Perfil molecular y características clínico-patológicas del carcinoma mamario, con énfasis en la expresión del Ki 67: Experiencia inicial en instituto oncológico del norte del Perú

Objetivo: Identificar el perfil molecular y las características clínicas y patológicas del carcinoma de mama de acuerdo a la variabilidad en la expresión del Ki 67. Material y métodos. Serie de casos, en el que se evaluaron 157 pacientes con diagnóstico anatomopatológico e inmunohistoquímico de cáncer de mama atendidas en el IREN Norte (Perú) durante el período 2008 – 2015. Se clasificaron los tumores en Luminal A, Luminal B, HER2 y Triple negativo. Se utilizo dos puntos de corte para evaluar el Ki 67:> 14% y > 20%, de acuerdo a lo sugerido en St. Gallen 2011 y 2013 respectivamente. Resultados. En el grupo de pacientes con Ki 67 > 20%, el subtipo molecular que predominó fue el Luminal B (n = 54; 34%). El tamaño tumoral más frecuente se ubicó en el grupo de > 2 a < 5 cm. (T2), representando 56% en el subtipo Luminal B, 28% en Luminal A, 69% en HER2 y 41% en el Triple negativo. En los pacientes con Ki 67 > 14%, el subtipo molecular y el tamaño tumoral predominante también fue el Luminal B (n = 73, 46%) y el T2. El tipo histológico más común fue el carcinoma ductal independientemente del punto de corte del valor de Ki 67. Conclusiones. La utilidad del valor porcentual del Ki 67 evaluado en dos puntos de corte es controversial; en nuestro estudio el perfil molecular y las características clínico-patológicas de cáncer de mama fueron relativamente similares en relación a Luminal A y Luminal B

A influência do alongamento associado ao tratamento farmacológico na mudança da funcionalidade em pacientes reumatológico / The influence of stretching associated with pharmacological treatment in changing functionality in rheumatological patients

Faz-se válida a ressalva de que inúmeras patologias convergem para o quadro clínico de dor crônica de caráter reumatológico, incluindo as doenças osteomusculares, transtornos dos discos intervertebrais, espondiloses, radiculopatias, fibromialgia. O objetivo da presente pesquisa foi avaliar os efeitos do alongamento muscular associado ao tratamento farmacológico em pacientes com doenças reumáticas. O estudo é do tipo coorte, de caráter analítico, prospectivo, quantitativo, longitudinal e intervencionista, com análise dos escores da escala visual analógica de dor (EVA) e da escala de avaliação de capacidade funcional (HAQ AÇORES), sem financiamento e em um único centro. No estudo realizado foram analisados dois grupos com um total de 30 participantes, sendo u m grupo com a proposta intervencionista composto por 15 pacientes (Grupo 1) e um outro sem a proposta de intervenção também com um total de 15 pacientes (Grupo 2). O grupo 1 foi composto por um total de 13 pacientes do sexo feminino e 2 do sexo masculino, já o grupo 2 foi composto por 14 pacientes do sexo feminino e somente 1 do sexo masculino. Obteve-se para a escala de Eva p-valor = 0,36 e para a escala HAQ AÇORES p-valor = 0,16; portanto o estudo mostrou-se estatisticamente não significativo em relação à associação ou não de alongamento ao tratamento farmacológico convencional. Com base na escala visual analógica (EVA) e por meio da escala Haq Açores, mostrou-se uma melhora no perfil de dor e na variação da capacidade funcional diante da prática do alongamento muscular

Ingestão Cáustica e Estenose Cáustica de Esôfago: Diagnóstico e Tratamento / Caustic Ingestion and Caustic Stenosis of the Esophagus: Diagnosis and Treatment

