BACKGROUND & AIMS: :A number of competing risks and benefits influence the rates of neonatal morbidity and mortality in elective cesarean delivery versus expectant management. To compare these rates, we developed complex decision trees to model the expected outcomes among hypothetical cohorts of 1,000,000 uncomplicated pregnancies undergoing elective cesarean delivery versus 1,000,000 comparable pregnancies undergoing routine pregnancy management. A separate tree was created for each complication, including neonatal death, respiratory morbidity, intracranial hemorrhage, and brachial plexus injury. We found that neonatal mortality was increased among elective cesarean deliveries, but perinatal mortality was higher with routine expectant management due to fetal deaths. Respiratory morbidity was substantially more common among infants delivered by elective cesarean delivery, whereas intracranial hemorrhage and brachial plexus injury were less common. We conclude that the fetal/neonatal impact of elective cesarean is mixed, but any improvement in perinatal health is likely to be small.

背景与目标： : 在选择性剖宫产与预期管理中，许多竞争性风险和收益会影响新生儿的发病率和死亡率。为了比较这些比率，我们开发了复杂的决策树来模拟假设队列中的预期结果，这些队列中的1,000,000例非复杂妊娠接受选择性剖宫产，而1,000,000例可比妊娠接受常规妊娠管理。为每种并发症 (包括新生儿死亡，呼吸系统疾病，颅内出血和臂丛神经损伤) 创建了单独的树。我们发现，选择性剖宫产分娩的新生儿死亡率增加，但由于胎儿死亡，常规预期治疗的围产期死亡率更高。在择期剖宫产分娩的婴儿中，呼吸系统的发病率明显更高，而颅内出血和臂丛神经损伤则较少见。我们得出的结论是，选择性剖宫产对胎儿/新生儿的影响是混合的，但是围产期健康的任何改善都可能很小。

BACKGROUND & AIMS: OBJECTIVE:A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and should alert the patient and physician to the possibility of underlying skeletal fragility. Therefore, the establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for the patients who suffer from osteoporosis. The objective of the present study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to assess the change of BMD at the distal radius in early postmenopausal women who receive hormone replacement therapy (HRT). METHODS:Twenty healthy early postmenopausal women who were diagnosed as osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin, deoxypyridinoline) every 6 months. RESULTS:The placebo group showed a significant decrease from the baseline in the trabecular BMD of the radius at 12 months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and placebo groups were statistically different at 12 months (p<0.05). On the other hand, in the cortical BMD of the radius, no significant differences were seen between the changes of bone densities in the HRT and control groups after 1 year of treatment. pQCT could detect a significant loss of BMD of the radius in early postmenopausal women after 1 year and HRT prevented its loss. CONCLUSION:Our preliminary clinical trial showed that pQCT might be useful for the early detection of bone loss in early postmenopausal women and for the monitoring BMD of the patients who receive HRT.

背景与目标：

BACKGROUND & AIMS: :There is a substantial need for a diagnostic tool to aid in the early diagnosis of heart failure and in the recognition of those at risk for its development, as well as in guidance of therapy. Testing for amino-terminal pro-brain natriuretic peptide (NT-proBNP) has been recognized to have utility in the diagnosis, prognosis and management of heart failure. In addition, numerous other applications for NT-proBNP testing are now recognized, such as evaluation of patients with heart disease in the absence of heart failure, as well as the diagnostic and prognostic evaluation of patients with acute coronary syndromes or pulmonary thromboembolism.

背景与目标： : 迫切需要一种诊断工具来帮助早期诊断心力衰竭，识别有发展风险的人以及指导治疗。氨基末端脑钠肽前体 (NT-proBNP) 的检测已被认为可用于心力衰竭的诊断，预后和管理。此外，NT-proBNP检测的许多其他应用现已得到认可，例如在没有心力衰竭的情况下评估心脏病患者，以及对急性冠状动脉综合征或肺血栓栓塞患者的诊断和预后评估。

BACKGROUND & AIMS: OBJECTIVE:To present a case of selective arterial embolization for the treatment of placenta increta in a patient with subsequent pregnancy. DESIGN:Case report and literature review. SETTING:Community-based hospital. PATIENT(S):A 31-year-old G2P1 woman with placenta increta presenting with delayed postpartum hemorrhage. INTERVENTION(S):Selective uterine artery embolization. MAIN OUTCOME MEASURE(S):Cessation of uterine hemorrhage, future pregnancy. RESULT(S):The patient's uterine bleeding immediately resolved. She subsequently delivered a healthy neonate at term without recurrence of abnormal placentation. CONCLUSION(S):Arterial embolization is effective for treating placenta increta in women who wish to preserve fertility. A review of the literature demonstrates a 76.9% success rate and an 11% complication rate.

