Background: The Rh blood group system is highly significant in transfusion medicine because of the strong immunogenicity of the D antigen. The RhD-negative phenotype arises through various molecular mechanisms in different populations, most commonly complete deletion of the RHD gene caused by unequal recombination between upstream and downstream Rhesus box sequences. Although this mechanism has been well documented in some populations, limited data are available from Iran, particularly its eastern regions. This study aimed to determine the molecular basis of the RhD-negative phenotype among blood donors in eastern Iran.

Materials and Methods: In this cross-sectional study, a total of 16,190 blood donors referred to blood transfusion centers in South Khorasan Province, eastern Iran, over a one-year period were screened serologically for RhD status. Among them, 2,198 individuals were identified as RhD-negative, and 100 serologically confirmed RhD-negative donors were randomly selected for molecular evaluation. RhD typing was performed using standard serologic methods and verified by indirect antiglobulin testing. Molecular investigations included PCR–sequence-specific priming (PCR-SSP) targeting RHD exons 5, 7, and 10, real-time PCR for confirmation, and PCR–restriction fragment length polymorphism (PCR-RFLP) to detect the hybrid Rhesus box and determine RHD zygosity.

Results: Among 16,190 blood donors screened during the study period, 2,198 (13.57%) were identified as RhD-negative. From this group, 100 samples were randomly selected for molecular analysis. Both PCR-SSP and real-time PCR confirmed the absence of RHD exons 5, 7, and 10 in all samples, indicating complete deletion of the RHD gene. PCR-RFLP analysis further confirmed that all donors were homozygous for the hybrid Rhesus box, with full concordance observed between exon-specific assays and hybrid Rhesus box genotyping.

Conclusion: These findings indicate that the RhD-negative phenotype in eastern Iran is primarily due to homozygous RHD gene deletion mediated by the hybrid Rhesus box. Hybrid Rhesus box analysis may therefore serve as a reliable molecular marker for accurate RhD typing, which could improve transfusion safety and perinatal management in this population.

Background: MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding gene expression, and alterations in their expression are associated with leukemic transformation of hematopoietic cells. This study analyzed bone marrow samples from Philadelphia chromosome-positive (Ph+) and Philadelphia chromosome-negative (Ph−) acute lymphoblastic leukemia (ALL) patients to assess miR-320a and miR-206 expression and their relationship with prognosis.

Materials and Methods: miR-206 and miR-320a expression levels were assessed using real-time PCR in 50 bone marrow specimens: 10 from healthy individuals (control group), 20 from Ph+ ALL patients, and 20 from Ph− ALL patients. Data were analyzed using GraphPad Prism version 7, one-way ANOVA, and Chi-square tests.

Results: The Ph− ALL group exhibited a significant 3.8-fold reduction in miR-206 expression (P = 0.004), while the Ph+ ALL group showed a significant 5.34-fold increase (P = 0.006) compared to the control group. No statistically significant differences were observed in miR-320a expression between the Ph+ and Ph− groups relative to controls (P = 0.496 and P = 0.645, respectively). Data analysis revealed no association between age, sex, and miRNA expression.

Conclusion: MiR-206 showed differential expression, being significantly upregulated in Ph+ ALL and downregulated in Ph− ALL patients. This miRNA may serve as a potential diagnostic biomarker for distinguishing between the two ALL subgroups. However, further studies incorporating clinical outcome data are needed to confirm its prognostic value.

Background: Cervical cancer is a major public health issue, particularly in low- and middle-income countries. Early detection through effective screening methods is crucial for reducing morbidity and mortality. Opportunistic cervical cytology testing in outpatient settings plays an important role in the early identification of precancerous lesions.

Materials and Methods: This cross-sectional study aimed to evaluate the effectiveness of liquid-based cytology (LBC) in detecting precancerous lesions and cervical cancer in a defined population. One hundred women aged between 25 and 75 years were screened using LBC. Cytological specimens were processed and analyzed by experienced cytopathologists.

Results: The detection rate of precancerous lesions was 13% (n = 13), and cervical cancer was detected in 2% (n = 2) of patients. Most patients attending the outpatient department (OPD) were in the fourth decade of life (30–39 years; 37 cases, 37%), followed by the third decade (20–29 years; 23 cases, 23%). Of the patients diagnosed with low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesions (HSIL), 72.7% (8 out of 11) were in the 51–70 years age group.

Conclusion: LBC demonstrated a detection rate of 13% for premalignant lesions and 2% for cervical cancer in this opportunistic screening population. The majority of LSIL/HSIL cases occurred in women aged 51–70 years, suggesting that older age groups may benefit from targeted screening efforts. These findings provide valuable insights into the performance of LBC in this setting and can inform the development of effective cervical cancer screening programs to reduce disease burden.

Background: This study aimed to analyze the effect of repeated intravenous injections of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs), administered at a dose of 1 × 10⁶ cells/kg four times at 3-month intervals, on insulin levels and weight gain in aging female rats.

Materials and Methods: Twelve female rats were divided into three groups: Group A (3-month-old young females, untreated control), Group B (24-month-old aged females injected with 0.4 mL of 0.9% NaCl as vehicle control), and Group C (24-month-old aged females injected with 1 × 10⁶ cells/kg of hWJ-MSCs suspended in 0.4 mL of 0.9% NaCl). Injections were administered at baseline and then every 3 months for a total of four doses. Twelve months after the first injection, the rats were anesthetized and sacrificed. Serum insulin levels were measured using ELISA, and immunohistochemical staining was performed to detect hWJ-MSCs homing to pancreatic tissue.

Results: Rats treated with hWJ-MSCs showed a trend toward lower body weight compared to the aged vehicle-control group. Insulin levels in treated aged rats were significantly higher than those in the aged control group (p < 0.05). Immunohistochemical analysis revealed that hWJ-MSCs were extensively distributed within the islets of Langerhans of treated aged rats.

Conclusion: Repeated intravenous administration of hWJ-MSCs (1 × 10⁶ cells/kg, four doses over 12 months) led to successful migration and homing to the islets of Langerhans in aging female rats. Treated animals exhibited significantly increased insulin levels and a trend toward reduced weight gain, suggesting a potential metabolic benefit of hWJ-MSC therapy in physiological aging.

Background: Multiple myeloma is a heterogeneous malignancy with patchy bone marrow involvement, often leading to discrepancies between biochemical and imaging-based response assessments. Site-specific bone marrow biopsies may miss focal disease, while FDG PET/CT detects metabolically active lesions, and the two approaches offer complementary prognostic value.

Materials and Methods: This prospective study included 44 newly diagnosed multiple myeloma patients. The primary aim was to assess the correlation between biochemical and PET/CT responses at six months post-induction. A secondary objective was to evaluate the impact of PET/CT response on 12-month event-free survival (EFS).

Results: The median age was 55.5 years. At baseline, more than 3 focal lesions and extramedullary disease (EMD) were observed in 61.4% and 34.1% of patients, respectively. After six months of induction therapy, 86.3% achieved at least a very good partial response (≥VGPR) biochemically, but 52.3% remained PET/CT-positive. Baseline >3 focal lesions and EMD significantly predicted persistent PET/CT positivity (p = 0.004). Notably, 50% of patients with ≥VGPR still showed PET/CT-positive findings. At 12 months, 75% of patients who experienced clinical events had been PET/CT-positive at six months, compared with 47.2% of those without events (p = 0.245). The 12-month event-free survival was lower in the PET/CT-positive group (73.9% vs. 90.4%, p = 0.182), though this difference was not statistically significant.

Conclusion: 18-FDG PET/CT can detect residual disease not captured by biochemical markers, highlighting the value of combined assessment in multiple myeloma. Baseline >3 focal lesions and EMD predicted persistent PET/CT positivity. Although PET/CT positivity at six months showed a trend toward worse 12-month EFS, larger studies are needed to confirm its prognostic significance.

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with diverse genetic alterations that influence prognosis and treatment outcomes. Isocitrate dehydrogenase (IDH) genes, particularly IDH1 and IDH2, have emerged as important prognostic biomarkers, but the impact of their mutations on survival remains controversial. This systematic review and meta-analysis aimed to evaluate the prognostic significance of IDH mutations in AML, focusing on overall survival (OS) and relapse-free survival (RFS).

Materials and Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science to identify eligible studies published up to February 2025. Studies reporting associations between IDH mutations (IDH1 and IDH2) and survival outcomes in AML were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted or derived when necessary.

Results: The analysis included 33 studies (n = 17,576). IDH2 mutations were associated with improved overall survival (HR = 0.70, 95% CI: 0.63–0.78) and relapse-free survival (HR = 0.65, 95% CI: 0.52–0.82), particularly in patients treated with IDH inhibitors. IDH1 mutations were associated with worse overall survival (HR = 1.16, 95% CI: 1.07–1.25) but showed no significant effect on relapse-free survival (HR = 1.03, 95% CI: 0.76–1.41). Subgroup analysis revealed a more favorable prognosis for IDH2 R140 mutations, whereas IDH2 R172 mutations showed heterogeneous outcomes across studies and treatment settings.

Conclusion: IDH mutations have a heterogeneous prognostic impact in AML, with IDH2 mutations generally associated with better outcomes than IDH1 mutations. Larger, well-designed studies with comprehensive molecular profiling are needed to further clarify their prognostic implications.

Invasive fungal infections are a leading cause of death in patients with hematological malignancies and those receiving bone marrow transplants. Although standard guidelines exist globally, their direct application in Iran is not always possible due to differences in the types of common fungi and limited diagnostic and therapeutic facilities. To address this challenge, a national committee of experts in the field was formed to carefully review internationally recognized protocols published up to 2024 and solicit opinions from selected experts across the country to develop the first national guideline specifically for prophylaxis. To ensure methodological rigor, the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were utilized. The resulting consensus established a localized risk-stratification model identifying acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and active graft-versus-host disease (GVHD) patients as high-risk, recommending posaconazole as the primary standard. Notably, the guideline advises against routine azole use in acute lymphoblastic leukemia (ALL) to prevent neurotoxicity. Furthermore, a resource-tiered framework was developed for centers with varying diagnostic capabilities. The result of this effort was to present a tiered and local model that provides a practical solution for both well-equipped and limited facilities. The existence of this national guideline creates a major advantage in that treatment approaches are unified and standardized across the country. By eliminating discretionary decisions, this document helps to better manage medication use and ultimately improve patient outcomes, regardless of the city in which they are treated or the facilities they are treated at.

Three-dimensional convolutional neural networks (3D CNNs) have transformed oncology imaging, excelling in tumor detection, classification, segmentation, and prognosis prediction. Unlike traditional two-dimensional CNNs, 3D CNNs effectively analyze volumetric medical imaging data, enhancing spatial feature extraction and diagnostic accuracy across modalities, including CT, MRI, PET, and ultrasound.

This systematic review and meta-analysis evaluates the diagnostic performance and clinical utility of 3D CNNs across 22 studies, of which 11 were eligible for quantitative synthesis. Pooled sensitivity, specificity, and AUC were 0.72, 0.73, and 0.77, respectively, with a diagnostic odds ratio of 10.38, indicating favorable discriminative ability. Subgroup analyses demonstrated superior accuracy in lung cancer and CT-based models, with DenseNet and ResNet architectures outperforming traditional CNNs.

Technical innovations—including multi-modal fusion, spatial context integration, and explainable AI techniques—enhance model robustness and clinician trust. However, substantial heterogeneity (I² > 95%) across studies, attributable to differences in imaging protocols, dataset quality, and model design, underscores the need for standardized methodologies. Persistent challenges include computational demands, annotation variability, and generalization limitations.

Future directions should prioritize the integration of explainable AI, PACS-compatible user interfaces, and federated learning frameworks to bridge institutional gaps. This review highlights the considerable promise of 3D CNNs in advancing precision oncology, while also identifying the infrastructural and methodological refinements necessary for widespread clinical adoption.

Post-HSCT COVID-19 Vaccination in Resource-Limited Settings: Why Adaptation Should Not Mean Compromise

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe toxicoderma characterized by a hypersensitivity reaction to medications, accompanied by eosinophilia and systemic manifestations. Apalutamide, a selective androgen receptor inhibitor approved for the treatment of prostate cancer, has been associated with various dermatological complications. This study aims to document the clinical case of a geriatric patient with stage IV prostate cancer who developed toxicoderma after initiating treatment with apalutamide. An 81-year-old patient with a diagnosis of stage IV acinar adenocarcinoma of the prostate presented with a 15-day history of generalized papular lesions and general malaise, without improvement despite the use of oral antihistamines. The patient reported having started apalutamide four weeks prior.

Physical examination revealed facial edema and erythema, with erythematous and edematous plaques with a desquamative surface covering more than 50% of the body surface. Laboratory results showed eosinophils at 3040 cells/µL and a rise in baseline creatinine from 1.76 mg/dL to 2.4 mg/dL. The RegiSCAR score was 3 points, classifying it as a possible case of DRESS. A skin biopsy revealed a dermoepidermal hypersensitivity reaction with eosinophilic infiltration. The patient improved with oral and topical corticosteroids and the discontinuation of apalutamide. The diagnosis of DRESS was confirmed, and the patient remains under follow-up by the Oncology service. Several medications have been associated with the development of DRESS syndrome. Early recognition allows for the suspension of the causative treatment, thus reducing patient morbidity and mortality. It also facilitates a timely change in oncological therapy in advanced stages, preventing the patient from being left without adequate cancer management.

Patients with acute leukemia are immunocompromised and highly susceptible to infections. Central nervous system (CNS) tuberculoma is a rare but serious complication in this population, particularly among those undergoing treatment for hematological malignancies. Early diagnosis is often challenging due to non-specific symptoms.

We report the case of a 28-year-old female recently diagnosed with CALLA-positive B-cell acute lymphoblastic leukemia, who presented with a two-month history of low-grade fever. Induction chemotherapy was initiated; however, during the third week, she developed new-onset seizures. A computed tomography scan of the brain revealed a heterogeneous ring-enhancing lesion in the right parietal lobe. Magnetic resonance imaging with spectroscopy demonstrated characteristic lipid peaks, supporting the diagnosis of a tuberculoma.

Antitubercular therapy comprising rifampicin, isoniazid, pyrazinamide, and ethambutol, along with pyridoxine and dexamethasone, was commenced. The patient showed a favorable response, with resolution of fever and no recurrence of seizures.

This case underscores the importance of considering CNS tuberculosis in the differential diagnosis of unexplained neurological symptoms and fever in patients with acute leukemia, particularly in tuberculosis-endemic regions. Prompt recognition and treatment can lead to favorable outcomes.