Characteristics associated with patient-reported treatment success in psoriatic arthritis.

OBJECTIVES: To determine characteristics associated with patient-reported treatment success in psoriatic arthritis (PsA). METHODS: Rheumatologist-diagnosed PsA patients fulfilling the CASPAR classification were recruited from a single center. PsA outcome measures included: 66/68 swollen/tender joint counts, Leeds/SPARCC dactylitis/enthesitis indices, psoriasis body surface area (BSA), and patient-reported outcomes (PROs) including PROMIS. The primary outcome was a patient-reported item: "Today, considering the level of control of your psoriatic arthritis and psoriasis, do you consider your treatment has been successful?" Descriptive and multivariate logistic regression analyses identified clinical predictors of patient-reported treatment success. Patient-reported reasons for lack of treatment success were explored. RESULTS: A total of 178 participants had a baseline visit. Mean (SD) CASPAR score was 3.7 (0.9), age 51.7 (13.5) years, and BMI 31.3 (7.2) kg/m2. Fifty-two percent were women, and 86.0% white. Treatment success was reported by 116/178(65%) patients in the analytic cohort. Among 76 patients who reported treatment failure, the most frequently selected reasons for lack of success were pain (n = 55, 72.4%), fatigue (n = 46, 60.5%), inflamed joints (n = 40, 52.6%), and stiffness (n = 40, 52.6%). Overall, 105 participants had complete data across variables in the logistic regression models. Patient-reported treatment success was independently associated with the 66-swollen/68-tender joint counts, psoriasis BSA, PROs (pain interference, physical function, fatigue), and TNF-inhibitor therapy, after controlling for BMI and demographics. CONCLUSION: Patient-reported treatment success in PsA may be achieved through improvement of inflammatory arthritis, psoriasis, pain, physical function, fatigue, and the use ofTNF-inhibitors. Patients reported treatment failure was most commonly due to symptoms of pain, fatigue and stiffness.

Combined erector spinae plane block with surgical intercostal nerve cryoablation for Nuss procedure is associated with decreased opioid use and length of stay.

BACKGROUND AND OBJECTIVES: Pain management for patients undergoing the Nuss procedure for treatment of pectus excavatum can be challenging. In an effort to improve pain management, our institution added bilateral single injection erector spinae plane (ESP) blocks to surgeon placed intercostal nerve cryoablation. We aimed to assess the efficacy of this practice change. METHODS: Retrospective clinical data from a single academic medical center were evaluated. Due to an institutional change in clinical management, we were able to perform a before and after study. Twenty patients undergoing Nuss procedure who received bilateral ultrasound-guided single-shot T6 level ESP blocks and intercostal nerve cryoablation were compared with a historical control cohort of 20 patients who underwent Nuss procedure with intercostal nerve cryoablation alone. The primary outcome variables included postoperative pain scores, total hospital opioid use, and hospital length of stay. RESULTS: Median total hospital intravenous morphine milligram equivalents was lower for the ESP group than for the control group (0.60 (IQR 0.35-0.88) vs 1.15 mg/kg (IQR 0.74-1.68), p<0.01). There was no difference in postoperative pain scores between the two groups. Mean hospital length of stay was 2.45 (SD 0.69) days for the control group and 1.95 (SD 0.69) days for the ESP group (p=0.03). No adverse events related to block placement were identified. CONCLUSIONS: In a single-center academic practice, the addition of bilateral single injection ESP blocks at T6 to surgeon performed cryoablation reduced opioid consumption without a change in subjectively reported pain scores. The results from this pilot study can provide effect size estimates to guide the design of future randomized trials.

Isolation and Characterization of Lytic Bacteriophages Targeting Diverse Enterobacter spp. Clinical Isolates.

Background: Enterobacter spp. are opportunistic pathogens that cause nosocomial infections. Bacteriophages could be used to treat antibiotic-resistant Enterobacter infections. Materials and Methods: We used 10 genetically diverse clinical Enterobacter spp. isolates to identify lytic bacteriophages in hospital and municipal wastewater. Comparative genomics was performed on host bacterial isolates and isolated phages. Activity of each phage against all 10 host isolates was determined. We also tested phage activity against paired isolates from two patients who developed ceftazidime-avibactam resistance. Results: Bacteria belonged to three Enterobacter species and Klebsiella aerogenes. We isolated 12 bacteriophages, most of which belonged to the Myoviridae and Autographiviridae families. Most phages were able to lyse multiple bacterial isolates, and many lysed isolates of different species. Ceftazidime-avibactam-resistant isolates were still phage susceptible, and one isolate showed increased susceptibility compared with the parent isolate. Conclusion: The phages we isolated expand the diversity of Enterobacter-targeting phages, and could be useful for treating antibiotic-resistant Enterobacter infections.

Genomic characterization of lytic bacteriophages targeting genetically diverse Pseudomonas aeruginosa clinical isolates.

Pseudomonas aeruginosa infections can be difficult to treat and new therapeutics are needed. Bacteriophage therapy is a promising alternative to traditional antibiotics, but large numbers of isolated and characterized phages are lacking. We collected 23 diverse P. aeruginosa isolates from people with cystic fibrosis (CF) and clinical infections, and used them to screen and isolate over a dozen P. aeruginosa-targeting phages from hospital wastewater. Phages were characterized with genome sequencing, comparative genomics, and lytic activity screening against all 23 bacterial host isolates. We evolved bacterial mutants that were resistant to phage infection for four different phages, and used genome sequencing and functional analysis to study them further. We also tested phages for their ability to kill P. aeruginosa grown in biofilms in vitro and ex vivo on CF airway epithelial cells. Overall, this study demonstrates how systematic genomic and phenotypic characterization can be deployed to develop bacteriophages as precision antibiotics.

Targeting Gbetagamma signaling to inhibit prostate tumor formation and growth.

Prostate cancer starts as androgen-dependent malignancy and responds initially to androgen ablative therapy. Beneficial effects of androgen ablation, however, are often temporary and the cancer reappears as androgen-independent tumor, suggesting the existence of additional factors responsible for progression of the disease. Attention has focused on receptor tyrosine kinases as the growth mediators of androgen-independent prostate cancer; overexpression of epidermal growth factor receptors or their ligand heparin-bound epidermal growth factor, for example, promotes transition to androgen independence. Emerging data demonstrate involvement of another class of cell membrane-anchored receptors, the heterotrimeric guanine-binding (G) protein-coupled receptors (GPCRs) in prostate cancer. In vitro, stimulation of many endogenous GPCRs induces mitogenic signaling and growth of prostate cancer cells. The GPCRs transduce mitogenic signals via activated G proteins in the form of Galpha-GTP and Gbetagamma subunits. Here, we show that expression of a Gbetagamma inhibitor peptide derived from carboxy terminus of G protein-coupled receptor kinase 2 obliterates serum-regulated prostate cancer cell growth in vitro and prevents prostate tumor formation in vivo. We also demonstrate that inhibition of Gbetagamma signaling retards growth of existing prostate tumors by inducing cell death. These data establish a central role for heterotrimeric G proteins in prostate cancer and suggest targeted inhibition of Gbetagamma signaling may serve as specific molecular therapy tool to limit pathologic growth of advanced prostate cancer.