背景与目标：

BACKGROUND & AIMS: :Many aspects of ventilatory management in patients with ARDS are still controversial and one of the major controversies is should HFO or CMV ideally be used to manage this patients. As shown by David et al. when the two approaches to ventilatory support are applied using similar principles the physiologic outcomes appear to be similar. With both approaches the use of lung recruitment maneuvers early in ARDS (1 to 3 day) after hemodynamic stabilization in patients without baratrauma is promising. The key to managing ARDS regardless of mode is to use an open lung protective ventilatory strategy. It is not the mode that makes the difference, it is the approach used to apply the mode!

背景与目标： : ARDS患者通气管理的许多方面仍然存在争议，主要争议之一是是否应理想地使用HFO或CMV来管理该患者。如David等人所示。当使用相似的原理应用两种通气支持方法时，生理结果似乎是相似的。对于两种方法，在没有baratrauma的患者中，在血流动力学稳定后的ARDS早期 (1至3天) 使用肺募集动作是有希望的。无论哪种模式，管理ARDS的关键是使用开放的肺保护性通气策略。与众不同的不是模式，而是用于应用模式的方法!

BACKGROUND & AIMS: :The transphenoidal procedure has become the preferred approach in the surgical management of sellar/parasellar tumors. Nevertheless, specific indications remain for the transcranial approach and the objective of this review is to evaluate the available data on outcomes following transcranial or transphenoidal approaches to sellar/parasellar tumors. We assess the indications used for each approach and parameters that favor one over the other. Factors such as tumor size, consistency and configuration are important variables in choosing the transcranial approach. Other important considerations include persistent visual loss after incomplete decompression via the transphenoidal route, ectatic midline carotid arteries, co-existent intracranial aneurysms and sphenoid sinusitis. We review the data on visual and endocrinological outcomes following the transcranial or transphenoidal approach and provide an argument that, while there appears to be a trend towards greater visual improvement after transcranial surgery for large-to-giant pituitary adenomas, this benefit is offset by a greater risk of postoperative pituitary dysfunction. There is no difference in the rate of recurrence between the two procedures in the published literature. Overall, craniotomies will continue to play a role in the management of patients with sellar/parasellar tumors, although patient selection and careful preoperative evaluation are key elements in choosing the most appropriate approach.

背景与目标： : 经蝶手术已成为鞍区/鞍旁肿瘤外科治疗的首选方法。尽管如此，经颅入路仍有特定的适应症，本综述的目的是评估经颅或经颅入路治疗鞍侧/鞍旁肿瘤后结果的可用数据。我们评估每种方法所使用的指示以及有利于另一种方法的参数。肿瘤大小，一致性和构型等因素是选择经颅入路的重要变量。其他重要的考虑因素包括通过经蝶入路不完全减压后持续的视力丧失，扩张中线颈动脉，并存的颅内动脉瘤和蝶窦炎。我们回顾了经颅或经蝶入路后的视觉和内分泌结果数据，并提出了一个论点，即尽管大到巨大垂体腺瘤经颅手术后似乎有更大的视觉改善趋势，但这种益处被术后垂体功能障碍的更大风险所抵消。在已发表的文献中，两种手术的复发率没有差异。总体而言，开颅手术将继续在鞍/鞍旁肿瘤患者的治疗中发挥作用，尽管患者选择和仔细的术前评估是选择最合适方法的关键因素。

BACKGROUND & AIMS: A 53-year-old man was admitted to the hospital for management of pneumonia and a giant fluid-filled bulla. He appeared acutely ill and had persistent fever despite prolonged therapy with parenteral antibiotics and aggressive bronchial drainage. Percutaneous placement of an 8.5F catheter into the bulla enabled drainage of both fluid and air within the bulla and led to resolution of his symptoms within 24 h. This report demonstrates that drainage of giant fluid-filled bullae may lead to rapid resolution of symptoms and describes a novel management technique for this condition.

