Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population.

BACKGROUND: The addition of everolimus to exemestane therapy significantly improves progression-free survival in postmenopausal patients with hormone-receptor (HR)-positive HER2-negative endocrine-resistant breast cancer. However, the safety profile of this schedule still might be optimized. METHODS: Patients included in the BALLET trial were assessed. The objectives of this analysis were to provide additional information on the safety profile of this schedule depending on prior anticancer therapies and to characterize the time course of adverse events (AEs) and serious AEs (SAEs) of clinical interest throughout the study period. Non-infectious pneumonitis (NIP), stomatitis, asthenia and weight loss were selected as AEs of clinical interest. RESULTS: The safety population of this analysis comprised 2131 patients. There were similar incidences of AEs and SAEs of clinical interest regardless of previous anticancer therapies. Most stomatitis and asthenia events occurred within the first three months. Incidence of weight loss appeared to plateau except in the case of grade 3-4 events, which occurred rarely. The incidence of any grade NIP (between 2 to 6%) and grade 3-4 NIP (between 0 to 1%) was low across the study, but steady. CONCLUSIONS: Everolimus plus exemestane is a well-known therapeutic option for aromatase inhibitor pretreated advanced breast cancer patients, and its toxicity profile is similar to that described in previous studies. Close monitoring, especially within the first three months, early intervention with preventive measures and patient education to help recognize the first signs and symptoms of AEs, will help to reduce their incidence and severity.

Antibacterial effect of sevoflurane and isoflurane.

OBJECTIVE: Multidrug resistant bacteria are increasing worldwide and therapeutic options are limited. Some anaesthetics have shown antibacterial activity before. In this study, we have investigated the antibacterial effect of the halogenated anaesthetic agents sevoflurane and isoflurane against a range of resistant pathogens. METHODS: Two experiments were conducted. In the first, bacterial suspensions of both ATCC and resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were exposed to liquid sevoflurane and isoflurane during 15, 30 and 60 minutes. In the second experiment clinical resistant strains of E. coli, Klebsiella pneumoniae, Enterobacter cloacae, P. aeruginosa, Acinetobacter baumannii, S. aureus, and Enterococcus faecium were studied. Previously inoculated agar plates were irrigated with the halogenated anaesthetic agents and these were left to evaporate before the plates were incubated. In both experiments colony forming units were counted in resultant plates. RESULTS: In the first experiment, isoflurane showed faster and higher antimicrobial effect than sevoflurane against all the strains studied. Gram-negative organisms were more susceptible. In the second experiment, E. faecium was found to be resistant to both halogenated agents; only isoflurane showed statistically significant activity against the rest of the strains studied. CONCLUSIONS: Both halogenated agents, but particularly isoflurane, showed in vitro antibacterial activity against pathogens resistant to conventional antibiotics. Further investigation is required to determine whether or not they also exhibit this property in vivo. This might then allow these agents to be considered as rescue treatment against multidrug resistant pathogens, including a topical use in infected wounds.

Long-term effect of hormone therapy on bone in early menopause: vertebral fractures after 20 years.

OBJECTIVE: The role of menopausal hormone therapy (HT) on vertebral fracture prevention after treatment discontinuation is controversial. The aim of this study was to assess the incidence of vertebral fracture in a group of women who received HT in early menopause compared with another group who did not receive such treatment after 20 years of follow-up. SUBJECTS AND METHODS: In 1990, we included 177 patients aged 43-57 years old (mean 49.1 ± 3.9 years) in a prospective study to evaluate the effect of different HT regimens on bone metabolism and mineral density. After 20-21 years, a total of 49 patients from the initial study were retrieved. These patients were divided into two groups: the first group included women who had taken HT, and those who constituted the control groups and had not taken HT formed the second group. Clinical and demographic data were analyzed and vertebral fracture was assessed by radiology using the Genant semiquantitative scale. RESULTS: Of the 49 patients enrolled, 32 (65.3%) received HT for an average of 5.5 (± 2.96) years while the 17 (34.7%) remaining belonged to the control group without treatment. A higher rate of vertebral fracture was observed in the group receiving HT (p = 0.03). Depending on the degree of fracture (Genant semiquantitative method), subsequent analysis by subgroups corroborated the higher rate in the group receiving HT in all cases (p < 0.05). Multivariate analysis ruled out the effect of the clinical and demographic variables (current age, age at menopause, body mass index, type of menopause and drugs for the treatment of osteoporosis) in the final result. CONCLUSION: In spite of the fact that this study does not have a large enough sample, our data suggest that HT used in the early years of menopause does not present a long-term protective effect on vertebral fracture after discontinuing treatment.

Specific improvement measures to reduce complications and mortality after urgent surgery in complicated abdominal wall hernia.

