Factors Associated with Chronic Rejection in Liver Transplant Recipients: A Retrospective Cohort Study From Shiraz Organ Transplant Center.

OBJECTIVES: Identification of chronic rejection risk factors in liver transplant recipients is critical for early detection and prevention of further graft loss. We investigated characteristics of liver transplant recipients who had experienced chronic rejection and the associated risk factors versus patients without chronic rejection. MATERIALS AND METHODS: Data from 3022 adult liver transplant recipients between 2011 and 2018 were analyzed; of these, 80 patients had experienced chronic rejection. The control group included 98 randomly selected liver transplant recipients who did not have chronic rejection. RESULTS: The age of the recipients and the donors was significantly lower in the group with chronic rejection versus the group without chronic rejection.The results indicated that chronic rejection was significantly associated with the sex of the recipients (hazard ratio 3.2, 95% CI 1.77-6.08; P < .001) and with the sex concordance between the recipients and donors (hazard ratio 2.93, 95% CI 1.67-5.13; P < .001, respectively). Also, in the group without chronic rejection, there were no male donors; however, the group with chronic rejection had mostly male donors (P <.001). Cold ischemia time was longer in patients with chronic rejection versus that shown in the control group (P = .031), and there was a significant difference between the 2 groups in acute rejection frequency (P < .001). CONCLUSIONS: Recipient sex and sex concordance were independent risk factors for chronic rejection. Most transplantrecipients with chronic rejection responded to medicaltreatment, and the rate of graftloss was low among our recipients.

Giant non-parasitic splenic cyst: a case report.

BACKGROUND: Splenic cysts are quite rare and asymptomatic. They may result from infection by a parasite, especially Echinococcus granulosus (hydatid cyst), or from non-parasitic causes. Since primary splenic cysts are not common, simple cysts can be misdiagnosed with a hydatid cyst in endemic areas. CASE PRESENTATION: We reported a 14-year-old Iranian girl initially presented with a vague abdominal pain, which progressed to left shoulder pain, fullness, early satiety, and shortness of breath and remained undiagnosed for 7 months despite seeking medical attention. Finally, imaging revealed a massive splenic cyst measuring 220 mm × 150 mm × 160 mm raising concern for a hydatid cyst due to regional endemicity. Consequently, the patient underwent total splenectomy. However, histopathological examination surprisingly revealed a simple non-parasitic cyst. CONCLUSIONS: Detecting rare simple spleen cysts requires early ultrasonography (US) and careful reassessment of diagnoses for non-responsive or worsening symptoms. Distinguishing them from splenic hydatidosis, especially in endemic areas, demands thorough paraclinical evaluations and patient history regarding potential parasitic exposure. While total splenectomy is the primary treatment for these huge cysts, the optimal surgical approach should be tailored case by case. These insights emphasize a comprehensive diagnostic approach to enhance accuracy and optimize patient care for these uncommon cysts.

Metabolic Syndrome in Celiac Disease: What Does Following a One-Year Gluten-Free Diet Bring?

Background: Metabolic syndrome (MetS) is a set of conditions that occur together and increase the risk of cardiovascular disease. Previous studies have linked a gluten-free diet (GFD) to obesity and MetS in some populations. However, others have suggested that weight gain is usually regulated only in underweight individuals with celiac disease (CD). Owing to the lack of sufficient data and the importance of GFD in controlling cardiovascular disease, we surveyed the prevalence of MetS and its components before and after a year of GFD in patients referred to the main celiac clinic in southern Iran. Methods: This was a repeated cross-sectional study conducted on 69 patients with a definite diagnosis of cardiovascular disease who were on follow-up and registered at the Shiraz Celiac Clinic. Demographic, anthropometric, and laboratory measurements at the time of diagnosis and one year after the GFD were extracted from their medical records. Results: The participants' mean age was 35.53, and 68.1% were women. The prevalence of MetS increased from 5.8% to 11.6% after a year of the GFD; however, this increase was not statistically significant. Waist circumference (WC) and serum triglyceride levels were significantly elevated during the study period. Conclusion: A GFD may contribute to the development of MetS in patients with cardiovascular disease; however, the rate of MetS is still lower than that in the general population. It is critical to educate patients about these potential risks and encourage them to have a healthy lifestyle that includes a balanced diet and physical activity.