背景与目标： 一名53岁的男子因治疗肺炎和巨大的充满液体的bulla而入院。尽管长期使用肠胃外抗生素治疗和积极的支气管引流，但他似乎病情严重，并持续发热。将8.5F导管经皮放置到大疱中，可以在大疱中排出液体和空气，并在24小时内缓解症状。该报告表明，巨大的充满液体的大疱的引流可能会导致症状的快速解决，并描述了一种针对这种情况的新颖管理技术。

BACKGROUND & AIMS: :With the increased incidence of terrorism worldwide, it is important for surgeons to understand the role of shrapnel injury in mass casualty events. Several diagnostic modalities are available, including plain radiography, computed tomography, ultrasound, angiography, and computerized surgical navigation based on real-time acquisition of fluoroscopic data. Shrapnel management techniques are selected based on the following chronologic phases: acute, subacute, and late.

背景与目标： : 随着全世界恐怖主义发生率的增加，对于外科医生来说，了解弹片损伤在大规模伤亡事件中的作用非常重要。有几种诊断方式可用，包括平片，计算机断层扫描，超声，血管造影和基于实时获取荧光镜数据的计算机手术导航。弹片管理技术是根据以下时间顺序选择的: 急性，亚急性和晚期。

BACKGROUND & AIMS: :Our knowledge about, and the availability of, orthobiologic materials has increased exponentially in the last decade. Although previously confined to the experimental or animal-model realm, several orthobiologics have been shown to be useful in a variety of clinical situations. As surgical techniques in vascular anastomosis, soft-tissue coverage, limb salvage, and fracture stabilization have improved, the size and frequency of bony defects (commensurate with the severity of the initial injury) have increased, as well. Because all methods of managing segmental bony defects have drawbacks, a need remains for a readily available, void-filling, inexpensive bone substitute. Such a bone substitute fulfills a permissive role in allowing new bone to grow into a given defect. Such potential osteoconductive materials include ceramics, calcium sulfate or calcium phosphate compounds, hydroxyapatite, deproteinized bone, corals, and recently developed polymers. Some materials that have osteoinductive properties, such as demineralized bone matrix, also display prominent osteoconductive properties.

背景与目标： : 在过去的十年中，我们对正交生物材料的了解和可用性呈指数增长。尽管以前仅限于实验或动物模型领域，但已显示几种原位生物制剂在各种临床情况下均有用。随着血管吻合，软组织覆盖，肢体挽救和骨折稳定方面的外科手术技术的改善，骨缺损的大小和频率 (与初始损伤的严重程度相称) 也增加了。由于所有处理节段性骨缺损的方法都有缺点，因此仍然需要一种容易获得的，填充空隙的，廉价的骨替代品。这种骨替代物在允许新骨长成给定的缺损方面发挥了允许的作用。此类潜在的骨传导材料包括陶瓷，硫酸钙或磷酸钙化合物，羟基磷灰石，脱蛋白骨，珊瑚和最近开发的聚合物。一些具有骨诱导特性的材料，如脱矿质骨基质，也显示出突出的骨传导特性。

BACKGROUND & AIMS: Marked increases in case rates of drug-resistant tuberculosis and nontuberculous mycobacterial infections have brought renewed urgency to the development of new treatment regimens for mycobacterial infections. Preclinical data, such as in vitro measures of drug activity and pharmacokinetics, are used in the design of new treatment regimens. This review surveys the extensive published clinical experience concerning the treatment of drug-susceptible tuberculosis to evaluate the use of these preclinical measures in predicting clinical outcomes of antimycobacterial therapy. In vitro measures of drug activity predict the potency of a drug to prevent the emergence of resistance to other antimycobacterial drugs but do not predict the sterilizing activity of a drug or the activity of drug combinations. In vitro measures of drug activity do not allow reliable predictions of the level at which an organism should be considered resistant. Assays of drug penetration in tissues and activity against intracellular bacilli add modestly to the predictive value of in vitro measures of drug activity but still do not predict sterilizing activity. In contrast, animal models of tuberculosis have predicted relative drug potency (including sterilizing activity), the efficacy of multidrug regimens, and the duration of therapy needed. Despite pharmacokinetic parameters that would suggest the need for multiple doses per day, all of the first-line antituberculous drugs are active when given as infrequently as twice weekly. It is difficult to predict the efficacy of therapy for an intracellular pathogen that has the capacity for dormancy. Better in vitro models are needed, particularly ones that predict sterilizing activity.

