic hepatitis C (CHC) called FIB-6 through machine learning with random forests algorithm using retrospective data of 7238 biopsy-proven CHC patients. Our aim is to validate this novel score in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHOD: Performance of the new score was externally validated in cohorts from one site in Egypt (n = 674) and in 5 different countries (n = 1798) in Iran, KSA, Greece, Turkey and Oman. Experienced pathologists using METAVIR scoring system scored the biopsy samples. Results were compared with FIB-4, APRI, and AAR. RESULTS: A total of 2472 and their liver biopsy results were included, using the optimal cutoffs of FIB-6 indicated a reliable performance in diagnosing cirrhosis, severe fibrosis, and significant fibrosis with sensitivity = 70.5%, specificity = 62.9%. PPV = 15.0% and NPV = 95.8% for diagnosis of cirrhosis. For diagnosis of severe fibrosis (F3 and F4), the results were 86.5%, 24.0%, 15.1% and 91.9% respectively, while for diagnosis of significant fibrosis (F2, F3 and F4), the results were 87.0%, 16.4%, 24.8% and 80.0%). Comparing the results of FIB-6 rule-out cutoffs with those of FIB-4, APRI, and AAR, FIB-6 had the highest sensitivity and NPV (97.0% and 94.7%), as compared to FIB-4 (71.6% and 94.7%), APRI (36.4% and 90.7%), and AAR (61.2% and 90.9%). CONCLUSION: FIB-6 score is an accurate, simple, NIT for ruling out advanced fibrosis and liver cirrhosis in patients with MAFLD.

Iranian Consensus Guideline for Pharmacotherapy with Biologics and Small Molecules Drugs in Adults with Inflammatory Bowel Diseases.

Background: Pharmacotherapy with biologics and small molecules, as the more effective therapies for moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), is complex. Choosing the best methods for their utilization in order to induce and maintain remission are critical for practicing gastroenterologists. We aimed to develop an Iranian consensus on the management of inflammatory bowel disease (IBD) patients with biologics and small molecules. Methods: A Delphi consensus was undertaken by experts who performed a literature summary and voting process. Quality of evidence was assessed using the Grading and Recommendations Assessment, Development, and Evaluation; and an additional risk of bias-protocol. Results: Following an extensive search of the literature, 219 studies were used to determine the quality of the evidence. After three rounds of voting, consensus (defined as≥80% agreement) was reached for 87 statements. Conclusion: We considered different aspects of pharmacotherapy in this consensus. This guideline, along with clinical judgment, can be used to optimize management of IBD patients.

A Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant.

BACKGROUND: The LIPA gene on chromosome 10q23.31 contains 10 exons and encodes lipase A, the lysosomal acid lipase (LAL) containing 399 amino acids. Pathogenic variants in the LIPA result in autosomal recessive Wolman disease and cholesteryl ester storage disease (CESD). Here, we report a novel missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of LIPA in an Iranian family with fatty liver disease identified by whole-exome sequencing and confirmed by Sanger sequencing. METHODS: A 28-year-old woman referred with lean NASH cirrhosis and extremely high cholesterol levels. Fatty liver disease was found in six of her family members using vibration-controlled transient elastography (VCTE). Baseline routine laboratory tests were performed and whole-exome sequencing and confirmation by Sanger sequencing were done. RESULTS: The index case had severe dyslipidemia and cirrhosis despite a body mass index of 21.09 kg/m2 . Six other family members had dyslipidemia and fatty liver or cirrhosis. A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of LIPA which caused LAL-D was found to be associated with fatty liver disease and/or cirrhosis. CONCLUSION: A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of the LIPA gene which caused LAL-D was found to be associated with dyslipidemia, fatty liver disease and/or cirrhosis in six members of an Iranian family. These results should be confirmed by functional studies and extending the study to at least three families.

The critical role of circular RNAs in drug resistance in gastrointestinal cancers.

