TET2, DNMT3A, IDH1, and JAK2 Mutation in Myeloproliferative Neoplasms in southern Iran.

Background: Five epigenetic regulator mutations are considered in myeloproliferative neoplasms (MPN) that have prognostic and therapeutic values. Objective: We aimed to evaluate these mutations in MPNs among the Iranian population. Methods: We selected 5 mutations in 4 epigenetic regulatory genes [TET2, DNMT3A, IDH1 (rs147001633&rs121913499), and JAK2)] and evaluated 130 patients with MPNs including 78 Philadelphia chromosome negative (49 ETs, 20 PVs, and 9 PMFs) and 52 Philadelphia chromosome-positive patients as well as 51 healthy controls. Results: Eight patients (6.5%) carried the DNMT3A mutation, 35 (27%) were positive for TET2 mutation and 64 (49.3%) had the JAK2V617F mutation. In the healthy controls, 16 (31.4%) cases had the TET2 mutation (15 Heterozygote + 1 Homozygote) and one had heterozygote JAK2 mutation. There was no statistically significant difference between patient groups for any of these mutations, except for JAK2. The JAK2 mutation rate was 18 (90%), 25 (51%), 7 (77.8%), 14 (26.9%) in polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myelocytic leukemia, respectively. Patients aged 60 and older were more likely to carry the TET2 mutation (23% vs. 39% in younger and older than 60 years old individuals, p=0.025). IDH1 was not detected at all and PV had the highest TET2 mutation 7(35%). Two PMF patients had a history of bone marrow transplantation that were negative for IDH1and DNMT3A and one was positive for TET2 mutation. Conclusion: In the normal Iranian population, the heterozygote form of TET2 mutation is significant, especially in the elderly. No association was found between JAK2 and TET2 mutations. Both of them are more prevalent in the age group of 60 years and older. DNMT3A mutation has a low prevalence and occurs in both positive and negative MPNs.

Frequency of thyroid nodules in patients with ß-thalassemias in Southern Iran.

BACKGROUND: Although thyroid nodules are a common finding in the general population, determining the clinically important nodules is essential. We investigated thyroid nodules or cysts by thyroid ultrasonography (US) in patients with ß-thalassemia major (ß-TM) and intermedia (ß-TI). We also report a ß-TI patient who was diagnosed with thyroid cancer six months before our screening. METHODS: In this cross-sectional study, 178 patients with ß-thalassemias referred to the Thalassemia Clinic in a tertiary hospital affiliated to Shiraz University of Medical Sciences were investigated, from January to June 2016, by US. RESULTS: Thyroid nodules or cysts were detected in 11 patients [total: 6.17 %; 8 patients with ß-TM (8.2%) and 3 patients with ß-TI (3.7%)]. All nodules were < 1 cm in diameter and were not suspicious of malignancy. All patients, after 1 year of thyroid US follow-up, did not show any significant change in favor of malignancy. CONCLUSION: Based on our results, the frequency of thyroid nodules was similar to what was reported in the general population. However, a long-term follow-up of these patients is recommended because of the potential carcinogenic effects of iron and hepatitis C infection (HCV). To achieve more precise information, collaborative multicenter studies should be considered.

Prevalence of endocrine disorders and their associated factors in transfusion-dependent thalassemia patients: a historical cohort study in Southern Iran.

PURPOSE: Transfusion-dependent beta-thalassemia (TDT) patients suffer from various endocrinopathies. The main contributing factor associated with these complications is iron overload, secondary to frequent blood transfusions. To improve patients' quality of life, we evaluated the prevalence of endocrine disorders while considering the associated factors for further assessment. METHODS: Seven hundred thirteen transfusion-dependent thalassemia patients with age range 10-62 years were enrolled in this study. Serum calcium, phosphorous, fast blood sugar, ferritin, 25-OH vitamin D, free thyroxin, thyroid-stimulating hormone and parathyroid hormone were assessed. Bone mineral density was measured by dual-energy X-ray absorptiometry. RESULTS: In total, 86.8% of the TDT patients suffered from at least one endocrinopathy. The prevalence of endocrinopathies in descending order of frequency was low bone mass (72.6%), hypogonadism (44.5%), diabetes mellitus (15.9%), hypoparathyroidism (13.2%), and hypothyroidism (10.7%). Age, body mass index and splenectomy were significantly associated with most of the endocrine disorders. CONCLUSION: Endocrine complications are frequently observed in TDT patients. Splenectomy is a major risk factor and should be generally avoided unless it is highly indicated. Periodic surveillance of endocrine function and proper management of iron overload are advised.

