Campylobacter assessment along the Spanish food chain: Identification of key points.

AIMS: Campylobacteriosis, caused by Campylobacter spp., is one of the most important foodborne zoonotic diseases in the world and a common cause of gastroenteritis. In the European Union, campylobacteriosis is considered the most common zoonotic disease, with over 10,000 cases in 2020 alone. This high occurrence highlights the need of more efficient surveillance methods and identification of key points. METHODS AND RESULTS: Herein, we evaluated and identified key points of Campylobacter spp. occurrence along the Spanish food chain during 2015-2020, based on the following variables: product, stage and region. We analysed a dataset provided by the Spanish Agency for Food Safety and Nutrition using a machine learning algorithm (random forests). Campylobacter presence was influenced by the three selected explanatory variables, especially by product, followed by region and stage. Among the studied products, meat, especially poultry and sheep, presented the highest probability of occurrence of Campylobacter, where the bacterium was present in the initial, intermediate and final stages (e.g., wholesale, retail) of the food chain. The presence in final stages may represent direct consumer exposure to the bacteria. CONCLUSSIONS: By using the random forest method, this study contributes to the identification of Campylobacter key points and the evaluation of control efforts in the Spanish food chain.

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Spatial and temporal analysis of African swine fever front-wave velocity in wild boar: implications for surveillance and control strategies.

The front-wave velocity of African swine fever (ASF) virus spread is depicted through a retrospective spatial and temporal analyses of wild boar outbreaks from Jan. 2014 to Jan. 2022 in Estonia, Latvia, Lithuania and Eastern Poland-regions responsible for more than 50% of all wild boar cases in the EU. The study uses empirical semivariograms in a universal kriging model to assess spatial autocorrelation in notification dates and identifies a discernable large-scale spatial trend. The critical parameter of ASF front-wave velocity was identified (Mean = 66.33 km/month, SD = 163.24) in the whole study area, and explored the variations across countries, wild boar habitat suitability, seasons, and the study period. Statistical differences in front-wave velocity values among countries and temporal clusters are explored, shedding light on potential factors influencing ASF transmission dynamics. The implications of these findings for surveillance and control strategies are discussed.

[Calciphylaxis, risk factors, treatment and outcomes. Retrospective study of 39 patients]. / Calcifilaxis, factores de riesgo, tratamiento y evolución. Estudio retrospectivo de 39 pacientes.

INTRODUCTION: Calciphylaxis is a serious vascular disorder characterized by calcification of tunica media, intimal hyperplasia, thrombosis, and skin necrosis. It was described in patients with renal failure (UC), although it can occur in its absence (NUC). Its risk factors are under study and its diagnosis can be complex. Over a decade ago, its mortality was estimated at 60-80%. Recent studies indicate that it has decreased (40%). METHODS: A retrospective study was carried out in the period between January 1, 2011 and December 31, 2019. The past medical record, clinical characteristics, laboratory and histopathological findings, and evolution of all patients with calciphylaxis evaluated at the Hospital Italiano de Buenos Aires were reviewed. RESULTS: Thirty-nine patients were included. Sixtyone percent were men and 39% were NUC cases. Eightytwo percent had arterial hypertension, 66% obesity and 46% diabetes. Of those, 49% received coumarin anticoagulants. All patients with NUC and 75% with UC presented ulcers with necrosis, located more frequently on the legs. In 72% of the cases the histological diagnosis was made with one biopsy. In all the treatment was multimodal and mortality at one year was 42%. CONCLUSION: We observed a high proportion of patients with NUC, in relation to what is reported in the literature, and that half received vitamin K antagonists. The histological diagnosis was made with one biopsy in most of the cases, as the surgical technique for taking the sample, the Von Kossa staining and the evaluation by an expert pathologist were the key of it.

Introducción: La calcifilaxis es un trastorno vascular grave caracterizado por depósito de calcio en túnica media arteriolar, trombosis y necrosis cutánea. Se describió en pacientes con insuficiencia renal (CU), aunque puede producirse en su ausencia (CNU). Sus factores de riesgo están en estudio y su diagnóstico puede ser complejo. Su mortalidad se estimaba en 60-80%, aunque trabajos recientes indican que ha disminuido (40%). Métodos: Estudio retrospectivo entre el 1/1/2011 y el 31/12/2019. Se revisaron los antecedentes, las características clínicas, los hallazgos de laboratorio e histopatológicos, y la evolución de todos los pacientes con diagnóstico de calcifilaxis evaluados en el Hospital Italiano de Buenos Aires. Resultados: Se incluyeron 39 pacientes. El 61.5% (24) eran hombres y 38.5% (15) fueron casos de CNU. De éstos, 82% presentaba hipertensión arterial, 66% obesidad y 46% diabetes. El 49% recibía anticoagulantes dicumarínicos. Todos los pacientes con CNU y 75% con CU presentaron úlceras de fondo necrótico, localizadas con mayor frecuencia en las piernas. En 72% de los casos el diagnóstico histológico se efectuó con una toma de biopsia. En todos, el tratamiento fue multimodal y la mortalidad al año fue de 42%. Conclusión: Observamos una elevada proporción de pacientes con CNU, en relación con lo comunicado en la literatura, y la mitad recibía anticoagulantes dicumarínicos. El diagnóstico histológico se efectuó por biopsia en la mayor parte de los casos, para lo cual la toma quirúrgica de la muestra, la tinción con Von Kossa y la evaluación por un patólogo experto fueron claves.

Effect of the COVID-19 Lockdown on Patients Valuation of Usability of Telemedicine.

The aim of this paper was to report patient valuation of usability with our telemedicine system and to explore the effect of pandemic in its behavior. We conducted a cross-sectional study based on the prospective recollection of the results of the Spanish abbreviated version of the Telehealth Usability Questionnaire (TUQ), from October 2019 to July 2020. We observed an inflection point of growth of answers during the pandemic era and a trend of decrease in usability valuations coinciding with the massive and forced implementation of the system after lockdown. This effect was transitory, evidencing an improvement over time. These results might be explained with a sociotechnical approach that includes considering the learning curve and suggest the importance of a telemedicine usability tool to guide decision-making. In conclusion, tools to assess telemedicine services may identify facilitators and barriers to its use in a highly changing social and technological context.

[Bazex syndrome: a rare paraneoplastic disease]. / Síndrome de Bazex: una enfermedad paraneoplásica infrecuente.

Bazex syndrome is a paraneoplastic disorder most commonly linked to squamous cell carcinomas of the upper aerodigestive tract, followed by lung cancer and other malignancies. It manifests through three stages of skin involvement that mirror the tumor's progression. Remarkably, skin lesions precede tumor symptoms or diagnosis in two-thirds of cases, underscoring the crucial role of suspecting this condition as it can promptly reveal an underlying neoplasm. Treatment primarily focuses on addressing the root neoplasm, with recurrent skin lesions potentially indicating tumor relapse. In this context, we present a clinical case involving a male patient whose manifestation of this syndrome facilitated the timely diagnosis of lung adenocarcinoma. This case underscores the significance of understanding this uncommon syndrome and its link to cancer, enabling early and accurate oncological diagnosis.

El síndrome de Bazex es una enfermedad paraneoplásica que se asocia con mayor frecuencia a carcinomas de células escamosas del tracto aerodigestivo superior, seguido en frecuencia por el cáncer de pulmón y otras neoplasias. Afecta a la piel en tres etapas que tienen un comportamiento paralelo al crecimiento del tumor. En dos tercios de los casos, las lesiones cutáneas preceden a los síntomas o al diagnóstico del tumor. De ahí la importancia de la sospecha de esta entidad, que puede desenmascarar a la neoplasia asociada en una etapa temprana. Su tratamiento consiste en tratar la neoplasia subyacente. La recurrencia de las lesiones cutáneas puede revelar la recaída del tumor. Comunicamos el caso clínico de un paciente de sexo masculino en el cual el hallazgo de este síndrome permitió realizar el diagnóstico de un adenocarcinoma de pulmón, lo cual destaca la importancia de conocer a esta rara enfermedad y su asociación con cáncer, para poder realizar el diagnóstico oncológico de forma temprana y oportuna.

Síndrome de Bazex: una enfermedad paraneoplásica infrecuente / Bazex syndrome: a rare paraneoplastic disease

Resumen El síndrome de Bazex es una enfermedad paraneoplá sica que se asocia con mayor frecuencia a carcinomas de células escamosas del tracto aerodigestivo superior, seguido en frecuencia por el cáncer de pulmón y otras neoplasias. Afecta a la piel en tres etapas que tienen un comportamiento paralelo al crecimiento del tumor. En dos tercios de los casos, las lesiones cutáneas preceden a los síntomas o al diagnóstico del tumor. De ahí la importancia de la sospecha de esta entidad, que puede desenmascarar a la neoplasia asociada en una etapa temprana. Su tratamiento consiste en tratar la neopla sia subyacente. La recurrencia de las lesiones cutáneas puede revelar la recaída del tumor. Comunicamos el caso clínico de un paciente de sexo masculino en el cual el hallazgo de este síndrome per mitió realizar el diagnóstico de un adenocarcinoma de pulmón, lo cual destaca la importancia de conocer a esta rara enfermedad y su asociación con cáncer, para poder realizar el diagnóstico oncológico de forma tem prana y oportuna.

