Abstract Introduction Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation. Method In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy. Results The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored. Conclusion: We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions. treatment however microenvironments tumorspecific specific finally timeconsuming time consuming process method geneediting gene editing therapy repeatsassociated repeats associated CRISPRCas9 CRISPRCas Cas9 Cas (CRISPR/Cas9 fields manipulation review CRISPR/Cas Tbased based immunotherapy explored Conclusion solutions (CRISPR/Cas

Abstract Objective Despite an increase in the rate of successful live donor renal transplantation done annually, the number of potential recipients with acceptable donors is relegated to the ever-expanding cadaver-donor waiting list due to sensitization to human leukocyte antigen (HLA) antibodies. If not sufficiently suppressed, these preformed HLA antibodies can trigger antimicrobial resistance (AMR) and early graft loss. To ameliorate this situation, various desensitization treatments are administered to provide a survival benefit to highly sensitized patients. Method One hundred and six patients in the time frame of January 2017 to March 2019 were included in the study group. The desensitization protocol included therapeutic plasma exchange and administration of low-dose intravenous immunoglobulin (100 mg/kg per therapeutic plasma exchange (TPE) session) to highly sensitized patients (treatment group) who subsequently underwent renal transplantation after negative pre-transplant Centers for Disease Control and Prevention Luminex crossmatch (CDC/LumXM). We compared graft survival rates between the group undergoing desensitization (treatment group) and matched control group of patients that underwent HLA-compatible transplantation. Results In the treatment group, Kaplan-Meier analysis estimates an average rate of patient graft survival of 95.2% at 3 years post-transplant, as compared with the rate of 86.9% in the same time frame for the control-matched group (p < 0.05 for both comparisons). Conclusion Desensitization treatment with TPE before live donor renal transplantation in the case of patients with HLA sensitization provides better survival benefits along with monitoring for donor-specific antibodies (DSAs) and other infections, rather than waiting for a compatible organ donor. The data lays out evidence that desensitization treatments can assist overcome HLA incompatibility barriers in live donor renal transplantation. annually everexpanding ever expanding cadaverdonor cadaver (HLA suppressed AMR (AMR loss situation 201 lowdose low dose 100 (10 mgkg mg kg (TPE session pretransplant pre transplant CDC/LumXM. CDCLumXM CDC/LumXM . CDC LumXM (CDC/LumXM) HLAcompatible KaplanMeier Kaplan Meier 952 95 2 95.2 posttransplant, posttransplant post transplant, post-transplant 869 86 9 86.9 controlmatched p 005 0 05 0.0 comparisons. comparisons comparisons) donorspecific specific DSAs (DSAs infections 20 10 (1 (CDC/LumXM 95. 8 86. 00 0. 1 (

Abstract The evolutionary conserved link between coagulation and innate immunity is a biological process characterized by the thrombosis formation stimulus of immune cells and specific thrombosis-related molecules. In physiological settings, the relationship between the immune system and thrombosis facilitates the recognition of pathogens and damaged cells and inhibits pathogen proliferation. However, when deregulated, the interplay between hemostasis and innate immunity becomes a pathological process named immunothrombosis, which is at the basis of several infectious and inflammation-related thrombotic disorders, including coronavirus disease 2019 (COVID-19). In advanced stages, alterations in both coagulation and immune cell function due to extreme inflammation lead to an increase in blood coagulability, with high rates of thrombosis and mortality. Therefore, understanding underlying mechanisms in immunothrombosis has become decisive for the development of more efficient therapies to treat and prevent thrombosis in COVID-19 and in other thrombotic disorders. In this review, we outline the existing knowledge on the molecular and cellular processes involved in immunothrombosis, focusing on the role of neutrophil extracellular traps (NETs), platelets and the coagulation pathway. We also describe how the deregulation of hemostasis is associated with pathological conditions and can significantly aggravate a patient's condition, using COVID-19 as a clinical model. thrombosisrelated related molecules settings proliferation However deregulated inflammationrelated disorders 201 COVID19. COVID19 COVID 19 . (COVID-19) stages coagulability mortality Therefore COVID-1 review NETs, NETs , (NETs) pathway patients patient s condition model 20 COVID1 1 (COVID-19 COVID- (NETs 2 (COVID-1 (COVID- (COVID

