Leveraging Policy Solutions for Diabetes Disparities: Suggestions for Improving the National Clinical Care Commission Report's Recommendations for Hispanic/Latino Populations.

In the U.S., Hispanic/Latino populations face increased disparities in both the prevalence and management of type 2 diabetes mellitus (T2DM). This article critically examines the multifaceted nature of T2DM disparities among Hispanic/Latino populations in the U.S. and identifies key factors contributing to T2DM prevalence within these communities, including socioeconomic status, cultural influences, and healthcare access. Utilizing a modified expert consensus procedure, we evaluate the ways in which the National Clinical Care Commission (NCCC) recommendations apply to the Hispanic/Latino community as well as propose recommendations for improved efficacy. Through a comprehensive analysis of government-community health initiatives, food security, environmental exposures, and housing inequalities, we emphasize the need for targeted interventions and health policies to effectively address and dismantle these disparities. Overall, while the National Clinical Care Commission's recommendations provide a valuable framework for the implementation of policies pertaining to diabetes management and prevention in the general population, our analysis suggests that recommendations may be strengthened by considering the unique cultural, social, and economic needs of the Hispanic/Latino population moving forward.

A patient with a rare co-occurrence of papillary and follicular thyroid carcinomas.

The occurrence of papillary and follicular thyroid carcinoma as a collision tumor is rare. We report on a case of a collision tumor consisting of papillary and follicular thyroid carcinoma treated successfully with surgery and radioiodine ablation.

Stress Load and Ascending Aortic Aneurysms: An Observational, Longitudinal, Single-Center Study Using Computational Fluid Dynamics.

Ascending aortic aneurysm (AAoA) is a silent disease with high mortality; however, the factors associated with a worse prognosis are not completely understood. The objective of this observational, longitudinal, single-center study was to identify the hemodynamic patterns and their influence on AAoA growth using computational fluid dynamics (CFD), focusing on the effects of geometrical variations on aortic hemodynamics. Personalized anatomic models were obtained from angiotomography scans of 30 patients in two different years (with intervals of one to three years between them), of which 16 (53%) showed aneurysm growth (defined as an increase in the ascending aorta volume by 5% or more). Numerically determined velocity and pressure fields were compared with the outcome of aneurysm growth. Through a statistical analysis, hemodynamic characteristics were found to be associated with aneurysm growth: average and maximum high pressure (superior to 100 Pa); average and maximum high wall shear stress (superior to 7 Pa) combined with high pressure (>100 Pa); and stress load over time (maximum pressure multiplied by the time interval between the exams). This study provides insights into a worse prognosis of this serious disease and may collaborate for the expansion of knowledge about mechanobiology in the progression of AAoA.

Long-Term Protective Effect of Tuberculosis Preventive Therapy in a Medium/High Tuberculosis Incidence Setting.

BACKGROUND: The duration of the protective effect of tuberculosis preventive therapy (TPT) is controversial. Some studies have found that the protective effect of TPT is lost after cessation of therapy among people with human immunodeficiency virus (HIV) in settings with very high tuberculosis incidence, but others have found long-term protection in low-incidence settings. METHODS: We estimated the incidence rate (IR) of new tuberculosis disease for up to 12 years after randomization to 4 months of rifampin or 9 months of isoniazid, among 991 Brazilian participants in a TPT trial in the state of Rio de Janeiro, with an incidence of 68.6/100 000 population in 2022. The adjusted hazard ratios (aHRs) of independent variables for incident tuberculosis were calculated. RESULTS: The overall tuberculosis IR was 1.7 (95% confidence interval [CI], 1.01- 2.7) per 1000 person-years (PY). The tuberculosis IR was higher among those who did not complete TPT than in those who did (2.9 [95% CI, 1.3-5.6] vs 1.1 [.4-2.3] per 1000 PY; IR ratio, 2.7 [1.0-7.2]). The tuberculosis IR was higher within 28 months after randomization (IR, 3.5 [95% CI, 1.6-6.6] vs 1.1 [.5-2.1] per 1000 PY between 28 and 143 months; IR ratio, 3.1 [1.2-8.2]). Treatment noncompletion was the only variable associated with incident tuberculosis (aHR, 3.2 [95% CI, 1.1-9.7]). CONCLUSIONS: In a mostly HIV-noninfected population, a complete course of TPT conferred long-term protection against tuberculosis.

Inibidores BTK e BCL-2 no Tratamento de Primeira Linha da Leucemia Linfocítica Crônica em Pacientes de Alto Risco: Revisão Sistemática e Meta-Análise em Rede / BTK and BCL-2 Inhibitors in the First-Line Treatment of Chronic Lymphocytic Leukemia in High-Risk Patients: Systematic Review and Network Meta-Analysis / Inhibidores de BTK Y BCL-2 en el Tratamiento de Primera Línea de la Leucemia Linfocítica Crónica en Pacientes de Alto Riesgo: Revisión Sistemática y un Metaanálisis en Red

Introdução: Pacientes com leucemia linfocítica crônica (LLC) com alto risco têm menores taxas de resposta, curso clínico mais agressivo e resistência à quimioterapia padrão, representando um desafio para o tratamento. Os inibidores da tirosina quinase de Bruton (BTK ­ ibrutinibe e acalabrutinibe) e o inibidor BCL-2 (venetoclax) podem ser utilizados nesses casos. Objetivo: Identificar e avaliar a eficácia e a segurança do uso de ibrutinibe, acalabrutinibe e venetoclax no tratamento de primeira linha em pacientes com LLC de alto risco. Método: Revisão sistemática de ensaios clínicos randomizados que avaliaram pacientes adultos com LLC, portadores de deleção 17p ou mutação TP53 e sem tratamento prévio. Foram pesquisadas as bases PubMed, EMBASE, LILACS e Cochrane Library, e realizadas avaliação do risco de viés pela ferramenta RoB 2 da Cochrane e avaliação da qualidade da evidência pelo GRADE. Resultados: Na meta-análise em rede para sobrevida livre de progressão (SLP), venetoclax + obinutuzumabe (RR: 0,62; IC 95% 0,41-0,95; p = 0,027) e acalabrutinibe + obinutuzumabe (RR: 0,74; IC 95% 0,55-0,99; p = 0,043) apresentaram menor risco de progressão ou óbito, com significância considerada limítrofe. Ibrutinibe + obinutuzumabe (RR: 0,93; IC 95% 0,86-1,00; p = 0,054) não apresentou diferença significativa na SLP para pacientes com LLC de alto risco. Conclusão: O tratamento de primeira linha com inibidores de BTK (ibrutinibe e acalabrutinibe) e o inibidor BCL-2 (venetoclax), associados a agentes monoclonais anti-CD20 ­ especialmente o obinutuzumabe ­, tem sido proposto como padrão para a maioria dos pacientes com LLC. Entretanto, pelos resultados desta revisão com meta-análise em rede, não foi possível confirmar essa recomendação.

Introduction: Patients with high-risk chronic lymphocytic leukemia (CLL) have lower response rates, a more aggressive clinical course, and resistance to standard chemotherapy, representing a treatment challenge. Bruton's tyrosine kinase inhibitors (BTK ­ ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) can be used in these cases. Objective: To identify and evaluate studies on the efficacy and safety of the use of ibrutinib, acalabrutinib and venetoclax in first-line treatment in patients with high-risk CLL. Method:Systematic review of randomized clinical trials that evaluated adult patients with CLL, carriers of 17p deletion or TP53 mutation and without prior treatment. The PubMed, EMBASE, LILACS and Cochrane Library databases were searched, and the risk of bias was assessed using the Cochrane RoB 2 tool and the quality of evidence was assessed with GRADE. Results: In the network meta-analysis for progression-free survival (PFS) venetoclax + obinutuzumab (RR: 0.62; 95%CI 0.41-0.95; p value 0.027) and acalabrutinib + obinutuzumab (RR: 0. 74; 95% CI 0.55-0.99; p value 0.043) presented a lower risk of progression or death, with significance considered borderline. Ibrutinib + obinutuzumab (RR: 0.93; 95% CI 0.86-1.00; p value 0.054) did not show a significant difference in PFS for patients with high-risk CLL. Conclusion: First-line treatment with BTK inhibitors (ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) associated with anti-CD20 monoclonal agents ­ especially obinutuzumab ­ have been proposed as the standard for most patients with CLL. However, based on the results of this review with network meta-analysis, it was not possible to confirm this recommendation.

Introducción: Los pacientes con leucemia linfocítica crónica (LLC) de alto riesgo tienen tasas de respuesta más bajas, un curso clínico más agresivo y resistencia a la quimioterapia estándar, lo que representa un desafío para el tratamiento. En estos casos se pueden utilizar los inhibidores de la tirosina quinasa de Bruton (BTK - ibrutinib y acalabrutinib) y el inhibidor de BCL-2 (venetoclax). Objetivo:Identificar y evaluar estudios sobre la eficacia y seguridad del uso de ibrutinib, acalabrutinib y venetoclax en el tratamiento de primera línea en pacientes con LLC de alto riesgo. Método: Revisión sistemática de ensayos clínicos aleatorios que evaluaron pacientes adultos con LLC, portadores de deleción 17p o mutación TP53 y sin tratamiento previo. Se realizaron búsquedas en las bases de datos PubMed, EMBASE, LILACS y Cochrane Library y se evaluó el riesgo de sesgo mediante la herramienta Cochrane RoB 2 y la calidad de la evidencia se evaluó mediante GRADE. Resultados: En el metaanálisis en red para la supervivencia libre de progresión (SSP) venetoclax + obinutuzumab (RR: 0,62; IC 95% 0,41-0,95; valor de p 0,027) y acalabrutinib + obinutuzumab (RR: 0,74; IC 95%). 0,55-0,99; valor de p 0,043) presentaron un menor riesgo de progresión o muerte, con una significación considerada límite. Ibrutinib + obinutuzumab (RR: 0,93; IC del 95 %: 0,86-1,00; valor de p 0,054) no mostró una diferencia significativa en la SSP para pacientes con LLC de alto riesgo. Conclusión: El tratamiento de primera línea con inhibidores de BTK (ibrutinib y acalabrutinib) y el inhibidor de BCL-2 (venetoclax), asociados con agentes monoclonales anti-CD20, especialmente obinutuzumab, se ha propuesto como estándar para la mayoría de los pacientes con LLC. Sin embargo, según los resultados de esta revisión con metaanálisis en red, no fue posible confirmar esta recomendación

Pituitary Crooke Cell Adenoma: Two Cases of an Aggressive Pituitary Adenoma.

