A blueprint for success: lessons learned from developing the official guide to Iranian undergraduate medical education accreditation.

We are excited to contribute our thoughts and insights to the discussion initiated by Gandomkar et al. in their article on the accreditation system in Iran (Gandomkar et al., BMC Med Educ 23:379, 2023). As individuals who have been directly involved in the process of meta-accreditation and possess a comprehensive understanding of the various stages of Undergraduate Medical Education (UME) accreditation in Iran, we would like to highlight additional points that were identified through a rigorous hermeneutic phenomenology process proposed by Gadamer (Gadamer, Truth and Method, 2013) and offer a complementary point of view to the previous work. By sharing our insights, we hope to contribute to the ongoing discourse surrounding UME accreditation.

Prevalence of Human Papillomavirus Genotypes in Tehran, Iran.

BACKGROUND: Human papillomavirus (HPV) infection is a major cause of cervical cancer worldwide. Knowledge of the geographical distribution and epidemiology of the most common HPV genotypes is a crucial step in developing prevention strategies. Therefore, this study aimed to investigate HPV genotype distribution among HPV-positive women and men in Tehran, Iran. STUDY DESIGN: A case series study. METHODS: The study was performed on 219 HPV-positive individuals (160 females and 59 males) from Tehran, Iran. Samples were obtained from the cervix and vagina of female subjects and the genital warts of male subjects. DNA was extracted from samples, and a polymerase chain reaction (PCR)-reverse dot blot genotyping chip was used to examine HPV genotypes. Formalin-fixed, paraffin-embedded tissue samples of 51 patients from the study population were also included in this study. RESULTS: The proportion of high-risk (HR)-HPV was 67.12%. The most common HR-HPV types were HR-HPV16 (17.4%), HR-HPV68 (11.4%), and HR-HPV51 (7.8%). The most common low-risk (LR)-HPV types included LR-HPV6 (31.1%), LR-HPV81 (11.9%), and LR-HPV62 (11.4%). The highest prevalence of HPV was in the age group of > 30 years (42.9%). Co-infection with multiple HR-HPV types was observed in 22.4% of specimens. Moreover, HR-HPV was found in 50% of women with normal cytology, 100% with a low-grade squamous intraepithelial lesion, and 84.61% with atypical squamous cells of undetermined significance. CONCLUSION: The results indicated the remarkable growth of HR-HPV68, which has rarely been reported in Iran. The findings add knowledge to HPV epidemiological investigation and emphasize the need for introducing educational programs in high schools and appropriate vaccination in Iran.

Disseminated intravascular coagulation with positive D-dimer: a controversial clinical feature in severe congenital factor XIII deficiency in southeast Iran.

Disseminated intravascular coagulation (DIC) is an extremely rare coagulopathy in the rare factor XIII (FXIII) deficiency. Compensated DIC occurs because of injuries that lead to systemic coagulation activation that is amplified by impaired fibrinolysis. This challenge translates into the widespread deposition of fibrin degradation products in the circulation. The aim of this study is to report three cases with severe FXIII deficiency who presented with DIC and positive D-dimer. Here we describe three patients affected by both FXIII deficiency and DIC; two girls aged 17 and 45 days and a 3.5-year-old boy. All patients had a positive family history for FXIII deficiency. Umbilical cord bleeding was the first presentation of FXIII deficiency in all of them, who presented also with ecchymosis; two of them had delayed wound bleeding. DIC occurred simultaneously with intracranial haemorrhage in two patients, whereas the third experienced DIC following extensive haematoma. D-dimer measured in all patients ranged between 5 and 20 µg/ml, whereas fibrinogen degradation product was between 4 and 8 µg/ml.

Genetic risk factors in patients with deep venous thrombosis, a retrospective case control study on Iranian population.

BACKGROUND: Venous thromboembolism (VTE) could be manifested as deep venous thrombosis (DVT) or pulmonary embolism (PE). DVT is usually the more common manifestation and is usually formation of a thrombus in the deep veins of lower extremities. DVT could occur without known underlying cause (idiopathic thrombosis) which could be a consequence of an inherited underlying risk factor or could be a consequence of provoking events, such as trauma, surgery or acute illness (provoked thrombosis). Our aim in this study was to assess the impact of some previously reported genetic risk factors including, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, plasminogen activator inhibitor-1(PAI-1) 4G/5G, prothrombin 20210 and FV Leiden on occurrence of DVT in a population of Iranian patients. METHODS: This long-term study was conducted on 182 patients with DVT and also 250 age and sex matched healthy subjects as control group. The diagnosis of DVT was based on patient's history, clinical findings, D-dimer test, and confirmed by Doppler ultrasonography. After confirmation of DVT, both groups were assessed for the five mentioned mutations. The relationship between mutations and predisposition to DVT was calculated by using logistic regression and expressed as an OR with a 95 % confidence interval (CI). RESULTS: Our results revealed that FV Leiden (OR 6.7; 95 % CI = 2.2 to 20.3; P = 0.001), MTHFR C677T (OR 6.0; 95 % CI = 2.2 to 16.4; P < 0.001), MTHFR A1298C (OR 8.3; 95 % CI = 4.4 to 15.8; P < 0.001), and PAI-1 4G/5G (OR 3.8; 95 % CI = 2.1 to 7.2; P < 0.001) mutations were all significantly associated with an increased risk of DVT. Prothrombin 20210 was found in none of the patients and controls. CONCLUSION: Our findings suggest that genetic risk factors have a contributory role on occurrence of DVT.

Lack of Association between Interleukin-10 Gene Promoter Polymorphisms with HIV Susceptibility and Progression to AIDS.

BACKGROUND: Interleukin (IL)-10 is an important anti-inflammatory and immunomodulatory cytokine. Some authors believe that single nucleotide polymorphisms (SNP) in the promoter region of the IL-10 gene have been associated with susceptibility to HIV infection and progression to AIDS, but its role is not clearly defined yet. The present study was undertaken to evaluate the association between HIV infection susceptibility and progression with SNP in the promoter region of the IL-10 gene. METHODS: This study was carried out in 70 HIV infected patients (39 treatment naïve and 31 under treatment) and 31 matched healthy controls. The biallelic polymorphisms in the IL-10 gene promoter (-592 ,-1082) were analyzed by polymerase chain reaction and direct sequencing. RESULTS: At position -1082, G/A was the most common genotype and A was the most prevalent allele and at position -592, A/C was the most prevalent genotype and -592 C was the most common allele in HIV positive patients; although there was not any significant difference between cases and controls regarding genotypes and alleles of these regions. CONCLUSION: Our study showed that genetic polymorphisms of IL-10 promoter region may not associate with HIV infection outcome and the lack of this association suggests that other genes may influence on HIV infection course.

No correlation between interleukin-10 gene promoter polymorphisms and hepatitis B virus infection outcome.

BACKGROUND: Single nucleotide polymorphisms (SNP) in the promoter region of the interleukin (IL)-10 genes have a role in determining hepatitis B virus (HBV) outcome. OBJECTIVES: This study evaluates the correlation between HBV infection and SNP in IL-10 gene promoter. PATIENTS AND METHODS: Ninety-six HBV-infected patients (32 chronic hepatitis B infection patients, 34 healthy carriers, 30 spontaneously recovered cases) and 31 healthy controls were enrolled. Three biallelic (-819,-592,-1082) regions in the IL-10 gene promoter were sequenced for all patients. RESULTS: Genotypes and haplotypes of IL-10 gene promoter region at position -1082, -819 and -592 were not significantly different among controls, HBV recovered cases, carriers and chronic HBV patients. Nevertheless, A/A genotype at position -592 and T/T genotype at position -819 were more frequently seen in the HBV clearance group, while frequency of G/G genotype at position -1082 was more prevalent in the persistence group. GCC/GCC and GCC/ACC haplotypes were significantly observed in anti-HBe positive individuals. CONCLUSIONS: Our findings showed that IL-10 promoter polymorphisms were not correlated with HBV infection prognosis. Nevertheless, individuals carrying high and intermediate producer of IL-10 haplotypes had a better ability to develop anti-HBe than low producer carriers.

