Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

Evolução do grau de incapacidade física e do escore olhos, mãos e pés em casos novos de hanseníase: do diagnóstico à alta medicamentosa / Evolution of the degree of physical disability and the eye, hand and foot score in new cases of leprosy: from diagnosis to medication discharge

Este estudo tem por objetivo avaliar a evolução do grau de incapacidade física e do escore olhos, mãos e pés, do diagnóstico à alta medicamentosa, segundo as variáveis sociodemográficas e clínicas, em pacientes diagnosticados com hanseníase. Trata-se de estudo transversal, baseado na análise de 71 pacientes com diagnóstico de hanseníase, acompanhados no Hospital Eduardo de Menezes, centro de referência em Belo Horizonte, Minas Gerais, Brasil, entre janeiro de 2017 a dezembro de 2020. Foi observado predomínio do sexo feminino (53,5%), média de idade de 46 anos, sendo a maioria procedente de outros municípios do interior de Minas Gerais (54,9%). A forma clínica mais frequente foi a dimorfa (64,8%), classificação operacional multibacilar (84,5%). O grau de incapacidade física 0 foi o mais prevalente no diagnóstico (56,5%) e na alta (53,1%), e em relação ao escore olhos, mãos e pés, houve variação entre 0 e 10 no diagnóstico e entre 0 e 8 na alta. Pelo teste de McNemar foi observado que dentre os pacientes que apresentavam algum grau de incapacidade física no momento do diagnóstico, 30,8% apresentaram ausência de incapacidade na alta. Ao comparar a evolução do grau de incapacidade física de paucibacilares e multibacilares no momento do diagnóstico e da alta, houve manutenção em 59,3% e melhora em 17,2% dos pacientes. Os dados apresentados indicam que muitos pacientes foram tratados tardiamente já apresentando as formas graves e com sequelas, já que o estudo foi desenvolvido em um centro de referência, que atende casos mais complexos e com complicações já instaladas. Os dados sugerem que pacientes assistidos que realizam o tratamento com poliquimioterapia podem ter melhora das incapacidades já instaladas. O mesmo ocorreu com o escore olhos, mãos e pés, que ao final do tratamento instituído houve melhora se comparado com a admissão.(AU)

This study aims to evaluate the evolution of the degree of physical disability and the eye, hand and foot score, from diagnosis to medication discharge, according to sociodemographic and clinical variables, in patients diagnosed with leprosy. This is a cross-sectional study, based on the analysis of 71 patients diagnosed with leprosy, followed by Hospital Eduardo de Menezes, a reference center in Belo Horizonte, Minas Gerais, Brazil, between January 2017 and December 2020. There was a predominance of females (53.5%), average age of 46 years old, the majority coming from other municipalities in the interior of Minas Gerais (54.9%). The most frequent clinical form was borderline (64.8%), multibacillary operational classification (84.5%). Degree of physical disability 0 was the most prevalent at diagnosis (56.5%) and at discharge (53.1%); in relation to the eye, hand and foot score, there was variation between 0 and 10 at diagnosis and between 0 and 8 at discharge. By the McNemar test, it was observed that of the patients who had degree of physical disability at the time of diagnosis, 30.8% had no disability at discharge. When comparing the evolution of the GIF in paucibacillary and multibacillary patients at the time of diagnosis and discharge, there was maintenance in 59.3% and improvement in 17.2% of the patients. The presented data indicates that many patients were treated late, already presenting severe forms and with sequelae, since the study was carried out in a reference center, which treats cases with complications already installed and more complex cases. The data suggest that assisted patients undergoing treatment with multidrug therapy may experience improvement in disabilities already established. The same occurred with eye, hand and foot score, at the end of the established treatment there was an improvement compared to admission.(AU)

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Clinical-epidemiological characterization of women who received post-exposure HIV prophylaxis in a public hospital in Porto Alegre, Rio Grande do Sul / Caracterização clínico-epidemiológica de mulheres que receberam a profilaxia pós-exposição ao HIV em um hospital público de Porto Alegre, Rio Grande do Sul

Introduction: Prevention strategies are key to combating the epidemic of infections such as HIV and syphilis. The epidemiological scenario of Porto Alegre/RS for these infections shows the need for greater efforts in the area of prevention, seeking to characterize both the population that uses these strategies and the services involved in the care of exposed people. Objective: This study aimed to characterize the clinical and epidemiological profile of patients who received post-exposure prophylaxis (PEP) to HIV treated in a public hospital in Porto Alegre/RS. Methods: This is a retrospective, research, descriptive study based on the Clinical Protocol and Therapeutic Guidelines for PEP, updated in 2018 by the Ministry of Health. Prophylaxis request forms and medical records of patients treated were analyzed. Results: The population consisted of 87 women who received PEP from January to September 2019. There was a predominance of women aged between 20 and 29 years old (55.2%). The most frequent sexual exposure was consensual (69.0%) followed by sexual assault (31.0%). Porto Alegre was the place of residence of most patients (73.6%). The most frequently used therapeutic regimen was the combination of atazanavir, ritonavir, and tenofovir plus lamivudine. On the first visit, 8.0% of the patients showed reactive results for the treponemal syphilis test. Only 23.0% and 14.9% of patients returned for anti-HIV tests in the first and third months after exposure, respectively, and the results were non-reactive. Only 19 patients (21.8%) attended the consultations between 0 and 28 days after PEP. Conclusion: It was identified that a considerable percentage of women already had reactive serology for syphilis, most women did not return for follow-up within 28 and 90 days after the first consultation, more than half of the women were aged between 20 and 29 years old, and the most frequent sexual exposure was consensual. In this sense, efforts are needed, such as adequate counseling, adoption of interventions such as sending messages by cell phone, telephone calls, and preparation of educational materials, seeking to improve adherence to treatment and follow-up in the service, which is important given the scenario of epidemiology in Porto Alegre.Keywords: HIV. Sexually transmitted diseases. Post-exposure prophylaxis. Disease prevention

Introdução: Estratégias de prevenção são fundamentais para o combate à epidemia de infecções como o vírus da imunodeficiência humana (HIV) e sífilis. O cenário epidemiológico de Porto Alegre/RS para essas infecções mostra a necessidade de maiores esforços na área de prevenção, buscando caracterizar tanto a população que utiliza essas estratégias quanto os serviços envolvidos no atendimento das pessoas expostas. Objetivo: Caracterizar o perfil clínico-epidemiológico das pacientes que receberam a profilaxia pós-exposição (PEP) ao HIV atendidas em um hospital público de Porto Alegre/RS. Métodos: Trata-se de um estudo retrospectivo, documental, descritivo e baseado no Protocolo Clínico e Diretrizes Terapêuticas para PEP, atualizado em 2021 pelo Ministério da Saúde. Foram analisados os formulários de solicitação da profilaxia e prontuários das pacientes atendidas. Resultados: A população foi composta de 87 mulheres que receberam a PEP no período de janeiro a setembro de 2019. Predominaram mulheres com idades entre 20 e 29 anos (55,2%). A exposição sexual mais frequente foi a consentida (69,0%), seguida pela violência sexual (31,0%). Porto Alegre foi o local de residência da maioria das pacientes (73,6%). O esquema terapêutico utilizado com maior frequência foi a combinação com atazanavir, ritonavir e tenofovir associado à lamivudina. No primeiro atendimento, 8,0% das pacientes demonstraram resultados reagentes para o teste treponêmico de sífilis. Retornaram para a realização dos testes anti-HIV no primeiro e terceiro mês após a exposição apenas 23,0 e 14,9% das pacientes, respectivamente, e os resultados foram não reagentes. Apenas 19 delas (21,8%) compareceram às consultas entre zero e 28 dias posteriores à PEP. Conclusão: Foi identificado que um percentual considerável de mulheres já apresentava sorologia reagente para sífilis, a maioria das mulheres não retornou para o seguimento no período de 28 e 90 dias após o primeiro atendimento, mais da metade delas tinha idade entre 20 e 29 anos e a exposição sexual mais frequente foi a consentida. Nesse sentido, são necessários esforços como aconselhamento adequado, adoção de intervenções como o envio de mensagens pelo celular, ligações telefônicas e elaboração de materiais educativos, buscando a melhoria da adesão ao tratamento e do acompanhamento no serviço, o que é importante diante do cenário epidemiológico de Porto Alegre.Palavras-chave: HIV. Infecções sexualmente transmissíveis. Profilaxia pós-exposição. Prevenção

Prevalencia de dolor y su abordaje terapéutico en niños pasibles de cuidados paliativos asistidos en un centro de referencia de Uruguay / Prevalence of pain and its therapeutic approach in children eligible for assisted palliative care in a reference hospital center in Uruguay / Prevalência de dor e sua abordagem terapêutica em crianças submetidas a cuidados paliativos atendidas em um centro hospitalar de referência no Uruguai

Introducción: el tratamiento del dolor es un derecho humano y constituye un pilar de los cuidados paliativos (CP). Este síntoma en niños suele ser subestimado e insuficientemente tratado. Objetivo: conocer la prevalencia del dolor y describir el perfil de uso de fármacos analgésicos, coadyuvantes y procedimientos invasivos en niños asistidos en la Unidad de Cuidados Paliativos Pediátricos del Centro Hospitalario Pereira Rossell (UCPP-CHPR) durante el período 2019-2021. Metodología: se realizó un estudio observacional, descriptivo y retrospectivo mediante revisión de historias clínicas. Resultados: se incluyeron 317 niños, 58% de sexo masculino, con una mediana de edad 6,9 años. Eran portadores de enfermedades neurológicas severas no evolutivas 64%, utilizaban prótesis o tecnología médica 51%. Se encontró registro de presencia de dolor en 35%, de tipo crónico 87%, mixto 55% y de fuentes múltiples 54%. Se detectó uso de escala para evaluación del dolor en 61%, la más utilizada fue r-FLACC. En el grupo de niños con dolor se encontró prescripción de analgésicos en 43% (48/111) y de coadyuvantes 87% (97/111), gabapentina en 78. En todos la vía de administración fue la oral/enteral. Se encontró uso off label de fármacos en 79% y polifarmacia en 82%. Se registraron efectos adversos en 10%. Conclusión: un tercio de los niños asistidos por la UCPP-CHPR, presentaba registros de presencia dolor. La mayoría de tipo crónico, mixto y de fuentes múltiples. Se encontró amplio uso de escalas validadas para evaluación del dolor y alta prescripción de coadyuvantes en relación a la de analgésicos.

Introduction: pain treatment is a human right and a pillar of palliative care (PC). This symptom in children is often underestimated and insufficiently treated. Objective: learn about the prevalence of pain and describe the analgesic drugs' usage profile, adjuvants and invasive procedures in children assisted in the Pediatric Palliative Care Unit of the Pereira Rossell Hospital Center (UCPP-CHPR) during the period 2019-2021. Methodology: observational, descriptive and retrospective study based on the review of medical records. Results: 317 children were included, 58% male, with a median age of 6.9 years. 64% were carriers of severe non-progressive neurological diseases, 51% used prosthetics or medical technology. A record of the presence of pain was found in 35%, chronic type 87%, mixed 55% and multiple sources 54%. The use of a pain assessment scale was detected in 61%, the most used was r-FLACC. In the group of children with pain, analgesics were prescribed in 43% (48/111) and adjuvants in 87% (97/111), gabapentin in 78. In all of them, the administration route was oral/enteral. Off-label use of drugs was found in 79% and polypharmacy in 82%. Adverse effects were recorded in 10%. Conclusion: a third of the children assisted by the UCPP-CHPR showed records of pain presence. Most chronic type, mixed and multiple sources. We found a vast use of validated scales for pain assessment and high prescription of adjuvants in relation to analgesics.

Introdução: o tratamento da dor é um direito humano e constitui um pilar dos Cuidados Paliativos (CP). Este sintoma em crianças é geralmente subestimado e insuficientemente tratado. Objetivo: conhecer a prevalência da dor e descrever o perfil do uso de medicamentos analgésicos, adjuvantes e procedimentos invasivos em crianças atendidas na Unidade de Cuidados Paliativos Pediátricos do Centro Hospitalar Pereira Rossell (UCPP-CHPR) durante o período de 2019-2021. Metodologia: foi realizado um estudo observacional, descritivo e retrospectivo por meio de revisão de prontuários. Resultados: foram incluídas 317 crianças, 58% do sexo masculino, com idade mediana de 6,9 anos. 64% eram portadores de doenças neurológicas graves não evolutivas, 51% usavam próteses ou tecnologia médica. Registro da presença de dor foi encontrado em 35%, do tipo crônica 87%, mista 55% e de origem múltipla 54%. A utilização de escala para avaliação da dor foi detectada em 61%, sendo a mais utilizada a r-FLACC. No grupo de crianças com dor, a prescrição de analgésicos foi encontrada em 43% (48/111) e adjuvantes em 87% (97/111), gabapentina em 78. Ao todo, a via de administração foi oral/enteral. Uso off-label de medicamentos foi encontrado em 79% e polifarmácia em 82%. Efeitos adversos foram registrados em 10%. Conclusão: um terço das crianças atendidas pela UCPP-CHPR apresentou registro da presença de dor. A maioria do tipo crônica, mista e de fontes múltiplas. Encontrou-se ampla utilização de escalas validadas para avaliação da dor e elevada prescrição de coadjuvantes em relação aos analgésicos.

Artemisinin drug resistance and monitoring: a narrative review

Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.

La résistance aux médicaments à base d'artémisinine est l'une des principales raisons des échecs du traitement du paludisme dans les pays d'Afrique subsaharienne où la polythérapie à base d'artémisinine (ACT) est le traitement de première intention du paludisme simple. L'apparition de polymorphismes mononucléotidiques (SNP) est corrélée à la résistance aux médicaments antipaludiques. Avec l'artémisinine, les SNP se produisent au locus du gène Kelch 13- propeller sur le chromosome 13. La stratégie de surveillance de la résistance aux médicaments à base d'artémisinine implique une surveillance continue du biomarqueur Kelch 13-propeller pour détecter l'émergence de mutations qui pourraient annoncer une résistance aux médicaments dans la région. Dans cet article de revue narrative, nous avons examiné la littérature existante pour combler le manque de connaissances et accentuer l'importance de la surveillance de routine de la résistance à l'artémisinine en Afrique subsaharienne. Nous avons effectué notre recherche sur la base de données PubMed et Google Scholar pour identifier des articles, des rapports et des résumés évalués par des pairs sur la résistance aux médicaments à base d'artémisinine en utilisant les mots-clés suivants; «résistance aux médicaments à base d'artémisinine¼, «résistance aux médicaments antipaludiques¼, «thérapie combinée à base d'artémisinine¼, «Kelch 13-propeller¼, «gène K13-propeller¼ et «marqueur moléculaire K13¼. L'examen a fourni des informations pertinentes sur les dérivés de l'artémisinine, la polythérapie à base d'artémisinine, l'action moléculaire de l'artémisinine, la définition de la résistance à l'artémisinine, la base génétique de la résistance aux médicaments à base d'artémisinine et la découverte de Kelch 13, ainsi que l'importance de la surveillance de la résistance à l'artémisinine. La surveillance moléculaire peut fournir aux responsables des politiques de santé une prévision des menaces imminentes pour le traitement du paludisme. C'est d'autant plus vrai lorsque les médicaments sont en thérapie combinée, par exemple, la surveillance moléculaire peut donner un indice qu'un médicament échoue malgré le fait qu'en combinaison, il est toujours apparemment cliniquement efficace.

Chinese Medicine as Supporting Therapy for Psoriasis: Past, Present, and Future / 中国结合医学杂志

Psoriasis is a chronic skin disease and an important health concern. Western medicine and therapies are the main treatment strategies for psoriasis vulgaris (PV); however, the overall prognosis of patients with PV is still poor. Therefore, PV prevention is especially crucial. Chinese medicine (CM) has a long history of treating psoriasis, and it has unique wisdom in different cognitive angles and treatment modes from modern medicine. In this review, we first summarized the herbs and ancient CM formulas that have therapeutic effects on PV. Second, the research status and obstacles to the current development of CM in modern medicine were reviewed. Finally, the future of CM in the context of precision medicine and integrated medicine was discussed. After a detailed reading of the abundant literature, we believe that CM, through thousands of years of continuous development and clinical practice, has achieved high effectiveness and safety for PV treatment, despite its surrounding controversy. Moreover, precise analyses and systematic research methods have provided new approaches for the modernization of CM in the future. The treatment of PV with CM is worth popularizing, and we hope it can benefit more patients.

Chinese expert consensus on intra-arterial drug and combined drug administration for primary hepatocellular carcinoma / 中华内科杂志

Transarterial interventional therapy is one of the most widely used treatment methods in patients with primary hepatocellular carcinoma. With the progress in interventional technology and the use of new drugs, transarterial interventional therapy has achieved favorable results in the treatment of primary hepatocellular carcinoma and has become the first choice non-surgical treatment for advanced liver cancer. However, at present, there are great differences in the drugs used in transarterial interventional treatment and the combined application of other drugs among centers, and there is no uniform consensus or guideline. Based on the latest research data and clinical practice experience, as well as the characteristics of Chinese patients, the Specialist Group of Interventional Drugs, Interventionalists Branch of the Chinese Medical Doctor Association was organized to formulate the Chinese expert consensus on intra-arterial drug and combined drug administration for primary hepatocellular carcinoma. The purpose of this consensus is to explore the efficacy and safety of drugs and drug combinations related to intra-arterial interventional therapy, the use of drugs in special populations, the management of adverse reactions, and adjuvant drugs to provide a reference for clinical practice.

Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori.@*METHODS@#This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed.@*RESULTS@#A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05).@*CONCLUSIONS@#The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.

Assessment of the safety and efficacy of combination chemotherapy and PD-1/PD-L1 inhibitor treatment of breast cancer: A meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment.@*METHODS@#Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses.@*RESULTS@#In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70-0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80-1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03-1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25-0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67-0.92, P = 0.002).@*CONCLUSIONS@#The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.

Bismuth, esomeprazole, metronidazole, and minocycline or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens.@*METHODS@#This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables.@*RESULTS@#As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups.@*CONCLUSION@#The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance.@*TRIAL REGISTRATION@#ClinicalTrials.gov, ChiCTR 1900023646.

Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial / 中华内科杂志

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

Clinical observation of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in patients with acute heart failure / 中华内科杂志

Objective: To observe the clinical effect of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in acute left heart failure patients 7 days after onset as well as the effects of plasma MDA and ET-1. Methods: In total, 240 hospitalized patients with acute left heart failure from October 2017 to May 2021 were selected from the Department of Emergency and Critical Care Center of Beijing Anzhen Hospital, Capital Medical University and the Department of Cardiology of the Jilin Provincial People's Hospital. They were randomly divided into routine treatment group and combined treatment group, with 120 cases in each group. The routine treatment group was treated with vasodilation, diuresis, cardiotonic and recombinant human brain natriuretic peptide. The combined treatment group was treated with Qiliqiangxin capsules based on the routine treatment group. One week later, the changes in clinical efficacy, ejection fraction, left ventricular commoid diameter, and plasma BNP, MDA, and ET-1 were compared between the two groups before and after treatment. SPSS 11.5 statistical software was used. The measurement data was expressed in x¯±s, the independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison before and after treatment within groups. Counting data was expressed as case (%), and the rank sum test was used for inter-group comparison. Result: In terms of clinical efficacy, the total effective rate of the combined treatment group was significantly higher than that of the conventional treatment group, and the difference was statistically significant (P<0.05). Compared with the routine treatment group, the left ventricular ejection fraction in the combined treatment group was significantly increased (P<0.05). The levels of plasma BNP, MDA and ET-1 were significantly decreased (P<0.05). Conclusion: Qiliqiangxin capsule combined with rhBNP treatment can effectively improve the clinical symptoms of acute heart failure, as well as reduce the lipid peroxidation product MDA content and endothetin ET-1 level in blood. The clinical application value of the Qiliqiangxin capsule needs to be further confirmed by further trials.

