A modal age at death approach to forecasting adult mortality.

Recent studies have shown that there are some advantages to forecasting mortality with indicators other than age-specific death rates. The mean, median, and modal ages at death can be directly estimated from the age-at-death distribution, as can information on lifespan variation. The modal age at death has been increasing linearly since the second half of the twentieth century, providing a strong basis from which to extrapolate past trends. The aim of this paper is to develop a forecasting model that is based on the regularity of the modal age at death and that can also account for changes in lifespan variation. We forecast mortality at ages 40 and above in 10 West European countries. The model we introduce increases forecast accuracy compared with other forecasting models and provides consistent trends in life expectancy and lifespan variation at age 40 over time.

Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Restrospective reappraisal of the prognostic classification of spitzoid melanocytic neoplasms after BRAF and NRAS mutation characterisation: a single institution experience.

AIMS: The current WHO classification of melanocytic tumours excludes neoplasms showing BRAF or NRAS mutations from the Spitz category. This study aimed to review and reclassify atypical melanocytic tumours with spitzoid morphological features diagnosed between 2009 and 2021 in our hospital after expanding the molecular profile, including BRAF and NRAS mutations in all cases. METHODS AND RESULTS: A total of 71 neoplasms showing spitzoid features (Spitz-like) and atypia were included. The risk of progression of tumours was first studied by integrating the morphology, immunohistochemistry (p16, Ki67, HMB45 and PRAME) and fluorescence in-situ hybridisation (FISH) results (melanoma multiprobe and 9p21). In a second step, after expanding the molecular study, including BRAF and NRAS mutational status, the neoplasms were finally classified into four subgroups: atypical Spitz tumour (AST, n = 45); BRAF-mutated naevus/low-grade melanocytoma with spitzoid morphology (BAMS, n = 2); Spitz melanoma (SM, n = 14); and BRAF or NRAS mutated melanoma with spitzoid features (MSF, n = 10). Follow-up of patients revealed uneventful results for AST and BAMS. Only one SM presented lymph node metastasis after 134 months. Conversely, patients with MSF showed an unfavourable outcome: three developed lymph node metastases after a mean time of 22 months, with one patient presenting distant metastasis and dying of the disease 64 months from diagnosis. The progression-free survival showed significant differences between the four groups of spitzoid tumours (P < 0.001) and between both melanoma subtypes (P = 0.012). CONCLUSIONS: The classification and prognostication of atypical neoplasms with spitzoid features requires the integration of histomorphology with the molecular investigation of tumours, which should include BRAF and NRAS mutational status.

Combined WNT-activated deep penetrating/plexiform melanocytoma: insights into clinicopathological and molecular characterization.

INTRODUCTION: A combined deep penetrating tumor redefined as WNT-activated deep penetrating/plexiform melanocytoma (DPM), may pose challenging clinical and histological diagnoses. OBJECTIVES: This study aims to review the clinicopathological characteristics of combined DPMs and characterize the molecular profile of atypical and malignant forms. METHODS: The study included 51 cases of combined DPMs diagnosed at the Hospital Clinic of Barcelona and the University of Florence between 2012 and 2020. Clinical data, dermoscopy images (when available), and histological characteristics were reviewed. Immunohistochemistry for ß-catenin, LEF1, HMB45, Ki67, p16, and PRAME was performed. Atypical forms underwent NGS panel analysis, including driver genes implicated in DPMs, TERT- promoter (p) mutation, and the investigation of the 9p21 locus via FISH. RESULTS: Among the 51 cases (32 females and 19 males, age range 4- 74), 68% with available clinical data were initially suspected of melanoma. Except for one case, complete excision resulted in no recurrences or metastases. One incompletely excised combined DPM developed a lymph node melanoma metastasis 10 years later. Ten cases (20%) showed atypical histological features; 7 cases (13%) exhibited a significant loss of p16 expression; and 2 cases (4%) showed a high-proliferative index (Ki67 over 5%). NGS analysis in these cases revealed a double mutation BRAFV600E and exon 3 CTNNB1; no TERT-p mutations were detected. CONCLUSIONS: Clinical suspicion of melanoma is common in combined DPMs, but the malignant progression is infrequent in tumors lacking high-grade atypia or proliferation. These findings are congruent with the consideration of these lesions as intermediate-grade tumors or melanocytomas.

Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

Morphological Description and Live Weight Prediction from Body Measurements of Socorro Island Merino Lambs.

