Association of Daily Step Count and Postoperative Complication among All of Us Research Participants.

BACKGROUND: The association between preoperative wearable device step counts and surgical outcomes has not been examined using commercial devices linked to electronic health records (EHR). This study measured the association between daily preoperative step counts and postoperative complications. STUDY DESIGN: Data was obtained using the All of Us (AOU) Research program, a nationwide initiative to collect EHR and health-related data from the population. Included were patients who underwent a surgical procedure included in the National Surgical Quality Improvement Program (NSQIP) targeted procedures dataset. Excluded were patients who did not have available physical activity FitBit data. Primary outcome was the development of a postoperative complication. All analyses were performed in the AOU researcher workbench. RESULTS: Of 27,150 patients who underwent a surgical procedure, 475 participants with preoperative wearable data were included. 74.7% were female and 85.2% were White. The average age was 57.2 years. The overall rate of postoperative complications was 12.6%. Patients averaging fewer than 7,500 daily steps were at increased odds for developing a postoperative complication (OR 1.83, 95% CI [1.01, 3.31]). Following adjustment for age, sex, race, comorbid disease, body mass index (BMI), and relative procedure risk, patients with a baseline average steps/day < 7,500 were at increased odds for postoperative complication (aOR = 2.06, 95% CI [1.05, 4.06]). CONCLUSIONS: This study found an increase in overall postoperative complication rate in patients recording lower average preoperative step counts. Patients with a baseline of less than 7,500 steps per day had increased odds of postoperative complications in this cohort. This data supports the use of wearable devices for surgical risk stratification and suggests step count may measure preoperative fitness.

From Alpha to Omicron and Beyond: Associations Between SARS-CoV-2 Variants and Surgical Outcomes.

INTRODUCTION: The COVID-19 pandemic has significantly influenced surgical practices, with SARS-CoV-2 variants presenting unique pathologic profiles and potential impacts on perioperative outcomes. This study explores associations between Alpha, Delta, and Omicron variants of SARS-CoV-2 and surgical outcomes. METHODS: We conducted a retrospective analysis using the National COVID Cohort Collaborative database, which included patients who underwent selected major inpatient surgeries within eight weeks post-SARS-CoV-2 infection from January 2020 to April 2023. The viral variant was determined by the predominant strain at the time of the patient's infection. Multivariable logistic regression models explored the association between viral variants, COVID-19 severity, and 30-d major morbidity or mortality. RESULTS: The study included 10,617 surgical patients with preoperative COVID-19, infected by the Alpha (4456), Delta (1539), and Omicron (4622) variants. Patients infected with Omicron had the highest vaccination rates, most mild disease, and lowest 30-d morbidity and mortality rates. Multivariable logistic regression demonstrated that Omicron was linked to a reduced likelihood of adverse outcomes compared to Alpha, while Delta showed odds comparable to Alpha. Inclusion of COVID-19 severity in the model rendered the odds of major morbidity or mortality equal across all three variants. CONCLUSIONS: Our study examines the associations between the clinical and pathological characteristics of SARS-CoV-2 variants and surgical outcomes. As novel SARS-CoV-2 variants emerge, this research supports COVID-19-related surgical policy that assesses the severity of disease to estimate surgical outcomes.

