Safety and efficacy of belantamab mafodotin with pembrolizumab in patients with relapsed or refractory multiple myeloma.

BACKGROUND: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM. METHODS: DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases. Patients were ≥18 years old with ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 agent. Patients received belamaf (2.5 or 3.4 mg/kg, part 1; 2.5 mg/kg, part 2) and 200 mg pembrolizumab for ≤35 cycles. RESULTS: Of 41 enrolled patients, 34 (n = 6 part 1, n = 28 part 2) who received 2.5 mg/kg belamaf plus pembrolizumab were included in this final analysis. Sixteen patients (47%) achieved an overall response. Minimal residual disease negativity was achieved in three of 10 patients who had very good partial response or better. Five of eight patients who had prior anti-B-cell maturation antigen therapy achieved partial response or better, including two who had B-cell maturation antigen-refractory disease. Common grade ≥3 adverse events were keratopathy (38%) and thrombocytopenia (29%). Despite belamaf-related ocular events, quality-of-life measures remained stable over time. No new safety signals were observed. CONCLUSIONS: The results of DREAMM-4 demonstrated clinical activity and a favorable safety profile of belamaf plus pembrolizumab in patients with RRMM. This trial is registered at www. CLINICALTRIALS: gov as NCT03848845.

Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP).

INTRODUCTION: Belantamab mafodotin (BM) is a new anti-BCMA antibody-drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). METHODS: We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Thirty-three patients were included with a median of 70 years of age (range, 46-79 years). Median time from diagnosis was 71 months (range, 10-858 months). Median prior lines was 5 (range, 3-8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1-16 doses), with a median follow-up of 11 months (6-15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92-5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10-0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107-740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient's decision (3%). CONCLUSIONS: BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.

Artificial Stone Silicosis: Accumulation of errors in the resurgence of an occupational disease: A qualitative study.

BACKGROUND: Exposure to artificial stone machining, under the conditions in which marble workers work with this new product, can cause silicosis. OBJECTIVE: To examine the experiences of marble workers affected, both in workshop and during home installation of countertops, before diagnosis of silicosis. METHODS: Qualitative study in which 10 open-ended semistructured interviews were conducted with marble workers diagnosed with silicosis after machining artificial stone countertops in Cádiz, Spain. Interviews were recorded, transcribed, and coded using a directed content analysis. Codes were organized into themes. RESULTS: Interviews up to 120 minutes and transcript analysis revealed three themes: 1) Heavy exposure for piecework: construction boom in an environment of labor deregulation and high demand for the novel product; 2) Poor working conditions: dry machining of artificial stone without proper protection in the workshop and greater exposure during home installation of countertops; 3) Concatenated legal transgressions: deficiencies in prevention and health surveillance without safety conditions for the correct handling of artificial stone. CONCLUSIONS: The fight against an emerging occupational disease-artificial stone silicosis-should focus on detecting affected workers and avoiding new cases, forcing joint efforts to achieve rigorous compliance with health surveillance and protecting marble workers to achieve healthy and safe workplaces.

Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients: polyfunctional immune responses and lessons for clinical practice.

Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.

PLAIN LANGUAGE SUMMARYWhat is the context?After haematopoietic stem cell transplantation, patients have impaired immunity from conditioning chemotherapy regimens, often exacerbated by underlying diseases, putting them at high risk of developing herpes zoster. In this population, antiviral prophylaxis is the current standard of care to reduce herpes zoster risk. Vaccination provides an additional means to prevent herpes zoster. Live-attenuated vaccines are generally contraindicated in immunocompromised patients. A non-live, adjuvanted recombinant zoster vaccine (RZV, Shingrix, GSK), has been approved for use in adults ≥50 years of age in the European Union, United States, Canada, Australia, Japan, and China. This vaccine is highly efficacious at preventing herpes zoster in adults over 50 years of age, as demonstrated in large, placebo-controlled randomised trials. Importantly, Shingrix use is not contraindicated in immunocompromised conditions, and was found to be highly efficacious in adults who had recently undergone autologous haematopoietic stem cell transplant.What is new?In autologous haematopoietic stem cell transplant recipients in whom Shingrix has demonstrated efficacy, two doses elicited high and persistent immune responses. Date presented here further support our understanding of the impact of specific factors such as age or underlying diseases on the vaccine's effect in the population studied, as well as the characteristics of the elicited cell-mediated immune responses.What is the impact?These results indicate that Shingrix, given shortly after haematopoietic stem cell transplant, can induce robust immune responses and reduce the risk of herpes zoster, even in individuals with immunosuppression due to underlying disease and/or use of immunosuppressive therapies, regardless of age or underlying disease.