Acute toxic effects of areca nut on central nervous system and liver: A case report.

Areca nut (AN) is an addictive substance widely used in different world regions. There are several side effects associated with the use of AN, which have already been reported. However, the reports on hepatotoxicity of AN are sporadic and non-conclusive. In the present case report, we investigated the hepatotoxicity of AN in a four-year-old Iranian girl who was transferred to our medical center with abdominal pain, vomiting, diarrhea, fever, and other symptoms such as hematuria, decreased mental status, multiple seizure episodes. After a comprehensive evaluation, it was concluded that these signs and symptoms were all attributed to AN consumption, which was given by her mother to control diarrhea. Eventually, the patient medical conditions were managed successfully, and she survived by intense medical care. In conclusion, we suggest AN should be considered a potential hepatotoxic agent.

Knowledge, attitude, and practice regarding stroke potential complications among stroke survivors' family members in Shiraz, Iran.

Objectives: This study aimed to evaluate stroke survivors' family members' knowledge, attitude, and practice about these sequelae. Patients and methods: In this cross-sectional survey, 105 family members (57 males, 48 females; mean age: 48.3±9.7 years; range 18 to 60 years) of stroke survivors were examined via a self-structured questionnaire between September 2019 and January 2020. Patients' medical characteristics, as well as participants' sociodemographic and opinions regarding studying variables, were surveyed. Results: The participants were mostly married and had relatively high scores in knowledge, attitude, and practice questionnaires. We found a significant correlation between participants' knowledge and practice. Moreover, data analysis revealed significantly higher knowledge scores in the employed participants and higher practice scores in the urban population. Furthermore, the relationship of patients with their family members can affect their attitude toward stroke complications. Conclusion: This study has revealed that caregivers in rural areas with lower education levels are less knowledgeable about potential stroke complications, and subsequently, the patients are more vulnerable to those sequelae. Stakeholders should consider these groups their priorities in education and empowerment processes for stroke survivors' caregivers.

Burden of knee osteoarthritis in the Middle East and North Africa (MENA): an epidemiological analysis from 1990 to 2019.

BACKGROUND: Knee is the most affected joint in osteoarthritis (OA) and accounts for almost four-fifths of the burden of OA globally. We aimed to explore the prevalence, incidence, trends, and burden of knee OA during 1990-2019 in the Middle East and North Africa (MENA) region, using the Global Burden of Disease (GBD) study data. METHODS: This is an epidemiological study based on the GBD data from 1990 to 2019 on knee OA in MENA countries. The prevalence, incidence, and years lived with disability (YLD) numbers of knee OA were obtained for both genders. Similarly, age-standardized rates of these indexes per 100,000 people and the proportion of total YLD caused by knee OA in each country and for the MENA region were evaluated. RESULTS: The prevalence of knee osteoarthritis in the MENA region increased 2.88-fold, from 6.16 million cases to 17.75 million, between 1990 and 2019. Furthermore, in 2019, knee osteoarthritis accounted for approximately 1.69 million (95% UI 1.46-1.95) incident cases in MENA. The age-standardized prevalence was higher in women between 1990 (3.94% [95% UI 3.39-4.55] in women and 3.24% [95% UI 2.79-3.72] in men) and 2019 (4.44% [95% UI 3.83-5.10] in women and 3.66% [3.14-4.21] in men). Total YLDs due to knee osteoarthritis increased by more than 2.88-fold, rising from 196.29 thousand [95% UI 97.17-399.29] in 1990 to 564.66 thousand [95% UI 275.06-1,150.68] in 2019. In the year 2019, Kuwait, Turkey, and Oman had the highest age-standardized prevalence (4.42% [95% UI 3.79-5.08]), YLD (132.41 [95% UI 65.79-267.56] per 100 000), and increase (21.17%) in YLD compared with 1990 in MENA region, respectively. CONCLUSION: The prevalence of and YLDs due to knee OA in MENA has escalated over the last three decades. Considering the expanding burden of knee OA in MENA, policymakers should be more concerned to implement preventive strategies.

Prope tolerance after pediatric liver transplantation: Experience at Shiraz Organ Transplant Center.