Dual therapy for Helicobacter pylori infection / 中华医学杂志(英文版)

Bismuth-containing quadruple therapy (BQT) has long been recommended for Helicobacter pylori ( H. pylori ) eradication in China. Meanwhile, in the latest national consensus in China, dual therapy (DT) comprising an acid suppressor and amoxicillin has also been recommended. In recent years, the eradication rate of H. pylori has reached >90% using DT, which has been used not only as a first-line treatment but also as a rescue treatment. Compared with BQT, DT has great potential for H. pylori eradication; however, it has some limitations. This review summarizes the development of DT and its application in H. pylori eradication. The H. pylori eradication rates of DT were comparable to or even higher than those of BQT or standard triple therapy, especially in the first-line treatment. The incidence of adverse events associated with DT was lower than that with other therapies. Furthermore, there were no significant differences in the effects of dual and quadruple therapies on gastrointestinal microecology. In the short term, H. pylori eradication causes certain fluctuations in the gastrointestinal microbiota; however, in the long term, the gastrointestinal microbiota eventually returns to its normal state. In the penicillin-naïve population, patients receiving DT have a high eradiation rate, better compliance, lower incidence of adverse reactions, and lower primary and secondary resistance to amoxicillin. These findings suggest the safety, efficacy, and potential of DT for H. pylori eradication.

Improving awareness of several combination therapies for acute myeloid leukemia among oncology and hematology team members in Colorado, USA

ABSTRACT Introduction: Although several combination therapies for acute myeloid leukemia (AML) have emerged recently, there has been a lack of published surveys and educational projects focused on these important treatment options. We aimed to improve the oncology team members' knowledge and awareness of several FDA approved combination therapies for AML, including glasdegib (DAURISMO®), venetoclax (VENCLEXTA®), GO (MYOLOTARG®),CPX-351 (VYXEOS®), and midostaurin (RYDAPT®). Additionally, we aimed to examine these teams' perspectives, views, and attitudes towards these topics and finally identify barriers to the implementationof such therapies in clinical practice. Method: Initially, we developed booklets and then distributed them to each participating oncology and hematology office. Subsequently, all participating oncology and hematology team members were asked to complete an anonymous online survey to test their knowledge of and attitudes toward the subjects. Main results: There was a total of 52 survey respondents. The correct answer regarding various combination therapies for AML was identified by nearly 70% or more of survey takers. The level of awareness of project subjects significantly improved after reading our printing materials. Many survey respondents were motivated to learn more about combination therapies for AML as well as discuss these topics with others. Conclusions: Our booklets effectively improved understanding and awareness of combination therapies for AML. Future studies should explore awareness, knowledge, and perception of other new and emerging combination therapies for AML amongoncology and hematology team members in other areas.

Combinación de antidepresivos vs. aumentación con antipsicóticos atípicos tras no lograr la remisión en la depresión unipolar / Combination of antidepressants vs. augmentation with atypical antipsychotics upon failure to achieve remission in unipolar depression

RESUMEN: Introducción: Lograr la recuperación funcional lo más rápido posible en el tratamiento de la depresión unipolar es un reto que la práctica clínica debe tratar de afrontar en la actualidad, ya que cualquier retraso en lograr la remisión de los síntomas es predictivo de un mayor número de recurrencias y mayores tasas de morbimortalidad. En esta revisión comprensiva, nuestro objetivo es guiar a los clínicos en su elección de aumentar con antipsicóticos atípicos o combinar el fármaco de referencia con un segundo antidepresivo, después de que se haya optimizado la dosis del antidepresivo seleccionado inicialmente y/o se haya cambiado el antidepresivo, sin lograr remisión, o bien cuando solo han obtenido una respuesta parcial después de un tiempo suficiente a una dosis apropiada. Estas decisiones surgen con frecuencia en la práctica clínica diaria. Metodología: Se realizó una búsqueda sistemática en PubMed bajo varias combinaciones clave de palabras, resultando en 230 informes. Después de aplicar los criterios de inclusión y según el título y el resumen, el número final de informes seleccionados para la revisión completa fue de 113. Se respondieron dos preguntas principales con base en estos estudios: 1) ¿Existe evidencia para recomendar claramente la combinación de antidepresivos versus potenciación con antipsicóticos (y el momento correcto para hacerlo) en la depresión unipolar no respondedora, una vez que las estrategias de optimización o de cambio han fallado en obtener la remisión? y 2) ¿Es posible identificar algunas características clínicas para guiar la decisión de combinación de antidepresivos versus potenciación con agentes antipsicóticos? Resultados: Según nuestro análisis, no hay datos disponibles para seleccionar una estrategia de otra de manera clara. Sin embargo, sugerimos favorecer una combinación o estrategia de aumento, basada en un enfoque de "tratamiento contra objetivos dianas" para perfilar al paciente, considerando una o dos características clínicas predominantes que permanecen activas como parte de una depresión mayor con respuesta parcial. Un adecuado análisis de los dominios sintomáticos presentes, una visión crítica de las guías clínicas actuales y de las opciones preferidas, considerar la bipolaridad oculta como uno de los principales diagnósticos diferenciales y adoptar una actitud enérgica pero lúcida en esta etapa del tratamiento son, a nuestro juicio, fundamentales para lograr recuperación ad integrum del paciente.

ABSTRACT Introduction: achieving functional recovery as quickly as possible in the treatment of unipolar depression is a challenge that clinical practice must try to meet nowadays, since any delay in accomplishing remission of the symptoms is predictive of a larger number of recurrences and higher morbidity and mortality rates. In this topical review we aim to guide clinicians in their choice to augment with atypical antipsychotics or to combine the baseline drug with a second antidepressant, after the dose of the antidepressant initially selected has been optimized and/or the antidepressant has been changed, not achieving remission, or resulting only in a partial response after sufficient time at an appropriate dose. These decisions arise frequently in everyday clinical practice. Methodology: a systematic search in PubMed was performed under several key combinations of words, resulting in 230 reports. After applying inclusion criteria and based in title and abstract, the final number of reports selected for full revision were 113. Two main questions were answered based on these studies: 1) Is there evidence to clearly recommend combination of antidepressants vs. augmentation with antipsychotics (and the correct moment to do it) in non-responsive unipolar depression, once optimization or switching strategies have failed to obtain remission? and 2) Is it possible to identify some clinical features to guide the decision of combination of antidepressants vs. augmentation with antipsychotic agents? Results: According to our analysis, there is no data available to select one strategy from another in a clear-cut manner. Nevertheless, we suggest favoring a combination or augmentation strategy, based in a "treating to target" approach to profile the patient, considering one or two predominant clinical features that remain active as part of a major depression with partial response. Proper analysis of the symptomatic domains present, a critical view of current clinical guidelines and preferred options, considering hidden bipolarity as one of the main differential diagnoses and adopting an energetic but lucid attitude at this stage of treatment are, in our view, fundamental for achieving ad integrum patient recovery.

Antiagregación plaquetaria: stents, isquemia y sangrado ¿Qué sabemos al respecto? / Platelet antiaggregation: stents, ischemia and bleeding What do we know about it?

Antiplatelet therapy and percutaneous coronary intervention are two of the most important interventions in the management of coronary artery disease. In the last 20 years there has been groundbreaking advances in the pharmacotherapy and stent technology. Bleeding is the most feared complication of antiplatelet therapy, mainly due to the increase in major adverse cardiovascular events besides the bleeding itself. Different clinical decision tools have developed with the aim to define which patients have a high ischemic or bleeding risk, thus individualizing treatment.

Características clínicas y microbiológicas de infecciones de piel y partes blandas en pacientes pediátricos de dos hospitales de Buenos Aires / Skin and soft tissue infections in pediatrics

Las infecciones de piel y partes blandas (IPPB) en niños son una de las principales causas de prescripción de antimicrobianos. El objetivo del estudio fue describir las características clínicas y microbiológicas de las IPPB ambulatorias de niños asistidos en dos hospitales zonales. Se realizó un estudio prospectivo entre el 1/11/2017 y el 1/11/2018. Se incluyeron pacientes entre 1 mes y 15 años internados en dos hospitales. Se evaluó: edad, sexo, localidad, factores predisponentes, tipo de IPPB, muestras biológicas realizadas, aislamiento microbiológico, tratamiento empírico indicado y evolución del cuadro. Se realizó antibiograma y determinación genética. Se calculó chi2, IC95, OR; α=5%. N= 94. 58,7% masculinos. 12 pacientes <1 año, 85 >1 año (promedio de edad 4 años, 1-15). El 36% de Tandil y 63,8% de Florencio Varela. El 59,6% corresponden a IPPB purulentas. Se aislaron microorganismos en un 59,6%. Los aislamientos principales: SAMR (40,4%), SAMS (7,4%), S. agalactiae (2,1%) y S. pyogenes (2,1%). El 100% de SAMR son portadores de gen mecA y SCCmec tipo IV, sin multirresistencia. No hubo diferencia estadística entre los factores de riesgo evaluados para el desarrollo de IPPB por SAMR. El 52,1% de los niños recibió tratamiento antibiótico combinado, siendo la más indicada TMS-SMX + CLI en 36 eventos. (38,3%). La evolución fue favorable: no hubo diferencia significativa entre el subgrupo que se aisló SAMR y el que no se aisló SAMR; 91,9% (34/37) y 92,6% (50/54) correspondientemente (chi2: 0,01; p= 0,97 IC95: 0,26-3,88). El principal agente etiológico fue SAMRco, debiendo adecuar los tratamientos a este microorganismo.

Skin and soft tissue infections (SSIs) in children are one of the main causes of antimicrobial prescription. The aim of the study was to describe the clinical and microbiological characteristics of outpatient SSIs in children attended in two hospitals. A prospective study was conducted between 11/1/2017 and 11/1/2018. Patients between 1 month and 15 years old, hospitalized were included. We evaluated: age, sex, locality, predisposing factors, type of IPPB, biological samples taken, microbiological isolation, empirical treatment indicated and evolution of the condition. An antibiogram and genetic determination were performed. Chi2, CI95, OR; α=5% were calculated. N= 94. 58.7% male. 12 patients <1 year, 85 >1 year (mean age 4 years, 1-15). 36% were from Tandil and 63.8% from Florencio Varela. 59.6% corresponded to purulent SSIs. The diagnostic yield was 59.6%. Main isolates: MRSA (40.4%), MSSA (7.4%), S. agalactiae (2.1%) and S. pyogenes (2.1%). 100% of MRSA carried the mecA gene and SCCmec type IV, with no multidrug resistance. There was no statistical difference between the risk factors evaluated. 52.1% of children received combined antibiotic treatment, the most indicated being TMS-SMX + CLI in 36 events. (38,3%). Evolution was favorable: there was no significant difference between the subgroup that isolated MRSA and the subgroup that did not isolate MRSA; 91.9% (34/37) and 92.6% (50/54) respectively (chi2: 0.01; p= 0.97 CI95: 0.26-3.88). The main etiological agent was MRSA, and treatments should be adapted to this microorganism

Amicrobial pustulosis of the folds: report of two cases / Pustulosis amicrobiana de los pliegues. Informe de dos casos

ABSTRACT Amicrobial Pustulosis of the Folds is a relapsing, chronic and rare neutrophilic dermatosis, characterized by papulopustular, eczematous and aseptic lesions on skin folds. This disorder usually occurs predominantly in females (30 years of age average) with a history of an autoimmune disorder, especially systemic lupus erythematosus. There is no standard therapy, but systemic corticosteroids, alone or in combination with other immunosuppressive drugs, are usually the first-line therapy. We report two females aged 37 and 20 years with the disease but without associated autoimmune diseases. They were successfully treated with non-steroidal treatments.

La pustulosis amicrobiana de los pliegues es una dermatosis neutrofílica crónica, recurrente y poco común. Se caracteriza por lesiones pápulo-pustulosas, eczematosas y asépticas de los pliegues cutáneos. Este cuadro se presenta predominantemente en mujeres de alrededor de 30 años con enfermedades autoinmunes, especialmente lupus eritematoso sistémico. No existe un tratamiento estándar pero los corticoides solos o con inmunosupresores se usan de primera línea. Informamos dos mujeres de 27 y 20 años sin patología autoinmune, con la enfermedad. Ellas fueron tratadas exitosamente sin usar esteroides.