Artificial Stone Silicosis: Rapid Progression Following Exposure Cessation.

BACKGROUND: Silicosis is rapidly emerging in high-income countries in relation to the replacement of natural stone with artificial stone, especially in the manufacturing and installation of kitchen and bathroom countertops. Progression of this form of silicosis following the cessation of exposure is unknown. RESEARCH QUESTION: The objective of this study was to determine the radiologic progression and lung function in individuals with artificial stone silicosis. STUDY DESIGN AND METHODS: Between 2009 and 2018, a total of 106 patients were diagnosed with artificial stone silicosis in the Bay of Cádiz area (southern Spain), 14.15% by using biopsy results and the remainder according to chest radiography and high-resolution CT imaging. Follow-up consisted of respiratory function tests and radiographic studies. All patients stopped working in the stone industry following diagnosis. RESULTS: All patients were men; their mean ± SD age at diagnosis was 36.2 ± 7.0 years, and the mean duration of exposure was 12.0 ± 4.3 years. At diagnosis, 99 patients were considered to have simple silicosis (93.4%) and seven to have progressive massive fibrosis (PMF) (6.6%). After a mean follow-up of 4.01 ± 2.1 years, disease in 56% of patients had progressed two or more International Labour Office subcategories, and the number of patients with PMF had increased to 40 (37.7%). Regarding lung function, there was a decrease in FVC and FEV1, with an average decrease of 86.8 and 83.4 mL per year, respectively; in 25% of patients, the annual decrease was > 157 mL in FVC and > 133 mL in FEV1. Multivariable analysis showed that lower FVC at diagnosis and longer duration of exposure to silica were associated with progression to PMF. INTERPRETATION: Artificial stone silicosis rapidly progresses to PMF even following exposure cessation, and a significant percentage of patients experience a very rapid decrease in lung function.

Costing of actions to safeguard vulnerable Mexican households with young children from the consequences of COVID-19 social distancing measures.

COVID-19 has imposed unprecedented challenges to society. As the pandemic evolves, the social distancing measures that have been globally enforced, while essential, are having undesirable socioeconomic side effects particularly among vulnerable populations. In Mexico, families who depend upon informal employment face increased threats to their wellbeing, and households who in addition have young children may face long-term consequences. The Mexican government has not yet taken actions, but a coalition of non-governmental organizations is advocating in partnership with academic institutions for social protection actions such as a cash transfer and basic services subsidies for families with young children, subsisting from the informal sector economy. To facilitate governmental action, we estimated the costs for implementation of these recommendations. The methodology used could be replicated in other countries facing similar challenges.

Silicosis por aglomerados artificiales de cuarzo: claves para controlar una enfermedad emergente / Silicosis Caused by Artificial Quartz Conglomerates: Keys to Controlling an Emerging Disease

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Exploring New Alleles Involved in Tomato Fruit Quality in an Introgression Line Library of Solanum pimpinellifolium.

