Myelodysplastic syndromes (MDS) arise in older adults through stepwise acquisitions of multiple somatic mutations. Here, analyzing 1809 MDS patients, we infer clonal architecture by using a stringent, the single-cell sequencing validated PyClone bioanalytic pipeline, and assess the position of the mutations within the clonal architecture. All 3,971 mutations are grouped based on their rank in the deduced clonal hierarchy (dominant and secondary). We evaluated how they affect the resultant morphology, progression, survival and response to therapies. Mutations of SF3B1, U2AF1, and TP53 are more likely to be dominant, those of ASXL1, CBL, and KRAS are secondary. Among distinct combinations of dominant/secondary mutations we identified 37 significant relationships, of which 12 affect clinical phenotypes, 5 cooperatively associate with poor prognosis. They also predict response to hypomethylating therapies. The clonal hierarchy has distinct ranking and the resultant invariant combinations of dominant/secondary mutations yield novel insights into the specific clinical phenotype of MDS.

Pure red cell aplasia is an orphan disease, and as such lacks rationally established standard therapies. Most cases are idiopathic; a subset is antibody-mediated. There is overlap between idiopathic cases and those with T-cell large granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas. In each of the aforementioned, the pathogenetic mechanisms may involve autoreactive cytotoxic responses. We selected 62 uniformly diagnosed pure red cell aplasia patients and analyzed their pathophysiologic features and responsiveness to rationally applied first-line and salvage therapies in order to propose diagnostic and therapeutic algorithms that may be helpful in guiding the management of prospective patients, 52% of whom were idiopathic, while the others involved large granular lymphocytic leukemia, thymoma, and B-cell dyscrasia. T-cell-mediated responses ranged between a continuum from polyclonal to monoclonal (as seen in large granular lymphocytic leukemia). During a median observation period of 40 months, patients received a median of two different therapies to achieve remission. Frequently used therapy included calcineurin-inhibitors with a steroid taper yielding a first-line overall response rate of 76% (53/70). Oral cyclophosphamide showed activity, albeit lower than that produced by cyclosporine. Intravenous immunoglobulins were effective both in parvovirus patients and in hypogammaglobulinemia cases. In salvage settings, alemtuzumab is active, particularly in large granular lymphocytic leukemia-associated cases. Other potentially useful salvage options include rituximab, anti-thymocyte globulin and bortezomib. The workup of acquired pure red cell aplasia should include investigations of common pathological associations. Most effective therapies are directed against T-cell-mediated immunity, and therapeutic choices need to account for associated conditions that may help in choosing alternative salvage agents, such as intravenous immunoglobulin, alemtuzumab and bortezomib.

Background The Coronavirus 2019 is a pandemic that has spread worldwide, threatening human health. The main cause of death in patients with COVID-19 is a systemic pro-inflammatory mechanism that quickly progresses to acute respiratory distress syndrome. Hematological ratios as affordable indicators of inflammatory response were studied in COVID-19 patients. The study aimed to study the importance of the blood cell indexes of the systemic inflammatory response, as the Aggregate Index of Systemic Inflammation (AISI), neutrophils lymphocyte to platelet ratio (NLPR), systemic immune-inflammation index (SII) and, systemic inflammation response index (SIRI) in predicting intensive care unit (ICU) admission of COVID-19 patients. Methods 495 COVID-19 patients managed in four tertiary centers; divided into non-ICU and ICU groups. Results Total leucocyte count (TLC), AISI, NLPR, SII, and SIRI were more elevated in the ICU group (P < 0.001 for all except AMC P = 0.006), while this group had less absolute lymphocyte count (ALC) (P = 0.047). We estimated the optimal cut-off values of the hematological ratio; AISI (729), NLPR (0.0195), SII (1346), and SIRI (2.5). SII had the highest specificity (95.6%), while NLPR had the highest sensitivity (61.3%). Age, AISI, CRP, D-dimer, and oxygen aid were the independent predictors for ICU admission in COVID-19 in multivariate logistic regression. Conclusion AISI is a predictor for severity and ICU admission in COVID-19 patients, SII is a predictor of survival, while NLPR and SIRI have an additive role that needs further evaluation.

The long-term impact of the COVID-19 infection on mental health in people and its relation to the severity is unclear. We aimed to study the long-term effect of post-COVID-19 disease on sleep and mental health and to detect possible relationship between severity of COVID-19 at onset and sleep and mental illness. We enrolled 182 participants 6 months post COVID-19 infection and grouped into non-severe(101),severe(60) and critical(20) according to according to WHO guidance. All participants were assessed using Pittsburgh Sleep Quality Index ", Post traumatic stress disorder (PTSD) Checklist for DSM-5, and Symptom Checklist90 test. Only 8.8% had no psychiatric symptoms while 91.2% had psychiatric symptoms as follow (poor sleep (64.8%), PTSD (28.6%), somatization (41.8%), obsessive-compulsive (OCD) (19.8%), depression (11.5%), anxiety (28%), phobic-anxiety (24.2%), psychoticism (17.6%)). Diabetes, oxygen support or mechanically ventilated were a risk for sleep impairment, while high Neutrophil/lymphocyte ratio (NLR) was the only risk factor for PTSD. Other psychiatric illnesses had several risk factors: being female, diabetes, oxygen support or mechanically ventilated. Abnormal sleep, somatization and anxiety are the most common mental illnesses in Post-Covid19. The critical group is common associated with PTSD, anxiety, and psychosis. Being female, diabetic, having oxygen support or mechanically ventilated, and high NLR level are more vulnerable for mental illness in post COVID19.

Somatic TET2 mutations (TET2MT) are frequent in myeloid neoplasia (MN), particularly chronic myelomonocytic leukemia (CMML). TET2MT includes mostly loss-of-function/hypomorphic hits. Impaired TET2 activity skews differentiation of hematopoietic stem cells toward proliferating myeloid precursors. This study was prompted by the observation of frequent biallelic TET2 gene inactivations (biTET2i) in CMML. We speculated that biTET2i might be associated with distinct clinicohematological features. We analyzed TET2MT in 1045 patients with MN. Of 82 biTET2i cases, 66 were biTET2MT, 13 were hemizygous TET2MT, and 3 were homozygous TET2MT (uniparental disomy); the remaining patients (denoted biTET2− hereafter) were either monoallelic TET2MT (n = 96) or wild-type TET2 (n = 823). Truncation mutations were found in 83% of biTET2i vs 65% of biTET2− cases (P = .02). TET2 hits were founder lesions in 72% of biTET2i vs 38% of biTET2− cases (P &lt; .0001). In biTET2i, significantly concurrent hits included SRSF2MT (33%; P &lt; .0001) and KRAS/NRASMT (16%; P = .03) as compared with biTET2−. When the first TET2 hit was ancestral in biTET2i, the most common subsequent hits affected a second TET2MT, followed by SRSF2MT, ASXL1MT, RASMT, and DNMT3AMT. BiTET2i patients without any monocytosis showed an absence of SRSF2MT. BiTET2i patients were older and had monocytosis, CMML, normal karyotypes, and lower-risk disease compared with biTET2− patients. Hence, while a second TET2 hit occurred frequently, biTET2i did not portend faster progression but rather determined monocytic differentiation, consistent with its prevalence in CMML. Additionally, biTET2i showed lower odds of cytopenias and marrow blasts (≥5%) and higher odds of myeloid dysplasia and marrow hypercellularity. Thus, biTET2i might represent an auxiliary assessment tool in MN.