Correlation between Trunk-Pelvis Inter-Segmental Coordination Parameters during Walking and Disability Level in Chronic Low Back Pain Patients.

BACKGROUND: Chronic low back pain (CLBP) disability has been particularly frustrating because its treatment has been a great therapeutic challenge. Disability has been suggested to depend on different factors that should be found and considered in the medical management. The inter-segmental coordination is often impaired in CLBP subjects; however, to the best of our knowledge, there is no evidence about the relationship between the existence of coordination problems and disability in CLBP patients. OBJECTIVE: To evaluate the correlation between sagittal plane trunk-pelvis inter-segmental coordination parameters during walking and disability level in CLBP patients. METHODS: Kinematic data were collected from 16 non-specific CLBP (18-40 years) volunteers during walking. Sagittal plane time-normalized segmental angles and velocities were used to calculate continuous relative phase for each data point. Coordination parameters, mean absolute relative phase (MARP) and deviation phase (DP) were derived to quantify the trunk-pelvis coordination pattern and variability during gait cycles, respectively. The disability level was quantified through Oswestry Disability Index (ODI) questionnaire. Pearson correlation coefficient was used to find the probable correlation between coordination parameters and disability level. RESULTS: The analysis demonstrated a significant correlation between sagittal plane MARP or DP and disability level (%ODI) in CLBP subjects during walking (r= -0.806 P<0.001 and r= -0.856, P<0.001, respectively). CONCLUSION: This study demonstrated that the lower the MARP (more in-phase pattern) and DP (less variable pattern) in the CLBP subjects, the more disability existing in such patients. The results suggest that clinicians should look beyond pain management when prescribing rehabilitation for CLBP and consider interventions that target segmental coordination improvement to manage CLBP induced disability.

A large case series on surgical outcomes in congenital factor XIII deficiency patients in Iran.

Essentials Data on surgery in factor XIII (FXIII) deficiency patients are scarce and lack standardized guidelines. Variable dosage of 10-50 U kg-1 was given to FXIII deficiency patients undergoing surgery. Surgical outcomes showed excellent hemostasis with a minimal risk of post-operative complications. Surgery can be performed safely in FXIII deficiency patients following FXIII administration. SUMMARY: Background The lack of accepted standardized surgical guidelines leads to dependence on the treating physicians' and centers' experiences. Aim Our aim is to evaluate the surgical outcomes of a large group of congenital factor XIII deficiency (FXIIID) patients. Methods A case series study was conducted prior to surgery on congenital FXIIID patients in two major referral centers located in Iran from 2010 to 2016. All patients were on prophylaxis using plasma factor XIII concentrate (10 U kg-1 , every 28 days) except for three patients. Single doses of 10 U kg-1 or 30 U kg-1 plasma factor XIII concentrate were given before a minor procedure and circumcision, respectively. Two doses of plasma factor XIII concentrate, one 30 U kg-1 prior to the procedure and the second dose of 30 U kg-1 on postoperative day 3, were given for major surgery. The dose was 50 U kg-1 both before and after neurosurgical procedures. Results One hundred and sixty-two FXIIID patients underwent minor, major and obstetrical/gynecological surgeries. Median age of the patients was 14 years (ages ranged 15 days to 47 years). The male-to-female ratio was 89/73. Five postoperative complications, two bleeding and three thrombosis, were recorded. Conclusion Our study showed excellent hemostasis in FXIIID patients undergoing surgeries. During the period of these surgeries, we observed only 1.8% postoperative complications. Surgery can be performed safely in FXIIID patients, and our proposed treatment regimens lead to adequate hemostatic coverage with minimal risk, for both minor and major surgeries.

Association of Serum Leptin Level with Obesity in Children with Acute Lymphoblastic Leukemia.

