Epidemiological profile and hospitalization data of patients with inflammatory bowel disease / Perfil epidemiológico e caráter de internação dos pacientes portadores de doença inflamatória intestinal

Abstract Objective: This study's objective was to understand the epidemiologic profile of the patients with inflammatory bowel disease in the state of Tocantins, Brazil. Methods: This is a descriptive study of secondary data, which was gathered by using the Informatics Department of the Brazilian Health System, and it corresponds to the cases registered from January of 2010 to December of 2017. The data of interest were those related to the total number of admissions, age range, gender, ethnicity, city of hospitalization, and type of care. Results: There were 340 hospital admissions due to inflammatory bowel diseases in Tocantins, of which 204 (60%) were female patients and 136 (40%), male patients; the predominant age group was between 20 and 59 years old (65.88%). These hospitalizations lasted an average of 4.7 days and 98.23% of them occurred as a matter of urgency. Conclusion: The study demonstrated that the epidemiological profile of the inflammatory bowel disease in the state of Tocantins consists of female patients, aged between 20 and 59 years, with hospitalizations lasting 4.7 days and mainly urgent, demonstrating that it is necessary to implement screening measures in order to make the diagnosis earlier, thus preventing possible complications.

Resumo Objetivo: Conhecer o perfil epidemiológico dos pacientes portadores da doença inflamatória intestinal no estado do Tocantins. Metodologia: Trata-se de estudo descritivo de dados secundários obtidos a partir do Sistema de Internações Hospitalares do Sistema Único de Saúde, que se compreendem entre Janeiro de 2010 e Dezembro de 2017. Os dados de interesse foram aqueles relacionados ao número total de internações, à faixa etária, sexo, raça, município de internação dos pacientes e caráter dos atendimentos. Resultados: Houve 340 internações hospitalares em razão das doenças inflamatórias intestinais em Tocantins, das quais 204 (60%) foram pacientes femininos e 136 (40%) pacientes masculinos, e a faixa etária predominante foi entre 20 e 59 anos (65,88%). Essas internações duraram em média 4,7 dias e 98,23% delas ocorreram com caráter de urgência. Conclusão: O estudo demonstrou que o perfil epidemiológico da doença inflamatória intestinal no Tocantins constitui-se por pacientes femininos, tendo de 20 a 59 anos, internações de 4,7 dias e predominantemente de urgência, o que torna necessário a implantação de medidas de rastreio de forma a tornar o diagnóstico mais precoce, prevenindo, então, possíveis complicações.

Thromboembolic Events Related to Treatment with Checkpoint Inhibitors: Report of Two Cases.

Despite the significant clinical benefits, checkpoint inhibition is associated with a unique spectrum of immune-related adverse events. It is sometimes difficult to distinguish some rare adverse effects from a cancer progression; thus, such effects should be reported in clinical trials to be diagnosed by physicians. Only a few cases of arterial embolic events have been described in studies related to patients treated by immunotherapy. In this article, we report the cases of 2 patients who presented rare and severe thromboembolic events after using checkpoint inhibitors. The first case describes multiple organ embolism at the same time, associated with other autoimmune symptoms. In the second case, distal digital necrosis emerged after the initiation of immunotherapy. There is insufficient data about the real incidence of thromboembolic and rheumatological events related to checkpoint inhibition. Future trials should be done to establish preventive strategies.

The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non-Clear Cell Renal Cell Carcinoma.

Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non-clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation are limited. In this multicenter analysis, we explored the efficacy of PD-1/PD-L1 inhibitors in patients with nccRCC or sarcomatoid/rhabdoid differentiation. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate. Secondary endpoints include time-to-treatment failure (TTF), overall survival (OS), and biomarker correlates. Forty-three patients were included: papillary (n = 14; 33%), chromophobe (n = 10; 23%), unclassified (n = 9; 21%), translocation (n = 3; 7%), and ccRCC with sarcomatoid differentiation (n = 7, 16%). Of those 43 patients, 11 patients (26%) had sarcomatoid and/or rhabdoid differentiation (n = 7 with ccRCC; n = 4 nccRCC). Overall, 8 patients (19%) objectively responded, including 4 patients (13%) who received PD-1/PD-L1 monotherapy. Responses were observed in patients with ccRCC with sarcomatoid and/or rhabdoid differentiation (n = 3/7, 43%), translocation RCC (n = 1/3, 33%), and papillary RCC (n = 4/14, 29%). The median TTF was 4.0 months [95% confidence interval (CI), 2.8-5.5] and median OS was 12.9 months (95% CI, 7.4-not reached). No specific genomic alteration was associated with clinical benefit. Modest antitumor activity for PD-1/PD-L1-blocking agents was observed in some patients with nccRCC. Further prospective studies are warranted to investigate the efficacy of PD-1/PD-L1 blockade in this heterogeneous patient population. Cancer Immunol Res; 6(7); 758-65. ©2018 AACR.

Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events.

The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti-PD-1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7-46.5) and median TTP was 18.4 months (95% CI, 4.7-54.3) per Kaplan-Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients (n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% (n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti-PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti-PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402-8. ©2018 AACR.

The Clinical Presentation, Survival Outcomes, and Management of Patients With Renal Cell Carcinoma and Cardiac Metastasis Without Inferior Vena Cava Involvement: Results From a Pooled Clinical Trial Database and Systematic Review of Reported Cases.

BACKGROUND: Cardiac metastases from renal cell carcinoma (RCC) are uncommon and there are limited data regarding the presentation and outcomes of this population. The objective of this study was to evaluate the characteristics and outcomes of patients with RCC with cardiac metastasis without inferior vena cava (IVC) involvement. MATERIALS AND METHODS: We conducted a pooled retrospective analysis of metastatic RCC patients treated in 4 clinical trials. Additionally, we conducted a systematic review of cases reported in the literature from 1973 to 2015. Patients with cardiac metastases from RCC without IVC involvement were included. Patient and disease characteristics were described. Additionally, treatments, response to therapy, and survival outcomes were summarized. RESULTS: Of 1765 metastatic RCC patients in the clinical trials database, 10 had cardiac metastases without IVC involvement. All patients received treatment with targeted therapy. There was 1 observed partial response (10%) and 6 patients showed stable disease (60%). The median progression-free survival was 6.9 months. The systematic review of reported clinical cases included 39 patients. In these patients, the most common cardiac site of involvement was the right ventricle (51%; n = 20). Patients were treated with medical (28%; n = 11) and/or surgical treatment (49%; n = 19) depending on whether disease was isolated (n = 13) or multifocal (n = 26). CONCLUSION: To our knowledge, this is the first series to report on the presentation and outcomes of patients with cardiac metastasis without IVC involvement in RCC. We highlight that although the frequency of patients with cardiac metastases without IVC involvement is low, these patients have a unique clinical presentation and warrant special multidisciplinary management.

Role of gemcitabine as second-line therapy after progression on FOLFIRINOX in advanced pancreatic cancer: a retrospective analysis.

BACKGROUND: Cancer of the exocrine pancreas is a highly lethal malignancy. Surgical resection is the only potentially curative treatment. Unfortunately, because of the late presentation, the majority have either locally advanced cancer at initial diagnosis. Systemic chemotherapy provides benefit to patients with advanced pancreatic cancer, improving disease-related symptoms and survival when compared to best supportive care alone. Based on fase III study, FOLFIRINOX regimen became the standard first-line treatment. But, the optimal management strategy for patients who fail initial FOLFIRINOX is undefined. Despite the lack of clinical trials that report the real benefit of gemcitabine in patients with advanced exocrine pancreatic cancer as second line treatment. We aim at reporting our experience with this regimen. METHODS: Patients with advanced exocrine pancreatic cancer who received gemcitabine (1.000 mg/m(2) on days 1, 8 and 15 every 4 weeks) until disease progression, as second-line therapy at our institution were retrospectively evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: A total of 20 patients were reviewed. Median age was 57 years (range, 43-74 years), and 55% were older than 60 years. Most patients were male (80%), had metastatic disease (60%), and ECOG performance status of 0 or 1 (65%). PFS and OS were 2.0 (95% CI, 1.2-2.8) and 5.7 months (95% CI, 3.9-7.4), respectively. There were no deaths due to the treatment. CONCLUSIONS: In this study, gemcitabine was a reasonable second-line treatment option for patients with advanced pancreatic adenocarcinoma and good ECOG performance status. Phase III trials are urgently needed comparing gemcitabine versus best supportive of care (BSC) can evaluate the real benefit of this chemotherapy after progression on FOLFIRINOX.

Low-dose bevacizumab is effective in radiation-induced necrosis.

BACKGROUND: Radiation-induced necrosis is a complication of brain irradiation. Treatment options are limited. METHODS: The response to treatment with low-dose bevacizumab in 2 patients with radiation-induced necrosis was reported. RESULTS: Both patients with metastatic melanoma, aged 48 and 51 years, had significant symptomatic and radiological improvement with low-dose bevacizumab treatment. Doses as low as 5 mg/kg every 6 weeks and 7.5 mg/kg i.v. every 4 weeks were used and were highly effective. CONCLUSIONS: Low-dose bevacizumab is a solid option in the management of edema associated with radiation necrosis.

