Paravalvular leak closure after TAVI with plugs: A literature review with a specific focus on arterio-arterial loop.

More than mild paravalvular leak (PVL) following transcatheter aortic valve implantation (TAVI) is associated with a twofold increase in all-cause mortality, heart failure hospitalizations, and the need for reintervention. Successfully addressing PVL in TAVIs is more challenging than in surgical valves. The arterial-arterial (A-A) rail technique emerges as a valuable strategy for post-TAVI PVL closure, enhancing success rates by enabling the effective use of lower-profile vascular plug devices. When standard approach is ineffective, generating an A-A loop for post-TAVI PVL closure is probably the most recommended strategy to ensure procedural success.

The Clinical Challenge of Prosthetic Valve Endocarditis: JACC Focus Seminar 3/4.

During the past 6 decades, there have been numerous changes in prosthetic valve endocarditis (PVE), currently affecting an older population and increasing in incidence in patients with transcatheter-implanted valves. Significant microbiologic (molecular biology) and imaging diagnostic (fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography) advances have been incorporated into the 2023 Duke-International Society for Cardiovascular Infectious Diseases infective endocarditis diagnostic criteria, thus increasing the diagnostic sensitivity for PVE without sacrificing specificity in validation studies. PVE is a life-threatening disease requiring management by multidisciplinary endocarditis teams in cardiac centers to improve outcomes. Novel surgical options are now available, and an increasing set of patients may avoid surgical intervention despite indication. Selected patients may complete parenteral or oral antimicrobial treatment at home. Finally, patients with prosthetic valves implanted surgically or by the transcatheter approach are candidates for antibiotic prophylaxis before invasive dental procedures.

CACS, CCTA and mCAD-LT score in the pre-transplant assessment of coronary artery disease and the prediction of post-transplant cardiovascular events.

BACKGROUND: The optimal cardiovascular assessment of liver transplant (LT) candidates is unclear. We aimed to evaluate the performance of CT-based coronary tests (coronary artery calcium score [CACS] and coronary CT angiography [CCTA]) and a modification of the CAD-LT score (mCAD-LT, excluding family history of CAD) to diagnose significant coronary artery disease (CAD) before LT and predict the incidence of post-LT cardiovascular events (CVE). METHODS: We retrospectively analysed a single-centre cohort of LT candidates who underwent non-invasive tests; invasive coronary angiography (ICA) was performed depending on the results of non-invasive tests. mCAD-LT was calculated in all patients. RESULTS: Six-hundred-and-thirty-four LT candidates were assessed and 351 of them underwent LT. CACS, CCTA and ICA were performed in 245, 123 and 120 LT candidates, respectively. Significant CAD was found in 30% of patients undergoing ICA. The AUROCs of mCAD-LT (.722) and CCTA (.654) were significantly higher than that of CACS (.502) to predict the presence of significant CAD. Specificity of the tests ranged between 31% for CCTA and 53% for CACS. Among patients who underwent LT, CACS ≥ 400 and mCAD-LT were independently associated with the incidence of CVE; in patients who underwent CCTA before LT, significant CAD at CCTA also predicted post-LT CVE. CONCLUSION: In this cohort, mCAD-LT score and CT-based tests detect the presence of significant CAD in LT candidates, although they tend to overestimate it. Both mCAD-LT score and CT-based tests classify LT recipients according to their risk of post-LT CVE and can be used to improve post-LT risk mitigation.

Comparative histologic features among liver biopsies with biliary-pattern injury and confirmed clinical diagnoses.

