First Responders and Criticality Accidents

Nuclear criticality accident descriptions typically include, but do not focus on, information useful to first responders. We studied these accidents, noting characteristics to help (1) first responders prepare for such an event and (2) emergency drill planners develop appropriate simulations for training. We also provide recommendations to help people prepare for such events in the future

Evaluation of the cardiac amyloidosis clinical pathway implementation: A real-world experience

AIMS: The aim of this study is to evaluate the implementation of the cardiac amyloidosis (CA) clinical pathway on awareness among referring cardiologists, diagnostic delay, and severity of CA at diagnosis. METHODS AND RESULTS: Patients with CA were retrospectively included in this study and divided into two periods: pre-implementation of the CA clinical pathway (2007–18; T1) and post-implementation (2019–20; T2). Patients’ and disease characteristics were extracted from electronic health records and compared. In total, 113 patients (mean age 67.8 ± 8.5 years, 26% female) were diagnosed with CA [T1 (2007–18): 56; T2 (2019–20): 57]. The number of CA diagnoses per year has increased over time. Reasons for referral changed over time, with increased awareness of right ventricular hypertrophy (9% in T1 vs. 36% in T2) and unexplained heart failure with preserved ejection fraction (22% in T1 vs. 38% in T2). Comparing T1 with T2, the diagnostic delay also improved (14 vs. 8 months, P < 0.01), New York Heart Association Class III (45% vs. 23%, P = 0.03), and advanced CA stage (MAYO/Gillmore Stage III/IV; 61% vs. 33%, P ≤ 0.01) at time of diagnosis decreased. CONCLUSION: After implementation of the CA clinical pathway, the awareness among referring cardiologists improved, diagnostic delay was decreased, and patients had less severe CA at diagnosis. Further studies are warranted to assess the prognostic impact of CA clinical pathway implementation

Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel genome-wide analysis

Some minor histocompatibility antigens (mHags) are expressed exclusively on patient hematopoietic and malignant cells, and this unique set of antigens enables specific targeting of hematological malignancies after human histocompatability leucocyte antigen (HLA)–matched allogeneic stem cell transplantation (allo-SCT). We report the first hematopoietic mHag presented by HLA class II (HLA-DQA1*05/B1*02) molecules to CD4+ T cells. This antigen is encoded by a single-nucleotide polymorphism (SNP) in the B cell lineage-specific CD19 gene, which is an important target antigen for immunotherapy of most B cell malignancies. The CD19L-encoded antigen was identified using a novel and powerful genetic strategy in which zygosity-genotype correlation scanning was used as the key step for fine mapping the genetic locus defined by pairwise linkage analysis. This strategy was also applicable for genome-wide identification of a wide range of mHags. CD19L-specific CD4+ T cells provided antigen-specific help for maturation of dendritic cells and for expansion of CD8+ mHag-specific T cells. They also lysed CD19L-positive malignant cells, illustrating the potential therapeutic advantages of targeting this novel CD19L-derived HLA class II–restricted mHag. The currently available immunotherapy strategies enable the exploitation of these therapeutic effects within and beyond allo-SCT settings

Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID-19 pandemic

Summary: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐associated coronavirus disease 2019 (COVID‐19) is primarily manifested as a respiratory tract infection, but may affect and cause complications in multiple organ systems (cardiovascular, gastrointestinal, kidneys, haematopoietic and immune systems), while no proven specific therapy exists. The challenges associated with COVID‐19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID‐19 may be particularly challenging in patients with AL amyloidosis, who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, patients with AL amyloidosis may be more susceptible to toxicities of drugs used to manage COVID‐19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences and treatment administration may need modification. Both patients and treating physicians need to adapt in a new realit

Carfilzomib, Pomalidomide, and Dexamethasone As Second-line Therapy for Lenalidomide-refractory Multiple Myeloma

This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide

Outcomes by Cardiac Stage in Patients With Newly Diagnosed AL Amyloidosis: Phase 3 ANDROMEDA Trial

BACKGROUND: Patients with amyloid light chain amyloidosis and severe cardiac dysfunction have a poor prognosis. Treatment options that induce rapid and deep hematologic and organ responses, irrespective of cardiac involvement, are needed. OBJECTIVES: The aim of this study was to evaluate the impact of baseline cardiac stage on efficacy and safety outcomes in the phase 3 ANDROMEDA trial. METHODS: Rates of overall complete hematologic response and cardiac and renal response at 6 months and median major organ deterioration–progression-free survival and major organ deterioration–event-free survival were compared across cardiac stages (I, II, or IIIA) and treatments (daratumumab, bortezomib, cyclophosphamide, and dexamethasone [D-VCd] or bortezomib, cyclophosphamide, and dexamethasone [VCd]). Rates of adverse events (AEs) were summarized for patients with and without baseline cardiac involvement and by cardiac stage. RESULTS: Median follow-up duration was 15.7 months. The proportions of stage I, II, and IIIA patients were 23.2%, 40.2%, and 36.6%. Across cardiac stages, hematologic and organ response rates were higher and major organ deterioration–progression-free survival and major organ deterioration–event-free survival were longer with D-VCd than VCd. AE rates were similar between treatments and by cardiac stage; serious AE rates were higher in patients with cardiac involvement and increased with increasing cardiac stage. The incidence of cardiac events was numerically greater with D-VCd vs VCd, but the rate of grade 3 or 4 events was similar. The exposure-adjusted incidence rate for cardiac events was lower with D-VCd than VCd (median exposure 13.4 and 5.3 months, respectively). CONCLUSIONS: These findings demonstrate the efficacy of D-VCd over VCd in patients with newly diagnosed amyloid light chain amyloidosis across cardiac stages, thus supporting its use in patients with cardiac involvement. (NCT03201965

Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients:results from a randomised phase III study

Background: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial. Patients and methods: Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients ≤60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24 months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences ≥10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients. Results: A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range: −3.8 to +4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months (−7.4 and −8.8, respectively). In irradiated patients (n = 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570. Conclusion: Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impact HRQoL over time. WBRT did not result in deterioration of HRQoL in the first 2 years