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Background: Lymphatic disorders such as protein-losing enteropathy, plastic bronchitis, and chylothorax are important complications of the Fontan circulation and ultimately result in an increased risk of early death. Several European centers are now performing lymphatic procedures. The aim of this study is to map the extent of these lymphatic disorders and treatments provided across European pediatric cardiology centers., Methods and Results: A survey was circulated to 49 European pediatric cardiology centers consisting of 37 questions including a mix of binary, categorical, and continuous variables. Thirty-one centers (63%) participated in the study, performing a median of 250 (interquartile range, 178 - 313) cardiopulmonary bypass procedures per year. Chylothorax emerged as the most prevalent lymphatic disorder followed by protein-losing enteropathy and plastic bronchitis. The most common diagnostic investigation method was noncontrast magnetic resonance lymphangiography (52%). Eleven centers (35%) conducted lymphatic interventions with a median of 3 (interquartile range, 1 - 4) procedures per year and 12 (interquartile range, 5 - 15) interventions in total per center., Conclusions: This study confirms the rarity of and variation in treatment approaches for lymphatic disorders across Europe. With at least 11 centers offering lymphatic interventions, the adoption of these procedures is on the rise in Europe. To improve the quality of care and treatment outcomes for these complex patients, it is crucial to consider evidence-based lymphatic diagnostics, interventional lymphatic procedures, and the centralization of services in Europe.

Objective: The recent publication of randomized trials comparing open bypass surgery to endovascular therapy in patients with chronic limb-threatening ischemia, namely, Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) and Bypass versus Angioplasty in Severe Ischaemia of the Leg-2 (BASIL-2), has resulted in potentially contradictory findings. The trials differed significantly with respect to anatomical disease patterns and primary end points. We performed an analysis of patients in BEST-CLI with significant infrapopliteal disease undergoing open tibial bypass or endovascular tibial interventions to formulate a relevant comparator with the outcomes reported from BASIL-2., Methods: The study population consisted of patients in BEST-CLI with adequate single segment saphenous vein conduit randomized to open bypass or endovascular intervention (cohort 1) who additionally had significant infrapopliteal disease and underwent tibial level intervention. The primary outcome was major adverse limb event (MALE) or all-cause death. MALE included any major limb amputation or major reintervention. Outcomes were evaluated using Cox proportional regression models., Results: The analyzed subgroup included a total of 665 patients with 326 in the open tibial bypass group and 339 in the tibial endovascular intervention group. The primary outcome of MALE or all-cause death at 3 years was significantly lower in the surgical group at 48.5% compared with 56.7% in the endovascular group (P = .0018). Mortality was similar between groups (35.5% open vs 35.8% endovascular; P = .94), whereas MALE events were lower in the surgical group (23.3% vs 35.0%; P<.0001). This difference included a lower rate of major reinterventions in the surgical group (10.9%) compared with the endovascular group (20.2%; P = .0006). Freedom from above ankle amputation or all-cause death was similar between treatment arms at 43.6% in the surgical group compared with 45.3% the endovascular group (P = .30); however, there were fewer above ankle amputations in the surgical group (13.5%) compared with the endovascular group (19.3%; P = .0205). Perioperative (30-day) death rates were similar between treatment groups (2.5% open vs 2.4% endovascular; P = .93), as was 30-day major adverse cardiovascular events (5.3% open vs 2.7% endovascular; P = .12)., Conclusions: Among patients with suitable single segment great saphenous vein who underwent infrapopliteal revascularization for chronic limb-threatening ischemia, open bypass surgery was associated with a lower incidence of MALE or death and fewer major amputation compared with endovascular intervention. Amputation-free survival was similar between the groups. Further investigations into differences in comorbidities, anatomical extent, and lesion complexity are needed to explain differences between the BEST-CLI and BASIL-2 reported outcomes., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: BEST-CLI, an international randomised trial, compared an initial strategy of bypass surgery with endovascular treatment in chronic limb threatening ischaemia (CLTI). In this substudy, overall amputation rates and risk of