Clinicopathological Features of Hereditary Nephritis in the Iranian Population: Analysis of a 14-Year Survey in Kidney Biopsies From a Large Referral Center.

BACKGROUND: Hereditary nephritis (HN), including Alport syndrome (AS) and thin basement membrane nephropathy (TBMN), is a rare genetic cause of hematuria. A definitive diagnosis requires electron microscopy (EM). Therefore, the clinical characteristics of these conditions are less known. This study aimed to determine the percentage and clinicopathological features of HN in patients from a referral center in Iran. METHODS: We checked kidney biopsy reports from 2007 to 2021 and extracted cases with HN. Fresh specimens of the cases diagnosed in the last two years were stained by immunofluorescence (IF) for collagen type IV alpha chains. EM findings in these cases were re-evaluated and categorized as diffuse glomerular basement membrane (GBM) thinning, definite, and suspicious features of AS. RESULTS: We analyzed 3884 pathology reports of kidney biopsies from 2007 to 2021 and identified 210 patients (5.4%) with HN, with a mean age of 13.78±12.42 years old. Hematuria with proteinuria (53.3%), isolated hematuria (44.2%), and proteinuria with hematuria and increased creatinine (2.5%) were found in these patients. The re-evaluation of EM findings revealed GBM thinning, definite, and suspicious findings of AS in 37.5%, 43.8%, and 18.8% cases, respectively. The most common diagnosis in 32 cases after the IF study was X-linked AS (71.9%), and 6.2% of cases were autosomal recessive AS. TBMN and autosomal dominant AS remained the differential diagnoses in 21.9%. CONCLUSION: It was found that EM is helpful for the primary diagnosis of patients with definite AS. Immunostaining improves the diagnostic sensitivity for the differentiation of those with suspicious EM findings and determines the inheritance pattern. However, a multidisciplinary approach for a subset of cases is required for the best diagnosis and management.

Evaluation of C4d expression and staining patterns by immunohistochemistry in renal biopsy samples with focal segmental glomerulosclerosis and minimal change disease.

INTRODUCTION: C4d is an activation product of lectin pathway of complement. Glomerular deposition of C4d is associated with poor prognosis in different types of immune-related glomerulonephritis. The present study was conducted to investigate expression level of C4d and its staining pattern in renal biopsy of patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) by immunohistochemistry method. MATERIALS AND METHODS: In this retrospective cross-sectional study, renal biopsy specimens from 46 samples of MCD, 47 samples of FSGS, and 15 samples without glomerular disease as the controls, were subjected to immunohistochemistry staining with C4d. Demographic characteristics and information obtained from light and electron microscopy (EM) of patients were also extracted from their files. RESULTS: C4d positive staining was observed in 97.9 % of FSGS and 43.5 % of MCD samples, which showed a statistically significant difference (P < 0.001). The sensitivity and specificity of C4d expression for diagnosing FSGS were 97.9 % and 56.5 %, respectively. There was no significant correlation between C4d expression and any of the light and electron microscopy findings, including presence of foam cells, mesangial matrix expansion, interstitial fibrosis and tubular atrophy, and basement membrane changes in MCD patients. Also, no significant correlation was observed between C4d expression and clinical symptoms of proteinuria or prolonged high level of creatinine in patients with MCD. DISCUSSION AND CONCLUSION: The expression of C4d marker had a good sensitivity and negative predictive value in the diagnosis of FSGS.

Analysis of Prevalence and Trends in the Biopsy-Proven Native Kidney Diseases in Iranian Population: A 12-year Survey from a Referral Center.

