Citations

Abstract Rationale Cardiovascular disease is a common comorbidity in patients with chronic obstructive pulmonary disease. Although β-blockers can be used safely in patients with chronic obstructive pulmonary disease, concerns remain regarding safety and efficacy interactions in patients using concomitant inhaled long-acting β-agonists. Objectives To compare the differential effects of long-acting β-agonist or inhaled corticosteroid use on clinical outcomes in patients with heightened cardiovascular risk treated and not treated with β-blockers. Methods We examined data from 16,485 participants in the SUMMIT study (Study to Understand Mortality and Morbidity in COPD) who were randomized to once-daily inhaled fluticasone furoate, vilanterol, fluticasone furoate/vilanterol combination, or placebo and examined the associations between treatment allocation and lung function, chronic obstructive pulmonary disease exacerbations, cardiovascular events, and all-cause mortality, stratified by baseline β-blocker therapy. Results Baseline β-blocker therapy was used by 31% (n = 5,159) of SUMMIT participants. There was no evidence of an interaction between baseline β-blocker therapy and the association between inhaled treatments and forced expiratory volume in 1 second at 3 months (P = 0.27), 6 months (P = 0.14), or 12 months (P = 0.33). The placebo-adjusted mean differences in post-bronchodilator forced expiratory volume in 1 second at 3 months in the vilanterol-alone group were 58 ml (95% confidence interval, 38–78) in those receiving baseline β-blocker therapy and 51 ml (95% confidence interval, 38–65) in those not receiving baseline β-blocker therapy. The placebo-adjusted mean differences in post-bronchodilator forced expiratory volume in 1 second at 3 months in the combination fluticasone furoate/vilanterol group were 85 ml (95% confidence interval, 65–105) in those receiving baseline β-blocker therapy and 68 ml (95% confidence interval, 54–82) in those not receiving baseline β-blocker therapy. Overall, there was no evidence of interaction by randomized treatment, including vilanterol alone or in combination with fluticasone furoate, for chronic obstructive pulmonary disease exacerbations (P = 0.18), cardiovascular composite events (P = 0.33), and all-cause mortality (P = 0.41). Conclusions There is no evidence to suggest that baseline β-blocker therapy reduces the respiratory benefits or increases the cardiovascular risk of inhaled long-acting β-agonists in patients with chronic obstructive pulmonary disease and heightened cardiovascular risk. Clinical trial registered with www.clinicaltrials.gov (NCT01313676).

Abstract Tumor-associated macrophages (TAM) play a critical role in cancer development and progression. However, the heterogeneity of TAM presents a major challenge to identify clinically relevant markers for protumor TAM. Here, we report that expression of adipocyte/macrophage fatty acid–binding protein (A-FABP) in TAM promotes breast cancer progression. Although upregulation of A-FABP was inversely associated with breast cancer survival, deficiency of A-FABP significantly reduced mammary tumor growth and metastasis. Furthermore, the protumor effect of A-FABP was mediated by TAM, in particular, in a subset of TAM with a CD11b+F4/80+MHCII−Ly6C− phenotype. A-FABP expression in TAM facilitated protumor IL6/STAT3 signaling through regulation of the NFκB/miR-29b pathway. Collectively, our results suggest A-FABP as a new functional marker for protumor TAM. Significance: These findings identify A-FABP as a functional marker for protumor macrophages, thus offering a new target for tumor immunotherapy. Cancer Res; 78(9); 2343–55. ©2018 AACR.

ABSTRACT We describe results from a multicenter study evaluating the Accelerate Pheno system, a first of its kind diagnostic system that rapidly identifies common bloodstream pathogens from positive blood cultures within 90 min and determines bacterial phenotypic antimicrobial susceptibility testing (AST) results within ∼7 h. A combination of fresh clinical and seeded blood cultures were tested, and results from the Accelerate Pheno system were compared to Vitek 2 results for identification (ID) and broth microdilution or disk diffusion for AST. The Accelerate Pheno system accurately identified 14 common bacterial pathogens and two Candida spp. with sensitivities ranging from 94.6 to 100%. Of fresh positive blood cultures, 89% received a monomicrobial call with a positive predictive value of 97.3%. Six common Gram-positive cocci were evaluated for ID. Five were tested against eight antibiotics, two resistance phenotypes (methicillin-resistant Staphylococcus aureus and Staphylococcus spp. [MRSA/MRS]), and inducible clindamycin resistance (MLSb). From the 4,142 AST results, the overall essential agreement (EA) and categorical agreement (CA) were 97.6% and 97.9%, respectively. Overall very major error (VME), major error (ME), and minor error (mE) rates were 1.0%, 0.7%, and 1.3%, respectively. Eight species of Gram-negative rods were evaluated against 15 antibiotics. From the 6,331 AST results, overall EA and CA were 95.4% and 94.3%, respectively. Overall VME, ME, and mE rates were 0.5%, 0.9%, and 4.8%, respectively. The Accelerate Pheno system has the unique ability to identify and provide phenotypic MIC and categorical AST results in a few hours directly from positive blood culture bottles and support accurate antimicrobial adjustment.

OBJECTIVE Patient-reported outcomes (PROs) play a pivotal role in defining the value of surgical interventions for spinal disease. The concept of minimum clinically important difference (MCID) is considered the new standard for determining the effectiveness of a given treatment and describing patient satisfaction in response to that treatment. The purpose of this study was to determine the MCID associated with surgical treatment for degenerative lumbar spondylolisthesis. METHODS The authors queried the Quality Outcomes Database registry from July 2014 through December 2015 for patients who underwent posterior lumbar surgery for grade I degenerative spondylolisthesis. Recorded PROs included scores on the Oswestry Disability Index (ODI), EQ-5D, and numeric rating scale (NRS) for leg pain (NRS-LP) and back pain (NRS-BP). Anchor-based (using the North American Spine Society satisfaction scale) and distribution-based (half a standard deviation, small Cohen’s effect size, standard error of measurement, and minimum detectable change [MDC]) methods were used to calculate the MCID for each PRO. RESULTS A total of 441 patients (80 who underwent laminectomies alone and 361 who underwent fusion procedures) from 11 participating sites were included in the analysis. The changes in functional outcome scores between baseline and the 1-year postoperative evaluation were as follows: 23.5 ± 17.4 points for ODI, 0.24 ± 0.23 for EQ-5D, 4.1 ± 3.5 for NRS-LP, and 3.7 ± 3.2 for NRS-BP. The different calculation methods generated a range of MCID values for each PRO: 3.3–26.5 points for ODI, 0.04–0.3 points for EQ-5D, 0.6–4.5 points for NRS-LP, and 0.5–4.2 points for NRS-BP. The MDC approach appeared to be the most appropriate for calculating MCID because it provided a threshold greater than the measurement error and was closest to the average change difference between the satisfied and not-satisfied patients. On subgroup analysis, the MCID thresholds for laminectomy-alone patients were comparable to those for the patients who underwent arthrodesis as well as for the entire cohort. CONCLUSIONS The MCID for PROs was highly variable depending on the calculation technique. The MDC seems to be a statistically and clinically sound method for defining the appropriate MCID value for patients with grade I degenerative lumbar spondylolisthesis. Based on this method, the MCID values are 14.3 points for ODI, 0.2 points for EQ-5D, 1.7 points for NRS-LP, and 1.6 points for NRS-BP.

OBJECTIVE The American Association of Neurological Surgeons launched the Quality Outcomes Database (QOD), a prospective longitudinal registry that includes demographic, clinical, and patient-reported outcome (PRO) data, to measure the safety and quality of neurosurgical procedures, including spinal surgery. Differing results from recent randomized controlled trials have established a need to clarify the groups that would most benefit from surgery for degenerative lumbar spondylolisthesis. In the present study, the authors compared patients who were the most and the least satisfied following surgery for degenerative lumbar spondylolisthesis. METHODS This was a retrospective analysis of a prospective, national longitudinal registry including patients who had undergone surgery for grade 1 degenerative lumbar spondylolisthesis. The most and least satisfied patients were identified based on an answer of “1” and “4,” respectively, on the North American Spine Society (NASS) Satisfaction Questionnaire 12 months postoperatively. Baseline demographics, clinical variables, surgical parameters, and outcomes were collected. Patient-reported outcome measures, including the Numeric Rating Scale (NRS) for back pain, NRS for leg pain, Oswestry Disability Index (ODI), and EQ-5D (the EuroQol health survey), were administered at baseline and 3 and 12 months after treatment. RESULTS Four hundred seventy-seven patients underwent surgery for grade 1 degenerative lumbar spondylolisthesis in the period from July 2014 through December 2015. Two hundred fifty-five patients (53.5%) were the most satisfied and 26 (5.5%) were the least satisfied. Compared with the most satisfied patients, the least satisfied ones more often had coronary artery disease (CAD; 26.9% vs 12.2%, p = 0.04) and had higher body mass indices (32.9 ± 6.5 vs 30.0 ± 6.0 kg/m 2 , p = 0.02). In the multivariate analysis, female sex (OR 2.9, p = 0.02) was associated with the most satisfaction. Notably, the American Society of Anesthesiologists (ASA) class, smoking, psychiatric comorbidity, and employment status were not significantly associated with satisfaction. Although there were no significant differences at baseline, the most satisfied patients had significantly lower NRS back and leg pain and ODI scores and a greater EQ-5D score at 3 and 12 months postoperatively (p < 0.001 for all). CONCLUSIONS This study revealed that some patient factors differ between those who report the most and those who report the least satisfaction after surgery for degenerative lumbar spondylolisthesis. Patients reporting the least satisfaction tended to have CAD or were obese. Female sex was associated with the most satisfaction when adjusting for potential covariates. These findings highlight several key factors that could aid in setting expectations for outcomes following surgery for degenerative lumbar spondylolisthesis.

