Efficacy and safety of convalescent plasma therapy in severe COVID-19 patients with acute respiratory distress syndrome.

Since SARS-CoV-2 infection is rapidly spreading all around the world, affecting many people and exhausting health care resources, therapeutic options must be quickly investigated in order to develop a safe and effective treatment. The present study was designed to evaluate the safety and efficacy of convalescent plasma (CP) for treating severe cases of COVID-19 who developed acute respiratory distress syndrome (ARDS). Among 64 confirmed cases of severe COVID-19 with ARDS in this study, 32 patients received CP besides first line treatment. Their clinical response and outcome in regard to disease severity and mortality rate were evaluated and compared with the other 32 patients in the control group who were historically matched while randomly chosen from previous patients with the same conditions except for receiving CP therapy. Analysis of the data was performed using SPSS software. Patients with plasma therapy showed improvements in their clinical outcomes including a reduction in disease severity in terms of SOFA and APACHE II scores, the length of ICU stay, need for noninvasive ventilation and intubation and also showed an increase in oxygenation. They also showed reduction in mortality which was statistically significant in less severe cases with mild or moderate ARDS. Early administration of the convalescent plasma could successfully contribute to the treatment of severe COVID-19 patients with mild or moderate ARDS at risk of progressing to critical state.

Interaction of perforin and granzyme B and HTLV-1 viral factors is associated with Adult T cell Leukemia development.

OBJECTIVES: Human T cell leukaemia virus type 1 (HTLV-1) is associated with adult T cell leukaemia (ATL), a malignant lymphoproliferative disease that infects CD4 T cells. It is not clear why the majority of HTLV-1-infected individuals remain asymptomatic carries (ACs) and a minority develop ATL. Cellular immune response has a critical role in ATL and destroys malignant and HTLV-1-infected cells. Perforin and granzyme have important functional roles in apoptosis and destruction of infected cells. In the present study we examined the role of perforin and granzyme in ATL patients and ACs. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from ATL patients and ACs by using Ficoll-hypaque density centrifugation. RNA was extracted and cDNA was synthesized. A real-time PCR TaqMan method was designed and optimized for evaluation of perforin, granzyme, tax, and HBZ gene expression. HTLV-1 proviral load (PVL) was quantified in patients with ATL and ACs. RESULTS: The mRNA expression of tax and HBZ was significantly higher in ATL patients than ACs (P=0.011 and P=0.0001,respectively). The HTLV-1 PVL was higher in ATL patients compared to with AC group (P=0.015). There was a significant increase in perforin gene expression in ACs compared with ATL patients (P=0.002). Furthermore, the expression of granzyme was also higher in ACs compared with ATL patients, and significant differences were observed between the two groups (P=0.036). CONCLUSION: Low expression of perforin and granzyme in ATL patients seems to influence the efficiency of CTL function and destruction of HTLV-1-infected cells, which might contribute to the disease pathogenesis.

Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: In this study, we investigate the effect of hydroxychloroquine on the prevention of Novel Coronavirus Disease (COVID-19) in cancer patients being treated. TRIAL DESIGN: This is a multi-centre, two-arm, parallel-group, triple-blind, phase 2-3 randomised controlled trial. PARTICIPANTS: All patients over the age of 15 from 5 types of cancer are included in the study. Patients with acute lymphoid and myeloid leukemias in the first line treated with curative intent, patients with high-grade non-Hodgkin's lymphoma treated with leukemia protocols and patients with non-metastatic breast and colon cancer in the first line of treatment will enter the study. The exclusion criteria will include known sensitivity to Hydroxychloroquine, weight below 35 kilograms, history of retinopathy, history of any cardiac disease, acute respiratory tract infection in the last 2 months, having COVID-19 in the first two weeks of entering the trial, having Diabetes Mellitus, having an immuno-suppressive disease other than cancer, having chronic pulmonary disease and taking immuno-suppressant drug other than chemotherapeutic agents for current cancer. This study is performed in five academic centres affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. INTERVENTION AND COMPARATOR: Patients are randomly assigned to two groups; one being given hydroxychloroquine and the other is given placebo. During two months of treatment, the two groups are treated with either hydroxychloroquine (Amin® Pharmaceutical Company, Isfahan, Iran) or placebo (identical in terms of shape, colour, smell) as a single 200 mg tablet every other day. Patients will be monitored for COVID-19 symptoms during the follow-up period. If signs or symptoms occur (fever, cough, shortness of breath), they will be examined and investigated with a high-resolution computed tomography (CT) scan of the lungs, COVID-19 specific IgM, IgG antibody assay and a nucleic acid amplification test (NAT) for the SARS-CoV-2 virus. MAIN OUTCOMES: The primary end point of this study is to investigate the incidence of COVID-19 in patients being treated for their cancer over a 2-month period. RANDOMISATION: Randomisation will be performed using randomly permuted blocks. By using an online website (www.randomization.com) the randomization sequence will be produced by quadruple blocks. The allocation ratio in intervention and control groups is 1:1. BLINDING (MASKING): Participants and caregivers do not know whether the patient is in the intervention or the control group. The outcome assessor and the data analyst are also blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 60 patients, with 30 patients in each group. TRIAL STATUS: The trial began on April 14, 2020 and recruitment is ongoing. Recruitment is anticipated to be completed by June 14, 2020 There has been no change in study protocol since approval, protocol version 1 was approved April 12, 2020. TRIAL REGISTRATION: This trial has been registered by the title of "Effect of Hydroxychloroquine on Novel Coronavirus Disease (COVID-19) prevention in cancer patients under treatment" in Iranian Registry of Clinical Trials (IRCT) with code "IRCT20200405046958N1", https://www.irct.ir/trial/46946. Registration date is April 14, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Complete sequence of human T cell leukemia virus type 1 in ATLL patients from Northeast Iran, Mashhad revealed a prematurely terminated protease and an elongated pX open reading frame III.

To gain insight into the origin, evolution, dissemination and viral factors affecting HTLV-1-associated diseases, knowing the complete viral genome sequences is important. So far, no full-length HTLV-1 genome sequence has been reported from Iran. Here we report the complete nucleotide sequence of HTLV-1 viruses isolated from adult T cell leukemia/lymphoma (ATLL) patients from this region. The genome size of HTLV-1-MhD (Mashhad) was found to be 9036 bp and sequence analysis of the LTR region showed that it belongs to cosmopolitan subtype A. Comparing the sequences with isolates from another endemic area (HTLV-1ATK) revealed variations in the U3 region (~3.4%), while there was 99.1% and 97.0% similarity in R and U5 regions, respectively. The nucleotide sequences of HTLV-1 gag, pro and pol genes had a difference of 1.1% compared with HTLV-1 ATK with 16 nucleotides replaced in the gag and 27 in the pol regions. There was no variability in the amino acid sequences in the p24gag, however three residues were different in the p19gag and one in the p15gag. The nucleotide sequence of env showed a divergence of 1.5% compared to ATK with 22-nucleotide variation. The HTLV-1-MhD Tax, p13, p30, and p12 had 99.1, 100, 98.8, and 98%, respectively similarity with the prototype strain. Four amino acid changes were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. The nucleotide identity between the isolates of Mashhad and those isolated from France, Germany, China, Canada and Brazil was 99.1%, 99.2%, 97.9%, 99% and 99.3%, respectively. Four amino acid changes compared with HTLV-1ATK from Japan were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. This data could provide information regarding the evolutionary history, phylogeny, origin of the virus and vaccine design.

Bilateral Conjunctival Infiltration as an Extramedullary Relapse of AML.

Acute myelogenous leukemia (AML) accounts for 1.2% of all cancer deaths. Relapse is the major cause of treatment failure in acute myeloid leukemia (AML) patients. AML rarely presents as ocular manifestation in relapse or at presentation. The M4 subtype of AML is most commonly presented with extramedullary involvement. In this report, we presented a young female with AML who was diagnosed and treated for AML about 40 months ago. She did not transplant because she did not have a full-match donor. About 4 months ago, she visited with a red eye and conjunctival infiltration. She was referred to an ophthalmologist for a biopsy, and the pathology report showed the relapse of AML which was treated with systemic chemotherapy. Red eyes with subconjunctival nodules in patients with a history of previous AML should raise the suspicion for recurrent disease that warrants urgent biopsy and systemic treatment. Eye involvement with leukemia is usually responsive to systemic chemotherapy.

