Measurement and validation of frailty as a predictor of outcomes in women undergoing major gynaecological surgery.

OBJECTIVE: Frailty is the loss of physical or mental reserve that impairs function, often in the absence of a defined comorbidity. Our aim was to determine whether a modified frailty index (mFI) correlates with morbidity and mortality in patients undergoing hysterectomy. DESIGN: Retrospective cohort study. SETTING: Hospitals across the USA participating in the National Surgical Quality Improvement Program (NSQIP). SAMPLE: Patients who underwent hysterectomy from 2008 to 2012. METHODS: An mFI was calculated using 11 variables in NSQIP. The associations between mFI and morbidity and mortality were assessed. Model fit statistics (c-statistics) were utilised to evaluate the ability of mFI to distinguish outcomes. MAIN OUTCOME MEASURE: Wound infection, severe complications and mortality. RESULTS: A total of 66 105 patients were identified. Wound complications increased from 2.4% in patients with an mFI of zero to 4.8% in those with mFI ≥ 0.5 (P < 0.0001). Similarly, severe complications increased from 0.98% to 7.3% (P < 0.0001), overall complications rose from 3.7% to 14.5% (P < 0.0001) and mortality increased from 0.06% to 3.2% (P < 0.0001) for patients with a frailty index of zero compared with those with an index of ≥ 0.5. Versus chance, the goodness-of-fit c-statistics suggested that mFI increases the ability to detect wound complications by 11.4%, severe complications by 22.0% and overall complications by 11.0%. CONCLUSIONS: The mFI is easily reproducible from routinely collected clinical data and predictive of outcomes in patients undergoing hysterectomy. Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery. TWEETABLE ABSTRACT: Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery.

Correlation electron cyclotron emission diagnostic and improved calculation of turbulent temperature fluctuation levels on ASDEX Upgrade.

A newly upgraded correlation electron cyclotron emission (CECE) diagnostic has been installed on the ASDEX Upgrade tokamak and has begun to perform experimental measurements of electron temperature fluctuations. CECE diagnostics measure small amplitude electron temperature fluctuations by correlating closely spaced heterodyne radiometer channels. This upgrade expanded the system from six channels to thirty, allowing simultaneous measurement of fluctuation level radial profiles without repeat discharges, as well as opening up the possibility of measuring radial turbulent correlation lengths. Newly refined statistical techniques have been developed in order to accurately analyze the fluctuation data collected from the CECE system. This paper presents the hardware upgrades for this system and the analysis techniques used to interpret the raw data, as well as measurements of fluctuation spectra and fluctuation level radial profiles.

Ventricular arrhythmias and K+ transfer during myocardial ischemia and intervention with procaine amide, insulin, or glucose solution.

To assess the relation of ventricular arrhythmias to myocardial K(+) movement during ischemia, we placed an electrode catheter in the left anterior descending coronary artery for thrombus production in intact anesthetized dogs. (85)Kr injections distal to the thrombus permitted serial coronary blood flow measurements. Animals of Group I with a moderate flow reduction exhibited no arrhythmia or myocardial egress of K(+). In Group II, marked flow reduction was accompanied by an injury potential and loss of K(+) from the ischemic site, before and during ventricular tachycardia. Therapeutic interventions were performed in animals having the same degree of ischemia as Group II. Systemic procaine amide in Group III interrupted the tachycardia and egress of K(+), despite persistent ischemia. Group IV did not respond to intracoronary insulin with K(+) uptake, as did normal dogs, and progressed to fibrillation. During the production of hyperglycemia in Group V, myocardial loss of K(+) ceased with maintenance of sinus rhythm. Hemodynamic factors did not appear to have a major role in the genesis of the arrhythmia.Since intracoronary infusion of K(+) in normal dogs similarly altered repolarization and produced fibrillation, it would appear that during ischemia egress of K(+) before development of the arrhythmia indicates a major role of the ion in pathogenesis. This view is supported by the myocardial loss of K(+) and arrhythmia induced in normal dogs by strophanthidin and by the fact that pharmacologic regulation of K(+) loss is associated with correction of the arrhythmia, despite persistence of low blood flow.

Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells.

Signal transducers and activators of transcription (STATs) are transcription factors activated in response to cytokines and growth factors. Constitutively active Stat3 has been shown to mediate oncogenic transformation in cultured cells and induce tumor formation in mice. An increasing number of tumor-derived cell lines as well as samples from human cancer have been reported to express constitutively active Stat3 protein. We previously demonstrated that ovarian cancer cell lines express high levels of constitutively active Stat3. In this study, we show that inhibition of the Stat3 signaling pathway using the Janus Kinase-selective inhibitor, AG490, and a dominant negative Stat3 (Stat3beta) significantly suppresses the growth of ovarian and breast cancer cell lines harboring constitutively active Stat3. In the ovarian cancer cell lines, AG490 also diminished the phosphorylation of Stat3, Stat3 DNA binding activity, and the expression of Bcl-x(L). Further, AG490 induced significant apoptosis in ovarian and breast cancer cell lines expressing high levels of constitutively active Stat3 but had a less profound effect on normal cells lacking constitutively active Stat3. AG490 also enhanced apoptosis induced by cisplatin in ovarian cancer cells. These results suggest that inhibition of Stat3 signaling may provide a potential therapeutic approach for treating ovarian and breast cancers.

Ischemic heart failure: sustained inotropic response to small doses of I-epinephrine without toxicity.

As a prelude to a study of severe ischemic heart failure, the therapeutic response of the ischemic ventricle to epinephrine and acetylstrophanthidin in nontoxic doses was determined in 24 intact anesthetized dogs undergoing a first episode of acute regional ischemia. A thrombotic obstruction was produced in the left ventricular dysfunction. The elevation of end-diastolic pressure and reduced stroke volume in control dogs were not significantly altered by administration of strophanthidin. Epinephrine (0.05 mug/kg per min) elicited a significant reduction in end-diastolic pressure and increase in stroke volume. The latter was not attended by an increased incidence of ventricular fibrillation, whereas fibrillation occurred in half of the group given strophantihidin. Thus, the catecholamine was selected to study pump failure. Severe ischemic heart failure was assessed in two groups with scar from previous infarction for up to 4 hours. By 60 minutes of ischemia the increase in end-diastolic pressure and volume and decrease in stroke volume and ejection fraction were comparable in both groups. Thereafter, alternate animals received small doses of epinephrine (0.05 to 0.15 mug/kg per min) with graded increments at 60 minute intervals to counter tachyphylaxis and findings were compared with those in control dogs. Over the subsequent 3 hours, there was progressive deterioration of left anterior descending coronary artery, affecting ventricular function in the untreated group with an increase in end-diastolic pressure from 10 plus or minus 1 to 33 plus or minus 2.4 mm Hg. End-diastolic volume increased by 63 percent; stroke volume and ejection fraction decreased by 48 and 66 percent, respectively. The infusion of epinephrine was attended by a significantly lower end-diastolic pressure of 20 plus or minus 2.5 mm Hg, whereas end-diastolic volume, stroke volume and ejection fraction were restored to control levels after 4 hours of ischemia. Mortality in the untreated group was 62 percent by 4 hours; all seven animals in the treated group survived.

Prolonged presence of metabolite in urine after compulsive cocaine use.

The authors studied the pattern of benzoylecgonine excretion in 35 male veterans who had recently used large amounts of cocaine. Following admission to a drug-free environment, the veterans completed a short structured interview and gave daily urine samples for benzoylecgonine analysis. Eleven (31.4%) patients excreted benzoylecgonine at levels of 300 ng/mL or above for 120 hours or longer after admission. Eight (22.9%) patients whose enzyme-multiplied immunoassay test results were negative subsequently tested positive. These findings corroborate recent case reports of prolonged presence of benzoylecgonine in the urine and have important implications for drug treatment programs.

A clinical comparison of Technegas and xenon-133 in 50 patients with suspected pulmonary embolus.

A comparison of "Technegas" and xenon-133 was performed in 50 patients presenting with a clinical diagnosis of pulmonary embolus. All patients underwent studies with xenon inhalation, Technegas inhalation, and macroaggregated albumin perfusion. Technegas is a new ultrafine ventilatory agent with a particle size of 50 to 200A produced from technetium pertechnetate and graphite in an argon environment. Although particulate in nature, Technegas is transported and diffuses like a gaseous agent. Its production results in a high specific activity yield with high efficiency. There is no significant deposition in the central airways, and good peripheral visualization of the lung is obtained. The study was designed to assess whether Technegas could be used as a ventilatory agent to obtain high-quality diagnostic images. All studies were reported as in normal clinical practice, and no statistical analysis was performed. The aim of the study was simply to see what role Technegas had in a busy clinical department and how well it reflected ventilation by comparison with xenon. Patient compliance with Technegas was 100 percent and for xenon was 94 percent. Technegas enables one to obtain high-quality ventilatory images and has an important role to play in the assessment of pulmonary ventilation.

Detoxification with phenobarbital of alprazolam-dependent polysubstance abusers.

Alprazolam appears to have an abuse liability among opiate addicts, and detoxification can be prolonged. The authors describe experience with five methadone maintenance patients who were polysubstance abusers and were admitted specifically for detoxification from alprazolam dependence. Phenobarbital in tapering doses adequately suppressed withdrawal symptoms and shortened hospitalization.

The preceptorship, an integral unit of the curriculum in community and family medicine.

A curriculum in community and family medicine at the University of Massachusetts Medical School, planned to include a primary care preceptorship as an integral unit, is described. The curriculum has been planned to allow for repeated and increasing exposure of medical students during their undergraduate years to a variety of health care settings within the state. An extensive program of courses is required for all students and consists of a three-week field clerkship in the first year, a field-oriented epidemiology course in the second year, and a six-week field clerkship in the third or fourth year. A preceptorship elective is available to all medical students after they have completed their first two years. Field visits by community and family medicine faculty to the preceptorship site provide overall guidance, facilitate the implementation of objectives, and provide opportunities to strengthen bonds between the practicing physicians of the Commonwealth of Massachusetts and the state medical school. The results to date are discussed.