Nowadays, drug resistance (DR) in gastrointestinal (GI) cancers, as the main reason for cancer-related mortality worldwide, has become a serious problem in the management of patients. Several mechanisms have been proposed for resistance to anticancer drugs, including altered transport and metabolism of drugs, mutation of drug targets, altered DNA repair system, inhibited apoptosis and autophagy, cancer stem cells, tumor heterogeneity, and epithelial-mesenchymal transition. Compelling evidence has revealed that genetic and epigenetic factors are strongly linked to DR. Non-coding RNA (ncRNA) interferences are the most crucial epigenetic alterations explored so far, and among these ncRNAs, circular RNAs (circRNAs) are the most emerging members known to have unique properties. Due to the absence of 5' and 3' ends in these novel RNAs, the two ends are covalently bonded together and are generated from pre-mRNA in a process known as back-splicing, which makes them more stable than other RNAs. As far as the unique structure and function of circRNAs is concerned, they are implicated in proliferation, migration, invasion, angiogenesis, metastasis, and DR. A clear understanding of the molecular mechanisms responsible for circRNAs-mediated DR in the GI cancers will open a new window to the management of GI cancers. Hence, in the present review, we will describe briefly the biogenesis, multiple features, and different biological functions of circRNAs. Then, we will summarize current mechanisms of DR, and finally, discuss molecular mechanisms through which circRNAs regulate DR development in esophageal cancer, pancreatic cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma.

Comparison of Disease Phenotype and Course among Elderly- and Early-Onset Inflammatory Bowel Diseases in the Middle East.

BACKGROUND: It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset inflammatory bowel disease (IBD). We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients. METHODS: This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) compared demographics, disease phenotype, disease activity, IBD-related surgery and medications between early- and elderly-onset IBD. A generalized linear regression model was used to investigate the relative risk of age at diagnosis adjusted for gender and disease duration for the outcomes. RESULTS: From 10048 IBD patients, 749 with early-onset (7.5%), and 472 (4.7%) elderly-onset IBD were enrolled: 855 (63.1%) ulcerative colitis (UC) and 366 (26.9%) Crohn's disease (CD). Left-sided colitis was more frequent among elderly-onset UC patients (P<0.001). Ileum and ileocolonic locations were the most common types in elderly-onset and early-onset CD patients, respectively. In comparison with elderly-onset UC, early-onset cases more often used prednisolone (22.1% vs. 11.4%, P=0.001), immunomodulators (44.9% vs 25.2%, P<0.001) and anti-tumor necrosis factors (TNF) (20.1% vs 11.9%, P=0.002). Elderly-onset UC patients had 0.7 times lower risk of aggressive phenotype (95%CI:0.6‒0.9, P=0.005). Early-onset CD was associated with higher use of prednisolone (27.7% vs 8.1%, P<0.001), immunomodulators (58.7% vs 41.8%, P=0.005) and anti-TNF (49.6% vs 35.4%, P=0.006). CONCLUSION: Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use.

Endoscopic or surgical treatment for necrotizing pancreatitis: Comprehensive systematic review and meta-analysis.

Background and study aims Treatment of necrotizing pancreatitis is changed over the past two decades with the availability of endoscopic, and minimally invasive surgical approaches. The aim of this systematic review was to assess outcomes of endoscopic drainage, and different types of surgical drainage approaches in necrotizing pancreatitis. Methods Medline, Embase, Scopus, and Web of Science were searched from 1998 to 2020 to assess outcomes in endoscopic drainage and various surgical drainage procedures. The assessed variables consisted of mortality, development of pancreatic or enteric fistula, new onset diabetes mellitus, and exocrine pancreatic insufficiency. Results One hundred seventy studies comprising 11,807 patients were included in the final analysis. The pooled mortality rate was 22 % (95 % confidence interval [CI]: 19%-26 %) in the open surgery (OS), 8 % (95 %CI:5 %-11 %) in minimally invasive surgery (MIS), 13 % (95 %CI: 9 %-18 %) in step-up approach, and 3 % (95 %CI:2 %-4 %) in the endoscopic drainage (ED). The pooled rate of fistula formation was 35 % (95 %CI:28 %-41 %) in the OS, 17 % (95 %CI: 12%-23 %) in MIS, 17 % (95 %CI: 9 %-27 %) in step-up approach, and 2 % (95 %CI: 0 %-4 %) in ED. There were 17 comparative studies comparing various surgical drainage methods with ED. The mortality rate was significantly lower in ED compared to OS (risk ratio [RR]: 30; 95 %CI: 0.20-0.45), and compared to MIS (RR: 0.40; 95 %CI: 0.26-0.6). Also, the rate of fistula formation was lower in ED compared to all other surgical drainage approaches. Conclusions This systematic review demonstrated lower rate of fistula formation with ED compared to various surgical drainage methods. A lower rate of mortality with ED was also observed in observational studies. PROSPERO Identifier: CRD42020139354.