Background & Objective: The prevalence of glomerular diseases, as the leading cause of chronic kidney disease, is increasing. Renal biopsy is still the gold standard for diagnosis of the most kidney disorders. Data on prevalence of the biopsy-proven kidney diseases in Iran is limited and none of the previously reported studies used electron microscopic (EM) evaluation for the diagnosis. This study was conducted to analyze the prevalence of biopsy-proven kidney diseases in a referral center in Iran. Methods: The reports of kidney biopsy samples from 2006 to 2018 referred to a pathology center, affiliated with Tehran University of Medical Sciences were reviewed. The prevalence of different disorders was assessed based on the clinical presentation in 3 age categories, including childhood, adulthood, and elderly. Results: Among 3455 samples, 2975 were analyzed after excluding transplant-related specimens, suboptimal specimens, and those with uncertain diagnoses. Nephrotic syndrome (NS) (39%) was the most common cause of biopsy followed by subnephrotic proteinuria (18%), hematuria in association with proteinuria (15%), renal failure (9%), isolated hematuria (6%), lupus (4%) and the other non-specific manifestations such as hypertetion or malaise (each one less than 2%). The most common diagnoses included membranous nephropathy (MGN) (17.9%), focal segmental glomerulosclerosis (FSGS) (15.9%), lupus nephritis (LN) (13.7%), minimal histopathological findings (unsampled FSGS versus Minimal Change Disease, 12.1%), Immunoglobulin-A (IgA) nephropathy (6.5%) and Alport syndrome (6.1%). MGN was the most frequent disease before 2013, but FSGS became more frequent after that. Conclusion: NS and proteinuria were the most indications for kidney biopsy. Although MGN was the most common disease, the prevalence of FSGS has been increasing in recent years and making it the most common disease after 2013. LN and IgA nephropathy are the most common causes of secondary and primary GN presenting with proteinuria and hematuria, respectively.

Spectrum and Distribution of Biopsy-proven Kidney Diseases: A 12-year Survey of a Single Center in Iran.

Data about the prevalence of biopsy-proven kidney diseases in Iran are rare, and none of the previous studies used electron microscopy for diagnosis. This study aimed to analyze the prevalence of biopsy-proven kidney diseases in Iran's primary referral center. To the best of our knowledge, this is the most extensive study carried out in Iran. Reports of kidney biopsy samples from patients referred to our center in 2007-2018 were reviewed for demographic data, clinical presentation, and final diagnosis. Statistical analyses were performed. Among the 3455 samples received, 2975 were analyzed. Nephrotic syndrome (39%) was the most common cause of biopsy, followed by subnephrotic proteinuria (18%), hematuria in association with proteinuria (15%), renal failure (9%), isolated hematuria (6%), and lupus nephritis (LN) (4%). The most common diagnoses were membranous glomerulonephritis (17.9%), focal segmental glomerulosclerosis (FSGS) (15.9%), LN (13.7%), minimal histopathological findings (unsampled FSGS vs. minimal change disease, 12.1%), Immunoglobin A nephropathy (IgAN) (6.5%) and Alport syndrome (6.1%). NS and proteinuria were the most common indications for a kidney biopsy. IgAN and LN were the most common causes of primary and secondary glomerulonephritis, presenting with hematuria and proteinuria, respectively. Although membranous glomerulonephritis was the most common disease, it has been replaced by FSGS in recent years.

Frequency and Underlying Causes of Alloimmunization Against Red Blood Cell Antigens in Patients Referred to the Blood Bank of the Tertiary Referral Hospital of Tehran from 2018 to 2020.

BACKGROUND: Alloimmunization against blood group antigens is an important non-infectious complication of blood transfusion, and early detection of these alloantibodies by antibody screening before transfusion is crucial. Identifying which underlying factors will affect the occurrence of alloimmunization will be necessary to manage this event as accurately as possible. We aimed to assess the prevalence rate and main determinants of RBC alloimmunization among patients referred to a large referral blood bank in Iran. METHODS: This retrospective cross-sectional study was conducted on all patients referred to a blood bank at Imam Khomeini Hospital between October 2018 and September 2020. Information was collected by referring to the archives of the hospital information system as well as the documents recorded at the blood bank ward and reviewed by two pathologists and completed documents. RESULTS: In total, 39270 cases were cross-matched. Accordingly, the frequency of alloimmunization cases was equal to 220 cases, which indicated a prevalence of 0.56%. The most common alloantibodies were anti-K (43.2%, 95% CI: 36.8‒49.5), anti-E (34%, 95% CI: 27.7‒40.5), and anti-C (16.3%, 95% CI: 11.4‒21.4). Among patients with positive alloimmunization, the most common blood groups were blood group B (34.6%), followed by blood group A (34.1%). Most of these patients were Rh-positive (77.3%). In patients with positive alloimmunization, the frequency of hemoglobinopathy was estimated to be 37.7%. Frequent blood transfusions were found in 42.2%, a history of malignancy in 17.3%, graft history in 11.3%, and a history of pregnancy in 35.0%. CONCLUSION: Alloimmunization was more prevalent and more predictable among patients with hemoglobinopathies and those receiving recurrent transfusions. Therefore, a history of repeated blood transfusions should be regarded as a risk factor contributing to alloimmunization.

Crescentic Glomerulonephritis, A Rare Presentation of Alport Syndrome.

Crescentic glomerulonephritis (GN) is a feature of severe glomerular injury. Anti-GBM disease, immune-complex mediated glomerulonephritis, and ANCA-associated vasculitis are the main causes of crescentic GN. Alport syndrome is a progressive form of hereditary nephritis presenting with hematuria and progression to proteinuria and renal failure. Herein we present a 16-year-old male with rapidly progressive glomerulonephritis syndrome, sensory-neural hearing loss, and a family history of hematuria and proteinuria in his mother and aunt. Light microscopic examination shows cellular crescent in glomeruli. In an electron microscopy study, GBM changes compatible with Alport syndrome were identified. Alport syndrome rarely can be presented as crescentic GN. Electron microscopy is necessary for the diagnosis of this type of pauci-immune crescentic glomerulonephritis.

The role of saliva PCR assay in the diagnosis of COVID-19.

INTRODUCTION: The introduction of a self-collection sampling method with less discomfort would be of great benefit in reducing the risk of medical provider's contamination and patient's acceptance. The aim of the present study was to investigate saliva samples' diagnostic performance for the COVID-19 RT-PCR test compared to pharyngeal swabs. METHODOLOGY: From individuals referred to a medical center with presentations compatible with COVID-19 who were eligible for molecular diagnostic tests, 80 cases were selected. Nasopharyngeal and oropharyngeal swabs (placed into the same transport tube) along with self-collected saliva sample were taken from each participant for COVID-19 RT-PCR assay. The results of pharyngeal swabs and saliva sample were compared. RESULTS: Sixty-two (78%) infected cases were detected, of whom 31 (39%) cases tested positive for both pharyngeal swab and saliva samples. 24 (30%) and 7 (9%) cases tested positive only for pharyngeal or saliva samples, respectively. The overall percentage of agreement between pharyngeal swab and saliva sample was 61%, with a kappa value of 0.24 (p-value = 0.019, 95% CI: 0.04-0.44), showing a fair level of agreement. The diagnostic sensitivity of pharyngeal swabs was 88.71% (95% CI: 78.11-95.34), and the diagnostic sensitivity of saliva samples was 61.29% (95% CI: 48.07-73.40). Compared to pharyngeal swabs (oropharyngeal and nasopharyngeal swabs in the same collection tube), an important observation was that seven more positive cases were detected among saliva samples. CONCLUSIONS: The findings of the present study indicated that self-collected saliva samples cannot replace pharyngeal swabs. Still, saliva samples significantly increased the case detection rate and can be used along with pharyngeal swabs.

The Performance of SARS-CoV-2 Serology Testing in the Diagnosis of COVID-19.

BACKGROUND & OBJECTIVE: COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) has been a reference test for diagnosing a disease since the very beginning of the pandemic. COVID-19 serology tests have also been developed and used to estimate the prevalence of individuals who have already been infected. We aimed to evaluate the performance of serology tests for the diagnosis of patients who had been referred to medical centers with acute symptoms. METHODS: In this cross-sectional study, 80 individuals suspected of COVID-19 who had been referred to Imam Khomeini Hospital Complex, Tehran, Iran, were examined. Upper respiratory tract specimens for RT-PCR and blood samples for COVID-19 IgM and IgG antibody level tests were collected and the results were compared. RESULTS: The overall proportion in agreement, the agreement between positive results, and the agreement between negative results when comparing RT-PCR and IgM serology test were 40% (kappa = -0.006, P = 0.9), 32%, and 66.6%, respectively, and when comparing RT-PCR and IgG serology test were 46% (kappa = -0.006, P = 0.94), 43.5%, and 55.5%, respectively. CONCLUSION: The absence of a gold standard method for the diagnosis of COVID-19 makes it very challenging to determine the true sensitivity and specificity of different methods. The study results revealed no agreement between the two methods; so the RT-PCR test for upper respiratory tract specimen cannot be replaced with COVID-19 serology test for the diagnosis of patients with acute symptoms.

Is There A Correlation Between COVID-19 and Hepatitis A and Hepatitis E Serum Antibody Level?

BACKGROUND & OBJECTIVE: The prevalence of COVID-19 and its severity have been observed to be on a lower level in underdeveloped countries with poorer standards of hygiene. This disparity may be attributed to the higher seroprevalence of other viral diseases, which can result in the presence of antibodies protective against COVID-19. Two of the widespread diseases in such countries are infection to hepatitis A and E viruses (HAV and HEV). In the present study, we explored the relationship between the level of antibodies against these viruses and the susceptibility to COVID-19. METHODS: Ninety patients were studied in two groups of controls and cases, each consisting 45 individuals. The cases were patients with the clinical symptoms of COVID-19 and positive RT-PCR test results. The controls were individuals referred to the respiratory triage of Imam Khomeini Hospital Complex and were not demonstrating relevant clinical symptoms of COVID-19 and their RT-PCR test results were negative. Levels of HAV and HEV antibodies were measured and compared in these two groups. RESULTS: The median of HAV antibody level was 13.6 (IQR=11.5-16.9) and 13.2 (IQR =10.7-14.7) in cases and controls, respectively, showing no statistically significant difference (P=0.1). Likewise, the median of HEV antibody level was 6.7 (IQR=5.3-7.1) and 7.1 (IQR=6.3-7.5) in cases and controls, respectively, which again showed no statistically significant difference (P=0.41). CONCLUSION: The present study was carried out in a region with a relatively high prevalence of HAV and HEV infections. Contrary to our expectations, no statistically significant relationship was observed between the levels of antibodies against these viruses and the susceptibility to COVID-19. Further studies with larger sample sizes and in other countries are needed to come to a definite conclusion.

Low-dose whole-lung irradiation in severe COVID-19 pneumonia: a controlled clinical trial.

INTRODUCTION: The COVID-19 pandemic has caused significant morbidity and mortality thus far. Considering the historical uses of high-voltage X-ray beams for unresolvable pneumonia, we aimed to assess whether low-dose whole-lung irradiation (WLI) could provide any benefits for patients with refractory COVID-19 pneumonia. METHODS: Eleven patients with refractory COVID-19 pneumonia were treated with WLI to a total dose of 1 Gy and compared to 11 patients in a matched control group from June to November 2020. The study's primary endpoint was improvement of chest X-ray severity score (CXRS), followed by changes in mean oxygen (O2) saturation and 28-day mortality as secondary endpoints. RESULTS: The final CXRS was significantly lower in the WLI group (8.7 ± 2.5) compared to the control group (12.3 ± 3.3) (P: 0.016). Change of CXRS from the first to the last chest X-ray was -2.2 ± 3.1 for the WLI group and 0.7 ± 3.9 for the control group, which showed a trend for lower CXRS in the WLI group (U = 30, p: 0.085). Mean O2 saturation showed insignificant improvement in the first 24 hours after radiotherapy (mean difference: 2.5 ± 4.1, Z=-1.6, P value: 0.11). Overall survival after 28 days was 32% in the WLI group and 11% in the control group (P: 0.48). The reason for death in many patients was not merely respiratory failure, but also other adverse situations like pneumothorax, cardiogenic shock and pulmonary thromboembolism. CONCLUSIONS: Low-dose WLI could improve the CXR severity score and O2 saturation in severely ill COVID-19 patients, but larger studies are required to determine its impact on mortality.

Mesonephric Adenocarcinoma of Uterine Cervix: A Case Report and Review of the Literature.

Mesonephric adenocarcinoma of the uterine cervix is an extremely rare tumor of the female genital tract which derives from the remnants of embryonic mesonephric ducts and its prognosis, diagnosis and treatment is rather challenging. We report a case of a 46-year-old woman with history of abnormal uterine bleeding and an enlarged uterine cervix on physical examination without obvious mass lesion. She was clinically underdiagnosed with cervical myoma and mesonephric hyperplasia. After simple hysterectomy, stage IB2 mesonephric adenocarcinoma was diagnosed. Despite adjuvant chemoradiation, she presented with peritoneal and locoregional recurrence in less than a year. So, in the presence of abnormal bleeding and cervical mass, mesonephric hyperplasia in cervical biopsy specimen should be suspected for adenocarcinoma. Radical hysterectomy and complete staging with or without salpingo-oophorectomy is the mainstay of treatment. Despite all ambiguities, due to the small number of reported cases, the overall prognosis seems to be less favorable than conventional cervical adenocarcinoma.

Measles and rubella serosusceptibity among population vaccinated with different schedules: the potential impact on measles-rubella elimination in Iran.