BACKGROUND: Obesity is a medical problem in survivors of childhood acute lymphoblastic leukemia. Obesity is associated with many complications, so it is important to investigate the respective etiology. Leptin is a protein synthesized in the fatty tissue and is effective in the control of obesity. Survey of leptin in acute lymphoblastic leukemia (ALL) survivors could be helpful in controlling obesity. MATERIALS AND METHODS: In this prospective study, 53 pediatric patients diagnosed with ALL between 2006 and 2012 from Southern Iran, were enrolled. We examined body mass index (BMI) status and performed laboratory measuring tests including triglyceride, cholesterol, fasting blood sugar, leptin at diagnosis time and then every 6 months and in the last visit. RESULTS: Participants consisted of 35 male and 18 female patients. At the time of diagnosis, 5.66% were overweight or obese, whereas at the end of treatment, approximately 13 patients (24.53%) were overweight or obese. The median and interquartile range (IQR) for blood leptin level were significantly higher for obese patients than other patients (885, 1120 vs. 246, 494 pg/ml), (P=0.030). The median and IQR were also significantly higher in females than in males (861, 969 vs. 204, 267 pg/ml), (P=0.006). CONCLUSION: Obesity is a complication of ALL treatment. It is associated with elevated blood leptin level. Hypothalamus leptin resistance in obese patients should be considered. In each visit, clinicians should weight and their patient's BMI take into account.

Combination therapy - deferasirox and deferoxamine - in thalassemia major patients in emerging countries with limited resources.

BACKGROUND: The problem of iron-overload observed in thalassemia patients can be overcome using chelating agents such as deferiprone (Ferroprox(®) ), deferasirox (Exjade(®) ) and deferoxamine (Desferal(®) ). Although these drugs can be used as monotherapy, combined therapy, especially deferiprone with deferoxamine, has led to promising outcomes in various studies. METHODS AND MATERIALS: In this quasi-experimental study, serum ferritin levels were evaluated in 32 ß-thalassemia major patients with severe iron overload before and after receiving combined deferasirox (30-40 mg kg(-1) day(-1) ) and deferoxamine (40-50 mg kg(-1) day(-1) ) 2 days a week. This study was conducted from September 2012 to September 2013 in Southern Iran. RESULTS: The mean of serum ferritin levels significantly reduced from 4031 ± 1955 to 2416 ± 1653 ng mL(-1) after 12 months of therapy (P < 0·001). Echocardiograph findings showed significant improvement 1year after end of the study (P < 0·001). No drug toxicity was observed by monitoring serum creatinine, liver enzymes and blood urea nitrogen (BUN) during the study period. We observed no correlation between mean serum ferritin change and age (P = 0·87). In addition, the mean serum ferritin change did not differ between male and female thalassemia patients (P = 0·454). No difference in mean serum ferritin change was observed between patients who had undergone splenectomy compared to those who had not done so (P = 0·307). CONCLUSION: The study suggests that combination chelating therapy with deferasirox and deferoxamine can effectively reduce iron burden in ß-thalassemia major patients with heavy iron overload without any significant complications.

Epidemiological and clinical characteristics of neuroblastoma in southern iran.

BACKGROUND: Neuroblastoma is the third most common malignancy in children with a very heterogeneous feature. In this study, the epidemiological and clinical characteristics of children with neuroblastoma treated in a referral oncology hospital in Shiraz, Southern Iran, were investigated. MATERIAL AND METHOD: In this historical cohort study, the medical files of 36 children under 18 years old with neuroblastoma were reviewed, who were admitted to Amir Oncology Hospital in Shiraz, Iran from 2006 to 2013. Overall survival and event free survival (EFS) curves were demonstrated by Kaplan Meier methods. Also the effects of demographic and clinical characteristics of the patients on survival were evaluated by Cox regression model. RESULTS: The median age of diagnosis was 30 months (age range: from 4 to144 months), with M/F ratio of 63.9%. Over 70% of the patients had stage 4 of neuroblastoma at their initial presentations. Adrenal gland comprised 72.2% of the primary tumor site. The most common presenting symptoms were gastrointestinal and constitutional symptoms. The mean overall survival and EFS were 30.75 and 20.56 months, respectively. Among the different variables analyzed, only liver metastasis had an adverse effect on EFS (p=0.025 Hazard ratios 2.83, CI: 1.14-7.02). CONCLUSION: This study revealed that the majority of children suffering from neuroblastoma in our center are high stage with disseminated disease at the time of detection. It also warns us about an urgent necessity for holding a re-educational program for general practitioners and pediatricians to review the warning signs of common pediatric cancers such as neuroblastoma.

Polymorphisms associated with sickle cell disease in Southern Iran.

