Iranian Journal of Medical Sciences
Volume:48 Issue: 1, Jan 2023

The role of the tumor microenvironment (TME), especially immune cell compartments, in tumor progression is inevitable and the heterogeneity and complexity of the TME-associated immune cells make it challenging to provide appropriate treatments for hematologic malignancies.

Progressive insulin resistance is a physiological condition during pregnancy that can lead to gestational diabetes. Given the association between low blood vitamin D levels and insulin resistance, the present meta-analysis evaluated the effect of vitamin D supplementation on serum 25-hydroxyvitamin D (25[OH]D) and the homeostatic model of insulin resistance (HOMA-IR) levels in non-diabetic pregnant women.

A comprehensive literature search was conducted using electronic databases and gateways such as Cochrane Library, Medline, Google Scholar, Science Direct, Web of Sciences, Embase, and Scopus. Articles up to 2020 in both English and Persian were included in the study. The effect of vitamin D supplementation on 25(OH)D and HOMA-IR was determined based on the differences in mean changes from baseline to post-intervention. Weighted mean and 95% confidence intervals (CI) were pooled using a random-effects model. Data were analyzed using STATA software. 

Four studies, including six trials with 380 participants, reported that vitamin D supplementation increased 25(OH)D (mean change: 13.72, 95% CI: 7.28-20.17) and decreased HOMA-IR (mean change: 1.46, 95% CI: 0.56-2.37) levels compared with the placebo group. A high weekly dose of vitamin D further reduced HOMA-IR levels (adjusted R2=77.99, I2 residuals=80.49%, P=0.047). There was no significant association between the dose of vitamin D and 25(OH)D (P=0.974). Intervention duration was not associated with an increase in 25(OH)D (P=0.102), nor with a decrease in HOMA-IR (P=0.623).

Vitamin D supplementation increased 25(OH)D and decreased HOMA-IR levels in non-diabetic pregnant women. Vitamin D in high doses further reduced HOMA-IR, but did not affect 25(OH)D concentrations.

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin’s mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders.

Non-Hodgkin lymphoma (NHL) is the eleventh leading cause of cancer-related death in the world. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL. Up to winter 2021-2022, the death toll caused by the coronavirus disease 2019 (COVID-19) has exceeded 5.6 million worldwide. Possible molecular mechanisms involved in the systemic inflammation, and cytokine storm in COVID-19 patients are still not fully understood. MicroRNA-155 (miR-155) plays a role in the post-transcriptional gene regulation of hematopoiesis, oncogenesis, and inflammation. The present study aimed to evaluate the expression of miR-155 in patients with DLBCL and/or COVID-19. A cross-sectional study was conducted from July to December 2020 in Tehran (Iran) to evaluate the expression of miR-155 in adult patients diagnosed with DLBCL and/or COVID-19. The real-time polymerase chain reaction technique was used to evaluate the expression of miR-155 in the sera of 92 adults who were either healthy or suffering from DLBCL and/or COVID-19. Relative quantification of gene expression was calculated in terms of cycle threshold (Ct) value. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant.  The expression of miR-155 was not associated with the sex or age of the participants. In comparison with healthy individuals (-ΔCt: -1.92±0.25), the expression of miR-155 increased in patients with COVID-19 (1.95±0.14), DLBCL (2.25±0.16), or both (4.33±0.65). The expression of miR-155 increased in patients with DLBCL and/or COVID-19.

Coronary heart disease is the leading cause of death worldwide. Myocardial infarction (MI) is a fatal manifestation of coronary heart disease, which can present as sudden death. Although the molecular mechanisms of coronary heart disease are still unknown, global gene expression profiling is regarded as a useful approach for deciphering the pathophysiology of this disease and subsequent diseases. This study used a bioinformatics analysis approach to better understand the molecular mechanisms underlying coronary heart disease. This experimental study was conducted in the department of cardiology, Aja University of Medical Sciences (2021-2022), Tehran, Iran. To identify the key deregulated genes and pathways in coronary heart disease, an integrative approach was used by merging three gene expression datasets, including GSE19339, GSE66360, and GSE29111, into a single matrix. The t test was used for the statistical analysis, with a significance level of P<0.05.  The limma package in R was used to identify a total of 133 DEGs, consisting of 124 upregulated and nine downregulated genes. KDM5D, EIF1AY, and CCL20 are among the top upregulated genes. Moreover, the interleukin 17 (IL-17) signaling pathway and four other signaling pathways were identified as the potent underlying pathogenesis of both coronary artery disease (CAD) and MI using a systems biology approach. Accordingly, these findings can provide expression signatures and potential biomarkers in CAD and MI pathophysiology, which can contribute to both diagnosis and therapeutic purposes. Five signaling pathways were introduced in MI and CAD that were primarily involved in inflammation, including the IL-17 signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and rheumatoid arthritis signaling pathway.