背景与目标： 耐药结核病和非结核分枝杆菌感染的病例率显着增加，为开发新的分枝杆菌感染治疗方案带来了新的紧迫性。临床前数据，例如药物活性和药代动力学的体外测量，用于设计新的治疗方案。这篇综述调查了有关药物敏感结核病治疗的广泛已发表的临床经验，以评估这些临床前措施在预测抗细菌治疗临床结果中的应用。药物活性的体外测量可以预测药物的效力，以防止对其他抗细菌药物的耐药性出现，但不能预测药物的灭菌活性或药物组合的活性。药物活性的体外测量无法可靠地预测生物体应被认为具有抗性的水平。药物在组织中的渗透和对细胞内杆菌的活性的测定适度增加了药物活性的体外测量的预测值，但仍不能预测灭菌活性。相反，结核病的动物模型已经预测了相对的药物效力 (包括灭菌活性)，多药疗法的功效以及所需的治疗持续时间。尽管药代动力学参数表明每天需要多次剂量，但所有一线抗结核药物在每周两次的情况下均具有活性。很难预测具有休眠能力的细胞内病原体的治疗效果。需要更好的体外模型，尤其是可以预测灭菌活性的模型。

BACKGROUND & AIMS: :Differential killing of the patient's cancer cells versus normal cells is a necessity for chemotherapy. Advantage can be taken of close regulations of gene expression and of enzyme activity that are essential for normal cell functioning, and that are altered during tumor progression. Summarized here is our research on four such progression changes of cancer cells; some deregulate proliferation control and others decrease programmed death (apoptosis). These processes will be illustrated with examples of potential chemotherapies based on them. Methods for discovery of such changes include Differential Display and microarrays.

背景与目标： : 对患者癌细胞与正常细胞的差异杀伤是化疗的必要条件。可以利用基因表达和酶活性的密切调节，这些调节对于正常细胞功能至关重要，并且在肿瘤进展过程中会发生改变。这里总结了我们对癌细胞四种此类进展变化的研究; 一些放松增殖控制，另一些减少程序性死亡 (凋亡)。这些过程将通过基于它们的潜在化学疗法的示例进行说明。发现这种变化的方法包括差分显示和微阵列。

BACKGROUND & AIMS: BACKGROUND:Although the benefit of thrombolytic therapy in reducing mortality in acute myocardial infarction is well established, the types of bleeding and risk factors for bleeding are less well described in large trials.

METHODS AND RESULTS:We analyzed the baseline characteristics, outcomes, and incidence of bleeding by location, severity, and treatment assignment among 41,021 patients in the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903 patients for whom there were complete data, 1.2% suffered severe bleeding and 11.4% experienced moderate hemorrhage at a variety of sites. The most common sources of bleeding were procedure related. The thrombolytic regimen was strongly related to the incidence of bleeding; comparatively more bleeding was seen with the therapies of streptokinase plus intravenous heparin and the streptokinase and tissue plasminogen activator plus intravenous heparin combination. In multivariate analysis, the four most powerful independent predictors of hemorrhage were older age, lighter body weight, female sex, and African ancestry; they remained the most important predictors of bleeding when multivariate analysis was performed on patients who did not undergo invasive procedures. The presence of serious hemorrhage was associated with other undesirable outcomes (recurrent events, left ventricular dysfunction, arrhythmia, or stroke).

CONCLUSIONS:Important predictors of bleeding in this population are increased age, lighter weight, female sex, African ancestry, and experiencing invasive procedures. Other nonhemorrhagic adverse clinical outcomes were associated with moderate and severe bleeding, which was in turn associated with increased length of hospital stay and mortality at 30 days.

背景与目标： 背景 : 尽管溶栓治疗在降低急性心肌梗死死亡率方面的益处已得到充分证实，但在大型试验中，出血类型和出血危险因素的描述较少。
方法和结果 : 在GUSTO-I急性心肌梗死溶栓试验中，我们分析了41,021名患者的基线特征，结局和出血发生率，按位置，严重程度和治疗分配。在40,903例有完整数据的患者中，1.2% 例严重出血，11.4% 例在不同部位出现中度出血。最常见的出血来源与手术有关。溶栓方案与出血发生率密切相关; 链激酶加静脉肝素以及链激酶和组织型纤溶酶原激活剂加静脉肝素联合治疗的出血相对较多。在多变量分析中，出血的四个最有效的独立预测因子是年龄较大，体重较轻，女性和非洲血统; 当对未接受侵入性操作的患者进行多变量分析时，它们仍然是出血的最重要预测因子。严重出血的存在与其他不良结果 (复发事件，左心室功能障碍，心律失常或中风) 相关。
结论 : 该人群出血的重要预测因素是年龄增加，体重减轻，女性，非洲血统，经历侵入性手术。其他非出血性不良临床结局与中度和重度出血相关，而中度和重度出血又与30天时的住院时间和死亡率增加相关。