Introduction The hemogram and hemogram-derivative ratios (HDRs) are becoming markers of the severity and mortality of COVID-19. We evaluated the hemograms and serial weekly HDRs [neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NPR) and systemic immune-inflammatory index (SII)] in the survivors and non-survivors of COVID-19. Methods We retrospectively reviewed the medical notes and serial hemograms of real-time reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 adults hospitalized from April 2020 to March 2021 from the time of diagnosis to the 3rd week of diagnosis. Results Of the 320 adults, 257 (80.3%) were survivors and had a lower mean age than the non-survivors (57.73 vs. 64.65 years, p < 0.001). At diagnosis, the non-survivors had lower hematocrit (p = 0.021), and lymphocyte (p = 0.002) and basophil (p = 0.049) counts and the hematocrit showed a p-value (Is this what you meant???) of 0.021); higher NLR (p < 0.001), PLR (p = 0.047), NPR (p = 0.022) and SII (p = 0.022). Using general linear models, the survivors and non-survivors showed significant variations with weekly lymphocyte count (p < 0.001), neutrophil count (p = 0.005), NLR (p = 0.009), MLR (p = 0.010) and PLR (p = 0.035). All HDRs remained higher in the non-survivors in the 2nd week and 3rd week of diagnosis and the HDRs were higher in the intubated patients than in the non-intubated patients. The NLR and SII were more efficient predictors of mortality in COVID-19 patients. Conclusions This study shows that serial lymphocyte and neutrophil counts, NLR, PLR, MLR, NPR and SII could serve as good and easily accessible markers of severity and predictors of outcomes in COVID-19 patients and should be used for the monitoring of treatment response. hemogramderivative derivative (HDRs COVID19. COVID19 COVID 19. 19 neutrophillymphocyte , (NLR) monocytelymphocyte monocyte (MLR) plateletlymphocyte platelet (PLR) neutrophilplatelet (NPR immuneinflammatory immune inflammatory (SII) nonsurvivors non realtime real reversetranscription reverse transcription RTPCRconfirmed RT PCR confirmed COVID-1 202 rd 32 25 80.3% 803 80 3 (80.3% 57.73 5773 57 73 (57.7 vs 6465 64 65 64.6 years 0.001. 0001 0.001 . 0 001 0.001) 0.021, 0021 0.021 021 0.021) 0.002 0002 002 0.049 0049 049 pvalue value Is meant meant??? 0.001, 0.047, 0047 0.047 047 0.047) 0.022 0022 022 0.022. models 0.005, 0005 0.005 005 0.005) 0.009, 0009 0.009 009 0.009) 0.010 0010 010 0.035. 0035 0.035 035 0.035) nd nonintubated response COVID1 1 (NLR (MLR (PLR (SII COVID- 20 2 80.3 8 (80.3 57.7 577 5 7 (57. 646 6 64. 000 0.00 00 0.02 02 0.04 004 04 meant?? 0.01 01 003 0.03 03 80. (80. 57. (57 0.0 meant? (80 (5 0. (8 (

Abstract To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety. date disease reallife real life attacks vasoocclusive vaso occlusive events syndrome transfusion which part physicians physician s report safety

Objective This study aimed to determine the clinical outcomes and risk factors affecting mortality in patients with COVID-19 following hematological malignancy (HM). Methods Patients diagnosed with HM and hospitalized for COVID-19 were included in this retrospective study. The age, demographic and clinical characteristics, prognosis and treatment of surviving and non-surviving patients were compared. Results A total of 49 patients were included in this study, 17 (34.6%) of whom died within 28 days of being diagnosed with COVID-19. Older age (p = 0.001), diabetes (p = 0.001), chronic obstructive pulmonary disease (p = 0.002), secondary infection (p < 0.001) and secondary bacterial infection (p = 0.005) were statistically significantly higher in non-survivors. The remission status of HM was higher in surviving patients (p < 0.001). In multivariate regression analysis, age (OR: 1.102, p = 0.035) and secondary infection (OR: 16.677, p = 0.024) were risk factors increasing mortality, the remission status of HM (OR: 0.093, p = 0.047) was a protective factor from mortality. Conclusion The older age, the remission status of HM and secondary infection due to COVID-19 were determined as prognostic factors predicting mortality in HM patients with following COVID-19. COVID19 COVID 19 COVID-1 HM. . (HM) characteristics nonsurviving non compared 4 1 34.6% 346 34 6 (34.6% 2 COVID19. 19. 0.001, 0001 0.001 , 0 001 0.002, 0002 0.002 002 0.002) 0.005 0005 005 nonsurvivors. nonsurvivors survivors. survivors non-survivors 0.001. analysis OR (OR 1102 102 1.102 0.035 0035 035 16677 16 677 16.677 0.024 0024 024 0093 093 0.093 0.047 0047 047 COVID1 COVID- (HM 34.6 3 (34.6 000 0.00 00 110 10 1.10 0.03 003 03 1667 67 16.67 0.02 02 009 09 0.09 0.04 004 04 34. (34. 0.0 11 1.1 166 16.6 (34 0. 1. 16. (3 (

Abstract Objective The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. Method This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Ceará (northeastern Brazil) over a period of five years. Results The mean age at diagnosis was 44.1 ± 16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). Conclusion The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the national average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing. clinicalepidemiological epidemiological profile AML, , (AML) followup. followup follow up. up follow-up 22 northeastern Brazil 441 44 1 44. 1.31. 131 1.3 1. 3 1.3:1 found wellestablished well established assessment 5year year 5 394 39 4 39.4 95%CI 95CI CI 95 (95%CI 3547 35 47 35.4 42.17. 4217 42.17 . 42 17 42.17) 37.72% 3772 37 72 (37.72% 84 31.58% 3158 31 58 (31.58% 70. 70 70) groups average expected testing (AML 2 1.31 13 1.3: 39. 9 354 35. 421 42.1 37.72 377 7 (37.72 8 31.58 315 (31.58 42. 37.7 (37.7 31.5 (31.5 37. (37. 31. (31. (37 (31 (3 (

Introduction Dendritic cell (DC) vaccines have demonstrated good efficacy in preventing relapse and in increasing survival of patients affected by a variety of both solid and hematological tumors. Most protocols used to generate these cells involve the automated separation of peripheral blood monocytes from patients. This approach requires specialized equipment, which elevates the cost of this type of therapy, potentially limiting the widespread access to patients. Method: In this study, we compare the yield and quality of dendritic cells generated from monocytes and isolated by an automated method or by manual methods using gradient centrifugation. Results The results demonstrate the equivalence of the 3 methods in relation to the yield and final quality of the product, however with considerable differences between the costs of these procedures. In addition, this study also demonstrates the feasibility of the antigenic pulse with autologous tumor cell lysates, constituting a source of antigens, not only easily obtained and manipulated, but also specific to the patient's tumor. Conclusion These findings may have important implications for emerging centers interested in using this medical approach and potentially increase the access of a greater number of patients to this therapeutic option. DC (DC tumors equipment therapy Method centrifugation product procedures addition lysates antigens manipulated patient s option