Visión general de las várices gástricas y su tratamiento / Overview of gastric varices and their treatment

Las várices gástricas (VG) son un complejo de colaterales vasculares entre la circulación portal y sistémica, condición que se desarrolla como resultado de la presión elevada en el sistema venoso portal. Se encuentran en el 20 % de los pacientes con cirrosis, y son menos frecuentes que las várices esofágicas. Según la clasificación de Sarin, las VG se dividen en cuatro tipos según su ubicación en el estómago y su relación con las várices esofágicas (GOV1, GOV2, IGV1 e IGV2). Entender su hemodinámica con respecto a las rutas de drenaje de las VG es importante para guiar su tratamiento.

Gastric varices (GV) are a complex of vascular collaterals between portal and systemic circulation, a condition that develops as a result of elevated pressure in the portal venous system. They are found in 20% of patients with cirrhosis, and are less common than esophageal varices. According to the Sarin classification, GV are divided into four types based on their location in the stomach and their relationship with esophageal varices (GOV1, GOV2, IGV1, and IGV2). Understanding their hemodynamics with respect to GV drainage routes is important to guide their treatment.

Estudo de fase II de pregabalina para prevenção de náuseas e vômitos induzidos por quimioterapia / Phase II study of pregabalin for the prevention of chemotherapy induced nausea and vomiting

Para avaliar o papel da pregabalina na proteção das náuseas e vômitos induzidos pela quimioterapia, foi realizado um ensaio clínico de fase II, aleatorizado, duplamente cego, controlado por placebo, para investigar se a pregabalina poderia melhorar o controle completo das náuseas e vômitos (desfecho primário). Inscrevemos 82 pacientes virgens de quimioterapia, programados para receber quimioterapia moderadamente e altamente emetogênica. Todos os doentes receberam ondansetron 8mg por via intravenosa, dexametasona 10mg antes da quimioterapia no primeiro dia e, dexametasona 4 mg por via oral, b.d., nos dias dois e três. Os doentes foram distribuídos aleatoriamente para tomar pregabalina 75 mg ou placebo, bd, desde a noite anterior à quimioterapia até ao quinto dia. A resposta completa global não foi estatisticamente significativa entre os grupos (53,7 versus 48,8%, respetivamente, no grupo da pregabalina e no grupo de controlo (P=0,65)). Também não houve diferença estatística significativa durante a fase aguda (primeiras 24 horas) e a fase tardia (24-120h): 80,5% versus 82,9% (P=0,77), 53,7 versus 51,2% (P=0,82), respectivamente. Neste estudo não foi identificada ação da pregabalina na prevenção de náuseas e vômitos induzidos por quimioterapia. Número de registo no Clinicaltrial.gov: NCT04181346.

To evaluate the role of pregabalin in the protection of chemotherapy-induced nausea and vomiting, we performed a phase II randomized, double-blind, placebo-controlled trial to investigate whether pregabalin could improve the complete control of nausea and vomiting (primary end point). We enrolled 82 chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy. All patients received IV ondansetron 8mg, dexamethasone 10mg before chemotherapy on day one and oral dexamethasone 4mg, b.d., on days two and three. Patients were randomly assigned to take pregabalin 75mg or placebo, bd, from the night before chemotherapy to day five. The overall complete response was not statistically significant between the groups (53.7 versus 48.8%, respectively, in the pregabalin group and the control group (P=0.65)). There was also no significant difference during the acute phase (first 24 hours) and delayed phase (24-120h): 80.5% versus 82.9% (P=0.77), 53.7 versus 51.2% (P=0.82), respectively. There is no role for pregabalin preventing chemotherapy-induced nausea and vomiting. Clinicaltrial.gov registration number: NCT04181346.

Tumor-targeted metabolic inhibitor prodrug labelled with cyanine dyes enhances immunoprevention of lung cancer

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Tamsulosin vs. Tadalafil as medical expulsive therapy for distal ureteral stones: a systematic review and meta-analysis

ABSTRACT Purpose: Medical expulsive therapy (MET) is recommended for distal ureteral stones from 5 to 10 mm. The best drug for MET is still uncertain. In this review, we aim to compare the effectiveness of tadalafil and tamsulosin for distal ureteral stones from 5 to 10 mm in terms of stone expulsion rate (SER), stone expulsion time (SET) and the side effect profile. Materials and methods: A comprehensive literature search was conducted on MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science, from inception until April 2023. Only randomized controlled trials were included in the analysis. Results: Eleven publications with 1,330 patients were included. We observed that tadalafil has a higher SER (OR 0.55, CI 95% 0.38;0.80, p=0.02, I2=52%) and the same efficacy in SET (MD 1.07, CI 95% -0.25; 2.39, p=0.11, I2=84%). No differences were found when comparing side effects as headache, backache, dizziness, and orthostatic hypotension. Conclusion: Tadalafil has a higher stone expulsion rate than tamsulosin as a medical expulsive therapy for patients with distal stones from 5 to 10 mm without differences in side effects.

Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in the Management of Arterial Stiffness and Target Organ Damage in Patients with Hypertension

Abstract Background Arterial stiffness and hypertension are strong predictors of cardiovascular disease and mortality. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are first-line antihypertensive agents in reducing blood pressure and arterial stiffness. Objective The objective of this study was to compare the effects of ACEI and ARB in reducing arterial stiffness and preventing target organ damage in patients with hypertension. Methods This observational study included 654 participants who attend routine consultations at an outpatient hypertension clinic in 2 university hospitals. Patients were interviewed, and they underwent central and peripheral blood pressure measurements. Doppler echocardiography, carotid ultrasound, biochemical tests, and anthropometric parameters were carried out. Shapiro-Wilk, chi-square, and Fisher's exact test were used. A significance level of 5% was adopted. Results A total of 659 participants were evaluated in the study (398 from the ARB group and 256 from the ACEI group). Age, body mass index (BMI), central and peripheral blood pressure measurements, pulse wave velocity (PWV), left ventricular mass index, and carotid intima-media thickness did not show differences between the groups (p > 0.05). After linear regression analysis, the ACEI group had lower values of total vascular resistance (TVR) (p = 0.003) and augmentation pressure (p = 0.008), when compared to the ARB group. Conclusion This study showed that the ACEI group had a greater reduction in augmentation pressure and PWV. There were no differences between the groups regarding the improvement of outcomes related to central arterial pressure, PWV, and cardiac and vascular target organ damage.

Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis / Antagonistas duais do receptor de orexina para o tratamento da insônia: revisão sistemática e metanálise em rede

Abstract Background Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. Objective To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia. Methods The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs). Results We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higherdoses relating to a longerTST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = −25.40; 95% confidence interval [95%CI] = −40.02- −10.78), followed by suvorexant 20/15mg (SMD = −25.29; 95%CI = −36.42- −14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = −23.70; 95%CI = −35.89- −11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%. Conclusion Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.

Resumo Antecedentes Inúmeros ensaios clínicos randomizados (ECRs) têm demonstrado que os antagonistas duais do receptor de orexina (dual orexin receptor antagonists, DORAs, em inglês) são eficazes no tratamento da insônia. Contudo, restam dúvidas quanto à superioridade de um DORA com relação aos outros. Objetivo Realizar uma meta-análise em rede para avaliar a eficácia de diferentes DORAs em pacientes com insônia. Métodos Foram feitas buscas nas bases de dados Medline, Embase e Cochrane Central por ECRs que comparassem DORAs e placebo em pacientes ≥ 18 anos de idade com diagnóstico de insônia. Os seguintes desfechos foram selecionados: tempo desperto após o início do sono (wake time after sleep onset, WASO, em inglês), latência para o sono persistente (latency to persistent sleep, LPS, em inglês), tempo total de sono (total sleep time, TST, em inglês), e efeitos adversos (EAs). Resultados Incluímos 10 ensaios clínicos com 7,806 pacientes, 4,849 dos quais receberam DORAs como intervenção. Os DORAs foram associados à melhoria de todos os desfechos de eficácia analisados. Em relação ao TST, um aparente padrão de dependência da dose foi identificado, com doses maiores se associando a um maior TST. Lemborexant 10 mg proporcionou a maior redução em WASO (no primeiro mês) em minutos (diferença padronizada das médias [standardized mean difference, [SMD], em inglês) = −25.40; intervalo de confiança de 95% [IC95%] = −40.02- −10.78), seguido de suvorexant 20/15mg (SMD = −25.29; IC95% = −36.42- −14.15), o qual também proporcionou a maior diminuição em WASO no longo prazo (SMD = −23.70; IC95% = −35.89- −11.51). Os EAs mais frequentes foram sonolência, nasofaringite e cefaleia, com taxas de até 14.8%. Conclusão Nossos resultados sugerem que os DORAs estão associados a uma maior eficácia quando comparados com placebo no tratamento da insónia, um complexo transtorno do sono de 24 horas. Além disso, a dosagem pode desempenhar um papel importante no manejo da insónia crônica.

Background cardiovascular risk factors in patients of metastatic prostate cancer on androgen deprivation therapy: A retrospective observational study from a tertiary care hospital of Eastern India

Background: Androgen deprivation therapy (ADT) is indispensable part of treatment for metastatic prostate cancer (MPC) patients. There is documented association between ADT and adverse cardiovascular (CV) events, with variability between the different modes. However, there is dearth of evidence on the background CV risk factors of these group of patients at diagnosis. Aims and Objectives: We envisaged this retrospective observational study in the department of oncology to document the background CV risk factors of MPC patients at diagnosis, to help us better select the available ADTs based on their CV risks. Materials and Methods: Over a period of 2 years, all patients registered for treatment with a diagnosis of MPC, indicated for ADT, and available detailed history and background cardiological evaluation at presentation, were included in the study. As indirect indicators of CV risks, history of smoking, presence and treatment of dyslipidemia, and type 2 diabetes mellitus (T2DM), were documented. As direct indicators of CV risks, presence and treatment of hypertension, ischemic heart disease (IHD), congestive cardiac failure (CCF), ECG, and echocardiography changes suggesting cardiac morbidity were documented and the data were analyzed using descriptive statistical methods. Results: Indirect indicators: dyslipidemia, habit of smoking, and T2DM were found in 74%, 29.3%, and 13.3% patients, respectively. Direct indicators: Presence of hypertension, IHD, CCF, abnormalities in ECG, and echocardiography were found in 38.7%, 10.6%, 4%, 28%, and 34.6% patients, respectively. ST-T changes on ECG, low EF, and IHD on echocardiography were seen in 28.5%, 23%, and 26.9%, respectively. Conclusions: MPC patients have a substantial pre-existing CV risk at diagnosis. Our findings warrant a meticulous screening of all MPC patients for CV risk factors, to help in judicious selection of their ADT.

Efficacy of 5-HT1F agonist versus CGRP-antagonists for treatment of acute migraine: A systematic review and network meta-analysis

Background: Two new classes of drugs approved by USFDA for the treatment of acute migraine are non-peptide Calcitonin Gene-Related Peptide (CGRP) receptor antagonists (rimegepant and ubrogepant) and 5-HT1F receptor agonist lasmiditan. There are no clinical trials comparing these two classes of newer drugs. Aim and Objectives: The present network meta-analysis was conducted with the objective to compare the efficacy of orally administered lasmiditan versus CGRP-receptor antagonists (rimegepant and ubrogepant) in the treatment of acute migraine. Materials and Methods: Electronic database search in PUBMED and Cochrane library was conducted using MeSH search terms “Lasmiditan” AND “Migraine” for articles on lasmiditan; while MeSH terms “Ubrogepant” AND “Migraine;” “Rimegeapnt” AND “Migraine” were used for articles on CGRP-antagonists. Randomized or cross-over studies comparing efficacy of oral lasmiditan and two FDA approved CGRP-antagonists (rimegepant, and ubrogepant) versus other active treatment or placebo in adults with acute attack of migraine were included in the analysis. Incidence of 2 h pain-free event was the primary outcome measure while the incidence of 24 h pain-free was the secondary outcome measure compared. Both frequent and Bayesian network meta-analysis were conducted by CRSU MetaInsight software. Results: In 12 eligible studies, seven interventions were compared with total 13795 patients analyzed in the network. Higher treatment ranking for 2 h and 24 h pain-free events was observed for lasmiditan 200 mg and rimegepant 150 mg, respectively. Conclusions: There is strong evidence to conclude that lasmiditan at 200 mg is better drug for immediate (2 h) headache freedom. There is limited evidence to support rimegepant for sustained effect (beyond 24 h).

The use of angiotensin receptor blockers in dementia prevention / O uso de bloqueadores de receptor de angiotensina na prevenção de demência

ABSTRACT: Alzheimer's disease (AD) and dementia are preventable and highly prevalent diseases, as is systemic arterial hypertension. Thus, it is speculated that angiotensin receptor blockers (ARBs) may be neuroprotective against AD. Objective: The aim of this study was to evaluate if the use of ARBs confers a neuroprotective effect on AD, through a systematic review. Methods: Studies published on Embase, LILACS, SciELO, and PubMed were evaluated. The selection of the studies included those that evaluated the use of antihypertensive drugs in individuals with a previous diagnosis of mild cognitive impairment. The data were extracted with the Cochrane Effective Practice and Organization of Care (EPOC) form. The risk of bias was evaluated by the EPOC "Risk of bias tool." Results: A total of 12 articles were identified, and 3 articles were selected. Two of them analyzed the use of ARB/ACEI versus other antihypertensives and the development of dementia. Conclusion: There is a tendency for ARBs to be superior to other antihypertensives in preventing dementia.

