Comparative associations of baseline frailty status and age with postoperative mortality and duration of hospital stay following metastatic brain tumor resection

Metastatic brain tumors are the most common intracranial neoplasms diagnosed in the United States. Although baseline frailty status has been validated as a robust predictor of morbidity and mortality across various surgical disciplines, evidence within cranial neurosurgical oncology is limited. Adult metastatic brain tumor patients treated with resection were identified in the National Inpatient Sample during the period of 2015–2018. Frailty was quantified using the 11-point modified frailty index (mFI-11) and its association with clinical endpoints was evaluated through complex samples multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. Among 13,650 metastatic brain tumor patients identified (mean age 62.8 years), 26.8% (n?=?3665) were robust (mFI?=?0), 31.4% (n?=?4660) were pre-frail (mFI?=?1), 23.2% (n?=?3165) were frail (mFI?=?2), and 15.8% (n?=?2160) were severely frail (mFI?≥?3). On univariable assessment, these cohorts stratified by increasing frailty were significantly associated with postoperative complications (13.6%, 15.9%, 23.9%, 26.4%; p?<?0.001), mortality (1.2%, 1.4%, 2.7%, 3.2%; p?=?0.028), and extended length of stay (eLOS) (15.7%, 22.5%, 28.9%, 37.7%; p?<?0.001). Following multivariable logistic regression analysis, frailty (by mFI-11) was independently associated with postoperative mortality (aOR 1.34, 95% CI 1.08, 1.65) and eLOS (aOR 1.26, 95% CI 1.17, 1.37), while increasing age was not associated with these endpoints. ROC curve analysis demonstrated superior discrimination of frailty (by mFI-11) in comparison with age for both mortality (AUC 0.61 vs. 0.58) and eLOS (AUC 0.61 vs. 0.53). Further statistical assessment through propensity score adjustment and decision tree analysis confirmed and extended the findings of the primary analytical models. Frailty may be a more robust predictor of postoperative outcomes in comparison with age following metastatic brain tumor resection.

     

Subclassification of alpha 1-adrenoceptor recognition sites by urapidil derivatives and other selective antagonists

1. The affinities of urapidil derivatives and other antagonists for alpha 1-adrenoceptors labelled by [3H]-prazosin were determined on membranes of six different rat tissues. 2. Urapidil and its 5-acetyl-, 5-formyl- and 5-methyl-derivative displaced [3H]-prazosin from alpha 1-adrenoceptor binding sites in a concentration-dependent manner which varied with tissue. IC50 values were lower in vas deferens, hippocampus and cerebral cortex than in heart, liver and spleen. For 5-methyl-urapidil, binding to two distinct sites could be demonstrated with mean K1 values of about 0.6 and 45 nM. Saturation binding studies with [3H]-prazosin in the presence of 5-methyl-urapidil indicated a competitive type of interaction between 5-methyl-urapidil and [3H]-prazosin. 3. The proportion of [3H]-prazosin binding sites with high affinity for 5-methyl-urapidil was 58% in vas deferens, 69% in hippocampus, 41% in cerebral cortex and 23% in myocardium. In liver and spleen virtually no high affinity sites were found. These values were in good agreement with the percentages of binding sites with high affinities for WB-4101 and phentolamine, indicating that all these antagonists bind to the same subtype of alpha 1-recognition sites, whereas other alpha-antagonists like BE 2254, yohimbine and unlabelled prazosin did not discriminate between two binding sites. 4. Preincubating membranes of the cerebral cortex with chloroethylclonidine preferentially inactivated [3H]-prazosin binding sites with low affinity for 5-methyl-urapidil. 5. The antagonist potencies of 5-methyl-urapidil and WB-4101 against alpha 1- adrenoceptor-mediated contractile responses were higher in vas deferens than in myocardium. The alpha 1-mediated effects in vas deferens but not in the heart were highly susceptible to nitrendipine. 6. Using 5-methyl-urapidil, the existence of two distinct alpha 1-adrenoceptor recognition sites could be demonstrated which correspond to the proposed alpha 1A- and alpha 1B-subtypes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Metaphyseal osteotomy for the treatment of tailor's bunions

There have been many surgical approaches described for the surgical treatment of tailor's bunions. The authors have been using a procedure that addresses both an elevated fourth to fifth intermetatarsal angle and an elevated lateral deviation angle, for the past 3 years. The metaphyseal osteotomy provides reliable correction of these two abnormalities and allows for uncomplicated rigid fixation.     