Crooke cell adenoma (CCA) is a rare and aggressive subtype of a corticotroph adenoma, which requires lifetime surveillance. There have been 106 cases of CCAs reported in the English literature. We describe 2 cases of CCA, a 48-year-old man and an 84-year-old woman who both presented with binocular diplopia and temple pain. Neither case had clinical Cushing syndrome. Laboratory values for the 48-year-old man revealed, adrenocorticotropin (ACTH) 103 pg/mL (22 pmol/L) (RR: 7-63 pg/mL) and evening cortisol 14 µg/dL (386 nmol/L) (RR: 2.7-10.5 µg/dL). Computed tomography imaging demonstrated a mass adjacent to the right cavernous sinus extending into the sphenoid sinus. He underwent tumor resection with adjuvant radiation and has had a stable residual tumor for 4 years. Preoperative laboratory values for the 84-year-old woman revealed, ACTH 69 pg/mL (15 pmol/L) (RR: 7-63 pg/mL) and evening cortisol 16.2 µg/dL (447 nmol/L) (RR: 2.7-10.5 µg/dL). Brain magnetic resonance imaging revealed, a mass compressing the optic chiasm. She underwent resection and has had a stable residual tumor for 2 years. Surgical pathology in both cases revealed cytoplasmic hyaline deposits of more than 50% of the tumor cells, consistent with CCA. The CCA although rare, should be considered when evaluating cases with subclinical Cushing disease and visual symptoms.

Amelioration of Paget Disease of Bone After Denosumab for Osteopenia.

Background/Objective: Denosumab is a monoclonal antibody that inhibits bone resorption and is indicated for the treatment of osteoporosis, bone metastases, and giant cell tumor of bone. We describe a woman with symptomatic Paget disease of the skull whose headaches and monostotic disease of the skull improved after receiving denosumab for concomitant low bone density. Case Report: A 75-year-old woman presented with unremitting headache of 1 month. She had a medical history of polymyalgia rheumatica, osteopenia, hypothyroidism, and gastroesophageal reflux disease. She reported taking prednisone 1 to 20 mg daily for polymyalgia rheumatica for 1 year and received a dose of denosumab 60 mg for osteopenia 1 month before presentation. The calcium, alkaline phosphatase, and bone-specific alkaline phosphatase levels were 8.2 mg/dL (reference range [RR], 8.5-10.5 mg/dL), 132 U/L (RR, 40-129 U/L), and 17.8 µg/L (RR, 7-22.4 µg/L), respectively. Skull radiography revealed sclerosis/hyperostosis, lytic lesions, and expansion of bone, consistent with Paget disease of bone (PDB). Five months after the initial presentation, her headache resolved, and her calcium and alkaline phosphatase levels were 9.7 U/L and 96 U/L, respectively. Discussion: Denosumab neutralizes the receptor activator of nuclear factor-kappa B ligand. To date, there have been 2 case reports reported in the English literature of denosumab used successfully in patients with PDB who could not tolerate or were not eligible for bisphosphonates. This case report describes a patient with PDB treated with denosumab for osteopenia who experienced improvement in PDB-related symptoms. Conclusion: Although denosumab was originally approved for the treatment of osteoporosis, the inhibition of bone resorption via inhibition of the receptor activator of nuclear factor-kappa B ligand may be potentially effective in the treatment of PDB.

Association between RAAS Antagonism and COVID-19-related Mortality in Patients with Overweight/Obesity-related Hypertension: A Retrospective Cohort Study. / Associação entre o Antagonismo do Sistema Renina-Angiotensina-Aldosterona e a Mortalidade Relacionada à COVID-19 em Pacientes com Hipertensão Relacionada ao Sobrepeso/Obesidade: um Estudo Retrospectivo de Coorte.

BACKGROUND: Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) increase the expression of ACE2, which is a receptor for entry of SARS-CoV-2 into cells. Though evidence suggests that ARB/ACEI are safe among the general population with COVID-19, their safety in patients with overweight/obesity-related hypertension deserves further evaluation. OBJECTIVE: We assessed the association between ARB/ACEI use and COVID-19 severity in patients with overweight/obesity-related hypertension. METHODS: This study included 439 adult patients with overweight/obesity (body mass index ≥ 25 kg/m2) and hypertension, diagnosed with COVID-19 and admitted to University of Iowa Hospitals and Clinic from March 1 to December 7, 2020. Mortality and severity of COVID-19 were evaluated based on length of stay in hospital, intensive care unit admission, use of supplemental oxygen, mechanical ventilation, and vasopressors. Multivariable logistic regression was used to examine the associations of ARB/ACEI use with mortality and other markers of COVID-19 severity, with a two-sided alpha set at 0.05. RESULTS: Exposure to ARB (n = 91) and ACEI (n = 149) before hospitalization was significantly associated with lower mortality (odds ratio [OR] = 0.362, 95% confidence interval [CI] 0.149 to 0.880, p = 0.025) and a shorter length of stay (95% CI -0.217 to -0.025, p = 0.015). Additionally, patients using ARB/ACEI showed a non-significant trend toward lower intensive care unit admission (OR = 0.727, 95% CI 0.485 to 1.090, p = 0.123), use of supplemental oxygen (OR = 0.929, 95% CI 0.608 to 1.421, p = 0.734), mechanical ventilation (OR = 0.728, 95% CI 0.457 to 1.161, p = 0.182), and vasopressors (OR = 0.677, 95% CI 0.430 to 1.067, p = 0.093). CONCLUSION: Results suggest that hospitalized patients with COVID-19 and overweight/obesity-related hypertension who were prescribed ARB/ACEI before admission to the hospital exhibit lower mortality and less severe COVID-19 than those who were not taking ARB/ACEI. The results also suggest that exposure to ARB/ACEI may protect patients with overweight/obesity-related hypertension from severe COVID-19 and death.