Outcomes of COVID-19 in Patients with Inflammatory Bowel Disease: Comparison with Household Members and the Role of IBD Medications.

BACKGROUND: Most data on the effect of inflammatory bowel disease (IBD) and its treatments on coronavirus disease 2019 (COVID-19) outcomes have not had non-IBD comparators. Hence, we aimed to describe COVID-19 outcomes in IBD compared to non-IBD patients. METHODS: We conducted a prospective cohort study of registered IBD patients with confirmed COVID-19 from six provinces in Iran from February to April 2020. Proven COVID-19 patients were followed up at four weeks and the frequency of outcomes was assessed. Multivariable logistic regression was used to assess associations between demographics, clinical characteristics and COVID-19 outcomes. RESULTS: Overall, 2159 IBD patients and 4721 household members were enrolled, with 84 (3.9%) and 49 (1.1%) participants having confirmed COVID-19, respectively. Household spread of COVID-19 was not common in this cohort (1.2%). While hospitalization was significantly more frequent in IBD patients compared with non-IBD household members (27.1% vs. 6.0%, P=0.002), there was no significant difference in the frequency of severe cases. Age and presence of IBD were positively associated with hospitalization in IBD compared with non-IBD household members (OR: 1.06, 95% CI: 1.03-1.10; OR: 5.7, 95% CI: 2.02- 16.07, respectively). Age, presence of new gastrointestinal symptoms, and 5-aminosalicylic acid (5-ASA) use were associated with higher hospitalization rate in IBD patients (OR: 1.13, 95% CI: 1.05-1.23; OR: 6.49, 95% CI: 1.87-22.54; OR: 6.22, 95% CI: 1.90-20.36, respectively). Anti-tumor necrosis factor (TNF) was not associated with more severe outcomes. CONCLUSION: Age, presence of new gastrointestinal symptoms and use of 5-ASA were associated with increased hospitalization rate among IBD patients, while anti-TNF therapy had no statistical association.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Susceptibility of Patients with Inflammatory Bowel Disease to COVID-19 Compared with Their Households.

BACKGROUND: Immunosuppressive agents used in the treatment of inflammatory bowel diseases (IBDs) could potentially increase the risk of coronavirus disease 2019 (COVID-19). We aimed to compare COVID-19 frequency in patients with IBD with their households and identify the related risk factors. METHODS: Firstly, a multi-centered, observational study on 2110 patients with IBD and 2110 age-matched household members was conducted to compare COVID-19 frequency. Secondly, the data of patients with IBD and COVID-19 who had called the COVID-19 hotline were added. Multivariable logistic regression was used to evaluate the effect of age, type and severity of IBD, the number of comorbidities, and medications on the frequency of COVID-19 among the patients with IBD. RESULTS: The prevalence of COVID-19 in patients with IBD and household groups was similar (34 [1.61%] versus 35 [1.65%]; P = 0.995). The prevalence of COVID-19 increased from 2.1% to 7.1% in those with three or more comorbidities (P = 0.015) and it was significantly higher in those with severe IBD (P = 0.026). The multivariable analysis only showed a significant association with anti-TNF monotherapy (OR: 2.5, CI: 0.97-6.71, P = 0.05), and other medications were not associated with COVID-19. CONCLUSION: The prevalence of COVID-19 in patients with IBD was similar to the household members. Only patients with IBD receiving anti-TNF monotherapy had a higher risk of COVID-19 susceptibility. This finding could be attributed to the higher exposure to the virus during administration in health care facilities.

Clinical Phenotype and Disease Course of Inflammatory Bowel Disease: A Comparison Between Sporadic and Familial Cases.