major amputation as an initial or subsequent outcome were evaluated., Methods: A total of 1 830 patients were randomised to receive surgical or endovascular treatment in two parallel cohorts: patients with adequate single segment great saphenous vein (SSGSV) (n = 1 434) were assigned to cohort 1; and patients without adequate SSGSV (n = 396) were assigned to cohort 2. Differences in time to first event and number of amputations were evaluated., Results: In cohort 1, there were 410 (45.6%) total amputation events in the surgical group vs. 490 (54.4%) in the endovascular group (p = .001) during a mean follow up of 2.7 years. Approximately one in three patients underwent minor amputation after index revascularisation: 31.5% of the surgical group vs. 34.9% in the endovascular group (p = .17). Subsequent major amputation was required significantly less often in the surgical group compared with the endovascular group (15.0% vs. 25.6%; p = .002). The first amputation was major in 5.6% of patients in the surgical group and 6.0% in the endovascular group (p = .72). Major amputation was required in 10.3% (74/718) of patients in the surgical group and 14.9% (107/716) in the endovascular group (p = .008). In cohort 2, there were 199 amputation events in 132 patients (33.3%) during a mean follow up of 1.6 years: 95 (47.7%) in the surgical group vs. 104 (52.3%) in the endovascular group (p = .49). Major amputation was required in 15.2% (30/197) of patients in the surgical group and 14.1% (28/199) in the endovascular group (p = .74)., Conclusion: In patients with CLTI, surgical bypass with SSGSV was more effective than endovascular treatment in preventing major amputations, mainly due to a decrease in major amputations subsequent to minor amputations., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Pregnancy is a vulnerable period of time during which pregnant people are prone to infections like COVID-19, which can increase risks for both the mother and fetus. These infections may lead to complications such as preterm birth, developmental delays, and congenital abnormalities. While COVID-19 poses additional risks like placental dysfunction and neonatal infections, studies on long-term effects remain limited. Ongoing research and monitoring are essential to understand and mitigate potential cognitive and developmental challenges in children born to mothers infected with COVID-19. This review aims to guide clinicians in managing these risks throughout childhood. Maternal COVID-19 infection during pregnancy can have significant implications for fetal development, even if the newborn is not infected at birth. The release of inflammatory cytokines may cross the placental barrier, potentially disrupting fetal brain development and increasing the risk of long-term cognitive and behavioral issues, such as ADHD or autism. Placental dysfunction, caused by inflammation or thrombosis, can lead to intrauterine growth restriction (IUGR), preterm birth, or hypoxia, affecting both neurological and respiratory health in newborns. Furthermore, a compromised fetal immune system can increase susceptibility to autoimmune conditions and infections. The early diagnosis and management of infections during pregnancy are crucial in mitigating risks to both the mother and fetus. Swift intervention can prevent complications like preterm birth and long-term developmental challenges, ensuring better health outcomes for both the mother and child. Long-term monitoring of children born to mothers infected with COVID-19 is necessary to understand the full extent of the virus's impact. This review evaluates the long-term systemic effects of maternal COVID-19 infection during pregnancy on fetuses, newborns, and children, focusing beyond vertical transmission. It highlights the broader impacts on fetal development, offering insights to help clinicians manage potential issues that may arise later in life., Competing Interests: The authors declare no conflicts of interest.

Objective: Female patients are less likely to be diagnosed with and treated for peripheral artery disease. When treated, there are also reported sex disparities in short- and long-term outcomes. We designed this study to compare outcomes after open and endovascular revascularization in the Best Endovascular vs best Surgical Therapy in patients with Critical Limb Ischemia (BEST-CLI) trial between females and males, and to examine outcomes of each revascularization type in an all-female cohort., Methods: In a secondary analysis of cohorts 1 and 2 of the BEST-CLI Trial, patients with chronic limb-threatening ischemia (CLTI) undergoing open surgical bypass (with or without adequate conduit) and endovascular therapy were stratified by sex. In addition, in a female-only cohort, we evaluated differences in outcomes between treatment arm (combined all bypasses from cohorts 1 