Faculty Bibliography

Carfilzomib-lenalidomide-dexamethasone (KRd) therapy has yielded promising results in patients with newly diagnosed multiple myeloma (NDMM). Cereblon (CRBN) is the direct molecular target of lenalidomide and genetic polymorphisms in CRBN have been associated with lenalidomide efficacy. In this study, we assessed the correlation of five single nucleotide variants (SNVs) in the CRBN gene with clinical response and outcomes in patients with NDMM administered KRd therapy with lenalidomide maintenance, achieving favorable trial endpoints in a prospective Phase II study (NCT01402284). Of the observed SNVs, no associations with KRd therapy response were found in this patient cohort, although strong trends in hypoalbuminemia grade and hyperbilirubinemia grade emerged across the CRBN rs1672753 genotype (P = 0.0008) and the rs1714327 genotype (P = 0.0010), respectively. Our results do not provide conclusive support for the predictive utility of CRBN gene polymorphisms as potential biomarkers of clinical response to lenalidomide-based therapy in our patient population. However, these findings remain to be validated in prospective studies using larger patient populations.

Staphylococcus aureus (S. aureus) is an important pathogen causing various limited or systemic infections. Methicillin resistant S. aureus (MRSA) in particular presents a major clinical and public health problem. Toxic shock syndrome toxin-1 (TSST-1) encoded by the gene tst is an important virulence factor of tst positive S. aureus, leading to multi-organ malfunction. However, the mechanism of TSST-1 in pathogenesis is only partly clear. In this study, we investigated the prevalence of the tst gene in clinical isolates of S. aureus. Then, animal experiments were performed to further evaluate the influence of the presence of the tst gene associated Staphylococcus aureus Pathogenicity Island (SaPI) on body weight, serum cytokine concentrations and the bacterial load in different organs. In addition, macrophages were used to analyze the secretion of cytokines in vitro and bacterial survival in the cytoplasm. Finally, pathological analysis was carried out to evaluate organ tissue impairment. The results demonstrated that the prevalence of tst gene was approximately 17.8% of the bacterial strains examined. BALB/c mice infected with tst gene associated SaPI positive isolates exhibited a severe loss of body weight and a high bacterial load in the liver, heart, kidney and spleen. Pathological analysis demonstrated that tissue impairment was more severe after infection with tst gene associated SaPI positive isolates. Moreover, the secretion of IL-6, IL-2 and IL17A by macrophages infected with tst gene associated SaPI positive isolates clearly increased. Notably, IL-6 secretion in BALB/c mice infected with tst gene associated SaPI positive isolates was higher than that in BALB/c mice infected with negative ones. Together, these results indicated that the tst gene associated SaPI may play a critical role in the pathological process of infection via a direct and persistent toxic function, and by promoting the secretion of inflammatory cytokines that indirectly induce immune suppression.

BACKGROUND:Prior studies have found that rescue and recovery workers exposed to the 9/11 World Trade Center (WTC) disaster have evidence of increased persistent hearing and other ear-related problems. The potential association between WTC disaster exposures and post-9/11 persistent self-reported hearing problems or loss among non-rescue and recovery survivors has not been well studied. METHODS:We used responses to the World Trade Center Health Registry (Registry) enrollment survey (2003-2004) and first follow-up survey (2006-2007) to model the association between exposure to the dust cloud and persistent hearing loss (n = 22,741). RESULTS:The prevalence of post-9/11 persistent hearing loss among survivors was 2.2%. The adjusted odds ratio (aOR) of hearing loss for those who were in the dust cloud and unable to hear was 3.0 (95% CI: 2.2, 4.0). Survivors with persistent sinus problems, headaches, PTSD and chronic disease histories had an increased prevalence of reported hearing problems compared to those without symptoms or chronic problems. CONCLUSIONS:In a longitudinal study, we observed an association between WTC-related exposures and post-9/11 self-reported hearing loss among disaster survivors.

Background:Gut microbes influence the development several chronic conditions marking them as targets for holistic care, prevention strategies, and potential treatments. Microbiome studies are relatively new to health research and present unfamiliar terms to clinicians and researchers. "Dysbiosis" often refers to an alteration in the gut microbiome, but conceptual clarification is rarely provided. Purpose: The purpose of this study is to refine a conceptual definition of dysbiosis based on a review of nursing literature. Method: A Rodgerian approach to concept analysis was used. CINAHL, PubMed, and Web of Science were queried using "dysbiosis" through December 2018. Each article was analyzed with regard to the antecedents, attributes, and consequences of dysbiosis. Essential elements were tabulated and compared across studies to determine recurring themes and notable outliers. Findings: Analysis revealed several important antecedences, attributes, and consequences of dysbiosis. The findings also elucidated notable gaps and highlighted the co-evolving nature of the proposed definition with advances in microbiome research. Conclusion: This article adds a proposed definition of dysbiosis, offering a contribution of conceptual clarity upon which to enhance dialogue and build research. The definition emphasizes risk factors and consequences of dysbiosis as implications for holistic nursing practice.

