Phase variation as a major mechanism of adaptation in Mycobacterium tuberculosis complex.

Phase variation induced by insertions and deletions (INDELs) in genomic homopolymeric tracts (HT) can silence and regulate genes in pathogenic bacteria, but this process is not characterized in MTBC (Mycobacterium tuberculosis complex) adaptation. We leverage 31,428 diverse clinical isolates to identify genomic regions including phase-variants under positive selection. Of 87,651 INDEL events that emerge repeatedly across the phylogeny, 12.4% are phase-variants within HTs (0.02% of the genome by length). We estimated the in-vitro frameshift rate in a neutral HT at 100× the neutral substitution rate at [Formula: see text] frameshifts/HT/year. Using neutral evolution simulations, we identified 4,098 substitutions and 45 phase-variants to be putatively adaptive to MTBC (P < 0.002). We experimentally confirm that a putatively adaptive phase-variant alters the expression of espA, a critical mediator of ESX-1-dependent virulence. Our evidence supports the hypothesis that phase variation in the ESX-1 system of MTBC can act as a toggle between antigenicity and survival in the host.

In-hospital outcomes of transesophageal versus intracardiac echocardiography guided left atrial appendage closure.

BACKGROUND: Transesophageal echocardiogram (TEE) is the preferred imaging modality to guide transcatheter left atrial appendage closure (LAAC). Intracardiac echocardiography (ICE) has evolved as a less invasive alternative to TEE. Several observational studies have shown similar success rates and perioperative complications between TEE and ICE for LAAC. OBJECTIVES: We sought to examine the temporal trends and patient characteristics of TEE versus ICE use in LAAC using a national database. We also evaluated hospital outcomes including periprocedural complications, mortality, and length of hospital stay. METHODS: This is a retrospective analysis of data from the National Readmission Database, collected from 2016 to 2018. The primary outcome was major adverse events (MAE) defined as in-hospital mortality, cardiac arrest, pericardial effusion with or without tamponade, pericardiocentesis or window pericardiocentesis and pericardial window, pericardial effusion and tamponade, and hemorrhage requiring transfusion. RESULTS: Trend analysis showed that TEE-guided LAAC increased from 96.6% in 2016 to 98.4% in 2018 (relative increase, 1.9%), while ICE-guided LAAC decreased from 3.4% to 1.6% during the same period (relative decrease, 53%, p for trend = 0.08). In the unmatched cohorts, the MAE was significantly lower in TEE-guided LAAC compared to ICE-guided LAAC (6.5% vs. 9.3%, p = 0.022). In the propensity score matching analysis, MAE remained significant (5.6% vs. 9.4%, p < 0.001). The incidence of pericardial effusion with or without tamponade remained significantly lower in the TEE group (2.3% vs. 5.8%, p < 0.001). Length of stay (3.4 vs. 1.9 days, p < 0.001) and hospitalization cost ($34,826 vs. $20,563, p < 0.001) remained significantly lower for TEE-guided LAAC. CONCLUSIONS: Compared to ICE, the incidence of MAE was significantly lower for TEE-guided LAAC, driven mainly by less pericardial effusion events. Large-scale randomized trials are needed to confirm the findings of the current and previous studies.

The transseptal puncture experience: Safety insights from FDA MAUDE database.