Mutation hot spots in hepatitis B surface antigen in chronic carriers from Khoozestan province, southern of Iran.

Mutations in the human hepatitis B virus (HBV) genome contribute to its escape from host immune surveillance and result in persistent infections. The aim of this study was to characterize the molecular variations of the surface gene and protein in chronically-infected patients from the southern part of Iran. The surface genes from 12 HBV chronic carriers were amplified, sequenced and subsequently aligned using international and national Iranian database. All strains belonged to genotype D, subgenotype D1 and subtype ayw2. Of all 30 mutations occurred at 22 nucleotide positions, 18 (60%) were missense (amino acid altering) and 12 (40%) were silent (no amino acid changing). The mean mutation frequency (missense to silent nucleotide ratio), was 1.5, indicating application of a high positive selection pressure on the surface proteins. At the amino acid level, of 17 substitutions, 15 (88%) occurred in different immune epitopes within surface protein, of which 7 (46.6%) in B cell epitopes in 5 residues; 7 (46.6%) in T helper epitopes in 6 positions; 1 (7%) in inside CTL epitopes in 1 residue. We therefore conclude that the distribution of 93.2% of amino acid mutations inside B and T helper immune epitopes as well as the ratio between silent and missense nucleotide mutations showed a positive, focused immune selection pressure on the surface protein, which led to the evolution and emergence of escape mutants in these patients.

Hyperglycemia after renal transplantation: frequency and risk factors.

BACKGROUND: Chronic renal failure is an important and common complication of diabetes mellitus; hence, renal transplantation is a frequent and the acceptable treatment in patients with diabetic nephropathy requiring renal replacement therapy. On the other hand, renal transplantation and its conventional treatment can lead to increased diabetes outbreak in normoglycemic recipients. Also, uncontrolled hyperglycemia may be increased and allograft lost thus decreasing patient survival. OBJECTIVES: We aimed to assess the frequency of hyperglycemia in transplant patients and its risk factors. PATIENTS AND METHODS: A large retrospective study was performed on 3342 adult kidney transplant recipients between 2008 and 2010. Demographic and laboratory data were gathered for each patient. All tests were done in a single laboratory and hyperglycemia was defined as a fasting plasma glucose of > 125 mg/dL. Univariate and multivariate logistic regression analyses were used to determine the risk factors of hyperglycemia following kidney transplantation. RESULTS: There were 2120 (63.4%) males and 1212 (36.3%) females. Prevalence of hyperglycemia was 22.5%. By univariate linear regression, hyperglycemia was significantly higher in patients with CMV infection (P = 0.001), elevated serum creatinine (P = 0.000), low HDL (P = 0.01), and increased blood levels of cyclosporine (P = 0.000). After adjusting for covariates by multivariate logistic regression, the hyperglycemia rate was significantly higher for patients with Cyclosporine trough level > 250 (P = 0.000), serum creatinine > 1.5 (P = 0.000) and HDL < 45 (P = 0.03). CONCLUSIONS: This study indicated that hyperglycemia is a common metabolic disorder in Iranian kidney transplant patients. Risk factors for hyperglycemia were higher Cyclosporine level, impaired renal function, and reduced HDL value.

Hyperglycemia after kidney transplantation: frequency and risk factors.