FUNDAMENTO: Os bloqueadores dos receptores da angiotensina (BRA) e os inibidores da enzima conversora da angiotensina (IECA) aumentam a expressão de ACE2, que é um receptor para entrada de SARS-CoV-2 nas células. Embora as evidências sugiram que os IECA/BRA são seguros entre a população geral com COVID-19, sua segurança em pacientes com hipertensão relacionada ao sobrepeso/obesidade merece uma avaliação mais aprofundada. OBJETIVO: Avaliamos a associação entre o uso de IECA/BRA e a gravidade da COVID-19 em pacientes com hipertensão relacionada ao sobrepeso/obesidade. MÉTODOS: O presente estudo incluiu 439 pacientes adultos com sobrepeso/obesidade (índice de massa corporal ≥ 25 kg/m2) e hipertensão, diagnosticados com COVID-19 e internados no University of Iowa Hospitals and Clinic entre 1º de março e 7 de dezembro de 2020. Foram avaliadas a mortalidade e a gravidade da COVID-19 com base no tempo de internação hospitalar, internação em unidade de terapia intensiva, uso de oxigênio suplementar, ventilação mecânica e uso de vasopressores. A regressão logística multivariável foi usada para examinar as associações do uso de IECA/BRA com a mortalidade e outros marcadores de gravidade de COVID-19, com um alfa bilateral definido em 0,05. RESULTADOS: A exposição aos BRA (n = 91) e IECA (n = 149) antes da hospitalização foi significativamente associada a menor mortalidade ( odds ratio [OR] = 0,362, intervalo de confiança [IC] de 95% 0,149 a 0,880, p = 0,025) e menor tempo de internação hospitalar (IC 95% −0,217 a −0,025, p = 0,015). Adicionalmente, os pacientes em uso de IECA/BRA apresentaram uma tendência não significativa de menor internação em unidade de terapia intensiva (OR = 0,727, IC 95% 0,485 a 1,090, p = 0,123), uso de oxigênio suplementar (OR = 0,929, IC 95% 0,608 a 1,421,p = 0,734), ventilação mecânica (OR = 0,728, IC 95% 0,457 a 1,161, p = 0,182) e vasopressores (OR = 0,677, IC 95% 0,430 a 1,067, p = 0,093). CONCLUSÃO: Os resultados sugerem que pacientes internados com COVID-19 e hipertensão relacionada ao sobrepeso/obesidade que receberam IECA/BRA antes da internação apresentam menor mortalidade e COVID-19 menos grave do que aqueles que não estavam tomando IECA/BRA. Os resultados também sugerem que a exposição aos IECA/BRA pode proteger pacientes com hipertensão relacionada ao sobrepeso/obesidade de COVID-19 grave e morte.

Systematic Transmission Electron Microscopy-Based Identification and 3D Reconstruction of Cellular Degradation Machinery.

Various intracellular degradation organelles, including autophagosomes, lysosomes, and endosomes, work in tandem to perform autophagy, which is crucial for cellular homeostasis. Altered autophagy contributes to the pathophysiology of various diseases, including cancers and metabolic diseases. This paper aims to describe an approach to reproducibly identify and distinguish subcellular structures involved in macroautophagy. Methods are provided that help avoid common pitfalls. How to distinguish between lysosomes, lipid droplets, autolysosomes, autophagosomes, and inclusion bodies are also discussed. These methods use transmission electron microscopy (TEM), which is able to generate nanometer-scale micrographs of cellular degradation components in a fixed sample. Serial block face-scanning electron microscopy is also used to visualize the 3D morphology of degradation machinery using the Amira software. In addition to TEM and 3D reconstruction, other imaging techniques are discussed, such as immunofluorescence and immunogold labeling, which can be used to classify cellular organelles, reliably and accurately. Results show how these methods may be used to accurately quantify cellular degradation machinery under various conditions, such as treatment with the endoplasmic reticulum stressor thapsigargin or ablation of the dynamin-related protein 1.