and 2 and compared with all endovascular treatment in cohorts 1 and 2). Outcomes included major amputation, reintervention, major adverse limb event (MALE, a composite of major amputation and reintervention), all-cause death, and composite outcome of MALE or all-cause death. Univariable and adjusted Cox regressions were used to assess outcome between males and females. Similar methods were used to assess differences in outcomes between treatment arm in females., Results: Among 1830 patients, females were significantly underrepresented, comprising only 28% (n = 519) of the BEST-CLI cohort. Overall, the characteristics of females enrolled in the trial had some differences compared with males: females were more likely to have rest pain alone (72% vs 60%; P < .0001) and when presenting with an ischemic wound, were less likely to have a wound infection (38% vs 47%; P = .01). Females were less likely to have an adequate single-segment greater saphenous vein (SSGSV) available (82% vs 89%; P = .01). Controlled for baseline clinical factors, at 1 year, females had significantly lower rates of major limb amputation compared with males (hazard ratio [HR], 0.70; P = .023), which drove better amputation- and MALE-free survival rates. All-cause death at 1 year was not statistically different between sexes (11.8% vs 11.2%; P = .286). In the all-female cohort, results paralleled the overall trial; open surgical bypass (with any conduit) had significantly better outcomes compared with endovascular therapy. Specifically, among females undergoing endovascular therapy, the rate of major reintervention was particularly high compared with females undergoing open surgical bypass (24.8% vs 10.5%; P < .001)., Conclusions: Despite being underrepresented in BEST-CLI, the primary results of the trial, namely, improved MALE-free survival with open surgical bypass with SSGSV, were mirrored in the all-female subset. Female patients enrolled in BEST-CLI had better amputation-free survival at 1 year compared with male patients. These findings suggest that in treating female patients with CLTI considered appropriate for both open and endovascular revascularization, surgical bypass with optimal conduit is the preferred treatment option and can potentially ameliorate poor limb preservation outcomes associated with sex., Competing Interests: Disclosures K.M. reports consultant for Medtronic Inc, and Vascular Technologies Inc; and research funding from NovoNordisk Foundation. K.R. reports consultant or member of a scientific advisory board for the following entities: Abbott Vascular, Althea Medical, Angiodynamics, Auxetics, Becton-Dickinson, Boston Scientific, Contego, Crossliner, Innova Vascular, Inspire MD, Janssen/Johnson and Johnson, Magneto, Mayo Clinic, MedAlliance, Medtronic, Neptune Medical, Penumbra, Philips, Surmodics, Terumo, Thrombolex, Truvic, Vasorum, and Vumedi; owns equity or stock options in the following entities: Access Vascular, Aerami, Althea Medical, Auxetics, Contego, Crossliner, Cruzar Systems, Endospan, Imperative Care/Truvic, Innova Vascular, InspireMD, JanaCare, Magneto, MedAlliance, Neptune Medical, Orchestra, Prosomnus, Shockwave, Skydance, Summa Therapeutics, Thrombolex, Vasorum, and Vumedi; and K.R. or his institution (on his behalf) receive research grants from the following entities: National Institutes of Health, Abiomed, Boston Scientific, Novo Nordisk Foundation, Penumbra, and Gettinge-Atrium; and serves as a member of the Board of Directors of the following organization: The National PERT Consortium. M.M. reports research grant from NovoNordisk Foundation; and advisory board for Janssen. A.F. reports grants from the Novo Nordisk Foundation; consultant for Sanifit, LeMaitre, and BioGenCell; and advisory board for Dialysis-X and iThera Medical. K.C. reports consultant for W.L. Gore & Associates and Venostent; and research support from Inari Medical, Vesper Medical, BD, and Johnson & Johnson. K.G. reports advisory board for Boston Scientific., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Perform literature review to analyze current practices in imaging patient with peripheral arterial disease (PAD) and examine patterns in our practice in order to assess whether a lower extremity computed tomography angiography (CTA) in addition to digital subtraction angiography enhanced the assessment of vessel calcification, percentage of stenosis, and affected outcomes in patients with PAD., Methods: The study included patients who underwent lower extremity imaging and were followed up to 12 months. This population was divided into cases who had both an angiogram and CTA performed within 30 days (n = 20), and controls who underwent angiography only (n = 19). Baseline characteristics, imaging results, and clinical outcomes were analyzed., Results: Thirty-nine patients met study criteria (mean age was 58.4 years, 69.2% were males, and 33.3% had diabetes). Patients mostly presented with tissue loss/rest pain (10.3%), claudication (15.4%), acute limb (10.3%), and trauma (15.4%). We have not observed any statistically significant differences in various examined blood vessels when their features (e.g., vessel diameter, stenosis, calcifications) were assessed by CTA combined with angiography versus angiography alone. The exceptions were external iliac artery, superficial femoral artery and dorsalis pedis vessels. In external iliac artery percentage of stenosis was 1.11% as determined by computed tomography (CT) scan versus 30% by angiography (P = 0.009). For superficial femoral artery stenosis, the percentage determined by CT was 48.68% vs. 81.41% by angiography, and observed difference between 2 modalities was statistically significant (P = 0.025). For dorsalis pedis percentage of stenosis detected by CT scan was 60.63% vs. 22.73% by angiography, and the differences in findings by these modalities were statistically significant (P = 0.039). The most frequent perioperative complication was cardiac-related (35.5%). Nineteen patients were readmitted and 8 had reinterventions within 12 months., Conclusions: Both imaging modalities yielded similar results for assessing vessel calcification and percentage of stenosis regardless of anatomic vessel location. Overall, utilization of CTA in addition to angiography for large vessels above the knee (e.g., iliac artery, superficial femoral artery) and below the knee for dorsalis pedis provided more detailed information on the properties of these vessels. Therefore, during preoperative assessments, CTA may be helpful in addition to angiography for planning surgical and endovascular interventions for symptomatic PAD treatment in larger vessels., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Several observational studies have demonstrated an association between diabetes mellitus (DM) and above-ankle amputation after lower extremity revascularization (LER). However, data from prospective randomized trials is lacking. This analysis compares the outcomes of patients with and without DM enrolled in the Best Endovascular vs Best Surgical Therapy in patients with Chronic Limb-Threatening Ischemia (BEST-CLI) trial., Methods: Baseline characteristics were compared between patients with and without DM in the BEST-CLI trial. Cox regression was used to determine the association between DM and major outcomes of major adverse limb events (MALE), reintervention, above-ankle amputation, and all-cause death., Results: Among 1777 patients who underwent LER, 69.2% had DM. Compared with patients without DM, those with DM were significantly younger, less likely to be White, and more likely to be Hispanic. Patients with DM were more likely to have hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, and renal disease and be on optimal medical therapy (antiplatelets and statins), whereas patients without DM were significantly more likely to be smokers and have chronic obstructive pulmonary disease. Patients with DM were significantly more likely to present with late Wound Ischemia foot Infection (WIfI) stages (3-4) (73.7% vs 45.9%; P < .001) that were driven predominantly by differences in wound and infection grade. Conversely, patients without DM had significantly lower ankle pressures and toe pressures and were significantly more likely to have WIfI ischemia grade 3 compared with patients with DM (60% vs 52.5%; P = .016). At 3 years, patients with DM exhibited higher rates of above-ankle amputation and all-cause death compared with patients without DM. Kaplan-Meier analysis demonstrated significantly higher MALE or all-cause death compared with patients without DM (3-year estimate: 53.5% vs 46.4%; P < .001). After adjusting for potential confounders, regression analysis demonstrated that DM was independently associated with increased above-ankle amputation (1.75 [1.22-2.51]), all-cause death (1.63 [1.31-2.03]), and MALE or all-cause death (1.24 [1.04-1.47])., Conclusions: Patients with DM undergoing LER for chronic limb-threatening ischemia experienced a greater incidence of MALE or all-cause death compared with patients without DM. The impact of DM seems to be mediated by more severe wounds and infections at the time of presentation, and a higher prevalence of cardiac and renal disease., Competing Interests: Disclosures J.S. reports education grants provided by Becton, Dickinson and Company and W. L. Gore & Associates; funds were paid to Boston University. A.F. reports consultant to LeMaitre, Sanifit, and BiogenCell, and is on the advisory board of iThera and DilaysisX. C.I.O.C. reports consultant for Envveno. Patent: U.S.S.N. 10,524,891 B1 “Inferior vena cava filter retrieval device and method of retrieving same.”, (Copyright © 2024. Published by Elsevier Inc.)

Objective: Single segment great saphenous vein (SSGSV) traditionally has been considered the gold standard conduit for infrainguinal bypass. There are data supporting similar outcomes with prosthetic femoral-popliteal bypass. Moreover, some investigators have advocated for prosthetic conduit for femoral tibial bypass when GSV is inadequate or unavailable. We sought to evaluate long-term outcomes of infrainguinal bypass based on conduit type for treating chronic limb-threatening ischemia (CLTI)., Methods: Data from the Best Endovascular vs Best Surgical Therapy of Patients with CLTI multicenter, prospective, randomized controlled trial, comparing infrainguinal bypass with endovascular therapy in patients with CLTI, were evaluated. In this as-treated analysis, we compared outcomes of infrainguinal bypass using prosthetic, alternative autogenous vein (AAV), and cryopreserved vein (Cryo) with SSGSV bypass. Kaplan-Meier and multivariable analyses were performed to examine the associations of conduit type with major adverse limb events (MALE), reinterventions, above-ankle amputations, and all-cause death rates., Results: In total, 784 bypasses were analyzed (120 prosthetic, 33 AAV, 21 Cryo, AND 610 SSGSV). For prosthetic and SSGSV, the distribution was 357 femoropopliteal (93 prosthetic and 264 GSV) and 373 infrapopliteal (27 prosthetic and 346 GSV). The mean age for the overall cohort was 67.1 years; 27.4% were female, 29.9% were non-White, and 11.5% were of Hispanic ethnicity. Patients undergoing prosthetic bypass were older (69.2 years vs 66.7 years); more likely to have chronic obstructive pulmonary disease (22.5% vs 14.0%), prior coronary artery bypass grafting (88.9% vs 66.5%), and prior stroke (23.3% vs 14%); but less often were of Hispanic ethnicity (5.8% vs 12.6%) and had diabetes (59.2% vs 71.3%) (P < .05 for all). For femoropopliteal bypass, use of prosthetic conduit was associated with increased major reinterventions at 3 years overall (19.0% vs 11.5%; P = .06) and on risk-adjusted analysis (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.09-4.2; P = .028). No significant differences in MALE or death, above-ankle amputation, or death were observed. Outcomes were similar for bypasses to above-knee popliteal targets and below-knee popliteal targets. For infrapopliteal bypass, the use of a prosthetic conduit was associated with increased major reintervention (25.3% vs 10.3%; P = .005), death (68.6% vs 34.8%; P < .001), and MALE or death (90.0% vs 48.1%; P < .001) at 3 years. After risk adjustment, infrapopliteal bypass with prosthetic conduit was associated with higher major reintervention (HR, 4.14; 95% CI, 1.36-12.6; P = .012), above-ankle amputation (HR, 4.64; 95% CI, 1.59-13.5; P = .005), death (HR, 2.96; 95% CI, 1.4-6.2; P = .004), and MALE or death (HR, 3.59; 95% CI, 1.64-7.86; P = .001) compared with bypass with SSGSV. Overall, AAV had similar outcomes at 3 years as SSGSV; however, Cryo had significantly higher above-ankle amputation (50.0% vs 12.8%) (HR, 4.2; 95% CI, 1.68-10.5; P = .002), major reintervention (41.9% vs 10.7%) (HR, 3.12; 95% CI, 1.18-8.22; P = .02), and MALE/death (88.8% vs 37.8%) (HR, 2.96; 95% CI, 1.43-6.14; P = .004)., Conclusions: The use of a prosthetic conduit in infrainguinal bypass is associated with inferior outcomes compared with bypass using SSGSV, particularly for bypass to infrapopliteal targets. Cryo grafts were infrequent and also demonstrated inferior outcomes. SSGSV remains the preferred conduit of choice for infrainguinal bypass., Competing Interests: Disclosures J.S. reports educational grants from W. L. Gore & Associates and BD. M.M. is a member of the scientific advisory board for Janssen. M.C. is on the Abbott Vascular DSMB. K.R. is a member of the Scientific Advisory Board or Consultant for Abbott Vascular, Access Vascular, Boston Scientific-BTG, Volcano-Philips, Surmodics, Cruzar Systems, Magneto, Summa Therapeutics, and University of Maryland; an unpaid member of the Scientific Advisory Board of Thrombolex, Inc; received grants from NIH and Boston Scientific; has equity from Access Vascular, Accolade, Contego, Endospan, Embolitech, Eximo, JanaCare, PQ Bypass, Primacea, MD Insider, Shockwave, Silk Road, Summa Therapeutics, Cruzar Systems, Capture, Vascular, Magneto, Micell, and Valcare; and is a board member of VIVA Physicians, a not-for-profit 501c3, and National PERT ConsortiumTM, a not for profit 501c3. A.F. is a grant recipient of the Novo Nordisk Foundation; a consultant for Sanifit, LeMaitre, and BioGenCell; and on the advisory board for Dialysis-X and iThera Medical., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Although cardiovascular surgery societies in Europe and the USA constantly