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.

Expression of miR-let7b and miR-19b in progressive familial intrahepatic cholestasis (PFIC) children / Expresión de miR-let7b y miR-19b en niños con colestasis intrahepática familiar progresiva (PFIC)

Background MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children. Methods 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control. Results qPCR on PFIC patients’ samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively. Conclusion In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future (AU)

Antecedentes Los microRNA (miRNA) son un grupo de pequeños RNA no codificantes que se unen al ARNm diana y regulan la expresión génica. Recientemente se han investigado los microRNA circulantes como marcadores de enfermedades y dianas terapéuticas. Aunque varios estudios analizan la expresión de miRNA en enfermedades hepáticas, estos estudios sobre PFIC son escasos. La colestasis intrahepática familiar progresiva (PFIC) es una enfermedad hepática rara con herencia autosómica recesiva. La mayoría de los niños con PFIC progresan a cirrosis e insuficiencia hepática y, en consecuencia, requieren de un trasplante de hígado. El objetivo de este trabajo es la investigación de los niveles de expresión de miR-19b y miR-17b en niños iraníes con PFIC. Métodos Se consideraron 25 pacientes con PFIC, 25 niños sanos y 25 pacientes con atresia biliar como grupos de casos y controles. Se obtuvieron muestras de sangre y se midieron las pruebas de función hepática (LFT). Después de la extracción de RNA y la síntesis de cDNA, se realizó PCR cuantitativa usando cebadores específicos para miR-19b y miR-17b. El gen U6 se utiliza como control interno. Resultados La qPCR en muestras de pacientes con PFIC demostró que la expresión de miR-19b y miR-17b disminuyó significativamente en los pacientes en comparación con dos grupos de control, con un valor de p<0,0001 y un valor de p=0,0006, receptivamente. Conclusión En conclusión, los micro-RNA circulantes, como miR-19b y miR-let7b, tienen una oportunidad potencial de ser un marcador de diagnóstico no invasivo o un objetivo terapéutico para PFIC en el futuro (AU)

Nanoparticles' Perspective in Skin Tissue Engineering: Current Concepts and Future Outlook.

Nanotechnology seems to provide solutions to the unresolved complications in skin tissue engineering. According to the broad function of nanoparticles, this review article is intended to build a perspective for future success in skin tissue engineering. In the present review, recent studies were reviewed, and essential benefits and challenging issues regarding the application of nanoparticles in skin tissue engineering were summarized. Previous studies indicated that nanoparticles can play essential roles in the improvement of engineered skin. Bio-inspired design of an engineered skin structure first needs to understand the native tissue and mimic that in laboratory conditions. Moreover, a fundamental comprehension of the nanoparticles and their related effects on the final structure can guide researchers in recruiting appropriate nanoparticles. Attention to essential details, including the designation of nanoparticle type according to the scaffold, how to prepare the nanoparticles, and what concentration to use, is critical for the application of nanoparticles to become a reality. In conclusion, nanoparticles were applied to promote scaffold characteristics and angiogenesis, improve cell behavior, provide antimicrobial conditions, and cell tracking.

Expression of miR-let7b and miR-19b in progressive familial intrahepatic cholestasis (PFIC) children.

BACKGROUND: MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children. METHODS: 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control. RESULTS: qPCR on PFIC patients' samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively. CONCLUSION: In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future.

The mutation spectrum and ethnic distribution of Wilson disease, a review.

Wilson's disease is a complicated medical condition caused by the accumulation of copper, mostly in the liver and brain. The genetic basis of Wilson's disease is attributed to the presence of pathogenic variants in the ATP7B copper-transporting gene, which prevents the excretion of copper through the biliary tract. To date, ATP7B remains the only identified gene that has been linked to the development of this disease. Our understanding of the disease has been associated with the identification of particular disease-causing variants that present specific impairments in copper transporters. It is crucial to identify the most frequent variant in terms of ethnicity to facilitate testing of its functionality. This study represents the initial comprehensive analysis of ATP7B variants, providing insights into the extensive range of disease-causing mutations. Here, we describe the 1275 distinct ATP7B variants documented so far, with particular emphasis on their regional and ethnic prevalence. The H1069Q missense variant is the most frequently reported in Europe, Northern America, and North Africa, whereas the R778L, C271*, and M645R variants are the most prevalent in the East Asian, Middle Eastern-South Asian, and South American populations, respectively. Acquiring such knowledge would facilitate the implementation of a selective mutation screening approach, targeting the most predominant variant identified within a specific ethnic group or geographic region for better diagnosis of the disease.