Associação entre o Antagonismo do Sistema Renina-Angiotensina-Aldosterona e a Mortalidade Relacionada à COVID-19 em Pacientes com Hipertensão Relacionada ao Sobrepeso/Obesidade: um Estudo Retrospectivo de Coorte / Association between RAAS Antagonism and COVID-19-related Mortality in Patients with Overweight/Obesity-related Hypertension: A Retrospective Cohort Study

Resumo Fundamento Os bloqueadores dos receptores da angiotensina (BRA) e os inibidores da enzima conversora da angiotensina (IECA) aumentam a expressão de ACE2, que é um receptor para entrada de SARS-CoV-2 nas células. Embora as evidências sugiram que os IECA/BRA são seguros entre a população geral com COVID-19, sua segurança em pacientes com hipertensão relacionada ao sobrepeso/obesidade merece uma avaliação mais aprofundada. Objetivo Avaliamos a associação entre o uso de IECA/BRA e a gravidade da COVID-19 em pacientes com hipertensão relacionada ao sobrepeso/obesidade. Métodos O presente estudo incluiu 439 pacientes adultos com sobrepeso/obesidade (índice de massa corporal ≥ 25 kg/m2) e hipertensão, diagnosticados com COVID-19 e internados no University of Iowa Hospitals and Clinic entre 1º de março e 7 de dezembro de 2020. Foram avaliadas a mortalidade e a gravidade da COVID-19 com base no tempo de internação hospitalar, internação em unidade de terapia intensiva, uso de oxigênio suplementar, ventilação mecânica e uso de vasopressores. A regressão logística multivariável foi usada para examinar as associações do uso de IECA/BRA com a mortalidade e outros marcadores de gravidade de COVID-19, com um alfa bilateral definido em 0,05. Resultados A exposição aos BRA (n = 91) e IECA (n = 149) antes da hospitalização foi significativamente associada a menor mortalidade ( odds ratio [OR] = 0,362, intervalo de confiança [IC] de 95% 0,149 a 0,880, p = 0,025) e menor tempo de internação hospitalar (IC 95% −0,217 a −0,025, p = 0,015). Adicionalmente, os pacientes em uso de IECA/BRA apresentaram uma tendência não significativa de menor internação em unidade de terapia intensiva (OR = 0,727, IC 95% 0,485 a 1,090, p = 0,123), uso de oxigênio suplementar (OR = 0,929, IC 95% 0,608 a 1,421,p = 0,734), ventilação mecânica (OR = 0,728, IC 95% 0,457 a 1,161, p = 0,182) e vasopressores (OR = 0,677, IC 95% 0,430 a 1,067, p = 0,093). Conclusão Os resultados sugerem que pacientes internados com COVID-19 e hipertensão relacionada ao sobrepeso/obesidade que receberam IECA/BRA antes da internação apresentam menor mortalidade e COVID-19 menos grave do que aqueles que não estavam tomando IECA/BRA. Os resultados também sugerem que a exposição aos IECA/BRA pode proteger pacientes com hipertensão relacionada ao sobrepeso/obesidade de COVID-19 grave e morte.

Abstract Background Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) increase the expression of ACE2, which is a receptor for entry of SARS-CoV-2 into cells. Though evidence suggests that ARB/ACEI are safe among the general population with COVID-19, their safety in patients with overweight/obesity-related hypertension deserves further evaluation. Objective We assessed the association between ARB/ACEI use and COVID-19 severity in patients with overweight/obesity-related hypertension. Methods This study included 439 adult patients with overweight/obesity (body mass index ≥ 25 kg/m2) and hypertension, diagnosed with COVID-19 and admitted to University of Iowa Hospitals and Clinic from March 1 to December 7, 2020. Mortality and severity of COVID-19 were evaluated based on length of stay in hospital, intensive care unit admission, use of supplemental oxygen, mechanical ventilation, and vasopressors. Multivariable logistic regression was used to examine the associations of ARB/ACEI use with mortality and other markers of COVID-19 severity, with a two-sided alpha set at 0.05. Results Exposure to ARB (n = 91) and ACEI (n = 149) before hospitalization was significantly associated with lower mortality (odds ratio [OR] = 0.362, 95% confidence interval [CI] 0.149 to 0.880, p = 0.025) and a shorter length of stay (95% CI −0.217 to −0.025, p = 0.015). Additionally, patients using ARB/ACEI showed a non-significant trend toward lower intensive care unit admission (OR = 0.727, 95% CI 0.485 to 1.090, p = 0.123), use of supplemental oxygen (OR = 0.929, 95% CI 0.608 to 1.421, p = 0.734), mechanical ventilation (OR = 0.728, 95% CI 0.457 to 1.161, p = 0.182), and vasopressors (OR = 0.677, 95% CI 0.430 to 1.067, p = 0.093). Conclusion Results suggest that hospitalized patients with COVID-19 and overweight/obesity-related hypertension who were prescribed ARB/ACEI before admission to the hospital exhibit lower mortality and less severe COVID-19 than those who were not taking ARB/ACEI. The results also suggest that exposure to ARB/ACEI may protect patients with overweight/obesity-related hypertension from severe COVID-19 and death.

Clinical Features and Survival Analysis of Patients after Mechanical Heart Valve Replacement, with an Emphasis on Prosthetic Valve Thrombosis. / Aspectos Clínicos e de Sobrevida de Pacientes pós Implante de Valva Mecânica, com Ênfase em Trombose de Prótese Valvar.

