Widespread vitiligo and poliosis following ipilimumab-nivolumab combination therapy.

INTRODUCTION: Combined immune checkpoint inhibitor therapy has been successfully used in the treatment of several malignancies. Adverse effects with the combination therapy may be more severe than the ones seen with single immune checkpoint inhibitors. CASE PRESENTATION: We report a unique case of a 59-year-old man of dark skin complexion who underwent treatment with intravenous ipilimumab-nivolumab every 3 weeks for metastatic malignant melanoma. After three cycles of this therapy, he developed extensive skin depigmentation that within 6 weeks, affected nearly the entire skin surface, along with progressive poliosis. MANAGEMENT AND OUTCOME: Ipilimumab-nivolumab therapy was subsequently discontinued due to grade 3 enterocolitis requiring high-dose steroids and intravenous infliximab. About six months later, imaging studies showed a relapse of malignant melanoma. At that juncture, vitiligo affected the total body surface area, resembling albinism, along with near-total poliosis and significant photosensitivity. Pembrolizumab was tried but had to be stopped after three cycles due to the reoccurrence of grade 3 enterocolitis. Progression of malignant melanoma with new brain, lung, liver, subcutaneous, and colonic metastases led to the patient's demise. CONCLUSION: We report a unique case of severe vitiligo and poliosis that involved total body surface area in a Caucasian man with dark complexion, resembling albinism. Further studies are warranted to evaluate the severity of dermatologic side effects with combination immune checkpoint inhibitor therapy.

Development of Monoclonal B-cell Lymphocytosis Shortly After Treatment with Nivolumab and Subsequent Progression to Chronic Lymphocytic Leukemia.

INTRODUCTION: Immune checkpoint inhibitors, such as programmed death (PD)-1 inhibitor nivolumab, are currently widely used in treatment of various malignancies. Due to their widespread application, any new potential adverse effects due to these agents necessitate careful assessment. CASE REPORT: We report a case of an 81-year-old man with recurrent high-risk malignant melanoma who underwent a 12-month adjuvant treatment with nivolumab. Shortly after the course of nivolumab, he developed monoclonal B-cell lymphocytosis (MBL) which subsequently progressed to chronic lymphocytic leukemia (CLL). MANAGEMENT AND OUTCOME: The patient is currently doing clinically well in Rai stage 0. Malignant melanoma remains in remission. CONCLUSION: Considering the pathophysiologic plausibility of nivolumab inducing B-cell dysregulation via PD-1 inhibition, we suggest further studies on potential association between nivolumab and B-cell malignancies.

Effects of corneal nerve density on the response to treatment in dry eye disease.

PURPOSE: To evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment. DESIGN: Phase IV, double-masked, randomized clinical trial. PARTICIPANTS: Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls. METHODS: Patients with DED were randomized to receive topical artificial tears, loteprednol etabonate 0.5%, or loteprednol etabonate 0.5%/tobramycin 0.3% twice daily for 4 weeks. At baseline, in vivo confocal microscopy of central cornea was performed in both eyes. Patients with DED were divided into 2 subgroups: those with low baseline SNFL and those with near-normal baseline SNFL for this purpose (the cutoff point: the mean SNFL in controls minus 2 standard deviations). Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups. MAIN OUTCOME MEASURES: Symptom questionnaires, corneal fluorescein staining (CFS), conjunctival staining with lissamine green, tear break-up time, Schirmer's test, and SNFL. RESULTS: In patients with DED, baseline SNFL (17.06±5.78 mm/mm(2)) was significantly lower than in controls (23.68±3.42 mm/mm(2), P = 0.001). In the artificial tear and loteprednol groups, although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL (<16.84 mm/mm(2)), subjects with near-normal baseline SNFL (≥16.84 mm/mm(2)) showed significant improvement in both symptoms and CFS score (all P < 0.05). In the loteprednol/tobramycin group, no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL. CONCLUSIONS: Significant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL. Consideration of SNFL may assist in explaining the variability of patients' response to DED therapy.