The aim of this study was to describe the morphology and estimate live weight from body measurements of Socorro Island Merino lambs. A group of Socorro Island Merino lambs was recorded from birth to year for live weight, rump width, rump length, withers height, body length, cannon bone perimeter, and chest girth, width, and depth. The effect of the lamb type on body measurements and live weight was analyzed using ANOVA, Pearson's correlation analysis was performed to estimate the relationship between body measurements and live weight, multiple linear regressions were fitted to obtain prediction equations of live weight from the body measurements and finally, chest girth was used to generate prediction equations using linear and exponential models. At birth and at year, differences were observed in body measurements, especially those related to the thoracic region, with crossbred males showing the highest values. Live weight was correlated with almost all the body measurements, with the highest coefficients observed with chest girth, chest width, and chest depth. Live weight can be accurately predicted from multiple regression equations using several body measurements, but using only chest girth (CG) as a predictor, the exponential equation W0-365 = 0.9142 exp(0.0462 CG) showed the best accuracy.

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: A Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

The treatment of head and neck and salivary gland tumours is complicated and is constantly evolving. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein-Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica - SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica - SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: A Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology / Recomendaciones para el uso de biomarcadores para cáncer de cabeza y cuello, incluyendo tumores de glándulas salivares: consenso de la Sociedad Española de Oncología Médica y la Sociedad Española de Patología

The treatment of head and neck and salivary gland tumours is complicated and is constantly evolving. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms.In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica – SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica – SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.(AU)

El tratamiento de los tumores de cabeza y cuello y de glándulas salivales es complejo, y evoluciona de forma constante. Los indicadores pronósticos y predictivos de respuesta al tratamiento son enormemente valiosos para diseñar terapias individualizadas, lo que justifica su investigación y validación. Algunos biomarcadores como p16, el virus de Epstein-Barr, PD-L1, los receptores de andrógenos o HER-2, ya se utilizan de manera rutinaria en la práctica clínica. Estos biomarcadores, junto con otros marcadores que están actualmente en desarrollo, y la secuenciación masiva de genes, aseguran los futuros avances en el tratamiento de estas neoplasias. En este consenso, un grupo de expertos en el diagnóstico y tratamiento de los tumores de cabeza y cuello y glándulas salivales seleccionado por la Sociedad Española de Anatomía Patológica (SEAP) y la Sociedad Española de Oncología Médica (SEOM) evalúan la información actualmente disponible y proponen una serie de recomendaciones para optimizar la determinación y utilización en la práctica clínica diaria de los biomarcadores.(AU)

Persistent lymph nodes after curative chemoradiotherapy for head and neck cancer: imaging predictors of response for decision-making.

PURPOSE: To identify response predictors in patients with head and neck squamous cell carcinoma (N + HNSCC) and persistent lymph nodes after curative chemoradiotherapy treatment (CCRT). MATERIALS AND METHODS: Consecutive patients with N + HNSCC treated with CCRT and persistent lymph nodes at first follow-up between 2015 and 2021 were identified and analyzed. Complete response was defined as the absence of lymph node metastatic involvement in patients with salvage lymphadenectomy or the absence of progression after 1 year of successive follow-ups. Tumour type and location, staging, and human papillomavirus (HPV) status were considered for analysis. The number and size of lymph nodes, type, shape, enhancement and margins on diagnostic and follow-up CT were also analyzed. RESULTS: The cohort included 46 patients with 134 pathological lymph nodes. Logistic regression models showed the following variables to be significant: performance of salvage lymphadenectomy (OR 0.094, [CI 95% 0.004-0.61], p = 0.037); the type of lymphadenopathy on diagnostic CE-CT (solid vs. cystic) (N1: OR = 4.11, [CI 95% 1.11-17.93], p = 0.042 and N3: OR 6.42, [CI 95% 1.2-42.56], p = 0.036); the change of shape (round to oval) on the follow-up CE-CT (OR 9.76, [CI 95% 1.79-8.57], p = 0.016) and the time in days between CCRT and the first follow-up CE-CT (OR 1.06, [CI 95% 1.004-1.13], p = 0.048). CONCLUSIONS: In our experience, the presence of solid lymph nodes on pre-treatment CT and the change in shape from round to oval on post-treatment CT are predictors of response to treatment in patients with N + HNSCC persistent lymph nodes after CCRT. Increasing the temporal interval between treatment and follow-up CT should be considered to avoid unnecessary nodal dissections.

