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Abstract Non-invasive diagnostic modalities are integral to cardiovascular care; however, current systems primarily measure peripheral pressure, limiting the breadth of cardiovascular prognostication. We report a novel approach for extracting left side heart sounds using a brachial cuff device. The technique leverages brachial cuff device enhanced signal resolution to capture pressure fluctuations generated by cardiohemic system vibrations, the sound pressure waveform. We analyze left heart catheterization data alongside simultaneous brachial cuff device measurements to correlate sound pressure waveform features with left ventricle (LV) contractility. The extracted sound pressure waveform reveals two prominent oscillatory wave packets, termed WP1 and WP2, originating from cardiac structure vibrations associated with LV contractions and relaxation. We demonstrate that WP1 originates from LV contraction during systolic blood ejection through the aortic valve (AV) and is correlated with LV isovolumetric contraction, clinically measured by LV dPdt-max (Pearson-R = 0.65, p

Abstract Colorectal cancer (CRC) is a global health concern, and the incidence of early onset (EO) CRC, has an upward trend. This study delves into the genomic landscape of EO-CRC, specifically focusing on pediatric (PED) and young adult (YA) patients, comparing them with adult (AD) CRC. In this retrospective monocentric investigation, we performed targeted next-generation sequencing to compare the mutational profile of 38 EO-CRCs patients (eight PED and 30 YA) to those of a ‘control group’ consisting of 56 AD-CRCs. Our findings reveal distinct molecular profiles in EO-CRC, notably in the WNT and PI3K-AKT pathways. In pediatrics, we observed a significantly higher frequency of RNF43 mutations, whereas APC mutations were more prevalent in adult cases. These observations suggest age-related differences in the activation of the WNT pathway. Pathway and copy number variation analysis reveal that AD-CRC and YA-CRC have more similarities than the pediatric patients. PED shows a peculiar profile with CDK6 amplification and the enrichment of lysine degradation pathway. These findings may open doors for personalized therapies, such as PI3K-AKT pathway inhibitors or CDK6 inhibitors for pediatric patients. Additionally, the distinct molecular signatures of EO-CRC underscore the need for age-specific treatment strategies and precision medicine. This study emphasizes the importance of comprehensive molecular investigations in EO-CRCs, which can potentially improve diagnostic accuracy, prognosis, and therapeutic decisions for these patients. Collaboration between the pediatric and adult oncology community is fundamental to improve oncological outcomes for this rare and challenging pediatric tumor.

Case summary A 12-year-old castrated male domestic shorthair cat was referred for investigation of lethargy, hindlimb weakness with plantigrade stance and ventroflexion of the neck. The cat was fed a balanced diet and had received methylprednisolone acetate at a dose of 20 mg intramuscularly every 6 months for 6 years. On blood work, severe hypokalaemia and marked elevation of muscle enzymes were noticeable. The findings were suggestive of hypokalaemic myopathy. Urine fractional excretion of potassium (FE k ) was moderately high (9.04%), and serum aldosterone was below the reference interval. An adrenocorticotropic hormone (ACTH) stimulation test was compatible with adrenal suppression. Upon hospitalisation, the patient was given intravenous (IV) Ringer lactate solution supplemented with potassium chloride and oral potassium citrate. The serum potassium concentration normalised by the fifth day of hospitalisation; therefore, IV potassium supplementation was suspended. The cat was discharged with oral potassium and the dose was gradually reduced over time. After 4 months, the cat was clinically normal; the serum potassium concentration remained within the normal range and the adrenal glands showed some response to ACTH stimulation. Potassium supplementation was therefore discontinued. One month later, the serum potassium concentration was still within normal limits and at the time of writing (7 months after presentation), no clinical signs had reoccurred. Relevance and novel information This report describes a case of hypokalaemic myopathy associated with iatrogenic hypercorticism in a cat. This condition was successfully treated with supplementation of potassium and a complete clinical remission was achieved within 4 months.

BACKGROUND AND OBJECTIVES: During the COVID-19 pandemic, health professionals have experienced a work overload that may be associated with increased pain intensity. The aim of this study was to analyze the frequency and intensity of musculoskeletal pain in the different anatomical regions reported by health professionals who worked in Intensive Care Units (ICU) during the pandemic and to investigate associations between clinical variables. METHODS: This is a cross-sectional, analytical, quantitative and multicenter study carried out in six ICU between July 2021 and February 2022. The Nordic Questionnaire of Musculoskeletal Symptoms (QNSO) was used for data collection, as well as a questionnaire prepared by the researchers on sociodemographic, work and clinical data, and the visual numeric scale (VNS) for pain assessment. Analyses were carried out using descriptive and inferential statistics. RESULTS: The sample consisted of 205 health professionals. With regard to pain intensity, according to the visual analog scale (VAS), an average of 3.76 was observed. The analysis of the association between the variables indicated a greater intensity of pain in females, with a higher frequency of mild and moderate pain, age over 40, in the professional categories of nursing technicians and doctors. The presence of severe pain was associated with poor general health and shorter time in professional practice. CONCLUSION: Most of the professionals reported pain of varying intensity and in different anatomical regions, the most frequently cited being the upper back and neck. Musculoskeletal disorders are directly related to work activity, age, gender and lack of leisure time.

Introduçao: Durante a pandemia por COVID-19, os profissionais de saúde passaram por uma sobrecarga de trabalho que pode estar associada com o aumento da intensidade da dor. Objetivo: analisar os níveis de estresse de profissionais de saúde que atuaram em UTIs COVID e associar com as variáveis clínicas, sociodemográficas e a dor. Método: estudo transversal, quantitativo e multicêntrico, com 205 participantes nas UTIs COVID de cinco municípios do Sul do Brasil. A coleta de dados utilizou questionário on-line autoaplicável. A análise dos dados utilizou estatística descritiva e inferencial.Resultados: a maioria dos participantes demonstrou estar em trabalho ativo (35,6%), 25,8% trabalho de baixa exigência, 20% trabalho de alta exigência e 18,6% trabalho passivo. Conclusão: foi observado alta demanda psicológica, alto controle sobre o trabalho e a presença de apoio social, caracterizando um trabalho ativo. Os técnicos de enfermagem e os que possuem carga horaria de 36 horas semanais apresentaram baixo controle sobre o trabalho. Também foi constatado que não ter dor ou dor leve esta relacionada com a baixa demanda psicológica e apoio social.

Abstract Background Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients’ reported symptomatology is still unclear. Methods Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. Results We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102–123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. Conclusions In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Abstract In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract. Enrolled patients received lanreotide ATG 120 mg plus oral metformin, up to a maximum dosage of 2550 mg/day. We enrolled 20 patients, of whom 18 (90%) and 2 (10%) had WDNETs of the GI and thoracic tract, respectively. Fourteen patients (70%) were non-diabetic. With a 5% incidence of SAEs, the study met its primary objective of demonstrating treatment safety. With a median follow-up of 39 months (95% CI 28-NE), median PFS was 24 months (95% CI 16-NE), with 12-month and 24-month PFS probability of 75% (95% CI 58–97) and 49% (95% CI 31–77), respectively. We found no statistically significant PFS differences between diabetic and non-diabetic patients. Among exploratory analyses, the presence of tumor genomic alterations in DNA damage pathways was associated with trend towards worse PFS, whereas a precocious reduction of HOMA-IR index and plasma cholesterol concentration showed a trend towards an association with better PFS. In conclusion, metformin plus lanreotide ATG is a safe and well tolerated combination treatment that is associated with promising antitumor activity in both non-diabetic and diabetic patients with WDNETs, and that warrants further investigation in larger clinical trials.