Degeneration and Regeneration of Subbasal Corneal Nerves after Infectious Keratitis: A Longitudinal In Vivo Confocal Microscopy Study.

PURPOSE: To investigate the longitudinal alterations of subbasal corneal nerves in patients with infectious keratitis (IK) during the acute phase, cessation of treatment, and the recovery phase by in vivo confocal microscopy (IVCM). DESIGN: Prospective, longitudinal, case-control, single-center study. PARTICIPANTS: Fifty-six eyes of 56 patients with the diagnosis of bacterial (n=28), fungal (n=15), or Acanthamoeba (n=13) keratitis were included in the study. Thirty eyes of 30 normal volunteers constituted the control group. METHODS: Corneal sensation and serial IVCM of the central cornea were performed prospectively using the Heidelberg Retina Tomograph 3/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany). The IVCM images were assessed at 3 time points: at the acute phase (first visit to the cornea service), at cessation of antimicrobial treatment, and up to 6 months after the resolution of infection. MAIN OUTCOME MEASURES: Total nerve number and length, main nerve trunks, branching, and corneal sensation were assessed during the follow-up period. RESULTS: Corneal nerves were reduced significantly during the acute phase in eyes with IK compared with controls across all subgroups, with total nerve length of 5.47±0.69 mm/mm2 versus 20.59±1.06 mm/mm2 (P<0.0001). At the cessation of treatment, corneal nerves in patients with IK had regenerated, including total nerve length (8.49±0.94 mm/mm2; P=0.02) and nerve branch length (4.80±0.37 mm/mm2; P=0.005). During the recovery phase, after resolution of infection, corneal nerves regenerated further, including total nerve length (12.13±1.97 mm/mm2; P=0.005), main nerve trunk length (5.80±1.00 mm/mm2; P=0.01), and nerve branch length (6.33±0.76 mm/mm2; P=0.003) as compared with the acute phase, but were still significantly lower when compared with controls (P<0.05 for all parameters). Corneal degeneration and regeneration correlated with corneal sensation (r=0.47; P=0.0009). CONCLUSIONS: Patients with IK who sustain profound loss of corneal nerves during the acute phase of infection demonstrate increased corneal nerve density during the first 6 months after the resolution of infection. However, despite significant nerve regeneration, corneal nerve density does not recover fully and remains low compared to controls. By providing an objective methodology to monitor corneal re-innervation, IVCM adds potentially important findings that may have implications for clinical management and surgical planning.

Quality of life in caregivers of severely disabled war survivors.

PURPOSE: To evaluate quality of life (QOL) of caregivers of severely disabled war survivors and identify variables threatening caregivers' QOL. METHODS: A cross-sectional study was performed on 532 caregivers of Iran-Iraq war related injured survivors by using Persian version of 36-item Short Form Health Survey (SF-36). FINDINGS: Caregivers had lower QOL compared to the Iranian female population (p < .001). Caregivers of amputees had better SF-36 scores compared to caregivers of two groups of chemical warfare survivors (p ranging from .01 to <.001). Caregiving to chemical warfare and being married at the time of trauma were the independent predictors of poor QOL in both the physical component summary (OR = 5.08, 95% CI = 3.35-7.7; OR = 0.57, 95% CI = 0.37-0.89) and the mental component summary (OR = 4.12, 95% CI = 2.68-6.32; OR = 0.63, 95% CI = 0.40-0.98). CONCLUSION AND CLINICAL RELEVANCE: Caregivers of war veterans suffer from poor QOL. Chemical warfare agents contribute to more persistent poor QOL in caregivers than the injuries caused by conventional weapons.

Worldwide inequality in production of systematic reviews.

