Can MiR-503 be used as a marker in diabetic patients with ischemic stroke?

BACKGROUND: Some microRNAs are involved in diabetes pathology and some are known to have role in stroke. MiR-503 causes endothelial dysfunction in diabetic patients, predisposing to ischemia. There has been no study evaluating Mir-503 level in diabetic patients with or without ischemic stroke. METHODS: We designed a cross-sectional study to assess and compare serum level of MiR-503 in 4 groups of diabetic patients with ischemic stroke (I), non-diabetic patients with stroke (II), diabetic patients (III), and healthy controls (IV) in acute phase and 3 months later. RESULTS: Our data analysis showed that mean relative expression of MiR-503 in group (I) was significantly higher than 3 other groups (p < 0.05). The level of miR-503 was related to the patients' fasting blood glucose, Cholesterol level, NIHSS score and acute-phase modified Rankin Scale (mRS) (r = 0.49, p = 0.001, r = 0.5, p = 0.009, r = 0.45, p = 0.009, r = 0.48, p = 0.003, CI = 95%). Relative expression of miR in patients with mRS ≤ 2 (good outcome) was lower than in patients with mRS > 2 (poor outcome) (p = 0.008). After 3 months, level of miR decreased significantly only in group (I) (p = 0.002). Mean relative expression of miR-503 in chronic phase was not significantly different among groups (p-value> 0.05). There was no relation between miRNA level and mRS in chronic phase. CONCLUSION: Hyperglycemia and ischemia together raise the level of MiR-503 acutely but it does not remain at high level after 3 months. Although higher miR was related to more disability in acute phase, it does not affect long-term outcome in ischemic patients. As MiR-503 is stable enough in blood it can be used as a potential diagnostic marker of an ischemic stroke in diabetic patient. Its level also is an indicator of stroke severity and patients' short-term outcome. It is recommended to study whether antagomiR-503 is a new therapeutic agent reducing the severity of and disability due to stroke.

Impaired IL-12- and IL-23-Mediated Immunity Due to IL-12Rß1 Deficiency in Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease.

PURPOSE: Inborn errors of IFN-γ-mediated immunity underlie Mendelian Susceptibility to Mycobacterial Disease (MSMD), which is characterized by an increased susceptibility to severe and recurrent infections caused by weakly virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccines and environmental, nontuberculous mycobacteria (NTM). METHODS: In this study, we investigated four patients from four unrelated consanguineous families from Isfahan, Iran, with disseminated BCG disease. We evaluated the patients' whole blood cell response to IL-12 and IFN-γ, IL-12Rß1 expression on T cell blasts, and sequenced candidate genes. RESULTS: We report four patients from Isfahan, Iran, ranging from 3 months to 26 years old, with impaired IL-12 signaling. All patients suffered from BCG disease. One of them presented mycobacterial osteomyelitis. By Sanger sequencing, we identified three different types of homozygous mutations in IL12RB1. Expression of IL-12Rß1 was completely abolished in the four patients with IL12RB1 mutations. CONCLUSIONS: IL-12Rß1 deficiency was found in the four MSMD Iranian families tested. It is the first report of an Iranian case with S321* mutant IL-12Rß1 protein. Mycobacterial osteomyelitis is another type of location of BCG infection in an IL-12Rß1-deficient patient, notified for the first time in this study.

Pregnancy, child bearing and prevention of giving birth to the affected children in patients with primary immunodeficiency disease; a case-series.

BACKGROUND: Patients with primary immunodeficiency disease (PID) who survive to adulthood and willing to have a child mostly are worried whether their disease affects their fertility and/or pregnancy and also if their child would be predisposed to PID. CASE PRESENTATION: We report the outcome of conception, pregnancy and their management in 9 families with definite diagnosis of PID. A chronic granulomatous disease subject with an uneventful pregnancy developed fungal sacral osteomyelitis few weeks after delivery. A pregnant common variable immunodeficiency disease (CVID) patient with idiopathic thrombocytopenia had platelet count dropped before delivery. A sever neutropenic mother who refused to get IFNγ delivered two healthy children. A CVID case intolerant to IVIg with eclampsia and PTE delivered a baby. Another CVID female gave birth to a baby without being on any treatment since she was not diagnosed with immunodeficiency disease at that time. A healthy girl was implanted via preimplantation gender selection in a family who owned a Wiskott Aldrich-affected son. A family who had two children with Ataxia Telangiectasia used donated oocyte for their 3rd child. Prenatal genetic diagnosis was used to screen the fetus for the impaired BTK and CVID genes detected in sibling and father respectively in 2 separate families. CONCLUSION: Pregnancy in PID patients is more complex than normal population. Because, not only it has the chance of being inherited by the offspring, but also there are some risks for the mother if she has any kind of immunity component defects. So consultation with a clinical geneticist is crucial to choose the best available approach. They also should be observed and followed by a clinical immunologist to take the best possible safe care.

