Obesity is associated with adverse outcomes in primary immune thrombocytopenia - a retrospective single-center study.

The pathophysiology of immune thrombocytopenia (ITP) involves immune-mediated platelet destruction. The presence of adipose tissue in obese individuals creates an inflammatory environment that could potentially impact the clinical course and outcomes of ITP. However the relationship between obesity and ITP outcomes has not been well described. We evaluated ITP outcomes in 275 patients diagnosed with primary ITP from 2012 to 2022. Patients were categorized into four groups based on their body mass index (BMI) at diagnosis. Female gender was associated with a lower platelet count at the time of diagnosis at any BMI. Patients with high BMI had lower platelet counts at diagnosis and at platelet nadir (p < 0.001), an increased likelihood of requiring therapy (p < 0.001) and requiring multiple lines of therapy (p = 0.032). Non-obese patients who required corticosteroid treatment experienced a longer remission duration compared to obese patients (p = 0.009) and were less likely to be steroid-dependent (p = 0.048). Our findings suggest that obesity may be a significant risk factor for developing ITP and for ITP prognosis. Future studies are needed to evaluate the role of weight loss intervention in improving ITP outcomes.

Experimental and Numerical Simulation Study of Oxygen Transport in Proton Exchange Membrane Fuel Cells at Intermediate Temperatures (80 °C-120 °C).

Investigating the oxygen transport law within the Membrane Electrode Assembly at intermediate temperatures (80-120 °C) is crucial for enhancing fuel cell efficiency. This study analyzed the resistance to oxygen transport within the Membrane Electrode Assembly at intermediate temperatures using limiting current density and electrochemical impedance spectroscopy. The study findings reveal that, as temperature progressively increases, the Ostwald ripening effect leads to a 34% rise in the local oxygen transport resistance (Rlocal) in relation to the pressure-independent resistance (Rnp) within the cathode catalytic layer. Concurrently, the total transport resistance (Rtotal) decreases from 27.8% to 37.5% due to an increase in the gas diffusion coefficient and molecular reactivity; additionally, there is a decrease in the amount of liquid water inside the membrane electrode. A three-dimensional multiphysics field steady-state model was also established. The model demonstrates that the decrease in oxygen partial pressure can be mitigated effectively by increasing the back pressure at intermediate temperatures to ensure the cell's performance.

Rituximab resistance in ITP and beyond.

The pathophysiology of immune thrombocytopenia (ITP) is complex and encompasses innate and adaptive immune responses, as well as megakaryocyte dysfunction. Rituximab is administered in relapsed cases and has the added benefit of inducing treatment-free remission in over 50% of patients. Nevertheless, the responses to this therapy are not long-lasting, and resistance development is frequent. B cells, T cells, and plasma cells play a role in developing resistance. To overcome this resistance, targeting these pathways through splenectomy and novel therapies that target FcγR pathway, FcRn, complement, B cells, plasma cells, and T cells can be useful. This review will summarize the pathogenetic mechanisms implicated in rituximab resistance and examine the potential therapeutic interventions to overcome it. This review will explore the efficacy of established therapies, as well as novel therapeutic approaches and agents currently in development.

Development of New Drugs for Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemia (AIHA) is a rare disorder characterized by the autoantibody-mediated destruction of red blood cells, and treatments for it still remain challenging. Traditional first-line immunosuppressive therapy, which includes corticosteroids and rituximab, is associated with adverse effects as well as treatment failures, and relapses are common. Subsequent lines of therapy are associated with higher rates of toxicity, and some patients remain refractory to currently available treatments. Novel therapies have become promising for this vulnerable population. In this review, we will discuss the mechanism of action, existing data, and ongoing clinical trials of current novel therapies for AIHA, including B-cell-directed therapy, phagocytosis inhibition, plasma cell-directed therapy, and complement inhibition.

Multiple Myeloma in Hispanics: Incidence, Characteristics, Survival, Results of Discovery, and Validation Using Real-World and Connect MM Registry Data.

BACKGROUND: Multiple myeloma (MM) in Hispanics has never been studied. We therefore sought to determine the clinical characteristics and overall survival in MM of Hispanics compared to non-Hispanic whites (NHW) and non-Hispanic blacks (NHB). PATIENTS AND METHODS: A single-center analysis of 939 patients diagnosed with MM from 2000 to 2017 with a large representation of NHB (n = 489), Hispanics (n = 281), and NHW (n = 169) was conducted to evaluate outcomes and disease characteristics. We used the Connect MM Registry, a large US multicenter prospective observational study with newly diagnosed MM patients, as a validation cohort. RESULTS: Hispanics had a higher incidence of MM compared to NHW. The median age at presentation was 5 years younger (median, 65 years) in Hispanics compared to NHW (median, 70 years), and patients were more likely to present with renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Hispanics had a higher proportion of Revised International Staging System (R-ISS) stage I disease compared to NHW and NHB (P = .03), while there was no difference in cytogenetics between Hispanics and NHB/NHW. In the multivariate analysis, only high-risk disease and response to first-line therapy significantly affected survival. CONCLUSION: In this first and largest analysis of MM in Hispanics, we found that Hispanics present at a younger age, have a higher incidence of renal dysfunction, and have low R-ISS stage disease at presentation. With equal access to therapy, Hispanics have survival similar to NHW/NHB.