BACKGROUND: Children receive transplants at a younger age, and the period of immunosuppression therapy may extend over decades. However, immunosuppression seems to be responsible for long-term mortality and morbidity. Pediatric liver transplant recipients can benefit from achieving immune tolerance and the opportunity of freedom from lifelong immunosuppression. This study aimed to investigate the frequency of prope tolerance among pediatric liver transplant recipients and the characteristics of these patients. METHODS: In this retrospective cohort study of pediatric liver transplant recipients, the medical records of transplant recipients treated at Shiraz Organ Transplant Center between 1994 and 2017 were reviewed. Prope tolerance was defined as normal laboratory values and stable clinical status on low-dose monotherapy. Children treated with low-dose monotherapy were categorized as the prope tolerant group. We compared the characteristics of prope tolerant recipients on low-dose monotherapy with patients on standard immunosuppression, i.e. full-dose tacrolimus plus steroids and mycophenolate mofetil. The data were analyzed with the t-test, chi-squared test, and a Cox proportional hazard model at a 5% significance level in SPSS software version 16. RESULTS: A total of 585 children with a mean age of 8.32 ± 5.23 years were enrolled. 341 patients were categorized as prope tolerant and 244 comprised the full immunosuppression regimen group. Mean age at transplantation and rejection frequency were lower in the prope tolerant group (p < 0.001, p < 0.001). Based on the underlying diseases, metabolic/genetic, biliary tract, and cryptogenic liver diseases were significantly more prevalent in the prope tolerant group (p < 0.001). However, autoimmune liver disease was found to be more prevalent in the full immunosuppression regimen group. Also, those who received living organs (p = 0.001) and recipients of organs from female donors had a greater likelihood of achieving prope tolerant. According to the multiple Cox regression results, age at transplantation (p = 0.022), rejection frequency (p < 0.001), and autoimmune liver diseases (p = 0.028) had a prognostic effect on prope tolerance. CONCLUSION: Factors as underlying disease, age at transplantation, and rejection frequency were factors that were predictive of prope tolerance in this sample of children. However, the risk of rejection should be considered during the tapering period.

The Revolutionary Impacts of the COVID-19 Pandemic on Mobile Health; Highlights of the Fourth Shiraz International Congress on Mobile Health.

Mobile health (m-health) is considered an undeniable part of health service delivery, planning, and marketing, which has dramatically changed due to the unique situation caused by the COVID-19 pandemic. The Forth International Congress of Mobile Health, from February 14th to 16th, 2021, in Shiraz, Iran, aimed to provide a venue to exchange ideas, techniques, relevant experiments, and applications with a particular focus on the COVID-19 pandemic impacts. More than 70 experts from different countries in engineering, biomedical sciences, and humanities presented their recent experiences in m-health advancements, particularly in response to the COVID-19 outbreak. In this article, highlights of the most valuable ideas presented at the congress are concisely summarized to give scientists, entrepreneurs, policymakers, and other stakeholders a better understanding of the growing opportunities, and challenges toward the development of m-health.

Questioning Diagnostic Value of Serum Matrix Metalloproteinase 7 for Biliary Atresia.

Background: Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing biliary atresia (BA). This study aimed to assess the diagnostic accuracy of serum MMP7 in BA in the Middle Eastern population. Methods and materials: In this cross-sectional study, neonates and infants with direct hyperbilirubinemia admitted to Namazi referral hospital, Shiraz, Iran, were studied. Baseline demographic and clinical characteristics and blood samples were obtained on admission. MMP7 serum concentration was measured using an enzyme-linked immunosorbent assay (ZellBio GmbH, Ulm, Germany). Results: 44 infants with a mean age of 65.59 days were studied. Of these patients, 13 cases were diagnosed with BA, and 31 cases' cholestasis related to other etiologies. Serum MMP7 concertation was 2.13 ng/mL in the BA group and 1.85 ng/mL in the non-BA group. MMP7 was significantly higher in those presented with either dark urine or acholic stool. The predictive performance capability of the MMP7 was not significant in the discrimination of BA from the non-BA group based on receiver operating characteristic curve analysis (area under curve: 0.6, 95% confidence interval: 0.45-0.75). In the optimal cut of point 1.9, the sensitivity and specificity were 84.6% and 45.1%, respectively. Further combination of MMP7 with Gamma-glutamyl transferase (GGT), alkaline phosphatase, direct and total bilirubin, and dark urine or acholic stool was not remarkably boosted the diagnostic accuracy of the test. Interestingly, GGT at a cut-off point of 230 U/L was 84.6% sensitive and 90.3% specific for BA. Conclusion: Our results are not consistent with previous studies on this subject. Considering more conventional and available tests like GGT besides conducting future studies with greater samples and different geographical areas is recommended.