A ocorrência da ingesta de substâncias cáusticas é considerada emergência médica que pode ocorrer em adultos e crianças e acarretar sequelas e agravos como a estenose cáustica de esfôfago. O diagnóstico e o manejo adequados são de extrema importância para a diminuição da mortalidade e para traçar o prognóstico desses pacientes. A diagnose se dará pela somatória de características clínicas, laboratoriais, radiológicas e endoscópicas, sendo fundamental e necessário a endoscopia digestiva alta somada à radiografia contrastada de esôfago, estomago e duodeno, para avaliar o grau da lesão e a estenose esofágica. A terapêutica inicial será realizada de acordo com grau estabelecido e posteriormente pode necessitar de condutas especificas para a dilatação esofágica, sendo o método mais indicado através de expansores endoscópicos associados a fármacos, principalmente a mitomicina C. Em casos recidivantes, ou não responsivos à terapêutica precoce, pode ser realizada, tardiamente, a intervenção cirúrgica que possui a sua eficiência bem descrita

PhageWeb – Web Interface for Rapid Identification and Characterization of Prophages in Bacterial Genomes

This study developed a computational tool with a graphical interface and a web-service that allows the identification of phage regions through homology search and gene clustering. It uses G+C content variation evaluation and tRNA prediction sites as evidence to reinforce the presence of prophages in indeterminate regions. Also, it performs the functional characterization of the prophages regions through data integration of biological databases. The performance of PhageWeb was compared to other available tools (PHASTER, Prophinder, and PhiSpy) using Sensitivity (Sn) and Positive Predictive Value (PPV) tests. As a reference for the tests, more than 80 manually annotated genomes were used. In the PhageWeb analysis, the Sn index was 86.1% and the PPV was approximately 87%, while the second best tool presented Sn and PPV values of 83.3 and 86.5%, respectively. These numbers allowed us to observe a greater precision in the regions identified by PhageWeb while compared to other prediction tools submitted to the same tests. Additionally, PhageWeb was much faster than the other computational alternatives, decreasing the processing time to approximately one-ninth of the time required by the second best software. PhageWeb is freely available at http://computationalbiology.ufpa.br/phageweb

Hepatites virais no contexto Amazônico: análise dos casos confirmados na região do baixo amazonas no ano de 2018 / Viral hepatitis in the Amazon context: analysis of confirmed cases in the low amazon region in the year 2018

Introdução: As hepatites virais são importante problema de saúde pública no Brasil. Elas possuem diferentes agentes etiológicos, mas com propensão de infectar o tecido hepático (BRASIL, 2008, p.07). Elas têm grande importância clínica e epidemiológica, tanto pelas complicações das formas agudas e crônicas, quanto pelo número expressivo de indivíduos atingidos. Sua transmissão ocorre por meio da ingestão de água e alimentos contaminados, mas principalmente através de sangue e secreções contaminados (BRASIL, 2005). Objetivo: Analisar a frequência das infecções pelos vírus das hepatites A, B, C, D e E, nos 15 municípios pertencentes à Região do Baixo Amazonas, no Estado do Pará. Métodos: Estudo transversal, retrospectivo, quantitativo, referente ao ano de 2018, cuja base de dados é disponibilizada pelo Departamento de Informática do Sistema Único de Saúde (DATASUS), considerando sexo, faixa etária, classificação etiológica, fonte de infecção e município de notificação. Resultados: Santarém liderou no número de notificações desses casos (91,66%), seguida de Oriximiná (4,16%), Alenquer (1,66%), Mojuí dos Campos (0,84%), Óbidos (0,84%) e Prainha (0,84%). Os casos confirmados se distribuíram em: vírus B (66,6%), vírus C (17,8%), vírus B + C (10%) e vírus A (5,6%). Não foram registradas infecções por vírus D e E. Observou-se que a maioria, 42,5%, contraíram por via sexual. A faixa etária de maior risco foi entre os 40 e 59 anos de idade (45%). Conclusão: Os dados demonstrados evidenciaram a necessidade de aprimorar a vigilância de novos casos de hepatite viral na Região do Baixo Amazonas, bem como a de aperfeiçoar métodos diagnósticos e preventivos por meio de estratégias de captação das infecções, no intuito de promover o diagnóstico e tratamento precoces. 

Effect of garlic on cardiovascular disorders: a review

Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field