Eficiencia diurética inicial como predictor de resistencia a diuréticos y evolución clínica en insuficiencia cardíaca aguda descompensada / Initial Diuretic Efficiency as Predictor of Diuretic Resistance and Clinical Outcome in Acute Decompensated Heart Failure

RESUMEN Introducción: En pacientes con insuficiencia cardíaca aguda descompensada (ICAD) la eficiencia diurética (ED) evaluada en forma precoz podría predecir la respuesta a diuréticos y la evolución clínica. Objetivos: Nuestro objetivo fue evaluar la asociación de la ED con la resistencia a diuréticos (RD), la mortalidad cardiovascular intrahospitalaria, y la mortalidad cardiovascular y las reinternaciones a 60 días en la ICAD. Material y métodos: Estudio prospectivo y multicéntrico que incluyó pacientes internados por ICAD. Recibieron 40 mg de furosemida dentro de las 2 horas del ingreso y 20 mg cada 8 horas en las primeras 24 horas. El escalamiento diurético posterior quedó a criterio del investigador según un protocolo preestablecido. Se definió la ED como balance hídrico/dosis de furosemida en las primeras 24 horas y la RD como el requerimiento de infusión de furosemida ≥240 mg/día en las primeras 72 horas. Se evaluaron variables clínicas y bioquímicas, y el punto final combinado (PFC) de mortalidad cardiovascular intrahospitalaria, y mortalidad cardiovascular y reinternaciones por ICAD a 60 días. Resultados: Se incluyeron 157 pacientes, mediana de edad de 74 años, 56 % hombres. La ED fue -15 mL/mg (rango intercuartílico, RIC, -20 a -11). Se evidenció la RD en el 13 % de los pacientes, el 8 % requirió bloqueo tubular y el 4 % terapia de reemplazo renal. El 22 % desarrolló empeoramiento de la función renal. La mortalidad cardiovascular intrahospitalaria fue del 5,7 % y en el seguimiento a 60 días, del 6 %. Las reinternaciones por ICAD a 60 días fueron del 12 %. Una peor ED se asoció al desarrollo de RD (p = 0,013) y los pacientes con ED superior a -11 mL/mg tuvieron mayor probabilidad de no desarrollar RD (área bajo la curva, AUC, 0,73; valor predictivo negativo, VPN, 92,5 %). Una peor ED se asoció al PFC (p = 0,025), mayor mortalidad cardiovascular intrahospitalaria (p = 0,003), persistencia de congestión a 48 horas (p = 0,007), mayor dosis de furosemida a 72 horas (p = 0,001) y empeoramiento de la ICAD en la internación (p = 0,004). Conclusión: La ED inicial baja se asoció a la RD, la dificultad en la descongestión y una mayor mortalidad cardiovascular intrahospitalaria en ICAD. Es un parámetro útil para detectar pacientes que podrían beneficiarse de un tratamiento diurético intensivo precoz.

ABSTRACT Background: In patients with acute decompensated heart failure (ADHF), early evaluation of diuretic efficiency (DE) could predict diuretic response and clinical outcome. Objectives: The aim of our study was to evaluate the association of DE with diuretic resistance (DR) in-hospital cardiovascular mortality, and readmission or cardiovascular mortality at 60 days in ADHF. Methods: We conducted a multicenter and prospective study of patients hospitalized for ADHF. All patients received 40 mg of furosemide within two hours of admission and 20 mg every 8 hours in the first 24 hours. Subsequent adjustment of diuretic dose was left to the discretion of the investigator as determined by a pre-established protocol. Diuretic efficiency was defined as the ratio of net fluid balance and cumulative amount of furosemide within the first 24 hours. Diuretic resistance was defined as requirement of furosemide infusion ≥240 mg/day during the first 72 hours. The clinical and biochemical variables were evaluated. The primary outcome was a composite of in-hospital cardiovascular mortality, and cardiovascular mortality or readmissions for ADHF at 60 days. Results: The cohort was made up of 157 patients; median age was 74 years and 56 % were men. Diuretic efficiency was -15 mL/ mg (interquartile range, IQR, -20 to -11). Diuretic resistance was evident in 13 % of patients, 8 % required sequential diuretic blockade, and 4 % required renal replacement therapy. Worsening renal function occurred in 22 % of patients. Cardiovascular mortality during hospitalization and at 60 days was 5.7 % and 6 %, respectively. Readmission rate for ADHF at 60 days was 12 %. Worse DE value was associated DR (p = 0.013), while patients in DE quartiles above -11 mL/mg were highly unlikely to develop DR (AUC 0.73, negative predictive value, NPV, 92.5 %). Worse DE value was associated with the CEP (p = 0.025), higher in-hospital cardiovascular mortality (p = 0.003), persistent congestion at 48 hours (p = 0.007), higher cumulative dose of furosemide at 72 hours (p = 0.001) worsening ADHF during hospitalization (p = 0.004). Conclusion: Low initial DE was associated with DR, persistent congestion, and higher in-hospital cardiovascular mortality in ADHF and constitutes a useful parameter to detect those patients who could benefit from early intensive diuretic treatment.

Lower Gastrointestinal Bleeding Because of Kasabach-Merritt Syndrome Showing an Impressive Response to Sirolimus.

Kasabach-Merritt syndrome is a rare but life-threatening disease in which a rapidly growing vascular tumor induces localized intravascular coagulation, causing thrombocytopenia, microangiopathic hemolytic anemia, and consumption coagulopathy. It presents mainly in infants and young children. We present an adult with recurrent and severe lower gastrointestinal bleeding due to Kasabach-Merritt syndrome, treated successfully with sirolimus after multiple other failed interventions.

Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies.

Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined.

Outcomes of an underserved Hispanic population with chronic hepatitis C treated with pegylated-interferon and ribavirin in a government-sponsored clinic.

OBJECTIVE: Treatment of hepatitis C virus (HCV) with interferon-based therapy has been shown to be less effective in Hispanics when compared to other populations. A pilot clinic was established at the University of Puerto Rico for the treatment of HCV in the government-insured population. The aim of this study was to describe the outcomes and treatment response to pegylated interferon and ribavirin in treatment-naive patients enrolled at this government-sponsored clinic. METHODS: A retrospective analysis was undertaken to investigate the treatment outcomes with weight based peg-interferon-alpha-2b and ribavirin in patients with chronic HCV enrolled in the pilot clinic during 2003-2005. Descriptive statistics were reported. Continuous variables were summarized as means and standard deviations. Frequency distributions and percents were used for categorical variables. Statistical analysis was performed using STATA. RESULTS: A total of 155 patients (105 males and 50 females) with mean age of 42 years started treatment; 79 (51%) patients had HCV genotype 1. Completion of treatment was achieved by 59 patients (38.1%), of whom end of treatment response (ETR) was observed in 30 (50.9%), representing 19.4% of the intention-to-treat population (ITT). Sustained viral response (SVR) was achieved in 17 (28.8%) patients who completed treatment, resulting in 11% (17/155) SVR by ITT. The only significant predictor of SVR was treatment onset within 5 years of the diagnosis of HCV (p = 0.026). Although no association was found between HCV genotype and SVR (p = 0.192), those patients with HCV genotypes 2 and 3 were more likely to complete treatment (p = 0.009). CONCLUSION: SVR to pegylated interferon and ribavirin seems to be lower than expected in our population. The high rate of incomplete treatment surpasses previously reported rates in U.S. Latinos and Caucasians. Further studies should explore reasons for lower response and higher treatment discontinuation in our population.

Prevalence of spondyloarthropathy in Puerto Rican patients with inflammatory bowel disease.

INTRODUCTION: Inflammatory arthritis is the most common extraintestinal manifestation in patients with inflammatory bowel disease (IBD). Approximately 20% of all IBD patients will present with peripheral arthritis, sacroiliitis, or spondylitis. The purpose of this study was to determine the prevalence of spondyloarthropathy and sacroiliitis in Puerto Rican patients with IBD. METHODS: Patients were obtained from the IBD specialty clinic and all had a diagnosis of ulcerative colitis or Crohn's disease. All the patients who agreed to participate were entered in the study. Patients completed a questionnaire and underwent a physical examination. Radiologic examination of the lumbosacral spine and sacroiliac joints was performed. Blood samples were obtained for determining human leukocyte antigen class I and were serologically analyzed in the pathology department laboratory. Data were analyzed by using SPSS 10.0 for Windows. RESULTS: One hundred patients were enrolled; 57% had ulcerative colitis, and 43% had Crohn's disease. Fifty percent were female, and the mean age was 37 years (standard deviation 14.96 years). Seventy-seven percent reported history of joint pain, and 47% reported limitation due to joint pain. Physical examination revealed peripheral synovitis in five patients and spinal tenderness in 46 patients. Of the 100 patients, 42 had inflammatory back pain and fulfilled the criteria for spondyloarthropathy. Radiographs were obtained in 76 patients. They revealed grade 2 or greater sacroiliitis in 10 patients (13%) and ankylosing spondylitis in two patients (2.6%). Of the 82 patients with blood samples, human leukocyte antigen B27 was found in five patients (6%). CONCLUSIONS: Of the study population of Puerto Ricans with IBD, 42% had spondyloarthropathy. This prevalence is higher than reported in Caucasians (20%-30%). Sacroiliitis had a similar prevalence as reported in Caucasians, but the prevalence of peripheral arthritis was much lower.