Abstract Bazex syndrome is a paraneoplastic disorder most commonly linked to squamous cell carcinomas of the upper aerodigestive tract, followed by lung cancer and other malignancies. It manifests through three stages of skin involvement that mirror the tumor's progression. Remarkably, skin lesions precede tumor symptoms or diagnosis in two-thirds of cases, underscoring the cru cial role of suspecting this condition as it can promptly reveal an underlying neoplasm. Treatment primarily focuses on addressing the root neoplasm, with recurrent skin lesions potentially indicating tumor relapse. In this context, we present a clinical case involving a male patient whose manifestation of this syndrome facilitated the timely diagnosis of lung adenocarcinoma. This case underscores the significance of understand ing this uncommon syndrome and its link to cancer, enabling early and accurate oncological diagnosis.

First detection of herpesvirus and hemosporidians in the endangered Pyrenean Capercaillie (Tetrao urogallus aquitanicus).

Pathogens affect wild bird populations worldwide, contributing to their decline. Considering the scarce health data regarding the endangered Pyrenean Capercaillie (Tetrao urogallus aquitanicus), we molecularly surveyed selected pathogens (Newcastle disease virus, Avian influenza virus, Chlamydia psittaci, avian pathogenic Escherichia coli, Campylobacter jejuni, and Salmonella spp.) in 30 Pyrenean Capercaillie feces collected in the field (Catalonia, northeastern Spain). Additionally, swab and tissue samples from eight wild Pyrenean Capercaillies of Catalonia and Andorra were molecularly tested for herpesvirus and hemosporidians (Plasmodium spp., Haemoproteus spp., and Leucocytozoon spp.). All fecal samples were negative for the pathogens tested. Nevertheless, we detected a novel herpesvirus in 50% (4/8) of the Pyrenean Capercaillies, and hemosporidian DNA in 62.5% (5/8) of the tissue samples (i.e., Haemoproteus sp. [4 of 8] and/or Leucocytozoon sp. [3 of 8]). To our knowledge, this is the first detection of herpesvirus and hemosporidians infections in Pyrenean Capercaillies. The putative novel herpesvirus belongs to the genus Iltovirus. The presence of hemosporidian parasites in this mountain bird species is of concern, and could be related to the marked increase in the average temperature in the Pyrenees as a consequence of climate change. Our findings are fundamental to improve the conservation plans for the endangered Pyrenean Capercaillie population.

Actualización práctica de diagnóstico y tratamiento de la urticaria crónica / Practical update for the diagnosis and treatment of chronic urticaria

Resumen La urticaria es un patrón distintivo de respuesta inflamatoria de piel y/o mucosas caracterizada por la aparición súbita de ronchas evanescentes, angioedema o ambos, asociados a prurito. Las formas agudas son frecuentes y se limitan a brotes de menos de 6 sema nas; mientras que las crónicas tienen una prevalencia menor al 1%, mayor duración y pueden ser espontáneas o inducibles. Los mecanismos etiopatogénicos involucrados en esta enfermedad incluyen la autoalergia, la autoinmunidad y la inflamación con la activación celular, principalmente del mastocito, lo que lleva a su degranulación con libe ración de mediadores vasoactivos. En su abordaje son fundamentales la confirmación diagnóstica; la búsqueda de indicadores de su etiopa togenia; la detección de cofactores que pueden modular su actividad; el reconocimiento de comorbilidades; la evaluación de posibles biomarcadores y, el impacto en la calidad de vida, el registro de la actividad y el control de la enfermedad. El manejo farmacológico tiene por objetivo controlar los síntomas, mientras la urticaria resuelve de forma espontánea. Este se describe de forma escalonada con una complejidad creciente.

Abstract Urticaria is a distinctive pattern of inflammatory re sponse of the skin and/or mucous membranes charac terized by the sudden appearance of vanishing wheals, angioedema, or both, associated with pruritus. Acute forms are frequent and limited to outbreaks of less than 6 weeks; while the chronic ones have a prevalence of less than 1%, longer duration and can be spontaneous or inducible. The etiopathogenic mechanisms involved in this disease include autoallergy, autoimmunity, and inflam mation with cell activation, mainly of the mast cell, leading to its degranulation with the release of vasoac tive mediators. Along its approach, diagnostic confirmation, search for indicators of its etiopathogenesis, detection of cofactors that can modulate its activity, recognition of comorbidi ties, evaluation of possible biomarkers and the assess ment of disease activity, impact and control are essential. The pharmacological management aims to control the symptoms, until the urticaria, which is self-resolv ing, is gone. This is described in a stepwise fashion with increasing complexity.

