Complex Tracheocarinal Reconstructions Using Extrathoracic Muscle Flaps as Airway Substitutes

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Regional anesthesia does not decrease opioid demand in pelvis and acetabulum fracture surgery

Introduction

Patients with pelvic and acetabular fractures often have considerable pain in the perioperative period. Regional anesthesia (RA) including peripheral nerve blocks and spinal analgesia may reduce pain. However, the real-world impact of these modalities on inpatient opioid consumption and outpatient opioid demand is largely unknown. The purpose of this study was to evaluate the impact of perioperative RA on inpatient opioid consumption and outpatient opioid demand.

Methods

This is a retrospective, observational review of inpatient opioid consumption and outpatient opioid demand in all patients ages 18 and older undergoing operative fixation of pelvic and acetabular fractures at a single Level, I trauma center from 7/1/2013–7/1/2018 (n = 205). Unadjusted and adjusted analyses were constructed to evaluate the impact of RA on inpatient opioid consumption and outpatient opioid demand while controlling for age, sex, race, body mass index (BMI), smoking, chronic opioid use, ASA score, injury mechanism, additional injuries, open injury, and additional inpatient surgery.

Results

Adjusted models demonstrated increases in inpatient opioid consumption in patients with RA (12.6 estimated OE’s without RA vs 16.1 OE’s with RA from 48 to 72 h post-op, p < 0.05) but no significant differences at other timepoints (17.5 estimated OE’s without RA vs 16.8 OE’s with RA from 0 to 24 h post-op, 15.3 vs 17.1 from 24 to 48 h post-op, p > 0.05). Estimated cumulative outpatient opioid demand was significantly higher in patients with RA at discharge to 90 days post-op (and 156.8 vs 207.9 OE’s to 90 days, p < 0.05) but did not differ significantly before that time (121.5 OE’s without RA vs 123.9 with RA from discharge to two weeks, 145.2 vs 177.2 OE’s to 6 weeks, p > 0.05).

Discussion

In pelvis and acetabulum fracture surgery, RA was associated with increased inpatient and outpatient opioid demand after adjusting for baseline patient and treatment characteristics. Regional anesthesia may not be beneficial for these patients.

     

p53-regulated autophagy is controlled by glycolysis and determines cell fate

The tumor suppressor p53 regulates downstream targets that determine cell fate. Canonical p53 functions include inducing apoptosis, growth arrest, and senescence. Non-canonical p53 functions include its ability to promote or inhibit autophagy and its ability to regulate metabolism. The extent to which autophagy and/or metabolic regulation determines cell fate by p53 is unclear. To address this, we compared cells resistant or sensitive to apoptosis by the p53 activator Nutlin-3a. In resistant cells, glycolysis was maintained upon Nutlin-3a treatment, and activated p53 promoted prosurvival autophagy. In contrast, in apoptosis sensitive cells activated p53 increased superoxide levels and inhibited glycolysis through repression of glycolytic pathway genes. Glycolysis inhibition and increased superoxide inhibited autophagy by repressing ATG genes essential for autophagic vesicle maturation. Inhibiting glycolysis increased superoxide and blocked autophagy in apoptosis-resistant cells, causing p62-dependent caspase-8 activation. Finally, treatment with 2-DG or the autophagy inhibitors chloroquine or bafilomycin A1 sensitized resistant cells to Nutlin-3a-induced apoptosis. Together, these findings reveal novel links between glycolysis and autophagy that determine apoptosis-sensitivity in response to p53. Specifically, the findings indicate 1) that glycolysis plays an essential role in autophagy by limiting superoxide levels and maintaining expression of ATG genes required for autophagic vesicle maturation, 2) that p53 can promote or inhibit autophagy depending on the status of glycolysis, and 3) that inhibiting protective autophagy can expand the breadth of cells susceptible to Nutlin-3a induced apoptosis.     

Simulated human serum profiles of one daily dose of ceftriaxone plus netilmicin in treatment of experimental streptococcal endocarditis.

We performed experiments in rats aimed at determining whether a combination of ceftriaxone (CRO) and netilmicin (NET), by using once-daily administration in rats, which simulated profiles of drug in human serum, was more effective than either agent alone in the treatment of endocarditis caused by viridans group streptococci. A programmable infusion pump system enabled the production of profiles of CRO in serum that simulate those found in humans after the intravenous administration of 2 g. The subcutaneous administration of 18 mg of NET per kg of body weight produced levels in the sera of rats comparable to those after the intravenous administration of a dose of 5 mg of NET per kg in humans. Rats with catheter-induced aortic vegetations were infected intravenously with two test strains, a CRO-susceptible Streptococcus sanguis strain (MICs of CRO and NET, 0.064 and 8 mg/liter, respectively) and a relatively CRO-resistant Streptococcus mitis strain (MICs of CRO and NET, 2 and 8 mg/liter, respectively). Against both strains, the combination of CRO and NET was synergistic in vitro as determined by time-kill curves. Treatment of rats was started 48 h postinfection and lasted for 3 days. CRO alone was effective against the susceptible strain (P < 0.001 compared with control animals) but was not effective against the resistant organism. A significantly enhanced antibacterial activity of the CRO-NET combination in reducing the valvular bacterial counts was observed with both test strains (P < 0.001). The synergistic effect was obtained with a single daily injection of NET which provided detectable levels in serum for only 8 h, suggesting that in vivo synergism in the treatment of infections caused by viridans group streptococci can be obtained without 24 h of aminoglycoside coverage. These experimental data might provide a rationale for clinical trials of a once-a-day dosing regimen in the treatment of streptococcal but nonenterococcal endocarditis.     

Variability of medial and posterior offset in patients with fourth-generation stemmed shoulder arthroplasty

Purpose  

Most anthropometric data on the proximal humerus has been obtained from deceased healthy individuals with no deformities. Endoprostheses are implanted for primary and secondary osteoarthritis, rheumatoid arthritis, humeral-head necrosis, fracture sequelae and other humeral-head deformities. This indicates that pathologicoanatomical variability may be greater than previously assumed. We therefore investigated a group of patients with typical shoulder replacement diagnoses, including posttraumatic and rheumatic deformities.     

A worksite prevention program for construction workers: design of a randomized controlled trial

Background  

A worksite prevention program was developed to promote the work ability of construction workers and thereby prolong a healthy working life. The objective of this paper is to present the design of a randomized controlled trial evaluating the effectiveness of that intervention program compared with usual care for construction workers.