INTRODUCTION: Kidney transplantation and its conventional treatment can lead to increased risk of diabetes mellitus outbreak in normoglycemic recipients. Also, uncontrolled hyperglycemia may increase allograft loss and decrease patient survival. We aimed to assess the frequency of hyperglycemia in transplant patients and its risk factors. MATERIALS AND METHODS: A retrospective study was performed on 3342 adult kidney transplant recipients between 2008 and 2010. Demographic and laboratory data were collected. All laboratory tests were done in a one laboratory, and hyperglycemia was defined as a fasting plasma glucose level greater than 125 mg/dL. Univariable and multivariable logistic regression analyses were used to determine the risk factors of hyperglycemia following kidney transplantation. RESULTS: There were 2120 men (63.4%) and 1212 women (36.3%) included in the study. The prevalence of hyperglycemia was 22.5%. Hyperglycemia was significantly higher in patients with cytomegalovirus infection (P = .001), elevated serum creatinine (P < .001), low high-density lipoprotein cholesterol (P = .01), and increased blood levels of cyclosporine (P < .001). After adjusting for covariates by multivariate logistic regression, the hyperglycemia rate was significantly higher for patients with a cyclosporine trough level greater than 250 ng/mL (P < .001), a serum creatinine level greater than 1.5 mg/dL (P < .001), and a high-density lipoprotein cholesterol less than 45 mg/dL (P = .03). CONCLUSIONS: This study indicated that hyperglycemia is a common metabolic disorder in Iranian kidney transplant patients. Risk factors for hyperglycemia were higher cyclosporine level, impaired kidney function, and reduced high-density lipoprotein cholesterol values.

Occult hepatitis B virus infection in hemodialysis patients with isolated hepatitis B core antibody: a multicenter study.

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Occult HBV infection harbors potential risk of HBV transmission through hemodialysis (HD). The aim of this study was to assess the occult HBV infection in hemodialysis patients with isolated hepatitis B core antibody (anti-HBc). A total of 289 HD patients from five dialysis units in Tehran, Iran, were included in this study. Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (anti-HBs), anti-HBc, Hepatitis C antibody (anti-HCV), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of HD patients with isolated anti-HBc (HBsAg negative, anti-HBs negative and anti-HBc positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler. Of 289 patients enrolled in this study, 18 subjects (6.2%, 95% confidence interval (CI), 3.5%-8.9%) had isolated anti-HBc. HBV-DNA was detectable in 9 of 18 patients (50%, 95% CI, 27%-73%) who had isolated anti-HBc. Plasma HBV-DNA load was less than 50 IU/ml in all of these patients. Our study showed that detection of isolated anti-HBc could reflect unrecognized occult HBV infection in HD patients. The majority of these infections are associated with low viral loads.

Lack of occult hepatitis B virus infection among blood donors with isolated hepatitis B core antibody living in an HBV low prevalence region of Iran.

BACKGROUND: Occult hepatitis B virus (HBV) infection in blood donors is considered a potential threat for the safety of the blood supply, however conclusive studies on this issue are lacking. The aim of this study was to assess the occult HBV infection in blood donors with isolated hepatitis B core antibody (anti-HBc) living in the city of Arak, in the Central Province of Iran, as a low prevalence region for HBV. METHODS: A total of 531 voluntary blood donors in Arak, Iran were included in this study. Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), anti-HBc, and hepatitis C antibody (anti-HCV) were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of cases with isolated anti-HBc (HBsAg-negative, anti-HBs-negative, and anti-HBc-positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler. RESULTS: Of 531 subjects enrolled in this study, 11 (2.1%, 95% confidence interval 0.8-3.2%) had isolated anti-HBc. HBV-DNA was not detected in any of the cases with isolated anti-HBc. CONCLUSIONS: Our study showed that all the blood donors with isolated anti-HBc were negative for HBV-DNA, and occult HBV infection did not occur in the blood donors of this low prevalence region for HBV infection.

The prevalence of low selenium levels in adult patients undergoing bone marrow transplantation: a brief communication.

