QTc prolongation across CDK4/6 inhibitors: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2- breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation. RESULTS: We included 14 RCTs comprising 16 196 patients, of whom 8576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR = 2.35, 95% CI = 1.67 to 3.29, P < .001; I2 = 44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a relative risk of 3.12 (95% CI = 2.09 to 4.65, P < .001; I2 = 12%), whereas the palbociclib subgroup had a relative risk of 1.51 (95% CI = 1.05 to 2.15, P = .025; I2 = 0%). CONCLUSION: Palbociclib was associated with QTc prolongation; however, the relative risk for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class.

Artificial intelligence for triaging of breast cancer screening mammograms and workload reduction: A meta-analysis of a deep learning software.

OBJECTIVE: Deep learning (DL) has shown promising results for improving mammographic breast cancer diagnosis. However, the impact of artificial intelligence (AI) on the breast cancer screening process has not yet been fully elucidated in terms of potential workload reduction. We aim to assess if AI-based triaging of breast cancer screening mammograms could reduce the radiologist's workload with non-inferior sensitivity. METHODS: PubMed, EMBASE, Cochrane Central, and Web of Science databases were systematically searched for studies that evaluated AI algorithms on computer-aided triage of breast cancer screening mammograms. We extracted data from homogenous studies and performed a proportion meta-analysis with a random-effects model to examine the radiologist's workload reduction (proportion of low-risk mammograms that could be theoretically ruled out from human's assessment) and the software's sensitivity to breast cancer detection. RESULTS: Thirteen studies were selected for full review, and three studies that used the same commercially available DL algorithm were included in the meta-analysis. In the 156,852 examinations included, the threshold of 7 was identified as optimal. With these parameters, radiologist workload decreased by 68.3% (95%CI 0.655-0.711, I² = 98.76%, p < 0.001), while achieving a sensitivity of 93.1% (95%CI 0.882-0.979, I² = 83.86%, p = 0.002) and a specificity of 68.7% (95% CI 0.684-0.723, I² = 97.5%, p < 0.01). CONCLUSIONS: The deployment of DL computer-aided triage of breast cancer screening mammograms reduces the radiology workload while maintaining high sensitivity. Although the implementation of AI remains complex and heterogeneous, it is a promising tool to optimize healthcare resources.

Effects of statin therapy in hospitalized adult COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: COVID-19 is associated with endothelial activation and systemic inflammation; consequently, statins can be used in its treatment as they have anti-inflammatory, antithrombotic, and profibrinolytic properties and may interfere with COVID-19 viral entry into cells through disruption of cell membrane lipid rafts. OBJECTIVE: We performed a meta-analysis of randomized clinical trials that compared statin therapy to placebo or to standard care in adult patients hospitalized for COVID-19. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Library databases for all-cause mortality, hospitalization duration, and admission to the intensive care unit. RESULTS: Of the 228 studies reviewed, four studies were included, with a total of 1,231 patients, of whom 610 (49.5%) were treated with statins. There was no significant difference in all-cause mortality (odds ratio [OR] 0.96; 95% confidence interval [95%CI]: 0.61-1.51; p=0.86; I2=13%), duration of hospitalization (mean difference [MD] 0.21; 95%CI: -1.74-2.16; p=0.83; I2=92%), intensive care unit admission (OR= 3.31; 95%CI: 0.13-87.1; p=0.47; I2=84%), need for mechanical ventilation (OR= 1.03; 95%CI: 0.36-2.94; p=0.95; I2=0%), or increase in liver enzyme levels (OR= 0.58; 95%CI: 0.27-1.25; p=0.16; I2=0%) between patients treated with or without statin therapy. CONCLUSION: Our findings suggest that in adult patients hospitalized with COVID-19, statin therapy results in no difference in clinical outcomes when compared to outcomes by placebo or standard of care. Prospero database registration: (www.crd.york.ac.uk/prospero) under the number CRD42022338283.

