Arash Jalali

Evaluation of subclinical left ventricular dysfunction in diabetic patients: longitudinal strain velocities and left ventricular dyssynchrony by two-dimensional speckle tracking echocardiography study.

We evaluated left ventricular (LV) subclinical systolic dysfunction in diabetes mellitus patients using two‐dimensional speckle tracking echocardiography (STE) for early detection of changes in LV longitudinal strain (ST) or synchronized contraction.

Cytokine Gene Polymorphisms in Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and an increased susceptibility to recurrent infections, autoimmunity and cancers. There are some conflicting results regarding the cytokine profile of CVID patients. While cytokine production could be associated with gene polymorphism, genetic profiles of a number of cytokines were analyzed in this study. The allele and genotype frequencies of the polymorphic genes coding for interleukin (IL)-2, IL-12, interferon-γ and transforming growth factor (TGF)-β were investigated in 30 patients with CVID in comparison with 140 controls. The genotype TGF-β CG at position +915 was significantly overrepresented in the patient group, while the frequencies of the genotypes TGF-β TT at +869 and GG at +915 were significantly decreased in the patient group in comparison with controls. TGF-β TC and IL-2 GT were the most frequent haplotypes in the patients, whereas the TGF-β TG haplotype was significantly decreased in the patient group. The allele and genotype frequencies of interferon-γ at position UTR +5644 and also IL-12 at position –1188 were similar in patients and controls. Cytokine single nucleotide polymorphisms could play a role in the pathophysiology of CVID. Considering the significantly lower frequency of the high production haplotype (TG) and the higher frequency of the low production halplotype (TC) of TGF-β, low production of this cytokine is expected in some CVID patients.

KIR3DL1+HLA-B Bw4Ile80 and KIR2DS1+HLA-C2 combinations are both associated with ankylosing spondylitis in the Iranian population

Contribution of killer cell immunoglobulin‐like receptors (KIR) and their human leucocyte antigen (HLA) class I ligands in the pathogenesis of autoimmune diseases has been shown in several studies. In this study, the possible association of KIR genes, their known HLA ligands and compound KIR/HLA genotypes with ankylosing spondylitis (AS) was assessed. Combined KIR/HLA ligand genotyping was performed by a polymerase chain reaction–sequence‐specific primers assay in 35 Iranian patients with AS, and genotypes were compared to those in 200 healthy individuals. The frequencies of telomeric cluster genes KIR2DL5A, KIR2DS1 and KIR3DS1 were significantly increased in AS patient group (Pc = 0.0082, Pc = 0.0195 and Pc = 0.0328, respectively). Conversely, HLA‐Bw4 ligand (the presence of one or more ‐B Bw4Ile80, ‐B Bw4Thr80 and ‐A Bw4 epitopes) (Pc = 0.0004) and HLA‐B Bw4Ile80 (Pc = 0.053) were less frequent in these patients. Meanwhile, compound KIR/HLA genotype analyses revealed lower frequency of KIR3DL1+HLA‐B Bw4Ile80 (Pc = 0.0343) and higher frequency of KIR2DS1+HLA‐C2 (Pc = 0.0308) combinations in patients with AS than in controls. In addition, the genotypes iKIR+HLA>aKIR+HLA (Pc = 0.0308) and iKIR+HLA>aKIR (Pc = 0.0258) were statistically less common, and genotypes iKIR+HLA=aKIR+HLA (Pc = 0.0081) and iKIR+HLA

Prevalence and determinants of elevated high-sensitivity cardiac troponin T in hypertrophic cardiomyopathy

BACKGROUND This study was designed to evaluate the prevalence and determinants of increased high-sensitivity cardiac troponin T (hs-cTnT) as a marker of cardiac injury in patients with hypertrophic cardiomyopathy (HCM). METHODS A total of 98 consecutive patients with HCM (71.4% males; mean age 51.18 ± 15.47 years) between 2012 and 2013 were evaluated by measuring the level of serum hs-cTnT along with other clinical assessments. RESULTS There were 42 (42.9%) patients with a minimum serum hs-cTnT level of 14 ng/L. The mean hs-cTnT level was 12.37 ng/L (6.94-24.26 ng/L). There were significant differences in chest pain New York Heart Association functional class, left ventricular hypertrophy in the surface electrocardiogram, non-sustained ventricular tachycardia in 24-h electrocardiogram-Holter monitoring, left atrial (LA) area index, ratio of peak early (E) transmitral filling velocity to peak early diastolic annular velocity (Ea septal) at the level of the septal mitral annulus (E/Ea septal), maximum left ventricular (LV) wall thickness ≥ 30 mm, and peak LV outflow gradient ≥ 30 mmHg in echocardiography between the patients with hs-cTnT<14 ng/L and those with hs-cTnT ≥ 14 ng/L. However, after multivariate analysis, age, maximum LV wall thickness, LA area index, and E/Ea septal remained as the independent determinants of elevated hs-cTnT in HCM. CONCLUSIONS The results demonstrated that hs-cTnT was elevated in a significant number of our HCM patients; therefore, hs-cTnT can be introduced as a valuable marker of myocardial injury in HCM patients.