A randomized, double-blind clinical trial of two doses of meloxicam compared with naproxen in children with juvenile idiopathic arthritis: short- and long-term efficacy and safety results

OBJECTIVE: In an international, multicenter, double-blind, randomized clinical trial we evaluated the short-term (3 months) and long-term (12 months) efficacy and safety of 2 different doses of meloxicam oral suspension compared with the efficacy and safety of naproxen oral suspension in children with oligoarticular-course (oligo-course) or polyarticular-course (poly-course) juvenile idiopathic arthritis (JIA). METHODS: Children ages 2-16 years who had active oligo-course or poly-course JIA and who required therapy with a nonsteroidal antiinflammatory drug were eligible for this trial. Patients were randomly allocated to receive therapy with meloxicam oral suspension, 0.125 mg/kg body weight in a single daily dose; meloxicam oral suspension, 0.25 mg/kg body weight in a single daily dose; or naproxen, 10 mg/kg body weight in 2 daily doses. The trial drugs were administered in a double-blind, double-dummy design for up to 12 months. Response rates were determined according to the American College of Rheumatology pediatric 30% improvement criteria (ACR pediatric 30). Safety parameters were assessed by evaluating the frequency of adverse events in the 3 groups. RESULTS: Of 232 patients enrolled, 225 received treatment, 6 were not eligible for randomization, and 1 randomized patient was not treated. One hundred eighty-two patients (81%) completed the 12-month treatment period. Response rates according to the ACR pediatric 30 criteria improved from month 3 to month 12, as follows: from 63% to 77% in the meloxicam 0.125 mg/kg group, from 58% to 76% in the meloxicam 0.25 mg/kg group, and from 64% to 74% in the naproxen group. No statistically significant differences in response rates were observed between the groups. There were no differences in the frequency of adverse events or abnormal laboratory values between the 3 groups. CONCLUSION: The short- and long-term safety and efficacy of meloxicam oral suspension appear to be comparable with the safety and efficacy of naproxen oral suspension in the treatment of oligo-course and poly-course JIA. The once-daily administration of meloxicam oral suspension might represent an improvement in the treatment of JIA.     

Functional studies on alpha 1-adrenoceptor subtypes mediating inotropic effects in rat right ventricle.

1. We have studied the alpha 1-adrenoceptor subtypes mediating inotropic effects of adrenaline in rat right ventricle and the Ca2+ sources used to elicit these effects. alpha 1A-Adrenoceptor-mediated contractile effects in rat vas deferens were studied for comparison in some cases. 2. Treatment with chloroethylclonidine did not affect the maximal beta-adrenoceptor-mediated inotropic effects in rat right ventricle or the maximal alpha 1A-adrenoceptor-mediated contractile effects in rat vas deferens; it did not alter the potency of isoprenaline in the ventricle and reduced the potency of the alpha-adrenoceptor antagonists in vas deferens only slightly. Treatment of right ventricular strips with CdCl2 markedly reduced resting tension and enhanced maximal inotropic effects of isoprenaline but did not affect its potency. 3. Inactivation of cardiac alpha 1B-adrenoceptors by treatment with chloroethylclonidine slightly enhanced the maximal inotropic effects of the full agonist, adrenaline and of several partial agonists. 4. Schild analysis of inhibition experiments with the alpha 1A-adrenoceptor-selective antagonists, 5-methyl-urapidil and (+/-)-tamsulosin, demonstrated that adrenaline causes its inotropic effects mainly via the alpha 1B-adrenoceptor subtype. Schild analysis of 5-methyl-urapidil inhibition experiments in chloroethylclonidine-treated ventricles indicated that only alpha 1A-adrenoceptors mediate the inotropic effects of adrenaline following inactivation of the alpha 1B-adrenoceptors. 5. In control ventricles the organic Ca2+ entry blocker, nitrendipine and treatment with the inorganic Ca2+ entry blocker, CdCl2 did not reduce inotropic effects of adrenaline whereas ryanodine treatment inhibited them. In contrast, nitrendipine and CdCl2 treatment had major inhibitory effects in chloroethylclonidine-treated but lacked inhibitory effects in phenoxybenzamine-treated ventricular strips. 6. We conclude that inotropic effects of adrenaline in rat heart are mediated mainly by alpha 1B-adrenoceptors via release of Ca2+ from an intracellular pool.(ABSTRACT TRUNCATED AT 250 WORDS)     

Some notes on uncertainty; Federal policy and innovation

The legislative background and current responsibilities of the new National Center for Health Care Technology (NCHCT) are discussed. The NCHCT's charge is to consider the stage of development, the actual or potential risks, costs and rate of use of health care technology. The role of Government in supporting new technologies, stimulating innovation and encouraging application of research products is considered. These issues are discussed in the context of the uncertainty inherent in planning and the formulation of public policy.     

Cytoplasmic gamma-actin expression in diverse animal models of muscular dystrophy

We recently showed that cytoplasmic gamma-actin (gamma(cyto)-actin) is dramatically elevated in striated muscle of dystrophin-deficient mdx mice. Here, we demonstrate that gamma(cyto)-actin is markedly increased in golden retriever muscular dystrophy (GRMD), which better recapitulates the dystrophinopathy phenotype in humans. Gamma(cyto)-Actin was also elevated in muscle from alpha-sarcoglycan null mice, but not in several other dystrophic animal models, including mice deficient in beta-sarcoglycan, alpha-dystrobrevin, laminin-2, or alpha7 integrin. Muscle from mice lacking dystrophin and utrophin also expressed elevated gamma(cyto)-actin, which was not restored to normal by transgenic overexpression of alpha7 integrin. However, gamma(cyto)-actin was further elevated in skeletal muscle from GRMD animals treated with the glucocorticoid prednisone at doses shown to improve the dystrophic phenotype and muscle function. These data suggest that elevated gamma(cyto)-actin is part of a compensatory cytoskeletal remodeling program that may partially stabilize dystrophic muscle in some cases where the dystrophin-glycoprotein complex is compromised.