Background Trastuzumab is a highly efficient drug in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority, especially in the presence of comorbidities. Left ventricle ejection fraction (LVEF) determination remains the most used technique to diagnose cardiotoxicity in clinical practice. The purpose of this study is to analyse the usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab. Methods The study included 66 patients who received trastuzumab. We collected the LVEF and NT-proBNP values measured during the course of treatment, and cardiovascular risk factors including diabetes, hypertension, smoking, hypercholesterolemia and BMI. Cardiotoxicity was diagnosed during the follow-up program considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. According to the literature, NT-proBNP cut-off points were considered to stablish normal or abnormal values in terms of patent age. Results 174 paired LVEF/NT-proBNP values were found. 27.3% of patients suffered cardiotoxicity during trastuzumab treatment and most of cases were diagnosed based on cardiac symptomatology (66.7 %). Logistic regression analysis of NT-proBNP and the cardiovascular risk factors showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2 - 28.5, p = 0.028) and NT-proBNP (OR 22.0, 95% CI 5.7 - 85.4, p = 0.000) with the development of cardiotoxicity during trastuzumab treatment, whereas the other variables were not statistically significant. Conclusions Diabetes and NT-proBNP values seem to be associated with an increased risk of cardiotoxicity in breast cancer patients during trastuzumab treatment. In diabetics, glycaemic control and a more intense cardiac monitoring could provide objective benefits during the treatment. Moreover, NT-proBNP determination could become an accessible way to evaluate cardiac risk in this context. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
Objective Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori (HP) infection. The culture-guided triple therapy (chosen on the basis of a preliminary in-vitro susceptibility test) might help to increase treatment success in high antibiotic resistance regions. The aim of this study was to evaluate the effectiveness of treatment with clarithromycin in patients with clarithromycin-sensitive culture compared with patients treated empirically. Methods In this prospective and controlled trial, 111 naive HP-positive patients were randomized to receive standard triple therapy omeprazole (20 mg twice daily), amoxicillin (1 g twice daily), and clarithromycin (500 mg twice daily) for 10 days (OAC) after antimicrobial susceptibility testing if there was no resistance to clarithromycin (ClariS) or empirical 10-day OAC for first-line therapy of HP (ClariNA). Eradication was confirmed using the 13C-labelled urea breath test 6 weeks after therapy. Our primary outcome was HP eradication. Treatment adherence and adverse effects were recorded. Results The effectiveness of eradication by protocol with 10-day OAC therapy in the ClariS was 94% [95% confidence interval (CI): 0.83–0.98], which was 22% higher than ClariNA 72% (95% CI: 0.58–0.85; P=0.006). The odds ratio of eradication in ClariS was 1.30 (95% CI: 1.10–1.60; P<0.05 by logistic regression) and the number needed to treat was 5 (95% CI: 3–13). We found no significant difference in the occurrence of adverse effects or in compliance between the two groups. Conclusion The eradication rate was significantly higher with clarithromycin-based triple therapy for patients with clarithromycin-susceptible HP isolates compared with those for whom no information on the corresponding susceptibility was available (ClinicalTrials.gov number NCT01486082).
The rate of eradication of Helicobacter pylori with standard triple therapy using omeprazole, amoxicillin and clarithromycin (OAC) is unacceptable in populations with high rates of clarithromycin resistance (15-20%). The aim of this study was to compare the efficacy of 10-day OAC therapy as the first-line treatment in patients diagnosed by culture with antimicrobial susceptibility or diagnosed by a (13) C-labelled urea breath test (UBT) without antimicrobial susceptibility in an area where the clarithromycin resistance rate was 15-20%. This was a retrospective cohort study of 266 patients, recruited consecutively throughout 2008. A total of 247 H. pylori-infected patients received antibiotic therapy (221 received the 10-day OAC therapy and 26 received other regimens) of which 134 patients were diagnosed by culture of gastric samples followed by antimicrobial susceptibility testing and 113 were diagnosed by UBT. In all patients, the eradication of H. pylori was checked by UBT. The cost of eradication by 10-day OAC treatment was assessed in each patient. The success rate of 10-day OAC therapy in patients diagnosed by culture and by UBT was 88% (103/117) and 49% (51/104), respectively (p <0.0005). The treatment was also more cost-effective in the former of these two groups (€571 versus €666). To perform culture and antimicrobial susceptibility of the H. pylori isolates was a more successful and cost effective strategy than empirical 10-day OAC treatment in populations with high rates of resistance to clarithromycin.