In December 2019, an outbreak of pneumonia caused by the novel coronavirus disease 2019 (COVID-19) became a pandemic and caused a global health crisis. This study evaluates the immunogenic potential of the Mediterranean fever (MEFV) gene in patients with COVID-19.  A cross-sectional study was conducted from March to April 2020 in various COVID-19 referral centers in Ardabil, Iran. Blood samples of 50 hospitalized patients with confirmed COVID-19 were evaluated for MEFV gene mutation using the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and Sanger sequencing. Statistical analysis was performed using SPSS software, version 22.0. Mutations of the MEFV gene were found in 6 (12%) of the patients. All mutations were heterozygous, and no homozygous or compound heterozygous forms were detected. The total mutant allele frequency was 6% and the carrier rate was 12%. The most common allele of the MEFV variant was E148Q, detected in 3 (6%) patients. No mutant variant of the MEFV gene was detected in deceased patients. None of the mutation carriers had familial Mediterranean fever (FMF) symptoms or a family history of FMF. MEFV gene mutations may have immunogenic potential in patients with COVID-19.A preprint version of this article has already been published at https://www.researchsquare.com/article/rs-69373/latest.pdf.

Primary spontaneous pneumothorax (PSP) is a spontaneous pneumothorax without underlying lung disease. The main goals of this study were to compare the outcomes of video-assisted thoracoscopic surgery (VATS) and open thoracotomy in patients with PSP. 

The current study is a retrospective cohort study of patients who were admitted to the emergency department or general surgery ward at Dr. Masih Daneshvari Hospital (Tehran, Iran) with the diagnosis of PSP and underwent surgery by open or VATS approach from 2006 to 2012. The groups were compared in terms of the length of operation, the length of hospitalization, recurrence, and postoperative complications. Data were analyzed using SPSS version 18.0, and Student’s t test, analysis of variance (ANOVA), Chi square, and Fisher’s exact test were employed. P values less than 0.05 were considered statistically significant.

PSP was diagnosed in 90 patients who underwent surgery. Open thoracotomy and VATS procedures were performed in 65 (72.2%) and 25 (27.8%) patients, respectively. VATS was converted to open in seven cases (7.7%). Recurrent pneumothorax was the most common surgical indication for PSP. There was no significant difference between the two groups in terms of mean age, sex, smoking, side of the involved lung, previous pneumothorax history, mean length of hospitalization for recurrence, post-operation bleeding, and failure of lung expansion. However, the length of surgery (P=0.011) and air leakage (P=0.048) significantly differed between the two groups. 

When compared to open thoracotomy, VATS could be the primary treatment option in the surgical treatment of PSP due to the shorter length of surgery and decreased complications such as air leakage.

Despite growing evidence, there is still uncertainty about potentially modifiable risk factors for neonatal early-onset sepsis (EOS). This study aimed to identify potential clinical risk factors for EOS based on a literature review and expert opinions.

A literature search was conducted in PubMed (MEDLINE), Cochrane, Embase, and Scopus databases. Articles in English, published up to May 2021, on clinical risk factors for neonatal EOS were included. Initially, a questionnaire on risk factors for EOS was developed and validated. The fuzzy Delphi method (FDM) was used to formulate the final version of the questionnaire. The validity of the risk factors was assessed using the Chi square test. P<0.05 was considered statistically significant.

