ACTN3R577X polymorphism and long-term survival in patients with chronic heart failure

Abstract Background Previous studies have shown the occurrence of actinin-3 deficiency in the presence of the R577X polymorphism in the ACTN3 gene. Our hypothesis is that this deficiency, by interfering with the function of skeletal muscle fiber, can result in a worse prognosis in patients with chronic heart failure. Methods A prospective cohort study was conducted from 2002 to 2004. The eligibility criteria included diagnosis of chronic heart failure stage C from different etiologies. We excluded all patients with concomitant disease that could be related to poor prognosis. ACTN3 rs1815739 (R577X) polymorphism was detected by high resolution melting analysis. Survival curves were calculated with the Kaplan-Meier method and evaluated with the log-rank statistic. The relationship between the baseline variables and the composite end-point of all-cause death was assessed using a Cox proportional hazards survival model. Results A total of 463 patients were included in this study. The frequency of the ACTN3 577X variant allele was 39.0%. The LVEF mean was 45.6 ± 18.7% and the most common etiology of this study was hypertensive. After a follow-up of five years, 239 (51.6%) patients met the pre-defined endpoint. Survival curves showed higher mortality in patients carrying RX or XX genotypes compared with patients carrying RR genotype (p = 0.01). Conclusion R577X polymorphism in the ACTN3 gene was independently associated with worse survival in patients with chronic heart failure. Further studies are necessary to ensure its use as a marker of prognosis for this syndrome

Adverse mucocutaneous reactions to chemotherapeutic agents: part I

O tratamento local e sistêmico das neoplasias pode causar alterações na pele, membranas mucosas, cabelos e unhas. O diagnóstico preciso e o tratamento adequado destes efeitos colaterais requerem conhecimento dos padrões das reações adversas mais comuns para as medicações que o paciente está utilizando. O dermatologista deve estar familiarizado com as manifestações tegumentares das neoplasias, bem como com os efeitos adversos mucocutâneos dos tratamentos antineoplásicos.The local and systemic treatment of tumors can cause changes in the skin, mucous membranes, hair and nails. Accurate diagnosis and appropriate treatment of side effects require knowledge about the patterns of the most common adverse reactions to drugs the patient may be using. The dermatologist must be familiar with the manifestations of certain soft tissue neoplasms, as well as with the adverse mucocutaneous forms of cancer treatment

Adverse fetal and neonatal outcomes in pregnancies with confirmed Zika Virus infection in Rio de Janeiro, Brazil: A cohort study.

OBJECTIVE: To analyze adverse fetal and neonatal outcomes of Zika virus infection by the timing of infection during pregnancy. Method: Cohort study of 190 pregnancies with 193 offspring with a positive RT-PCR test for Zika virus (March/2016 to April/2017). RESULTS: Death or defects related to congenital Zika virus infection were identified in 37.3% of fetuses and newborns, and microcephaly in 21.4% of the newborns. The proportion of small for gestational age newborns was 21.9%. Maternal symptoms in the first trimester were significantly associated with the birth of newborns with microcephaly/cerebral atrophy, small for gestational age and with the deaths (one abortion, one stillbirth and the two neonatal deaths). Maternal infection during the second trimester was further associated with asymptomatic newborns at birth. The study showed that 58.5% of the offspring with microcephaly and / or cortical atrophy were small for gestational age, with an evident decrease in symptomatic offspring without microcephaly, 24.1%, and with only 9.1% in the asymptomatic group. CONCLUSION: This study showed that the earlier the symptoms appear during gestation, the more severe the endpoints. We found a higher percentage of small for gestational age newborns exposed to Zika virus early in gestation. We also found a group of apparently asymptomatic newborns with proven Zika infection, which highlights the importance of follow up studies in this population

Quality of life scores differs between genotypic groups of patients with suspected hereditary hemochromatosis

Background: Hereditary hemochromatosis (HH) encompasses a group of autosomal recessive disorders mainly characterized by enhanced intestinal absorption of iron and its accumulation in parenchymal organs. HH diagnosis is based on iron biochemical and magnetic resonance imaging (MRI) assessment, and genetic testing. Questionnaires, such as SF-36 (short form health survey), have been increasingly used to assess the impact of diseases on the patient's quality of life (QL). In addition, different genotypes are identified as results of genetic tests in patients with suspected primary iron overload. In the present study, our aim was to evaluate whether domains of QL are different according to genotypic groups in patients suspected of HH. Methods: Seventy-nine patients with primary iron overload were included and two genotypic groups were formed (group 1: homozygous genotype for the HFE p.Cys282Tyr mutationgroup 2: other genotypes). Results: Group 1 had higher means of plasma transferrin saturation (86 +/- 19%) and serum ferritin (1669 +/- 1209 ng/mL) compared to group 2 (71 +/- 12%, 1252 +/- 750 ng/mL, respectivelyp = 0.001). Four domains were significantly different among groups 1 and 2: physical functioning (p = 0.03), bodily pain (p = 0.03), vitality (p = 0.02) and social functioning (p = 0.01). Conclusions: Our main finding was that patients with p. Cys282Tyr homozygosity had a worse QL scenario assessed by SF-36, compared with patients with iron overload without the same genotype. Being aware of this relationship between genotypes and QL might be helpful in the overall management of patients suspected of hereditary hemochromatosis.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [2013/09295-3]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil [2013/20614-3]Univ Sao Paulo, Heart Inst InCor, Lab Genet & Mol Cardiol, Med Sch, Av Doutor Eneas de Carvalho Aguiar 44, BR-05403900 Sao Paulo, SP, BrazilSanta Casa Med Sch, Hematol & Hemotherapy Sect, Sao Paulo, BrazilAcad Ciencia & Tecnol, Sao Jose Do Rio Preto, BrazilFundacao Pro Sangue, Hemoctr Sao Paulo, Sao Paulo, SP, BrazilUniv Sao Paulo, Sao Paulo, SP, BrazilUniv Sao Paulo, Med Sch, Hosp Clin, Hematol Serv, Sao Paulo, BrazilUniv Sao Paulo, Med Sch, Hosp Clin, Hematol & Hemotherapy Discipline, Sao Paulo, BrazilUniv Rennes, Pontchaillou Univ Hosp, Liver Dis Unit, Rennes, FranceNatl Reference Ctr Rare Iron Overload Dis Genet O, Rennes, FranceUniv Fed Sao Paulo UNIFESP, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, Dept Pharmacol, Sao Paulo, BrazilCAPES: 2013/09295-3FAPESP: 2013/20614-3Web of Scienc

Avaliacao dos efeitos da aplicacao de enemas com sucralfato em modelo experimental de colite de exclusao

Diversion colitis (DC) is an inflammatory disease that develops in segments with fecal diversion. Sucralfate (SCF) complex, which consists of sucrose octasulfate and polyaluminum hydroxide, has been demonstrated to be effective in the treatment of different forms of colitis. However, until now, the effects of SCF have not been evaluated in DC.OBJECTIVE:to evaluate whether the use of enemas containing SFC improves histological findings in experimental DC.METHODS:Thirty-six rats underwent right colon bypass procedure through the creation of a proximal colostomy and a distal mucous fistula. The animals were divided into two groups according to the euthanization procedure to be performed two to four weeks after surgery. Each experimental group was divided into three subgroups of six animals, which were submitted to daily application of enemas containing saline solution 0.9% or SCF at concentrations of 1.0 g/kg/day or 2.0 g/kg/day, respectively. The diagnosis of DC in segments with fecal diversion was established by histopathological study considering the following variables: epithelial loss, formation of crypt abscesses, the population of goblet cells, inflammatory infiltrate and presence of fibrosis. For statistical analysis, the nonparametric Mann-Whitney and Kruskal-Wallis tests were used, with a significance level of 5% (p &lt;0.05).RESULTS:It was observed that the daily application of SCF enemas decreased epithelial loss, formation of colon crypt abscesses, inflammatory infiltrate and tissue fibrosis (p &lt;0.05), unrelated to time of intervention. The intervention with SCF preserves the goblet cell population. The effects of the substance on the preservation of colonic epithelium; the decrease in the inflammatory process and subsequent abscess formation in the colon crypts are associated with the concentration used, whereas tissue fibrosis decrease is associated with the concentration and time of intervention.CONCLUSION:Preventive application of SCF enemas reduces the inflammatory process in the colon with fecal diversionA colite de exclusão (CE) é uma doença inflamatória que se desenvolve em segmentos desprovidos de trânsito fecal. O sucralfato (SCF) complexo formado pelo octossulfato de sacarose e hidróxido de polialumínio vem se demonstrando eficaz para o tratamento de diferentes formas de colite, porém, até a presente data, os efeitos do SCF ainda não foram avaliados na CE.OBJETIVO:avaliar se a aplicação de clisteres contendo SFC melhora as alterações histológicas encontradas em modelo experimental de CE.MÉTODOS:trinta e seis ratos foram submetidos à derivação do trânsito no cólon direito pela confecção de colostomia proximal e fístula mucosa distal. Os animais foram divididos em dois grupos experimentais de acordo com o sacrifício ser realizado após duas ou quatro semanas do procedimento cirúrgico. Cada grupo experimental foi dividido em três subgrupos de seis animais segundo terem sidos submetidos à aplicação diária com enemas contendo solução fisiológica a 0,9% ou SCF nas concentrações de 1,0g/kg/dia ou 2,0 g/kg/dia. O diagnóstico de CE nos segmentos sem trânsito foi estabelecido por estudo histopatológico considerando-se as seguintes variáveis: perda epitelial, formação de abscessos nas criptas, população de células caliciformes, infiltrado inflamatório e a presença de fibrose. Para análise estatística adotou-se os testes não paramétricos de Mann-Withney e Kruskal-Wallis estabelecendo-se para ambos, nível de significância de 5% (p < 0,05).RESULTADOS:verificou-se que a aplicação diária de enemas com SCF diminui a perda epitelial, a formação de abscessos nas criptas cólicas, o infiltrado inflamatório e a presença de fibrose tecidual (p < 0,05), não relacionada ao tempo de intervenção. A intervenção com SCF preserva a população de células caliciformes. Os efeitos da substância na preservação do epitélio cólico, na redução do processo inflamatório e consequente formação de abscessos nas criptas cólicas encontram-se relacionado à concentração utilizada, enquanto a redução da fibrose tecidual a concentração e ao tempo de intervenção.CONCLUSÃO:a aplicação preventiva de enemas com SCF reduz o processo inflamatório em segmentos cólicos desprovidos de transito intestinal.18219

Pharmaceutical Care Increases Time in Therapeutic Range of Patients With Poor Quality of Anticoagulation With Warfarin

Thromboembolic events are associated with high mortality and morbidity indexes. In this context, warfarin is the most widely prescribed oral anticoagulant agent for preventing and treating these events. This medication has a narrow therapeutic range and, consequently, patients usually have difficulty in achieving and maintaining stable target therapeutics. Some studies on the literature about oral anticoagulant management showed that pharmacists could improve the efficiency of anticoagulant therapy. However, the majority of these studies included general patients retrospectively. The aim of this study was to prospectively evaluate a pharmacist’s warfarin management in patients with poor quality of anticoagulation therapy (Time in the Therapeutic Range- TTR &lt; 50%). We included 268 patients with atrial fibrillation (AF) and without stable dose of warfarin (TTR &lt; 50%, based on the last three values of International Normalized Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when necessary, the dose adjustments were performed. During the first four visits, patient’s INR was measured every 7 days. Then, if INR was within the target therapeutic range (INR: 2–3), the patient was asked to return in 30 days. However, if INR was out the therapeutic target, the patient was asked to return in 7 days. Adherence evaluation was measured through questionnaires and by counting the pills taken. Comparison between basal TTR (which was calculated based on the three last INR values before prospective phase) and TTR of 4 weeks (calculated by considering the INR tests from visits 0 to 4, in the prospective phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the INR tests from visits 0 to 12, in the prospective phase of the study) revealed significant statistical differences (0.144 ± 0.010 vs. 0.382 ± 0.016; and 0.144 ± 0.010 vs. 0.543 ± 0.014, p &lt; 0.001, respectively). We also observed that the mean TTR of 1 year before (retrospective phase) was lower than TTR value after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 ± 0.015; 0.540 ± 0.015, p &lt; 0.001). In conclusion, pharmaceutical care was able to improve TTR values in patients with AF and poor quality of anticoagulation with warfarin

Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure

Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination. LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akti NEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.Conselho Nacional de Desenvolvimento Cientifico e TecnologicoFAPESPNove de Julho Univ, Lab Biophoton, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Lab Cardiac Physiol, Sao Paulo, SP, BrazilNove de Julho Univ, Program Med, Sao Paulo, BrazilUniv Sao Judas Tadeu, Brazil Phys Educ & Aging Sci Program, Translat Physiol Lab, Sao Paulo, BrazilUniv Fed Sao Paulo, Lab Cardiac Physiol, Sao Paulo, SP, BrazilCNPq: 4400851/2014-8FAPESP: 09-54225/8FAPESP: 15/11028-9Web of Scienc

Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.Univ Sao Paulo, Inst Canc Estado Sao Paulo, BR-01246000 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Radiol & Oncol, BR-01246903 Sao Paulo, BrazilHosp Sirio Libanes, BR-01308050 Sao Paulo, BrazilHosp Moinhos de Vento Porto Alegre, BR-90035000 Porto Alegre, RS, BrazilOncoctr, BR-30360680 Belo Horizonte, MG, BrazilUniv Fed Rio Grande do Sul, Dept Cirurgia, BR-90040060 Porto Alegre, RS, BrazilHosp Clin Porto Alegre, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Ceara, Fac Med, Dept Fisiol & Farmacol, BR-60020180 Fortaleza, Ceara, BrazilHosp Univ Walter Cantidio, BR-60430370 Fortaleza, Ceara, BrazilInst Nacl Canc, BR-20230240 Rio De Janeiro, BrazilUniv Sao Paulo, Fac Med, Disciplina Endocrinol & Metabol, BR-01246903 Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Surg, BR-01509010 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Gastroenterol, Sao Paulo, BrazilUniv Fed Ciencias Saude Porto Alegre, BR-90050170 Porto Alegre, RS, BrazilHosp Albert Einstein, BR-05652900 Sao Paulo, BrazilHosp Base, Fac Med Sao Jose do Rio Preto, BR-15090000 Sao Paulo, BrazilSanta Casa Sao Jose do Rio Preto, BR-15025500 Sao Jose Do Rio Preto, BrazilPontificia Univ Catolica Parana, Hosp Erasto Gaertner, BR-81520060 Curitiba, Parana, BrazilUniv Fed Rio Grande do Norte, BR-59300000 Natal, RN, BrazilUniv Sao Paulo, Inst Coracao, BR-05403900 Sao Paulo, BrazilAC Camargo Canc Ctr, Med Oncol, BR-01509010 Sao Paulo, BrazilUniv Fed Sao Paulo, Disciplina Gastroenterol, BR-04021001 Sao Paulo, BrazilHosp Sao Rafael, BR-41253190 Salvador, BA, BrazilHosp Canc Barretos, Dept Cirurgia Aparelho Digest Alto & Hepatobiliop, BR-14784400 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Patol, BR-01246903 Sao Paulo, BrazilClin AMO, BR-1950640 Salvador, BA, BrazilHosp Sao Jose, BR-01323001 Sao Paulo, BrazilUniv Nove de Julho, BR-02111030 Sao Paulo, BrazilUniv Fed Sao Paulo, Disciplina Gastroenterol, BR-04021001 Sao Paulo, BrazilWeb of Scienc