Better alone? The impact of living arrangements on mortality of Costa Rican older adults / Melhor sozinho? O impacto de arranjos domiciliares na mortalidade de idosos costarriquenhos / ¿Mejor solo? El impacto de los arreglos de vivienda en la mortalidad de las personas adultas mayores costarricenses

Abstract Previous research has shown differentiated effects of living arrangement types on mortality. However, little is known about this phenomenon in Latin America and its multigenerational households. This study measures the relationship between older adults' living arrangement types and subsequent mortality. Gompertz event history models were performed to estimate mortality differences across living arrangements. We used the Costa Rica Longevity and Aging Study (CRELES) pre-1945 cohort in the 2005, 2007, and 2009 waves. The results show that older adults who live with a partner have the highest survival rates among the categories tested. When controlling for sex and age in the model, the effect of living alone is not different from partnered living. When controlling for socioeconomic and health factors as well, older adults living with their children or others show an increased risk of death by at least 40% (p-value<0.05). The study demonstrates an association between living arrangements and older adult mortality in Costa Rica. Results show that the highest survival chances rely on being partnered and suggest that support exchanges with other family members are not equally effective. Including this variable type in mortality studies is crucial to better understanding how household conditions relate to health and mortality outcomes.

Resumo Pesquisas anteriores mostraram efeitos diferenciados dos tipos de arranjos residenciais sobre a mortalidade. Entretanto, pouco se sabe sobre os fenômenos na América Latina e suas residências multigeracionais. Este estudo aborda a relação entre os tipos de arranjos residenciais de idosos e a mortalidade subsequente. A análise de sobrevivência foi realizada por meio do modelo Gompertz, estimando as diferenças de mortalidade entre os diferentes arranjos domiciliares. Foi utilizado o Estudo da Longevidade e Envelhecimento da Costa Rica (CRELES) pré-1945, de 2005, 2007 e 2009. Os resultados mostram que os idosos que vivem com companheiro apresentam as maiores taxas de sobrevivência entre as categorias testadas. Ao controlar por sexo e idade no modelo, o efeito de morar sozinho não é diferente de morar com companheiro. Se os fatores socioeconômicos e de saúde forem controlados, os idosos que vivem com seus filhos ou outras pessoas possuem um risco aumentado de morte em pelo menos 40% (p-valor <0,05). O estudo demonstra que existe uma associação entre os arranjos domiciliares e a mortalidade de idosos na Costa Rica. Os resultados mostram que as maiores chances de sobrevivência estão entre os idosos que possuem um parceiro, sugerindo que os cuidados providos por membros da família não são igualmente efetivos. A inclusão desse tipo de variável nos estudos de mortalidade é crucial para entender como as condições domiciliares se relacionam com os resultados de saúde e mortalidade.

Resumen La literatura anterior a este artículo ha mostrado efectos diferenciados de los tipos de arreglos de vivienda en la mortalidad. Sin embargo, poco se sabe sobre el fenómeno en Latinoamérica y sus viviendas multigeneracionales. Este estudio mide la relación entre los tipos de arreglos de vivienda de las personas adultas mayores y la subsecuente mortalidad. Modelos de historia de eventos Gompertz se hicieron para estimar las diferencias de mortalidad entre los arreglos de vivienda. Se utilizó el Estudio de Longevidad y Envejecimiento Saludable (CRELES) en la cohorte pre-1945 y las rondas 2005, 2007 y 2009. Los resultados muestran que las personas adultas mayores que viven con una pareja tienen las mayores tasas de sobrevivencia entre las categorías comparadas. Al controlar por sexo y edad en el modelo, el efecto de vivir solo no es diferente del de estar emparejado. Si también se controlan los factores socioeconómicos y de salud, los las personas adultas mayores que viven con hijos o hijas o con otros muestran un riesgo de muerte al menos 40 % mayor (p-valor <0,05). El estudio demuestra que existe una relación entre los arreglos de vivienda y la mortalidad de las personas adultas mayores en Costa Rica. Los resultados muestran que las mayores probabilidades de supervivencia recaen en estar emparejado y sugieren que los intercambios de apoyo con otros miembros de la familia no son igualmente efectivos. La inclusión de este tipo de variables en los estudios de mortalidad es crucial para entender cómo se relacionan las condiciones de vivienda con los resultados de salud y mortalidad.

Analysis of the Consumption of Sports Supplements in Open Water Swimmers According to the Competitive Level.