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.

A massive immature mediastinal teratoma treated with chemotherapy and surgical resection: a case report.

BACKGROUND: Teratoma is a type of germ cell tumor consisting of one or multiple tissues derived from germinal layers. The location and size of the tumor can cause various presentations. Here we report one of the largest ever cases of immature cystic teratoma. CASE PRESENTATION: In this report, we presented a 24-year-old patient with dyspnea, chest pain, nausea, and anorexia. A computed tomography scan revealed a giant, right-sided mass measuring about 190 × 150 × 140 mm. Chemotherapy was initiated for the patient, followed by thoracotomy. Histopathological evaluation revealed the nature of the mass to be an immature mediastinal teratoma. CONCLUSION: the incidence of immature mediastinal teratoma is uncommon, and due to its rarity, the diagnosis needs more profound evaluation studies such as radiological and pathological assessments. Immature teratomas are optimally treated by a combination of chemotherapy and complete resection.

A pediatric case series of catastrophic gastrointestinal complications of posttransplant lymphoproliferative disease with increasing incidence, high association with coronavirus disease 2019, higher mortality, and a plea for early endoscopy to prevent late fatal outcome.

BACKGROUND: Posttransplant lymphoproliferative disorder is one of the most severe complications after transplantation, caused by uncontrolled proliferation of Epstein-Barr virus-positive B-cells in the setting of chronic immunosuppression. As one of the biggest transplant centers worldwide, we observed a potential increase in the number of patients with posttransplant lymphoproliferative disorder presenting with gastrointestinal symptoms in 1 year, during the coronavirus disease 2019 pandemic. There is limited information about dysregulation of the immune system following coronavirus disease 2019 infection, which may lead to Epstein-Barr virus reactivation in Epstein-Barr virus-positive B-cells and development of posttransplant lymphoproliferative disorder. Furthermore, there is no consensus in literature on a modality that can help in early diagnosis of posttransplant lymphoproliferative disorder with nonspecific gastrointestinal presentations before late and fatal complications occur. CASE PRESENTATION: Our case series includes five Iranian (Persian) patients, three female (2, 2.5, and 5 years old) and two male (2 and 2.5 years old), who developed gastrointestinal posttransplant lymphoproliferative disorder after liver transplantation. All of our patients were on a similar immunosuppressant regimen and had similar Epstein-Barr virus serologic status (seronegative at time of transplantation but seropositive at time of posttransplant lymphoproliferative disorder diagnosis). Four patients had either a positive coronavirus disease 2019 polymerase chain reaction test or exposure within the family. Although all of our patients presented with nonspecific gastrointestinal symptoms, four patients developed late posttransplant lymphoproliferative disorder complications such as bowel perforation and obstruction. All five patients with gastrointestinal posttransplant lymphoproliferative disorder received chemotherapy, but only two survived and currently are continuing the therapy. In one of the surviving patients, prompt endoscopic investigation resulted in early diagnosis of posttransplant lymphoproliferative disorder and a better outcome. CONCLUSION: Since 80% of our patients had exposure to coronavirus, a potential relationship might be suggested between the two. Furthermore, as we witnessed in one case, urgent endoscopic investigation in immunocompromised patients presenting with gastrointestinal symptoms can improve the clinical outcomes and therefore should be considered for early diagnosis of posttransplant lymphoproliferative disorder.

Sclerosing angiomatoid nodular transformation of the spleen in a child with anemia: a case report and review of the literature.

