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Driveline infection (DLI) is common after left ventricular assist device (LVAD). Limited data exist on DLI prevention and management. We investigated the impact of standardized driveline care initiatives, specific pathogens, and chronic antibiotic suppression (CAS) on DLI outcomes. 591 LVAD patients were retrospectively categorized based on driveline care initiatives implemented at our institution (2009-2019). Era (E)1: nonstandardized care; E2: standardized driveline care protocol; E3: addition of marking driveline exit site; E4: addition of "no shower" policy. 87(15%) patients developed DLI at a median (IQR) of 403(520) days. S. aureus and P. aeruginosa were the most common pathogens. 31 (36%) of DLI patients required incision and drainage (I&D) and 5 (5.7%) device exchange. P. aeruginosa significantly increased risk for initial I&D (HR 2.7, 95% CI, 1.1-6.3) and recurrent I&D or death (HR 4.2, 95% CI, 1.4-12.5). Initial I&D was associated with a significant increased risk of death (HR 2.92 (1.33-6.44); P = 0.008) when compared to patients who did not develop DLI. Implementation of standardized driveline care protocol (E2) was associated with increased 2-year freedom from DLI compared to nonstandardized care (HR 0.36, 95% CI, 0.2-0.6, P < 0.01). Additional preventive strategies (E3&E4) showed no further reduction in DLI rates. 57(65%) DLI patients received CAS, 44% of them required escalation to intravenous antibiotics and/or I&D. Presence of P. aeruginosa DLI markedly increased risk for I&D or death. Conditional survival of patients progressing to I&D is diminished. Standardized driveline care protocol was associated with a significant reduction in DLI, while additional preventive strategies require further testing.

Introduction Effective tacrolimus (TAC) dosing is hampered by complex pharmacokinetics and significant patient variability. The gut microbiome, a key mediator of endotoxemia, inflammation and oxidative stress in advanced heart failure (HF) patients, is a possible contributor to interindividual variations in drug efficacy. The effect of alterations in the gut microbiome on TAC dosing requirements after heart transplant (HT) has not been explored. Methods We enrolled 24 patients (mean age = 55.8 ±2.3 years) within 3 months post-HT. Biomarkers of endotoxemia ((lipopolysaccharide (LPS)), inflammation (tumor necrosis factor-α (TNF-α)) and oxidative stress (8,12-iso-Isoprostane F-2alpha-VI) were measured in 16 blood samples. 22 stool samples were analyzed using 16S rRNA sequencing. TAC dose and serum trough level were measured at the time of stool and blood collection. TAC doses were reported in mg/kg/day and as level-to-dose (L/D) ratio, and categorized as � vs. > median.

Background Monitoring COVID-19 infection risk among health care workers (HCWs) is a public health priority. We examined the seroprevalence of SARS-CoV-2 among HCWs following the fall infection surge in Minnesota, and before and after COVID-19 vaccination. Additionally, we assessed demographic and occupational risk factors for SARS-CoV-2 infection. Methods We conducted two rounds of seroprevalence testing among a cohort of HCWs: samples in round 1 were collected from 11/22/20–02/21/21 and in round 2 from 12/18/20–02/15/21. Demographic and occupational exposures assessed with logistic regression were age, sex, healthcare role and setting, and number of children in the household. The primary outcome was SARS-CoV-2 IgG seropositivity. A secondary outcome, SARS-CoV-2 infection, included both seropositivity and self-reported SARS-CoV-2 test positivity. Results In total, 459 HCWs were tested. 43/454 (9.47%) had a seropositive sample 1 and 75/423 (17.7%) had a seropositive sample 2. By time of sample 2 collection, 54% of participants had received at least one vaccine dose and seroprevalence was 13% among unvaccinated individuals. Relative to physicians, the odds of SARS-CoV-2 infection in other roles were increased (Nurse Practitioner: OR[95%CI] 1.93[0.57,6.53], Physician’s Assistant: 1.69[0.38,7.52], Nurse: 2.33[0.94,5.78], Paramedic/EMTs: 3.86[0.78,19.0], other: 1.68[0.58,4.85]). The workplace setting was associated with SARS-CoV-2 infection (p = 0.04). SARS-CoV-2 seroprevalence among HCWs reporting duties in the ICU vs. those working in an ambulatory clinic was elevated: OR[95%CI] 2.17[1.01,4.68]. Conclusions SARS-CoV-2 seroprevalence in HCW increased during our study period which was consistent with community infection rates. HCW role and setting—particularly working in the ICU—is associated with higher risk for SARS-CoV-2 infection.

Background The enterosalivary nitrate–nitrite–nitric oxide (NO 3 –NO 2 –NO) pathway generates NO following oral microbiota‐mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross‐sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO 2 , NO, or ammonia [NH 3 ]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation‐to‐depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH 3 summary ratio was inversely associated with a −0.10 (false discovery rate q =0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH 3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q =0.04) higher composite cardiometabolic Z score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

Background: Trimethylamine N-oxide (TMAO)—a gut-derived metabolite—is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis. Methods: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF-α (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I–IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity. Results: ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52–1.94] µM) versus either class II, III, or IV (1.99 [95% CI, 1.68–2.30], 1.97 [95% CI, 1.71–2.24], and 2.09 [95% CI, 1.83–2.34] µM, respectively; all P <0.05). In comparison to class II–IV, ln-TMAO was lower 1 month post-LVAD (1.58 [95% CI, 1.32–1.83] µM) and 1 week and 1 month post-HT (0.97 [95% CI, 0.60–1.35] and 1.36 [95% CI, 1.01–1.70] µM). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76–2.22] µM) and HT (>6 months: 1.86 [95% CI, 1.66–2.05] µM) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity. Conclusions: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.

Aims Infections are common following left ventricular assist device (LVAD) implantation and predict adverse events. Infections are frequent prior to LVAD implantation although their impact on postoperative outcomes remains unknown. Gut and nasal microbial imbalance may predispose to mucosal colonization with pathogens. Herein, we investigated the predictive role of pre‐LVAD infections, and explored the association of nasal Staphylococcus aureus (SA) colonization and gut microbiota, on postoperative outcomes. Methods and results Overall, 254 LVAD patients were retrospectively categorized based on pre‐LVAD infection status: Group 1, bacterial/fungal bloodstream infection (BSI); Group 2, other bacterial/fungal; Group 3, viral; and Group 4, no infection. In a subset of patients, nasal SA colonization (n = 140) and pre‐LVAD stool (n = 25) were analysed using 16S rRNA sequencing. A total of 75 (29%) patients had a pre‐LVAD infection [Group 1: 22 (29%); Group 2: 41 (55%); Group 3: 12 (16%)]. Pre‐LVAD BSIs were independent predictors of 1‐year postoperative mortality and infections [Group 1 vs. 4: hazard ratio (HR) 2.70, P = 0.036 vs. HR 1.8, P = 0.046]. In an unadjusted analysis, pre‐LVAD infections other than BSIs, INTERMACS profile ≤2, higher serum creatinine, lower serum albumin and nasal SA colonization were also significantly associated with postoperative infections. Patients with early post‐LVAD infections exhibited decreased microbial diversity (P < 0.05). Conclusions Pre‐LVAD infections are common. BSIs independently predict postoperative mortality and infections. Additional studies are needed to confirm our findings that pre‐LVAD SA nasal colonization and gut microbial composition can help stratify patients' risk for infectious complications after LVAD implantation.

Periodontitis affects up to 50% of individuals worldwide, and 8.5% are diagnosed with diabetes. The high-comorbidity rate of these diseases may suggest, at least in part, a shared etiology and pathophysiology. Changes in oral microbial communities have been documented in the context of severe periodontitis and diabetes, both independently and together. However, much less is known about the early oral microbial markers of these diseases. We used a subset of the ORIGINS project dataset, which collected detailed periodontal and cardiometabolic information from 787 healthy individuals, to identify early microbial markers of periodontitis and its association with markers of cardiometabolic health. Using state-of-the-art compositional data analysis tools, we identified the log-ratio of Treponema to Corynebacterium bacteria to be a novel Microbial Indicator of Periodontitis (MIP), and found that this MIP correlates with poor periodontal health and cardiometabolic markers early in disease pathogenesis in both subgingival plaque and saliva.