Physicians’ preference towards the non-evidence based hydroxychloroquine treatment for COVID-19: the pandemic effect

OBJECTIVE: To evaluate whether there is a "pandemic effect" promoting irrational medical reasoning. METHODS: Cross-sectional study. Setting state medical councils were asked to send all registered physicians two sequential email invitations to complete a Google Form questionnaire. Between April 15 and May 3, 2020, 370 doctors answered our questionnaire with questions about the prescription of hydroxychloroquine for COVID-19 and vitamin C for sepsis. The questionnaire had a five-point Likert scale (greater number, greater support) on the degree of propensity to prescribe the medication and a binary question (yes or no) to express the doctor's final decision to prescribe. These two questions, in the same order, were asked for scenarios of mild, moderate and severe cases. RESULTS: The propensity to prescribe hydroxychloroquine for COVID-19 increased with the severity of the clinical presentation: for mild cases, 37% (95% CI 32%-42%) of the physicians chose "yes", increasing to 68% (95% CI 63%-72%) and 89% (95% CI 85%-92%) for moderate or severe cases, respectively (Cochran's Q test: P<0.001). The medians and interquartile ranges of the Likert scales for hydroxychloroquine were 2 (1-4), 4 (2-4), 4 (4-5) in mild, moderate and severe cases of COVID-19 (Friedman test: P<0.001). CONCLUSIONS: The propensity of the Brazilian physician to prescribe hydroxychloroquine for COVID-19 is high and, according to the severity of the disease, ranged from 37 to 89%. On the contrary, the propensity to prescribe vitamin C for sepsis, a non-pandemic situation, was lower and not associated with clinical severity. Our data suggest a "pandemic effect" promoting irrationality in medical reasoning

Effects of administration of pentoxifylline in pancreatic isquemiareperfusion injury: experimental study in rats

Introdução: O pâncreas é um órgão suscetível a lesões de isquemia-reperfusão (I/R). Estratégias terapêuticas para reduzir os danos produzidos pela I/R podem melhorar os resultados nos transplantes de pâncreas-rim. Apesar dos efeitos hemorreológicos da pentoxifilina, esta droga tem ação anti-inflamatória através da inibição da ativação de NF-kB e da produção de TNF-alfa. Foi demonstrado previamente que a pentoxifilina diminui a resposta inflamatória em modelos experimentais de pancreatite aguda e I/R hepática. Assim, a pentoxifilina pode contribuir na redução da lesão pancreática e da reposta inflamatória sistêmica em um modelo de I/R pancreática. Objetivo: Avaliar o efeito da administração de pentoxifilina em um modelo experimental de I/R pancreática em ratos. Métodos: A I/R pancreática foi realizada em sessenta ratos Wistar, por um período de uma hora através da oclusão da artéria esplênica. Os animais deste experimento foram divididos em três grupos: Grupo 1 (sham; realizado procedimento cirúrgico sem indução da I/R), grupo 2 (controle; realizado indução da I/R) que recebeu solução salina por via endovenosa e grupo 3 (pentoxifilina; realizado indução da I/R associado ao tratamento) que recebeu pentoxifilina (25mg/kg) por via endovenosa. Foram colhidas amostras de sangue para dosagem de amilase, creatinina, ureia, fator de necrose tumoral ? (TNF-alfa), interleucina-6 (IL-6) e interleucina-10 (IL-10). Os níveis de malondialdeído (MDA) pancreático, da mieloperoxidase (MPO) pulmonar e a histologia pancreática também foram avaliados. Resultados: A inibição do TNF-alfa pela pentoxifilina apresentou efeitos benéficos neste modelo experimental. O grupo de animais tratados com pentoxifilina apresentou níveis séricos significantemente menores de TNF-alfa, IL-6 e IL-10 em comparação ao grupo controle (p < 0,05). Não foram observadas diferenças significantes entre estes grupos em relação aos níveis de amilase, creatinina, ureia, MDA pancreático e MPO pulmonar. Entretanto, no grupo de animais tratados com pentoxifilina, o dano histológico pancreático foi menor em comparação ao grupo controle (p < 0,05). Conclusão: A administração de pentoxifilina reduziu a resposta inflamatória sistêmica e a lesão histológica pancreáticaIntroduction: The pancreas is an organ extremely susceptible to periods of ischemia. Therapeutic strategies to reduce the occurrence of pancreatic ischemiareperfusion (I/R) injury might improve outcomes in human pancreas and kidney transplantation. In addition to its haemorrheologic effects, pentoxifylline has an antiinflammatory effect by inhibiting NF-?B activation and TNF-alfa production. It has been previously demonstrated that pentoxifylline induces an anti-inflammatory response in acute pancreatitis and liver I/R models. This led to the hypothesis that pentoxifylline might reduce pancreatic lesion and the systemic inflammatory response in pancreatic I/R injury. Objective: The aim of this experimental study was to evaluate the effect of pentoxifylline administration in a rat model of pancreatic I/R injury. Methods: Pancreatic I/R was performed in sixty Wistar rats over one hour by clamping the splenic vessels. The animals of this study were divided into three groups: group 1 (sham, surgical procedure without pancreatic I/R induction), group 2 (control, I/R induction) received saline solution administered intravenously, and group 3 (pentoxifylline, I/R induction plus treatment) rats received pentoxifylline (25 mg/kg) administered intravenously. Blood samples were collected to enable the determination of amylase, creatinine, urea, tumour necrosis factor-? (TNF-alfa), interleukin-6 (IL-6) and interleukin-10 (IL-10). Pancreatic malondialdehyde (MDA) content, pulmonary myeloperoxidase (MPO) and pancreas histology were also assessed. Results: Inhibition of TNF-alfa by pentoxifylline shows beneficial effects in this experimental model. Significant reductions in serum TNF-?, IL-6 and IL-10 were observed in pentoxifylline group compared with control group (p < 0.05). No significant differences in serum amylase, creatinine, urea, pancreatic MDA or pulmonary MPO were observed between these two groups. However, the pancreatic histological damage was significantly lower in pentoxifylline treated group compared with control group (p < 0,05). Conclusion: Pentoxifylline administration reduced the systemic inflammatory response and the pancreatic histological lesio

METACHRONOUS COLORECTAL LIVER METASTASES HAS BETTER PROGNOSIS - IS IT TRUE?

ABSTRACT BACKGROUND: Liver metastases from colorectal cancer are an important public health problem due to the increasing incidence of colorectal cancer worldwide. Synchronous colorectal liver metastasis has been associated with worse survival, but this prognosis is controversial. OBJECTIVE: The objective of this study was to evaluate the recurrence-free survival and overall survival between groups of patients with metachronous and synchronous colorectal hepatic metastasis. METHODS: This was a retrospective analysis of medical records of patients with colorectal liver metastases seen from 2013 to 2016, divided into a metachronous and a synchronous group. The Cox regression model and the Kaplan-Meier method with log-rank test were used to compare survival between groups. RESULTS: The mean recurrence-free survival was 9.75 months and 50% at 1 year in the metachronous group and 19.73 months and 63.3% at 1 year in the synchronous group. The mean overall survival was 20.00 months and 6.2% at 3 years in the metachronous group and 30.39 months and 31.6% at 3 years in the synchronous group. Patients with metachronous hepatic metastasis presented worse overall survival in multivariate analysis. The use of biological drugs combined with chemotherapy was related to the best overall survival prognosis. CONCLUSION: Metachronous colorectal hepatic metastasis was associated with a worse prognosis for overall survival. There was no difference in recurrence-free survival between metachronous and synchronous metastases

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele