American journal of blood research最新文献

Objectives: Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by the excessive production of lymphocytes in the bone marrow. One of the emerging therapeutic strategies for CLL is chimeric antigen receptor (CAR) T-cell therapy, wherein T-cells are genetically modified to recognize and target cancer cells more effectively. The present study aims to systematically compare the therapeutic impact of high-dose versus low-dose status of CAR T-cell therapy targeting CD19 (CART-19) in patients with relapsed or refractory CLL.

Methods: To identify relevant studies, a comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases up to April 2023. The primary outcome measures included treatment response rates, assessed as complete response (CR) and partial response (PR), and toxicity, as indicated by the incidence of cytokine release syndrome (CRS). Additionally, sensitivity and bias analyses were performed to evaluate the robustness of the findings.

Results: Four randomized controlled trials (RCTs) comprising 89 patients with relapsed or refractory CLL met the inclusion criteria. Comparison of treatment response rates between high-dose and low-dose CART-19 therapy demonstrated a significantly higher complete and partial response rate in the high-dose group (SMD [95% CI]: 1.02 [0.10, 1.94]; P<0.05). However, no significant association was observed between CTL019 dosage and the incidence of CRS (P>0.05).

Conclusion: This meta-analysis suggests that high-dose CART-19 is associated with improved response rates and survival outcomes in patients with CLL compared to low-dose therapy. However, due to variability in study results, further large-scale, well-designed trials are required to establish the optimal therapeutic dosing strategy for CART-19 therapy in CLL.

Portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS) are rare vascular disorders with both well-recognized and less commonly identified etiologies.

Objectives: This study aims to investigate the etiologies of portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS), thereby enhancing improving early detection and management strategies for these conditions. A retrospective review was undertaken to identify the etiologies of PVT and BCS.

Methods: A detailed clinical evaluation was performed and all underlying diseases, such as MPD, and related conditions (e.g. surgery) associated with thrombosis were recorded.

Results: The study comprised a total of 73 patients, with 58 diagnosed with PVT and 15 with BCS. Of these patients, 56 (76.7%) had at least one underlying disease. The most prevalent underlying diseases in patients with PVT were cirrhosis (32/58, 55.2%), myeloproliferative disease (3/58, 5.2%), malignancy (4/58, 6.9%), and rheumatological conditions (4/58, 6.9%). For BCS, 11/15 patients (73.3%) had at least one predisposing condition, including cirrhosis in six cases. Congenital causes were identified in 16/58 cases of PVT (27.6%), in 7/15 cases of BCS (46.7%). Thirty-two patients had previously undergone gastrointestinal surgery (PVT 24/58, BCS 8/15); surgery was the sole etiology in 15/73 patients (20.5%). Homocysteinemia was common (PVT 20/58, BCS 5/15). A multitude of rare etiologies were identified, including paroxysmal nocturnal haemoglobinuria, Crohn's disease, nephrotic syndrome, drug therapies, pregnancy, JAK2 mutation, and elevated factor VIII or fibrinogen.

Conclusions: The presence of a wide range of diverse frequent-infrequent etiologies of congenital or acquired splanchnic vein thrombosis in this cohort underscores the necessity for the implementation of appropriate diagnostic strategies in a broad spectrum of at-risk patients.

Iron deficiency anaemia (IDA) makes an individual prone to bacterial infections. The antimicrobial defence mechanism of neutrophils is orchestrated by Nicotinamide Adenine Dinucleotide Phosphate Hydrogen (NADPH) oxidative burst which is iron-dependent. The few previous studies documenting a decrease in neutrophil oxidative burst in iron-deficient children have been based mainly on the Nitro blue tetrazolium test (NBT). Very few studies have been conducted using the more robust flow cytometry-based dihydro rhodamine (DHR) assay in this regard worldwide and none in India.

Aim: To estimate the effect of iron deficiency on neutrophil oxidative burst activity in children under 5 years of age by flow cytometry-based dihydro rhodamine (DHR) assay and compare it with the control group.

Methods: Thirty-six children between 6 months to 5 years of age diagnosed with moderate (Hb 7-10 gm/dl) to severe (Hb <7 gm/dl) iron deficiency anaemia were selected as cases with equal number of sex/age matched controls. The peripheral blood was analyzed for hematological and biochemical parameters such as complete iron profile, serum vitamin B12, and folate levels. The oxidative burst activity of neutrophils in peripheral blood was assessed using a flow-cytometry-based Dihydrorhodamine (DHR) assay.

Results: The percentage of neutrophils showing stimulation, Mean Fluorescence Index in stimulated neutrophils, and Neutrophil oxidative index (NOI) were significantly reduced in iron deficiency anaemia patients as compared to controls. In cases, haemoglobin showed significant positive correlation with NOI and percentage of neutrophils showing stimulation.

Conclusion: To conclude, a significant decrease in neutrophil oxidative burst parameters depicts an insufficient innate immune response to pathogens and makes Iron deficiency anaemia patients more susceptible to infections, further aggravated by the severity of anaemia.

Objectives: Heparin-induced thrombocytopenia (HIT) is clinically the most relevant non-hemorrhagic complication of heparin, which is associated with the increased risk of thrombosis and mortality. This study was conducted to determine platelet activation in HIT-II in hospitalized patients with surgery or deep vein thrombosis (DVT). The clinical outcomes of the patients was also assayed.

Methods: In this descriptive/cross-sectional study, 754 heparin-receiving-hospitalized patients with surgery or DVT were evaluated for the incidence of thrombocytopenia 7 days after heparin therapy. Clinical assessment 4Ts and ELISA for heparin-platelet factor 4 (HPF4) antibodies were performed to diagnose HIT-II. Production of platelet microparticles (PMPs), soluble P-selectin (sP-selectin), IL-1, IL-6, and tumor necrosing factor-α (TNF-α) were evaluated in the HIT suspected patients.

Results: The frequency of HIT-II was 4.50%. More HIT-II was diagnosed in the elder patients (P = 0.008) and female (P = 0.005). Thrombosis rate was higher in the HIT-II (P = 0.0001). More PMPs, sP-selectin, IL-1, IL-6, and TNF-α was detected in the HIT-II patients. The length of hospital stay was significantly different in HIT-II (P = 0.015). Mortality rate of the HIT-II patients was higher than non-HIT ones (P = 0.0007).

Conclusion: Platelet activation in the HIT-II patients mediated more thrombosis formation. It was associated with the increased length of hospital stay and mortality.

Background: TLR7, the receptor accountable for immune response to RNA viruses, has been studied extensively to identify its variants related to the severity of Covid-19 in different populations worldwide. However, the genotype of Pakistani population is still unknown. This study aimed to determine the TLR7 genotypes and their relation with severity in our population.

Methods: This cross sectional study collected data on 151 Covid-19 positive patients (aged 18-80 years), from June 2022 to May 2023, after an informed consent, from Ziauddin University and Hospital. Prior to that approval from ethics review committee was taken. The demographic variables and comorbidities were recorded along with health status till LAMA (Leave Against Medical Advise), recovery or death. The DNA was extracted from collected blood samples, PCR and Sanger sequencing was done for identification of TLR7 variants. SPSS was used for data analyses and Chi-Square for categorical variables. P-values of <0.05 was considered significant.

Results: Out of 151 patients' sequencing was done for 59 samples. The restriction site, rs864058 of TLR7 gene, identified G/A and G/G variants. This missense variant of TLR7 identified at rs864058 of TLR7 gene, has not been previously reported in population control databases. The genotype G/G was main variant of 49 (83%) patients, whereas, G/A was found in 10 (17%). Majority, 25 (51%) of patients with mild covid-19 had GG genotype but results were not significant (P=0.684). Among female patients the main genotype was GA 8 (80%) while male had G/G 29 (59.2%) with significant results (P=0.024). Since G/G genotype was the major genotype, high percentage was found in hypertensives [20 (40.8%)], Diabetics [13 (26.5%)], depression [24 (49%)] and pneumonia patients [20 (40.8%)]. However, significant association (P=0.023) was only found with pneumonia. Males, in majority had severe [17 (68%)] infection and death [40 (26.4%)], whereas, females had mild [14 (25%)] with [12 (7.9%)] deaths.

Conclusion: A variant rs864058 "G/A" of TLR7, in relation to covid-19 were found in our population. Males were found more at risk of morbidity and mortality due to covid-19. Larger studies are required to further confirm these results.

Background: Advanced chronic kidney disease (ACKD) is common in patients undergoing percutaneous coronary intervention (PCI). Post-PCI bleeding has been shown to increase mortality and remains an important challenge in these patients. Previous studies have shown increased post-PCI bleeding in CKD patients but often ACKD patients are excluded from these trials. The goal of this study was to evaluate if patients undergoing PCI with advanced renal disease have higher bleeding complications.

Methods: We analyzed the National Inpatient Sample (NIS) database to compare the post-PCI bleeding rates for ACKD (CKD stage 3 and above) undergoing PCI between 2006 and 2011 to those without ACKD in patients over the age of 40. Specific ICD-9 CM codes were used to identify these patients.

Results: A total of 49,192 patients had post-PCI bleeding during the study period of which 3,675 (7.5%) had ACKD. Patients with ACKD were older (68.7±11.7 years). During the study period, there was a decline in post-PCI bleeding rates in both ACKD and control groups. Patients with ACKD have significantly higher post-PCI bleeding rates compared to the control group. For example, in 2006, 133.9 in patients with ACKD had bleeding vs. 104.4 per 100,000 in patients without ACKD (P<0.05). After multivariate adjustment for bassline comorbidities, ACKD remained independently associated with post-PCI bleeding risk (OR: 1.07, CI: 1.03-1.11, P<0.001).

Conclusion: Despite the overall decline in post-PCI bleeding in patients undergoing PCI, ACKD remains independently associated with post-procedural bleeding.

Factor V Leiden is an inheritable pro-thrombotic genetic condition caused by a point mutation at the 506^th codon, resulting in activated protein C resistance. APC resistance has been shown to contribute to the development of venous thrombosis. However, the role of FVL in AMI has yet to be well defined in the current literature. To assess whether a mutation carrier is more apt to develop an AMI, we conducted a retrospective observational analysis of two populations aged 18-40 and 18 through end of life. We used ICD-10 codes to search the NIS, an electronic nationwide patient database, to establish our populations and obtain our data. The ICD-10 codes were specific for activated protein C resistance and acute myocardial infarction. Preliminary data indicated that FVL was related to AMI; however, this finding became insignificant in both populations when stratified for age. We concluded there was no association between Factor V Leiden and acute myocardial infarction across both examined populations. Future investigations into this field of research are warranted as there remains a need for more consensus among the scientific community.

Background: Medical literature regarding the correlation between Factor V Leiden (FVL) and acute myocardial infarctions (AMI) is controversial. We aim to investigate the association between FVL and AMI.

Materials and methods: Using the Nationwide Inpatient Sample database, we evaluated any association between Factor V Leiden and acute myocardial infarction in 2016 using ICD-10 codes.

Results: Univariate analysis (18-40) showed an increase of AMI in patients with FVL 0.6% vs. 0.4%. However, after adjustment for age and comorbid conditions in multivariate analysis, FVL was not significantly associated with acute myocardial infarction (OR 1.44 (95% CI 0.913-2.273, p-value 0.117)). Univariate analysis (all patients over 18 years old) found that 2.9% of patients with FVL experienced AMI vs. 4.4% without the mutation. Multivariate analysis of the entire population ultimately showed no correlation between FVL and AMI.

Conclusion: In a population over 18, Factor V Leiden did not correlate with an increased risk of acute myocardial infarction in our studied population.

Background: Sickle cell disease (SCD) is the most common inherited blood disorder, affecting primarily Black and Hispanic individuals. In 2016, 30-day readmissions incurred 95,445 extra days of hospitalization, $152 million in total hospitalization costs, and $609 million in total hospitalization charges.