RESUMO: A doença de Alzheimer (DA) e a demência são doenças potencialmente preveníveis, assim como a hipertensão arterial sistêmica. Dessa forma, especula-se que os bloqueadores dos receptores de angiotensina (BRA) tenham efeito neuroprotetor contra a DA. Objetivo: Avaliar se o uso de BRA confere efeito neuroprotetor para DA, por meio de uma revisão sistemática. Métodos: Foram avaliados estudos publicados nas plataformas Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Scientific Electronic Library Online (SciELO) e United States National Library of Medicine (PubMed). Os estudos incluídos avaliaram o uso de anti-hipertensivos em indivíduos com diagnóstico prévio de comprometimento cognitivo leve. Os dados foram extraídos com base no formulário da EPOC. Risco de viés foi avaliado por meio da ferramenta da Cochrane Effective Practice and Organisation of Care (EPOC) "Risk of bias tool". Resultados: Foram encontrados 12 artigos e três foram selecionados. Dois analisaram o uso de BRA/IECA vs. o uso de outros anti-hipertensivos e o desenvolvimento de demência. Conclusão: Há uma tendência de que os BRA sejam superiores a outros anti-hipertensivos na prevenção da demência.

The cannabinoids mechanism of action: an overview / Mecanismo de ação dos canabinoides: visão geral

ABSTRACT BACKGROUND AND OBJECTIVES: The discovery of the psychoactive agent of Cannabis sativa (tetrahydrocannabinol - THC) in the second half of the 20th century originated the research that later came to identify dozens of other substances from this plant, including cannabinoids, terpenes and flavonoids. Ensuing description of their interaction sites in animals and humans, together with endogenous ligands, transport proteins as well as synthesis and degradation enzymes, revealed what came to be known as the endocannabinoid system. Several receptors participate in this system. CONTENTS: The first receptors to be discovered were called CB1 and CB2, both are G protein-coupled (GPCR). It is noteworthy that CB1 receptors are among the most abundant and widely distributed GPCR in the mammalian brain, with marked expression in basal ganglia, cerebellum and hippocampus, for instance; on the other hand, they are scarce in areas of the brainstem related to breathing control. In light of the multiplicity of pharmacological effects of cannabinoids, concomitant with the lack of more clarifying studies on their mechanisms of action despite the great interest in research on their therapeutic application, it is necessary to deepen the knowledge in this area. CONCLUSION: Considering the literature research conducted for the composition of this article, it is possible to conclude that cannabinoids have a broad spectrum of action mechanisms in the human body, and that more robust clinical studies are needed to better understand their broad therapeutic potential.

RESUMO JUSTIFICATIVA E OBJETIVOS: A descoberta do princípio psicoativo da Cannabis sativa (tetrahidrocanabinol - THC) na segunda metade do século XX inaugurou pesquisas que posteriormente vieram a identificar dezenas de outras substâncias a partir dessa planta, incluindo canabinoides, terpenos e flavonoides. A subsequente descrição dos sítios de interação dessas substâncias em animais e humanos, assim como seus ligantes endógenos, proteínas de transporte e enzimas de síntese e degradação, revelou o que veio a ser conhecido como sistema endocanabinoide. Diversos receptores participam deste sistema. CONTEÚDO: Os primeiros receptores a serem descobertos foram denominados CB1 e CB2, ambos são acoplados à proteína G (GPCR). É importante ressaltar que os receptores CB1 estão entre os GPCRs mais abundantes e amplamente distribuídos do encéfalo de mamíferos, com marcada expressão, por exemplo, em gânglios da base, cerebelo e hipocampo; em contrapartida, são escassos em áreas do tronco cerebral relacionadas ao controle da respiração. Diante da multiplicidade de efeitos farmacológicos dos canabinoides, concomitante à falta de estudos mais esclarecedores sobre seus mecanismos de ação apesar do grande interesse na pesquisa de sua aplicação terapêutica, é preciso aprofundar o conhecimento nessa área. CONCLUSÃO: Considerando as pesquisas bibliográficas realizadas para a composição deste artigo, é possível concluir que os canabinoides possuem um amplo espectro de mecanismos de ação no organismo humano, e que mais estudos clínicos robustos são necessários para que seja possível entender melhor o seu amplo potencial terapêutico.

