Control of oceanic circulation on sediment distribution in the southwestern Atlantic margin (23 to 55º S)

In this study, we interpret the role played by ocean circulation in sediment distribution on the southwestern Atlantic margin using radiogenic Nd and Pb isotopes. The latitudinal trends for Pb and Nd isotopes reflect the different current systems acting on the margin. The utilization of the sediment fingerprinting method allowed us to associate the isotopic signatures with the main oceanographic features in the area. We recognized differences between Nd and Pb sources to the Argentinean shelf (carried by the flow of Subantarctic Shelf Water) and slopes (transported by deeper flows). Sediments from Antarctica extend up to the Uruguayan margin, carried by the Upper and Lower Circumpolar Deep Water. Our data confirm that, for shelf and intermediate areas (the upper 1200 m), the transfer of sediments from the Argentinean margin to the north of 35∘ S is limited by the Subtropical Shelf Front and the basin-wide recirculated Antarctic Intermediate Water. On the southern Brazilian inner and middle shelf, it is possible to recognize the northward influence of the Río de la Plata sediments carried by the Plata Plume Water. Another flow responsible for sediment transport and deposition on the outer shelf and slope is the southward flow of the Brazil Current. Finally, we propose that the Brazil–Malvinas Confluence and the Santos Bifurcation act as boundaries of geochemical provinces in the area. A conceptual model of sediment sources and transport is provided for the southwestern Atlantic margin

Transforming growth factor beta receptor II polymorphisms are associated with Kawasaki disease

PurposeTransforming growth factor beta receptor 2 (TGFBR2) is a tumor suppressor gene that plays a role in the differentiation of striated cells and remodeling of coronary arteries. Single nucleotide polymorphisms (SNPs) of this gene are associated with Marfan syndrome and sudden death in patients with coronary artery disease. Cardiovascular remodeling and T cell activation of TGFBR2 gene suggest that the TGFBR2 gene SNPs are related to the pathogenesis of Kawasaki disease (KD) and coronary artery lesion (CAL).MethodsThe subjects were 105 patients with KD and 500 healthy adults as controls. Mean age of KD group was 32 months age and 26.6% of those had CAL. We selected TGFBR2 gene SNPs from serum and performed direct sequencing.ResultsThe sequences of the eleven SNPs in the TGFBR2 gene were compared between the KD group and controls. Three SNPs (rs1495592, rs6550004, rs795430) were associated with development of KD (P=0.019, P=0.026, P=0.016, respectively). One SNP (rs1495592) was associated with CAL in KD group (P=0.022).ConclusionEleven SNPs in TGFBR2 gene were identified at that time the genome wide association. But, with the change of the data base, only six SNPs remained associated with the TGFBR2 gene. One of the six SNPs (rs6550004) was associated with development of KD. One SNP associated with CAL (rs1495592) was disassociated from the TGFBR2 gene. The other five SNPs were not functionally identified, but these SNPs are notable because the data base is changing. Further studies involving larger group of patients with KD are needed

Severe infections and infection-related mortality in a large series of haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide

Severe infections and their attributable mortality are major complications in recipients of allogeneic hematopoietic stem cell transplantation (alloSCT). We herein report 236 adult patients who received haploSCT with PTCy. The median follow-up for survivors was 37 months. The overall incidence of bloodstream infections by gram-positive and gram-negative bacteria at 37 months was 51% and 46%, respectively. The incidence of cytomegalovirus infection was 69%, while Epstein Barr virus infections occurred in 10% of patients and hemorrhagic cystitis in 35% of cases. Invasive fungal infections occurred in 11% at 17 months. The 3-year incidence of infection-related mortality was 19%. The median interval from transplant to IRM was 3 months (range 1-30), 53% of IRM occurred >100 days post-haploSCT. Risk factors for IRM included age >50 years, lymphoid malignancy, and developing grade III-IV acute GvHD. Bacterial infections were the most common causes of IRM (51%), mainly due to gram-negative bacilli BSI. In conclusion, severe infections are the most common causes of NRM after haploSCT with PTCy, with a reemergence of gram-negative bacilli as the most lethal pathogens. More studies focusing on the severe infections after haploSCT with PTCy and differences with other types of alloSCT in adults are clearly warranted

Real‐world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B‐cell lymphoma

Tisagenlecleucel (tisa-cel) is a second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa-cel in the standard-of-care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa-cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa-cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non-relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow-up of 14.1 months from CAR T-cell infusion, median progression-free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa-cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses

Heterogeneity in Health Insurance Coverage Among US Latino Adults

We sought to determine the differences in observed and unobserved factors affecting rates of health insurance coverage between US Latino adults and US Latino adults of Mexican ancestry. Our hypothesis was that Latinos of Mexican ancestry have worse health insurance coverage than their non-Mexican Latino counterparts. The National Health Interview Survey (NHIS) database from 1999–2007 consists of 33,847 Latinos. We compared Latinos of Mexican ancestry to non-Mexican Latinos in the initial descriptive analysis of health insurance coverage. Disparities in health insurance coverage across Latino categories were later analyzed in a multivariable logistic regression framework, which adjusts for confounding variables. The Blinder-Oaxaca technique was applied to parse out differences in health insurance coverage into observed and unobserved components. US Latinos of Mexican ancestry consistently had lower rates of health insurance coverage than did US non-Mexican Latinos. Approximately 65% of these disparities can be attributed to differences in observed characteristics of the Mexican ancestry population in the US (e.g., age, sex, income, employment status, education, citizenship, language and health condition). The remaining disparities may be attributed to unobserved heterogeneity that may include unobserved employment-related information (e.g., type of employment and firm size) and behavioral and idiosyncratic factors (e.g., risk aversion and cultural differences). This study confirmed that Latinos of Mexican ancestry were less likely to have health insurance than were non-Mexican Latinos. Moreover, while differences in observed socioeconomic and demographic factors accounted for most of these disparities, the share of unobserved heterogeneity accounted for 35% of these differences

Real-world evidence of brexucabtagene autoleucel for the treatment of relapsed or refractory mantle cell lymphoma

Altres ajuts: Beca PERIS 2018-2020 de la Generalitat de Catalunya (BDNS357800

Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis

BACKGROUND: The genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant. METHODS: We analyzed the I/D polymorphism in the ACE gene (g.11417_11704del287) in 171 subjects comprising 91 TCP and 80 FCPD patients and compared the allelic and genotypic frequency in them with 99 healthy ethnically matched control subjects. RESULTS: We found 46% and 21% of TCP patients, 56% and 19.6% of FCPD patients and 54.5% and 19.2% of the healthy controls carrying the I/D and D/D genotypes respectively (P>0.05). No significant difference in the clinical picture was observed between patients with and without the del allele at the ACE in/del polymorphism in both categories. No association was observed with the presence or absence of N34S SPINK1 mutation in these patients. CONCLUSION: We conclude that the ACE insertion/deletion variant does not show any significant association with the pathogenesis, fibrosis and progression of tropical calcific pancreatitis and the fibro-calculous pancreatic diabetes