In the review phase, 30 risk factors were approved by two neonatologists and included in the FDM phase. In total, 25 risk factors met the consensus criteria and entered the validation phase. During the observational study, 114 neonates (31 with and 83 without EOS) were evaluated for two months. The results of the Chi square test showed that cesarean section was not a significant risk factor for EOS (P=0.862). The need for mechanical ventilation and feed intolerance was observed in about 70% of neonates with EOS, and therefore considered significant risk factors for EOS (P<0.001). Finally, 26 potential clinical risk factors were determined.

Neonatal-related risk factors for EOS were birth weight, one-min Apgar score, and prematurity. Maternal-related risk factors were gestational age and urinary tract infection. Delivery-related risk factors were premature rupture of membranes, chorioamnionitis, and intrapartum fever.

Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN.

A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group (n=14) included hospitalized patients due to CBZ- or LTG-induced SJS/TEN. The drug-tolerant group (n=17) included individuals receiving CBZ or LTG for at least three months with no adverse effects. In addition, 46 healthy individuals (control group) were recruited. The frequency of HLA-A, -B, and -DRB1 alleles in patients with CZB- or LTG-induced SJS/TEN was investigated. HLA typing was performed using the allele-specific polymerase chain reaction method. The Chi square test and Fisher’s exact test were used to determine a potential association between SJS/TEN and HLA alleles. P<0.05 was considered statistically significant.

CBZ- or LTG-induced SJS/TEN was not significantly associated with HLA alleles. However, HLA-DRB1*01 showed a significantly higher frequency in patients with CBZ-induced SJS/TEN than the CBZ-tolerant patients (30% vs. 9%, P=0.07). 

Overall, no significant association was found between CBZ- or LTG-induced SJS/TEN and HLA alleles. Further large-scale studies are required to substantiate our findings.

Azoospermia is a risk factor for infertility affecting approximately 1% of the male population. Genetic factors are associated with non-obstructive azoospermia (NOA). Pygo2 and PRDM9 genes are involved in the spermatogenesis process. The present study aimed to assess the association of single nucleotide polymorphism (SNP) in the Pygo2 (rs61758740 and rs61758741) and PRDM9 (rs2973631 and rs1874165) genes with idiopathic azoospermia (IA). A cross-sectional study was conducted from October 2018 to August 2019 at Rooya Infertility Centre (Qom, Iran). A total of 100 infertile patients with NOA and 100 men with normal fertility were enrolled in the study. Tetra-primer amplification refractory mutation system-PCR method was used to detect SNPs rs61758740, rs61758741, and rs2973631. The restriction fragment length polymorphism method was used for SNP rs1874165. In addition, luteinizing, follicle-stimulating, and testosterone hormone levels were measured.  The results showed a significant increase in luteinizing and follicle-stimulating hormone levels in the patient group (P<0.001), but a non-significant difference in testosterone levels in both groups. SNP rs61758740 (T>C) was associated with the increased risk of azoospermia (OR: 2.359, 95% Cl: 1.192-4.666, P=0.012). SNP rs2973631 showed a significant difference in genotype frequency between the patient and control groups in the dominant, recessive, and codominant models. However, in the case of SNP rs1874165, the difference was significant in the dominant, codominant, and overdominant models.  There is an association between azoospermia and SNPs in Pygo2 and PRDM9 genes in Iranian infertile male patients with IA. SNPs can be considered a risk factor for male infertility. It should be noted that this article was published in preprint form on the website of europepmc (https://europepmc.org/article/ppr/ppr416800).

Conjunctival nevi (CN) are common benign ocular tumors. Given their low risk of malignancy, surgical removal of nevi is primarily requested by patients. Herein, we introduce Atmospheric Low-temperature Plasma (ALTP) as a novel noninvasive method for the removal of CN.  A clinical case series was conducted from 2020 to 2021 at the Vision Health Ophthalmic Center in Tehran, Iran. CN in one of the eyes of seven patients was treated. In all patients, the benignity of CN was confirmed by ocular oncologists. The white handpiece of the Plexr device, which generates plasma with the lowest output, was used to apply plasma spots on the nevi. In addition, the Ocular Surface Disease Index (OSDI) questionnaire was completed by all patients before and six months after the treatment.  In all patients, the nevi outside the limbus area completely disappeared. The mean size of pre- and post-operative nevi was 3.89×11.7 and 0.54×1.69 mm, respectively. Results of the OSDI questionnaire showed significantly lower scores after the surgery in all patients. The ALTP method is a simple, cost-effective, and office-based surgery to remove CN safely and effectively.

Recently, due to the coronavirus disease 2019 (COVID-19) pandemic, much concern has been raised about patients with chronic diseases who may become more susceptible to the disease. The present cross-sectional study aimed to characterize the clinical course of COVID-19 in patients with systemic lupus erythematosus (SLE). In addition, a possible correlation between the immunosuppression state and the incidence of COVID-19 is investigated. In May 2020, 500 SLE patients registered in the database of Golestan Rheumatology Research Center (Golestan province, Iran) were selected for this cross-sectional study. Using a questionnaire, patients were contacted by telephone to collect data including demographic characteristics, disease status, drug use, and new clinical symptoms. Data were analyzed using SPSS software version 24.0. Of the 500 selected patients, 355 responded to the phone calls and subsequently enrolled in the study. Among the enrolled patients, 25 were classified as COVID-19 positive, including eight hospitalized patients, of which two required intensive care and subsequently died. COVID-19 incidence was significantly lower in the immunosuppressed patients (2.2% vs. 10%, P=0.01). There was no significant correlation between hydroxychloroquine consumption and the incidence of COVID-19 in SLE patients. Fever, fatigue, dyspnea, and dry cough were the most common clinical symptoms. Our results showed that COVID-19 incidence was lower in immunosuppressed than the non-immunosuppressed SLE patients. Further studies are required to substantiate the role of immunosuppression in the development of COVID-19.A preprint version of this study was published at https://www.researchsquare.com/article/rs-78704/v1 with doi: https://doi.org/10.21203/rs.3.rs-78704/v1

Coronavirus disease 2019 (COVID-19) causes ocular manifestations in approximately 11% of patients. Most patients typically develop ocular symptoms within 30 days of the onset of the first COVID-19 symptoms. The most common ocular manifestation is conjunctivitis, which affects nearly 89% of patients with eye problems. Other much less common anterior segment abnormalities caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are scleritis, episcleritis, and acute anterior uveitis. Posterior segment abnormalities caused by SARS-CoV-2 are mainly vascular, such as hemorrhages, cotton wool spots, dilated veins, and vasculitis. Herein, we report a rare manifestation of COVID-19 and multiple evanescent white dot syndrome (MEWDS) of the retina. In April 2021, a 40-year-old female patient was admitted to the Eye Clinic of Clinical Center of Montenegro (Podgorica, Montenegro). The patient’s main complaint was sudden vision impairment, which occurred 14 days after a positive polymerase chain reaction (PCR) test result for SARS-CoV-2 infection. A complete eye examination was performed, followed by fundoscopy, optical coherence tomography (OCT), and fluorescein angiography (FA) tests. The results showed retinal changes associated with MEWDS. The patient underwent additional examinations to rule out common causes of multifocal retinitis, all of which were unremarkable. Therefore, it was concluded that retinitis was a complication of COVID-19. Given its non-invasive nature, fundus examination should be used as a standard screening method for retinal changes in patients with COVID-19.

Nasal swab tests are widely used to screen for coronavirus disease 2019 (COVID-19). Pain, discomfort, and the urge to sneeze are the most common complications of this screening method. We report a case of a 55-year-old female patient with beta-thalassemia major suffering from a nasal septal abscess (NSA) as a complication of a COVID-19 nasal swab test. Following the test, the patient only had mild nasal congestion. However, three days later, her clinical condition deteriorated, and she developed fever, and her level of consciousness decreased to lethargy and drowsiness. Physical examinations revealed a bilateral nasal abscess. She underwent surgical intervention, and the abscess was removed. For the first time in Iran, a case of NSA after a COVID-19 nasal swab test is reported. It is strongly recommended to exercise caution while performing nasal swab tests, especially in the elderly and patients at risk of bleeding or hemoglobinopathy.

The majority of health professionals are aware of the importance of social determinants of health (SDOH).