Estado nutricional de gestantes adolescentes assistidas pela Atenção Básica: um estudo de série temporal com dados do estado de Minas Gerais / Nutritional status of pregnant adolescents assisted in Primary Care: A time series study with data from the state of Minas Gerais

Estudo ecológico, de série temporal, que teve como objetivo analisar a tendência do estado nutricional de gestantes adolescentes assistidas pela atenção primária à saúde em Minas Gerais. Os dados foram provenientes do Sistema de Vigilância Alimentar e Nutricional, referente ao estado nutricional de 140.969 gestantes adolescentes entre os anos de 2010 a 2019; apresentados em variação percentual anual por meio da regressão linear simples. O baixo peso mostrou tendência decrescente nas macrorregiões Sul e Triângulo do Norte com variação anual de -0,88% (IC95% -1,67; -0,09) e -0,79% (IC95% -1,06; -0,51) e o excesso de peso registrou tendência crescente nas macrorregiões Nordeste, Noroeste, Norte, Triângulo do Sul e Vale do Aço com a variação anual de 0,28% (IC95% 0,04;0,52), 0,37% (IC95% 0,23;0,51), 0,64% (IC95% 0,32;0,95), 0,44% (IC95% 0,18;0,70) e 0,57% (IC95% 0,26;0,88), respectivamente. Conclui-se que, no período avaliado, houve a tendência de aumento do excesso de peso entre as gestantes adolescentes no estado de Minas Gerais, acompanhando o processo de transição nutricional no país (AU).

An ecological and time-series study to analyze trends in the nutritional status of pregnant adolescents assisted in Primary Health Care in Minas Gerais. The data came from the Food and Nutrition Surveillance System, referring to the nutritional status of 140,969 pregnant adolescents between 2010 and 2019, presented in annual percentage change using simple linear regression. Low weight showed a decreasing trend in the South and Northern Triangle macro-regions with annual variations of -0.88% (95% CI: -1.67;-0.09) and -0.79% (95% CI: -1.06;-0.51); in turn, excess weight recorded an increasing trend in the Northeast, Northwest, North, Southern Triangle and Vale do Aço macro-regions, with annual variations of 0.28% (95% CI: 0.04;0.52), 0.37% (95% CI: 0.23;0.51), 0.64% (95% CI: 0.32;0.95), 0.44% (95% CI: 0.18;0.70), and 0.57% (95% CI: 0.26;0.88), respectively. It is concluded that, during the evaluated period, there was an increasing trend in excess weight among pregnant adolescents in the state of Minas Gerais, following the nutritional transition process in the country (AU).

[Practical update for the diagnosis and treatment of chronic urticaria]. / Actualización práctica de diagnóstico y tratamiento de la urticaria crónica.

Urticaria is a distinctive pattern of inflammatory response of the skin and/or mucous membranes characterized by the sudden appearance of vanishing wheals, angioedema, or both, associated with pruritus. Acute forms are frequent and limited to outbreaks of less than 6 weeks; while the chronic ones have a prevalence of less than 1%, longer duration and can be spontaneous or inducible. The etiopathogenic mechanisms involved in this disease include autoallergy, autoimmunity, and inflammation with cell activation, mainly of the mast cell, leading to its degranulation with the release of vasoactive mediators. Along its approach, diagnostic confirmation, search for indicators of its etiopathogenesis, detection of cofactors that can modulate its activity, recognition of comorbidities, evaluation of possible biomarkers and the assessment of disease activity, impact and control are essential. The pharmacological management aims to control the symptoms, until the urticaria, which is self-resolving, is gone. This is described in a stepwise fashion with increasing complexity.