Effects of Tezepelumab on Quality of Life of Patients with Moderate-to-Severe, Uncontrolled Asthma: Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: To assess the effects of tezepelumab on quality of life (QoL) in patients with moderate-to-severe, uncontrolled asthma. RECENT FINDINGS: Tezepelumab improves pulmonary function tests (PFTs) and reduces the annualized asthma exacerbation rate (AAER) in patients with moderate-to-severe, uncontrolled asthma. We searched MEDLINE, Embase, and Cochrane Library from inception to September 2022. We included randomized controlled trials comparing tezepelumab versus placebo in patients aged ≥ 12 years with asthma on medium- or high-dose inhaled corticosteroids with ≥ 1 additional controller medication for ≥ 6 months and who had ≥ 1 asthma exacerbation in the 12 months before enrollment. We estimated effects measures with a random-effects model. Of 239 records identified, three studies were included, with a total of 1,484 patients. Tezepelumab significantly decreased biomarkers of T helper 2-driven inflammation, including blood eosinophil count (MD -135.8 [95% CI -164.37, -107.23]) and fractional exhaled nitric oxide (MD -9.64 [95% CI -13.75, -5.53]); improved PFTs, including pre-bronchodilator forced expiratory volume in 1 s (MD 0.18 [95% CI 0.08-0.27]); reduced the AAER (MD 0.47 [95% CI 0.39-0.56]); improved asthma-specific health-related QoL in the Asthma Control Questionnaire-6 (MD -0.33 [95% CI -0.34, -0.32]), Asthma Quality of Life Questionnaire for 12 Years and Older (MD 0.34 [95% CI 0.33, -0.35]), Asthma Symptom Diary (MD -0.11 [95% CI -0.18, -0.04]), and European Quality of Life 5 Dimensions 5 Levels Questionnaire (SMD 3.29 [95% CI 2.03, 4.55]) scores, although not clinically important; and did not change key safety outcomes, including any adverse event (OR 0.78 [95% CI 0.56-1.09]).

The Effects of Hydrolyzed Collagen and Collagen Peptide in the Treatment of Superficial Chondral Lesions: An Experimental Study.

Objective To evaluate the effects of hydrolyzed collagen and collagen peptide in the treatment of superficial chondral lesions in rats. Method This research employed 18 Rattus norvegicus . A single intraarticular infiltration of sodium iodoacetate (2 mg solution) through the patellar ligament induced joint damage in previously anesthetized animals. We divided the animals into three groups: a control group, a collagen peptide group, and a hydrolyzed collagen group. Treatment consisted of oral administration of collagen peptide or hydrolyzed collagen for 30 days. Afterwards, we euthanized the animals and studied the joint chondral changes. We evaluated the results according to the chondrocyte clusters count and a histological evaluation, as per Pritzker et al. Results There was no statistical significance in injury stages between the control, hydrolyzed collagen, and collagen peptide groups ( p = 0.11). Regarding scores, there was a statistical significance between the groups treated with hydrolyzed collagen and collagen peptide ( p < 0.05), but not in comparison with the control group. Conclusion The proposed treatments of the induced chondral lesion with the oral administration of hydrolyzed collagen or collagen peptides were effective, resulting in lesion stabilization or regression, and warranting further experimental research to understand and improve the primary outcome of this study.

The Effects of Hydrolyzed Collagen and Collagen Peptide in the Treatment of Superficial Chondral Lesions: An Experimental Study / Os efeitos do colágeno hidrolisado e do peptídeo de colágeno no tratamento de lesões condrais superficiais: Um estudo experimental

Abstract Objective To evaluate the effects of hydrolyzed collagen and collagen peptide in the treatment of superficial chondral lesions in rats. Method This research employed 18 Rattus norvegicus. A single intraarticular infiltration of sodium iodoacetate (2 mg solution) through the patellar ligament induced joint damage in previously anesthetized animals. We divided the animals into three groups: a control group, a collagen peptide group, and a hydrolyzed collagen group. Treatment consisted of oral administration of collagen peptide or hydrolyzed collagen for 30 days. Afterwards, we euthanized the animals and studied the joint chondral changes. We evaluated the results according to the chondrocyte clusters count and a histological evaluation, as per Pritzker et al. Results There was no statistical significance in injury stages between the control, hydrolyzed collagen, and collagen peptide groups (p= 0.11). Regarding scores, there was a statistical significance between the groups treated with hydrolyzed collagen and collagen peptide (p< 0.05), but not in comparison with the control group. Conclusion The proposed treatments of the induced chondral lesion with the oral administration of hydrolyzed collagen or collagen peptides were effective, resulting in lesion stabilization or regression, and warranting further experimental research to understand and improve the primary outcome of this study.