Extra-intestinal manifestations of Celiac disease in children: their prevalence and association with human leukocyte antigens and pathological and laboratory evaluations.

BACKGROUND: Celiac disease (CD) is an autoimmune disease caused by gluten intake. Traditionally CD was believed to be a disease of the gut, although a wide range of extra-intestinal manifestations (EIM) was recognized. The exact prevalence of EIM and the associated risk factors have not been well studied. AIM: We aimed to assess the prevalence of EIM in children with CD and their association with human leukocyte antigen (HLA) typing, and pathological and laboratory indices. METHOD: We conducted a cross-sectional study on children and adolescents with a definite diagnosis of CD. They were followed in the main Celiac Clinic of Southern Iran. RESULTS: We included 204 children who were visited between 2012 and 2017. Nearly 85% of them were positive for HLA-DQ2 and 40.6% for HLA-DQ8. The most prevalent intestinal complaints reported were abdominal pain (42.6%) and chronic constipation (19.1%). Failure-to-thrive (32.7%), iron deficiency anemia (25%), short stature (20.5%), and eczema (18.6%) were the most common EIMs. However, failure-to-thrive and short stature were presented at significantly younger ages, whereas those patients with concomitant type 1 diabetes mellitus (DM) were significantly older. We also found significant relationships between autoimmune thyroid disease and HLA-DQ5, and the presence of headaches with HLA-DQ7. The prevalence of HLA types of DQ2, DQ8, DQ6, and DQ7 significantly varied among different Marsh groups. Patients who were positive for HLA-DQ8, were significantly older, taller, and weightier. No significant association was found between HLA types and any of the gastrointestinal symptoms, anti-tTG and compliance to gluten free diet. Moreover, there were no statistically significant differences detected between the presence of each individual EIM, the level of IgA anti-tTG, sex, and Marsh typing. CONCLUSION: This study highlights the presence of EIM in CD and their associated factors. We show the potential role of HLA typing in some EIMs, which may shed light for future studies.

Frailty as a predictor of poor outcomes among patients awaiting liver transplant: a systematic review and meta-analysis.

Aim: This review sought to evaluate the significance of a functional assessment for liver transplant candidates, i.e., frailty, in the pre-transplant setting and its association with mortality and morbidities. Background: Liver transplantation (LT) remains the treatment of choice for patients with end-stage liver disease. Due to the shortage of organs for LT, a careful selection of suitable recipients is essential. Frailty, a measure of physiologic reserve and increased vulnerability to stressors, was initially used in geriatrics and then introduced to the field of transplantation for better patient selection. Methods: PubMed, Scopus, and Web of Science databases were reviewed up until January 2023. The search terms included: "frail*", "liver", and "transplant*". A Meta-analysis was conducted for the hazard ratios (HRs) obtained from the COX regression models. Fifty-five studies were included in this review; ten were included in the meta-analysis. Results: The prevalence of frailty varied from 2.82% to 70.09% in the studies. Meta-analysis showed that overall frailty had a significant association with mortality (pooled adjusted HR [95%CI]: 2.66 [1.96-3.63]). Subgroup analyses revealed that both the Liver Frailty Index and Fried Frailty Index were significantly associated with mortality. Furthermore, these studies have demonstrated that this population's frailty is associated with ascites, hepatic encephalopathy, and esophageal varices. Conclusion: According to emerging evidence, frailty is associated with increased morbidity and mortality of the patients on the LT waiting list. Further randomized trials are required to determine the efficacy and safety of variable interventions in the frail population.

Cohort Profile: Shiraz Pediatric Liver Cirrhosis Cohort (SPLCCS).