BACKGROUND: There is a paucity of literature on safety and efficacy of various transseptal puncture (TSP) needles. OBJECTIVES: To assess the reported mechanisms of failure, complications, and outcomes among the most frequently used transseptal needles in the United States. METHODS: We queried the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database between January 2011 and January 2021 for reports on the most commonly used transseptal needles: NRG (Baylis Medical, Montreal, Canada), and BRK (St. Jude, Saint Paul, MN)]. The primary outcome was the mechanism of failure. Secondary outcomes included clinical consequences of device failure. RESULTS: The final analysis included 306 reports of failure/complication with TSP needles (NRG n = 70, BRK n = 236). The most commonly reported mode of failure was detachment of the needle component (i.e., clip, hub, stopcock, shaft, spring, or needle tip) (14.7% overall; 17.8% BRK; and 4.3% NRG). Among these reports, cardiac perforation was the most common complication (69.9% overall; 69.1% for BRK; and 72.9% for NRG). Pericardiocentesis was the second most commonly reported complication (45.1% overall; 48.3% for BRK; and 34.3% for NRG). The procedure was successfully completed in 33.3% of all cases (36.4% for BRK and 22.9% for NRG), while surgical conversion was needed in (13.4% overall; 14% for BRK and 11.4% for NRG) of the reports. Death occurred in 3.9% of all cases overall (3.4% for BRK and 5.7% for NRG). CONCLUSIONS: Needle detachment was the most common mode of failure, and cardiac perforation was the most common complication reported with TSP needles. Future efforts should focus on innovative TSP needle design, best practice guidelines, including role of imaging guidance, and increased TSP training.

Use of novel antiplatelet agents in acute coronary syndromes.

Acute coronary syndromes (ACS) encompass a broad spectrum of clinical presentations based on underlying pathology that results in myocardial ischemia and/or infarction. Despite advancements in invasive management and secondary preventive therapies, recurrent atherothrombotic coronary events remain a prevalent cause of death and recurrent cardiac events after ACS and, in those who survive, the root of long-standing cardiac comorbidities. Antiplatelet drug therapy has proven beneficial in the reduction of these events, and novel antiplatelet agents have resulted in significant improvement in clinical outcomes over the last decade. However, the balance of optimal platelet inhibition with minimal bleeding complications remains a clinical challenge. This review focuses on more recent advances in antiplatelet therapies used in the treatment of ACS.

Temporal trends of fluoroscopy time and contrast utilization in coronary chronic total occlusion revascularization: insights from a multicenter United States registry.

BACKGROUND: The impact of operator experience on fluoroscopy time and contrast utilization during percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTOs) has received limited study. METHODS: We evaluated temporal trends in fluoroscopy time and contrast utilization among 1,363 consecutive CTO PCIs performed at three US institutions between January 2006 and November 2011. RESULTS: Mean age was 65 ± 11 years, 85% of patients were men, 40% had diabetes, 37% had prior coronary artery bypass graft surgery, and 42% had prior PCI. The CTO target vessel was the right coronary artery (55%), circumflex (23%), left anterior descending artery (21%), and left main or bypass graft (1%). The retrograde approach was used in 34% of all procedures. The technical and procedural success rates were 85.5 and 84.2%, respectively. The mean procedural time, fluoroscopy time, and contrast utilization were 113 ± 61 min, 42 ± 29 min, and 294 ± 158 mL, respectively. Years since initiation of CTO PCI were independently associated with higher technical success rate (odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.52-1.70, P < 0.001), lower fluoroscopy time (OR = 0.84, 95% CI = 0.75-0.95, P = 0.005), and contrast utilization (OR = 0.84, 95% CI = 0.62-0.79, P < 0.001) during the study period. CONCLUSIONS: Among selected US-based institutions performing CTO PCI, we observed a significant reduction in total fluoroscopy time and contrast utilization paralleled with an improved technical success rate over time.

Outcomes of small coronary artery stenting with bare-metal stents versus drug-eluting stents: results from the NHLBI Dynamic Registry.