BACKGROUND:Few studies have documented patient attitudes and experiences with extended-release naltrexone (XR-NTX) opioid relapse prevention in criminal justice settings. This study assessed barriers and facilitators of jail-to-community reentry among adults with opioid use disorder (OUD) treated with XR-NTX, buprenorphine, methadone, and no medications. METHODS:This qualitative study conducted individual interviews with a purposeful and convenience sample of adults with OUD who were recently released from NYC jails. XR-NTX, no medication, and methadone participants were concurrently enrolled in a large randomized controlled trial evaluating XR-NTX vs. a no medication Enhanced Treatment As Usual (ETAU) condition, or enrolled in a non-randomized quasi-experimental methadone maintenance cohort. Buprenorphine participants were referred from NYC jails to a public hospital office-based buprenorphine program and not enrolled in the parent trial. Interviews were audio recorded, transcribed, independently coded by two researchers, and analyzed per a grounded theory approach adapted to the Social Cognitive Theory framework. The research team reviewed transcripts and coding to reach consensus on emergent themes. RESULTS:N = 33 adults with OUD (28 male, 5 female) completed a single individual interview. Purposeful sampling recruited persons leaving jail on XR-NTX (n = 11), no active medication treatment (n = 9), methadone (n = 9), and buprenorphine (n = 4). Emergent themes were: (1) general satisfaction with XR-NTX's long-acting antagonist effects and control of cravings; (2) "testing" XR-NTX's blockade with heroin upon reentry was common; (3) early discontinuation of XR-NTX treatment was most common among persons with high self-efficacy and/or heavy exposure to drug use environments and peers; (4) similar satisfaction regarding effects of methadone and buprenorphine maintenance among retained-in-treatment individuals, alongside general dissatisfaction with daily observed dosing requirements and misinformation and stigmas regarding methadone adverse effects; (5) unstable housing, economic insecurity, and exposure to actively using peers were attributed to early termination of treatment and relapse; (6) individual motivation and willpower as central to long-term opioid abstinence and reentry success. CONCLUSIONS:In the context of more familiar agonist maintenance treatments, XR-NTX relapse prevention during jail-to-community reentry was viewed as a helpful and unique intervention though with important limitations. Commonly described barriers to treatment retention and heroin abstinence included homelessness, economic insecurity, and drug-using peers. Trial registration ClinicalTrials.gov, NCT01999946 (XOR), Registered 03 December 2013, https://clinicaltrials.gov/ct2/show/NCT01999946 .

Fatty acids derived from fish oil are long chain omega-3 (n-3) polyunsaturated fatty acids. The important polyunsaturated fatty acids of fish oil are eicosapentaenoic acid, and docosahexaenoic acid. For decades, there has been a debate about the use of omega-3 fatty acid supplements and their benefits on cardiovascular health. The more recent trials including the JELIS, REDUCE-IT, VITAL, STRENGTH, and the ASCEND trials addressed the paucity of data of omega-3 Fatty acids on primary as well as secondary prevention of cardiovascular events and risk-benefit balance of these supplements. Prior to these studies, many large randomized controlled trials have shown conflicting results on the effect of polyunsaturated fatty acids in patients with prior coronary artery disease, stroke or major vascular events. These inconsistent results warrant a better understanding of the effects of omega-3 fatty acids on the subtypes of cardiovascular diseases, and their use in primary and secondary prevention. More recently, the REDUCE-IT study showed a possible protective benefit of fish oil supplements (in purified form and higher than normal doses) in the reduction of Triglyceride levels. It is also noteworthy that omega-3 fatty acids have found their mention in the most recent American College of Cardiology guidelines for the management of hypertriglyceridemia as an adjunct to statins and fibrates. The aim of this review is to discuss these recent updates on use of fish oil in cardiometabolic diseases, and their surrounding controversies.

Background. Pneumonia (PNU) is the second most common nosocomial infection in the United States and is associated with substantial morbidity and mortality. While definitions from CDC were developed to increase the reliability of surveillance data, reduce the burden of surveillance in healthcare facilities, and enhance the utility of surveillance data for improving patient safety - the algorithm is still laborious. We propose an implementation of a refined algorithm script which combines two CDC definitions with the use of natural language processing (NLP), a tool which relies on pattern matching to determine whether a condition of interest is reported as present or absent in a report, to automate PNU surveillance. Methods. Using SAS v9.4 to write a query, we used a combination of National Healthcare Safety Network's (NHSN) PNU and ventilator-associated event (VAE) definitions that use discrete fields found in electronic medical records (EMR) and trained an NLP tool to determine whether chest x-ray report was indicative of PNU (Fig1). To validate, we assessed sensitivity/specificity of NLP tool results compared with clinicians' interpretations. Results. The NLP tool was highly accurate in classifying the presence of PNU in chest x-rays. After training the NLP tool, there were only 4% discrepancies between NLP tool and clinicians interpretations of 223 x-ray reports - sensitivity 92.2% (81.1-97.8), specificity 97.1% (93.4-99.1), PPV 90.4% (79.0-96.8), NPV 97.7% (94.1- 99.4). Combining the automated use of discrete EMR fields with NLP tool significantly reduces the time spent manually reviewing EMRs. A manual review for PNU without automation requires approximately 10 minutes each day per admission. With a monthly average of 2,350 adult admissions at our hospital and 16,170 patient-days for admissions with at least 2 days, the algorithm saves approximately 2,695 review hours. Conclusion. The use of discrete EMR fields with an NLP tool proves to be a timelier, cost-effective yet accurate alternative to manual PNU surveillance review. By allowing an automated algorithm to review PNU, timely reports can be sent to units about individual cases. Compared with traditional CDC surveillance definitions, an automated tool allows real-time critical review for infection and prevention activities