Associating liver partition and portal vein ligation for staged hepatectomy: A surgical technique for liver resections.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel surgical technique liver resection in traditionally nonresectable primary intrahepatic tumors or colorectal liver metastases. MATERIALS AND METHODS: From June 2013 to March 2014, patients with primary tumor of liver or colorectal tumors with liver metastasis were selected to evaluate whether they met the initial criteria for ALPPS procedure. RESULTS: Nine patients enrolled in the study with primary diagnoses of colon and rectosigmoid cancer, carcinoid tumor, gastrointestinal stromal tumor of small intestine, hepatocellular carcinoma, and pancreatic neuroendocrine tumor (PNET). Four candidates excluded from the study prior or during the first step operation due to fatty liver, hepatic fibrosis, peritoneal seeding, and multiple small intestine metastases. Five patients underwent two stages of ALPPS with the interval of about 1 week. Liver hypertrophy was 100% among our candidates after the initial step. One postoperative death happened because of massive pulmonary thromboembolism Recurrence of liver metastasis was seen in one patient. Hepatic failure Class B and A were observed in two patients which did not progress during follow-up period. One patient developed an enterocutaneous fistula. DISCUSSION: We recommend to use 2 organ bags, one for wrapping right lobe and the other one for covering visceral organs and also do liver biopsy in suspicious cases of damaged liver parenchyma and laparoscopic exploration of abdomen for seeding and multiple metastases prior to laparotomy. CONCLUSION: As the procedure has not been well established and verified by oncologists yet, further studies are required to define the exact indications of ALPPS.

Invasive Fungal Infection in Febrile Patients with Hematologic Malignancies Undergoing Chemotherapy in Iran.

BACKGROUND: Patients with hematological malignancies undergoing cytotoxic chemotherapy are susceptible to develop invasive fungal infections particularly Aspergillus and Candida spp. Early detection of these infections is required to start immediate antifungal therapy and increase the survival of these patients. METHOD: Our study included consecutive patients of any age with hematologic malignancies who were hospitalized to receive chemotherapy and suffer from persistent fever (rectal temperature >38.5°C) for more than 5 days despite receiving broad-spectrum antibiotics. A whole blood sample was taken and sent for blood culture. PCR was also conducted for Aspergillus and Candida species. RESULTS: One hundred and two patients were investigated according to the inclusion criteria. The most common hematologic malignancy was AML affecting 38 patients (37.2%). Six patients were diagnosed with invasive fungal infections (A. fumigatus n=3, C. albicans n=2, A. flavus n=1) by PCR (5.8%) while blood culture showed fungus only in 1 patient. Three more cases were known as probable IFI since they responded to antifungal therapy but the PCR result was negative for them. AML was the most prevalent malignancy in IFI patients (83.3%) and odds ratio for severing neutropenia was 21.5. Odds for each of the baseline characteristics of patients including gender, age>60, diabetes mellitus, previous IFI, history of using more than 3 antibiotics, antifungal prophylaxis, episodes of chemotherapy> 8 and chemotherapy regimen of daunarubicin+cytarabine were calculated. CONCLUSION: We found that multiplex real-time PCR assay is more accurate than blood culture in detecting fungal species and the results are prepared sooner. Among all factors, the only type of cancer (AML) and severe neutropenia, were found to be risk factors for the development of fungal infections in all hematologic cancer patients and previous IFI was a risk factor only AML patients.

Micrometastasis in colorectal cancer: does it affect staging?

BACKGROUND: Micrometastasis (MM) in colorectal cancer (CRC) is not considered in tumour-node-metastasis (TNM) staging currently and also the prognostic significance of these occult tumoural cells is not proven yet. This study was designed to find whether MM to bone marrow (BM) and/or liver cause upstaging of the tumour according to conventional staging system and if it may alter the survival rate. METHODS: Thirty-eight CRC patients who were candidates of surgical procedure were enrolled in our cross-sectional study. Liver and BM biopsy were obtained during the surgery to be looked for tissue-specific marker of CRC, CK20. CK20 expression in BM and liver was assessed by the two methods of reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: Among the 38 submitted patients, a total number of 14 MM, including 10 BM (23%) and seven hepatic (18%) were detected. There was no significant difference in clinicopathological aspects including size, location, stage, grade, local invasion to vessels and neurons, TNM staging and relapse rate of tumour among patients with/without disseminated tumoural cells. The result did not demonstrate a survival difference between patients receiving neoadjuvant chemotherapy compared to other patients. CONCLUSION: Our study did not confirm that the presence of MM influences TNM staging and overall survival of the patients. Additional clinical investigations with longer follow-up period and larger number of cases are required to decide on administration of neoadjuvant therapy in CRC patients.