OBJECTIVES: Examine 1-year outcomes of patients with small coronary arteries in the National Heart, Lung, and Blood Institute Dynamic Registry (NHLBI) undergoing drug-eluting stent (DES) vs. bare-metal stent (BMS) placement. BACKGROUND: While randomized trials of DES vs. BMS demonstrate reduced target vessel revascularization, it is unclear whether similar outcomes are seen in unselected patients after percutaneous coronary intervention (PCI) for small coronary arteries. METHODS: Utilizing patients from the NHLBI Registry Waves 1-3 for BMS (1997-2002) and Waves 4-5 for DES (2004 and 2006), demographic, angiographic, in-hospital, and 1-year outcome data of patients with small coronary arteries treated with BMS (n = 686) vs. DES (n = 669) were evaluated. Small coronary artery was defined as 2.50-3.00 mm in diameter. RESULTS: Compared to BMS-treated patients, the mean lesion length of treated lesions was longer in the DES treated group (16.7 vs. 13.1 mm, P < 0.001) and the mean reference vessel size of attempted lesions was smaller (2.6 vs. 2.7 mm, P < 0.001). Adjusted analyses of 1-year outcomes revealed that DES patients were at lower risk to undergo coronary artery bypass graft surgery (Hazard Ratio [HR] 0.40, 95% confidence interval [CI] 0.17-0.95, P = 0.04), repeat PCI (HR 0.53, 95% CI 0.35-0.82, P = 0.004), and experience the combined major adverse cardiovascular event rate (HR 0.59, 95% CI 0.42-0.83, P = 0.002). There was no difference in the risk of death and myocardial infarction (MI) (HR 0.78, 95% CI 0.46-1.35, P = 0.38). CONCLUSIONS: In this real-world registry, patients with small coronary arteries treated with DES had significantly lower rates of repeat revascularization and major adverse cardiovascular events at 1 year compared to patients treated with BMS, with no increase in the risk of death and MI. These data confirm the efficacy and safety of DES over BMS in the treatment of small coronary arteries in routine clinical practice.

Modes of failure of guide catheter extensions: Insights from the MAUDE database.

OBJECTIVES: Guide catheter extensions (GCEs) are commonly used to facilitate percutaneous coronary interventions (PCIs). We investigated the incidence and modes of failure of GCEs.. METHODS: Data from the Manufacturer and User Facility Device Experience (MAUDE) database between 2012 and 2022 were used to investigate the most common modes of failure and related adverse events with the use of GCEs. We performed analysis of 4 commonly used catheters: GuideLiner (Teleflex), Guidezilla (Boston Scientific), TrapLiner (Teleflex), and Telescope (Medtronic). The first event reported for GuideLiner was in 2012, Guidezilla in 2018, TrapLiner in 2017, and Telescope in 2019. RESULTS: During the study period, a total of 651 events were reported to the database. A total of 429 true GCE device failures were identified: 59 (14%) for GuideLiner, 297 (69%) for Guidezilla, 47 (11%) TrapLiner, and 26 (6%) for Telescope. Catheter detachment or fracture was the most frequently reported device failure for all 4 GCEs; these failures included shaft fractures, tip deformations, and collar detachments. We identified 222 reported events as unspecified adverse events; these events included device-to-device incompatibility, difficulty to advance, and device fractures outside the patient body. Only 58 (8.9%) events resulted in patient complication. Of these, coronary artery dissection was the most frequently reported complication. CONCLUSIONS: Device detachment/fracture is the most common mode of device failure in all 4 GCEs, and coronary dissection is the most common patient complication.

Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection.

BACKGROUND: Persistent symptoms among some persons who develop COVID-19 has led to the hypothesis that SARS-CoV-2 may, in some form or location, persist for long periods following acute infection. Several studies have shown data in this regard but are limited by non-representative and small study populations, short duration since acute infection, and lack of a true-negative comparator group to assess assay specificity. METHODS: We evaluated adults with RNA-confirmed COVID-19 at multiple time points following acute infection (pandemic-era participants) and adults with specimens collected prior to 2020 (pre-pandemic era). Using once-thawed plasma, we employed the Simoa® (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens. RESULTS: Compared to 250 pre-pandemic participants who had 2% assay positivity, detection of any SARS-CoV-2 antigen was significantly more frequent among 171 pandemic-era participants at three different time periods in the post-acute phase of infection. The absolute difference in SARS-CoV-2 plasma antigen prevalence was +11% (95% CI: +5.0% to +16%) at 3.0-6.0 months post-onset of COVID-19; +8.7% (95% CI: +3.1% to +14%) at 6.1 to 10.0 months; and +5.4% (95% CI: +0.42% to +10%) at 10.1-14.1 months. Hospitalization for acute COVID-19 and, among the non-hospitalized, worse self-reported health during acute COVID-19 were associated with greater post-acute phase antigen detection. CONCLUSIONS: Compared to uninfected persons, there is an excess prevalence of SARS-CoV-2 antigenemia in SARS-CoV-2-infected individuals up to 14 months after acute COVID-19. These findings motivate an urgent research agenda regarding the short-term and long-term clinical manifestations of this viral persistence.