We determined if changes in the irregular motor activity of phase II, the dominant motility phase in awake fasting humans, are associated with fluctuations in pancreatic secretion by intubating the upper gastrointestinal tract of 15 healthy humans and recording antral and duodenal motility and obtaining duodenal samples for one or two interdigestive motility cycles. Antral phase II activity was graded as having low, intermediate, or high frequency of contractions and related to duodenal trypsin output and plasma concentrations of motilin and human pancreatic polypeptide (HPP), a marker of vagal cholinergic tone. Low, intermediate, and high phase II motor activities were significantly associated with trypsin outputs (U/10 min; mean +/- SE) of 576 +/- 137, 1,441 +/- 225, and 3,621 +/- 521, respectively (P less than 0.001). Plasma motilin levels did not vary with the grades of phase II motility (P greater than 0.1), but levels of plasma HPP and the grades of phase II motility were positively correlated (P less than 0.001). The close correlation among motility, pancreatic secretion, and plasma HPP during phase II suggests that vagal cholinergic pathways are involved in the common regulatory mechanism controlling phase II interdigestive motility and pancreatic secretion.

AbstractBackgroundBefore the 2014 policy change pertaining to infectious disease screening, many organ procurement organizations (OPOs) were supplementing serologic screening of deceased organ donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV‐1), hepatitis B virus (HBV), and hepatitis C virus (HCV). The number of seronegative,NAT‐positive donors has not been directly measured.MethodsHIV,HBV, andHCVscreening results of 11 229 donor referrals evaluated from 2010 to 2013 were obtained from 3OPO‐affiliated laboratories, capturing 35% of all donors in the United States. Laboratories used either polymerase chain reaction assay or transcription‐mediated amplification assay to test 9643 deceased donors byNAT.ResultsTheNATresults were positive in 21 (0.2%), 1 (0.02%), and 11 (0.1%) donors who were seronegative forHIV,HBV, andHCV, respectively. All discordantHIV‐1 results were from one laboratory using a polymrease chain reaction assay. Thirteen of the reactiveHIV NATresults in seronegative referrals were repeated and were non‐reproducibly positive (NRP). Ten (0.1%), 452 (7.8%), and 197 (2.2%) ofHIV‐,HBV‐, andHCV‐seropositive donors, respectively, were negative byNAT.ConclusionsThis study highlights the importance of robust quality assurance to minimizeNRP NATresults.NATmay allow for increased utilization of organs fromHBV‐ andHCV‐seropositive,NAT‐negative donors.

Increasing rates of burnout—with accompanying stress and lack of engagement—among faculty, residents, students, and practicing physicians have caused alarm in academic medicine. Central to the debate among academic medicine’s stakeholders are oft-competing issues of social accountability; cost containment; effectiveness of academic medicine’s institutions; faculty recruitment, retention, and satisfaction; increasing expectations for faculty; and mission-based productivity. The authors propose that understanding and fostering what contributes to faculty and institutional vitality is central to preventing burnout during times of change. They first look at faculty vitality and how it is threatened by burnout, to provide a framework for a greater understanding of faculty well-being. Then they draw on higher education literature to determine how vitality is defined in academic settings and what factors affect faculty vitality within the context of academic medicine. Next, they propose a model to explain and examine faculty vitality in academic medicine, followed by a discussion of the need for a greater understanding of faculty vitality. Finally, the authors offer conclusions and propose future directions to promote faculty vitality. The authors encourage institutional decision makers and other stakeholders to focus particular attention on the evolving expectations for faculty, the risk of extensive faculty burnout, and the opportunity to reduce burnout by improving the vitality and resilience of these talented and crucial contributors. Faculty vitality, as defined by the institution, has a critical role in ensuring future institutional successes and the capacity for faculty to thrive in a complex health care economy.