CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study.

BACKGROUND: Outcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed B-cell surface antigen and the efficacy of a CD22-directed CAR T-cell therapy (CAR22) in large B-cell lymphoma is unknown, which was what we aimed to examine in this study. METHODS: In this single centre, open-label, dose-escalation phase 1 trial, we intravenously administered CAR22 at two dose levels (1 million and 3 million CAR22-positive T cells per kg of bodyweight) to adult patients (aged ≥18 years) who relapsed after CAR19 or had CD19-negative large B-cell lymphoma. The primary endpoints were manufacturing feasibility, safety measured by the incidence and severity of adverse events and dose-limiting toxicities, and identification of the maximum tolerated dose (ie, the recommended phase 2 dose). This study is registered with ClinicalTrials.gov (NCT04088890) and is active, but closed for enrolment. FINDINGS: From Oct 17, 2019, to Oct 19, 2022, a total of 41 patients were assessed for eligibility; however, one patient withdrew. 40 patients underwent leukapheresis and 38 (95%) had CAR T-cell products manufactured successfully. The median age was 65 years (range 25-84), 17 (45%) were women, 32 (84%) had elevated pretreatment lactate dehydrogenase, 11 (29%) had refractory disease to all previous therapies, and patients had received a median of four lines of previous therapy (range 3-8). Of the 38 patients treated, 37 (97%) had relapsed after previous CAR19. The identified maximum tolerated dose was 1 million CAR T cells per kg. Of 29 patients who received the maximum tolerated dose, no patients developed a dose-limiting toxicity or grade 3 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome. INTERPRETATION: This trial identifies CD22 as an immunotherapeutic target in large B-cell lymphoma and demonstrates the durable clinical activity of CAR22 in patients with disease progression after CAR19 therapy. Although these findings are promising, it is essential to recognise that this is a phase 1 dose-finding study. Further investigations are warranted to establish the long-term efficacy and to delineate the patient subgroups that will derive the most benefit from this therapeutic approach. FUNDING: National Cancer Institute, National Institutes of Health, Stanford Cancer Institute, Leukemia & Lymphoma Society, Parker Institute for Cancer Immunotherapy, Lymph & Co, and the European Hematology Association.

Comparison of molecular responses and outcomes between BCR::ABL1 e14a2 and e13a2 transcripts in chronic myeloid leukemia.

Several studies have compared the molecular responses between e14a2 and e13a2 BCR::ABL1 transcripts in chronic myeloid leukemia (CML) patients treated with front-line imatinib, but there were very limited studies on nilotinib or dasatinib-treated patients. We retrospectively analyzed the molecular responses in 1124 CML patients with the e14a2 or e13a2 transcript receiving front-line imatinib, nilotinib or dasatinib treatment. Patients with the e14a2 transcript had higher optimal response rates than those with the e13a2 transcript at 12 months in the imatinib-treated group, and 6 and 12 months in the nilotinib-treated group. The optimal response rates were not significantly different between the two transcripts in the dasatinib-treated group at landmark molecular responses. With a median follow-up time of 48.4 months, higher cumulative incidences of BCR::ABL1 International Scale ≤1% and major molecular response were observed in patients with the e14a2 rather than the e13a2 transcript receiving front-line imatinib or nilotinib treatment, but not in dasatinib-treated patients. The progression-free survival and overall survival did not differ between the two transcripts in all three treatment groups. In view of the speed and depth of molecular responses, BCR::ABL1 transcript subtypes might provide helpful information in selecting a front-line tyrosine kinase inhibitor for individual young patients with future potential treatment-free remission.

A genomic-augmented multivariate prognostic model for the survival of natural-killer/T-cell lymphoma patients from an international cohort.