Transfemoral use of the GuideLiner catheter in complex coronary and bypass graft interventions.

The GuideLiner catheter (Vascular Solutions, Minneapolis, MN) is a novel, rapid exchange catheter that allows deep vessel intubation. We describe 21 patients in whom the GuideLiner catheter [7 French (F) in 76% and 6F in 24%] was used to facilitate equipment delivery (n = 14) or vessel engagement (n = 7). Pressure dampening after GuideLiner catheter insertion was observed in 12 patients (57%). The procedure was successfully completed in 19 patients (90%) and one patient developed acute vessel closure, likely due to dissection. The GuideLiner catheter can facilitate complex coronary interventions but should be used with caution to minimize the risk for vessel injury.

Effective medium theory and its limitations for the description of MoO3films doped with nanoparticles.

The present work analyses the transmittance and reflectance spectra of molybdenum trioxide film doped by silver nanoparticles as a function of angle of incidence and wavelength. As will be seen in this work, at values of angle of incidence below 40 degrees and with volume filling fraction below 1% also, some differences between the two effective medium theories are presented. First, the volume filling fraction is limited for low values (<1%) and second the scattering amplitude cannot be ignored for these cases. The novelty of this work is that the use of the effective medium model (refractive index) shows limitations in the description of the optical properties when it was applied to thin solid films.

Enhancing occupational safety in the X-ray laboratory.

Despite more than 80% of interventional operators reporting one or more orthopedic injuries attributed to the X-ray laboratory, there has been limited adoption of various strategies and equipment to minimize these injuries. A comprehensive review of these methods to reduce musculoskeletal strain is lacking in the current literature, and is essential in order to ensure a long, healthy, and productive interventional career.

Extinction Coefficient Modulation of MoO3 Films Doped with Plasmonic Nanoparticles: From an Effective Medium Theory Description.

This work focused on the application of the effective medium theory to describe the extinction coefficient (Qext) in molybdenum trioxide (MoO3) doped with different kinds of plasmonic nanoparticles, such as silver (Ag), gold (Au), and copper (Cu). Usually, in studies of these materials, it is normal to analyze the transmission or absorption spectra. However, the effect of this type or size of nanoparticles on the spectra is not as remarkable as the effect that is found by analyzing the Qext of MoO3. It was shown that the ß-phase of MoO3 enhanced the intensity response of the Qext when compared to the α-phase of MoO3. With a nanoparticle size of 5 nm, the Ag-doped MoO3 was the configuration that presents the best response in Qext. On the other hand, Cu nanoparticles with a radius of 20 nm embedded in MoO3 was the configuration that presented intensities in Qext similar to the cases of Au and Ag nanoparticles. Therefore, implementing the effective medium theory can serve as a guide for experimental researchers for the application of these materials as an absorbing layer in photovoltaic cells.

Ascites and Edema After Bicaval Orthotopic Heart Transplant.

IVC stenosis is a rare complication of bicaval orthotopic heart transplant. IVC stenosis can occur at either the cavo-atrial anastomosis, or the caval cannulation site, with presentations ranging from acute shock early post transplant to a more indolent course. Causes include extensive hemostatic suturing, fibrous contraction, and donor-recipient size mismatch. Treatment strategies include percutaneous balloon angioplasty, stenting, and surgical revision. Evaluating for IVC stenosis is recommended for unexplained lower-extremity edema, new-onset ascites, or liver abnormalities after bicaval heart transplant.

Effective medium theory to the description of plasmonic resonances: Role of Au and Ti nanoparticles embedded in MoO3 thin films.