BACKGROUND: Investment in science is vital for the development and well-being of societies. This study aims to assess the scientific productivity of countries by quantifying their publication of systematic reviews taking the gross national income per capita (GNIPC) into account. METHODS: Medline and ISI Web of Science were searched for systematic reviews published between 1st January 2006 and 31st December 2010. The productivity of each country was quantified by exploring the authors' affiliation. The GNIPC was used according to the World Bank Report. Concentration index (CI) was calculated as the index of inequality. RESULTS: CI of percentage of systematic reviews as a function of percentage of countries ranked by GNIPC was 0.82 which indicates inequality in production of systematic reviews in pro rich countries. Countries with high income produced 206.23 times more systematic reviews than low income countries, while this ratio for lower middle and upper middle countries was 9.67 and 12.97, respectively. The highest concentration index was observed in clinical sciences (0.76) and the lowest in public health (0.61). CONCLUSION: This study demonstrates a significant gap between industrialized and nonindustrialized countries in the production of systematic reviews. Addressing this gap needs tremendous national and international efforts.

Aspiration and sclerotherapy versus hydrocoelectomy for treating hydrocoeles.

BACKGROUND: Hydrocoeles are common cystic scrotal abnormalities, described as a fluid-filled collection between the visceral and parietal layers of the tunica vaginalis of the scrotum. There are two approaches for treatment of hydrocoeles: surgical open hydrocoelectomy and aspiration followed by sclerotherapy.  OBJECTIVES: We compared the benefits and harms of aspiration and sclerotherapy versus hydrocoelectomy for the management of hydrocoeles. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 2 August 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing aspiration and sclerotherapy versus hydrocoelectomy for the management of hydrocoeles. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias in the included studies. Random effects meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We found four small studies that met the inclusion criteria. These studies enrolled 275 patients with 282 hydroceles. Participants were randomised to aspiration and sclerotherapy (155 patients with 159 hydroceles) and surgery (120 patients with 123 hydroceles). All studies were assessed as having low or unclear risk of bias for selection bias, detection bias, attrition bias and selective reporting bias. Blinding was not possible for participants and investigators based on the type of interventions. Blinding for statisticians was not reported in any of included studies.There were no significant difference in clinical cure between the two groups (3 studies, 215 participants: RR 0.45, 95% CI 0.18 to 1.10), however there was significant heterogeneity (I² = 95%). On further investigation one study contributed all of the heterogeneity. This could be due to the agent used or perhaps due to the fact that this is a much older study than the other two studies included in this analysis. When this study was removed from the analysis the heterogeneity was 0% and the result was significant (in favour of surgery) (2 studies, 136 participants: RR 0.74; 95% CI 0.64 to 0.85).There was a significant increase in recurrence in those who received sclerotherapy compared with surgery (3 studies, 196 participants: RR 9.37, 95% CI 1.83 to 48.4). One study reported a non-significant decrease in fever in the sclerotherapy group (60 participants: RR 0.25, 95% CI 0.06 to 1.08). There was an increased number of infections in the surgery group however this increase was not statistically significant (4 studies, 275 participants): RR 0.31, 95% CI 0.09 to 1.05; I² = 0%). Three studies reported the frequency of pain in the surgery group was higher than aspiration and sclerotherapy group but because of different measurement tools applied in these studies, we could not pool the results. Radiological cure was not reported in any of the included studies. There was no significant difference in haematoma formation between the two groups (3 studies, 189 participants: RR 0.57, 95% CI 0.17 to 1.90; I² = 0%). Only one study reported patient satisfaction at three and six months; there was no significant difference between the two groups. AUTHORS' CONCLUSIONS: Postoperative complications as well as cost and time to work resumption were less in the aspiration and sclerotherapy group; however the recurrence rate was higher. The cure rate in short-term follow-up was similar between the groups, however there is significant uncertainty in this result due to the high heterogeneity. There is a great need for further methodologically rigorous RCTs that assess the effectiveness of different type of sclerosant agents, sclerosing solution concentration and injection volume for the treatment of hydrocoeles. It is important that the RCTs have sufficiently large sample size and long follow-up period. Studies should evaluate clinical outcomes such as pain, recurrence, satisfaction, complications and cure using validated instruments. The protocols for all studies should be registered in clinical trial registries and the reports of these studies should conform with international guidelines of trial reporting such as CONSORT. Cost-effectiveness studies should also be undertaken.