Mortality of lung cancer as a second primary malignancy: A population-based cohort study.

Lung cancer as a second primary malignancy (lung-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall and cancer-specific survival of patients diagnosed with lung-2 compared to lung-1. Primary lung cancer patients diagnosed from 1988 to 2014 in the Surveillance, Epidemiology, and End Results (SEER) program were included. Lung-2 was identified in patients with a previous diagnosis of nonlung primary malignancy in SEER. Hazard ratios (HRs) of overall and lung cancer-specific mortality were estimated among patients with lung-2 compared to lung-1, adjusting for age and calendar period at diagnosis, sex, race, socioeconomic status, tumor stage, histology, tumor grade, and treatment. A total of 679 541 and 85 758 patients were identified as lung-1 and lung-2, respectively. Compared to lung-1, patients with lung-2 were more likely to be diagnosed at localized stage, with smaller primary tumor, and treated with surgery. Lung-2 patients were at lower risk of lung cancer-specific mortality in the first 5 years (HR, 0.77; 95% CI, 0.76-0.78 at <1 year; HR, 0.87; 95% CI, 0.86-0.89 from 1 to <5 years) but at higher risk thereafter (HR, 1.32; 95% CI, 1.27-1.37 from 5 to 10 years), independent of tumor characteristics and cancer treatment. Similar pattern was found for overall mortality, although the survival benefit was restricted to the first year after diagnosis. Patients diagnosed with lung-2 face a favorable lung cancer-specific survival within the early period after diagnosis. A conservative approach to manage lung-2 solely based on malignancy history is not supported.

MDR1 polymorphisms affect the outcome of Chinese multiple myeloma patients.

OBJECTIVE: To illustrate the association of MDR1 (Multidrug Resistance 1) polymorphisms at loci 1236, 2677, 3435 and the prognosis of multiple myeloma (MM) in Jiangsu population. METHODS: A total of 129 MM patients were recruited from Jiangsu Province, China. The DNA was extracted from white blood cells (WBC) of peripheral blood and was amplified by polymerase chain reaction-allele specific primers (PCR-ASP). MDR1 polymorphisms at 3 loci were analyzed by electrophoresis followed by photograph or DNA direct sequencing. The association between the MDR1 and clinical outcomes were calculated by Graphpad and SPSS. RESULTS: MDR1 alleles at locus C1236T with T had significant lower calcium level in MM patients compared with C. The genotype CT had a significantly prolonged progress free survival (PFS) compared genotype CC at locus C1236T (median time: 48 months vs. 28 months, respectively; p=0.0062; HR=0.21; 95%CI0.061-0.715) while patients carrying T allele (CT and TT) at locus C3435T had a longer PFS than patients without T allele (CC) (median time: 60 months vs. 29 months, respectively; p=0.038; HR=0.508; 95%CI 0.264-0.978). And a borderline significance was found in haplotype at loci 2677-3435 and PFS. No significant findings were revealed between OS and MDR1 polymorphisms. CONCLUSION: MDR1 polymorphisms could affect the prognosis of multiple myeloma whereas more samples and a longer follow-up are also needed.

Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/ Refractory Diffuse Large B Cell Lymphoma.

Since the improvement of chemotherapy and innovation of rituximab, about 60% of patients with diffuse large B cell lymphoma (DLBCL) could receive long-term survival after firstline therapy. Around 30% fail to respond or experience relapse considered as the relapsed/refractory DLBCL, the highdose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) has been used as the second-line treatment. However, the patients relapse after auto-HSCT or not eligible for the auto-HSCT have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the potentially curative way in such kind of patients. In this paper, we collected the published data about patients with relapsed/refractory DLBCL who underwent allo-HSCT, demonstrated the appropriate candidate for allo-HSCT, identified the effect of the donor types on the recipients, presented the major conditioning regimens for allo-HSCT and figured out the outcomes of each conditioning regimen. We also tried to identify the prognostic factors on the outcome which might shed some light on the further clinical application.

Association of MDR1 single-nucleotide polymorphisms and haplotype variants with multiple myeloma in Chinese Jiangsu Han population.

