Causes of Erythropoiesis-Stimulating Agent Resistant Anemia in Children with Chronic Kidney Disease at a Tertiary Hospital

PBackground and Aim: Routine clinical and laboratory assessments facilitate the diagnosis of erythropoietin (EPO) resistant anemia. Resistance to erythropoietin (EPO) rarely occurs in children with chronic kidney disease (CKD). It may be caused by several factors, such as poor compliance, hyperparathyroidism, malnutrition, inadequate dosages, and medication. This study was conducted to evaluate the frequency and causes of EPO resistant anemia in CKD children.Methods: This observational retrospective study was performed in Ali Asghar Children’s Hospital in 2008. Children who were treated by EPO and still had hemoglobin concentrations (Hb) below 10 g/dl or required very high erythropoietin doses (more than 150 IU/kg/week) were considered as EPO resistant anemic cases. Therefore, their data including demographic data, EPO dosage, medications, underlying diseases, mode of dialysis, and lab test results were collected from their medical records.Results: The Hb concentration was below 8 g/dl in eight cases (40%). The male to female ratio was 1.66 and the median age was 7.9 years old. The median hemoglobin concentration was 6.25 g/dL. Three patients (37.5%) were true cases of resistance in EPO (two patients had bone marrow fibrosis due to hyperparathyroidism and one had EPO Ab) while five cases (62.5%) received inadequate doses of EPO (anemia improved upon an acceptable EPO dosage).Conclusion: True resistance to erythropoisis stimulatin agent is not frequent and because of there are heterogeneous causes for Lack of appropriate response to EPO, so full investigation is needed especially complete history to find the underlying reason. Keywords: Anemia; Chronic Kidney Disease; Erythropoietin

Assessment of Effectiveness and Adverse Effect of New Combination Chemotherapy (irinotecan, cisplatin, and dexamethasone) in Relapse and Refractory Hodgkin Lymphoma

Background: Chemotherapy with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD regimen) cannot cure all patients with Hodgkin lymphoma. In this study, we evaluated the efficacy and adverse effect of a new regimen consist irinotecan, cisplatin, and dexamethasone (ICD) in relapsed and refractory Hodgkin lymphoma as the second to fifth line of treatment. Materials and Methods: We performed a retrospective study in 26 relapsed or refractory patients with Hodgkin lymphoma receiving at least the first-line chemotherapy regimen (ABVD) and (ICD) as salvage therapy in Thaleghany Hospital from 2012 to 2018. This regimen consisted of irinotecan 65mg/m2 D1, D8, cisplatin 30mg/m2 D1, D8, and dexamethasone 40mg D1, 2, 8, and 9 was administered every 3 weeks for 6 cycles.  Treatment was discontinued in cases of disease progression or severe toxicity. Response to treatment was evaluated after two cycles. Patients with complete and partial remission were candidate high dose chemotherapy and autologous stem cell transplantation. Twenty-four patients were enrolled in the study. The mean age of 22 patients was 31.5 (19-67) years. Seven patients (29.1%) were in the first recurrence, and 17 (70.8%) were in the second or subsequent recurrence. Results: According to this study, three patients (12.5%) had complete response, 13 (45%) had partial response, four (16.6%) had stable disease, and four (16.6%) had progressive disease. Nine patients (37.5%) received high-dose chemotherapy and autologous stem cell support after ICD regimen. None of the cycles of chemotherapy were delayed due to treatment-related adverse event. Overall survival after six months in all patients was 91%, and mortality rate was 8.3% at the end of the study. Conclusion: The goal of salvage chemotherapy in relapsed or refractory Hodgkin Lymphoma is achieving CR or PR preparation patients for stabilization with BMT. Thus, we recommend ICD as one of the most effective protocols with overall response rate of 66% in this population.  

Semi-quantitative Detection of Pseudouridine Modifications and Type I/II I/Ii Hypermodifications in Human mRNAs Using Direct Long-Read Sequencing

Here, we develop and apply a semi-quantitative method for the high-confidence identification of pseudouridylated sites on mammalian mRNAs via direct long-read nanopore sequencing. A comparative analysis of a modification-free transcriptome reveals that the depth of coverage and specific k-mer sequences are critical parameters for accurate basecalling. By adjusting these parameters for high-confidence U-to-C basecalling errors, we identify many known sites of pseudouridylation and uncover previously unreported uridine-modified sites, many of which fall in k-mers that are known targets of pseudouridine synthases. Identified sites are validated using 1000-mer synthetic RNA controls bearing a single pseudouridine in the center position, demonstrating systematic under-calling using our approach. We identify mRNAs with up to 7 unique modification sites. Our workflow allows direct detection of low-, medium-, and high-occupancy pseudouridine modifications on native RNA molecules from nanopore sequencing data and multiple modifications on the same strand