Biliary-pattern injury in the liver (eg, duct injury, ductular reaction, cholestasis) can occur in several conditions, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), large duct obstruction (LDO), and drug-induced liver injury (DILI). While the histologic changes in these conditions have been individually well described, distinguishing among them remains often challenging, particularly when biopsy samples are limited in size, robust clinical information is unavailable, and/or the pathologist does not feel confident in evaluating liver disease. This study evaluated histologic features that could aid the diagnosis of biliary-pattern injury on biopsy. We reviewed 121 liver biopsies from clinically confirmed cases of PBC, PSC, chronic LDO, or DILI for multiple clinical and histologic parameters. The rates of these histologic findings were then compared among different entities. Onion-skin fibrosis was seen in 14% of PSC in comparison to 0%, 5%, and 0% of PBC, DILI, and chronic LDO (P = 0.031). Florid duct lesions were identified in 21% of PBC compared to 2% of PSC and 0% of DILI and LDO (P = 0.0065). Similarly, 42% of PBC showed lobular granulomas, compared to 7% of PSC, 11% of DILI, and 33% of chronic LDO (P = 0.0001). Cholestasis was more commonly seen in DILI (42%) and chronic LDO (83%) than in PBC (4%) and PSC (16%) (P < 0.0001). Lobular chronic inflammation was found in a significantly higher percentage of PBC and LDO than of PSC and DILI (P = 0.0009). There were significantly fewer cases of PBC showing neutrophils in ductular reaction than PSC, DILI, and LDO (P = 0.0063). Histologic findings that can help suggest a diagnosis in liver biopsies with biliary-pattern injury include florid duct lesions, lobular granulomas, lack of neutrophils in ductular reaction, and lobular chronic inflammation in PBC; onion-skin fibrosis in PSC; cholestasis and feathery degeneration in DILI; and lobular granulomas, lobular chronic inflammation, cholestasis, and feathery degeneration in chronic LDO. These findings are likely most helpful when complicating factors interfere with biopsy interpretation.

Repair of mitral prolapse: comparison of thoracoscopic minimally invasive and conventional approaches.

OBJECTIVES: Surgical repair remains the best treatment for severe primary mitral regurgitation (MR). Minimally invasive mitral valve surgery is being increasingly performed, but there is a lack of solid evidence comparing thoracoscopic with conventional surgery. Our objective was to compare outcomes of both approaches for repair of leaflet prolapse. METHODS: All consecutive patients undergoing surgery for severe MR due to mitral prolapse from 2012 to 2020 were evaluated according to the approach used. Freedom from mortality, reoperation and recurrent severe MR were evaluated by Kaplan-Meier method. Differences in baseline characteristics were adjusted with propensity score-matched analysis (1:1, nearest neighbour). RESULTS: Three hundred patients met inclusion criteria and were divided into thoracoscopic (N = 188) and conventional (sternotomy; N = 112) groups. Unmatched patients in the thoracoscopic group were younger and had lower body mass index, New York Heart Association class and EuroSCORE II preoperatively. After matching, thoracoscopic group presented significantly shorter mechanical ventilation (9 vs 15 h), shorter intensive care unit stay (41 vs 65 h) and higher postoperative haemoglobin levels (11 vs 10.2 mg/dl) despite longer bypass and cross-clamp times (+30 and +17 min). There were no differences in mortality or MR grade at discharge between groups nor differences in survival, repair failures and reinterventions during follow-up. CONCLUSIONS: Minimally invasive mitral repair can be performed in the majority of patients with mitral prolapse, without compromising outcomes, repair rate or durability, while providing shorter mechanical ventilation and intensive care unit stay and less blood loss.

Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis.

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.

Heart Valve Involvement in Patients with Antiphospholipid Syndrome: A Long-Term Follow-Up Study of a Single Centre.

BACKGROUND: Valve involvement is the most common cardiac manifestation in antiphospholipid syndrome (APS). The objective of the study was to describe the prevalence, clinical and laboratory features, and evolution of APS patients with heart valve involvement. METHODS: A retrospective longitudinal and observational study of all APS patients followed by a single centre with at least one transthoracic echocardiographic study. RESULTS: 144 APS patients, 72 (50%) of them with valvular involvement. Forty-eight (67%) had primary APS, and 22 (30%) were associated with systemic lupus erythematosus (SLE). Mitral valve thickening was the most frequent valve involvement present in 52 (72%) patients, followed by mitral regurgitation in 49 (68%), and tricuspid regurgitation in 29 (40%) patients. Female sex (83% vs. 64%; p = 0.013), arterial hypertension (47% vs. 29%; p = 0.025), arterial thrombosis at APS diagnosis (53% vs. 33%; p = 0.028), stroke (38% vs. 21%; p = 0.043), livedo reticularis (15% vs. 3%; p = 0.017), and lupus anticoagulant (83% vs. 65%; p = 0.021) were more prevalent in those with valvular involvement. Venous thrombosis was less frequent (32% vs. 50%; p = 0.042). The valve involvement group suffered from higher mortality (12% vs. 1%; p = 0.017). Most of these differences were maintained when we compared patients with moderate-to-severe valve involvement (n = 36) and those with no or mild involvement (n = 108). CONCLUSIONS: Heart valve disease is a frequent manifestation in our cohort of APS patients and is associated with demographic, clinical and laboratory features, and increased mortality. More studies are needed, but our results suggest that there may be a subgroup of APS patients with moderate-to-severe valve involvement with its own characteristics that differs from the rest of the patients with mild valve involvement or without valve involvement.