strive for the exchange of knowledge and best practices in coronary artery bypass grafting (CABG), the available evidence on whether such efforts result in similar patient outcomes is limited. Therefore, in the present analysis, we sought to compare patient profiles and overall survival outcomes for up to 3 years between large European and US patient cohorts who underwent isolated CABG., Methods: Patients from the European DuraGraft Registry ( n  = 2,522) who underwent isolated CABG at 45 sites in eight different European countries between 2016 and 2019 were compared to randomly selected patients from the US STS database who were operated during the same period ( n  = 294,725). Free conduits (venous and arterial grafts) from the DuraGraft Registry patients were intraoperatively stored in DuraGraft, an endothelial damage inhibitor, before anastomosis, whereas grafts from the STS Registry patients in standard-of-care solutions (e.g., saline). Propensity score matching (PSM) models were used to account for differences in patient baseline and surgical characteristics, using a primary PSM with 35 variables (2,400 patients matched) and a secondary PSM with 25 variables (2,522 patients matched, sensitivity analysis). The overall survival for up to 3 years after CABG was assessed as the primary endpoint., Results: The comparison of patient profiles showed significant differences between the European and US cohorts. The European patients had more left main disease, underwent more off-pump CABG, and received more arterial grafts together with more complete arterial grafting procedures. In contrast, the US patients received more distal anastomoses with more saphenous vein grafts (SVGs) that were mainly harvested endoscopically. Such differences, however, were well balanced after PSM for the mortality comparison. Mortality comparison at 30 days, 12 months, and 24 months between the European and US patients was 2.38% vs. 1.96%, 4.32% vs. 4.79%, and 5.38% vs. 6.96%, respectively. At 36 months, the mortality was significantly lower in the European patients than that of their US counterparts (7.37% vs. 9.65%; p -value = 0.016). The estimated hazard ratio (HR) was 1.29 (95% CI 1.05-1.59)., Conclusion: This large-scale transatlantic comparative analysis shows that there are some significant differences in patient profiles between large cohorts of European and US patients. These differences were adjusted by using PSM for the mortality analysis. No significant difference in mortality was detected between groups through 2 years, but survival was significantly better in the European DuraGraft Registry patients at 3 years post-CABG., Competing Interests: EC, MM, JA, SS, Y-HC, and AB are members of the registry advisory committee (RAC). LP is a member of the RAC and is a consultant for Marizyme. ME is the principal investigator of the registry, the chair of the RAC, and a consultant for Marizyme. EF received research grants from Somalution, a Marizyme company. Other authors have nothing to disclose. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Caliskan, Misfeld, Sandner, Böning, Aramendi, Salzberg, Choi, Perrault, Tekin, Cuerpo, Lopez-Menendez, Weltert, Böhm, Krane, González-Santos, Tellez, Holubec, Ferrari, Doros and Emmert.)

Objective: Cardiovascular complications after revascularization to treat chronic limb-threatening ischemia (CLTI) are a major concern that guides treatment. Our goal was to assess periprocedural cardiac and vascular serious adverse events (SAEs) in the Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial., Methods: BEST-CLI was a prospective randomized trial comparing surgical (OPEN) and endovascular (ENDO) revascularization for patients with CLTI. Thirty-day SAEs, classified as cardiac or vascular, were analyzed. Adverse events are defined as serious when they affect safety in the trial, require prolonged hospitalization, result in significant disability or incapacitation, are life-threatening, or result in death. Interventions were analyzed in a per protocol fashion., Results: In the BEST-CLI trial, 850 OPEN and 896 ENDO interventions were evaluated. Forty (4.7%) and 34 (3.8%) patients experienced at least one cardiac SAE after OPEN and ENDO intervention, respectively (P = .35). Overall, there were 53 cardiac SAEs (0.06 per patient) after OPEN and 40 (0.045 per patient) after ENDO interventions. Cardiac SAEs in the OPEN arm were classified as related to ischemia (50.9%), arrhythmias (17%), heart failure (15.1%), arrest (13.2%), and heart block (3.8%); in the ENDO arm, they were classified as ischemia (47.5%), heart failure (17.5%), arrhythmias (15%), arrest (15%), and heart block (5%). Approximately half of SAEs were classified as severe for