BACKGROUND: Sclerosing angiomatoid nodular transformation of the spleen is a relatively rare benign vascular lesion in both adult and pediatric age groups with unclear etiopathogenesis and variable clinical presentations. Many benign and also malignant splenic masses could mimic sclerosing angiomatoid nodular transformation, both clinically and radiologically. Herein, we report our experience with a case of sclerosing angiomatoid nodular transformation in a 3-year-old girl. CASE REPORT: A 3-year-old Iranian girl presented with abdominal pain, back pain, and constipation for 2 weeks. She was being followed up by a pediatrician due to her short stature and persistent anemia. Physical examination showed stable vital signs, short stature, pallor, and a puffy face. Laboratory evaluation showed normochromic normocytic anemia with a normal reticulocyte count, ferritin, and hemoglobin electrophoresis. Radiologic assessments revealed a hypoechoic lesion in the spleen with high vascularity, clinically suspected to be lymphoma. She was operated on, and after partial splenectomy, pathologic evaluation of the spleen showed a solitary, well-demarcated, and unencapsulated dark mass. Microscopic examination revealed micronodular appearance composed of irregular-shaped vascular spaces lined by plump endothelial cells and surrounded by concentric collagen fibers, features in keeping with sclerosing angiomatoid nodular transformation. The patient's anemia was resolved after surgery, and no clinical or radiologic deficits were noted during the 10-month follow-up visits. CONCLUSION: Although sclerosing angiomatoid nodular transformation is exceedingly rare in children, it should be considered a differential diagnosis in pediatric splenic neoplasms with concurrent hematologic manifestations, such as anemia.

Type distribution of human papillomaviruses in ThinPrep cytology samples and HPV16/18 E6 gene variations in FFPE cervical cancer specimens in Fars province, Iran.

BACKGROUND: There exists strong evidence that human papillomavirus (HPV) is associated with cervical cancer (CC). HPV E6 is a major oncogene whose sequence variations may be associated with the development of CC. There is not sufficient data on the distribution of HPV types in ThinPrep cytology specimens and HPV 16/18 E6 gene variations among CC patients in the southwest of Iran. This study was conducted to contribute to HPV screening and vaccination in Iran. METHODS: A total of 648 women screened for cervicitis, intraepithelial neoplasia or CC were included in the study. All participants underwent ThinPrep cytology testing, single-step HPV DNA detection and allele-specific reverse hybridization assays. Moreover, a total of 96 specimens previously tested positive for single infection with HPV16 or 18 were included for variant analysis. HPV16/18 lineages and sublineages were determined by PCR assays followed by sequencing the E6 gene and the construction of neighbor-joining phylogenetic trees. RESULTS: Overall, HPV DNA was detected in 62.19% of all the screened subjects. The detection rates of HPV DNA among individuals with normal, ASC-US, ASC-H, LSIL, and HSIL cervical cytology were 48.9%, 93.6%, 100%, 100%, and 100%, respectively. Low-risk HPVs were detected more frequently (46.9%) than high-risk (38.9%) and possible high-risk types (11.1%). Of 403 HPV-positive subjects, 172 (42.7%) had single HPV infections while the remaining 231 (57.3%) were infected with multiple types of HPV. Our results indicated a remarkable growth of high-risk HPV66 and 68 and low-risk HPV81 which have rarely been reported in Iran and HPV90 and 87 that are reported for the first time in the country. In addition, 3 lineages (A, D, and C) and 6 sublineages (A1, A2, A4, C1, D1, and D2) of HPV16, and one lineage and 4 sublineages (A1, A3, A4, and A5) of HPV18 were identified. The studied HPV16 and 18 variants mainly belonged to the D1 and A4 sublineages, respectively. CONCLUSION: The present study suggests that the prevalence of HPV infection in women of all age groups with or without premalignant lesions in the southwestern Iran is high and the predominant HPV types in the southwest of Iran may differ from those detected in other parts of the country. This study also highlights the necessity of not only initiating HPV vaccination for the general population but also developing new vaccines that confer immunity against the prevalent HPV types in the area and national cervical screening programs using a combination of thinPrep cytology test and HPV detection assays in order to improve the accuracy of the screening.

Biocompatible scaffolds based on collagen and oxidized dextran for endothelial cell survival and function in tissue engineering.

Angiogenesis is a vital step in tissue regeneration. Hence, the current study aimed to prepare oxidized dextran (Odex)/collagen (Col)-hydrogels with laminin (LMN), as an angiogenic extracellular matrix (ECM) component, for promoting human umbilical vein endothelial cell (HUVEC) proliferation and function. Odex/Col scaffolds were constructed at various concentrations and temperatures. Using oscillatory rheometry, scanning electron microscopy (SEM), and cell viability testing, the scaffolds were characterized, and then HUVEC proliferation and function was compared with or without LMN. The gelation time could be modified by altering the Odex/Col mass ratio as well as the temperature. SEM showed that Odex/Col hydrogels had a more regular three-dimensional (3D) porous structure than the Col hydrogels. Moreover, HUVECs grew faster in the Col scaffold (12 mg/mL), whereas the Odex (30 mg/mL)/Col (6 mg/mL) scaffold exhibited the lowest apoptosis index. Furthermore, the expression level of vascular endothelial growth factor (VEGF) mRNA in the group without LMN was higher than that with LMN, and the Odex (30 mg/mL)/Col (6 mg/mL) scaffold without LMN had the highest VEGF protein secretion, allowing the cells to survive and function effectively. Odex/Col scaffolds, with or without LMN, are proposed as a tissue engineering construct to improve HUVEC survival and function for angiogenesis.

Decreased frequency of Th22 cells and IL-22 cytokine in kidney transplant patients with active cytomegalovirus infection.

BACKGROUND: The immunity of CD4+ T cell subsets against human cytomegalovirus (HCMV) is considerable due to their essential role in controlling the infection in transplant individuals. Previously explained CD4+ subsets such as T helper (Th) 1 have been proven to have a protective role against HCMV infection, while the role of the recently identified Th22 subset has not been described yet. Here, the frequency changes of Th22 cells and the IL-22 cytokine production were investigated in kidney transplant recipients with and without HCMV infection. METHODS: Twenty kidney transplant patients and ten healthy controls were enrolled in this study. Patients were categorized into HCMV + and HCMV- groups based on the HCMV DNA real-time PCR results. After isolating CD4+ T cells from PBMCs, the phenotype (CCR6+CCR4+CCR10+) and cytokine profile (IFN-γ-IL-17-IL-22+) of Th22 cells were analyzed by flow cytometry. The gene expression of Aryl Hydrocarbon Receptor (AHR) transcription factor was analyzed by real-time PCR. RESULTS: The phenotype frequency of these cells was lower in recipients with infection than in those without infection and healthy controls (1.88 ± 0.51 vs. 4.31 ± 1.05; P = 0.03 and 4.22 ± 0.72; P = 0.01, respectively). A lower Th22 cytokine profile was observed in patients with infection than in the two other groups (0.18 ± 0.03 vs. 0.20 ± 0.03; P = 0.96 and 0.33 ± 0.05; P = 0.04, respectively). AHR expression was also lower in patients with active infection. CONCLUSIONS: Overall, this study for the first time suggests that the reduced levels of Th22 subset and IL-22 cytokine in patients with active HCMV infection might indicate the protective role of these cells against HCMV.

Immunogenicity of Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV; Sinopharm) and Short-Term Clinical Outcomes in Vaccinated Solid Organ Transplant Recipients: A Prospective Cohort Study.

BackgroundImmunocompromised patients have lower seroconversion rate in response to COVID-19 vaccination. The aim of this study is to evaluate the humoral immune response with short-term clinical outcomes in solid organ transplant recipients vaccinated with SARS-CoV-2 vaccine (BBIBP-CorV; Sinopharm).MethodsThis prospective cohort was conducted from March to December 2021 in Abu Ali Sina hospital, Iran. All transplant recipients, older than 18 years were recruited. The patients received two doses of Sinopharm vaccine 4 weeks apart. Immunogenicity was evaluated through assessment of antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 after the first and second dose of vaccine. The patients were followed up for 6 months after vaccination.ResultsOut of 921 transplant patients, 115 (12.5%) and 239 (26%) had acceptable anti S-RBD immunoglobulin G (IgG) levels after the first and second dose, respectively. Eighty patients (8.68%) got infected with COVID-19 which led to 45 (4.9%) of patients being hospitalized. None of the patients died during follow-up period. Twenty-four (10.9%) liver transplant recipients developed liver enzyme elevation, and increased serum creatinine was observed in 86 (13.5%) kidney transplant patients. Two patients experienced biopsy-proven rejection without any graft loss.ConclusionOur study revealed that humoral response rate of solid organ transplant recipients to Sinopharm vaccine was low.

Bronchobiliary fistulae as a complication of untreated pulmonary hydatid cyst presenting with bilioptysis: A report of two cases.

We reported two patients, a 45-year-old lady and a 48-year-old man, known cases of untreated liver and lung hydatid cysts complicated with bronchobiliary fistulae. Surgery was performed, and bronchobiliary fistulae were diagnosed intraoperatively. Lobectomy was done on the lobe, which was chronically infected. Symptoms resolved after surgery in both cases. Green-colored sputum in a patient with a history of echinococcosis should raise the physician's attention to the probability of a connection between the bronchial tree and the biliary tract. Surgery in advanced cases is a suitable therapeutic option.

Indirect co-culture of islet cells in 3D biocompatible collagen/laminin scaffold with angiomiRs transfected mesenchymal stem cells.

Diabetes is an autoimmune disease in which the pancreatic islets produce insufficient insulin. One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM-MSCS with angiomiR-126 and -210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN). AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrow-mesenchymal stem cells (BM-MSCs), followed by 3-day indirect co-culturing with islets laden in collagen (Col)-based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN-containing scaffolds, particularly in the miRNA-126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM-MSCs/miRNA-126 treated group. VEGF was upregulated in the LMN-containing scaffolds in both miRNA-treated groups, specifically in the miRNA-210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN-free scaffolds; while a drastic downregulation was seen in the LMN-containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/ColLMN+ group with miRNA-126. LMN-containing biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status.

Mast Cell Sarcoma of Small Intestine, Early Diagnosis, and Good Prognosis: An Extremely Rare Case Report and Review of the Literature.

Gastrointestinal mast cell sarcoma is a rare variant of mastocytosis. It is a unifocal tumor with high destructive capacity and metastatic potential. Diagnosis of mast cell sarcoma can be challenging and might be so delayed that unfavorable prognosis may be expected. In this case report, we will describe our experience with a case of mast cell sarcoma in the small intestine of an elderly woman, which was diagnosed early on throughout the course of her disease and successfully treated. The patient was a 59-year-old woman who presented with abdominal pain, flushing, weight loss, and vomiting. Imaging studies supported the existence of an infiltrative neoplasm in the jejunum. Then, surgical removal of the tumor was performed. The presence of mast cells in the resected tumor was confirmed by immunohistochemistry, histopathology, and Giemsa staining. After almost a year of follow-up, the patient's overall condition was fine, and no signs of recurrence were found. This is the first reported case of successfully treated gastrointestinal mast cell sarcoma. All of the previously reported cases had been diagnosed after recurrence with no response to treatment. Our case shows the significance of early diagnosis and treatment in this condition and its impact on outcome and prognosis. That could be achieved only if the pathologist has a high suspicion for this rare disease and keeps it in the back of one's mind.

Cavernous mediastinal hemangioma presenting with persistent cough: a rare case report and review of literature.

BACKGROUND: Cavernous hemangioma is a rare benign tumor which can sometimes mimic the clinical presentation and radiological findings of malignant tumors. Here we present a rare presentation of cavernous hemangioma in the mediastinum (CHM), along with a literature review among the main databases. CASE PRESENTATION: We present a 48-year-old male who had suffered from persistent cough as the sole symptom of an anterior CHM. Computed tomography scan demonstrated a 12.5 × 10.8 cm mass in the anterior mediastinum. The mass was surgically resected, and histopathological evaluation established the diagnosis of CHM. The patient was discharged in good condition, in which during his four-month follow-up period, no recurrence of the tumor has been observed. CONCLUSION: Although cavernous hemangioma rarely present in the mediastinum, it should be considered in the differential diagnosis of mediastinal tumors. However, our review of literature demonstrated a female dominance and average age of 40 years, with a 52% mortality rate based on previous reports.

Identification of a novel mutation in the ALDOB gene in hereditary fructose intolerance.

OBJECTIVES: Hereditary fructose intolerance (HFI) is caused by aldolase B enzyme deficiency. There has been no report about HFI from Iran and the type of mutations has not been reported in the Iranian population so far. CASE PRESENTATION: Herein we report a 2 year old girl presented with failure to thrive, hepatomegaly, and liver dysfunction. The primary impression has been hepatic glycogen storage disease type 1 or 6. This diagnosis was not confirmed by laboratory data and liver biopsy. Therefore, targeted-gene sequencing (TGS) covering 450 genes involved in inborn errors in metabolic diseases was performed. The results of TGS showed a rare novel homozygous pathogenic variant c.944del (p.Gly315ValfsTer15) in the ALDOB gene. CONCLUSIONS: This report introduces a novel variant that expands the mutational spectrum of the ALDOB gene in patients with HFI.

Outcome of liver transplantation in hepatic glycogen storage disease: A systematic review and meta-analysis.

INTRODUCTION: Liver transplantation (LT) is the choice of therapeutic option for end-stage hepatic GSD patients; however, reports about the long-term outcome of LT in these patients have remained controversial. METHODS: We performed a systematic review and meta-analysis of observational studies published until Dec 31, 2021, that investigated the long-term outcome of LT in hepatic GSD patients. A literature search in the MEDLINE/PubMed, EMBASE,Cochrane Library, Scopus and Web of Science Core Collection databases was performed. RESULTS: 14 studies with 210 patients were included in our analysis. As the results showed, the pooled proportion of GSD patients with complications after liver transplant (e.g., hemorrhagic shock, biliary complications, tacrolimus encephalopathy, chronic hepatitis, hepatic artery thrombosis, hepatic adenoma, sepsis, liver dysfunction, chronic rejection, acute cellular rejection, and CMV infection) was 27.7% (95% CI: 20.42-35.67) without heterogeneity (I2  = 24.04%), as calculated by the random-effect model. The pooled proportion of GSD patients with complications related to GSD after LT, including HCC (Hepatocellular carcinoma), renal complication, muscle problems, delayed menarche, persistent neutropenia, pneumonitis, renal failure, and hepatic adenoma was 22.2% (95% CI: 7.97-40.01) with high heterogeneity (I2  = 82.47%). Subgroup analysis including the age of patients (adult/pediatric), duration of follow-up, and type of donor was conducted to investigate the resources of heterogeneity. CONCLUSION: According to our investigation and review analysis, most GSD patients showed significant outcome improvement after liver transplantation. Overall, our findings showed an excellent outcome of liver transplantation in GSD patients; however, it needs further investigations to be confirmed.

Assessment of Risk Factors and Clinical Outcomes in Hospitalized COVID-19 Patients with Candida spp. Co-infections: Species Distribution and Antifungal Susceptibility Patterns of Isolates.

INTRODUCTION: Fungal co-infections are considered an important complication in hospitalized patients with SARS-CoV-2 that can be attributed to disease aggravation, increased mortality, and poor outcomes. This study was conducted to determine the species distribution and antifungal susceptibility patterns of Candida isolates from hospitalized COVID-19 patients in Shiraz, Iran, in addition to associated risk factors and outcomes of co-infections with Candida species. MATERIALS AND METHODS: In this single-center study, a total of 106 hospitalized COVID-19 patients were evaluated for clinical characteristics and outcomes. Species identification was performed by ITS1-5.8S-ITS2 gene sequencing. Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, amphotericin B, and nystatin was determined according to the M27-A3/S4 CLSI protocol. RESULTS: Candida species were recovered from 48% (51/106) of hospitalized COVID-19 patients. Statistical analysis showed that patients who had heart failure, bacterial co-infection, and were receiving empirical antifungal therapy had a higher risk of developing Candida co-infection. In total, 71 Candida isolates were recovered, of which C. albicans (69%) was the most prevalent isolate. The majority of the Candida isolates were susceptible to all classes of tested antifungal drugs. DISCUSSION: Our results elucidate a high rate of Candida co-infections among hospitalized COVID-19 patients. Comorbidities such as heart failure, HTN, COPD, bacterial infections as well as therapeutic interventions including catheterization, mechanical ventilation, and ICU admission increased the risk of Candida spp. isolation from the bloodstream, respiratory tract and urine samples, which led to a higher in-hospital mortality rate. Additionally, obtained data clarified that empirical antifungal therapy was not as successful as anticipated.