BACKGROUND: Valvular heart diseases are highly prevalent in the world, and surgical valve replacement has improved patients' survival. OBJECTIVES: To describe clinical and laboratory data of patients undergoing mechanical valve replacement, and to determine the incidence of prosthetic valve thrombosis (PVT). METHODS: Retrospective cohort study with a follow-up of up to nine years. The study variables were collected from conventional and electronic medical charts. Statistical calculations were performed using the Jamovi software version 1.2.2.; a p<0.05 was considered statistically significant. Kaplan Meier curves were constructed, and Cox regression analysis was performed for analysis of factors related to mortality. RESULTS: A total of 473 patients were included, mean age of 46.9 ±11.3 years. Rheumatic disease was the most common etiology. In a mean follow-up period of 4.43 years, mortality rate was 16.1%. Patients with aortic prosthesis showed higher survival than patients with double implant (mitral and aortic) (p=0.026). Of the factors adjusted for mortality, only functional class and chronic renal failure showed statistically significant association. The incidence of PVT was 0.24/100 patients/year, and the first event occurred more than 1000 days after the implant. Smoking and pannus formation were significantly associated with PVT. No differences were found in INR variability between patients with and without thrombosis by prosthetic position, but significant differences were found in INR before thrombosis as compared with patients without thrombosis (INR= 2.20 [1.80-2.20] vs. 2.80 [2.20-3.40]; p= 0.040). The incidence of stroke and bleeding was 4.4% and 5.2% respectively. CONCLUSIONS: The study population was young, and rheumatic valve disease was common in this group. The prevalence of PVT was similar to that described in the literature, despite the low income and low educational level of our sample.

FUNDAMENTO: As doenças oro-valvares têm prevalência mundial expressiva, e a cirurgia de troca valvar melhorou a sobrevida dos pacientes. OBJETIVOS: Descrever aspectos clínico-laboratoriais dos pacientes submetidos a implante valvar mecânico e determinar a incidência de trombose de próteses valvares (TPV). MÉTODOS: Estudo de coorte retrospectivo com seguimento até nove anos; as variáveis de estudo foram buscadas em prontuários físicos e eletrônicos. Os cálculos foram realizados pelo programa Jamovi 1.2.2.; p<0,05 foi considerado estatisticamente significante. Foram construídas curvas de Kaplan Meier, e realizada análise de regressão de Cox para fatores relacionados à mortalidade. RESULTADOS: Foram incluídos 473 pacientes com média de idade de 46,9 ±11,3 anos. A doença reumática foi a principal etiologia. Em média de acompanhamento de 4,43 anos, a mortalidade foi de 16,1%. Pacientes com implantes de próteses na posição aórtica tiveram sobrevida melhor que os portadores em posição mitro-aórtica (p=0,026). Entre os fatores ajustados para mortalidade, apenas classe funcional e insuficiência renal crônica apresentaram significância estatística. A incidência de TPV foi de 0,24/100 pacientes/ano, com primeiro evento após 1000 dias da cirurgia. Tabagismo e pannus foram estatisticamente associados a TPV. Não houve diferenças na variabilidade de INR entre pacientes com e sem trombose por posição protética, mas houve diferença estatística no INR pré-evento trombótico comparado aos que não apresentaram trombose (INR= 2,20[1,80-2,20] vs 2,80[2,20-3,40]; p= 0,040). Identificamos 4,4% de acidentes vasculares cerebrais e 5,2% de sangramentos. CONCLUSÕES: A população mostrou-se jovem e valvopatia reumática foi frequente. A frequência de TPV foi semelhante à descrita na literatura, apesar da baixa renda e escolaridade da amostra.

Mechanisms and pharmacotherapy of hypertension associated with type 2 diabetes.

Type 2 diabetes is often complicated with hypertension, such that 73.6 % of patients ≥ 18 years with type 2 diabetes also have hypertension. With increasing age, the risk of developing these conditions rises significantly. Co-existence of type 2 diabetes and hypertension suggests that there are overlapping genetic, physiologic, and environmental factors at play. Research has shown several overlying metabolic abnormalities including sympathetic nervous system overactivation, insulin resistance, inflammatory and endothelial dysfunction, deleterious expression of microRNAs, and obstructive sleep apnea. Though diet and physical activity are the mainstays of treatment early in the disease course, they are generally not a viable long-term strategy. Treatment with novel hypoglycemic and anti-hypertensive medications can greatly assist in preventing long-term complications of these chronic conditions. Recognition of the common causes and consequences of type 2 diabetes and comorbid hypertension allows for a robust response towards being proactive regarding prevention and treatment of this unique patient population. Thus, the purpose of this current review is four-part: to (1) review the latest discoveries into the mechanisms of hypertension in the setting of type 2 diabetes, (2) discuss the latest treatments of hypertension with a brief discussion about novel hypoglycemic agents in patients with type 2 diabetes, (3) summarize blood pressure targets and (4) to address evidence gaps in treating patients with diabetes and resistant hypertension, and elderly individuals with both hypertension and diabetes.