La urticaria es un patrón distintivo de respuesta inflamatoria de piel y/o mucosas caracterizada por la aparición súbita de ronchas evanescentes, angioedema o ambos, asociados a prurito. Las formas agudas son frecuentes y se limitan a brotes de menos de 6 semanas; mientras que las crónicas tienen una prevalencia menor al 1%, mayor duración y pueden ser espontáneas o inducibles. Los mecanismos etiopatogénicos involucrados en esta enfermedad incluyen la autoalergia, la autoinmunidad y la inflamación con la activación celular, principalmente del mastocito, lo que lleva a su degranulación con liberación de mediadores vasoactivos. En su abordaje son fundamentales la confirmación diagnóstica; la búsqueda de indicadores de su etiopatogenia; la detección de cofactores que pueden modular su actividad; el reconocimiento de comorbilidades; la evaluación de posibles biomarcadores y, el impacto en la calidad de vida, el registro de la actividad y el control de la enfermedad. El manejo farmacológico tiene por objetivo controlar los síntomas, mientras la urticaria resuelve de forma espontánea. Este se describe de forma escalonada con una complejidad creciente.

Salmonella assessment along the Spanish food chain: Likelihood of Salmonella occurrence in poultry and pig products is maintained across the food chain stages.

Salmonellosis is one of the most important foodborne diseases worldwide, including the European Union. Despite the One Health approach measures for risk assessment and risk management implemented by the European Union, the occurrence of disease and disease outbreaks remains high (e.g. 694 outbreaks were reported in 2020), highlighting the need of new assessment methods. Herein we applied machine learning using the random forests method to evaluate and identify key points regarding the occurrence of Salmonella sp. along the Spanish food chain during 2015-2020, using data provided by the Spanish Agency for Food Safety and Nutrition. We compared the role of the three categorical variables [product (20 categories), region (18 categories) and stage (11 categories)]. Salmonella presence was influenced by the three explanatory variables considered: first by product, followed by region and stage. The most determinant product for Salmonella probability was 'meat', while the most important stage was 'slaughterhouse'. Specifically, the highest values were found in pig and poultry meats. In these products, the Salmonella probability was high at the early and final stages of the food chain, although not at intermediate stages. The presence of Salmonella in the final stages (retail) of the food chain is of concern, as it can cause human cases of salmonellosis, including outbreaks. This study demonstrates the utility of the random forest method to identify key points and evaluate the control efforts. We recommend improving the surveillance and control measures, especially in the product and stages pointed out by our analysis, and enhancing the data collection harmonization among the different autonomous communities.

Múltiples reacciones adversas graves a fármacos en un paciente luego de la infección por COVID-19: informe de un caso / Drug-induced severe cutaneous adverse reactions in a patient after COVID-19 infection: case report

Durante la pandemia por COVID-19 se observaron diversas reacciones adversas a fármacos. Esto pudo haber estado relacionado con una mayor susceptibilidad inmunológica de los pacientes con SARS-CoV-2 a presentar este tipo de cuadros, así como también con la exposición a múltiples medicamentos utilizados en su tratamiento. Comunicamos el caso de un paciente con una infección respiratoria grave por COVID-19, que presentó 2 reacciones adversas graves a fármacos en un período corto de tiempo. (AU)

During the COVID-19 pandemic, various adverse drug reactions were observed. This could have been related to a greater immunological susceptibility of patients with SARS-CoV-2 to present this type of symptoms, as well as exposure to multiple drugs used in their treatment. We report the case of a patient with a severe respiratory infection due to COVID-19, who presented 2 serious adverse drug reactions associated with paracetamol in a short period of time. (AU)

A Dalbavancin for Successful Treatment of Infective Endocarditis Caused by Enterococcus faecalis.

Infective endocarditis is a relatively uncommon infection that requires a high index of suspicion, which can sometimes delay its diagnosis. It requires several weeks of intravenous antibiotics, which traditionally requires long hospital stays. Dalbavancin is a novel antibiotic with high activity against several Gram-positive pathogens. Its weekly administration allows the outpatient management of complicated infections requiring parenteral treatment, but only a few cases of Enterococcus faecalis endocarditis treated with dalbavancin have been reported in the literature. We here report a case of successful treatment with dalbavancin of an infectious endocarditis caused by E. faecalis. LEARNING POINTS: Infective endocarditis is a relatively uncommon infection that requires a high index of suspicion and its diagnosis can sometimes be challenging.Endovascular infections require long-term parenteral treatment, so outpatient parenteral antibiotic therapy (OPAT) is an option for stable patients in order to avoid prolonged hospital stays.Dalbavancin is a novel antibiotic with high activity against Gram-positive pathogens and can be administered weekly.There is growing experience in the ambulatory treatment of Gram-positive cocci endovascular infections.

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer.

PURPOSE: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS: We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. RESULTS: By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor-positive, 25.2% (n = 131) human epidermal growth factor receptor 2-positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19-specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. CONCLUSION: Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status.

BACKGROUND: Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown. METHODS: We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated. RESULTS: We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS. CONCLUSION: We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results.