Students' concerns about the pre-internship objective structured clinical examination in medical education.

BACKGROUND: Despite several studies on implementation, reliability and validity of the Objective Structured Clinical Examination (OSCE), the perceptions of examinees toward this evaluation tool remain unclear. The aim of the current study was to assess students' perceptions of the OSCE. METHODS: All students in their final year of studies, who participated in the pre-internship OSCE in September 2010, were included in the study. A 16-item questionnaire was designed to assess: Characteristics of respondents; organization, content and structure of the OSCE; and perceptions of validity, reliability and rating of the OSCE with respect to other assessment methods. Questionnaires were administered immediately after all students had finished the OSCE and before leaving the examination venue. RESULTS: Response rate was 86.2%, with 77% of the students indicating the OSCE as a useful learning experience. A majority of the students (62%) agreed that a wide range of clinical skills was covered in this exam. However, 66% had concerns about the wide coverage of knowledge assessed. A total of 81% of students did not prefer the OSCE to multiple choice question exams and 88% found the OSCE intimidating and more stressful than other forms of assessment. DISCUSSION: Our study demonstrates that although the majority of students believe in the reliability and validity of the OSCE, they have concerns about it and report poor acceptance of the OSCE. Further studies are necessary to assess the important concerns of the students and the effectiveness of interventions in improving the acceptability of the OSCE.

Occult Gastrointestinal Hemorrhage From a Meckel's Adenocarcinoma: A Diagnostic Dilemma.

Gastrointestinal bleeding from Meckel's diverticulum can be challenging to diagnose. We present a case of a 78-year-old man with painless hematochezia. Despite undergoing standard investigations, the source of bleeding remained elusive until arteriography localized bleeding from Meckel's diverticulum. Prompt management involved embolization followed by laparoscopic resection. This case underscores the need to consider Meckel's diverticulum as a source of obscure gastrointestinal bleeding even in the elderly, as well as the need to use non-conventional diagnostic approaches when standard methods fail. The successful management of the case through embolization and laparoscopic resection highlights the crucial role interventional radiologists and surgeons play in the management of Meckel's diverticulum-related complications.

Protein kinase D1 mediates anchorage-dependent and -independent growth of tumor cells via the zinc finger transcription factor Snail1.

We here identify protein kinase D1 (PKD1) as a major regulator of anchorage-dependent and -independent growth of cancer cells controlled via the transcription factor Snail1. Using FRET, we demonstrate that PKD1, but not PKD2, efficiently interacts with Snail1 in nuclei. PKD1 phosphorylates Snail1 at Ser-11. There was no change in the nucleocytoplasmic distribution of Snail1 using wild type Snail1 and Ser-11 phosphosite mutants in different tumor cells. Regardless of its phosphorylation status or following co-expression of constitutively active PKD, Snail1 was predominantly localized to cell nuclei. We also identify a novel mechanism of PKD1-mediated regulation of Snail1 transcriptional activity in tumor cells. The interaction of the co-repressors histone deacetylases 1 and 2 as well as lysyl oxidase-like protein 3 with Snail1 was impaired when Snail1 was not phosphorylated at Ser-11, which led to reduced Snail1-associated histone deacetylase activity. Additionally, lysyl oxidase-like protein 3 expression was up-regulated by ectopic PKD1 expression, implying a synergistic regulation of Snail1-driven transcription. Ectopic expression of PKD1 also up-regulated proliferation markers such as Cyclin D1 and Ajuba. Accordingly, Snail1 and its phosphorylation at Ser-11 were required and sufficient to control PKD1-mediated anchorage-independent growth and anchorage-dependent proliferation of different tumor cells. In conclusion, our data show that PKD1 is crucial to support growth of tumor cells via Snail1.

