Immediate versus delayed chemotherapy in patients with asymptomatic incurable metastatic cancer

Aim: To examine the evidence of benefit in initiating immediate chemotherapy in patients with newly diagnosed asymptomatic metastatic incurable cancer, compared with delaying chemotherapy until symptomatic progression. Methods: Through an extensive review of published reports, we examined the biological, clinical, psychological and ethical background of the issue and reported on the available clinical trial evidence in a variety of tumor types. Results: Only a limited number of clinical trials have directly examined the role of immediate versus delayed chemotherapy in patients with incurable asymptomatic metastatic cancer. Small studies in mesothelioma, colorectal cancer, breast cancer, myeloma, and low‐grade lymphoma suggest no survival benefit for the immediate initiation of chemotherapy. However, there was no evidence in other tumor types. Conclusion: The appropriate timing of chemotherapy initiation in an asymptomatic patient with metastatic cancer remains a substantial question in oncology. Many factors are likely to impact on the decision. However, little if any evidence demonstrates a clear advantage in the immediate initiation of chemotherapy in this setting.     

奥利司他对肥胖青少年体重和机体组分的影响——随机对照试验

背景：儿童和青少年超重和肥胖正迅速增加。在该人群，单纯行为疗法减肥及维持体重下降的效果有限，但是对药物治疗尚未进行广泛的研究。 目的：确定奥利州他（Orlistat）在青少年体重治疗方面的效果及其安个性。 设计、地点和病例：于美国和加拿大32个中心、539例肥胖青少年（12—16岁；体重指数[body mass index，BMI]在第95百分化之上≥2单位）进行的多ln0、54剧（2000年8月至2002年10月）随机双盲研究。 干预：给予奥利司他（n=357）或安慰剂（n=182）120mg，每口3次，持续1年；加适度低热卡饮食（脂肪占30％）、运动和行为治疗。 主要观察指标：BMI变化；二级指标包括腰围和髋用、体重下降、脂质测量以及机体对口服葡萄糖的血糖和胰岛素反心。 结果：至12周时，两组BMI均有下降；此后，奥利司他组体重维持稳定而安慰剂组则超过基线。研究结束时，奥利司他组BMI下降0．55。而安慰剂组则增加0．31（P=0．001）。与安慰剂组的15．7％相比，奥利司他组26．5％的病例BMI下降≥5％（P=0．005）；BMI下降≥10％者分别为4．5％和13．3％（P=0．002）。在研究结束时，奥利司他组体重增加0．53kg，安慰剂组增加3．14kg（P〈0．001）。双能X线吸收测量娃示，这种差异可用脂肪体再的变化解释。奥利司他组腰围下降，安慰剂组腰围上升（-1．33cm比＋0．12cm；P〈0．05）。奥利司他组发生轻至中度胃肠道不良事件者为9％-50％，安慰剂组为1％～13％。 结论：与安慰剂比较，奥利司他与饮食、运动和行为改善联合可显著改善肥胖青少年体重的治疗。在这个青少年人群，连续使用奥利司他1年并无重要安全问题，尽管奥利司他组胃肠道不良事件较为常见。     

Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate.

This study evaluated factors influencing fracture (n = 197) and osteotomy (n = 200) healing in children with moderate to severe OI. Pamidronate treatment was associated with delayed healing after osteotomy, but not after fracture. The data suggest that both pamidronate and mechanical factors influence bone healing in this cohort. INTRODUCTION: Intravenous pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). However, the effect of this treatment on bone healing is not well characterized. We therefore retrospectively analyzed the healing of lower limb fractures and osteotomies in children with moderate to severe OI, both before and after the start of pamidronate treatment. MATERIALS AND METHODS: Bone healing was evaluated on standard radiographs after 197 lower limb fractures (132 femur and 65 tibia) in 82 patients (age at fracture, 0.0-19.9 years) and 200 intramedullary rodding procedures in 79 patients (age at surgery, 1.2-19.8 years). Delayed healing was diagnosed when a fracture or osteotomy line was at least partially visible 12 months after the event. RESULTS: Delayed fracture healing was observed more frequently during than before pamidronate treatment. However, the effect of pamidronate was no longer significant when age differences were taken into account (odds ratio [OR], 1.76; 95% CI, 0.61-5.10). Better mobility status was a strong independent predictor of delayed healing after fractures that occurred during pamidronate treatment. After osteotomies, delayed healing was more frequent when pamidronate had been started before surgery (OR, 7.29; 95% CI, 2.62-20.3), and this effect persisted after adjustment for multiple confounders. During pamidronate treatment, older age (OR per year of age, 1.25; 95% CI, 1.06-1.47) and osteotomy of the tibia (OR, 3.51; 95% CI, 1.57-7.82) were independent predictors of delayed healing. CONCLUSIONS: This study suggests that pamidronate therapy is associated with delayed healing of osteotomy sites after intramedullary rodding procedures. Better mobility status, but not pamidronate treatment, seems to be predictive of delayed healing after fractures.     