Assessment and comparison of anticholinergic exposure in older adults at a Basic Health Unit in Porto Alegre / Avaliação e comparação da exposição anticolinérgica em idosos de uma Unidade Básica de Saúde de Porto Alegre

Objectives: To estimate the anticholinergic burden in geriatric patients using two scales and to assess the degree of agreement between them. Methods: Data from an observational study conducted in a primary health care service were used. Anticholinergic burden was assessed using the Belgian Scale Muscarinic Acetylcholinergic Receptor ANTagonist Exposure Scale and the Brazilian Scale of Medicines with Anticholinergic Activity. The cumulative anticholinergic burden score was classified using a categorical approach: Brazilian scale (0: none; 1 ­ 2: low; ≥ 3: high) and Belgian scale (0: none; 0.5 ­ 1.5: low; ≥ 2: high). The degree of agreement between the two instruments was obtained through Cohen's kappa coefficient. Results: A total of 374 older people were included, most of them female and aged between 60 and 69 years. At least one potentially inappropriate drug with anticholinergic activity was used by 60.70% of patients according to the Brazilian scale and 32.89% by the Belgian scale. On average, 20.85% were under high anticholinergic exposure. Overall, on both scales, the most commonly recurrent medications were those indicated for the treatment of psychiatric disorders. Agreement between the scales was moderate (Kappa = 0.43). Conclusions: A high percentage of older adults was exposed to drugs with an anticholinergic burden, posing risks to health and quality of life. Consensus is needed on how anticholinergic burden is calculated by these scores, as well as standardization of the list of included drugs.

Objetivos: Estimar a carga anticolinérgica em idosos com base em duas escalas e avaliar o grau de concordância entre estas. Metodologia: Foram utilizados dados de um estudo observacional realizado em um serviço de atenção primária. A carga anticolinérgica foi avaliada pela escala belga Muscarinic Acetylcholinergic Receptor ANTagonist Exposure Scale e da Escala Brasileira de Medicamentos com Atividade Anticolinérgica. A pontuação da carga anticolinérgica cumulativa foi classificada utilizando uma abordagem categórica: escala brasileira (0: nenhuma, 1 ­ 2: baixa, ≥ 3: alta) e escala belga (0: nenhuma, 0,5 ­ 1,5: baixa, ≥ 2: alta). O grau de concordância entre as duas ferramentas foi obtido por meio do coeficiente Capa de Cohen. Resultados: Foram incluídos 374 idosos, a maioria do sexo feminino e com idade entre 60 a 69 anos. O uso de pelo menos um medicamento potencialmente inapropriado com atividade anticolinérgica foi verificado em 60,70% dos idosos com a aplicação da escala brasileira e em 32,89% com a escala belga. Em média, 20.85% estavam sob alta exposição anticolinérgica. De modo geral, os medicamentos mais recorrentes, para ambas as escalas, foram os indicados para o tratamento de transtornos psiquiátricos. A concordância entre as escalas foi moderada (Capa = 0,43). Conclusão: Um percentual elevado de idosos estava exposto a medicamentos com carga anticolinérgica, representando riscos para a saúde e a qualidade de vida. É necessário um consenso sobre como calcular a carga anticolinérgica nos diferentes escores, bem como a padronização da lista de medicamentos incluídos.

Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis / Efeitos cognitivos de drogas anticolinérgicas individuais: uma revisão sistemática e meta-análise

ABSTRACT. Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. Objective: The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. Methods: This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Results: Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. Conclusion: The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.

RESUMO. Os anticolinérgicos (ACs) estão entre os medicamentos mais prescritos. Investigar os domínios cognitivos prejudicados devido ao uso individual de ACs está associado a achados controversos. Objetivo: Investigar os efeitos de ACs individuais em diferentes aspectos da função cognitiva, com base em estudos de ensaios clínicos. Métodos: Esta revisão sistemática foi realizada em acordo com a declaração PRISMA. Uma busca sistemática foi realizada nos bancos de dados Embase, PubMed, Cochrane Library, Scopus e Web of Science. O risco de viés (risk of bias - RoB) foi avaliado pelas listas de verificação do Joanna Briggs Institute e a meta-análise foi realizada através do software CMA. Resultados: Foram incluídos 138 estudos dos 3.026 resultados da pesquisa. Trinta e oito estudos que avaliam os impactos cognitivos da escopolamina foram incluídos na meta-análise. Os estudos incluídos relataram efeitos cognitivos de escopolamina, mecamilamina, atropina, biperideno, oxibutinina, triexifenidil, benzhexol, diciclomina; no entanto, glicopirrolato, tróspio, tolterodina, darifenacina, fesoterodina, tiotrópio e ipratrópio não foram associados ao declínio cognitivo. Com base nas meta-análises, a escopolamina foi associada a reconhecimento reduzido (DPM -1,84; IC95% -2,48 a -1,21; p<0,01), recordação imediata (DPM -1,82; IC95% -2,35 a -1,30; p<0,01), correspondência com a amostra (DPM -1,76; IC95% -2,57 a -0,96; p<0,01), recordação atrasada (DPM -1,54; IC95% -1,97 a -1,10; p <0,01), tarefas de memória complexas (DPM -1,31; IC95% -1,78 a -0,84; p<0,01), recordação livre (DPM -1,18; IC95% -1,63 a -0,73; p<0,01), função cognitiva (DPM -0,95; IC95% -1,46 a -0,44; p<0,01), atenção (DPM -0,85; IC95% -1,38 a -0,33; p<0,01) e amplitude de memória de dígitos (DPM -0,65; IC95% -1,21 a -0,10; p=0,02). Houve um alto RoB em nosso estudo, especialmente quanto aos possíveis confundidores. Conclusão: As limitações deste estudo sugerem a necessidade de estudos mais bem delineados e com maior duração de acompanhamento sobre o tema para alcançar evidências mais confiáveis.

Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial

Abstract Objectives Evidence suggests that ketamine's influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD). Methods Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards. Results There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms. Conclusion There was no significant treatment impact on BDNF serum levels - neither with ketamine nor esketamine - despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion. This clinical trial is registered on the Japan Primary Registries Network: UMIN000032355.

Relationship between anticholinergic load and self-perceived health in a population aged 44 years or older / Relação entre carga anticolinérgica e autopercepção de saúde em população com mais de 44 anos

OBJECTIVE: To investigate the relationship between anticholinergic load (ACL) and self-perceived general health in adults in a medium-sized municipality in southern Brazil. METHODS: This cross-sectional study was based on 2015 data from a medium-sized municipality in southern Brazil. All respondents aged 44 years or older who reported using drugs in the 2 weeks before the interview were included (n = 662). The Anticholinergic Drug Scale was used to measure the ACL. Self-perceived health was categorized as positive self-perception (PSP) or negative self-perception (NSP). Crude and adjusted Poisson regression analyses were conducted to investigate the association between ACL and self-perceived health. RESULTS: NSP was found in 50.91% of 662 respondents. Significant ACL, older age, lower economic status, lower education, polypharmacy, and depression correlated with a higher frequency of NSP. Individuals with significant ACL had a prevalence of NSP of 1.27 (95% confidence interval: 1.02 ­ 1.58), and each additional ACL level represented a 6.10% higher chance of worse self-perceived health, regardless of confounding factors. CONCLUSIONS: An association was found between significant ACL and NSP, with an effect dependent on ACL level

OBJETIVO: Investigar a relação entre carga anticolinérgica (CAC) e autopercepção de saúde em adultos de um município de médio porte do sul do Brasil. METODOLOGIA: Trata-se de um estudo transversal com dados de 2015, realizado em um município de médio porte do sul do Brasil. Todos os entrevistados com 44 anos ou mais que relataram uso de drogas nas duas semanas anteriores à entrevista foram incluídos (n = 662). A Anticholinergic Drug Scale (ADS) foi utilizada para medir a CAC. A autopercepção da saúde foi categorizada em autopercepção positiva (APP) ou autopercepção negativa (APN). Análises de regressão de Poisson bruta e ajustada foram realizadas para investigar a associação entre CAC e autopercepção de saúde. RESULTADOS: Entre os 662 participantes, a CAC foi encontrada em 50,91% dos respondentes. CAC significativa, idade avançada, situação econômica mais baixa, menor escolaridade, polifarmácia e depressão foram correlacionados com maior frequência de APN. Indivíduos com CAC significativo apresentaram prevalência de APN de 1,27 (intervalo de confiança de 95%: 1,02 ­ 1,58), e cada nível adicional de CAC representou uma chance 6,10% maior de pior autopercepção de saúde, independentemente de fatores de confusão. CONCLUSÕES: Encontrou-se associação entre ACL significativo e APN, com efeito dependente do valor do CAC

De-escalação de inibidores dos receptores P2Y12 após intervenção coronária percutânea / P2Y12 inhibitor de-escalation after percutaneous coronary interventions