Medical students' health-related quality of life: roles of social and behavioural factors.

OBJECTIVES: The long and demanding course of medical education may be accompanied by distress with serious consequences. This study was conducted to assess the multidimensional health-related quality of life (HR-QoL) in medical students in different stages of medical education and its associations with behavioural and social factors. METHODS: A cross-sectional study was conducted in medical students at three medical schools at, respectively, Tehran University of Medical Sciences, Aja University of Medical Sciences and Baghiyatalah Medical School, in November and December 2011 using stratified sampling. Data were obtained on participants' characteristics, including gender, current education stage, living situation, smoking status, physical activity, and membership of associations or teams. Health-related QoL was measured using the Persian version of the 36-item Short Form Health Survey (SF-36), which generates a physical component score (PCS) and a mental component score (MCS). Logistic regression was applied to measure the adjusted associations between variables. RESULTS: Of the 1350 students invited, 1086 individuals completed the survey to give a response rate of 80.4%. Logistic regression showed male gender (odds ratio [OR] = 2.88, p < 0.001), living with family versus in a dormitory (OR = 2.72, p < 0.001) and participation in daily physical activity (OR = 16.96, p < 0.001) to be significantly associated with a higher PCS. Being in an internship versus in the basic sciences stage of medical education showed a significant association with a lower PCS (OR = 0.12, p < 0.001). Similarly, male gender (OR = 1.67, p < 0.05), living with family rather than in a dormitory (OR = 16.91, p < 0.001), daily physical activity (OR = 25.36, p < 0.001), and membership of associations or teams (OR = 3.67, p < 0.001) were associated with a higher MCS. Likewise, studying in internship rather than in the basic sciences stage was accompanied by a lower MCS (OR = 0.12, p < 0.001). CONCLUSIONS: This large, multi-institution study, despite its limitations, indicates that medical students in internships show lower scores in all domains of QoL. Social engagement is an important associate of higher HR-QoL. Further studies should address the efficacy of interventions, such as self-awareness programmes and initiatives to encourage students to be more physically and socially active, in improving students' health.

Novel Application of Conjunctival Anterior Segment Optical Coherence Tomography Angiography to Assess Ocular Redness.

PURPOSE: The aim of this study was to determine anterior segment optical coherence tomography angiography (AS-OCTA) parameters to assess ocular redness severity. METHODS: AS-OCTA analyses of 60 eyes of 40 patients were grouped according to ocular redness stages using the 5-category validated bulbar redness scale in a cross-sectional retrospective study (groups 1-5). A subset of patients with slit-lamp photographs, total 35 eyes of 23 patients, were assessed with 10-category validated bulbar redness scale for comparison. AS-OCTA images of nasal and temporal bulbar conjunctiva were analyzed. Vessel density (VD) represented the blood flow pixels by the total pixels of image (%); vessel diameter index represented the VD by the skeletonized density; fractal dimension, measured with the box-count method, represented the vessel branching complexity. Averaged nasal and temporal parameters for each eye were correlated to validated bulbar redness scales. RESULTS: There was no statistical difference between groups for age ( P = 0.118), sex ( P = 0.501), eye laterality (OD/OS; P = 0.111), or location (nasal/temporal; P = 0.932). In the 5-category scale, VD significantly increased from group 1 to 2 (31.5 ± 1.9% and 33.4 ± 2.2%, P = 0.023), 2 to 3 (36.0 ± 3.5%, P < 0.001), and 4 to 5 (40.2 ± 2.9 and 46.5 ± 2.8, P < 0.001). The correlations were 0.805 ( P < 0.001) and 0.893 ( P < 0.001) for the 5-category and 10-category scales, respectively. Vessel diameter index showed a significant increase from 1 to 2 (2.90 ± 0.17 and 3.00 ± 0.15; P = 0.004) and 4 to 5 (2.92 ± 0.31 and 3.33 ± 0.08; P = 0.001). The correlations were 0.550 ( P < 0.001) and 0.625 ( P < 0.001) for the respective scales. The fractal dimension showed no significant differences between subsequent groups. The correlations were 0.445 ( P < 0.001) and 0.583 ( P < 0.001), respectively. CONCLUSIONS: Conjunctival AS-OCTA VD was the most reliable parameter to assess ocular redness.