Sickle cell disease (SCD) is an inherited autosomal recessive disorder. We aimed to describe the spectrum of haplotyes of BS-gene and to investigate a relationship with disease phenotype in patients with SCD in Southern Iran. We didn't find any significant association between BS-globin gene haplotypes and clinical severity of the disease in an Iranian population. The exact mechanism by which the BS-globin gene polymorphism affects clinical presentation is not obvious; however, further detailed studies at the molecular level, with a larger sample size are required to show the mechanisms that influence the clinical presentation of SCD in Iranian population.

Attitudes of haemophilic patients towards their health and socio-economic problems in Iran.

Although new technologies and treatments have improved the quality of life of people with haemophilia, they still face many health and socio-economic problems. We designed this study to identify some of these problems according to patients' attitudes towards efforts to solve them. This cross-sectional study was conducted in Shiraz, southern Iran, during January and May 2010. The participants were 100 patients with haemophilia who were referred to Shiraz Hemophilia Center, a major referral centre in southern Iran. A questionnaire was used to obtain data on the attitudes of haemophilic patients about some of their health and socio-economic problems. Mean age of the patients was 28.2 ± 9.0 (range of 16-67 years). In univariate analysis, disease severity, joint involvement, HCV status, income level and educational level of the patients were found to have possible effect on patients' attitude towards their health and socio-economic problems. However, in multivariate model we found that only income level, educational level and HCV status as independent factors influencing the patients' attitude towards childbearing, employment problems, occupational problems, social and friend relationship and continuing education. Haemophilic patients had many social and health problems, which could be alleviated with interdisciplinary interventions to improve their quality of life. Financial support of these patients should be taken into account to reduce their economic problems. Also, encouraging them and providing facilities to achieve a higher educational level could help them to have a better attitude towards their health and overcome the disease-related problems.

Efficacy of prophylaxis and genotype-phenotype correlation in patients with severe Factor X deficiency in Iran.

We aimed to evaluate the effect of regular prophylaxis with a Factor X (FX) concentrate for patients with severe FXD in Iran and to assess the correlation of the genotype and phenotype in these patients. Ten patients with severe FXD (FX activity <1%) were enrolled and characterized during 2010-2011. Prophylaxis with 20 IU FX P Behring per kg body weight was administered once a week. FX levels, were monitored at baseline, 15 and 30 min, 1, 3, 6, 12, 24, 48, 72 and 96 h after starting prophylaxis. All patients were followed for 1 year. The mean age of the patients was 15 ± 7.8 years (age range of: 6-27 years). One patient had anaphylactic reaction after the first infusion, and the treatment was stopped. During one-year follow-up after starting prophylaxis, no bleeding symptoms occurred in any patient who tolerated and remained on the prophylaxis programme and all of them had a FX level of 1% or above. The maximum level of FX activity has been observed at 15 min after starting prophylaxis. A level of 1.5-3.5% was detected after 96 h. Homozygous mutations p.Arg40Thr (Arg-1Thr), p.Gly51Arg and p.Glu69Lys were detected in patients with intracranial haemorrhage. In our patients, significant decrease in symptoms without any complication after administration of FX, was demonstrated in all except one patient who had an anaphylactic reaction. It seems that the dose of 20 IU kg(-1) could be probably the best choice for patients with severe FXD, who require regular prophylaxis.

Oral health status in Iranian hemodialysis patients.

Due to increased survival among hemodialysis (HD) patients, new problems including concerns of oral health have appeared. In this study, we aimed to evaluate the oral health status and related risk factors in Iranian HD patients. Demographic information, medical history, laboratory findings, and dental health status were gathered. The decayed, missing and filled teeth (DMFT) index in accordance with the World Health Organization (WHO) criteria was obtained. Kt/V was calculated for patients. A P-value of <0.05 was considered statistically significant. Seventy-two patients were evaluated, with a mean age and HD time of 53.4±15.3 years and 36.9±33.8 months, respectively. Thirty-five (48.6%) complained of dry mouth, 33 (49.3%) of taste change, 22 (31%) of malodor mouth, and 30 (46.9%) had dental calculus. The overall mean DMFT score was 18.6±9.9. DMFT score had a negative significant correlation with Kt/V (r=-0.4, P=0.004). Women and singles as well as patients with a low educational level and/or lesser dialysis time had a significantly higher DMFT score (P<0.05). Kt/V was significantly lower in patients suffering from dry mouth and dental calculus (P<0.05). Interestingly DMFT score was significantly lower in patients with dental calculus compared to patients without it (P=0.001). It seems that our patients have a poor dental hygiene level and high DMFT score especially women, singles, patients with low Kt/V and a low education level. The oral health maintenance program for a patient receiving dialysis should be reinforced in our centers.

