Patients with acute cholecystitis should be admitted to a surgical service.

BACKGROUND: In bowel obstruction and biliary pancreatitis, patients receive more expedient surgical care when admitted to surgical compared with medical services. This has not been studied in acute cholecystitis. METHODS: Retrospective analysis of clinical and cost data from July 2013 to September 2015 for patients with cholecystitis who underwent laparoscopic cholecystectomy in a tertiary care inpatient hospital. One hundred ninety lower-risk (Charlson-Deyo) patients were included. We assessed admitting service, length of stay (LOS), time from admission to surgery, time from surgery to discharge, number of imaging studies, and total cost. RESULTS: Patients admitted to surgical (n = 106) versus medical (n = 84) service had shorter mean LOS (1.4 days vs. 2.6 days), shorter time from admission to surgery (0.4 days vs. 0.8 days), and shorter time from surgery to discharge (0.8 days vs. 1.1 days). Surgical service patients had fewer CT (38% vs. 56%) and magnetic resonance imaging (MRI) (5% vs. 16%) studies. Cholangiography (30% vs. 25%) and endoscopic retrograde cholangiopancreatography (ERCP) (3 vs. 8%) rates were similar. Surgical service patients had 39% lower median total costs (US $7787 vs. US $12572). CONCLUSION: Nonsurgical admissions of patients with cholecystitis are common, even among lower-risk patients. Routine admission to the surgical service should decrease LOS, resource utilization and costs. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

A Double-Blind Randomized Comparison of Continuous Interscalene, Supraclavicular, and Suprascapular Blocks for Total Shoulder Arthroplasty.

BACKGROUND AND OBJECTIVES: Continuous brachial plexus blocks at the interscalene level are associated with known diaphragm dysfunction from phrenic nerve paresis. More distal blocks along the brachial plexus may provide postsurgical analgesia while potentially having less effect on diaphragm function. Continuous interscalene, continuous supraclavicular, and continuous suprascapular nerve blocks were evaluated for respiratory function and analgesia after total shoulder arthroplasty. METHODS: After ethics board approval, subjects presenting for total shoulder arthroplasty were planned for randomization in a 1:1:1 ratio of a continuous interscalene, supraclavicular, or suprascapular block. The primary outcome was the assessment of vital capacity after 24 hours of continuous nerve block infusion (6 mL/h; 0.2% ropivacaine), without an initial bolus of local anesthetic during catheter placement. Additional outcomes included diaphragm excursion, pain scores, opioid consumption, and adverse effects. RESULTS: Seventy-five subjects, 25 per group, completed the study. At 24 hours of continuous infusion only (no initial block bolus), the mean vital capacity reduction in the continuous interscalene control group was 991 mL (95% confidence interval [CI], 820-1162). Compared to the interscalene group, the continuous supraclavicular group had a mean vital capacity reduction of 803 mL (95% CI, 616-991; P = 0.322). The continuous suprascapular group had a significantly improved mean vital capacity reduction of 464 mL (95% CI, 289-639; P < 0.001) when similarly compared against the interscalene group. A relative compromise in ultrasound-measured diaphragm excursion was identified in the interscalene group compared to both the supraclavicular group (P = 0.012) and the suprascapular group (P < 0.001). Mean pain scores on an 11-point scale (2.2, 1.6, and 2.6) and 24-hour opioid consumption (13.8 mg, 9.9 mg, and 21.8 mg) for groups interscalene, supraclavicular, and suprascapular, respectively, did not show statistically significant differences. Less adverse effects (Horner syndrome, dyspnea, and hoarseness) were noted in the suprascapular group when compared with the interscalene group (P = 0.002). CONCLUSIONS: A continuous suprascapular block may be a useful analgesic alternative to the interscalene or supraclavicular approaches when the preservation of lung function is a priority after shoulder replacement surgery.

Reduced Length of Hospitalization in Primary Total Knee Arthroplasty Patients Using an Updated Enhanced Recovery After Orthopedic Surgery (ERAS) Pathway.

Decreasing hospital length of stay may attenuate costs associated with total knee arthroplasty. The purpose of this study was to determine if updates to an existing orthopedic enhanced recovery after surgery (ERAS) pathway would improve length of hospitalization. Clinical and demographic data were collected on 252 primary total knee arthroplasties between January 2012 and July 2013. Pre-updated and post-updated ERAS pathway cohorts were analyzed for length of stay, clinical outcomes, and re-admissions. The mean length of stay decreased from 76.6 hours to 56.1 hours after implementation of the evidence-based orthopedic enhanced recovery after surgery pathway (P<0.001). This improvement was possible without a concomitant increase in readmission rates.

Comparative study of guanidine-based and lysine-based brush copolymers for plasmid delivery.

Polyethylenimine (PEI), one of the most frequently used polycations for non-viral nucleic acid delivery, exhibits good transfection efficiency to cultured cells but generally has to be used in restricted concentration ranges due to high cytotoxicity. We recently reported a family of HPMA-co-oligolysine brush copolymers that show nucleic acid delivery efficiencies approaching that of PEI. Guanidine-containing polymers have been reported in some systems to be more effective at cellular delivery of cargo than their primary-amine analogs. The goal of this work is to investigate the effect of guanidinylation on gene transfer ability of HPMA-co-oligolysine copolymers. Several parameters were evaluated: arginine versus homoarginine monomers, oligopeptide length, and charge density within the peptide. Using reversible addition-fragmentation chain transfer (RAFT) polymerization, a series of six copolymers were synthesized containing the cationic peptides K10, R10, K5, and (GK)5. Lysine-containing copolymers were functionalized with guanidine by reaction with O-methylisourea to generate an additional five homoarginine-based copolymers. All eleven copolymers readily condensed DNA into small, < 150 nm polyplexes and remained stable in physiological salt conditions. The best performing copolymers provided more efficient gene transfection with less associated cytotoxicity than PEI. Reducing the number of charge centers (from 10 to 5) further reduced toxicity while retaining comparable transfection efficiency to PEI.

Melittin-grafted HPMA-oligolysine based copolymers for gene delivery.

Non-viral gene delivery systems capable of transfecting cells in the brain are critical in realizing the potential impact of nucleic acid therapeutics for diseases of the central nervous system. In this study, the membrane-lytic peptide melittin was incorporated into block copolymers synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The first block, designed for melittin conjugation, was composed of N-(2-hydroxypropyl)methacrylamide (HPMA) and pyridyl disulfide methacrylamide (PDSMA) and the second block, designed for DNA binding, was composed of oligo-l-lysine (K10) and HPMA. Melittin modified with cysteine at the C-terminus was conjugated to the polymers through the pyridyl disulfide pendent groups via disulfide exchange. The resulting pHgMelbHK10 copolymers are more membrane-lytic than melittin-free control polymers, and efficiently condensed plasmid DNA into salt-stable particles (~100-200 nm). The melittin-modified polymers transfected both HeLa and neuron-like PC-12 cells more efficiently than melittin-free polymers although toxicity associated with the melittin peptide was observed. Optimized formulations containing the luciferase reporter gene were delivered to mouse brain by intraventricular brain injections. Melittin-containing polyplexes produced about 35-fold higher luciferase activity in the brain compared to polyplexes without melittin. Thus, the melittin-containing block copolymers described in this work are promising materials for gene delivery to the brain.

Optimization of brush-like cationic copolymers for nonviral gene delivery.

Polyethylenimine (PEI) is one of the most broadly used polycations for gene delivery due to its high transfection efficiency and commercial availability but materials are cytotoxic and often polydisperse. The goal of current work is to develop an alternative family of polycations based on controlled living radical polymerization (CLRP) and to optimize the polymer structure for efficient gene delivery. In this study, well-defined poly(glycidyl methacrylate)(P(GMA)) homopolymers were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization followed by decoration using three different types of oligoamines, i.e., tetraethylenepentamine (TEPA), pentaethylenehexamine (PEHA), and tris(2-aminoethyl)amine (TREN), respectively, to generate various P(GMA-oligoamine) homopolycations. The effect of P(GMA) backbone length and structure of oligoamine on gene transfer efficiency was then determined. The optimal polymer, P(GMA-TEPA)(50), provided comparable transfection efficiency but lower cytotoxicity than PEI. P(GMA-TEPA)(50) was then used as the cationic block in diblock copolymers containing hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA) and oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA). Polyplexes of block copolymers were stable against aggregation in physiological salt condition and in Opti-MEM due to the shielding effect of P(HPMA) and P(OEGMA). However, the presence of the HPMA/OEGMA block significantly decreased the transfection efficacy of P(GMA-TEPA)(50) homopolycation. To compensate for reduced cell uptake caused by the hydrophilic shell of polyplex, the integrin-binding peptide, RGD, was conjugated to the hydrophilic chain end of P(OEGMA)(15)-b-P(GMA-TEPA)(50) copolymer by Michael-type addition reaction. At low polymer to DNA ratios, the RGD-functionalized polymer showed increased gene delivery efficiency to HeLa cells compared to analogous polymers lacking RGD.