both OPEN and ENDO. SAEs were definitely or probably related to the procedure in 30.2% and 25% in the OPEN and ENDO arms, respectively (P = .2). Vascular SAEs occurred in 58 (6.8%) and 86 (9.6%) of patients after OPEN and ENDO revascularization, respectively (P = .19). In total, there were 59 (0.07 per patient) and 87 (0.097 per patient) vascular SAEs after OPEN and ENDO procedures. Vascular SAEs in the OPEN arm were classified as distal ischemia/infection (44.1%), bleeding (16.9%), occlusive (15.3%), thromboembolic (15.3%), cerebrovascular (5.1%), and other (3.4%); in the ENDO arm, they were distal ischemia/infection (40.2%), occlusive (31%), bleeding (12.6%), thromboembolic (8%), cerebrovascular (1.1%), and other (4.6%). SAEs were classified as severe for OPEN in 45.8% and ENDO in 46%. SAEs were definitely or probably related to the procedure in 23.7% and 35.6% in the OPEN and ENDO arms (P = .35), respectively., Conclusions: Patients undergoing OPEN and ENDO revascularization experienced similar degrees of cardiac and vascular SAEs. The majority were not related to the index intervention, but approximately half were severe., Competing Interests: Disclosures J.J.S. reports education grants from WL Gore and BD paid to Boston University. A.F. is a consultant for Sanifit. M.T.M. has served on the scientific advisory board for Janssen. M.S.C. is on the Data Safety Monitoring Board for Abbott Vascular. K.R. is a member of the scientific advisory board or a consultant for Abbott Vascular, Access Vascular, Boston Scientific-BTG, Volcano-Philips, Surmodics, Cruzar Systems, Magneto, Summa Therapeutics, and University of Maryland; is an unpaid member of the scientific advisory board of Thrombolex, Inc; received grants from the National Institutes of Health and Boston Scientific; has equity from Access Vascular, Accolade, Contego, Endospan, Embolitech, Eximo, JanaCare, PQ Bypass, Primacea, MD Insider, Shockwave, Silk Road, Summa Therapeutics, Cruzar Systems, Capture Vascular, Magneto, Micell, and Valcare; and is a board member of VIVA Physicians, a not-for-profit 501c3, and National PERT Consortium, a not-for-profit 501c3. The remaining authors report no conflicts., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Sustained clinical and hemodynamic benefit after revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI after endovascular (ENDO) vs bypass (OPEN) revascularization in the Best-Endovascular-versus-best-Surgical-Therapy-in-patients-with-CLTI (BEST-CLI) trial., Methods: As planned secondary analyses of the BEST-CLI trial, we examined the rates of (1) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); (2) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to an initial increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); (3) time to resolution of presenting CLTI symptoms; and (4) incidence of recurrent CLTI. Time-to-event analyses were performed by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N = 1434; cohort 2: lacking suitable SSGSV, N = 396), and multivariate stratified Cox regression models were created., Results: In cohort 1, there was a significant difference in time to clinical failure (log-rank P < .001), hemodynamic failure (log-rank P < .001), and resolution of presenting symptoms (log-rank P = .009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank P = .006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with a significantly lower risk of clinical and hemodynamic failure in both cohorts and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end-stage renal disease [ESRD], prior revascularization, smoking, diabetes, age >80 years, WIfI stage, tissue loss, and infrapopliteal disease). Factors independently associated with clinical failure included age >80 years in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2., Conclusions: Durable clinical and hemodynamic benefit after revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions, and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms., Competing Interests: Disclosures M.T.M. is the advisor for Janssen. A.F. grants from Novo Nordisk Foundation; is a consultant for Sanifit, LeMaitre, and BioGenCell; and is on the advisor board of Dialysis-X and iThera Medical. L.C.C. is a consulting speaker for Cook Medical. P.A.S. is a consultant for Medtronic, Boston Scientific, Philips, Silk Road, Surmodics, Cagent, and Limflow. B.M.H. reports research grants (site PI for clinical trials, no compensation) from Boston Scientific and NIH/NHLBI. M.D.D. is a consultant for Cook Medical, W.L. Gore, and Boston Scientific. K.R. receives income as a consultant or member of a scientific advisory board for the following entities: Abbott Vascular, Althea Medical, Angiodynamics, