Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer strongly associated with BRCA mutation. Standard neoadjuvant chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is still a matter of discussion. Other agents, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and anti-vascular endothelial growth factor (VEGF) antibodies were evaluated in the neoadjuvant setting. This systematic review and meta-analysis intend to evaluate the impact of neoadjuvant treatments in pCR rates in TNBC gBRCA mutation, beyond traditional standard chemotherapy. METHODS: PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase and key oncological meetings for trials were searched for studies reporting neoadjuvant chemo-immunotherapy in BRCA positive TNBC. RESULTS: Out of 1238 records reviewed, thirty-one trials were included, resulting in a total 619 BRCA-mutated TNBC patients. In BRCA mutated TNBC patients who received cisplatin in monotherapy the proportion of patients who achieved pCR was 0.53 (95%CI [0.30, 0.76]), and when treatment combined standard chemotherapy and platin derivatives the proportion of pCR increased to 0.62 (95% CI [0.48, 0.76]). The group of patients treated with platin derivatives, anthracyclines ± taxanes achieved the highest proportion of pCR, 0.66. Patients treated with PARPi alone show a pCR proportion of 0.55 (95% CI [0.30, 0.81]); and when standard chemotherapy and platin derivatives were combined with PARPi the proportion of pCR did not vary. CONCLUSIONS: Patients with BRCA mutated TNBC treated with cisplatin in monotherapy demonstrate inferior proportion in the pCR achievement when compared with standard chemotherapy plus platin derivates. The best pCR was achieved with platin derivates in association with anthracyclines ± taxanes. No difference in pCR was found between PARPi alone vs PARPi with standard chemotherapy.

Real-World Healthcare Resource Use Associated with Recurrent or Metastatic Head and Neck Cancer Patients Care in Portugal-TRACE Study.

Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50-69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management.

[Effects of acute exercise on postprandial lipemia in sedentary men]. / Efeitos do exercício agudo na lipemia pós-prandial em homens sedentários.

OBJECTIVE: To examine the effects of a single session of isometric physical exercise on postprandial triglyceridemia in sedentary male individuals with fasting triglycerides values < 150 mg/dl (NTG) or > " 150 mg/dl (TG ALT). METHODS: Twenty-seven individuals (10 NTG and 17 TG ALT), aged between 30-55 years were assessed in the study. Triglycerides were determined in the beginning, and at two, four and six hours after the oral ingestion of a solution with 50 g/m2 of fat in two occasions: at rest and after treadmill isometric exercise. RESULTS: Acute exercise did not affect the levels of postprandial triglycerides or the area under the curve (AUC) of triglycerides. However, the abnormal pattern of postprandial lipemia curve was associated with higher basal triglyceridemia with exercise (basal TG: 147 +/- 90 vs. 238 +/- 89 mg/dl, p = 0.02) and without exercise (basal TG: 168 +/- 93 vs. 265 +/- 140 mg/dl, p = 0.04). Analysis of the receiver operating characteristics (ROC) curves showed cut-off values for basal triglycerides with exercise of 166.5 mg/dl (sensitivity: 0.78; specificity: 0.72) and AUC of 0.772 [CI 95%: 0.588-0.955], and without exercise of 172 mg/dl (sensitivity: 0.78; specificity: 0.61) and AUC: 0.722 [CI 95%: 0.530-0.914]. CONCLUSION: Acute exercise did not affect postprandial triglyceridemia in sedentary male individuals, and basal triglyceride levels are predictors of an abnormal response of postprandial triglycerides.

Comparison between the effects of soy milk and non-fat cow milk on lipid profile and lipid peroxidation in patients with primary hypercholesterolemia.

OBJECTIVE: This study assessed whether the consumption of soy milk could add significantly to the lipid profile and lipid peroxidation in comparison with non-fat milk. METHODS: A double-blind, randomized, crossover study was conducted on 60 outpatients with primary hypercholesterolemia following a lipid-lowering diet for at least 6 wk. Lipid profile was obtained at baseline and at 6 and 12 wk, with the patients randomly assigned to receive initially 1 L/d of soy milk or non-fat cow milk for 6 wk. Lipid peroxidation was estimated by plasma thiobarbituric reactive substances. Apolipoprotein E genotypes were examined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: The soy milk diet was associated with low-density lipoprotein cholesterol reduction (baseline = 157 +/- 5 mg/dL; soy milk = 148 +/- 4 mg/dL; non-fat cow milk = 158 +/- 4 mg/dL; P < 0.05, soy milk versus other treatments) and with high-density lipoprotein cholesterol increase (baseline = 58 +/- 2 mg/dL; soy milk = 62 +/- 2 mg/dL; non-fat cow milk = 57 +/- 2 mg/dL; P < 0.05, soy milk versus other treatments). In addition, plasma thiobarbituric reactive substances were reduced by the soy milk diet (baseline = 1.82 +/- 0.12 nM/L; soy milk = 1.49 +/- 0.09 nM/L; non-fat cow milk = 1.91 +/- 0.11 nM/mL; P < 0.05, soy milk versus non-fat cow milk). Changes in lipid profile were not influenced by APOE genotypes. CONCLUSIONS: These results indicate that soy milk as part of a lipid-lowering diet has beneficial effects in improving lipid profile and reducing lipid peroxidation.

Risk Factors, biochemical markers, and genetic polymorphisms in early coronary artery disease.

OBJECTIVE: To assess the risk factors, lipid and apolipoprotein profile, hemostasis variables, and polymorphisms of the apolipoprotein AI-CIII gene in early coronary artery disease (CAD). METHODS: Case-control study with 112 patients in each group controlled by sex and age. After clinical evaluation and nutritional instruction, blood samples were collected for biochemical assays and genetic study. RESULTS: Familial history of early CAD (64 vs 39%), arterial hypertension (69 vs 36%), diabetes mellitus (25 vs 3%), and previous smoking (71 vs 46%) were more prevalent in the case group (p<0.001). Hypertension and diabetes were independent risk factors. Early CAD was characterized by higher serum levels of total cholesterol (235 +/-6 vs 209 +/- 4 mg/dL), of LDL-c (154 +/- 5 vs 135 +/- 4 mg/dL), triglycerides (205 +/- 12 vs 143 +/- 9 mg/dL), and apolipoprotein B (129 +/- 3 vs 105 +/- 3 mg/dL), and lower serum levels of HDL-c (40 +/- 1 vs 46 +/- 1 mg/dL) and apolipoprotein AI (134 +/- 2 vs 146 +/- 2mg/dL) [p<0.01], in addition to an elevation in fibrinogen and D-dimer (p<0.02). The simultaneous presence of the rare alleles of the APO AI-CIII genes in early CAD are associated with hypertriglyceridemia (p=0.03). CONCLUSION: Of the classical risk factors, hypertension and diabetes mellitus were independently associated with early CAD. In addition to an unfavorable lipid profile, an increase in the thrombotic risk was identified in this population. An additive effect of the APO AI-CIII genes was observed in triglyceride levels.

Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study.

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n=386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39, p<0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes.

High glucose levels abolish antiatherosclerotic benefits of ACE inhibition in alloxan-induced diabetes in rabbits.

Renin-angiotensin system activation is recognized to play an important role in atherosclerosis. This study aimed to verify the antiatherosclerotic effects of ACE inhibition on an experimental model of diabetes and hypercholesterolemia. Diabetes was induced in New Zealand male rabbits with a single dose of alloxan (100 mg/kg, i.v.), and, according to plasma glucose levels obtained after 1 week, the animals were divided into 2 groups (> or =250 mg/dL or <250 mg/dL). Each group was randomly assigned to receive or not quinapril (30 mg/d) added to a 0.5% cholesterol-enriched diet. Animals with high glucose levels at 1 week and that remained high after 12 weeks presented higher triglyceride levels (P < 0.02 versus basal). Those initially hyperglycemic but presenting <250 mg/dL glucose at the end of study formed an additional group. Plasma ACE activity was lower in quinapril-treated animals (P < 0.01 versus untreated groups). However, aorta intima/media ratio and intima area were lower only in the subgroups of quinapril-treated animals with low glucose levels (P < 0.05). Our results support the hypothesis that high plasma glucose may abolish the antiatherosclerotic effect of ACE inhibitors.

Early benefits of pravastatin to experimentally induced atherosclerosis.

There is little information regarding the time of hypolipidemic treatment of changes in atherosclerotic plaque, tissue cholesterol content, and also for the recovery of endothelial function. To assess the early effects of lipid-lowering treatment on these parameters, six groups of New Zealand male rabbits were studied. Animals in groups I and II were fed regular chow; groups III and IV received a 12-week 0.5% cholesterol diet followed by 12 weeks of 0.05% cholesterol diet. Finally, groups V and VI were fed a 12-week 0.5% cholesterol diet and were then shifted to a regular diet for 12 weeks. During the last four weeks, the rabbits in groups I, III, and V received low-dose pravastatin (2 mg/day), added to the diet. Group IV animals had the highest cholesterol plasma levels (vs. groups I, II, III, and V, p < 0.01) and presented atherosclerotic plaques in a more advanced stage. Nonatherogenic diet was insufficient to restore endothelial function in animals previously fed cholesterol-enriched diets (groups IV and VI). Conversely, pravastatin treatment promoted significant improvement in endothelial function and reduced the progression of atherosclerosis. Marked increase in cholesterol content was seen in aorta and liver in response to the atherogenic diet. However, neither treatment with pravastatin nor nonatherogenic diet was capable of modifying the tissue cholesterol content. Our study supports the hypothesis that the early use of statins can attenuate the progression of atherosclerosis and ameliorate endothelial function. In addition, significant changes in the tissue cholesterol pool probably need a longer period of treatment.

Efeitos do exercício agudo na lipemia pós-prandial em homens sedentários / Effects of acute exercise on postprandial lipemia in sedentary men

OBJETIVO: Examinar os efeitos de uma sessão isolada de exercício físico isométrico na trigliceridemia pós-prandial em homens sedentários com valores de triglicérides em jejum < 150 mg/dl (NTG) ou > 150 mg/dl (TG ALT). MÉTODOS: Foram avaliados 27 indivíduos (10 NTG e 17 TG ALT), com idade entre trinta e 55 anos. Os triglicérides foram determinados no início, e após duas, quatro e seis horas da ingestão oral de uma solução com 50g/m² de gordura em duas oportunidades, em repouso e após exercício isométrico em esteira. RESULTADOS: O exercício agudo não modificou os níveis pós-prandiais de triglicérides, ou a área sob a curva (AUC) de triglicérides. Entretanto, o padrão anormal da curva de lipemia pós-prandial associou-se a maior trigliceridemia basal com exercício (TG basais: 147 ± 90 versus 238 ± 89 mg/dl, p = 0,02) e sem exercício (TG basais: 168 ± 93 versus 265 ± 140 mg/dl, p = 0,04). A análise das curvas ROC (receive operating characteristics) mostrou valores de corte de triglicérides basais com atividade física de 166,5 mg/dl (sensibilidade: 0,78; especificidade: 0,72) e AUC de 0,772 [IC 95 por cento: 0,588-0,955], e sem atividade física de 172 mg/dl (sensibilidade: 0,78; especificidade: 0,61) e AUC de 0,722 [IC 95 por cento: 0,530-0,914]. CONCLUSÃO: A trigliceridemia pós-prandial em homens sedentários não foi modificada pelo exercício agudo, sendo os valores basais de triglicérides preditores de uma resposta anormal dos triglicérides pós-prandiais.