Selenium (Se) is an essential trace element, and its deficiency is considered to be important in various types of cancer. There are just a few data regarding this issue among adult patients with hematological malignancy. Serum Se levels were determined in 22 adult patients candidates for bone marrow transplantation (BMT) in Iran. The mean serum Se levels before BMT was 19.91 microg/l (from 12.00 to 62.00 microg/l), and almost all the patients had low Se serum levels (normal serum Se level: 46-143 microg/l). The level of Se 20 days after BMT was 22.53 microg/l, which did not show any significant changes. Most of the patients did not suffer from malnutrition, as they had mostly normal albumin levels. Even though the results of this study showed that Se deficiency is common among our hematological malignant patients, it can not be concluded that these low Se levels are causally related to cancers for which BMT is undertaken. Further studies are needed to evaluate the Se levels at diagnosis before treatment effects.

Association of human leukocyte antigen polymorphism with outcomes of hepatitis B virus infection.

BACKGROUND AND AIM: Host genetic and environmental factors are viewed as a common basis of the different outcomes of hepatitis B virus (HBV) infection. Human leukocyte antigen (HLA) plays an important role in immunological reaction to HBV infection. In this study, we aimed to determine the association between HBV infection and HLA-A, B, and DRB1 alleles in northern Iran. METHODS: HLA-A, B, and DRB1 alleles in 33 patients with chronic hepatitis B (CHB) and 31 healthy carriers as the persistent group, and 30 subjects who had spontaneously recovered from HBV infection were analyzed by using the polymerase chain reaction (PCR)-sequence-specific primer (PCR-SSP) technique. RESULTS: The frequency of the HLA-A*33 allele was higher in the persistent group than in the recovered group (10.16% vs 0%, P < 0.008); the frequency of the DRB1*13 allele was lower in the persistent group than in the recovered group (3.13% vs 11.67%, P < 0.03). The frequency of the B*52 allele was higher in CHB patients than healthy carriers (7.58% vs 0%, P < 0.05). The logistic regression model showed that the presence of the HLA-DRB1*13 allele was the significant factor associated with protection against the persistency of HBV. There were significant differences between the HBV recovered group, CHB patients, and healthy carriers regarding age, hepatitis B e antigen, and anti-hepatitis B e positivity. CONCLUSION: HLA-A*33 was closely related with susceptibility to persisting hepatitis B infection, and HLA-DRB1*13 was closely related with protection against persisting hepatitis B in an Iranian population. These findings emphasized that the host HLA polymorphism is an important factor in determining the outcome of HBV infection.

Persistence of hepatitis B vaccine immunity in hemodialysis patients.

Although the efficacy of hepatitis B vaccines in patients undergoing chronic hemodialysis (HD) treatment has been documented, the persistence of immunity in this population remains largely unknown. In this study we evaluated the persistence of hepatitis B vaccine immunity in HD patients. We followed 37 hepatitis B vaccinated HD patients (following a four-dose vaccination schedule of 40 mug injections intramuscularly in the deltoid muscle at 0, 1, 2, and 6 months) for up to one year to evaluate the persistence of immunity (as indicated by serum levels of hepatitis B surface antibody (anti-HBs) equal to or higher than 10 IU/L). One year after vaccination, 18.9% of patients had lost their anti-HBs (transient responders), while 81.1% still had detectable antibodies in the serum (persistent responders). From 81.1% of persistent responders 11.5% and 88.5% were weak and high responders, respectively. There was no significant difference between persistent and transient responders regarding age, sex, or nutritional factors. We did not find any factors that related to maintaining protective levels of anti-HBs in HD patients. It seems that an antibody titer above 100 IU/L following vaccination is necessary in order to maintain that level of antibody one year later.

The risk factors of prostate cancer: a multicentric case-control study in Iran.