With lowering costs of sequencing and genetic profiling techniques, genetic drivers can now be detected readily in tumors but current prognostic models for Natural-killer/T cell lymphoma (NKTCL) have yet to fully leverage on them for prognosticating patients. Here, we used next-generation sequencing to sequence 260 NKTCL tumors, and trained a genomic prognostic model (GPM) with the genomic mutations and survival data from this retrospective cohort of patients using LASSO Cox regression. The GPM is defined by the mutational status of 13 prognostic genes and is weakly correlated with the risk-features in International Prognostic Index (IPI), Prognostic Index for Natural-Killer cell lymphoma (PINK), and PINK-Epstein-Barr virus (PINK-E). Cox-proportional hazard multivariate regression also showed that the new GPM is independent and significant for both progression-free survival (PFS, HR: 3.73, 95% CI 2.07-6.73; p < .001) and overall survival (OS, HR: 5.23, 95% CI 2.57-10.65; p = .001) with known risk-features of these indices. When we assign an additional risk-score to samples, which are mutant for the GPM, the Harrell's C-indices of GPM-augmented IPI, PINK, and PINK-E improved significantly (p < .001, χ2 test) for both PFS and OS. Thus, we report on how genomic mutational information could steer toward better prognostication of NKTCL patients.

Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study in multiple populations.

BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL; nasal type) is an aggressive malignancy with a particularly high prevalence in Asian and Latin American populations. Epstein-Barr virus infection has a role in the pathogenesis of NKTCL, and HLA-DPB1 variants are risk factors for the disease. We aimed to identify additional novel genetic variants affecting risk of NKTCL. METHODS: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL. FINDINGS: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants. INTERPRETATION: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention. FUNDING: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute.

Application of comprehensive geriatric assessment in predicting early mortality among elder patients with B-cell lymphoma receiving immunochemotherapy.

OBJECTIVES: Early mortality, defined as death within 120 days after initiated antitumor therapy, is an important issue especially for elder patients with B-cell lymphoma. This study aimed to evaluate the clinical value of comprehensive geriatric assessment (CGA) in early mortality prediction in elderly patients with B-cell lymphoma receiving immunochemotherapy. METHODS: Seventy-six consecutive patients with newly diagnosed B-cell lymphoma receiving immunochemotherapy from a medical center in Taiwan were prospectively enrolled. Patients were divided into fit (n = 49) and frail (n = 27) groups per pretreatment CGA for early mortality comparison. RESULTS: The early mortality rate in our patient cohort was 16% (n = 12): from 6% in patients with no CGA domain impairment to 43% in patients with ≥4 CGA domain impairment. The early mortality rate was 6% and 33% in fit and frail patients (odds ratio, 7.67; 95% CI, 1.86-31.6; P = .005), respectively. Frailty was the significant predictor for early mortality in univariate and multivariate analysis. CONCLUSION: In this study, the number of geriatric domain impairment is positively associated with the early mortality risk in elderly patients with B-cell lymphoma. Therefore, CGA can help clinicians to identify the risk of early mortality in elderly patients and provide alternative treatment.

Haploidentical allogeneic hematopoietic stem cell transplantation increases the risk of cytomegalovirus infection in adult patients with acute leukemia.

BACKGROUND: Owing to the shortage of hematopoietic stem cells from matched sibling donors (MSD) and matched unrelated donors (MUD), the number of patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) has rapidly increased. Despite a comparable overall survival (OS) and leukemia-free survival using this approach, some evidence suggests that haploidentical allo-HSCT recipients have a higher incidence of cytomegalovirus (CMV) infection, though this has not been clearly established. METHODS: This study retrospectively compared the cumulative incidence of CMV DNAemia, 2-year OS, and leukemia-free survival rates in acute leukemia patients with MSD (n = 41), MUD (n = 18), and haploidentical donor allografts (n = 21). RESULTS: The cumulative incidences of CMV DNAemia at day 180 in the MSD, MUD, and haploidentical groups were 39.0, 55.6, and 85.7%, respectively (P < 0.000). As less than 50% of patients in the MSD group were detected to have CMV DNAemia, the median time to CMV DNAemia detection in patients allografted with MSD could not be obtained. However, it was 42 and 29 days, respectively, for the MUD and haploidentical groups. Multivariate analysis revealed that haploidentical allo-HSCT (MSD vs. haploidentical: HR: 0.26; 95% CI: 0.09-0.78; P = 0.017) and age (HR: 1.03; 95% CI: 1.01-1.06; P = 0.011) increased CMV infection. Finally, MSD, MUD, and haploidentical allo-HSCT provided comparable 2-year OS rates (52.1%, 65.5%, and 65.6%; P = 0.425) and 2-year leukemia-free survival rates (67.1%, 68.3%, and 80.7%, P = 0.837). CONCLUSION: The CMV incidence was higher for haploidentical allo-HSCT than for MSD and MUD allo-HSCT; this could be explained by graft-versus-host disease prophylaxis by multiple immunosuppressants.