Diet and non-Hodgkin's lymphoma risk.

BACKGROUND: The role of dietary factors in the epidemiology of Non-Hodgkin's lymphoma (NHL) remains largely undefined. Dietary habits may play a role in the etiology of NHL by influencing the immune system. METHODS: Dietary patterns and the risk of NHL were analyzed in a case control study; including 170 NHL cases and 190 controls. All subjects completed a validated food-frequency questionnaire. The dietary pattern was investigated separately and in nine nutritional groups. Crosstab tables were used to estimate the odds ratios (OR), and P(trend). RESULTS: Consumption of highest versus lowest quartile of proteins (OR, 8.088 P(trend)=0.000), fats (OR, 6.17 P(trend)=0.000) and sweets (OR, 8.806 P(trend)=0.000) were associated with a significantly increased NHL risk. The inverse association was found for fresh fruits (OR, 0.117 P(trend)=0.000) and vegetables (OR, 0.461 P(trend)=0.010). CONCLUSION: An association between dietary intake and the risk of NHL is biologically plausible due to immunosuppressive effects of fat and animal proteins, and antioxidant properties of vegetables and fruits.

Chronic lymphocytic leukemia and prognostic factors.

BACKGROUND: The clinical course of individual chronic lymphocytic leukemia (CLL) is highly variable and clinical staging systems do not help us to predict if and at what rate there will be disease progression in an individual patient diagnosed with early stage disease. Recently, several important observations related to other prognostic factors including lymphocyte doubling time (LDT), ß2-microglobulin (ß2-MG), and percent of smudge cell in peripheral blood smears, cytogenetic and molecular analysis have been made. The aim of this study was to evaluate a range of prognostic factors in our CLL patients. DESIGN AND METHODS: Seventy patients with CLL were enrolled. Prognostic factors of disease including Binet staging, LDT, ß2-MG, ESR, LDH, percent of smudge cell in peripheral blood smear, absolute lymphocyte count, and conventional cytogenetic (CC) analysis were evaluated at diagnosis, and the patients were followed up to determine their outcome. We compared factors with each other and with Binet staging and prognosis. RESULTS: Enrolled patients aged 37-85 years at diagnosis or during follow up. There was no relationship between serum LDH level (P=0.3), ESR (P=0.11), percent of smudge cells in peripheral blood smear (P=0.94), and absolute lymphocyte count (P=0.18) with the stage of disease and prognosis, but the ß2 macroglobulin level (p<0.0001), LDT (p<0.001) had direct and significant relation with staging and outcome. In 19% of patients cytogenetic alteration were seen. CONCLUSION: The detection of cytogenetic alteration only using the CC method is not sufficient and we need to use FISH, but because FISH study is an expensive method not available in all areas, we believe that ß2 MG can be applied in its place as a good prognostic factor for CLL at diagnosis and during follow up. We suggest to add it to Binet staging for prognostic subgrouping of CLL.

Iron Balance in Regular Blood Donors.

SUMMARY: BACKGROUND: Numerous reports have shown that iron stores decrease in blood donors after donation. As we need healthy donors, it is essential to test hemoglobin and ferritin levels for preventing reduced of iron stores in donors. METHODS: This study was conducted on 235 healthy men. The donors were divided into three groups: group I) control group with no donation; group II)  case group 1 with two donations within 1 year; group III)  case group 2 with three donations within 1 year. RESULTS: The mean level of hemoglobin was 15.9 and 14.7 g/dl in the control group and in the case group, respectively (p < 0.0000). The mean level of serum ferritin in group I, II and III, was 108, 56 and 26 µg/l, respectively (p < 0.0000). When studying various stages of iron deficiency in donors, it could be shown that 58% of group III donors but only 1% of control group donors had a negative iron balance. Moreover, iron deficiency anemia was observed in 20% of group III donors. CONCLUSION: Just measuring the hemoglobin level is not sufficient for selecting donors. In addition, testing of the ferritin level and iron supplementation are recommended in regular donors with more than one donation per year.