Em pacientes que apresentam síndromes coronárias agudas e são tratados com intervenção coronária percutânea, a prescrição do esquema antiplaquetário duplo, composto de ácido acetilsalicílico e um inibidor dos receptores P2Y12, é mandatória, contribuindo para a redução de eventos cardíacos maiores. No entanto, ao mesmo tempo em que previne eventos isquêmicos, essa associação pode precipitar complicações hemorrágicas maiores, o que é mais comumente observado quando são prescritos os medicamentos mais potentes, como o prasugrel ou o ticagrelor. Essas constatações levaram à procura de alternativas terapêuticas capazes de manter a proteção contra eventos isquêmicos e, ao mesmo tempo, prevenir a ocorrência de hemorragias. Uma das estratégias que está em estudo é a de-escalação dos inibidores P2Y12, que consiste no uso dos medicamentos mais potentes numa fase precoce após o procedimento, com substituição deles pelo clopidogrel, após um período de, em geral, 30 dias de evolução; outra possibilidade seria a simples redução da dose do fármaco de maior potência, algo que, até o momento, só pode ser cogitado com o prasugrel. A de-escalação pode ser feita de forma guiada, utilizando testes de mensuração objetiva da agregação plaquetária ou exames para avaliar o perfil genético dos pacientes, ou não guiada, na qual o cardiologista simplesmente faz a substituição ou redução da dose ao fim do período estipulado, sem o auxílio de exames complementares. A literatura contempla ensaios clínicos com essas duas opções de estratégia, os quais são discutidos nesta revisão. Até o momento, nenhuma diretriz médica recomenda de forma explícita o uso regular dessa alternativa terapêutica.

In patients who have acute coronary syndromes and are treated with percutaneous coronary intervention, the prescription of a dual antiplatelet regimen, consisting of acetylsalicylic acid and a P2Y12 receptor inhibitor, is mandatory, contributing to the reduction of major cardiac events. However, while preventing ischemic events, this association may precipitate major bleeding complications, which is more commonly seen when more potent drugs, such as prasugrel or ticagrelor, are prescribed. These findings led to the search for therapeutic alternatives that could maintain the protection against ischemic events and, at the same time, prevent the occurrence of hemorrhages. One of the strategies being studied is de-escalation of P2Y12 inhibitors, which consists of the use of more potent drugs in an early phase after the procedure, replacing them with clopidogrel, after a period of, in general, 30 days of clinical course. Another possibility would be to simply reduce the dose of the most potent drug, which so far can only be considered with prasugrel. De-escalation can be done in a guided way, using objective measuring tests of platelet aggregation or exams to assess the genetic profile of patients, or unguided, in which the cardiologist simply replaces or reduces the dose at the end of the stipulated period, with no ancillary tests. The literature includes clinical trials with these two strategy options, which are discussed in this review. So far, no medical guideline explicitly recommends the regular use of this therapeutic alternative.

Role of α7nAChR in penehyclidine hydrochloride-induced reduction of endotoxin-induced acute lung injury in mice / 中华麻醉学杂志

Objective:To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in penehyclidine hydrochloride-induced reduction of endotoxin-induced acute lung injury (ALI) in mice.Methods:Forty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-25 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), ALI group, penehyclidine hydrochloride group (PHC group), and α7nAChR inhibitor MLA group (MLA group). ALI was induced by intraperitoneal injection of lipopolysaccharide 15 mg/kg in anesthetized animals, while normal saline was given instead in group C. In PHC group, penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected at 30 min before developing the model. MLA 10 mg/kg was intraperitoneally injected at 10 min before administration of penehyclidine hydrochloride in MLA group. Mice were sacrificed at 6 h after lipopolysaccharide administration, and lung tissues were collected for microscopic examination of the pathological changes (by HE staining) and for determination of the wet/dry weight ratio (W/D ratio), content of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-10 (by enzyme-linked immunosorbent assay) and expression of α7nAChR (by Western blot). Results:Compared with C group, the W/D ratio and contents of TNF-α and IL-1β were significantly increased, the content of IL-10 was decreased, and the expression of α7nAChR was up-regulated in ALI, PHC and MLA groups ( P<0.05). Compared with ALI group, the W/D ratio and contents of TNF-α and IL-1β were significantly decreased, the content of IL-10 was increased, and the expression of α7nAChR was up-regulated in PHC group ( P<0.05). Compared with PHC group, the W/D ratio and contents of TNF-α and IL-1β were significantly increased, the content of IL-10 was decreased, and the expression of α7nAChR was down-regulated in MLA group ( P<0.05). Compared with ALI group, the pathological changes of lung tissues were significantly mitigated in PHC group, while this effect of PHC was partially reversed by α7nAChR inhibitor MLA. Conclusions:α7nAChR is involved in penehyclidine hydrochloride-induced reduction of endotoxin-induced ALI in mice.