PURPOSE: Morbidity and mortality are increased after urgent surgery for complicated abdominal wall hernia. We analysed prospectively early morbidity and mortality after implementing specific management measures in patients undergoing urgent hernia repair. METHODS: The study population included 244 patients with complicated abdominal wall hernia requiring surgical repair on an emergency basis over 1-year period. Patients were managed according to a protocol that included specific actions to be implemented in the pre-, intra- and postoperative periods. Outcomes of these patients were compared with those of 402 undergoing similar operations before development of the protocol. RESULTS: Patients in whom acute complication was the first hernia symptom had higher mortality (7.2% vs 2.5%; P = 0.07) and were consulted later than 24 h (49.4% vs 36%; P = 0.044). Patients consulting later than 24 h had higher mortality (8.1% vs 1.4%, P = 0.017). Femoral hernias exhibited specific characteristics and were associated with higher mortality (13% vs 1.6%; P = 0.001). Overall, both groups had similar mortality (4.5% vs 4.1%; P = 0.8); complications (38.8% vs 37.7%; P = 0.2), and bowel resection rates (12.2% vs 11.5%; P = 0.8). Excluding the group of femoral hernias, the measures achieved a lower rate of severe complications (21.2% vs 10.3%; P = 0.04) and a decrease in mortality (2.9% vs 0.6%; P = 0.05) after bowel resection. CONCLUSIONS: Specific measures for improvement of management and prevention of complications and mortality were effective in patients without femoral hernia. To reduce mortality, the best applicable measure is early detection and to prioritize the scheduled operation of femoral hernias and those affecting high risk patients. The implementation of preventive and educational programs in high risk patients is essential.

Cord occlusion followed by laser cord transection in monochorionic monoamniotic discordant twins.

OBJECTIVE: To compare the outcomes of a consecutive case series of monochorionic (MC) monoamniotic (MA) discordant twins treated with umbilical cord occlusion and transection, with those of a cohort of MC diamniotic (DA) twins treated with conventional cord occlusion. METHODS: This study included 17 MCMA twins (12 true MA and five iatrogenic) treated with cord occlusion and transection and a control group of 72 MCDA discordant twins treated during the same period with cord occlusion in a single center. Duration of surgery, rates of preterm delivery (PTD) or preterm premature rupture of membranes (PPROM) < 32 weeks and intrauterine fetal demise (IUFD), perinatal outcome and neonatal survival were prospectively recorded in both groups. RESULTS: Median durations of surgery were 28.5 (range, 14.0-74.0) min and 24.0 (3.0-60.0) min in the cord transection and control groups, respectively (P = 0.24). There were no significant differences between cord transection and control groups in the rates of PPROM (35.3% vs. 20.8%, P = 0.22), PTD (41.2% vs. 28.2%, P = 0.29), IUFD (0% vs. 2.8%, P = 1.0) and neonatal survival (76.5% vs. 80.6%, P = 1.0). Gestational age at delivery (median 35.0 (24.5-39.0) vs. 37.1 (26.2-41.0) weeks, P = 0.21) and fetal birth weight (2215 (800-3200) g vs. 2605 (588-3830) g, P = 0.51) were similar between study groups. CONCLUSION: Cord occlusion and transection in MCMA discordant twins resulted in similar perinatal outcomes to those of MCDA discordant twins treated with cord occlusion.

Risk of death after emergency repair of abdominal wall hernias. Still waiting for improvement.

PURPOSE: The precise importance of factors affecting morbidity and mortality in patients with complicated abdominal wall hernias undergoing emergency surgical repair has been not completely elucidated. PATIENTS AND METHODS: A retrospective multicentric study of all patients (n = 402) with abdominal wall hernia who underwent urgent operations over 1-year period was conducted in ten hospitals. Logistic regression analysis was used to evaluate variables that affect morbidity and mortality. RESULTS: Thirty-five percent of patients had inguinal hernia, 22% femoral hernia, 20% umbilical hernia, and 15% incisional hernia. Mesh repair was used in 92.5% of cases. Intestinal resection was required in 49 patients. Perioperative complications occurred in 130 patients, and 18 patients died (mortality rate 4.5%). Complications and mortality rate were significantly higher in the group of intestinal resection. Patients older than 70 years also showed more complications, required intestinal resection more frequently, and had a higher mortality rate than younger patients. In the logistic regression analysis, age over 70 years, intestinal resection, and American Society of Anesthesiologists (ASA) III/IV class emerged as independent predictors of a poor outcome. Based in our results, we propose a simple schema to calculate risk of death in these patients. CONCLUSION: Using multivariate logistic regression analysis, probabilities of death after complicated abdominal wall hernia surgery are increased in patients with: age over 70 years, high ASA class, and associated intestinal resection. Guidelines should be developed to improve prognosis in these patients.

Hernia estrangulada. ¿Todavía mortal en el siglo XXI? / Strangulated hernia. Still fatal in the XXI century?

Introducción. El conocimiento de los factores que predisponen a la aparición de complicaciones tras cirugía herniaria urgente es de gran importancia tanto para la priorización de la cirugía electiva como para seleccionar los casos que pueden ser susceptibles de seguimiento clínico. Objetivos. Analizar los factores que condicionan la morbilidad y la mortalidad de la resección intestinal asociada a la reparación herniaria urgente. Pacientes y método. Revisión retrospectiva de las historias clínicas de los pacientes intervenidos urgentemente por afección herniaria desde enero de 2000 hasta diciembre de 2005. Se compararon los resultados obtenidos en función de si fue o no necesaria una resección intestinal. Resultados. De un total de 2.367 pacientes intervenidos por hernias en ese período, en 362 (15,3%; media de edad, 69,5 años; 146 varones y 216 mujeres) fue de forma urgente. Precisaron resección intestinal 60 (16,6%). Presentaron complicaciones 108 (29,8%) y 17 (4,7%) fallecieron tras la intervención. El límite de 70 años discriminó una mortalidad significativamente mayor (el 7 frente al 2%, entre mayores y menores de 70 años, respectivamente; p = 0,01). El grupo de pacientes que precisó resección intestinal tenía una media de edad mayor (75,4 frente a 68,3 años; p = 0,002), más prevalencia de complicaciones totales (el 40,7 frente al 6,2%; p < 0,0001) y una mortalidad significativamente mayor (el 20 frente al 1,6%; p < 0,0001). El análisis de discriminación identificó la resección intestinal como variable independiente predictiva de mortalidad (l de Wilks = 0,89; p = 0,0001; valor predictivo del 85%). Conclusiones. La morbilidad y la mortalidad de la cirugía herniaria urgente que precisa resección intestinal son muy elevadas, especialmente en pacientes de edad avanzada y cuando se trata de hernias crurales (AU)

Introduction. Knowledge of the risk factors that may lead to complications after emergency hernia repair is of great importance, as much for the prioritisation of the elective surgery, as selecting those cases that require clinical follow up. Objectives. To analyse the factors conditioning the morbidity and mortality of bowel resection associated to emergency hernia repair. Patients and method. A retrospective review was carried out on the clinical histories of patients who had emergency operations for hernia problems from January 2000 to December of 2005. The clinical results obtained were compared based on whether or not a bowel resection was required. Results. A total of 2367 patients were operated for hernia in this period, 362 of them (15.3%); for a complicated hernia (mean age 69.5 years; 146 males/216 females); 60 patients needed bowel resection. Complications appeared in 108 patients (29.8%) and 17 (4.7%) died after operation. The limit of 70 years discriminated a significantly greater mortality (> 70: 7% vs < 70 2%; p = 0.01).The group of patients who needed bowel resection showed differences in statistical analysis both in age (75.4 vs 68.3 years; p = 0.002), prevalence of complications (40.7% vs 6.2%; p < 0.0001), and mortality (20% vs 1.6%; p < 0.0001). The discriminant analysis identified bowel resection as the only predictive independent variable of mortality (l Wilks = 0.89; p = 0.0001; predictive value, 85%). Conclusions. Morbidity and the mortality of urgent hernia surgery, when bowel resection was required, are elevated; especially in older patients, and in crural hernias (AU)

[Strangulated hernia. Still fatal in the XXI century?]. / Hernia estrangulada. Todavía mortal en el siglo XXI?

INTRODUCTION: Knowledge of the risk factors that may lead to complications after emergency hernia repair is of great importance, as much for the prioritisation of the elective surgery, as selecting those cases that require clinical follow up. OBJECTIVES: To analyse the factors conditioning the morbidity and mortality of bowel resection associated to emergency hernia repair. PATIENTS AND METHOD: A retrospective review was carried out on the clinical histories of patients who had emergency operations for hernia problems from January 2000 to December of 2005. The clinical results obtained were compared based on whether or not a bowel resection was required. RESULTS: A total of 2367 patients were operated for hernia in this period, 362 of them (15.3%); for a complicated hernia (mean age 69.5 years; 146 males/216 females); 60 patients needed bowel resection. Complications appeared in 108 patients (29.8%) and 17 (4.7%) died after operation. The limit of 70 years discriminated a significantly greater mortality (> 70: 7% vs < 70 2%; p = 0.01). The group of patients who needed bowel resection showed differences in statistical analysis both in age (75.4 vs 68.3 years; p = 0.002), prevalence of complications (40.7% vs 6.2%; p < 0.0001), and mortality (20% vs 1.6%; p < 0.0001). The discriminant analysis identified bowel resection as the only predictive independent variable of mortality (lambda Wilks = 0.89; p = 0.0001; predictive value, 85%). CONCLUSIONS: Morbidity and the mortality of urgent hernia surgery, when bowel resection was required, are elevated; especially in older patients, and in crural hernias.