Objectives: 1) To estimate hospital readmissions within 30 days among patients with SCD in the State of California. 2) Identify the factors associated with readmission within 30 days for SCD patients in California.

Methods: We conducted a retrospective observational study of adult SCD patients hospitalized in California between 2005 and 2014. Descriptive statistics and logistic regression models were used to examine significant differences in patient characteristics and their association with hospital readmissions.

Results: From 2,728 individual index admissions, 70% presented with single admission, 10% experienced one readmission, and 20% experienced ≥ two readmissions within 30 days. Significant predictors associated with zero vs. one readmission were male gender (OR=1.37, CI: 1.06-1.77), Black ethnicity (OR=3.27, CI: 1.71-6.27) and having Medicare coverage (OR=1.89, CI: 1.30-2.75). Lower likelihood of readmission was found in those with a Charlson Comorbidity index of three or more (OR=0.53, CI: 0.29-0.97). For zero vs. ≥ two readmissions, significant predictors were male gender (OR=1.43, CI: 1.17-1.74), Black ethnicity (OR=6.90, CI: 3.41-13.97), Hispanic ethnicity (OR=2.33, CI: 1.05-5.17), Medicare coverage (OR=3.58, CI: 2.68-4.81) and Medi-Cal coverage (OR=1.70, CI: 1.31-2.20). Lower likelihood for having two or more readmissions were associated with individuals aged 65+ (OR=0.97, CI: 0.96-0.98) and those with self-payment status (OR=0.32, CI: 0.12-0.54).

Conclusions: In California, male, Black, and Hispanic patients, as well as those covered by Medicare or Medi-Cal, were found to have an increased risk of hospital readmissions. Redirecting outpatient goals to address these patient populations and risk factors is crucial for reducing readmission rates.

Cardiovascular disease (CVD) is a major cause of death worldwide. Although there are many variables that contribute to the development of this disease, it is predominantly the activity of platelets that provides the mechanisms by which this disease prevails. While there are numerous platelet receptors expressed on the surface of platelets, it is largely the consensus that there are 10 main platelet receptors that contribute to a majority of platelet function. Understanding these key platelet receptors is vitally important for patients suffering from myocardial infarction, CVD, and many other diseases that arise due to overactivation or mutations of these receptors. The goal of this manuscript is to review the main platelet receptors that contribute most to platelet activity.

Background: Heparin-induced thrombocytopenia (HIT) is an extremely serious and potentially fatal condition that can develop in patients taking heparin-based medications, such as unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The incidence and risk factors for HIT in critically ill patients, however, are not well defined.

Methods: We retrospectively collected data on HIT test results, route of heparin administration, age, sex, heparin type (UFH or LMWH), and date of illness from patients admitted to the intensive care unit (ICU) and regular nursing floor (non-ICU) at our hospital between January 2011 and December 2014. We screened patients for HIT using the 4T score and confirmed the diagnosis through laboratory testing (direct enzyme immunoassay immunoglobulin G [IgG] or a platelet-activating antibody).

Results: We screened a total of 946 patients, 56 (5.9%) of whom were positive for HIT. Among 776 patients receiving UFH and 180 receiving LMWH, 2.8 and 6.6% developed HIT, respectively (P = 0.051). We then classified our patients into two groups: ICU, and non-ICU. In the non-ICU group (n = 317), 4 (2.7%) patients receiving LMWH and 25 (5.1%) receiving UFH were positive for HIT (P = 0.221). In the ICU group (n = 639), 1 (3.1%) patient receiving LMWH and 26 (9.1%) receiving UFH were positive for HIT (P = 0.249). The ICU group, therefore, had a higher cumulative incidence rate of HIT than the non-ICU group (8.5 vs. 4.5%).

Conclusion: HIT was more common in ICU patients than non-ICU patients and in more patients receiving UFH than LMWH, although the differences were not statistically significant. Early diagnosis and appropriate treatment are essential to prevent adverse outcomes in patients with HIT.