CASO CLÍNICOMujer de 59 años de edad que ingresó en octubre del 2009 por presentar ictericia, dolor abdominal, vómitos y fiebre de 38,5 ºC de un mes de evolución.Refería el antecedente de colecistectomía por colelitiasis múltiple y de coledocotomía para extracción de cálculo intracoledocal hace 24 años.El colédoco se cerró sobre tubo de Kher con nylon 4/0 no reabsorbible.Entre los datos analíticos destacaban: bilirrubina 3,9 mg/dl, FA 525 U/l (40-129), GGTP 1313 U/l (8-61), GOT 377 U/l (6-38), GPT 909 U/l (6-41), lipasa 95 U/l (0-60) y VSG 53 mm/h.Se solicitó una ecografía abdominal que mostró dilatación moderada de la vía biliar principal.Se realizó colangiorresonancia que puso de manifiesto un colédoco de 13 mm de diámetro con una imagen tubular de 30 x 5 mm en su interior con núcleo hiperintenso y que no dejaba sombra acústica (Fig. 1).Se hizo una CPRE que objetivó un defecto de replección intracoledocal de 30 x 5 mm (Fig. 2).Tras esfinterotomía, se pasó el balón de Fogarty y se extrajeron varios microcálculos.A continuación se canalizó el cístico y se pasó de nuevo el balón sin obtener
BACKGROUND:Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drug's ability to prevent type 2 diabetes in individuals at high risk of developing the condition.METHODS:5269 adults aged 30 years or more with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive rosiglitazone (8 mg daily; n=2365) or placebo (2634) and followed for a median of 3 years. The primary outcome was a composite of incident diabetes or death. Analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00095654.FINDINGS:At the end of study, 59 individuals had dropped out from the rosiglitazone group and 46 from the placebo group. 306 (11.6%) individuals given rosiglitazone and 686 (26.0%) given placebo developed the composite primary outcome (hazard ratio 0.40, 95% CI 0.35-0.46; p<0.0001); 1330 (50.5%) individuals in the rosiglitazone group and 798 (30.3%) in the placebo group became normoglycaemic (1.71, 1.57-1.87; p<0.0001). Cardiovascular event rates were much the same in both groups, although 14 (0.5%) participants in the rosiglitazone group and two (0.1%) in the placebo group developed heart failure (p=0.01).INTERPRETATION:Rosiglitazone at 8 mg daily for 3 years substantially reduces incident type 2 diabetes and increases the likelihood of regression to normoglycaemia in adults with impaired fasting glucose or impaired glucose tolerance, or both.
The present trial was designed to determine the efficacy of the combination of gemcitabine/doxorubicin/paclitaxel (GAT) delivered every other week as first-line therapy in patients with metastatic breast cancer. From February 1998 to September 1999, 41 patients were included in this trial. Doses delivered were doxorubicin 30 mg/m2 on day 1 and paclitaxel 135 mg/m2 plus gemcitabine 2500 mg/m2 both given on day 2, every 14 days. Doses were selected from a previous phase I trial conducted at our institution. Eligibility criteria for the phase II trial included histologically confirmed metastatic breast cancer with bidimensionally measurable lesions; no prior therapy for metastatic disease; adjuvant or neoadjuvant chemotherapy was allowed if given more than 1 year before and cumulative doses of doxorubicin or epirubicin were less than 200 mg/m2 or 360 mg/m2, respectively; Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less; and adequate hematological, hepatic, and renal function. Prophylactic use of granulocyte colony-simulating factor (G-CSF) was allowed if patients were not fully recovered (absolute neutrophil count greater than 1500/microL) from chemotherapy administration before the next dose. Left ventricular ejection fraction was determined initially, at the end of the study, and every 6 months thereafter. The patients' median age was 55 years (range, 33-68 years), and their median ECOG performance status was 0 (range, 0-1). Twenty-eight patients had received adjuvant therapy, 17 with epirubicin (none with doxorubicin). Metastases were present in the bone (19 patients), lung (19 patients), liver (11 patients), and soft tissues (18 patients). Twenty patients had one metastatic site and 21 had two or more sites. Efficacy was assessed on an intent-to-treat basis. A total of 216 cycles of GAT were given. Twenty-two percent of the courses were delayed or given at reduced doses mostly due to neutropenia or thrombocytopenia. G-CSF was required in 58% of the cycles. Grade 3/4 neutropenia was the main toxicity and appeared in 17 patients, one of whom had an episode of febrile neutropenia. Nonhematological toxicities consisted mainly of neurotoxicity and myalgias. A drop of 10%-20% in the left ventricular ejection fraction was detected in two patients and another patient had a decrease greater than 20%, although none developed symptoms of heart failure. Overall response rate was 80.4% (95% confidence interval: 68.3-92.5), with 15 patients (36.6%) achieving a complete response. Median survival time was 27 months and median time to progression was 15 months. The GAT combination is feasible and very active in patients with metastatic breast cancer, with an encouraging response rate including a high rate of complete responses. No congestive heart failure was documented and other toxicities were mild, with the exception of neutropenia.
The efficacy and toxicity of the combination of paclitaxel and carboplatin with concurrent radiotherapy (RT) in patients with locally advanced head and neck cancer has been determined.The study was carried out in 25 patients from December 1996 to October. 1998. Mean age was 59.3 years (41-74) and performance status was 0-1. Tumour locations were: 2 nasopharynx. 10 larynx, 11 oropharynx and 2 adenopathies of unknown origin.The treatment course comprised 2 cycles of Paclitaxel (175 mg/m(2)) and carboplatin (AUC = 6) every 3 weeks, followed by Paclitaxel (escalated dose 40/45/50 mg/m(2)) and cnrboplatin (AUC=2) with weekly RT Co60 (50Gy).Seventeen patients were assessed for toxicity and response. Grade 3-4 mucositis was the main non-haematological toxicity (58%): grade 3-4 neutropenia (41%). Other toxicities such as radiodermatitis or gastrointestinal were mild. An OR of 71% was obtained. After a median follow-up of 14 months. 10 patients have progressed (4 distantly and 6 locally) with an overall survival of 53%.