Objetivo: Analizar el dolor musculoesquelético en los profesionales de la salud de atención primaria y sus experiencias durante la pandemia de COVID-19. Método: estudio de métodos mixtos realizado en el sur de Brasil entre junio de 2021 y febrero de 2022. Una muestra de 50 participantes, mediante cuestionarios relacionados con el dolor y los síntomas musculoesqueléticos y entrevistas con guiones preparados de antemano. Análisis de datos mediante estadísticas descriptivas e inferenciales y análisis temático de contenido. Resultados: La mayoría de las participantes pertenecían al sector de la enfermería y trabajaban 40 horas semanales. Regiones más afectadas: hombros, parte superior de la espalda y cuello, con dolores que van de moderados (42%) a intensos (10%). Diferencias estadísticamente significativas relacionadas con el dolor y el miedo a contraer COVID-19 entre las personas con problemas de salud previos y las enfermeras. Conclusión: Dado que el dolor puede estar asociado a las condiciones de trabajo, es esencial identificar los factores de riesgo y evitar mayores daños a la salud de los trabajadores.

Objective: To analyze musculoskeletal pain in primary care health professionals and their experience during the COVID-19 pandemic. Method: A mixed-methods study carried out in southern Brazil between June 2021 and February 2022. A sample of 50 participants, using questionnaires related to pain and musculoskeletal symptoms and interviews with pre-prepared scripts. Data analysis using descriptive and inferential statistics and Thematic Content Analysis. Results: Most of the nursing sector participants worked 40 hours a week. The most affected areas are the shoulders, upper back, and neck, ranging from moderate (42%) to severe (10%) pain. Statistically significant differences related to pain and fear of contracting COVID-19 between those with previous health problems and nurses. Conclusion: Given that pain can be associated with working conditions, it is essential to identify risk factors to avoid further damage to workers' health.

Objetivo: analisar a dor musculoesquelética em profissionais de saúde na atenção primária e sua vivência durante a pandemia da COVID-19. Método: estudo de métodos mistos, realizado no sul do Brasil, entre junho de 2021 e fevereiro de 2022. Amostra de 50 participantes, utilizando os questionários relacionados à dor e aos sintomas osteomusculares e entrevistas com roteiros pré-elaborados. Análise de dados com estatísticas descritivas, inferenciais e Análise Temática de Conteúdo. Resultados: a maior parte dos participantes foram da área da Enfermagem, com 40 horas semanais. Regiões mais acometidas: ombros, parte superior das costas e pescoço, variando de dor moderada (42%) e intensa (10%). Diferenças estatísticas significativas relacionadas à dor e medo de contrair a COVID-19, entre aqueles com problemas prévios de saúde e enfermeiros. Conclusão: tendo em vista que a dor pode estar associada às condições de trabalho, torna-se essencial a identificação dos fatores de risco, evitando maiores agravos para a saúde do trabalhador.

Background Noninvasive pulse waveform analysis is valuable for central cardiovascular assessment, yet controversies persist over its validity in peripheral measurements. Our objective was to compare waveform features from a cuff system with suprasystolic blood pressure hold with an invasive aortic measurement. Methods and Results This study analyzed data from 88 subjects undergoing concurrent aortic catheterization and brachial pulse waveform acquisition using a suprasystolic blood pressure cuff system. Oscillometric blood pressure (BP) was compared with invasive aortic systolic BP and diastolic BP. Association between cuff and catheter waveform features was performed on a set of 15 parameters inclusive of magnitudes, time intervals, pressure–time integrals, and slopes of the pulsations. The evaluation covered both static (subject‐averaged values) and dynamic (breathing‐induced fluctuations) behaviors. Peripheral BP values from the cuff device were higher than catheter values (systolic BP–residual, 6.5 mm Hg; diastolic BP–residual, 12.4 mm Hg). Physiological correction for pressure amplification in the arterial system improved systolic BP prediction (r2=0.83). Dynamic calibration generated noninvasive BP fluctuations that reflect those invasively measured (systolic BP Pearson R=0.73, P0.5, P