The growing interest in functional transition metal oxides for efficient energy consumption or in the bio-sensing process; indicates that is necessary to develop a new theoretical method that describes experiments. This article presents a new theoretical methodology to characterize molybdenum trioxide (MoO3) thin films doped with resonant gold - nanoparticles (Au - NPs) and non-resonant titanium - nanoparticles (Ti - NPs). The modulation of surface plasmon resonance (SPR) and the implications in the MoO3 transmittance spectrum is described by applying an effective medium theory. The transmittance modulation was modified by variating three parameters, the radius of the NPs, the concentration of the NPs as well as the variation of the MoO3 thin films thickness. It was found that the nanoparticles concentration is the most important parameter in the transmittance modulation. Additionally, the orthorhombic and monoclinic structure of MoO3 was studied, from which it was obtained that the monoclinic structure of the MoO3 doped with Au - NPs favors the reduction in the transmittance values in the visible region which is associated with the increase of the SPR signal. Similar analyses are performed for non-resonant nanoparticles such as Ti, where it was found that optical modulation is not as marked as the case of gold nanoparticles.

Clinical Outcomes and Cost Comparisons of Stent and Non-Stent Interventions in Infrainguinal Peripheral Artery Disease: Insights From the Excellence in Peripheral Artery Disease (XLPAD) Registry.

BACKGROUND: The contemporary limb outcomes and costs of stent-based vs non-stent based strategies in endovascular revascularization of femoropopliteal (FP) peripheral artery disease (PAD) are not well understood. METHODS AND RESULTS: We present data from the ongoing United States multicenter Excellence in Peripheral Artery Disease Registry between 2006-2016 to compare stent vs non-stent treatment outcomes and associated costs in FP interventions. A total of 2910 FP interventions were performed in 2162 patients (mean age, 66 years), comprising 1339 stent based (superficial femoral artery, 93%) in 1007 patients and 1571 non-stent interventions (superficial femoral artery, 85%) in 1155 patients. A growing trend for non-stent based interventions and a declining trend in repeat revascularization rate at 1 year were observed across years of registry enrollment. Stent implantation was the prevailing strategy in treating longer FP lesions (mean length, 152 mm vs 105 mm; P<.001) and chronic total occlusions (65% vs 40%; P<.001), while stent implantation was employed less frequently when treating in-stent restenotic lesions (14% vs 20%; P<.001). Stent and non-stent interventions had similar 1-year limb outcomes in all-cause death, target-limb revascularization, target-vessel revascularization, and major or minor amputation. The average procedure costs for the stent group were significantly higher than the non-stent group ($6215 vs $4790; P<.001). CONCLUSION: There is a growing trend for non-stent FP artery interventions, with a significant decline in 1-year target-limb revascularization rates over time. One-year limb outcomes in stent-based compared to non-stent interventions are similar; however, at a significantly higher procedural cost.

Radiation Safety in the Catheterization Laboratory: Current Perspectives and Practices.

BACKGROUND: There is great variability in radiation safety practices in cardiac catheterization laboratories around the world. METHODS: We performed an international online survey on radiation safety including interventional cardiologists, electrophysiologists, interventional radiologists, and vascular surgeons. RESULTS: A total of 570 responses were received from various geographic locations, including the United States (77.9%), Asia (7.9%), Europe (6.8%), Canada (2.8%), and Mexico and Central America (2.1%). Most respondents (73%) were interventional cardiologists and 23% were electrophysiologists, with 14.4 ± 10.2 years in practice. Most respondents (75%) were not aware of their radiation dose during the past year and 21.2% had never attended a radiation safety course; 58.9% are "somewhat worried" and 31.5% are "very worried" about chronic radiation exposure. Back pain due to lead use was reported by 43.0% and radiation-related health complications including cataracts and malignancies were reported by 6.3%. Only 37.5% of respondents had an established radiation dose threshold for initiating patient follow-up. When comparing United States operators with the other respondents, the former were more likely to attend radiation safety courses (P<.001), wear dosimeters (P<.001), know their annual personal radiation exposure (P<.001), and have an established patient radiation dose threshold (P<.001). They were also more likely to use the fluoro store function, under-table shields, leaded glasses, ceiling lead glass, and disposable radiation shields, and were more concerned about the adverse effects of radiation. CONCLUSIONS: Radiation safety is of concern to catheterization laboratory personnel, yet there is significant variability in radiation protection practices, highlighting several opportunities for standardization and improvement.