Perfil clínico-demográfico e indicadores de qualidade da insuficiência cardíaca em uma área rural / Clinical and demographic profile and quality indicators for heart failure in a rural area / Perfil clínico demográfico e indicadores de calidad de la insuficiencia cardíaca en un área rural

Fundamentos: Os dados sobre insuficiência cardíaca (IC) no Brasil são provenientes de centros terciários. Esses dados não podem ser extrapolados para a população rural, pois refletem características socioeconômico-culturais distintas. Objetivo: Estabelecer o perfil clínico-demográfico e indicadores de qualidade da IC em área rural. Métodos: Estudo de coorte transversal, incluindo 166 pacientes da área rural do município de Valença-RJ. Após avaliação dos dados clínicos, laboratoriais e ecocardiográficos e utilizados o teste do qui-quadrado e o exato de Fisher para a análise das proporções, assim como o teste t de Student para as variáveis numéricas, com o intuito de estabelecer as características da população. Resultados: A idade média foi de 61±14 anos, sendo 85 (51 por cento) homens; 88 (53 por cento) afrobrasileiros e 85 (51 por cento) com ICFER. Comorbidades prevalentes: HAS em 151 (91 por cento) e síndrome metabólica (SM) em 103 (62 por cento). Etiologias mais comuns: hipertensiva em 77 (46 por cento), isquêmica em 62 (37 por cento). Indicadores de qualidade na IC: 43 (26 por cento) com ecocardiograma prévio; 102 (62 por cento) utilizavam betabloqueador; 147 (88 por cento) receberam IECA ou BRA; e 22 por cento dos portadores de FA utilizavam anticoagulação oral. Na ICFEN, predominou o sexo feminino p=0,001 RC 0,32 CI (0,17-0,60); SM p=0,004 RC 0,28 CI (1,31-4,78); e etiologia hipertensiva p<0,0001 RC 6,83 CI (3,45-13,5). Na ICFER, predominou o sexo masculino p=0,001, RC 0,32 CI (0,170-0,605) e etiologia isquêmica p<0,0001 RC 0,16 CI (0,079-0,330). Conclusão: Na área rural, a IC mostra semelhanças em relação ao sexo, cor e classificação da IC. A etiologia mais comum foi a hipertensiva. A ICFEN foi mais prevalente em mulheres e na SM. A ICFER associou-se a homens e etiologia isquêmica.

Background: data on heart failure (HF) in Brazil are ensued from tertiary centers. This information can not be extended to the rural population, for it reflects distinct social, economic and cultural characteristics. Objective: To establish the clinical and demographic profile and quality indicators for HF in rural areas. Methods: Transversal cohort study that included 166 patients from the rural area of Valença, Rio de Janeiro, Brazil. After the evaluation of clinical, laboratorial and echocardiograph data, chi-square and Fisher's exact tests were used for analysis of proportion, as well as the Student's t-test for numeric variables, in order to establish the population's characteristics. Results: Mean age was 61±14 years old, as 85 of them (51 percent) were men, 88 (53 percent) were afro-Brazilian and 85 (51 percent) had heart failure with reduced ejection fraction (HFREF). Systemic arterial hypertension (151 patients, 91 percent) and metabolic syndrome (103 patients, 62 percent) were prevalent comorbidities. The most common etiologies were: hypertensive (77 patients, 46 percent) and ischemic (62 patients, 37 percent). Quality indicators in HF were: 43 patients (26 percent) with previous echocardiogram, 102 patients (62 percent) were in use of beta-blockers, 147 patients (88 percent) received angiotensin converter enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB), and 22 percent of the patients with atrial fibrillation (AF) were under treatment with oral anticoagulation. For heart failure with normal ejection fraction (HFNEF), females (p=0.001; OD: 0.32; CI=0.17-0.60), metabolic syndrome (p=0.004; OD: 0.28; CI=1.31-4.78) and hypertensive etiology (p<0.0001; OD: 6.83; CI=3.45-13.5) were predominant. For CIREF, males (p=0.001; OD: 0.32; CI=0.170-0.605) and ischemic etiology (p<0.0001; OD: 0.16; CI=0.079-0.330) were predominant...

Fundamentos: Los datos sobre insuficiencia cardíaca (IC) en Brasil provienen de centros terciarios. Estos datos no pueden ser extrapolados para la población rural, pues reflejan características socioeconómicas y culturales distintas. Objetivo: Establecer el perfil clínico-demográfico e indicadores de calidad de la IC en área rural. Métodos: Estudio de cohorte transversal, incluyendo 166 pacientes del área rural del municipio de Valença - RJ. Después de la evaluación de los datos clínicos, de laboratorio y ecocardiográficos, y utilizados el test de chi-cuadrado y el exacto de Fisher para el análisis de las proporciones, así como el test t de Student para las variables numéricas, con el objetivo de establecer las características de la población. Resultados: La edad promedio era de 61±14 años, siendo 85 (51 por ciento) hombres; 88 (53 por ciento) afrobrasileños y 85 (51 por ciento) con ICFER. Comorbilidades prevalentes: HAS 151 (91 por ciento) y síndrome metabólico (SM) 103 (62 por ciento). Etiologías más comunes: hipertensiva 77 (46 por ciento), isquémica 62 (37 por ciento). Indicadores de calidad en la IC: 43 (26 por ciento) con ecocardiograma previo; 102 (62 por ciento); utilizaban betabloqueante; 147 (88 por ciento) recibieron IECA o BRA; y 22 por ciento de los portadores de FA utilizaban anticoagulación oral. En la ICFEN predominó el sexo femenino p=0,001 RR 0,32 CI (0,17-0,60); SM p=0,004 RR 0,28 CI (1,31-4,78); y etiología hipertensiva p<0,0001 RR 6,83 CI (3,45-13,5). En la ICFER predominó el sexo masculino p=0,001, RR 0,32 CI (0,170-0,605) y etiología isquémica p<0,0001 RR 0,16 CI (0,079-0,330). Conlclusión: En el área rural, la IC muestra semejanzas con relación al sexo, color y clasificación de la IC. La etiología más común fue la hipertensiva. La ICFEN fue más prevalente en mujeres y en el SM. La ICFER se asoció a hombres y etiología isquémica.

Clinical and demographic profile and quality indicators for heart failure in a rural area.

BACKGROUND: data on heart failure (HF) in Brazil are ensued from tertiary centers. This information can not be extended to the rural population, for it reflects distinct social, economic and cultural characteristics. OBJECTIVE: To establish the clinical and demographic profile and quality indicators for HF in rural areas. METHODS: Transversal cohort study that included 166 patients from the rural area of Valença, Rio de Janeiro, Brazil. After the evaluation of clinical, laboratorial and echocardiograph data, chi-square and Fisher's exact tests were used for analysis of proportion, as well as the Student's t-test for numeric variables, in order to establish the population's characteristics. RESULTS: Mean age was 61+/-14 years old, as 85 of them (51%) were men, 88 (53%) were afro-Brazilian and 85 (51%) had heart failure with reduced ejection fraction (HFREF). Systemic arterial hypertension (151 patients, 91%) and metabolic syndrome (103 patients, 62%) were prevalent comorbidities. The most common etiologies were: hypertensive (77 patients, 46%) and ischemic (62 patients, 37%). Quality indicators in HF were: 43 patients (26%) with previous echocardiogram, 102 patients (62%) were in use of beta-blockers, 147 patients (88%) received angiotensin converter enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB), and 22% of the patients with atrial fibrillation (AF) were under treatment with oral anticoagulation. For heart failure with normal ejection fraction (HFNEF), females (p=0.001; OD: 0.32; CI=0.17-0.60), metabolic syndrome (p=0.004; OD: 0.28; CI=1.31-4.78) and hypertensive etiology (p<0.0001; OD: 6.83; CI=3.45-13.5) were predominant. For CIREF, males (p=0.001; OD: 0.32; CI=0.170-0.605) and ischemic etiology (p<0.0001; OD: 0.16; CI=0.079-0.330) were predominant. CONCLUSION: In rural areas, HF shows similarity with regard to sex, ethnicity and classification. Hypertensive etiology was the most commonly present. HFNEF was prevalent among women and in the presence of metabolic syndrome, while HFREF was associated with males and ischemic etiology.

O avanço do polimorfismo gênico na insuficiência cardíaca / Advances of gene polymorphism in heart failure

Grandes estudos clínicos comprovam a diferença das respostas terapêuticas em indivíduos com características semelhantes. Parte dessses estudos vem utilizando o mapeamento genético dos grupos tratados. A farmacogenômica surge como uma promessa para otimizar e individualizar a terapêutica baseada na diversidade gênica. Os principais polimorfismos estudados na IC são os dos receptores betaadrenérgicos, que parecem estar envolvidos com menor capacidade funcional e pior resposta ao uso de betabloqueador; o da ECA, cujo homozigoto DD está relacionado com uma pior fração de ejeção e dilatação do VE; e o da aldosterona e óxido nítrico que evidenciaram respostas diferentes a determinados farmacos...