Extranodal NK/T-cell lymphoma, nasal type: Clinical features, outcome, and prognostic factors in 101 cases.

OBJECTIVES: We aimed to define the clinical features, outcome, and prognostic factors for extranodal NK/T-cell lymphoma (ENKTL) patients in Taiwan. METHODS: We retrospectively reviewed 101 ENKTL patients diagnosed between February 1998 and October 2015. RESULTS: The median age of 101 patients was 52 years old (range 22-85); 76.2% of patients were Ann Arbor stage I/II disease. The 5-year progression-free survival (PFS) and overall survival (OS) were 49.9% and 54.8%, respectively. Patients with log[EBV-DNA] ≥ 3.8 and bone marrow hemophagocytosis at diagnosis had inferior PFS and OS. Most stage I/II patients received combined chemoradiotherapy with anthracycline-containing regimen, with overall response rate of 96.7%, complete response rate 86.9%, 5-year PFS 65%, and OS 72%. The relapse rate was 29.3% with a short median disease-free survival of 6.2 months. In advanced stage patients, overall response rate was only 13.6%, with median PFS 2.3 months, and OS 4.8 months. Age ≥ 60 (HR 3.773, 95% CI 1.733-8.215, P = 0.001) and stage III/IV (HR 7.785, 95% CI 2.312-26.213, P = 0.001) were unfavorable prognostic factors for PFS and OS by multivariate analyses. CONCLUSIONS: Age ≥ 60 and stage III/IV are independent poor prognostic factors for PFS and OS. Early-stage ENKTL patients had good response to combined chemoradiotherapy with anthracycline-containing regimen but with a high relapse rate and short disease-free survival. Anthracycline-containing regimen in advanced stage had poor response and dismal outcome.

Major impact of prognosis by age and sex in patients with primary mediastinal large B­cell lymphoma.

The effective prognostic factors for primary mediastinal large B-cell lymphoma (PMLBCL) vary among published studies. The aim of the present study was to explore the factors influencing the overall survival (OS) and progression-free survival (PFS) of patients with PMLBCL at a single institute in Taiwan. This retrospective study was conducted to analyze the prognostic impact of age, sex, disease stage, International Prognostic Index (IPI) score, treatment modality and initial response. A total of 72 patients with a median age of 28 years were included in the study. The mean OS and PFS were 171.40 and 159.77 months, respectively. Female sex, age ≤60 years, receiving radiotherapy (RT) and achieving a complete response were found to be associated with a significantly improved OS and PFS. In addition, high-intensity chemotherapy and an IPI score ≤1 were associated with longer OS, and early-stage disease was associated with a PFS superior to that of advanced-stage disease. The predictive value of IPI is limited in PMLBCL. Therefore, it is necessary to develop a novel prognostic system. The present study revealed the impact of sex on prognosis and, therefore, this factor should be considered in future prognostic evaluations. Since a complete post-treatment response was found to be important, high-intensity chemotherapy is recommended. However, low-intensity treatment followed by RT consolidation appears to be a feasible approach in elderly patients.

Clinical features of neurotoxicity after CD19 CAR T-cell therapy in mantle cell lymphoma.

ABSTRACT: CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development after CD19 CAR T-cell therapy in patients with MCL. All patients (N = 26) who received standard-of-care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (grade ≥3) ICANS. All patients with ICANS had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. Overall, 92% of EEGs revealed interictal changes; no patients experienced frank seizures because of ICANS. In total, 86% of patients with severe ICANS with postinfusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of postinfusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in patients with severe ICANS, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.