We have studied a genomic library of introgression lines from the Solanum pimpinellifolium accession TO-937 into the genetic background of the "Moneymaker" cultivar in order to evaluate the accession's breeding potential. Overall, no deleterious phenotypes were observed, and the plants and fruits were phenotypically very similar to those of "Moneymaker," which confirms the feasibility of translating the current results into elite breeding programs. We identified chromosomal regions associated with traits that were both vegetative (plant vigor, trichome density) and fruit-related (morphology, organoleptic quality, color). A trichome-density locus was mapped on chromosome 10 that had not previously been associated with insect resistance, which indicates that the increment of trichomes by itself does not confer resistance. A large number of quantitative trait loci (QTLs) have been identified for fruit weight. Interestingly, fruit weight QTLs on chromosomes 1 and 10 showed a magnitude effect similar to that of QTLs previously defined as important in domestication and diversification. Low variability was observed for fruit-shape-related traits. We were, however, able to identify a QTL for shoulder height, although the effects were quite low, thus demonstrating the suitability of the current population for QTL detection. Regarding organoleptic traits, consistent QTLs were detected for soluble solid content (SSC). Interestingly, QTLs on chromosomes 2 and 9 increased SSC but did not affect fruit weight, making them quite promising for introduction in modern cultivars. Three ILs with introgressions on chromosomes 1, 2, and 10 increased the internal fruit color, making them candidates for increasing the color of modern cultivars. Comparing the QTL detection between this IL population and a recombinant inbred line population from the same cross, we found that QTL stability across generations depended on the trait, as it was very high for fruit weight but low for organoleptic traits. This difference in QTL stability may be due to a predominant additive gene action for QTLs involved in fruit weight, whereas epistatic and genetic background interactions are most likely important for the other traits.

Aportaciones de la tomografía axial computarizada de alta resolución en la detección precoz de silicosis / Contributions of the high resolution computed tomography in the early detection of silicosis

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Silicosis: diferencias relevantes entre marmolistas y mineros / Silicosis: relevant differences between marble workers and miners

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Outbreak of silicosis in Spanish quartz conglomerate workers.

OBJECTIVES: To describe the epidemiological and clinical characteristics of an outbreak of occupational silicosis and the associated working conditions. METHODS: Cases were defined as men working in the stone cutting, shaping, and finishing industry in the province of Cádiz, diagnosed with silicosis between July 2009 and May 2012, and were identified and diagnosed by the department of pulmonology of the University Hospital of Puerto Real (Cádiz). A census of workplaces using quartz conglomerates was carried out to determine total numbers of potentially exposed workers. A patient telephone survey on occupational exposures and a review of medical records for all participants were conducted. RESULTS: Silicosis was diagnosed in 46 men with a median age of 33 years and a median of 11 years working in the manufacturing of countertops. Of these cases, 91.3% were diagnosed with simple chronic silicosis, with an abnormal high-resolution computerized tomography (HRCT) scan. One patient died during the study period. Employer non-compliance in prevention and control measures was frequently reported, as were environmental and individual protection failures. CONCLUSIONS: The use of new construction materials such as quartz conglomerates has increased silicosis incidence due to intensive occupational exposures, in the context of high demand fuelled by the housing boom. This widespread exposure poses a risk if appropriate preventive measures are not undertaken.

Brote de faringoamigdalitis de origen alimentario por estreptococo betahemolítico A / Tonsillopharyngitis outbreak caused by foodborne group A beta-hemolytic streptococcus

Fundamento: Aunque no son frecuentes, algunos autores han comunicado brotes de faringoamigdalitis de origen alimentario. El 11 de mayo de 2010 se notificó a la Red de Vigilancia Epidemiológica de Andalucía (SVEA) que había personas con cuadro de faringoamigdalitis que tenían en común haber asistido a una comunión celebrada el día 8. El objetivo de este trabajo es la caracterización epidemiológica del brote Método: Estudio observacional descriptivo de casos notificados y análisis de casos control por exposición a los alimentos implicados. Se analizaron las variables edad, sexo, sintomatología y fecha de inicio de síntomas. Fuentes de información fueron los registros del SVEA e historia digital individual (DIRAYA). Se calcularon frecuencias, tasas de ataque, y análisis bayesiano de comparación de diferencia de proporciones de enfermar para un intervalo de probabilidad o credibilidad (IP) del 95%. Resultados: De 130 asistentes a una celebración se detectaron 41 casos de faringoamigdalitis (tasa ataque 31,5%) y se aisló en frotis Estreptococo betahemolítico A. El grupo de edad más afectado fue el de 25-44 años: 16 (39,0%);hubo más afectación de las mujeres 24 (68,6%) mujeres. La ensaladilla de huevo presentó una probabilidad mayor del 80% P(Delta>0,10 y Delta>0,15) para un IP del 95% de enfermar tras su consumo y la probabilidad de tener menos riesgo de no enfermar. Conclusiones: Se trató de un brote por estreptococo betahemolítico A. El análisis epidemiológico evidenció exposición a fuente única y común, siendo plausible la hipótesis del origen alimentario, posiblemente por la ensaladilla de huevo contaminada por algún manipulador de alimentos. Como factores contribuyentes se identificaron inadecuadas medidas higiénico-sanitarias en la manipulación y conservación de los alimentos(AU)