Multidrug resistance 1 (MDR1) gene encodes P-glycoprotein (P-gp), which acts as an efflux pump and provides cell protection against various substances, and its single-nucleotide polymorphisms (SNPs) are associated with the development of malignant hematologic diseases. The present study aimed at investigating whether the MDR1 SNPs and haplotype variants were correlated with the susceptibility to multiple myeloma (MM). A total of 115 MM patients and 153 healthy controls from Jiangsu Han population were enrolled and genotyped by polymerase chain reaction-allele-specific primer (PCR-ASP) method or DNA direct sequencing at MDR1 loci of C1236T, G2677T/A, and C3435T. No significance was found in the distribution of alleles and genotypes in MDR1 three loci. Diplotype analysis has also demonstrated no effect in susceptibility to MM. But, in haplotype analysis, the haplotype of T-G-T was significantly more common than healthy controls (12.6 % in MM group vs. 1.7 % in control group, odds ratios (ORs) = 8.7, 95 % confidence interval (CI) 3.3-22.8, Pc < 0.01). Our results pointed out that comparable allele, genotype, and diplotype frequencies among MM patients and controls in Chinese Jiangsu Han population were found; the frequency of T-G-T haplotype was significantly increased in MM group compared with the control group, which indicated that this haplotype might be associated with the susceptibility to MM.

MDR1 polymorphisms have an impact on the prognosis of Chinese diffuse large B cell lymphoma patients.

MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP)-dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health. The present study was aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A, and C3435T were focused on, and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele-specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6 vs. 60.0 %, respectively; hazard ratio (HR) = 0.1, 95 % confidence interval (CI) 0.01-0.6, p = 0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7 vs. 51.9 %, respectively; p = 0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4 % in with T group vs. 73.7 % in without T group, respectively; HR = 1.9, 95 % CI 1.0-3.6, p = 0.045). At locus G2677T/A, the age for genotypes AG and AT groups was significantly younger than the other genotypes (51.1 ± 12.6 vs. 57.7 ± 13.4 years, respectively; p = 0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0 vs. 50.6 %, respectively; HR = 7.8, 95 % CI 1.9-32.6, p = 0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT + TT at locus C1236T, allele C, and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL.

Concurrent Epstein-Barr virus associated NK/T cell lymphoma after immunosuppressive therapy for aplastic anemia: report of a case and review of literature.

Aplastic anemia (AA) patients with prolonged immunosuppression have a risk of development of lymphoproliferative disorders (LPDs), especially combined with Epstein-Barr virus (EBV) infection. However, development of nature killer/T (NK/T) cell lymphoma, in a nontransplantation setting, has not been documented for AA patients with immunosuppressive therapy (IST). Herein, we described a middle-aged man, Han ethnic, who presented with swelled parotid gland after a long history of IST for AA. Fever, night sweating, weight loss had not been found. Increased heterotypic lymphocytes had been detected in the left side of parotid gland demonstrated as cCD3(+), CD56(+), GranB(+), TIA-1(+), MUM-1(+), KI-67 (50%-75%)(++), Bcl-6(-), MPO(-) by immunohistochemistry, and in-situ hybridization (ISH) indicated EBER positive. Chromosome analysis by R banding method revealed 46, XY [20]. NK/T cell lymphoma concurrent with aplastic anemia was diagnosed and a mild chemotherapy regimen including vincristine, prednisone, L-asparaginase was administered. The parotid mass was gradually regressed after the first cycle of chemotherapy. The patient discharged from the hospital voluntarily and lost the follow-up.

The single nucleotide polymorphism and haplotype analysis of MDR1 in Chinese diffuse large B cell lymphoma patients.

We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR=1.48, 95% CI: 1.08-2.02, Pc=0.03; GT: OR=1.96, 95% CI: 1.25-3.07, Pc<0.01), while genotype AT in this locus seemed to be protective (OR=0.29, 95% CI: 0.02-0.72, Pc=0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR=2.38, 95% CI: 1.52-3.74, Pc<0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR=5.21, 95% CI: 2.58-10.54, Pc<0.01); haplotype of G-T in 2677-3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR=3.97, 95% CI: 2.31-6.85, Pc<0.01; 2677GT/3435TT: OR=4.55, 95% CI: 2.02-10.22, Pc<0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677-3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.

Mantle cell lymphoma concurrent with T-large granular lymphocytic leukemia: report of a case and review of literature.

Mantle cell lymphoma is one of the B-cell lymphomas. The concurrent presentation of mantle cell lymphoma with large granular lymphocytic leukemia simultaneously has never been reported. In this case we present an old man with concomitant mantle cell lymphoma and large granular lymphocytic leukemia diagnosed by the morphology of the bone marrow aspiration, immunophenotyping of the peripheral blood by flow cytometry detecting the increased CD3+CD4-CD8+ cells, immunohistochemical studies of lymph node showed cyclinD1+, chromosome analysis by fluorescence in situ hybridization (FISH) showed t(11,14), positive results of IGH and TCR rearrangement studies. The patient discharged from the hospital voluntarily and lost the follow-up. A brief discussion is also presented.