Prostate cancer (PC), in Iran, is the third most frequently diagnosed visceral cancer among men and the seventh most common underlying cause of cancer mortality. We evaluated the relation between speculated factors and PC risk using data from a multicentric case-control study conducted in Iran from 2005 to 2007 on 130 cases of incident, clinicopathologically confirmed PC, and 75 controls admitted to the same network of hospitals without any malignant disease. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression models. The risk of PC was increased with aging (OR: 5.35, 95% CI: 2.17-13.19; P<0.0001), and with the number of sexual intercourse >or=2 times/week (OR: 3.14, 95% CI: 1.2-8.2; P=0.02). One unit elevation in serum estradiol and testosterone concentration was related to increase (OR: 1.04, 95% CI: 1.01-1.06; P=0.006) and decrease (OR: 0.79; 95% CI: 0.64-0.96; P=0.02) of PC risk, respectively. Cases were less likely to have a history of diabetes (OR: 0.34, 95% CI: 0.12-0.98; P=0.04). Increasing in dietary consumption of lycopene and fat was associated with declined (OR: 0.45, 95% CI: 0.09-2.12) and increased (OR: 2.38, 95% CI: 0.29-19.4) PC development, respectively. Other factors including educational level, marriage status, dietary meat consumption, vasectomy and smoking have not been shown to affect PC risk in the Iranian population. Our study adds further information on the potential risk factors of PC and is the first epidemiologic report from Iran. However, justification of these results requires more well-designed studies with a larger number of participants.

Associations of Human Leukocyte Antigen (HLA) haplotypes with risk of developing lymphoproliferative disorders after renal transplantation.

BACKGROUND: Genetic susceptibility to lymphomas associated with human leukocyte antigens (HLA) has been broadly reported for many years. In this study, we aimed to evaluate the potential impact of various HLA antigens on the incidence of lymphoproliferative disorders in renal allograft recipients. MATERIAL/METHODS: In this retrospective cross-sectional study, we analysed data of PTLD patients from two of the major Iranian transplant centers and compared them with 1155 normal kidney recipients. Potential impact of previously reported relevant HLA antigens was assessed. For assessing independent impact of various factors, we used a multivariate proportional hazard analysis using Cox regression. RESULTS: Patients in the two groups were similar in their age at transplantation. PTLD group was significantly female predominated (61% vs. 33%). chi(2) showed a higher frequency of HLA-BW22 in the PTLD group. HLA-A2, HLA-A11, HLA-B5 and HLA-B35 concomitant with azathioprine based immunosuppression were significantly associated with PTLD occurrence. CONCLUSIONS: Our findings can further alert us toward the initial signs of PTLDs in high risk kidney allograft recipients. Future prospective studies with larger patient population seem necessary for confirming our findings.

Frequency of HFE gene mutations in Iranian beta-thalassaemia minor patients.

OBJECTIVES: Beta-thalassaemia minor (BTM) alone does not lead to iron overload, however, some gene modifiers and acquired causes are reported. When it is inherited together with a mutation in the HFE (HLA-H) gene associated with hereditary haemochromatosis, iron overload may ensue. To analyse the relationship between iron status and HFE mutations in Iranian BTM patients, we compared the frequency of the C282Y and H63D HFE mutations and ferritin level in a group of BTM patients from the National Thalassaemia Transfusion and Care Centre with that of healthy individuals. PATIENTS AND METHODS: Ninety-three (56 females) documented BTM cases and 104 (54 females) controls were enrolled in the study. Serum ferritin level was measured in all subjects by immuno-radiometric assay and HFE genotypes were determined using restriction fragment length polymorphism analysis of PCR-amplified HFE gene fragment. RESULTS: Eighteen (19.4%) BTM patients vs. 12 (11.5%) controls were H63D heterozygotes, while there were three (3.2%) cases and three (2.9%) controls with H63D homozygosity. All three C282Y mutations were found in BMT patients with one of them being a compound heterozygote. A significant difference was observed in the total number of HFE mutations in favour of BTM patients over the controls (P < 0.05, OR = 2.064). The H63D and C282Y allele frequencies were 12.9 and 1.61 in patients and 8.65 and 0 in controls, respectively. The mean ferritin level in cases with HFE mutations showed no significant difference from that of the patients without mutations (P > 0.05). CONCLUSIONS: Our results suggest that HFE mutations C282Y and H63D are more frequent in Iranian BTM patients than in the normal population, causing no significant changes in serum ferritin level.