Resumo Objetivo Avaliar os efeitos do colágeno hidrolisado e do peptídeo de colágeno no tratamento de lesões condrais superficiais de ratos. Método Foram utilizados 18 Rattus norvegicus nesta pesquisa. O dano articular foi induzido por uma única infiltração intra-articular de iodoacetato de sódio (solução 2 mg), injetada através do ligamento patelar da articulação dos animais previamente anestesiados. Os animais foram distribuídos em três grupos: grupo controle, grupo peptídeo de colágeno e grupo colágeno hidrolisado. O tratamento foi realizado por 30 dias com a administração via oral do peptídeo de colágeno ou do colágeno hidrolisado. Posteriormente, foi realizada a eutanásia dos experimentos e seguiu-se para o estudo das alterações condrais articulares. Os resultados foram avaliados conforme contagem de condrócitos por cluster e através da avaliação histológica segundo Pritzker et al. Resultados Ao observar os estágios de lesão, não foi observada significância estatística entre os grupos controle, colágeno hidrolisado e peptídeo de colágeno (p= 0,11). Ao observar os escores, houve significância estatística na comparação do grupo tratado com colágeno hidrolisado e o grupo peptídeo colágeno (p< 0,05), porém sem diferença estatística em relação ao grupo controle. Conclusão Os tratamentos propostos da lesão condral induzida com uso de colágeno hidrolisado ou peptídeos de colágeno via oral mostraram-se eficazes, com estabilização ou regressão da lesão apresentada em ratos, merecendo novas pesquisas experimentais com o intuito de compreender e melhorar o desfecho primário deste trabalho.

Low cost and easy acquisition: corn grain in microsurgery training.

OBJECTIVES: develop an easily accessible model for training the initial motor practice in microsurgery using corn kernels. METHODS: ten corn kernels (Zea mays) were used. A 7mm longitudinal cut was made on one side of the corn grain. The training consisted of performing 4 simple knots between the edges of the incision, using 10-0 mononylon thread. The parameters analyzed were 1) cost of the model; 2) assembly time of the model test system; 3) time for performing the knots; 4) distance between the knots. RESULTS: in all corn kernels tested, it was possible to perform the proposed microsurgical suture training, without any difficulty in the procedure. The average time to perform the 4 knots was 6.51±1.18 minutes. The total cost of the simulator model was R$3.59. The average distance between the knots was 1.7±0.3mm. The model developed from corn grains has an extremely low cost when compared to the use of animals or high-tech simulators. Other advantages are the easy availability of canned corn kernels and the possibility of making more than four knots along the 7mm incision. CONCLUSION: the training model developed has low cost, is easy to acquire and viable for training basic manual skills in microsurgery.

Effects of statin therapy in hospitalized adult COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Introduction COVID-19 is associated with endothelial activation and systemic inflammation; consequently, statins can be used in its treatment as they have anti-inflammatory, antithrombotic, and profibrinolytic properties and may interfere with COVID-19 viral entry into cells through disruption of cell membrane lipid rafts. Objective We performed a meta-analysis of randomized clinical trials that compared statin therapy to placebo or to standard care in adult patients hospitalized for COVID-19. Methods We searched the MEDLINE, EMBASE, and Cochrane Library databases for all-cause mortality, hospitalization duration, and admission to the intensive care unit. Results Of the 228 studies reviewed, four studies were included, with a total of 1,231 patients, of whom 610 (49.5%) were treated with statins. There was no significant difference in all-cause mortality (odds ratio [OR] 0.96; 95% confidence interval [95%CI]: 0.61-1.51; p=0.86; I2=13%), duration of hospitalization (mean difference [MD] 0.21; 95%CI: -1.74-2.16; p=0.83; I2=92%), intensive care unit admission (OR= 3.31; 95%CI: 0.13-87.1; p=0.47; I2=84%), need for mechanical ventilation (OR= 1.03; 95%CI: 0.36-2.94; p=0.95; I2=0%), or increase in liver enzyme levels (OR= 0.58; 95%CI: 0.27-1.25; p=0.16; I2=0%) between patients treated with or without statin therapy. Conclusion Our findings suggest that in adult patients hospitalized with COVID-19, statin therapy results in no difference in clinical outcomes when compared to outcomes by placebo or standard of care. Prospero database registration: (www.crd.york.ac.uk/prospero) under the number CRD42022338283.