Aspectos Clínicos e de Sobrevida de Pacientes pós Implante de Valva Mecânica, com Ênfase em Trombose de Prótese Valvar / Clinical Features and Survival Analysis of Patients after Mechanical Heart Valve Replacement, with an Emphasis on Prosthetic Valve Thrombosis

Resumo Fundamento As doenças oro-valvares têm prevalência mundial expressiva, e a cirurgia de troca valvar melhorou a sobrevida dos pacientes. Objetivos Descrever aspectos clínico-laboratoriais dos pacientes submetidos a implante valvar mecânico e determinar a incidência de trombose de próteses valvares (TPV). Métodos Estudo de coorte retrospectivo com seguimento até nove anos; as variáveis de estudo foram buscadas em prontuários físicos e eletrônicos. Os cálculos foram realizados pelo programa Jamovi 1.2.2.; p<0,05 foi considerado estatisticamente significante. Foram construídas curvas de Kaplan Meier, e realizada análise de regressão de Cox para fatores relacionados à mortalidade. Resultados Foram incluídos 473 pacientes com média de idade de 46,9 ±11,3 anos. A doença reumática foi a principal etiologia. Em média de acompanhamento de 4,43 anos, a mortalidade foi de 16,1%. Pacientes com implantes de próteses na posição aórtica tiveram sobrevida melhor que os portadores em posição mitro-aórtica (p=0,026). Entre os fatores ajustados para mortalidade, apenas classe funcional e insuficiência renal crônica apresentaram significância estatística. A incidência de TPV foi de 0,24/100 pacientes/ano, com primeiro evento após 1000 dias da cirurgia. Tabagismo e pannus foram estatisticamente associados a TPV. Não houve diferenças na variabilidade de INR entre pacientes com e sem trombose por posição protética, mas houve diferença estatística no INR pré-evento trombótico comparado aos que não apresentaram trombose (INR= 2,20[1,80-2,20] vs 2,80[2,20-3,40]; p= 0,040). Identificamos 4,4% de acidentes vasculares cerebrais e 5,2% de sangramentos. Conclusões A população mostrou-se jovem e valvopatia reumática foi frequente. A frequência de TPV foi semelhante à descrita na literatura, apesar da baixa renda e escolaridade da amostra.

Abstract Background Valvular heart diseases are highly prevalent in the world, and surgical valve replacement has improved patients' survival. Objectives To describe clinical and laboratory data of patients undergoing mechanical valve replacement, and to determine the incidence of prosthetic valve thrombosis (PVT). Methods Retrospective cohort study with a follow-up of up to nine years. The study variables were collected from conventional and electronic medical charts. Statistical calculations were performed using the Jamovi software version 1.2.2.; a p<0.05 was considered statistically significant. Kaplan Meier curves were constructed, and Cox regression analysis was performed for analysis of factors related to mortality. Results A total of 473 patients were included, mean age of 46.9 ±11.3 years. Rheumatic disease was the most common etiology. In a mean follow-up period of 4.43 years, mortality rate was 16.1%. Patients with aortic prosthesis showed higher survival than patients with double implant (mitral and aortic) (p=0.026). Of the factors adjusted for mortality, only functional class and chronic renal failure showed statistically significant association. The incidence of PVT was 0.24/100 patients/year, and the first event occurred more than 1000 days after the implant. Smoking and pannus formation were significantly associated with PVT. No differences were found in INR variability between patients with and without thrombosis by prosthetic position, but significant differences were found in INR before thrombosis as compared with patients without thrombosis (INR= 2.20 [1.80-2.20] vs. 2.80 [2.20-3.40]; p= 0.040). The incidence of stroke and bleeding was 4.4% and 5.2% respectively. Conclusions The study population was young, and rheumatic valve disease was common in this group. The prevalence of PVT was similar to that described in the literature, despite the low income and low educational level of our sample.

The use of very low-calorie diets in subjects with obesity complicated with nonalcoholic fatty liver disease: A scoping review.

This scoping review synthesizes the existing research on the use of very low-calorie diets (VLCDs) in subjects with nonalcoholic fatty liver disease (NAFLD) and end-stage liver disease (ESLD). 19 studies were included, of which 5 were clinical trials, 11 were cohort studies, 1 was a case-control study, and 2 were case series totaling 968 subjects. About 17 studies were focused on patients with NAFLD while the two case series described in patients with ESLD on the transplant list or post-liver transplant. Six studies included subjects managed with VLCDs prior bariatric surgery. Most studies were short term and demonstrated acute improvement of diverse liver biomarkers including liver function tests, indices of hepatosteatosis and reduction in liver size. Adherence rates in these studies were between 69% and 93%. Eight studies did not report any adverse events and four subjects were reported to have discontinued VLCD due to adverse effects in two different studies. Aggregated adverse events were mild. Treatments based on VLCD in subjects with NAFLD seem to be safe and tolerable but can result in mild adverse effects. The findings of this scoping review suggest that the use of VLCD in patients with obesity complicated with NAFLD and potentially in ESLD appear to be effective to induce weight loss and to acutely reduce hepatosteatosis.

Association between preoperative serum albumin levels with risk of death and postoperative complications after bariatric surgery: a retrospective cohort study.