Corneal nerve regeneration is affected by scar location in herpes simplex keratitis: A longitudinal in vivo confocal microscopy study.

PURPOSE: To assess the effect of corneal scar location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer. METHODS: Prospective, longitudinal, case-control study. Bilateral corneal nerve density and corneal sensation were analyzed centrally and peripherally in 24 healthy controls and 23 patients with unilateral HSV-related corneal scars using IVCM. RESULTS: In the central scar (CS) group, total nerve density in the central cornea remained significantly lower compared to controls at follow-up (11.05 ± 1.97mm/mm2, p < 0.001), and no significant nerve regeneration was observed (p = 0.090). At follow-up, total nerve density was not significantly different from controls in the central and peripheral cornea of the peripheral scar (PS) group (all p > 0.05), but significant nerve regeneration was observed in central corneas (16.39 ± 2.39mm/mm2, p = 0.007) compared to baseline. In contralateral eyes, no significant corneal nerve regeneration was observed in central or peripheral corneas of patients with central scars or peripheral scars at 1-year follow-up, compared to baseline (p > 0.05). There was a positive correlation between corneal nerve density and sensation in both central (R = 0.53, p < 0.0001) and peripheral corneas (R = 0.27, p = 0.0004). In the CS group, the corneal sensitivity was <4 cm in 4 (30.8%) and 7 (53.8%) patients in the central and peripheral corneas at baseline, and in 5 (38.5%) and 2 subjects (15.4%) at follow-up, whereas in the PS group only 1 patient (10%) showed a corneal sensation < 4 cm in the central cornea at baseline, and only 1 (10.0%), 3 (30.0%) and 1 (10.0%) patients at follow-up in the central, affected and opposite area of the cornea, respectively. CONCLUSION: The location of HSV scarring in the cornea affects the level of corneal nerve regeneration. Eyes with central corneal scar have a diminished capacity to regenerate nerves in central cornea, show a more severe reduction in corneal sensation in the central and peripheral corneas that persist at follow-up, and have a reduced capability to restore the corneal sensitivity above the cut-off of 4 cm. Thus, clinicians should be aware that CS patients would benefit from closer monitoring for potential complications associated with neurotrophic keratopathy, as they have a lower likelihood for nerve regeneration.

Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study.

Background: The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods: A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings: In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3-27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05-2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31-3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36-0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02-4.64) and phenobarbital (HR = 2.99, 95% CI 1.07-8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44-3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38-4.49), and ICU admission (OR = 1.96, 95% CI 1.19-3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40-3.82), 90-day (HR = 1.78, 95% CI 1.18-2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06-2.24). Interpretation: AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Evaluation of health related quality of life in irritable bowel syndrome patients.

BACKGROUND: Quality of life (QOL) is an important measure in the management of Irritable Bowel Syndrome (IBS). Controversy exists in the findings of studies evaluating QOL in IBS subtypes, and little is known about this issue in Iranian patients. Determination of the factors affecting QOL in IBS patients may influence treatment outcomes. The aims of this study are to: 1) compare QOL between subtypes in a sample of Iranian IBS patients, 2) determine the factors associated with QOL in IBS. METHODS: This cross sectional study included two hundred and fifty IBS patients with the mean age (± standard deviation) of 31.62 (± 11.93) years that were referred to outpatient gastroenterology clinic. IBS patients were diagnosed based on Rome-3 criteria by a gastroenterologist, and then they were categorized into three subtypes according to the predominant type of bowel habit. The "QOL specific for IBS", "Stait-trait anxiety inventory", and "Beck depression inventory-2" questioners were used to evaluate QOL, anxiety, and depression symptoms, respectively. RESULTS: The mean QOL scores in IBS mixed subtype (71.7 ± 25.57), constipation predominant subtype (80.28 ± 25.57), and diarrhea predominant subtype (76.43 ± 19.13) were not different. (P value: 0.05) In multivariate linear regression analysis, anxiety symptom scores were inversely correlated with QOL scores. [Standardized beta: -0.43, (95% confidence interval: -0.70, -0.39), P value: < 0.01] CONCLUSION: It seems reasonable to manage anxiety symptoms properly in IBS patients since this might increase their QOL.

Serum adenosine deaminase may predict disease activity in rheumatoid arthritis.

To determine the relationship between serum adenosine deaminase (ADA) and disease activity, and to develop a new disease activity index based on serum ADA in rheumatoid arthritis (RA). Seventy RA patients were included. Disease activity based on Disease Activity Score 28-ESR (DAS28-ESR) and Disease Activity Score 28-CRP (DAS28-CRP) and serum ADA were measured. There were correlations when serum ADA compared with DAS28-ESR and DAS28-CRP. (R (2) = 0.014, 0.175, respectively, P values < 0.00). New disease activity index was developed by replacing ADA with ESR and CRP in DAS28-ESR and DAS28-CRP. There were strong correlations when new model compared with DAS28-ESR and DAS28-CRP. (R (2) = 0.94 and 0.95, respectively, P values < 0.00) The best new model values corresponding to DAS28-ESR values of 2.6, 3.2, and 5.1 were 2.79, 3.4, and 4.82, respectively; and new model values corresponding to DAS28-CRP values of 2.3, 2.7, and 4.1 were 2.1, 2.9, and 4, respectively. There were agreements when the new model compared with DAS28-ESR and DAS28-CRP for determination of patients in different disease activity categories. (Kappa = 0.81 and 0.71, respectively, P values < 0.00). The new disease activity index that applies serum ADA may help in predicting disease activity in RA.

Serum anti-cyclic citrullinated peptide antibodies may predict disease activity in rheumatoid arthritis.

To define the relationship between serum anti-cyclic citrullinated peptide antibodies (anti-CCP) and disease activity, and to construct a new disease activity index by using anti-CCP in rheumatoid arthritis (RA). One hundred and five RA patients were included. Disease activity based on DAS28-ESR and serum anti-CCP was measured. There was correlation between serum anti-CCP and DAS28-ESR. (R (2) = 0.71, P value < 0.01). New disease activity index was developed by replacing anti-CCP with ESR in DAS28-ESR. There was correlation between new model and DAS28-ESR. (R (2) = 0.91, P value < 0.01) The new composite index best cut-off values corresponding to DAS28-ESR values of 2.6, 3.2, and 5.1 were 3.21, 3.38, and 4.74, respectively. There was agreement between new model and DAS28-ESR for determination of patients in different disease activity categories. (Kappa = 0.71, P value < 0.01). The new disease activity index that applies serum anti-CCP may predict disease activity in RA.

The Effects of Helicobacter Pylori Eradication on Liver Function and Metabolic Profile in Non-diabetic Non-alcoholic Steatohepatitis: A 5-year Randomized Clinical Trial.