The emerging role of induced hypothermia in the management of acute stroke.

Current treatment of acute stroke remains unsatisfactory. This review presents experimental and clinical data which suggest that mild induced hypothermia could be a potent and practicable neuroprotective treatment of acute ischaemic stroke and intracerebral haemorrhage. Hypothermia, if proven to be safe, effective and widely practicable in patients with acute stroke, could have an enormous positive impact on reducing the burden of stroke worldwide. Critical issues that will need to be considered in a well designed randomised controlled trial of induced hypothermia in acute stroke patients are discussed.     

GnRH receptor signalling to ERK: kinetics and compartmentalization.

Many hormones, neurotransmitters and growth factors influence their target cells by activation of mitogen-activated protein kinase cascades. The consequences of such activation reflect not only the magnitude, but also the kinetics and cellular compartmentalization of kinase activity. Gonadotropin-releasing hormone (GnRH) receptors are seven-transmembrane receptors that have undergone a period of rapidly accelerated molecular evolution in which the advent of type I mammalian GnRH receptors has been associated with the loss of the carboxyl-terminal tail, a structure present in all other seven-transmembrane receptors. Here, we review spatiotemporal aspects of extracellular-signal-regulated kinase activation by gonadotropin-releasing hormone receptors, emphasizing how the absence or presence of the carboxyl-terminal tail dictates the receptors' ability to engage and signal via arrestins.     

Coronary venous retroperfusion of arterial blood for the treatment of acute myocardial ischemia

Synchronized coronary venous retroperfusion of autologous arterial blood was offered to patients referred for medically refractory unstable angina or evolving myocardial infarction with contraindications to thrombolytic therapy. Primary endpoints of angina, ST segment deviation, and two-dimensional echocardiographic systolic wall motion were followed to determine the efficacy of retroperfusion in patients prior to and then during angioplasty, surgical intervention, or pharmacological management, as the clinical picture warranted. Over a 12 month period, 21 patients were referred and 15 received retroperfusion. All experienced full relief of angina (p = 0·008). ST segment deviations and systolic wall motion of ischemic zones were observed to improve (p = 0·06 ST changes; p = 0·0001 wall motion changes) with synchronized retrograde perfusion. During attempts to remove patients from retroperfusion, statistically significant (p < 0·01) reproducible changes in these same endpoints were documented. Retroperfusion appears to improve acute myocardial ischemia. This technique functions well in the intensive care unit environment with only fluoroscopy as technical imaging support.     

Total shoulder replacement

It appears that total shoulder replacement can be performed with a high degree of patient satisfaction, with few complications, and with long-term results which certainly appear to rival the success of other arthroplasties. However, the technique is extremely demanding and requires an experienced shoulder surgeon, who must successfully resolve numerous intraoperative variables and problems, must be able to deal with factors which may affect the stability and strength of the implant, and must individualize the postoperative rehabilitation according to quality of bone and soft tissue, as well as the specific needs and desires of the patient. However, when performed technically satisfactorily with proper patient selection, with meticulous attention to the details of the soft tissue surrounding the implant, and with attention to the postoperative rehabilitation, the results have been impressive. Total shoulder replacement has successfully taken its place in the armamentarium of other total joint replacements which have dramatically altered the quality of life in the arthritic patient.