BACKGROUND: Sports supplements (SS) are widely consumed by many types of athletes to improve their performance. These SS are classified according to their level of scientific evidence, by the ABCD system from the Australian Institute of Sport (AIS). In open water swimming, their use may be necessary due to the physiological challenges posed by this sport discipline. However, there is currently little literature on the use of SS in open water swimmers. The aim of this work is to analyze the pattern of consumption of SS by open water swimmers, by studying the differences according to the competitive level (regional vs. national). METHODS: Descriptive and cross-sectional study on the consumption and use of SS by federated open water swimmers in Spain in the 2019/2020 and 2020/2021 seasons. The data were collected through a validated questionnaire. RESULTS: 79.5% of the participants consumed SS, with significant differences according to their level, being higher in athletes at the national level. The most-consumed SS by the swimmers studied were sports drinks, energy bars, caffeine, vitamin C, and vitamin D. CONCLUSIONS: It was observed that the consumption of SS in open water swimmers was high, and of the five most-consumed SS, four of them belonged to the category of greatest scientific evidence.

CO2-TOLMS for laryngeal cancer in the elderly, pushing the boundaries of partial laryngectomy.

INTRODUCTION: CO2 transoral laser microsurgery (CO2-TOLMS) has pushed the indications of partial surgery of the larynx regardless the age of the patient. OBJECTIVE: To evaluate the complications and the oncologic and functional outcomes of CO2-TOLMS in patients older and younger than 70 years. METHODS: Retrospective analysis of 1244 consecutive laryngeal carcinomas treated with CO2-TOLMS. Complications, length of hospitalization, functional and survival outcomes were evaluated. RESULTS: The mean age was 64.2 ±â€¯11.1 years (20-96). Four hundred and sixteen patients were older than 70 years and 104 older than 80 years. The main location was the glottis (912), followed by the supraglottis (332). There were no differences in pT classification between the age groups. No differences were observed in voice outcomes. A higher rate of signs of aspiration at the glottic location was observed for those older than 70 years (2.1 % vs 5 %, p = 0.027). The need for definitive gastrostomy in supraglottic tumours was higher in those older than 70 years (0 % vs 6.5 %, p: 0.001). In the glottis, no differences in tracheostomy or gastrostomy rates were observed. Five-year overall survival was lower in the older than 70 years. No differences in disease-specific survival were observed in early stages for both locations, but a lower survival was observed in stage III glottic cancer for the older than 70 years. CONCLUSIONS: CO2-TOLMS is a valid treatment for laryngeal carcinomas in the elderly, with a reduced number of complications and good functional and oncologic outcomes.

Morphological evaluation of melanocytic lesions with three-dimensional line-field confocal optical coherence tomography: correlation with histopathology and reflectance confocal microscopy. A pilot study.

BACKGROUND: Line-field confocal optical coherence tomography (LC-OCT) is a new in vivo emerging technique that provides cellular resolution, allows deep imaging (400 µm) and produces real-time images in both the horizontal and vertical plane and in three dimensions. No previous description of different subtypes of melanocytic lesions and their correlation with histopathology and reflectance confocal microscopy has been reported. AIM: To describe the features of melanocytic lesions by LC-OCT and their correlation with histopathology and reflectance confocal microscopy (RCM) findings. METHODS: Selected melanocytic benign lesions and melanomas were imaged in vivo with RCM and LC-OCT at the Fundación Hospital Clinic (Barcelona, Spain). A minimum area of 4 × 4 mm (block image) at four depths (stratum granulosum, suprabasal, layer dermoepidermal junction and upper dermis) were acquired with RCM and a minimum of three cubes with LC-OCT. Horizontal, vertical sections and three-dimensional (3D) cubes of LC-OCT were matched with RCM (Vivablock two-dimensional composite mosaic) and histopathology, with ~5 µm lateral resolution accuracy (the same cell nuclei were measured in X, Y and Z) and evaluated by three observers experienced in using RCM and histopathology. RESULTS: In total, 12 melanocytic tumours (2 in situ melanomas, 2 invasive melanomas, 4 atypical naevi, 2 intradermal naevi, 1 compound naevus and 1 junctional naevus) were included. High correlation with 5 µm accuracy between RCM and LC-OCT was observed for each tumour. The 3D images of melanocytic lesions were obtained with cellular resolution and correlated with both RCM and histopathology, allowing an understanding of the architecture and precise correlation at the cellular level with RCM. Similarities between LC-OCT and RCM for the described diagnostic features and architecture (nests of melanocytic cells, ringed and meshwork pattern, and cellular details of tumour cells as dendritic and pagetoid cells) were confirmed. The main advantage of diagnosis by RCM fixed probe was the ability to produce larger scans of the lesion using mosaicing compared with an LC-OCT handheld probe. CONCLUSION: LC-OCT allows the architectural and cellular description of different types of melanocytic lesions. LC-OCT showed high correlation with histopathology (vertical sections) and RCM (horizontal sections) in melanocytic lesions. Diagnostic criteria for RCM were similar to those for LC-OCT.