Selective Inhibition of Bromodomain-Containing Protein 4 Reduces Myofibroblast Transdifferentiation and Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a lethal disease driven by myofibroblast expansion. Currently no therapies exist that target the epigenetic mechanisms controlling myofibroblast transdifferentiation, which is responsible for unregulated extracellular matrix (ECM) production. We have recently shown that bromodomain-containing protein 4 (BRD4), an epigenetic regulator that forms a scaffold for nuclear activators and transcription factors, is essential for TGFß-induced myofibroblast transdifferentiation. However, its role in the development and progression of pulmonary fibrosis in vivo has not been established. Here, we evaluate the hypothesis that BRD4 bromodomain interactions mediate myofibroblast expansion and fibrosing disease in vivo. C57BL/6J mice challenged with intratracheal bleomycin were systemically treated with a selective allosteric inhibitor of the BRD4 bromodomain 1 (BD1), ZL0591 (10 mg/kg), during the established fibrotic phase (14 days post-bleomycin) in a rigorous therapeutic paradigm. Eleven days after initiation of ZL0591 treatment (25 days post-bleomycin), we detected a significant improvement in blood O2 saturation compared to bleomycin/vehicle control. Twenty-eight days post-bleomycin, we observed a reduction in the volumetric Hounsfield Unit (HU) density by micro computed tomography (µCT) in the ZL0591-treated group, as well as a reduction in collagen deposition (hydroxyproline content) and severity of injury (Ashcroft scoring). Myofibroblast transdifferentiation was measured by smooth muscle α-actin (αSMA) staining, indicating a loss of this cell population in the ZL0591-treated group, and corresponded to reduced transcript levels of myofibroblast-associated extracellular matrix genes, tenascin-C and collagen 1α1. We conclude that BRD4 BD1 interactions are critical for myofibroblast transdifferentiation and fibrotic progression in a mouse model of pulmonary fibrosis.

Redundancy in aromatic O-demethylation and ring opening reactions in Novosphingobium aromaticivorans and their impact in the metabolism of plant derived phenolics.

Lignin is a plant heteropolymer composed of phenolic subunits. Because of its heterogeneity and recalcitrance, the development of efficient methods for its valorization still remains an open challenge. One approach to utilize lignin is its chemical deconstruction into mixtures of monomeric phenolic compounds followed by biological funneling into a single product. Novosphingobium aromaticivorans DSM12444 has been previously engineered to produce 2-pyrone-4,6-dicarboxylic acid (PDC) from depolymerized lignin by simultaneously metabolizing multiple aromatics through convergent routes involving the intermediates 3-methoxygallic acid (3-MGA) and protocatechuic acid (PCA). We investigated enzymes predicted to be responsible for O-demethylation and oxidative aromatic ring opening, two critical reactions involved in the metabolism of phenolics compounds by N. aromaticivorans The results showed the involvement of DesA in O-demethylation of syringic and vanillic acids, LigM in O-demethylation of vanillic acid and 3-MGA, and a new O-demethylase, DmtS, in the conversion of 3-MGA into gallic acid (GA). In addition, we found that LigAB was the main aromatic ring opening dioxygenase involved in 3-MGA, PCA, and GA metabolism, and that a previously uncharacterized dioxygenase, LigAB2, had high activity with GA. Our results indicate a metabolic route not previously identified in N. aromaticivorans that involves O-demethylation of 3-MGA to GA. We predict this pathway channels ∼15% of the carbon flow from syringic acid, with the rest following ring opening of 3-MGA. The new knowledge obtained in this study allowed for the creation of an improved engineered strain for the funneling of aromatic compounds that exhibits stoichiometric conversion of syringic acid into PDC.IMPORTANCE For lignocellulosic biorefineries to effectively contribute to reduction of fossil fuel use, they need to become efficient at producing chemicals from all major components of plant biomass. Making products from lignin will require engineering microorganisms to funnel multiple phenolic compounds to the chemicals of interest, and N. aromaticivorans is a promising chassis for this technology. The ability of N. aromaticivorans to efficiently and simultaneously degrade many phenolic compounds may be linked to having functionally redundant aromatic degradation pathways and enzymes with broad substrate specificity. A detailed knowledge of aromatic degradation pathways is thus essential to identify genetic engineering targets to maximize product yields. Furthermore, knowledge of enzyme substrate specificity is critical to redirect flow of carbon to desired pathways. This study described an uncharacterized pathway in N. aromaticivorans and the enzymes that participate in this pathway, allowing the engineering of an improved strain for production of PDC from lignin.