Liver diseases in children and adolescents are a significant and arising public health issue and should be surveyed from different dimensions (clinical and para-clinical, psychological, socio-economic) and in diverse populations. Shiraz Liver Transplant Center, Shiraz, Iran is the only center for pediatric liver transplantation and its pre-operative evaluations. This provides a unique and valuable situation for studying this vulnerable population. The Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) was established to assess cirrhotic children, the course of their disease, and treatment over time. This cohort study aimed to prospectively evaluate the natural course and factors that contributed to complications and death of children with chronic liver disease in the region. SPLCCS was launched in September 2018 after obtaining ethical approval; until August 2022, 370 children with end-stage liver disease were enrolled and followed every six months. Here, the cohort's features, the included population's baseline characteristics, and primary outcomes are reported.

Isoniazid prophylaxis in liver transplant recipient with latent tuberculosis: Is it harmful for transplanted liver?

BACKGROUND: Liver transplantation (LT) is considered the only treatment for patients with end-stage liver disease and, despite its incredible impacts on the patients' health status, places them in an immunocompromised state in which opportunistic infection would find a way to present. Latent tuberculosis infection (LTBI) is the most common form of TB and can be diagnosed through tuberculin skin test (TST) or Interferon-Gamma Release Assays (IGRA). LT recipients are at significant risk of TB activation. There is no strict guideline to approaching these cases though, in most centers, Isoniazid (INH) would be prescribed prophylactically. INH is a hepatotoxic medication and can have adverse effects on the transplanted liver. There is no consensus on this issue; therefore, we aimed to survey the potential hepatotoxic effects of INH among LT recipients in Shiraz, Iran. METHODS: A retrospective cohort study was conducted among LT candidates and recipients at Abu Ali Sina Organ Transplantation Center between 1993 and 2019. All the cases underwent TST and chest X-ray to detect LTBI. All the LTBI were treated with INH from 6-9 months and followed by the level of liver enzymes for quick detection of hepatotoxicity. A control group was selected among LT recipients and matched for age, gender, MELD score, and donor age. RESULTS: Among 4895 medical records reviewed, 55 (1.12%) cases had LTBI. Neither INH-related hepatotoxicity, nor signs and symptoms that were suspicious to TB reactivation were reported. Overall, three deaths were reported, two because of myocardial infarction and one due to pneumonia. Ten patients (18.2%) experienced acute rejection as confirmed with pathology and responded to methylprednisolone. Aspartate aminotransferase (AST) was diminished from pre-LT time to the first time after transplantation; after that, it showed a steady pattern. Meanwhile, Alanine transaminase (ALT) was constant before and one stage later and decreased after that. Statistical analyses only showed significant changes in the total bilirubin titer between the case and control groups. CONCLUSION: This survey showed prophylactic management of LTBI with INH in LT candidates and recipients was associated with no hepatotoxicity or related death. It seems that INH prophylaxis is safe in LT settings and can efficiently prevent TB activation; however, careful monitoring for adverse effects and liver enzymes elevation is highly recommended.

Different types and epidemiological patterns of calcaneal fractures based on reviewing CT images of 957 fractures.

INTRODUCTION: Calcaneal fractures may have lifelong debilitating sequences, if not treated properly. Identifying different types of calcaneal fractures based on the computed tomography (CT) scans can increase our conception about these fractures. METHODS: In a cross-sectional study, the available CT images of all consecutive patients with the diagnosis of calcaneal fracture, from January 2015 to December 2018, were reviewed to determine different patterns and types of these fractures. RESULTS: CT images of 886 patients (mean age, 41.29 ± 14.9; range, 3-89 years; male/female, 4.86; pediatric: 3.7%) with 957 calcaneal fractures were evaluated. The peak incidence of calcaneal fractures was seen in patients between 30 to 39 years of age (29%). The rate of open fractures and bilateral involvements were 2.4% and 8.0%, respectively. Among 680 (71.0%) intra-articular calcaneal fractures, subtalar calcaneal fractures were the most common type (94.3%). The majority of intra-articular subtalar calcaneal fractures were displaced (95.0%) with calcaneocuboid joint (CCJ) involvement (59.9%). Fracture lines were extended to the CCJ in about 86.9% of Sanders type IV, 66.3% of type III, and 60.2% of type II. Among 261 extra-articular fractures (27.3%), calcaneal body fracture (55.6%) was the most frequent type, followed by medial tubercle fracture (24.1%), calcaneal tuberosity fracture (10.4%), Degan type I anterior process fractures (5.4%), Degan type II anterior process fracture (3.4%), and isolated lateral tubercle fracture (1.1%). Most of bilateral calcaneal fractures were intra-articular subtalar fractures with involvement of CCJ. Although majority of intra-articular calcaneal fractures were displaced; less than half of the extra-articular fractures were displaced. CONCLUSION: Displaced intra-articular subtalar calcaneal fractures with CCJ involvement are the most frequent type of unilateral and bilateral calcaneal fractures. It appears that there is a correlation between Sanders type and the probability of CCJ involvement. Unlike intra-articular subtalar calcaneal fractures, the CCJ in the majority of extra-articular calcaneal body fractures was intact. LEVEL OF EVIDENCE: Level IV.

Risk perception, attitude, and practice related to COVID-19: A cross-sectional study among 1085 Iranian healthcare workers.

BACKGROUNDS: Healthcare workers are at risk of mental illness during COVID-19 pandemic. We investigated the level of perceived risk and adherence to preventive behaviors regarding COVID-19 among medical students and physicians. MATERIALS AND METHODS: We conducted an online nationwide cross-sectional survey among Iranian physicians and medical students. We collected data regarding perceived risk, perceived stress scale (P·S·S.), attitude, practice, and information sources. We assessed the association of four main outcomes (risk perception, P·S.S. score, attitude, and practice) with demographic variables. RESULTS: A total of 1085 participants with an overall fear score of 6.48 ± 2.29 out of 10 filled the questionnaires. Older and more educated participants had a higher risk perception level and adherence to protective measures. In contrary, participants in lower-risk workplaces had lower risk perception scores. Main sources of information did not affect the scores of risk perception, P·S·S., and practice. Higher risk perception scores were observed in those with higher practice and P·S.S. scores.Contrary to risk perception, the P·S.S. score was not affected by many of the demographic variables, except gender. The most positive attitude was observed in individuals with a higher level of trust in governmental information sources. Participants with higher P·S.S. scores adhered more to protective measures. CONCLUSION: Risk perception had the greatest impact on adherence to preventive behaviors. Therefore, policymakers should consider perceived risk as a predictor of the extension of the pandemic. Both risk perception and P·S.S. reflect the severity of fear from COVID-19; however, P·S.S. is less affected by sociodemographic and workplace characteristics.

COVID-19 clinical manifestations and treatment strategies among solid-organ recipients: A systematic review of cases.

BACKGROUND: COVID-19 has been spreading worldwide with a significant death toll. Solid-organ transplantation (SOT) recipients are at higher risk due to their suppressed immune system. In this study, we aimed to conduct a systematic review on COVID-19 clinical manifestations and treatment strategies in SOT recipients. METHODS: We searched three databases for relevant terms related to COVID-19 and transplantation. 50 studies, including 337 patients, were reviewed. RESULTS: Two hundred thirty six patients were male, with a mean age of 49.9 years. The most prevalent group was the kidney 57.0%, followed by 17.2% heart and 13.6% liver. Fever and cough were the most reported clinical presentations. Infiltration (55.4%) in chest x-ray and ground-glass opacity (67.1%) in CT scans were the most radiological findings. It was found that 96.8% and 72.4% of patients present with CRP level and lymphocytopenia, respectively, and 70.6% of kidney recipients patients presented with high creatinine levels. The most common baseline immunosuppressants were calcineurin inhibitors (88.9%) and antimetabolites (73.2%). Antimetabolites (84.3%) and calcineurin inhibitors (54.3%) were discontinued/decreased 84.3% whereas glucocorticoids dosage almost has no change (77.9%) or even increased. 18.4% of cases had died, and 65.9% were discharged. CONCLUSIONS: Patients' demographics, signs, symptoms, and radiographic findings in SOT recipients are almost similar to the general population. However, gastrointestinal symptoms appear to be more common. There are different treatment strategies, but in most of them, antimetabolite and calcineurin inhibitors were decreased or discontinued, while corticosteroids were increased. Finally, COVID-19 seems to be more severe and has higher mortality in SOT recipients compared to the general population.