The impact of HLA-E polymorphisms on relapse following allogeneic hematopoietic stem cell transplantation.

Since relapse following allogeneic hematopoietic stem cell transplantation (HSCT) can be due to the escape of the residual malignant cells from the graft-versus-leukemia (GvL) effect and given the role of NK cells in GvL and the importance of HLA-E in the modulation of NK cell function, we investigated whether polymorphisms of HLA-E molecule could impact on the incidence of relapse and the improvement of Disease-free Survival (DFS) after allogeneic HSCT. The study group included 56 pairs of donors and patients with malignant hematological disorders undergoing HLA-E matched allogeneic HSCT. The median follow-up was 43.6 (range 20.5-113.1) months. They were genotyped for HLA-E locus using a sequence-specific primer (SSP)-PCR. We found a lower incidence of relapse (p=0.02) in the patients with HLA-E*0103/0103 genotype compared to those with other genotypes of HLA-E. We also showed an association between HLA-E*0103/0103 genotype and a better DFS (p=0.001). Our results suggest a protective role for HLA-E*0103/0103 genotype against relapse and an association between this genotype and an improved DFS following HLA-E matched allogeneic HSCT.

Efficiency of allogeneic hematopoietic SCT from HLA fully-matched non-sibling relatives: a new prospect of exploiting extended family search.

The best donors for hematopoietic SCT (HSCT) are fully-matched siblings. In patients without fully-matched siblings, HLA registries or cord blood banks are alternative strategies with some restrictions. Owing to the high rate of consanguineous marriage in our country, between 2006 and 2013, extended family searches were undertaken in Hematology-Oncology Research Center and Stem Cell Transplantation (HORCSCT), Tehran, Iran, in 523 HSCT candidates with parental consanguinity and no available HLA identical sibling. Fully-matched other-relative donors were found for 109 cases. We retrospectively studied the HSCT outcome in these patients. Median time to neutrophil engraftment was 13 days (range: 9–31days). In 83 patients, full chimerism and in 17 patients, mixed chimerism was achieved. Acute GvHD (aGvHD) grade II–IV appeared in 36 patients (33%). The frequency of aGvHD development in various familial subgroups was NS. Five patients expired before day+100. In the surviving 104 cases, chronic GvHD developed in 20 patients (19.2%). The distantly related subgroup had significantly a higher rate of cGvHD (P=0.04). The 2-year OS and disease-free survival (DFS) were 76.7±4.5% and 71.7±4.7%, respectively. No significant difference in OS (P=0.30) and DFS (P=0.80) was unraveled between various familial relationships. Our considerable rate of fully-matched non-sibling family members and the favorable outcome support the rationale for extended family search in regions where consanguineous marriage is widely practiced.

Susceptibility to pulmonary tuberculosis in Iranian individuals is not affected by compound KIR/HLA genotype

Natural killer (NK) cells have distinctive functional capacities that are likely to contribute both to innate and adaptive immunity to Mycobacterium tuberculosis. Killer cell immunoglobulin-like receptors (KIR) and their ligands, i.e. human leukocyte antigen (HLA) class I molecules contribute partly in regulation of NK cell activity. In this study, the impact of compound KIR/HLA genotype on susceptibility to pulmonary tuberculosis (TB) has been evaluated in Iranian individuals. A total of 107 TB patients and 100 matched healthy controls were genotyped for 17 KIR genes and their three major HLA class I ligand groups (-C1, -C2 and -Bw4: -B Bw4(Ile80) , -B Bw4(Thr80) and -A Bw4) by a polymerase chain reaction-sequence-specific primers assay. Various analyses including distribution of KIR and HLA ligand genes and genotypes, frequency of inhibitory and activating KIR+HLA combinations and compound genotype status regarding balance of inhibitory and activating components showed no significant difference between patient and control groups. These findings may suggest that compound KIR/HLA genotype has no major impact on limiting Mycobacterium tuberculosis infection.