Anemia and iron deficiency in adolescent school girls in kavar urban area, southern iran.

BACKGROUND: Anemia is one of the most common public health problems especially in developing countries. We investigated the prevalence of anemia, iron deficiency anemia and related risk factors in adolescent school girls in Kavar urban area in southern Iran. METHODS: A total of 363 adolescent school girls were evaluated by a cross sectional study. Socioeconomic, demographic and related risk factors were obtained by a questionnaire. Hematological parameters and serum iron indices were measured. RESULTS: There were 21 cases of anemia (5.8%), 31 (8.5%) iron deficiency and 6 (1.7%) iron deficiency anemia.  Most of anemic girls (85.7%) had mild anemia.  MCV, TIBC, age, and BMI had statistically significant relationship with hemoglobin. Only parasites infestation in the last three months had a 6.83 times more risk of anemia than those without this history (95% CI, 1.66-28.11). CONCLUSION: The prevalence of anemia and iron deficiency anemia in this study were substantially less than what reported in many other regions of Iran as well as other developing countries. It seems that related implemented strategies in the recent years have been successful. More especial attention to prevention of parasite infestation should be considered in this area.

Effect of intralesional verapamil for treatment of Peyronie's disease: a randomized single-blind, placebo-controlled study.

PURPOSE: We aimed to assess the effect of intralesional verapamil on the treatment of Peyronie's disease. MATERIALS AND METHODS: This randomized study involved 80 patients. First, they were divided into two groups. The first group (case: 40 patients) received intralesional verapamil and the second group (control: 40 patients) local saline injection. They were followed about 24 weeks and evaluated for the size of plaques, plaque softening, reduction of pain and amelioration of penile deformity and erectile dysfunction (estimated by the International Index of Erectile Function) before and after treatment. RESULTS: Reduction of plaque size was seen in 17.5% of the case group and 12.8% of the control group (P: 0.755). Pain was reduced in 30% of the case group and 28.2% of the control group (P: 0.99). Curvature was decreased in 17.5% of the case group and 23.1% the control group (P: 0.586). Plaque softening was seen in 30% of the case group compared with 25.6% improvement in the control group (P: 0.803). Also we found 5% and 2.6% improvement in sexual dysfunction in the case and control groups, respectively. (P: 0.985). CONCLUSION: Although in some studies verapamil has been found to be effective in the treatment of Peyronie's disease, we did not find any improvement in comparison with the control group. Furthermore, larger scale studies are warranted to assess the effect of this drug on the treatment of Peyronie's disease.

Normal values of F wave in lower extremities of 73 healthy individuals in Iran.

F wave latency has been shown to be a simple and valuable method in evaluation of proximal part of peripheral nerves. According to our previous study of F wave of upper extremity nerves (1), maximum normal F wave latency for the median nerve was 28 ms with stimulation at wrist and 25 ms with stimulation at elbow. These values for the ulnar nerve were 29 ms and 25 ms respectively. Maximum normal difference between right and left F wave latency with wrist stimulation was 2 ms for median nerve and 2.5 ms for ulnar nerve. Maximum normal difference between median and ulnar nerve F latency was 3.5 ms with stimulation at wrist. In this study we measured F wave of lower extremity nerves in 73 healthy individuals in Shiraz. Maximum normal F wave latency for tibial nerve was 55 ms with stimulation at ankle and 46 ms with stimulation at popliteal area. Maximum normal F wave latency for the peroneal nerve was 54 ms with stimulation at ankle and 47 ms with stimulation at fibular head. Mean F ratio for both nerves was 1.29 with stimulation at knee. Maximum normal difference in F wave latency between right and left lower extremities was 3.5 ms with stimulation at ankle and 3 ms with stimulation at knee for the peroneal nerve. These values were 3 ms and 2.5 ms for the tibial nerve respectively. Maximum normal difference in F wave latency between tibial and peroneal nerve was 4 ms with stimulation at ankle and 3 ms with stimulation at knee.