Impact of Chronic Total Occlusion Revascularization Attempts on Subsequent Clinical Outcomes.

OBJECTIVES: We examined a contemporary, unselected cohort of patients with coronary chronic total occlusions (CTOs) to determine the impact of CTO revascularization on long-term outcomes. METHODS: We retrospectively assessed the impact of CTO revascularization on clinical outcomes of consecutive patients found to have a CTO during coronary angiography performed at our institution during 2011 and 2012. The primary endpoint was the incidence of a major adverse cardiac event (MACE, defined as a composite of death, myocardial infarction, stroke, and target-vessel revascularization [TVR]). Survival analysis was performed in the overall and propensity-matched retrospective cohorts of patients stratified by prior coronary artery bypass graft (CABG) surgery. Propensity-adjusted hazard ratio (HR) and 95% confidence interval (95% CI) were calculated with Cox proportional hazards analysis. All analyses were by intention to treat. RESULTS: Of 624 patients (319 without prior CABG and 305 with prior CABG) included in the present analysis, CTO revascularization (surgical or percutaneous) was attempted in 60% and 16% of patients without and with prior CABG, respectively. During a median follow-up of 26 months (range, 18-40 months), the incidence of MACE was 20.6%. CTO revascularization (achieved or attempted) was associated with lower incidence of MACE among patients without prior CABG (propensity-adjusted HR, 0.51; 95% CI, 0.27-0.94; P=.03), but not among prior CABG patients (propensity-adjusted HR, 1.38; 95% CI, 0.64-2.96; P=.41). CONCLUSION: In a large, unselected patient population with coronary CTOs, a CTO revascularization attempt was associated with lower incidence of subsequent MACE among patients without prior CABG, but not among prior CABG patients.

Optical coherence tomography findings after chronic total occlusion interventions: Insights from the "AngiographiC evaluation of the everolimus-eluting stent in chronic Total occlusions" (ACE-CTO) study (NCT01012869).

BACKGROUND: There is limited information on optical coherence tomography (OCT) findings after percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs). OCT allows high resolution imaging that can enhance understanding of the vascular response after stenting of chronically occluded vessels. METHODS: The Angiographic Evaluation of the Everolimus-Eluting Stent in Chronic Total Occlusions (ACE-CTO) study collected angiographic and clinical outcomes from 100 patients undergoing CTO PCI with the everolimus-eluting stent (EES). OCT was performed 8-months post stenting in 62 patients. Every third frame was analyzed throughout the course of the stented arterial segment. Lumen contours were semi-automatically traced and stent struts were manually delineated, with automatic measurement of the strut to lumen distance. Struts on the luminal side of the lumen contour were classified as malapposed if the distance to the lumen contour exceeded 0.108mm. RESULTS: A total of 44,450 struts in 6047 frames were analyzed, of which 4113 9.3%, 95% confidence intervals [CI] 9.0% to 9.5%) were malapposed and 1230 (2.8%, 95% CI 2.6% to 2.9%) were uncovered. Fifty-five of 62 patients (88.7%, 95% CI 78.5% to 98.4%) had at least one malapposed stent strut and 50 patients (80.7%, 95% CI 69.2% to 88.6%) had at least one uncovered stent strut. Mean strut-intimal thickness of the apposed and malapposed struts was 0.126±0.140mm and -0.491±0.440mm, respectively. CONCLUSION: High rates of stent strut malapposition and incomplete stent strut coverage were observed after CTO PCI using EES, highlighting unique challenges associated with stent implantation in CTOs.