The outcome of allogeneic hematopoietic stem cell transplants without total body irradiation in pediatric patients with acute lymphoblastic leukemia: single centre experience.

The most widely accepted conditioning regimen to allogeneic hematopoietic stem cell transplantation consists of total body irradiation, especially in patients affected by acute lymphoblastic leukemia (ALL). In this retrospective study, we report our experience on hematopoietic stem cell transplantation in 44 pediatric patients with acute lymphoblastic leukemia using a non-radiation–based conditioning regimen (busulfan/cyclophosphamide). Median age at transplantation was 12.5 years (range, 4 to 14 y). 39 out of 44 patients received transplants in complete remission. At a median follow-up of 390 days, the probabilities of 3-year disease-free survival and overall survival were 50% and 68%, respectively. Disease status of hematopoietic stem cell transplantation was the only significant variable affecting the overall survival. Acute and chronic graft-versus-host disease occurred in 23 (64%) and 12(18%) patients, respectively. Relapse was significantly higher among patients transplanted in advanced disease status. The results of the study indicate that non-radiation–based preparative regimens can be used in pediatric patients with ALL. However, well-designed comparative trials are needed to better clarify the difference between radiation and non-radiation–based conditioning regimens in pediatric ALL.

Percutaneous Coronary Intervention to Treat Chronic Total Occlusion: Predictors of Technical Success and One-Year Clinical Outcome

We investigated the overall success rate of percutaneous coronary intervention (PCI) as a treatment for coronary chronic total occlusion and sought to determine the predictive factors of technical success and of one-year major adverse cardiac events (MACE). These factors have not been conclusively defined. Using data from our single-center PCI registry, we enrolled 269 consecutive patients (mean age, 56.13 ± 10.72 yr; 66.2% men) who underwent first-time PCI for chronic total occlusion (duration, ≥3 mo) from March 2006 through September 2010. We divided them into 2 groups: procedural success and procedural failure. We compared occurrences of in-hospital sequelae and one-year MACE between the groups, using multivariate models to determine predictors of technical failure and one-year clinical outcome. Successful revascularization was achieved in 221 patients (82.2%). One-year MACE occurred in 13 patients (4.8%), with a predominance of target-vessel revascularization (3.7%). The prevalence of MACE was significantly lower in the procedural-success group (1.8% vs 18.8%; P <0.001). In the multivariate model, technical failure was the only predictor of one-year MACE. The predictors of failed procedures were lesion location, multivessel disease, the occurrence of dissection, a Thrombolysis In Myocardial Infarction flow grade of 0 before PCI, the absence of tapered-stump arterial structure, and an increase in serum creatinine level or lesion length. In our retrospective, observational study, PCI was successful in a high percentage of chronic total occlusion patients and had a low prevalence of complications. This suggests its safety and effectiveness as a therapeutic option.

Novel approach to reduce postsurgical adhesions to a minimum: Administration of losartan plus atorvastatin intraperitoneally

BACKGROUND Intraperitoneal adhesions are the most important cause of intestinal obstruction, pelvic pain, and female infertility. MATERIALS AND METHODS Losartan (1, 5, and 10 mg/kg), atorvastatin (1, 20, and 30 mg/kg), losartan (10 mg/kg) plus atorvastatin (20 mg/kg), and sodium hyaluronate/carboxymethylcellulose (HA/CMC) were administered intraperitoneally in 90 male NMRI mice. After 7 d, the grade of adhesions was scored by two scaling methods and the concentrations of TGF-β1, tPA, and PAI-1 were also evaluated. RESULTS Simultaneous intraperitoneal administration of losartan and atorvastatin led to a much higher reduction of adhesions compared with that in the HA/CMC group (P < 0.05). When losartan plus atorvastatin was administered, significant changes in the serum concentration and mRNA expression, including the increase of tPA and the decrease of TGF-β1 and PAI-1, were observed compared with those in other groups. CONCLUSIONS Our findings suggest that the simultaneous application of losartan and atorvastatin leads to an enhanced reduction in adhesion bands more than that of HA/CMC treatment, compared with the control group, possibly through balancing the expression of TGF-β1, tPA, and PAI-1.