9 research outputs found
The role and uses of antibodies in COVID-19 infections: a living review
Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity
T cell phenotypes in COVID-19 - a living review
COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation
A multicenter retrospective comparison of induction chemoimmunotherapy regimens on outcomes in transplant-eligible patients with previously untreated mantle cell lymphoma
Mantle cell lymphoma (MCL) is an uncommon and typically aggressive form of lymphoma. Although often initially chemosensitive, relapse is common. Several induction and conditioning regimens are used in transplant-eligible patients, and the optimal approach remains unknown. We performed an international, retrospective study of transplant-eligible patients to assess impact of induction chemoimmunotherapy and conditioning regimens on clinical outcomes. We identified 228 patients meeting inclusion criteria. Baseline characteristics were similar among the induction groups except for some variation in age. The type of induction chemoimmunotherapy received did not influence overall response rates (ORRs) (0.43), progression-free survival (PFS) (P > .67), or overall survival (OS) (P > .35) on multivariate analysis (PFS and OS). Delivery of autologous stem cell transplant (ASCT) was associated with favorable PFS and OS (0.01) on univariate analysis only; this benefit was not seen on multivariate analysis—PFS (0.36) and OS (0.21). Compared with busulfan and melphalan (BuMel), the use of the carmustine, etoposide, cytarabine, melphalan (BEAM)–conditioning regimen was associated with inferior PFS (HR = 2.0 [95% CI 1.1-3.6], 0.02) but not OS (HR = 1.1 [95% CI 0.5-2.3], 0.81) on univariate analysis only. Within the limits of a retrospective study and modest power for some comparisons, type of induction therapy did not influence ORR, PFS, or OS for transplant-eligible patients with MCL. International efforts are required to perform randomized clinical trials evaluating chemoimmunotherapy induction regimens
The impact of residual neuromuscular blockade, oversedation, and hypothermia on adverse respiratory events in a postanesthetic care unit : a prospective study of prevalence, predictors, and outcomes
BACKGROUND: Residual neuromuscular blockade (RNMB) has been linked to adverse respiratory events (AREs) in the postanesthetic care unit (PACU). However, these events are often not attributed to RNMB by anesthesiologists because they may also be precipitated by other factors including obstructive sleep apnea, opioids, or hypnotic agents. Many anesthesiologists believe RNMB occurs infrequently and is rarely associated with adverse outcomes. This study evaluated the prevalence and predictors of RNMB and AREs. METHODS: This prospective cohort study included 599 adult patients undergoing general anesthesia who received neuromuscular blocking agents. Baseline demographic, surgical, and anesthetic variables were collected. RNMB was defined as a train-of-four ratio below 0.90 measured by electromyography on admission to the PACU. AREs were defined based on the modified Murphy’s criteria. RESULTS: RNMB was present in 186 patients (31% [95% confidence interval (CI), 27%–35%]) on admission to the PACU. One or more AREs were experienced by 97 patients (16% [95% CI 13–19]). AREs were more frequent in patients with RNMB (21% vs 14%, P = .033). RNMB was significantly associated with age (adjusted relative risk [RR], 1.17 [95% CI, 1.06–1.29] per 10-year increase), type of operation (adjusted RR, 0.59 [95% CI, 0.34–0.99] for laparoscopic surgery compared with open abdominal surgery), and duration of operation (adjusted RR, 0.59 [95% CI,
0.39–0.86] for ≥90 minutes compared with <90 minutes). Using multivariate logistic regression, AREs were found to be independently associated with decreased level of consciousness (adjusted RR, 4.76 [95% CI, 1.49–6.76] for unrousable/unconscious compared with alert/awake) and lower core temperature (adjusted RR, 1.43 [95% CI, 1.04–1.92] per 1°C decrease). Although univariate
analysis found a significant association between AREs and RNMB, the significance became borderline after adjusting for other covariates (adjusted RR, 1.46 [95% CI, 0.99–2.08]). CONCLUSIONS: The prevalence of RNMB in the PACU was >30%. Older age, open abdominal surgery, and duration of operation <90 minutes were associated with increased risk of RNMB in our patients. Our RR estimate for AREs was highest for depressed level of consciousness. When AREs
occur in the PACU, potentially preventable causes including RNMB, hypothermia, and reduced level of consciousness should be readily identified and treated appropriately. Delaying extubation until the patient is awake and responsive may reduce AREs
Outcomes of stage I/II follicular lymphoma in the PET era: an international study from the Australian Lymphoma Alliance
Management practices in early-stage (I/II) follicular lymphoma (FL) are variable and include radiation (RT), systemic therapy, or combined modality therapy (CMT). There is a paucity of data regarding maintenance rituximab in this cohort. We conducted an international retrospective study of patients with newly diagnosed early-stage FL staged with positron emission tomography (PET)-computed tomography and bone marrow biopsy. Three hundred sixty-five patients (stage I, n = 221), median age 63 years, treated from 2005-2017 were included, with a median follow-up of 45 months. Management included watchful waiting (WW; n = 85) and active treatment (n = 280). The latter consisted of RT alone (n = 171) or systemic therapy (immunochemotherapy [n = 63] or CMT [n = 46]). Forty-nine systemically treated patients received maintenance rituximab; 72.7% of stage I patients received RT alone, compared to 42.6% with stage II ( < .001). Active therapies yielded comparable overall response rates ( = .87). RT alone and systemic therapy without maintenance rituximab yielded similar progression-free survival (PFS) (hazard ratio [HR], 1.32; 95% confidence interval [CI], 0.77-2.34; = .96). Maintenance rituximab improved PFS (HR, 0.24; 95% CI, 0.095-0.64; = .017). The incidence of transformation was lower with systemic therapy compared to RT or WW (HR, 0.20; 95% CI, 0.070-0.61; = .034). Overall survival was similar among all practices, including WW ( = .40). In the largest comparative assessment of management practices in the modern era, variable practices each resulted in similar excellent outcomes. Randomized studies are required to determine the optimal treatment in early-stage FL
Outcomes of Stages I and II Follicular Lymphoma in the Era of 18F-FDG PET-CT Staging: An International Collaborative Study from the Australian Lymphoma Alliance
Kitty Crowther, Mon Ami Jim, Pastel, 1996. Quelques phrases pour résonner une sublime fable du racontage : Elle déroule son fil sur des galets - six par double page - qui voient s'effectuer la rencontre de Jack, le corbeau, et de Jim, la mouette. Des moments contemplatifs ou plutôt de spauses dans la profondeur des galets nous arrêtent sur une pleine page. Puis l'amour sur un galet s'avoue tête bêche dans un lit. Le village n'accueille pas l'étranger mais quand les histoires que racontent les..