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.

     

Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor

Staphylococcus aureus infections are known triggers for skin inflammation and can modulate immune responses. The present studies used model systems consisting of platelet-activating factor receptor-positive and -negative (PAF-R-positive and -negative) cells and PAF-R-deficient mice to demonstrate that staphylococcal lipoteichoic acid (LTA), a constituent of Gram-positive bacteria cell walls, acts as a PAF-R agonist. We show that LTA stimulates an immediate intracellular Ca2+ flux only in PAF-R-positive cells. Intradermal injections of LTA and the PAF-R agonist 1-hexadecyl-2-N-methylcarbamoyl glycerophosphocholine (CPAF) induced cutaneous inflammation in wild-type but not PAF-R-deficient mice. Systemic exposure to LTA or CPAF inhibited delayed-type hypersensitivity (DTH) reactions to the chemical dinitrofluorobenzene only in PAF-R-expressing mice. The inhibition of DTH reactions was abrogated by the addition of neutralizing antibodies to IL-10. Finally, we measured levels of LTA that were adequate to stimulate PAF-R in vitro on the skin of subjects with infected atopic dermatitis. Based on these studies, we propose that LTA exerts immunomodulatory effects via the PAF-R through production of the Th2 cytokine IL-10. These findings show a novel mechanism by which staphylococcal infections can inhibit Th1 reactions and thus worsen Th2 skin diseases, such as atopic dermatitis.     

Pregnancy-induced severe left ventricular systolic dysfunction in a patient with hypertrophic cardiomyopathy

This paper reports the first case of hypertrophic cardiomyopathy (HCM) that developed postpartum congestive heart failure (CHF) and severe left ventricular (LV) systolic dysfunction. Review of the literature and clinical implications are discussed.     

Knowledge of Sleep Apnea in a Sample Grouping of Primary Care Physicians

The purpose of this pilot study was to examine four groups of primary care physicians knowledge of sleep apnea. Methods: Using a 36-item questionnaire, we investigated how cognizant primary care physicians in Ontario, Canada, were of sleep apnea and its different symptoms. The questions covered incidence, diagnosis, treatment, and medical and social ramifications of sleep apnea. Sleep apnea surveys were administered to small groups of primary care physicians attending educational conferences or were distributed by mail to physicians who had previously referred patients to the sleep clinic. Results: A total of 151 physicians responded to the survey. An overall average score of 69% was obtained on the questionnaire. Conclusions: This score suggests that the physicians sampled in this pilot study are relatively underinformed about the clinical features and medical and social ramifications associated with sleep apnea.     

Levofloxacin efficacy in the treatment of community-acquired legionellosis

BACKGROUND: Although fluoroquinolones possess excellent in vitro activity against Legionella, few large-scale clinical trials have examined their efficacy in the treatment of Legionnaires disease. Even fewer studies have applied rigorous criteria for diagnosis of community-acquired Legionnaires disease, including culture of respiratory secretions on selective media. METHODS: Data from six clinical trials encompassing 1,997 total patients have been analyzed to determine the efficacy of levofloxacin (500 mg qd or 750 mg qd) in treating patients with community-acquired pneumonia (CAP) due to Legionella. RESULTS: Of the 1,997 total patients with CAP from the clinical trials, 75 patients had infection with a Legionella species. Demographics showed a large portion of these patients were < 55 years of age and nonsmokers. More than 90% of mild-to-moderate and severe cases of Legionella infection resolved clinically at the posttherapy visit, 2 to 14 days after treatment termination. No deaths were reported for any patient with Legionnaires disease treated with levofloxacin during the studies. CONCLUSIONS: Levofloxacin was efficacious at both 500 mg for 7 to 14 days and 750 mg for 5 days. Legionnaires disease is not associated only with smokers, the elderly, and the immunosuppressed, but also has the potential to affect a broader demographic range of the general population than previously thought.     

Treatment with proton pump inhibitors in acute non-variceal upper gastrointestinal bleeding: a meta-analysis

Medical therapy is an attractive adjuvant to endoscopic treatment in upper gastrointestinal (UGI) bleeding. This review aims to assess the treatment effects of proton pump inhibitor (PPI) therapy in acute non-variceal UGI bleeding. Outcome measures evaluated were further bleeding, surgery, all-cause deaths, ulcer deaths and non-ulcer deaths. We searched MEDLINE (1966-2002) and EMBASE (1974-2002) using the terms 'gastrointestinal hemorrhage', 'peptic ulcer hemorrhage', 'proton pump inhibitor', 'omeprazole', 'pantoprazole', 'lansoprazole', 'rabeprazole' and 'esomeprazole'. The search was extended to the Cochrane controlled trials registry database, published abstracts from five international gastroenterology conferences, manufacturers of PPI, known contacts and bibliographies from each full-length published report. We included trials published in English and non-English languages. Eligible studies were randomized controlled trials that compared the treatment effects of PPI therapy with placebo or H2 receptor antagonists in patients with acute non-variceal UGI bleeding. Of the 175 articles screened, 26 controlled trials including 4670 subjects (2317 in treatment arm and 2353 in control arm) were analyzed. The methodology, population, intervention, and outcomes of each selected trial were evaluated using duplicate independent review. Disagreements were resolved by consensus. PPI therapy significantly reduced rates of further bleeding (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40-0.57) and surgery (OR, 0.61; 95% CI, 0.48-0.76). All-cause deaths were unaffected (OR, 1.02; 95% CI, 0.76-1.37). Ulcer deaths showed a significant reduction (OR, 0.58; 95% CI, 0.35-0.96), while non-ulcer deaths showed a significant increase (OR, 1.60; 95% CI, 1.06-2.41) in the PPI therapy group. Sensitivity analysis of 22 trials published in peer-reviewed journals, 10 trials with double-blind design and 19 trials with high quality score and 22 trials using omeprazole in the treatment group showed results similar to those seen in the analysis of all 26 trials, confirming the stability of the conclusions. Subgroup analysis revealed that summary outcome measures were not influenced by control group therapy (placebo vs H2 receptor antagonists) or the use of prior endoscopic treatment to achieve hemostasis (given vs not given). However, the summary treatment effects for further bleeding and need for surgery were significant in only those trials enrolling patients with peptic ulcers having high risk for rebleeding and not in those trials enrolling patients with all causes of UGI bleeding. The summary treatment effects for further bleeding and need for surgery were significant in trials using intravenous as well as oral PPI. However, summary OR for all-cause deaths and non-ulcer deaths in trials using intravenous PPI were higher in the treatment group and not in trials using oral PPI. This raised the possibility of intravenous PPI-therapy-associated non-ulcer deaths in high-risk patients. PPI therapy in acute non-variceal UGI bleeding reduced rates of further bleeding, surgery and deaths caused by ulcer complications. However, non-ulcer deaths were increased. The overall mortality was unaffected. PPI therapy is useful only in a selected group of patients with acute non-variceal UGI bleeding, namely those with peptic ulcers having endoscopic high-risk stigmata for rebleeding.     

Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate

Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp^r) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp^s) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp^r but not in the Imp^s isolate. Notably, this finding is corroborated by an increase in the motility of the Imp^r strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success.