BACKGROUND & AIMS: PURPOSE:A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues. EXPERIMENTAL DESIGN:Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models. RESULTS:Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (

BACKGROUND & AIMS: :Passive immunity against gastrointestinal infections has recently been successfully applied as prophylaxis and therapy in patients in a variety of virally and bacterially induced infections. Campylobacter jejuni is frequently associated with acute diarrhoea in humans, and several species of animals have been shown to transmit the disease, although birds have been implicated as the main source of infection. We used bovine and chicken immunoglobulin preparations from the milk and eggs, respectively, of immunized animals for prophylactic and therapeutic treatment of chickens infected with C. jejuni. A marked prophylactic effect (a >99% decrease in the number of bacteria) was noted using either antibody preparation, whereas the therapeutic efficacy, i.e. when antibodies were given after the infection was established, was distinctly lower (80-95%) as judged by faecal bacterial counts. These observations may serve as a starting point for experiments aimed at elimination of the infection in an industrial or farm setting. It may also encourage future attempts to treat, prophylactically or therapeutically, patients with Campylobacter-induced diarrhoea.

背景与目标： : 针对胃肠道感染的被动免疫最近已成功地应用于各种病毒和细菌诱导感染的患者的预防和治疗。空肠弯曲菌经常与人类急性腹泻有关，尽管鸟类是主要传染源，但已显示几种动物可以传播这种疾病。我们分别使用免疫动物的牛奶和鸡蛋中的牛和鸡免疫球蛋白制剂对感染空肠杆菌的鸡进行预防和治疗。使用任一种抗体制剂观察到显著的预防效果 (细菌数量99% 减少)，而治疗效果，即当在感染建立后给予抗体时，如通过粪便细菌计数判断，明显较低 (80-95%)。这些观察结果可以作为旨在消除工业或农场环境中感染的实验的起点。它还可能鼓励将来尝试预防或治疗弯曲杆菌引起的腹泻患者。

BACKGROUND & AIMS: OBJECTIVES:Cases of hypophosphataemia (often coincident with renal dysfunction) have been reported in HIV-infected patients taking tenofovir disoproxil fumarate (TDF), but randomized placebo-controlled trials of HIV-infected persons with normal baseline renal function have found a comparable incidence of hypophosphataemia in the TDF and placebo groups. We assessed the incidence of grade 2 and higher hypophosphataemia in the HIV Outpatient Study (HOPS). METHODS:We analysed a prospective cohort of patients who initiated either a TDF-containing highly active antiretroviral therapy (HAART) regimen [TDF-exposed (TDF+) group; n = 165] or a TDF-sparing HAART regimen [TDF-unexposed (TDF-) group; n = 90], and who had normal baseline phosphate and creatinine values. RESULTS:The TDF+ and TDF- groups had comparable median follow-up times (10.9 vs 8.8 months, respectively; P = 0.18) and number of phosphate measurements (median = 3 for both) and were similar on most clinical and demographic factors. During follow up, 12.7% of TDF+vs 6.7% of TDF-patients developed grade 2 hypophosphataemia (2.0-2.4 mg/dL), and 2.4% of TDF+ patients vs 0% of TDF-patients developed grade 3 hypophosphataemia (1.0-1.9 mg/dL); none developed grade 4 hypophosphataemia (<1.0 mg/dL). The incidence of grade 2 or higher hypophosphataemia was 16.7 per 100 person-years among TDF+ patients vs 8.0 per 100 person-years among TDF-patients (P = 0.11). CONCLUSIONS:The incidence of hypophosphataemia was somewhat elevated in HOPS patients who took TDF-containing HAART compared with those who took TDF-sparing HAART during the first 1 to 2 years of observation, but the difference was not statistically significant. Longer follow-up of a larger population is needed to determine if this trend towards an association achieves statistical significance and to evaluate the clinical consequences of hypophosphataemia.

背景与目标：