C oronavirus disease is a novel infectious disease that primarily manifests as an acute respiratory syndrome but can also cause multiorgan dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been documented to cause vasoocclusive crisis and acute chest syndrome in patients with sickle cell anemia (1). We report another potentially major complication of infection in a patient with a common enzymatic disorder. Glucose 6-phosphate dehydrogenase (G6DP) deficiency is an X-linked enzymatic disorder that affects 400 million persons worldwide and has a high prevalence (5%-20%) in African and Asian populations (2). G6DP catalyzes the formation of nicotinamide adenine dinucleotide phosphate (NADPH) (3). NADPH maintains hemoglobin in the ferrous state by forming reduced glutathione, which prevents oxidative damage (3). G6DP deficiency increases the risk for intravascular hemolysis upon exposure to oxidative agents, such as fava beans, sulfonamides, and hydroxychloroquine, the subject of clinical trials for persons with SARS-CoV-2 infection. G6PD deficiency can induce methemoglobinemia by inhibiting NADPH-flavine reductase, which prevents the reduction of methemoglobin. Methemoglobin is unable to bind to oxygen, and the remaining oxyhemoglobin develops heightened oxygen affinity and diminished delivery, leading to tissue hypoxia (4). Viral infections, including HIV, hepatitis viruses (A, B, and E), and cytomegalovirus, can precipitate intravascular hemolysis in patients with G6PD deficiency (5,6). Concurrent methemoglobinemia has also been reported in the context of viral-induced hemolysis (5). RESEARCH LETTERS During the coronavirus disease pandemic in Spain, from April 10-24, 2020, a total of 5,869 persons were screened for severe acute respiratory syndrome coronavirus 2 at nursing homes. Among residents, 768 (23.9%) tested positive; among staff, 403 (15.2%). Of those testing positive, 69.7% of residents and 55.8% of staff were asymptomatic.
Aims: Cytokeratin(CK) based real-time RT-PCR assays (QRT-PCR) are now available for peripheral blood circulating tumor cell (CTC) evaluations in colorectal cancer(CRC) patients. Results are non-existent for the application of these techniques to the determination of progression and therapy response in Dukes stage D CRC patients.
Patients and methods: Each month 30 ml peripheral blood of 30 Dukes D patients (17 with progression) were drawn. CEA, CA19-9, CA72-A and TPA-M determinations were made. CK20, thymidilate synthase(TS) QRT-PCR was performed, as well. Buffy coat was used for immunmagnetic cancer cell isolation and CTC counting. Correlation between elevated CTC and macroscopic progression within 3 months was determined by Chi2 test.
Results: Microscopic CTC single cell, doublet, cluster number were found in correlation with CK20 QRT-PCR results (p <
0.01). There was a significant increase in microscopic CTC number, CK20 and decrease in TS QRT-PCR levels (p < 0.05) in
the peripheral blood of the non-responder as compared to responder patients. Elevation of the CTC was in significant correlation
with macroscopic progression of the disease in 3 months (p < 0.01).
Conclusions: CTC number reflects the chemotherapeutic sensitivity of CRC patients. Elevation of circulating tumor cell number in peripheral blood is in correlation with macroscopic progression.
Several tumor-associated antigens (TAAs) were recently identified, that could qualify as targets for immunotherapy, they could qualify (on RNA-level) for monitoring of tumor load. Here, we studied the expression levels of the immunogenic antigens PRAME (preferentially expressed antigen of melanoma), WT1 (Wilms’ tumor gene), and PR3 (proteinase 3) on myeloid blasts by real-time quantitative polymerase chain reaction and correlated these data to the state and course of disease and to the defined subgroups of acute myeloid leukemia (AML). At first diagnoses, 41 of 47 patients tested showed overexpression of PRAME (87%), 38 of WT1 (81%), and 26 of PR3 (55%), with the highest expression levels for PRAME (2048-fold), followed by WT1 (486-fold) and PR3 (196-fold). Thereby, with 70%, the most frequent combination at first diagnoses was detected to be PRAME and WT1 (33/47 patients). Overall, 21 patients (45%) revealed overexpression for all 3 TAAs. Moreover, the highest expression levels of PRAME were found to be correlated with the FAB subtype M5, cytogenetic unfavorable risk groups, and AMLs arising from myelodysplasia (secondary AML; P=0.02). To compare TAA expression levels in the course of disease, expression data were calculatory adjusted to 100% blasts, revealing a relative increase in the PRAME expression levels during the course of persistent disease (3/4 cases). Independent of stage of disease, by trend, higher TAA expression levels were found on blasts derived from peripheral blood than those derived from the bone marrow. In conclusion, it is suggested that vaccine strategies for cancer immunotherapy should comprise different TAA peptides anticipating the diverse TAA expression levels on blasts evolving during the course of disease or treatment.
Chronic Kidney Disease (CKD) is a frequent complication in patients with multiple myeloma (MM) and is associated with adverse outcomes. The use of autologous stem cell transplantation (ASCT) has improved disease outcomes, however, the safety and efficacy of ASCT in patients with CKD has been the subject of debate. To investigate this, we conducted a retrospective analysis of 370 MM patients who underwent their first ASCT, including those with mild, moderate and severe CKD as well as normal renal function at the time of transplant. No significant difference in ASCT-related mortality, Progression-Free or Overall Survival was noted between the different renal function groups. A decline in estimated glomerular filtration rate (eGFR) at 1-year of >8.79% was associated with poorer overall survival (p < 0.001). The results of this study show that ASCT is a safe and effective option for myeloma patients with CKD, including those on dialysis. Patients who demonstrate renal deterioration at 1-year post-transplant should be closely monitored as this is a predictor for poor survival.
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