BACKGROUND: The role of genetic and environmental factors in inflammatory bowel disease's (IBD) clinical course is not fully clear. We aimed to assess the clinical phenotype, disease course, and prognosis of familial IBD in comparison with sporadic cases. METHODS: We conducted a prospective national matched case-control study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) recruited from 2017 until 2020. Sporadic and familial IBD patients were matched based on age, sex, and disease duration. Data on demographics, past medical disease, family history of IBD, disease type, clinical phenotype, extraintestinal manifestations, IBD medications, IBD activity using the IBD-control-8 questionnaire and the Manitoba IBD index, emergency visits in the past 12 months, admissions in the past 3 months, history of colon cancer, IBD-related surgeries, and aggressive phenotype were gathered. Variable distributions were compared between sporadic and familial cases. RESULTS: Overall, 5231 patients with ulcerative colitis (UC, 18.3% familial) and 1438 patients with Crohn's disease (CD, 16.7% familial) were registered in the IRCC. Age at diagnosis was similar between familial and sporadic cases. After matching, 3523 UC patients and 908 CD patients were enrolled in the study. Extraintestinal manifestations, UC extent, CD location and behavior, anti-TNF use, disease activity, colon cancer, IBD-related surgeries and the aggressive phenotype were similar between these sporadic and familial cases. CONCLUSIONS: The prevalence of familial UC and CD cases in Iran was more similar to western countries, and family history did not show a predictive value for disease phenotype, course, and outcomes in our study.

Long-term Efficacy of Combined Treatment in Patients with Idiopathic Achalasia.

BACKGROUND Several treatment strategies are available to treat achalasia. Although combined therapy has been used for several years, there are limited data on long-term outcomes. We aimed to determine its long-term efficacy in patients who were resistant or those with rapid relapse. METHODS In this prospective study, we reviewed the records of 1100 patients with achalasia, who were candidates for pneumatic balloon dilatation (PBD) in our center from 1996 to 2018. We enrolled 197 patients resistant to initial treatment or with rapid relapse of symptoms after three sessions of PBD. Clinical evaluation and time barium esophagogram (TBE) were done before treatment, a month afterward, and when clinical symptoms increased in order to confirm relapse, and at the end of follow-up. RESULTS A total of 168 patients accepted combined therapy. The mean duration of follow-up was 9.04 years. Achalasia symptom score (ASS) dropped from 10.82 to 3.62 a month after treatment and was 3.09 at the end of the follow-up (p = 0.0001 and 0.001). TBE had a decrease in mean height of barium one month after treatment (9.23 vs. 5.10, p = 0.001), and this reduction persisted until the end of follow-up (3.39, p = 0.001). Vantrappen score at the end of the follow-up showed 56 patients in excellent, 51 in good, 33 in moderate, and 14 in poor condition (89% acceptable response rate). CONCLUSION Our results showed the long-term efficacy of combined treatment in patients with achalasia who otherwise had to undergo a high-risk and costly procedure, which makes it a safe and effective alternative for myotomy.

Efficacy and Safety of Tofacitinib for Treatment of Moderate to Severe Active Ulcerative Colitis: First Report from Iran.

BACKGROUND: Tofacitinib, a selective inhibitor of JAK/STAT pathway, has recently become available in our region. Here, we examined the safety and efficacy of tofacitinib in active ulcerative colitis (UC). METHODS: In a prospective, non-randomized, placebo-free, 52-week clinical trial defined in two phases of induction and maintenance, adult patients with active UC and no response or loss of response to previous conventional treatments, or anti-TNF were recruited (IRCT20181217042020N2). Patients received 10 mg/BID of tofacitinib for 8 weeks. Clinically responding patients were entered into the maintenance phase and received tofacitinib 5 mg/BID for 44 weeks. Clinical evaluation, biochemical tests and endoscopy at time points of baseline, 8, 24 and 52 weeks were performed. The primary outcome was clinical remission at 8 and 52 weeks. RESULTS: Fifty out of 53 enrolled patients completed the induction phase. Clinical response and clinical remission at 8 weeks occurred in 84% and 9.5%, respectively. Forty-two patients who had clinical response entered the maintenance phase. Clinical remission based on the total Mayo score and the partial Mayo score occurred in 38.9% and 55.3% at 24 weeks and in 61.1% and 72.2% at 52 weeks, respectively. There was significant correlation between the total and partial Mayo score with regard to clinical remission in both 24 and 52 weeks. No serious adverse events, no case of herpes zoster, but two cases of deep vein thrombosis were seen. CONCLUSIONS: Our study showed acceptable efficacy and safety for tofacitinib and suggested a correlation between the total Mayo score with partial Mayo score with regard to clinical remission.