Recurrent Vulvovaginal Candidiasis: Could It Be Related to Cell-Mediated Immunity Defect in Response to Candida Antigen?

BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) is a common cause of morbidity affecting millions of women worldwide. Patients with RVVC are thought to have an underlying immunologic defect. This study has been established to evaluate cell-mediated immunity defect in response to candida antigen in RVVC cases. MATERIALS AND METHODS: Our cross-sectional study was performed in 3 groups of RVVC patients (cases), healthy individuals (control I) and known cases of chronic mucocutaneous candidiasis (CMC) (control II). Patients who met the inclusion criteria of RVVC were selected consecutively and were allocated in the case group. Peripheral blood mononuclear cells were isolated and labeled with CFSE and proliferation rate was measured in exposure to candida antigen via flow cytometry. RESULTS: T lymphocyte proliferation in response to candida was significantly lower in RVVC cases (n=24) and CMC patients (n=7) compared to healthy individuals (n=20, <0.001), but no statistically significant difference was seen between cases and control II group (P>0.05). Family history of primary immunodeficiency diseases (PID) differed significantly among groups (P=0.01), RVVC patients has family history of PID more than control I (29.2 vs. 0%, P=0.008) but not statistically different from CMC patients (29.2 vs. 42.9%, P>0.05). Prevalence of atopy was greater in RVVC cases compared to healthy individuals (41.3 vs. 15%, P=0.054). Lymphoproliferative activity and vaginal symptoms were significantly different among RVVC cases with and without allergy (P=0.01, P=0.02). CONCLUSION: Our findings revealed that T cells do not actively proliferate in response to Candida antigen in some RVVC cases. So it is concluded that patients with cell-mediated immunity defect are more susceptible to recurrent fungal infections of vulva and vagina. Nonetheless, some other cases of RVVC showed normal function of T cells. Further evaluations showed that these patients suffer from atopy. It is hypothesized that higher frequency of VVC in patients with history of atopy might be due to allergic response in mucocutaneous membranes rather than a functional impairment in immune system components.

Gene mutations responsible for primary immunodeficiency disorders: A report from the first primary immunodeficiency biobank in Iran.

BACKGROUND: Primary immunodeficiency (PID) is a heterogeneous group of inheritable genetic disorders with increased susceptibility to infections, autoimmunity, uncontrolled inflammation and malignancy. Timely precise diagnosis of these patients is very essential since they may not be able to live with their congenital immunity defects; otherwise, they could survive with appropriate treatment. DNA biobanks of such patients could be used for molecular and genetic testing, facilitating the detection of underlying mutations in known genes as well as the discovery of novel genes and pathways. METHODS: According to the last update of the International Union of Immunological Societies (IUIS) classification, patients are registered in our biobank during a period of 15 years. All patients' data were collected via questionnaire and their blood samples were taken in order to extract and protect their DNA content. RESULTS: Our study comprised 197 patients diagnosed with PID. Antibody deficiency in 50 patients (25.4%), phagocytic defect in 47 patients (23.8%) and combined immunodeficiency with associated/syndromic feature in 19 patients (9.6%) were the most common PID diagnoses, respectively. The most common variant of PID in our study is common variable immunodeficiency, which accounted for 20 cases (10.1%), followed by chronic mucocutaneous candidiasis in 15 patients (7.9%) and congenital neutropenia in 13 patients (7%). Mean age at onset of disease was 4 years and mean age of diagnosis was 9.6 years. The average diagnostic delay was 5.5 years, with a range of 6 months to 46 years. Parental consanguinity and history of PID in family were observed in 70.2 and 48.9% of the patients, respectively. The majority of PID patients (93.3%) were from families with low socioeconomic status. CONCLUSION: This prospective study was designed to establish a PID Biobank in order to have a high quality DNA reservoir of these patients, shareable for international diagnostic and therapeutic collaborations. This article emphasizes the need to raise the awareness of society and general practitioners to achieve timely diagnosis of these patients and prevent current mismanagements.