Terapia combinada de colestiramina e inibidores da HMAG-CoA redutase na prevençäo secundária da doença coronária / Combinedtherapy with cholestyramine and HMG-CoA reductase inihibtors in secondary prevention of coronary disease

OBJETIVO: Avaliar as alteraçöes obridas no perfil lipídico de coronariopatas dislipidêmicos, após a adiçäo de colestiramina, em pacientes tratados com inibidores da HMG-Co redutase, e que näo atingiram os valores ideais de LDL-colesterol. MÉTODOS: Vinte coronariopatas (12 submetidos à revascularizaçäo do miocárdio, 3 à angioplastia coronária e 5 mantidos sob tratamento clínico), com média de idade de 60,78 anos, que já realizavam dieta hipolipemiante e eram medicados com lovastatina 20 mg/dia ou sinvastatina 10 mg/dia, receberam também colestiramina na dose de 8 a 16 g/dia durante 8 semanas, com o objetivo de reduzir LDL-colesterol para valores inferiores a 100 mg/dl. RESULTADOS: Houve significante reduçäo do colesterol total (valor médio inicial 239,52 mg/dL e ao final 199,00mg/dL), obtendo-se um decréscimo percentual médio de 16,92 "por cento". O valor médio de LDL-colesterol também se reduziu, significantemente, de 172,73 mg/dL para 118,26 mg/dL, com decréscimo percentual médio de 31,53 "por cento". A trigliceridemia média aumentou, ainda dentro da faixa de refência normal, de 145,05 mg/dL para 162,00 mg/dL, (diferença percentual média de 11,69 "por cento". Houve significante aumento da fraçäo HDL-colesterol de um valor médio inicial de 38,00 mg/dL para um valor médio final de 48,21 mg/dL (diferença média percentual 26,87 "por cento"). Näo houve efeitos adversos que impedissem a continuidade do tratamento. CONCLUSÄO: A associaçäo de colestiramina a doses baixas de vastatinas em pacientes com hipercolesterolemia primária e de alto risco coronária é uma boa opçäo terapêutica, podendo atingir benefícios sobre o perfil lipídico semelhantes àqueles obtidos quando esses fármacos säo utilizados,isoladamente, ou em associaçäo, e em doses mais elevadas.

Comparação entre lovastatina e o gemfibrozil no tratamento de hiperlipidemias primárias / Comparison between lovastatin and gemfibrozil in treatment of primary hyperlipidemias

Purpose - To compare the effects of lovastatin and gemfibrozil in patients with primary hyperlipidemias. Patients and Methods - Forty patients with cholesterolemia over 200 mgldl and triglyceridemia not higher than 350 mp/dl, excluded secondary causes, were selected. Twenty patients received lovastatin and 20 gemfibrozil. In order to establish the lipid profile, blood samples were taken after 2 months without medication, after 4 weeks of diet and placebo and after 6 and 12 weeks active treatment. Biochemic profile was determined before and after the treatment with active drug. Results - Thirty nine patients completed the study. Total and LDL-cholesterol were significantly reduced (p < 0.05) by both drugs but lovastatin had greater effect. Only gemfibrozil reduced triglycerides significantly. Neither drug had significant effects on HDL-cholesterol. The tolerance was satisfactory; only one patient (using gemfibrozil) needed to stop the treatment due to gastrointestinal side effects. The biochemic profïle did not present any significant alteration. Conclusion - Both drugs produced useful effects on the lipid profile. Lovastatin produced greater reductions of total and LDL-cholesterol, while gemfibrozil was more active reducing triglycerides. Neither drug changed significantly the HDL-cholesterol

Fatores de risco, marcadores bioquímicos e polimorfismos genéticos na doença arterial coronariana prematura / Risk Factors, biochemical markers, and genetic polymorphisms in early coronary artery disease

OBJECTIVE: To assess the risk factors, lipid and apolipoprotein profile, hemostasis variables, and polymorphisms of the apolipoprotein AI-CIII gene in early coronary artery disease (CAD). METHODS: Case-control study with 112 patients in each group controlled by sex and age. After clinical evaluation and nutritional instruction, blood samples were collected for biochemical assays and genetic study. RESULTS: Familial history of early CAD (64 vs 39 percent), arterial hypertension (69 vs 36 percent), diabetes mellitus (25 vs 3 percent), and previous smoking (71 vs 46 percent) were more prevalent in the case group (p<0.001). Hypertension and diabetes were independent risk factors. Early CAD was characterized by higher serum levels of total cholesterol (235 ± 6 vs 209 ± 4 mg/dL), of LDL-c (154 ± 5 vs 135 ± 4 mg/dL), triglycerides (205 ± 12 vs 143 ± 9 mg/dL), and apolipoprotein B (129 ± 3 vs 105 ± 3 mg/dL), and lower serum levels of HDL-c (40 ± 1 vs 46 ± 1 mg/dL) and apolipoprotein AI (134 ± 2 vs 146 ± 2mg/dL) [p<0.01], in addition to an elevation in fibrinogen and D-dimer (p<0.02). The simultaneous presence of the rare alleles of the APO AI-CIII genes in early CAD are associated with hypertriglyceridemia (p=0.03). CONCLUSION: Of the classical risk factors, hypertension and diabetes mellitus were independently associated with early CAD. In addition to an unfavorable lipid profile, an increase in the thrombotic risk was identified in this population. An additive effect of the APO AI-CIII genes was observed in triglyceride levels

Stress no médico plantonista em unidade de terapia intensiva / Stress of physicians on duty in Intensive care units

A autora faz um trabalho sobre a presença de stress em médicos plantonistas em Unidade de Terapia Intensiva,baseado em conhecimentos teóricos-práticos,assim como nas respostas obtidas a partir de um questionário distribuído a 19 médicos de duas Unidades de Terapia Intesiva para adultos,na cidade de Campos dos Goytacazes-RJ,no período de junho a agosto de 1999,e também em entrevistas efetuadas com dois chefes de equipe.Como conclusão desta pesquisa,a autora atesta a existência de stress(em naior ou menor intensidade) e seus indicadores(em maior ou menor número)entre os profissionais observados

Fibrogênio como fator de risco independente de doença vascular cerebral / Fibrinogen as independent risk factor for ischemic stroke

No protocolo de avaliaçäo clínico-laboratorial de pacientes com acidente vascular cerebral (AVC) aterotrombótico dosamos e analisamos níveis de fibrinogênio plasmático (técnica de Clauss automatizada), para determinar seu possível papel como fator de risco trombogênico em 29 pacientes (20 homens e 9 mulheres) com idades entre 25 a 79 anos (mediana=55); todos tinham tido AVC aterotrombótico. Eles foram classificados em 2 grupos segundo alteraçöes de fluxo nas carótidas: g1 - sem alteraçäo de fluxo (n=19) e g2 - com alteraçöes de fluxo (n=10). Resultados- A média das dosagens de fibrinogênio no g1 foi de 269 e no g2 de 353 mg/dl. Quarenta e sete por cento dos pacientes do g1 e 80 por cento do g2, apresentaram medidas >300 mg/dl. As diferenças obtidas entre os grupos neste estudo foram significante. Conclusäo- Considerando o nível de risco epidemiológico de 300 mg/dl, nossos resultados sugerem que o fibrinogênio é um fator de risco independente para AVC aterotrombótico, especialmente naqueles com alteraçäo de fluxo carotídeo.

Avaliaçäo da eficácia e tolerabilidade do Bezafibrato Retard no tratamento das hiperlipidemias primárias / Evaluation of efficacy and tolerability of bezafibrate retard in the treatment of primary hyperlipidemia

Num estudo aberto, näo comparativo, foram avaliados 20 pacientes portadores de hiperproteinemia primária, com níveis de colesterol plasmático acima de 200mg/dl e/ou triglicérides acima de 250 mg/dl, após, pelo menos, 30 dias de orientaçäo dietética. Os pacientes foram tratados com bezafibrato retard, na posologia de um comprimido de 400 mg ao dia, durante três meses. Ao término do tratamento, houve uma reduçäo significativa dos níveis séricos de colesterol total (-14,6%), triglicérides (-39,7%), bem como aumento significativo dos níveis de HDL-colesterol (+ 19,6%). As provas de funçäo hepática e renal e o hemograma dos 20 pacientes avaliados permaneceram inalterados durante o transcorrer do estudo