Giant Pancreatic Pseudocyst after Coronary Artery Bypass Graft in a Hemodialysis Patient: A Case Report.

End-stage renal disease (ESRD) patients have a high prevalence of coronary artery disease, and coronary artery bypass graft (CABG) is one of the essential treatments. ESRD patients undergoing CABG surgery have an increased risk of postoperative complications, including acute pancreatitis. Here, we present the unique case of an exceptionally large pancreatic pseudocyst caused by pancreatitis in an ESRD patient after CABG surgery. A 45-year-old male with ESRD under maintenance hemodialysis received CABG surgery for significant coronary artery disease. Two weeks later, he experienced worsening abdominal pain and a palpable mass was noticed in the epigastric region. Computer tomography revealed an unusually large pseudocyst measuring 21 × 17 cm in the retroperitoneum due to necrotizing pancreatitis. The patient underwent percutaneous cystic drainage, and the symptoms were significantly improved without surgical intervention. Factors such as prolonged cardiopulmonary bypass time, postoperative hypotension, and intradialytic hypotension appeared to have contributed to the development of severe pancreatitis in this case. This report highlights the rarity of a giant pancreatic pseudocyst in an ESRD patient after CABG surgery and emphasizes the importance of vigilant postoperative care.

Pretreatment frailty is an independent prognostic factor among elderly patients with B-cell lymphoma undergoing immunochemotherapy: A prospective observational cohort study in Taiwan.

BACKGROUND/PURPOSE: Frailty is a common clinical syndrome among the elderly; however, it is frequently neglected in patients with hematological malignancies, especially among the Asian population. This study is aimed to evaluate the prevalence and effect of frailty on survival outcomes in elderly Asian patients with B-cell lymphoma. METHODS: We prospectively enrolled 76 consecutive patients with age ≥ 65 years and newly diagnosed B-cell lymphoma and were receiving immunochemotherapy in a medical center in Taiwan between August 2016 and December 2017. The frailty of all patients was assessed using a comprehensive geriatric assessment (CGA) within 7 days before immunochemotherapy. RESULTS: Twenty-seven patients (36%) were allocated to the frail group based on CGA. With a median follow-up duration of 26.5 (range, 1.7-39.8) months, the 1- and 2-year survival rates were 68% and 58%, respectively, for all group of patients. In patients in the non-frail group, the 1-year and 2-year survival rates were 81% and 71%, respectively, compared to 44% and 33%, respectively, in the frail group (hazard ratio [HR], 3.57, 95% confidence interval [CI], 1.74-7.30; p = 0.001). Age ≥ 75years (adjusted HR 2.57, 95% CI 1.02-6.47, p = 0.045), presence of B-symptoms (adjusted HR 2.43, 95% CI 1.05-5.60, p = 0.038), and frailty (adjusted HR 3.03, 95% CI 1.29-7.11, p = 0.011) were independent prognostic factors in the multivariate analysis. CONCLUSION: Frailty significantly influenced the survival outcome as an independent prognostic factor in elderly patients with B-cell lymphoma undergoing immunochemotherapy. Pretreatment frailty assessment is critical to assist clinicians and patients with B-cell lymphoma with prognosis prediction and counseling on an appropriate treatment goal.

Different patterns of failure in two treatment regimens for primary central nervous system lymphoma, a retrospective analysis of 124 cases in Taiwan.

To explore prognostic factors and outcomes of primary central nervous system lymphoma (PCNSL) of diffuse large B-cell lymphoma (DLBCL) in Taiwan, 124 PCNSL-DLBCL patients (from 1995 to 2021) were retrospectively analyzed. Mainly, two treatment modalities including sandwich chemoradiotherapy and modified MATRix regimen were employed in these patients. Overall survival (OS) was determined by log-rank test and time-dependent Cox analysis. Median OS of all patients was 27.1 months. 47 (37.9%) patients who underwent sandwich chemoradiotherapy had a complete remission (CR) rate of 87.2%, median OS of 53.9 months, and progression free survival (PFS) of 42.9 months. 11 (8.9%) patients who underwent modified MATRix regimen had CR rate of 72.7%, median OS of 18.9, and PFS of 11.2 months. There are no significant OS differences between treatment groups or addition of Rituximab. Patients treated with the modified MATRix regimen experienced a higher early mortality rate followed by a survival plateau. IELSG low-risk group had significantly improved OS and PFS than IELSG intermediate- or high-risk group. In multivariant analysis, age > 60 years old and bilateral cerebral lesions are associated with significantly inferior OS. Sandwich chemoradiotherapy demonstrated better early survival and reduced treatment-related toxicity for PCNSL patients compared to the modified MATRix regimen. However, the long-term follow-up revealed a higher rate of treatment failure events in the sandwich chemoradiotherapy group. IELSG and MSKCC scores served as reliable risk assessment models. Incorporating bilateral cerebral lesions as a risk factor further improved risk evaluation.

Beta2-microglobulin is a valuable marker and identifies a poor-prognosis subgroup among intermediate-risk patients with diffuse large B cell lymphoma.

Prognosis of diffuse large B cell lymphoma (DLBCL) can be predicted by various factors. The most widely used tool for prediction is the international prognostic index (IPI). ß2-microglobulin is a tumor marker commonly used in hematological malignancies. ß2-microglobulin is well correlated with outcome of DLBCL. It has been used as an adjunctive tool in some scoring systems for prognostication of DLBCL. In this study, we collected data of patients with diagnosis of DLBCL between 2015 and 2019 in our institute. For each patient, IPI was calculated according to published literature. At diagnosis, serum levels of ß2-microglobulin were measured in the clinical laboratory and the results were retrieved from medical records. A total of 516 patients (269 male and 247 female) were enrolled for retrospective analysis. The median age was 64 (range 22-96). The median follow-up period was 32.2 months. The median level of ß2-microglobulin was 2319 µg/L (normal range < 2366 µg/L in the clinical laboratory). Level of ß2-microglobulin was significantly different between survivors and patients who succumbed to the disease. ß2-microglobulin level was correlated with tumor stage, extranodal involvement, B symptoms and IPI, suggesting that it may be a good surrogate marker for disease severity and outcome prediction. We selected the intermediate-risk patients for further analysis. Patients with intermediate-risk IPI and high ß2-microglobulin levels have overall survival comparable to patients with high-risk IPI, suggesting an important role of ß2-microglobulin in subdivision of DLBCL patients. In conclusion, ß2-microglobulin levels correlated with outcome of DLBCL. It may be used independently as a prognostic factor. Subdivision of patients with intermediate-risk IPI may identify a group of high-risk patients, which can be helpful in refining plans of treatment and follow-up.

Bone Marrow Hypocellularity in Patients with End-Stage Kidney Disease.

BACKGROUND: Anemia and pancytopenia are not uncommon in patients with chronic kidney disease (CKD). Nevertheless, there is insufficient literature analyzing bone marrow pathology in patients with CKD or end-stage kidney disease (ESKD) receiving dialysis. METHODS: This observational cohort study included 22 patients with ESKD and 23 patients with CKD that received bone marrow biopsy and aspiration at Chang Gung Memorial Hospital. Demographic, hematological, and biochemical data were collected at the time of bone marrow study for analysis. RESULTS: Bone marrow aspiration demonstrated that patients with ESKD had a lower percentage of blasts than patients with CKD (0.52 ± 0.84 versus 1.06 ± 0.78 %, p = 0.033). Bone marrow biopsy revealed that the overall incidence of hypocellular bone marrow was 55.6%. Furthermore, patients with ESKD had higher proportion of hypocellular bone marrow than patients with CKD (72.7% versus 39.1%, p = 0.023). In a multivariate logistic regression model, it was revealed that ESKD status (odds ratio 9.43, 95% confidence interval 1.66-53.63, p = 0.011) and megakaryocyte count within bone marrow (odds ratio 0.48, 95% confidence interval 0.29-0.79, p = 0.004) were significant predictors for bone marrow hypocellularity. CONCLUSION: Bone marrow hypocellularity is common in patients with kidney dysfunction. Hypocellular marrow occurs more frequently in patients with ESKD than patients with CKD.

Correlation between Poynting flux and soft electron precipitation in the dayside polar cap boundary regions.

Observations have revealed large Poynting flux and soft electron precipitation around the cusp region, which have strong impacts on the polar ionosphere/thermosphere. Simulations also confirmed that Poynting flux and soft electron precipitation significantly change the neutral density and dynamics around the dayside polar cap boundary regions. However, no detailed study has been conducted to show if they should coincide with each other or not. Our analysis of Defense Meteorological Satellite Program (DMSP) satellite data reveals a complex correlation between them. Poynting flux and soft particle precipitation are coincident in some cases (match cases), but a clear displacement between them can also be identified in others (nonmatch cases). In the 29 cusp crossings from F13 we investigated, the ratio between nonmatch and match cases is close to 1:4. In nonmatch cases, the displacement between the Poynting flux enhancement and soft particle precipitation enhancement can be as large as 1° in geomagnetic latitude.

Environmental carbon monoxide level is associated with the level of high-sensitivity C-reactive protein in peritoneal dialysis patients.

Inflammation is highly prevalent among peritoneal dialysis (PD) patients. High-sensitivity C-reactive protein (hs-CRP) is the most widely used inflammatory marker in clinical medicine and is correlated with mortality in PD patients. Air pollution is associated with systemic inflammation. The aim of this cross-sectional study was to assess the role of air pollutants and other clinical variables on hs-CRP values in PD patients.We recruited a total of 175 patients who had been undergoing continuous ambulatory PD or automated PD for at least 4 months and regularly followed up. Air pollution levels were recorded by a network of 27 monitoring stations near or in the patients' living areas throughout Taiwan. The 12-month average concentrations of particulate matter (PM) with an aerodynamic diameter of <10 and <2.5 µm (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were included.In stepwise linear regression, after adjustment for related factors, white blood cell count (ß: 0.27, 95% confidence interval [CI] [0.71, 2.11]) and CO level (ß: 0.17, 95% CI [2.5, 21.32]) were positively associated with hs-CRP and serum albumin levels (ß: -0.25, 95% CI [-13.69, -3.96]) and normalized protein nitrogen appearance (ß: -0.18, 95% CI [-17.7, -2.51]) was negatively associated with hs-CRP. However, serum indoxyl sulfate and p-cresyl sulfate levels were not significantly associated with hs-CRP (P > 0.05).In PD patients, the environmental CO level was positively correlated with hs-CRP level.

Impact of environmental particulate matter and peritoneal dialysis-related infection in patients undergoing peritoneal dialysis.

In patients undergoing peritoneal dialysis (PD), PD-related infection is a major cause of PD failure and hospital admission. Good air quality is required when dialysate exchange or exit site wound care is performed. To our knowledge, investigation of air pollution as a factor for PD-related infection in patients undergoing dialysis is limited. This study aimed to assess the effect of environmental particulate matter (PM) and other important risk factors on 1-year PD-related infection in patients undergoing PD.A total of 175 patients undergoing PD were recruited in this 1-year retrospective observational study. Differences in environmental PMs (PM10 and PM2.5) were analyzed with respect to the patients' living areas. The patients undergoing PD were categorized into 2 groups according to PM2.5 exposure: high (n = 61) and low (n = 114). Demographic, hematological, nutritional, inflammatory, biochemical, and dialysis-related data were analyzed. Multivariate binary logistic and multivariate Cox regression analyses were used to analyze 1-year PD-related infection.A total of 175 patients undergoing PD (50 men and 125 women) were enrolled. Thirty-five patients had PD-related infection within 1 year. Multivariate Cox regression analysis showed that high environmental PM2.5 exposure (hazard ratio (HR): 2.0, 95% confidence interval [CI] [1.03-3.91]; P = .04) and female sex (HR: 2.77, 95% CI [1.07-7.19]; P = .03) were risk factors for 1-year PD-related infection.Patients undergoing PD with high environmental PM2.5 exposure had a higher 1-year PD-related infection rate than that in those with low exposure. Therefore, air pollution may be associated with PD-related infection in such patients.