Accelerometer-Derived Patterns of Physical Activity and Incident Frailty

Low physical activity (PA) is a common phenotype of frailty, but whether disengagement of daily lifestyle PA signals impending frailty remains unexplored. Using STURDY (Study to Understand Fall Reduction and Vitamin D in You) data from 499 robust/prefrail adults (mean age=76 + 5 years; 42% women), we examined whether accelerometer patterns (activity counts/day, active minutes/day, and activity fragmentation) were prospectively associated with incident frailty over 2 years of follow-up; 48 (10%) participants developed frailty. In Discrete-Cox hazard models adjusted for demographics, medical conditions, and device wear days, every 30 min/day higher baseline active time, 100,000 more activity counts/day, and 1% lower activity fragmentation was associated with a 13% (p=0.003), 10% (p=0.001), and 8% (p<0.001) lower risk of frailty, respectively. Our results show that both reduced amounts and fragmented patterns of daily PA captured from accelerometry are associated with phenotypic frailty and might signal frailty onset.

Reverse Trigger in Ventilated Non-ARDS Patients: A Phenomenon Can Not Be Ignored!

IntroductionThe role of reverse trigger (RT) was unknown in ventilated non-acute respiratory distress syndrome (ARDS) patients. So we conducted a retrospective study to evaluate the incidence, characteristics and physiologic consequence of RT in such population.MethodSix ventilated non-ARDS patients were included, the esophageal balloon catheter were placed for measurements of respiratory mechanics in all patients. And the data were analyzed to identified the occurrence of RT, duration of the entrainment, the entrainment pattern or ratio, the phase difference (dP) and the phase angle (θ), phenotypes, Effects and clinical correlations of RT.ResultRT was detected in four patients of our series (66.7%), and the occurrence of RT varying from 19 to 88.6% of their recording time in these 4 patients. One patient (No.2) showed a stable 1:1 ratio and Mid-cycle RT was the most common phenotype. However, the remained patients showed a mixed ratios, and Late RT was the most common phenotype, followed by RT with breath stacking. The average values of mean phase delay and phase angles were 0.39s (0.32, 0.98) and 60.52° (49.66, 102.24). Mean phase delay and phase angles were shorter in early reverse triggering with early and delayed relaxation, and longer in mid, late RT and RT with breath stacking. Pmus was variable between patients and phenotypes, and larger Pmus was generated in Early RT, Delayed Relaxation and mid cycle RT. When the RT occurred, the Peso increased 17.27 (4.91, 19.71) cmH2O compared to the controlled breathing, and the average value of incremental ΔPeso varied widely inter and intra patients (Table 3B and Figure 1). Larger ΔPeso was always generated in Early RT, Delayed Relaxation and mid cycle RT, accompanied by an significant increase of PL with 19.12 (0.75) cmH2O and 16.10 (6.23) cmH2O.ConclusionRT could also be observed in ventilated non-ARDS patients. The characteristics of pattern and phenotype was similar to RT in ARDS patients to a large extent. And RT appeared to alter lung stress and delivered volumes.

1629. Vancomycin Resistance in Enterococcus faecium Clinical Isolates Responsible for Bloodstream Infections in US Hospitals Over Ten Years (2010-2019) and Activity of Oritavancin

Background Enterococcus faecium (EFM) causes difficult-to-treat infections due to its intrinsic resistance (R) and ability to acquire R to many antimicrobials. This study evaluated the vancomycin (VAN)-R rates over time and the activity of oritavancin (ORI) against a collection of EFM causing bloodstream infections (BSI). Methods A total of 1,081 BSI EFM isolates collected from 36 US hospitals in a prevalence mode design during 2010-2019 were evaluated. Bacterial identification was confirmed by MALDI-TOF MS. Susceptibility testing was performed by reference broth microdilution. For comparison, the ORI breakpoint for VAN-susceptible E. faecalis was applied to EFM. Isolates were characterized as VanA or VanB phenotypes based on their susceptibility (S) to VAN and teicoplanin (TEC). The VanB phenotype was confirmed by PCR and/or whole genome sequencing. Results Overall, 72.3% (782/1,081) of EFM were VAN-R (Table). VanA was the most common phenotype (97.7%; 764/782). The yearly VAN-R rates decreased from 81.8% in 2010 to 58.7% in 2019. A total of 18 (2.3%) isolates exhibited a VanB phenotype (TEC MIC, 0.5-8 mg/L); however, the vanB gene only was confirmed in 9 EFM isolates (TEC MIC, 0.5-1 mg/L), which were all collected in 2010-2012. The remaining 9 (50.0%) VanB phenotype EFM isolates carried a vanA gene (TEC MIC, 4-8 mg/L). ORI was very active against VAN-susceptible EFM (MIC50/90, ≤ 0.008/≤0.008/mg/L), VanA (MIC50/90, 0.03/0.12 mg/L; MIC100, 0.5 mg/L), and VanB (MIC50/90, ≤ 0.008/0.015 mg/L; MIC100, 0.03 mg/L) subsets. Only linezolid (LZD) and ORI (MIC, ≤ 0.12 mg/L) showed > 95.0%S against EFM and VAN-R subsets. Daptomycin (DAP)-R rarely was observed (0.8%), but it was more frequently found in the last 5 years. However, 49.9% of EFM isolates showed elevated DAP MICs (2 and 4 mg/L). ORI inhibited 77.8%, and 100.0% of DAP-R and LZD-nonsusceptible EFM isolates at ≤ 0.12 mg/L, respectively. Conclusion VAN-R rates among EFM causing BSI in the US decreased during 2010-2019. VanA remains the most common phenotype, whereas vanB-carrying isolates became rarer in later years. Interestingly, half of VanB-phenotype isolates carried a vanA gene. ORI was very active against EFM causing BSI, including isolates R to VAN, DAP, and/or nonsusceptible to LZD. Table 1 Disclosures Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Emery–Dreifuss muscular dystrophy–linked genes and centronuclear myopathy–linked genes regulate myonuclear movement by distinct mechanisms

Muscle cells are a syncytium in which the many nuclei are positioned to maximize the distance between adjacent nuclei. Although mispositioned nuclei are correlated with many muscle disorders, it is not known whether this common phenotype is the result of a common mechanism. To answer this question, we disrupted the expression of genes linked to Emery–Dreifuss muscular dystrophy (EDMD) and centronuclear myopathy (CNM) in Drosophila and evaluated the position of the nuclei. We found that the genes linked to EDMD and CNM were each necessary to properly position nuclei. However, the specific phenotypes were different. EDMD-linked genes were necessary for the initial separation of nuclei into distinct clusters, suggesting that these factors relieve interactions between nuclei. CNM-linked genes were necessary to maintain the nuclei within clusters as they moved toward the muscle ends, suggesting that these factors were necessary to maintain interactions between nuclei. Together these data suggest that nuclear position is disrupted by distinct mechanisms in EDMD and CNM.