BACKGROUND: Iranian children were vaccinated with the scheduled two doses of monovalent measles vaccine (mMV) from 1984. In December 2003, a nationwide campaign of measles-rubella (MR) immunization was established to vaccinate 5-25 year- old individuals. In 2004, the mMV was replaced with measles- mumps- rubella (MMR) vaccine. Despite the high vaccination coverage, the outbreaks of measles still occur in the country. In this Study, the MR immunity status of various age groups, vaccinated with different schedules was investigated, and the immunologic response of seronegative subjects to revaccination was examined. METHODS: This cross-sectional study was conducted among 7-33-year-old healthy individuals with a documented history of measles vaccination from November 2017 to June 2018. The subjects were categorized as follows: group A, including 20-33 year-old individuals; vaccinated with 1-2 doses of mMV at ages 9 and 15 months, and revaccinated with MR, group B, including 15-19-year-old individuals, vaccinated with two doses of mMV at 9 and 15 months of age, and received additional dose of MMR upon school entrance, group C, including 11-14 year-old individuals, vaccinated with two-doses of MMR at the ages of 15 months and 6 years, and group D, including 7-10 year-old individuals vaccinated with two-doses of MMR vaccine at the ages 12 and 18 months, respectively. Levels of antimeasles- antirubella IgG antibodies in the collected sera were measured. Also antimeasles- antirubella IgM and IgG of seronegative individuals were reexamined at 4-6 weeks after MMR revaccination. The collected data were analyzed using descriptive statistical methods. RESULTS: A total of 635 individuals were investigated in this study. Group A, 98; group B, 295; group C, 139; and group D, 103 persons. Overall, 12.3 and 18.4% of the population were seronegative for measles and rubella antibodies. This rate varied greatly between the 4 groups: group A, 0/0-2%; group B,15.2-25.0%; group C,11.5-17.2%; and groupD,14.6-18.4%. After revaccination, 92 and 94.9% of seronegative individuals showed IgG response to measles and rubella vaccines, respectively. CONCLUSION: Despite the high coverage rate of M-R containing vaccines, a significant number of vaccinated subjects were seronegative for measles and rubella, possibly because of secondary vaccine failure; this may negatively affect measles-rubella elimination targets in the country. If these findings are confirmed in similar future studies, a more robust regional/national supplementary immunization activity will be considered.

Short-course versus long-course neoadjuvant chemoradiotherapy in patients with rectal cancer: preliminary results of a randomized controlled trial.

PURPOSE: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. MATERIALS AND METHODS: Patients in group I received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/m2 from day 1-5 twice daily and oxaliplatin 50 mg/m2 on day 1 once daily). Patients in group II received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/m2 twice daily. Both groups underwent delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. RESULTS: In this preliminary report on complications and pathological response, 66 patients were randomized into study groups. Mean duration of radiotherapy in the two groups was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the short-course and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). CONCLUSION: For patients with rectal cancer located 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.

Outcomes of Neoadjuvant Chemoradiation in Patients with Gastro-esophageal Junction Adenocarcinoma: a Retrospective Cohort Study in Iran.

PURPOSE: The optimal treatment for locally advanced GEJ and cardia adenocarcinoma is controversial. Several studies have shown that treating these patients with neoadjuvant chemoradiotherapy followed by surgery leads to survival benefits, and there are also studies that have declared conflicting results. It seems that there is still room for discussion. We calculated the survival rates and pathologic responses in our patients with characteristics which we mentioned above. METHODS: Patients with locally advanced, non-metastatic GEJ and cardia adenocarcinomas (only patients with Siewert's type I and II), who were referred to Imam Khomeini hospital (Institute of cancer) between 2005 and 2014 and received neoadjuvant chemoradiation and underwent surgery were enrolled in this retrospective cohort study. Evaluations were done every 3 months. RESULTS: Thirty-two patients enrolled in this study. Median follow up time was 23 months (Reverse Kaplan-Meier method). The rates of 1-year survival, 2-year survival, 3-year survival, 4-year survival, and 5-year survival were 75%, 52%, 52%, 37%, and 37%, respectively. No local recurrences occurred among patients; however, four patients experienced distal recurrence in the following locations: two cases (6.3%) in the liver, one case (3.1%) in the lung, and one case (3.1%) in the peritoneum. The rate of complete pathologic response (T0N0) was 21.9%. CONCLUSIONS: Neoadjuvant chemoradiation in patients with locally advanced GEJ and cardia adenocarcinoma will lead to a survival benefit.

Lipomatous Angiomyofibroblastoma of the Vulva: Report of a Rare Variant.

Angiomyofibroblastoma is a rare and benign tumor that usually involves vulvovaginal area in women of reproductive age and early menopause. We report a lipomatous angiomyofibroblastoma in a 55-year-old multigravid woman. This tumor measured 9 cm in size and contained prominent mature adipose tissue that comprised approximately 50% of the tumor.