Analysis of factors related to the efficacy of Tamsulosin monotherapy for overactive bladder symptoms in benign prostatic hyperplasia patients with the prostate volume <40 ml / 中华老年医学杂志

Objective:To assess the efficacy of Tamsulosin monotherapy for overactive bladder(OAB)symptoms in benign prostatic hyperplasia(BPH)patients with the prostate volume(PV)<40 ml, and to analyze related factors affecting the efficacy.Methods:300 BPH patients with OAB were enrolled, with an average age of(66.9±7.7)years and the PV<40 ml.Smoking, drinking and other living habits were investigated.Data on the Overactive Bladder Symptom Score(OABSS), International Prostate Symptom Score(IPSS)and Quality of Life Scale(QOLS)were collected before and after 4 weeks of treatment with Tamsulosin 0.2 mg QN.The maximum urine flow rate(Qmax)and bladder residual urine volume(PVR)were measured before and after treatment.OBASS was used as the main assessment parameter to analyze the correlation of efficacy with age, lifestyle, pre-treatment symptom scores, PV, Qmax and PVR.Results:257 patients completed the study, and 169 patients were treated effectively, with an overall effectiveness rate of 65.8%.The effectiveness rates of the mild, moderate and severe OAB groups were 83.6%, 62.4% and 38.5%, respectively, with statistical significance( χ2=13.037, P=0.001).3 patients showed adverse drug reactions, including 2 patients with mild dizziness and 1 patient with nausea.The baseline OABSS score, the proportion of smoking patients and the proportion of drinking patients in the effectively treated OAB group were significantly lower than those in the ineffectively treated group.Multivariate analysis showed that baseline OABSS score( OR=0.735, P<0.001)and smoking( OR=2.111, P=0.029)were correlated with tamsulosin's efficacy in treating BPH patients with OAB with PV<40 ml. Conclusions:The effectiveness rate of Tamsulosin for the treatment of BPH patients with mild OAB with PV<40 ml is high.The baseline OABSS score and smoking are factors affecting the efficacy of Tamsulosin on OAB symptoms in these patients.

Development of fibroblast activation protein-targeted molecular probes in non-neoplastic diseases / 中华核医学与分子影像杂志

Fibroblast activation protein (FAP) is an important molecular marker of cancer-associated fibroblasts (CAFs). FAP is selectively expressed in more than 90% of epithelial carcinomas, but barely expressed in normal tissues. In recent years, a variety of radiolabeled molecular probes based on FAP inhibitor (FAPI) have been developed and used for imaging of malignant tumors. FAP is also highly expressed in some non-neoplastic diseases related to chronic inflammation and tissue remodeling, including arthritis, atherosclerosis, fibrosis of myocardial infarction, cirrhosis, and idiopathic pulmonary fibrosis. FAPI imaging shows a potential in these diseases. This paper reviews the current status of radionuclide labeled FAPI and the application of which in non-neoplastic diseases.

Relationship between the SUV max of primary lesion on 18F-FAPI-42 PET/CT imaging and the clinicopathological characteristics of patients with gastric cancer / 中华核医学与分子影像杂志

Objective:To explore the relationship between 18F-fibroblast activation protein inhibitor (FAPI)-42 SUV max of primary gastric cancer and clinicopathological factors of patients. Methods:Fifty-one patients (31males, 20 females, age: 51(47, 65) years) with gastric cancer who underwent 18F-FAPI-42 PET/CT before surgical resection in Nanfang Hospital, Southern Medical University from February 2022 to January 2023 were analyzed retrospectively. The clinicopathological factors that might affect tumor SUV max (including gender, age, tumor location, pathological type, histological grade, Lauren classification, vascular and(or) neural invasion, programmed cell death-ligand 1 (PD-L1) expression, pathologic(p)T stage, pN stage and pTNM stage) were evaluated by the univariate analysis (Mann-Whitney U test or Kruskal-Wallis rank sum test) and multivariate analysis (multiple linear regression analysis). Results:The sensitivity of 18F-FAPI-42 PET/CT in the diagnosis of patients with primary gastric cancer was 82.35% (42/51). The diagnostic sensitivities for early gastric cancer (T1) and locally advanced gastric cancer (T2-T4) were 59.09%(13/22) and 100%(29/29), respectively. The SUV max of primary lesion was 4.90(1.71, 12.51). The univariate analysis showed that SUV max of primary gastric cancer was related to tumor location ( z=-2.00, P=0.046), pT stage ( H=36.94, P<0.001), pN stage ( z=-3.89, P<0.001), pTNM stage ( H=31.49, P<0.001) and vascular and(or) nerve invasion ( z=-5.22, P<0.001), but not related to pathological type, histological grade, Lauren typing, and PD-L1 expression ( z values: from -1.78 to -0.09, all P>0.05). pT stage was found to be a significant independent factor for SUV max in primary gastric lesion by multivariate analysis ( t=2.52, P=0.015). Conclusions:The 18F-FAPI-42 SUV max of primary tumor was related to tumor location, pT stage, pN stage, pTNM stage, and vascular and(or) nerve invasion; pT stage is an independent factor affecting tumor SUV max. The ability of 18F-FAPI-42 PET/CT to detect gastric cancer is mainly affected by pT stage.