Low cost and easy acquisition: corn grain in microsurgery training / Baixo custo e fácil aquisição: grãos de milho no treinamento microcirúrgico

ABSTRACT Objectives: develop an easily accessible model for training the initial motor practice in microsurgery using corn kernels. Methods: ten corn kernels (Zea mays) were used. A 7mm longitudinal cut was made on one side of the corn grain. The training consisted of performing 4 simple knots between the edges of the incision, using 10-0 mononylon thread. The parameters analyzed were 1) cost of the model; 2) assembly time of the model test system; 3) time for performing the knots; 4) distance between the knots. Results: in all corn kernels tested, it was possible to perform the proposed microsurgical suture training, without any difficulty in the procedure. The average time to perform the 4 knots was 6.51±1.18 minutes. The total cost of the simulator model was R$3.59. The average distance between the knots was 1.7±0.3mm. The model developed from corn grains has an extremely low cost when compared to the use of animals or high-tech simulators. Other advantages are the easy availability of canned corn kernels and the possibility of making more than four knots along the 7mm incision. Conclusion: the training model developed has low cost, is easy to acquire and viable for training basic manual skills in microsurgery.

RESUMO Objetivo: desenvolver um modelo facilmente acessível para o treinamento da prática motora inicial em microcirurgia a partir da utilização de grãos de milho. Métodos: foram utilizados dez grãos de milho (Zea mays). Realizou-se um corte longitudinal de 7mm em uma das faces do grão de milho. O treinamento consistiu na realização de 4 pontos simples entre as bordas da incisão, utilizando fio de mononáilon 10-0. Os parâmetros analisados foram 1) custo do modelo; 2) tempo de montagem do sistema de teste do modelo; 3) tempo de realização dos nós; 4) distância entre os pontos. Resultados: em todos os grãos testados foi possível realizar o treinamento de sutura microcirúrgica proposto, sem dificuldade ao procedimento. O tempo médio para a realização dos 4 pontos foi de 6,51±1,18 minutos. O custo total do modelo simulatório foi de R$3,59. A distância média entre os pontos foi de 1,7±0,3mm. O modelo desenvolvido a partir de grãos de milhos apresenta custo extremamente baixo quando comparado ao uso de animais ou de simuladores de alta tecnologia. Outras vantagens são fácil disponibilidade de grãos de milho em conserva e possibilidade de serem realizados mais de quatro pontos ao longo da incisão de 7mm. Conclusão: o modelo de treinamento desenvolvido é de baixo custo, de fácil aquisição e viável para o treinamento de habilidades manuais básicas em microcirurgia.

The expression of FOXP3 in lesions of several forms of leprosy in patients co-infected with HIV.

BACKGROUND: Brazil remains endemic for infection by the human immunodeficiency virus (HIV) and leprosy, having a major impact on public health and the life quality of affected patients. Although the relevance of this co-infection is recognized, several aspects, such as the immune response, are not yet fully understood. The objective of this study was to investigate the expression of FOXP3+ Treg cells in leprosy skin lesions and to correlate their clinical forms, laboratory characteristics (CD4, CD8, and CV), and the immune reconstitution syndrome in HIV-leprosy co-infection. METHODOLOGY/PRINCIPAL FINDINGS: An observational, cross-sectional, and analytical study was carried out comparing four groups of patients: those with concomitant diagnosis of leprosy and HIV infection without a leprosy reaction, those with leprosy and HIV co-infection patients with a reverse reaction (RR), those with leprosy without HIV and without reaction, and those with leprosywithout HIV and with RR. The patients were diagnosed at a dermatology outpatient clinic located in Belém, Pará, Brazil, from 2003 to 2017. In the sample studied, there was a positive correlation between FOXP3+ cell density and viral load, negative correlation with blood CD4+ (not statistically significant), significant positive correlation in CD8 count in patients with leprosy reaction, and positive relationship in patients with IRIS. The density of cells expressing FOXP3 was higher in the BL/LL forms in patients without HIV, although the difference was not statistically significant. However, the cell mean was higher in the TT/BT forms in patients co-infected with leprosy and HIV, showing contradictory results. CONCLUSIONS/SIGNIFICANCE: These findings support that higher activity of the HIV may stimulate or result in a higher expression of FOXP3-Tregs and that they may be involved in active immunosuppression observed at the infection site at the tissue level. This supports the need to expand studies on FOXP3+ Treg cells in co-infected patients.

Apropriações da Instrução ao Sósia na análise da atividade de trabalho / Appropriations of the Instruction to the double in the analysis of work activity / Apropiaciones de la Instrucción al doble en el análisis de la actividad de trabajo

Resumo Este artigo fundamenta-se em quatro experiências de pesquisa nas quais foi utilizada a técnica de Instrução ao Sósia (IaS) para análise da atividade de trabalho em variados contextos laborais. São apresentadas e discutidas as aplicações da técnica nessas pesquisas norteadas pela abordagem teórica e metodológica da Clínica da Atividade. As experiências mencionadas efetivaram-se em diferentes ambientes laborais - hospitais, universidades, praias - com seus respectivos participantes (profissionais de saúde, professores e trabalhadores informais). O uso da técnica ensejou diversos fenômenos psíquicos, dentre os quais se destaca a reflexão do trabalhador sobre sua atividade, tanto no âmbito da dimensão clínica da atividade de trabalho como na esfera da identificação de competências diante os possíveis desenrolar da atividade. As contribuições oriundas de tais experiências permitem indicar a técnica para futuros estudos em diferentes contextos laborais, o que evidencia amplas possibilidades de utilização.

Abstract This article is grounded on four research experiences in which has been used the Instruction to the double technique to analyze the work activity in a variety of workplace settings. The applications of the technique are presented and discussed in those researches, guided by the theoretical and methodological approach of the Clinic of Activity. The experiences reported occurred in different working environments - hospitals, universities, beaches - with their participants (health professionals, teachers and informal workers). The use of the technique allow various psychic phenomena, among which stand out the worker's reflection on its activity, in the clinical dimension of work activity, and competence identification dimension in front of possible developments of the activity. Contributions from these experiences allow to indicate the technique for future studies in different work contexts, thereby demonstrating their broad possibilities of use.

Resumen Este artículo se basa en cuatro experiencias de investigación en las cuales fue utilizada la técnica de Instrucción al doble para el análisis de la actividad de trabajo en contextos laborales variados. Son presentadas y discutidas las aplicaciones de la técnica en esas investigaciones, orientadas por la perspectiva teórica y metodológica de la Clínica de la Actividad. Las experiencias mencionadas se realizaron en diferentes ambientes laborales - hospitales, universidades, playas - con sus respectivos participantes (profesionales de la salud, profesores y trabajadores informales). El uso de la técnica posibilitó diversos fenómenos psíquicos, entre los cuales se destacan la reflexión del trabajador sobre su actividad, tanto en el ámbito de la dimensión clínica de la actividad de trabajo, como en el ámbito referente a la identificación de competencias frente a los posibles desenvolvimientos de la actividad. Las contribuciones oriundas de tales experiencias permiten indicar la técnica para futuros estudios en diferentes contextos laborales, lo que evidencia amplias posibilidades de utilización.

Caracterização da atividade laboral de trabalhadores informais em praia de Natal (RN) - Brasil / Labour activity of street vendors in a beach at Natal (RN-Brazil)

Este artigo analisa os modos de organização de uma atividade laboral, especificamente a de vendedor ambulante, situada na economia informal em uma praia urbana do nordeste do Brasil. São analisados resultados de pesquisa de natureza quantitativa e qualitativa, oriundos de questionário e observações de campo, realizados com grupo de sessenta vendedores ambulantes na praia de Ponta Negra (Natal, RN). As informações oriundas dos questionários passaram por análises estatísticas descritivas e inferenciais e foram integradas à análise clínico-interpretativa. Evidenciou-se a construção de um contexto específico para o exercício de sua atividade, caracterizado por necessidade constante de superação de obstáculos, estabelecimento de relações de submissão e diferenciação em coletivos de trabalho e mobilização de diversas competências e habilidades apoiadas em conhecimentos práticos. Conclui-se que a informalidade, para além da precariedade, abarca aspectos comuns ao trabalho formal, o que a sitia como atividade laboral legítima, do ponto de vista psicossocial, permitindo ultrapassar a perspectiva de antinomia entre essas duas modalidades de atividade.

This article analyzes the ways of organization of a labor activity, specifically the street marketer, as example of informal economy in an urban beach in northeastern Brazil. Quantitative and qualitative research data issued from answers to a questionnaire and field observations of a group of sixty vendors from Ponta Negra Beach (Natal-RN) are discussed. Data from the questionnaires underwent descriptive and inferential statistical analyzes, which were crossed to clinical-interpretative analysis. Results showed the construction of a specific context for the exercise of their activity, characterized by constant need of overcoming obstacles, establishing relations of submission and differentiation in labor collectives and mobilization of diverse competencies, abilities and skills supported by practical knowledge. We conclude that informality goes beyond its insecurity and precarity, showing various aspects in common with formal work, which allows the consideration of informal work as legitimate labor activity, from a psychosocial point of view. This assumption allows to overcome the antinomy between these two modalities of labor activity.