Correction: Effectiveness of Polypill for Prevention of Cardiovascular Disease (PolyPars): Protocol of a Randomized Controlled Trial.

This corrects the article "Effectiveness of polypill for prevention of cardiovascular disease (PolyPars): protocol of a randomized controlled trial" published on 2020: Volume 23, Issue 08, Pages 548-556. Correction to: Arch Iran Med. 2020;23(8):548-556. doi: 10.34172/aim.2020.58. In the original version of this article, the recruitment period was wrongly reported to last from December 2014 to December 2015 in abstract and methods sections of the article. This is corrected into "from December 2015 to December 2016" in the PDF and HTML versions of the article. Also the "PolyIran" is changed to "PolyPars" in the last paragraph of the discussion section in the PDF and HTML versions of the article.

A Reliable Prognostic Marker for Liver Dysfunction in COVID-19 Infection.

BACKGROUND In December 2019, COVID-19 emerged from China and spread to become a pandemic, killing over 1,350,000 up to November 18, 2020. Some patients with COVID-19 have abnormal liver function tests. We aimed to determine the clinical significance of liver chemistries in patients with COVID-19. METHODS We performed a cross-sectional study of 1044 consecutive patients with confirmed COVID-19 in two referral hospitals in Tehran, Iran, from February to April 2020. All cases were diagnosed by clinical criteria and confirmed by characteristic changes in the spiral chest computed tomography (CT) and nucleic acid testing of the nasopharyngeal samples. We evaluated the association between abnormal liver enzymes or function tests and survival, intensive care unit (ICU) admission and fatty liver changes in CT scans. RESULTS The mean age was 61.01 ± 16.77 years, and 57.68% were male. Of 495 patients with elevated alanine transaminase (ALT) levels, 194 had chest CT scans, in which fatty liver disease was seen in 38.1%. 41 patients (21.13%) had moderate to severe, and 33 (17.01%) had borderline fatty liver disease. Bilirubin, albumin, and partial thromboplastin time (PTT), along with other markers such as HCO3, C-reactive protein (CRP), triglyceride, and length of admission, were significantly associated with ICU admission and mortality. Prothrombin time (PT), platelet count, and low-density lipoprotein (LDL) levels were also correlated with mortality. Fasting blood sugar (FBS) and pH were important indices in ICU admitted patients. CONCLUSION Liver function tests accurately predict a worse prognosis in patients with COVID-19. However, liver enzymes were only slightly increased in those who died or needed ICU admission and were not related to the fatty liver changes.

Comparison of Treatment Response in Different Types of Achalasia: A Long-Term Study.

BACKGROUND Three manometric patterns are seen in high-resolution manometry (HRM). Response to treatment has been reported to be different in these subtypes. We aimed to investigate the frequency and response to treatment in subtypes of achalasia. METHODS 306 patients between 15 to 60 years old, naïve to treatment with idiopathic achalasia (IA) were evaluated prospectively in a cohort study for 8 years. The patients were treated with pneumatic balloon dilation (PBD), and evaluated before and one month after PBD with Achalasia Symptom Score (ASS) and timed barium esophagogram (TBE) and then every 6 months with ASS. The primary study outcome was defined as a reduction in ASS (equal to or less than 4) and a reduction greater than 80% in the volume of barium in TBE at 1 month after PBD compared with baseline values. RESULTS According to HRM, 57 were classified as type I (18.62%), 223 as type II (72.9%), and 26 as type III (8.5%). The mean lower esophageal sphincter (LES) residual pressures before treatment were 34.05 ± 31.55, 32.99 ± 17.90, and 37.47 ± 14.07 mmHg in types I, II, and III, respectively (p = 0.18). The mean ASS values before treatment were 12.23, 11.50, and 11.50, for types I, II, and III, respectively (p = 0.29). The ASS dropped to 2.50 in type I, 2.40 in type II, and 2.12 in type III at 1 month after treatment (p = 0.83). Eventually, at the end of follow-up, 24 patients with type I (83%), 82 patients with type II (67%), and five patients with type III (83%) showed sustained good responses (p = 0.528). CONCLUSION Manometric subtypes of achalasia did not have an important role in clinical success in the long term. Achalasia has no definite cure, but with current treatment modalities, palliation of symptoms is possible in over 90% of patients.