BACKGROUND: Hypoalbuminemia is common among individuals with obesity who qualify for bariatric surgery, but its relevance to clinical outcomes after bariatric surgery remains to be established. OBJECTIVES: To examine the association of preoperative serum albumin with 30-day postoperative outcomes. SETTING: Data from the 2015-2019 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Participant Use Files were used. METHODS: Preoperative serum albumin level was categorized as hypoalbuminemia (<3.5 g/dL), and normoalbuminemia (3.5-5.5 g/dL) among patients who underwent bariatric surgery. Multivariate logistic regression models were used to determine the association of preoperative hypoalbuminemia with 30-day postoperative mortality and other co-morbid outcomes. RESULTS: Among 633,011 adult patients, 85.1% were women and the mean (standard deviation) age was 44.8 (12.0) years. The prevalence of hypoalbuminemia was 6.13% (n = 38,792). After adjustment for procedure type and demographic, lifestyle, and co-morbidity covariates, the odds ratio (OR) (95% confidence interval [CI]) for mortality was 1.42 (1.10, 1.82) for hypoalbuminemia. For all other outcomes, the ORs (95% CIs) for hypoalbuminemia ranged from 1.03 (.67-1.60) for cardiac arrest requiring CPR to 2.32 (1.66-3.25) for failure to be discharged by day 30. The ORs for several associations were higher for severe hypoalbuminemia than marginal hypoalbuminemia. CONCLUSION: Preoperative hypoalbuminemia was associated with several negative 30-day postoperative bariatric surgery outcomes and tended to be worse for severe hypoalbuminemia compared with marginal hypoalbuminemia. These findings suggest that serum albumin may be a useful biomarker to screen for negative bariatric surgery outcomes.

Highlights of mechanisms and treatment of obesity-related hypertension.

The prevalence of obesity has increased two to three times from 1975 to 2015. Large-scale epidemiological and longitudinal prospective studies link obesity with hypertension. Research suggests that excessive weight gain, particularly when associated with visceral adiposity, may account for as much as 65% to 75% of the risk of incident hypertension. Also, exercise and bariatric/metabolic surgery significantly lowers blood pressure, whereas weight gain increases blood pressure, thus establishing a firm link between these two factors. The mechanisms underpinning obesity-related hypertension are complex and multifaceted, and include, but are not limited to, renin-angiotensin-aldosterone system/sympathetic nervous system overactivation, overstimulation of adipokines, insulin resistance, immune dysfunction, structural/functional renal, cardiac, and adipocyte changes. Though weight loss is the mainstay of treatment for obesity-related hypertension, it is often not a feasible long-term solution. Therefore, it is recommended that aggressive treatment with multiple antihypertensive medications combined with diet and exercise be used to lower blood pressure and prevent complications. The research regarding the mechanisms and treatment of obesity-related hypertension has moved at a blistering pace over the past ten years. Therefore, the purpose of this expert review is two-fold: to discuss the pathophysiological mechanisms underlying obesity-related hypertension, and to revisit pharmacotherapies that have been shown to be efficacious in patients with obesity-related hypertension.

COVID-19 in patients with cardiac disease: Impact and variables associated with mortality in a cardiology center in Brazil.

BACKGROUND: Cardiovascular disease is associated with severe COVID-19. Our aim was to describe clinical and laboratory features (including electrocardiographic and echocardiographic ones) and outcomes of patients with cardiac disease hospitalized with COVID-19. METHODS: This is an observational retrospective study of consecutive adult patients admitted, between March and September of 2020, with confirmed SARSCoV-2 infection. Data were collected as per the ISARIC case report form and complemented with variables related to heart disease. RESULTS: One hundred twenty-one patients were included. Mean age was 60 SD 15.2 years and 80/121(66.1%) were male. Two-thirds of the patients (80/121, 66.1%) had COVID-19 at the time of hospital admission and COVID-19 was the reason for hospitalization in 42 (34.7%). Other reasons for hospital admission were acute coronary syndrome (26%) and decompensated heart failure (14.8%). Chronic cardiac diseases were found in 106/121 (87.6%), mostly coronary artery disease (62%) or valve disease (33.9%). A transthoracic echocardiogram was performed in 93/121(76.8%) and enlarged cardiac chambers were found in 71% (66/93); admission ECG was done in 93 cases (93/121, 76.8%), and 89.2% (83/93) were abnormal. Hospital-acquisition of COVID-19 occurred in 20 (16.5%) of patients and their mortality was 50%. On bivariate analysis for mortality, BNP levels and troponin levels were NOT associated with mortality. On multivariate analysis, only C reactive protein levels and creatinine levels were significant. CONCLUSIONS: COVID-19 impacted the profile of hospital admissions in cardiac patients. BNP and troponin levels were not associated with mortality and may not be good prognostic discriminators in cardiac patients.

Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes.

Ubiquitination represents a post-translational modification (PTM) essential for the maintenance of cellular homeostasis. Ubiquitination is involved in the regulation of protein function, localization and turnover through the attachment of a ubiquitin molecule(s) to a target protein. Ubiquitination can be reversed through the action of deubiquitinating enzymes (DUBs). The DUB enzymes have the ability to remove the mono- or poly-ubiquitination signals and are involved in the maturation, recycling, editing and rearrangement of ubiquitin(s). Ubiquitin-specific proteases (USPs) are the biggest family of DUBs, responsible for numerous cellular functions through interactions with different cellular targets. Over the past few years, several studies have focused on the role of USPs in carcinogenesis, which has led to an increasing development of therapies based on USP inhibitors. In this review, we intend to describe different cellular functions, such as the cell cycle, DNA damage repair, chromatin remodeling and several signaling pathways, in which USPs are involved in the development or progression of cancer. In addition, we describe existing therapies that target the inhibition of USPs.