Background: Although infrequent, some authors have reported outbreaks of foodborne tonsillopharyngitis. On May 11, 2010 a series of cases of tonsillopharyngitis among those attending a fellowship meeting on 8 March was notified to the Epidemiological Surveillance Network in Andalusia (SVEA). The aim of this study is to epidemiologically characterise the outbreak . Methods: Descriptive analysis of reported cases and case -control exposure to the implicated food. The variables taken into account were age, sex, symptoms and start date. Sources of information used were the records of the SVEA and individual digital report (DIRAYA). Frequencies and attack rates were calculated, and a Bayesian analysis for the comparison of difference in proportions of disease was carried out for a 95% probability or credibility range (IP). Results: Among the 130 attendees at a communion 41 cases of tonsillopharyngitis (attack rate 31.5%) were detected, and in smears Group A Beta-Hemolytic Streptococcus was isolated. The most affected age group was the 25-44 year-olds, 16 (39,0%); 68.6% (24) female. The egg salad showed a probability greater than 80% P(Delta>0.10 and Delta>0.15) for a 95% IP of risk of disease after intake and a probability of having a lower risk of no disease. Conclusions: It was a Group A Beta-Hemolytic Streptococcal outbreak, the epidemiological evidence indicates exposure to common single source, hence the hypothesis of dietary origin, the implicated food was egg salad. Contributing factors could be cross-contamination after preparation favoured by the bad practice and the conditions of the place(AU)

[Tonsillopharyngitis outbreak caused by foodborne group A beta-hemolytic Streptococcus]. / Brote de faringoamigdalitis de origen alimentario por estreptococo betahemolítico A.

BACKGROUND: Although infrequent, some authors have reported outbreaks of foodborne tonsillopharyngitis. On May 11, 2010 a series of cases of tonsillopharyngitis among those attending a fellowship meeting on 8 March was notified to the Epidemiological Surveillance Network in Andalusia (SVEA). The aim of this study is to epidemiologically characterise the outbreak. METHODS: Descriptive analysis of reported cases and case - control exposure to the implicated food. The variables taken into account were age, sex, symptoms and start date. Sources of information used were the records of the SVEA and individual digital report (DIRAYA). Frequencies and attack rates were calculated, and a Bayesian analysis for the comparison of difference in proportions of disease was carried out for a 95% probability or credibility range (IP). RESULTS: Among the 130 attendees at a communion 41 cases of tonsillopharyngitis (attack rate 31.5%) were detected, and in smears Group A Beta-Hemolytic Streptococcus was isolated. The most affected age group was the 25-44 year-olds, 16 (39,0%); 68.6% (24) female. The egg salad showed a probability greater than 80% P(Δ>0.10 and Δ>0.15) for a 95% IP of risk of disease after intake and a probability of having a lower risk of no disease. CONCLUSIONS: It was a Group A Beta-Hemolytic Streptococcal outbreak, the epidemiological evidence indicates exposure to common single source, hence the hypothesis of dietary origin, the implicated food was egg salad. Contributing factors could be cross-contamination after preparation favoured by the bad practice and the conditions of the place.