BACKGROUND: To evaluate the effects of Helicobacter pylori (HP) eradication on liver function tests (LFT) and fat content (LFC) in non-diabetic non-alcoholic steatohepatitis (NASH). METHODS: This randomized clinical trial included dyspeptic HP infected non-diabetic NASH participants. The intervention arm received HP eradication treatment, while the control arm did not get any HP treatment. In the meantime, the standard management of NASH was performed in both trial arms. Mean alterations in LFT were the primary outcome and the secondary outcomes included the mean changes in LFC and serum metabolic profile. The trial follow-up period was 5 years. RESULTS: 40 participants (female: 20), with a mean age of 41.58 (±12.31) years, were enrolled in the study. The HP eradication arm included 20 participants (female: 11) with a mean age of 40.25 (±10.59) years, and the control arm consisted of 20 individuals (female: 9) with a mean age of 42.90 (±13.97) years. The tests of within-subjects effects showed a significant decrease in mean serum alanine aminotransferase (ALT; P=0.007), triglyceride (TG; P=0.04), cholesterol (P=0.004), and fasting blood sugar (FBS; P<0.001), and an increase in high-density lipoprotein (HDL; P=0.04) in both research groups during the study period. The tests of between-subjects effects demonstrated a more significant decrement of FBS in HP eradicated patients than the controls (P=0.02). The reduction in waist circumference, aspartate aminotransferase (AST), ALT, alkaline phosphatase, triglyceride, cholesterol, low-density lipoprotein, insulin, and LFC were more prominent in the intervention group than the controls; however, these differences were not statistically significant. CONCLUSION: Adding HP eradication treatment to standard NASH treatment showed more therapeutic effect thanthe standard NASH treatment protocol alone regarding the decrement of FBS in participants with dyspeptic non-diabetic NASH. Considering the non-statistically significant improvement in other metabolic indices and LFT in this trial, further studies are recommended.

Automated Image Threshold Method Comparison for Conjunctival Vessel Quantification on Optical Coherence Tomography Angiography.

Purpose: To determine the impact of image binarization and the best thresholding method for conjunctival optical coherence tomography angiography (OCTA). Methods: Vessel density (VD) of 14 OCTA conjunctival images (nine nasal and five temporal conjunctivas, and eight right and six left eyes) from normal subjects was analyzed. The binarization of gold-standard images, created by removing pixels that do not represent vessels on ImageJ software, was assessed by three masked graders to determine consistency of VD for images. Various thresholding methods on ImageJ, including manual, 1-, 2- and 3-step processes, were performed on unprocessed images for comparison. Interclass correlation coefficient (ICC) ≥0.750 were classified as good reliability and selected for calculation of the performance of the pixel location in the binarized images of each method. Results: Analysis of the gold-standard threshold method achieved an ICC of 0.816 with excellent agreement (R2 = 0.965, P < 0.001). From a total 28 different methods and variations performed, only nine methods performed with good reliability, including two 1-step thresholds, six 2-step thresholds, and one 3-step threshold method. Overall, 2-step threshold methods were more reliable than 3-step threshold methods. The 2-step method of Bandpass filter + Phansalkar local threshold (LT) showed the best performance with mean pixel accuracy of 86.9% ± 6.8%, area under the curve of 0.826, sensitivity of 79.0%, and specificity 86.1%. Conclusions: Bandpass filter + Phansalkar LT was the best method for VD measurement in conjunctival OCTA. Most commonly reported threshold methods showed unsatisfactory agreement. There is a need in the OCTA field for a standardized method to allow comparison between different studies. Translational Relevance: The proposed threshold method using a widely accessible and commonly used software provides an accurate VD measurement for future OCTA studies.

Acute pancreatitis as an adverse effect of COVID-19 vaccination.

While vaccination against COVID-19 has significantly improved the morbidity and mortality of the disease, with the increase in the administration of COVID-19 vaccines, it is more likely to observe their rare side effects in the clinical settings. Herein, we report a case of an 82-year-old man with history of coronary artery disease, prostate cancer in remission, gastroesophageal reflux disease, and hypothyroidism, who presented with acute pancreatitis few hours after receiving the third dose of Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine, without other identified etiology. His symptoms were mild and he was discharged in a stable condition after improvement in his condition with supportive care.