Reappraisal of [18F]FDG-PET/CT for diagnosis and management of cardiac implantable electronic device infections.

INTRODUCTION AND OBJECTIVES: The role of [18F]FDG-PET/CT in cardiac implantable electronic device (CIED) infections requires better evaluation, especially in the diagnosis of systemic infections. We aimed to determine the following: a) the diagnostic accuracy of [18F]FDG-PET/CT in each CIED topographical region, b) the added value of [18F]FDG-PET/CT over transesophageal echocardiography (TEE) in diagnosing systemic infections, c) spleen and bone marrow uptake in differentiating isolated local infections from systemic infections, and d) the potential application of [18F]FDG-PET/CT in follow-up. METHODS: Retrospective single-center study including 54 cases and 54 controls from 2014 to 2021. The Primary endpoint was the diagnostic yield of [18F]FDG-PET/CT in each topographical CIED region. Secondary analyses described the performance of [18F]FDG-PET/CT compared with that of TEE in systemic infections, bone marrow and spleen uptake in systemic and isolated local infections, and the potential application of [18F]FDG-PET/CT in guiding cessation of chronic antibiotic suppression when completed device removal is not performed. RESULTS: We analyzed 13 (24%) isolated local infections and 41 (76%) systemic infections. Overall, the specificity of [18F]FDG-PET/CT was 100% and sensitivity 85% (79% pocket, 57% subcutaneous lead, 22% endovascular lead, 10% intracardiac lead). When combined with TEE, [18F]FDG-PET/CT increased definite diagnosis o fsystemic infections from 34% to 56% (P=.04). Systemic infections with bacteremia showed higher spleen (P=.05) and bone marrow metabolism (P=.04) than local infections. Thirteen patients without complete device removal underwent a follow-up [18F]FDG-PET/CT, with no relapses after discontinuation of chronic antibiotic suppression in 6 cases with negative follow-up [18F]FDG-PET/CT. CONCLUSIONS: The sensitivity of [18F]FDG-PET/CT for evaluating CIED infections was high in local infections but much lower in systemic infections. However, accuracy increased when [18F]FDG-PET/CT was combined with TEE in endovascular lead bacteremic infection. Spleen and bone marrow hypermetabolism could differentiate bacteremic systemic infection from local infection. Although further prospective studies are needed, follow-up [18F]FDG-PET/CT could play a potential role in the management of chronic antibiotic suppression therapy when complete device removal is unachievable.

Forty-Year Trends in Cardiac Implantable Electronic Device Infective Endocarditis.

Background: Studies investigating cardiac implantable electronic device infective endocarditis (CIED-IE) epidemiological changes and prognosis over long periods of time are lacking. Methods: Retrospective single cardiovascular surgery center cohort study of definite CIED-IE episodes between 1981-2020. A comparative analysis of two periods (1981-2000 vs 2001-2020) was conducted to analyze changes in epidemiology and outcome over time. Results: One-hundred and thirty-eight CIED-IE episodes were diagnosed: 25 (18%) first period and 113 (82%) second. CIED-IE was 4.5 times more frequent in the second period, especially in implantable cardiac defibrillators. Age (63 [53-70] vs 71 [63-76] years, P < .01), comorbidities (CCI 3.0 [2-4] vs 4.5 [3-6], P > .01), nosocomial infections (4% vs 15.9%, P = .02) and transfers from other centers (8% vs 41.6%, P < .01) were significantly more frequent in the second period, as were methicillin-resistant coagulase-negative staphylococcal (MR-CoNS) (0% vs 13.3%, P < .01) and Enterococcus spp. (0% vs 5.3%, P = .01) infections, pulmonary embolism (0% vs 10.6%, P < .01) and heart failure (12% vs 28.3%, p < .01). Second period surgery rates were lower (96% vs 87.6%, P = .09), and there were no differences in in-hospital (20% vs 11.5%, P = .11) and one-year mortalities (24% vs 15%, P = .33), or relapses (8% vs 5.3%, P = 0.65). Multivariate analysis showed Charlson index (hazard ratios [95% confidence intervals]; 1.5 [1.16-1.94]) and septic shock (23.09 [4.57-116.67]) were associated with a worse prognosis, whereas device removal (0.11 [.02-.57]), transfers (0.13 [.02-0.95]), and second-period diagnosis (0.13 [.02-.71]) were associated with better one-year outcomes. Conclusions: CIED-IE episodes increased more than four-fold during last 40 years. Despite CIED-IE involved an older population with more comorbidities, antibiotic-resistant MR-CoNS, and complex devices, one-year survival improved.