Systemic lupus erythematosus presenting as acute iceric hepatitis: a case report.

Liver involvement in systemic lupus erythematosus (SLE) is infrequent. The coexistence of SLE and autoimmune hepatitis is rare (1.3-1.7%). We report a case of a 27 year old female with no history of systemic illnesses or alcohol abuse that presented with acute hepatitis with jaundice, abdominal pain, and increased liver function tests. Viral markers were negative. ANA was strongly positive. Patient was suspected to have SLE but no definite diagnosis made. She remained asymptomatic for 9 years but then she had recurrence of hepatitis. She also presented with malar rash, arthritis, and proteinuria. At that time a liver biopsy showed autoimmune hepatitis. Other tests which confirmed SLE included a positive antidsDNA, positive antismith antibody and decreased complement levels. She was started on prednisone 40 mg with mild improvement of symptoms and transaminase values, but when azathioprine 100 mg was added a marked improvement in liver function tests was observed. After a year in azathioprine she remained with SLE in remission. To our knowledge this is the third reported case and the first in the Western Hemisphere of jaundice as the initial presentation of SLE.

A government sponsored clinic for the evaluation and treatment of chronic hepatitis C in an underinsured population in Puerto Rico.

BACKGROUND: Chronic hepatitis C (CHC) is a major health problem in Puerto Rico (PR). More than 50% of the population is insured by a government-sponsored managed care system that does not cover treatment for CHC. Lack of access to treatment will result in an increase in end-stage liver disease with its high socioeconomic impact in the future. In an attempt to identify strategies for the treatment of CHC in the publicly insured population, the PR Health Department and the University of Puerto Rico (UPR) Gastroenterology (GI) Division have developed a pilot clinic for the evaluation and treatment of CHC. METHODS: UPR and the PR Health Department negotiated a fee per patient to include all medical care and follow-up laboratories. Viral studies were covered by a grant to the Health Department. Medications were bought at a discount price by the government and dispensed at a government pharmacy. The Health Department allocated funds for 200 patients with government insurance. A dedicated clinic was established at the UPR, staffed by an internist under the supervision of the GI faculty. Patients with a positive HCVab were referred to this clinic. The public insurance covered the CBC, liver tests, metabolic panel, TSH, HBsAg, HIV, ultrasound and liver biopsy, which were required prior to evaluation for possible treatment. In the initial visit, patients underwent a medical evaluation, including assessment of suitability for therapy and counseling. Those deemed to be candidates who still needed a liver biopsy had it performed by the GI staff. Genotype and viral titers were ordered after the decision on treatment had been made. The clinic physician prescribed pegylated interferon and ribavirin, which were dispensed by the government pharmacy. Instruction on proper drug administration was given. Clinic visits were scheduled for 1, 3, 6 and 12 months but also allowed on demand. Laboratory tests were done at the clinic and reviewed by the physician expediently to monitor for toxicity. Any medical problems or treatment for complications of therapy were covered by the primary insurer. Viral load was repeated at 12 weeks to discontinue therapy in those unlikely to respond. The budget per patient for medical visits and laboratory tests was dollars 1,500.00, HCV RNA titers plus genotype costs dollars 200.00, and HCV qualitative RNA costs dollars 123.00 RESULTS: 405 patients have been referred between February 2002 and April 2003 (the number was increased at adjust for no-shows and those not treated). 30% are female, the major risk factor is IVDU, and 80% are unemployed. 101 have started treatment and 48 are awaiting biopsy. A support group has been established at the clinic. CONCLUSIONS: The treatment for CHC in practice is not only costly but also resource consuming. Most gastroenterologists in our community refer these patients for treatment. The establishment of a dedicated clinic with a primary physician supervised by the specialists reduces costs and facilitates caring for a larger number of patients. The volume of services allows for negotiation of medical, laboratory and drug costs. In allocating funds for this project, the PR Health Department recognized the importance in reducing the potential spread in the community by treating infected patients as well as reducing the future medical and socioeconomic burden of end-stage liver disease. Although the outcome of this project is still unseen, we believe that this model may serve to establish other clinics for the treatment of CHC at lower costs with the same effectiveness.