Relationship among Streptococcus gallolyticus Subsp. gallolyticus, Enterococcus faecalis and Colorectal Neoplasms in Recurrent Endocarditis: A Historical Case Series.

OBJECTIVES: The role of colorectal neoplasms (CRN) as a common potential source of recurrent Streptococcus gallolyticus subsp. gallolyticus (SGG) and Enterococcus faecalis (EF) endocarditis remains unstudied. We aimed to investigate what proportion of episodes of recurrent endocarditis are caused by a succession of SGG and EF, or vice versa, and to assess the role of a colonic source in such recurrent episodes. METHODS: we conducted a retrospective analysis of two prospective endocarditis cohorts (1979-2019) from two Spanish hospitals, providing descriptive analyses of the major features of the endocarditis episodes, colonoscopy findings, and histologic results. RESULTS: among 1552 IE episodes, 204 (13.1%) were caused by EF and 197 (12.7%) by SGG, respectively. There were 155 episodes (10%) of recurrent IE, 20 of which (12.9%) were due to a succession of SGG/EF IE in 10 patients (the first episode caused by SGG in eight cases, and by EF in two cases). The median follow-up was 86 (interquartile range 34-156) months. In 8/10 initial episodes, the causative microorganism was SGG, and all patients were diagnosed with CRN either during the initial episode or during follow-up. During the second episode of IE or follow-up, colonoscopies revealed CRN in six patients. CONCLUSIONS: There seems to be an association between SGG and EF in recurrent endocarditis that warrants further investigation. Our findings reinforce the need for systematically performing colonoscopy in the event of endocarditis caused by both microorganisms.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

Infective Endocarditis: New Challenges in a Classic Disease.

Infective endocarditis is a relatively rare, but deadly infection, with an overall mortality of around 20% in most series. Clinical manifestations have evolved in response to significant epidemiological shifts in industrialized nations, with a move toward a nosocomial or health-care-related pattern, in older patients, with more episodes associated with prostheses and/or intravascular electronic devices and a predominance of staphylococcal and enterococcal etiology.Diagnosis is often challenging and is based on the conjunction of clinical, microbiological, and imaging information, with notable progress in recent years in the accuracy of echocardiographic data, coupled with the recent emergence of other useful imaging techniques such as cardiac computed tomography (CT) and nuclear medicine tools, particularly 18F-fluorodeoxyglucose positron emission/CT.The choice of an appropriate treatment for each specific case is complex, both in terms of the selection of the appropriate agent and doses and durations of therapy as well as the possibility of using combined bactericidal antibiotic regimens in the initial phase and finalizing treatment at home in patients with good evolution with outpatient oral or parenteral antimicrobial therapies programs. A relevant proportion of patients will also require valve surgery during the active phase of treatment, the timing of which is extremely difficult to define. For all the above, the management of infective endocarditis requires a close collaboration of multidisciplinary endocarditis teams.

Pembrolizumab Improves Survival After Resection of Intracardiac Metastatic Cervical Carcinoma.

Intracardiac metastasis of cervical squamous cell carcinoma (C-SCC) is rare, with historically poor long-term survival. We report the case of a 55-year-old woman with prior metastatic C-SCC who was found to have a right ventricular mass causing functional pulmonic stenosis and multiple pulmonary emboli 19 months after her initial diagnosis. She underwent surgical resection to prevent further embolization and heart failure. Pathology confirmed metastatic C-SCC and she was maintained on adjuvant pembrolizumab. She remained well 32 months later without further disease progression. Surgical resection of intracardiac metastasis of C-SCC combined with pembrolizumab therapy may result in improved postoperative life expectancy.

Abdominal normothermic regional perfusion in controlled donation after circulatory determination of death liver transplantation: Outcomes and risk factors for graft loss.

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.

Pilot Gene Expression and Histopathologic Analysis of Tracheal Resections in Tracheobronchomalacia.

BACKGROUND: The airway structures and messenger RNA expression of genes that regulate airway inflammation and remodeling may be altered in the trachea of patients with tracheobronchomalacia (TBM). METHODS: Fourteen tracheal specimens obtained from 2005 to 2018 were used in this study. Surgical resection specimens from patients with TBM and tracheal stenosis (TS) were compared with control tracheal specimens obtained from autopsy cases. We investigated the messenger RNA expression of genes encoding fibroblast growth factor (FGF) binding protein 2 (FGFBP2), FGF receptor R3 (FGFR3), interleukin-1ß (IL1ß), tumor growth factor-ß1 (TGFß1), tissue inhibitor of metalloproteinases 1 (TIMP1), and intercellular adhesion molecule 1 (ICAM1) as well as established markers of airway inflammation including interferon-γ (IFNγ) and tumor necrosis factor (TNF). The relative expression of target transcripts was assessed by quantitative real-time polymerase chain reaction. A histologic examination of the same resected airway specimens was performed on formalin-fixed paraffin-embedded tissue sections. RESULTS: FGFBP2 and FGFR3 showed higher expression in TBM compared with TS and control groups (P < .05 and P < .01, respectively). Furthermore, both TGFß1 and TIMP1 were elevated in TBM patients compared with control subjects (P < .05). Conversely ICAM1 was downregulated in TBM versus TS and control subjects (P < .05). IL1ß, IFNγ, and TNF were increased in TBM, although it did not achieve statistical significance. Histologically compared with control airways both TBM and TS demonstrated submucosal fibrotic changes, with TBM additionally demonstrating alterations in elastin fiber quality and density in the posterior membrane. CONCLUSIONS: Significant changes in gene expression are observed in the tracheal walls of patients with TBM and TS compared with control subjects.

Development of High-Level Daptomycin Resistance in Abiotrophia and Granulicatella Species Isolates from Patients with Infective Endocarditis.

Abiotrophia and Granulicatella species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal antibiotic treatment for these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profiles of Abiotrophia and Granulicatella IE isolates, investigate high-level daptomycin resistance (HLDR) development, and evaluate daptomycin activity in combination therapy. In vitro studies with 16 IE strains (6 Abiotrophia defectiva strains, 9 Granulicatella adiacens strains, and 1 G. elegans strain) were performed using microdilution to determine MICs and time-kill methodology to evaluate combination therapy. Daptomycin nonsusceptibility (DNS) (MIC ≥ 2 mg/liter) and HLDR (MIC ≥ 256 mg/liter) were based on existing Clinical and Laboratory Standards Institute (CLSI) breakpoints for viridans group streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% versus 0% and 67% versus 33%) but less susceptible to ceftriaxone and daptomycin (56% versus 83% and 11% versus 50%). HLDR developed in both A. defectiva (33%) and G. adiacens (78%) after 24 h of exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains), or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in G. adiacens, whereas in A. defectiva, HLDR reversed to the baseline MIC at day 10. This study is the first to demonstrate rapid HLDR development in Abiotrophia and Granulicatella species in vitro. Resistance was stable, and most combination therapies did not prevent it.

Argon Plasma Coagulation (APC) for the Treatment of Excessive Dynamic Airway Collapse (EDAC): An Animal Pilot Study.

BACKGROUND: Surgical stabilization of the airway through tracheobronchoplasty (TBP) is the current treatment modality for patients with severe symptomatic excessive dynamic airway collapse. However, TBP is associated with increased morbidity and mortality. Bronchoscopic treatment of the posterior membrane using argon plasma coagulation (APC) may be a safer alternative to TBP in highly selected patients. This study aimed to evaluate the effect of APC in the tracheobronchial tree of a sheep animal model. PATIENTS AND METHODS: Two adult sheep were used for this study. Under flexible bronchoscopy, the posterior tracheal membrane was treated with precise APC using different power settings. Chest computed tomography was done at 2 days and bronchoscopy was performed at 30 days following initial procedure, before euthanasia. The airways were assessed for the presence of treatment-related histopathologic changes along with expression of genes associated with fibrosis. RESULTS: There was no perioperative or postoperative morbidity or mortality. Chest computed tomography showed no signs of pneumomediastinum or pneumothorax. Flexible bronchoscopy showed adequate tracheobronchial tissue healing process, independent of the power settings used. Histologic changes demonstrated an increased extent of fibroblastic collagen deposition in the treated posterior membrane when higher power settings were used. In a similar manner, APC treatment managed to activate fibrosis-associated gene transcription factors, with higher settings achieving a higher level of expression. CONCLUSION: APC at high-power settings achieved higher levels of fibroblast collagen deposition at the posterior membrane and higher expression of fibrosis-associated gene transcription factors, when compared with lower settings.

Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis.

OBJECTIVES: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. METHODS: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. RESULTS: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. CONCLUSIONS: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE.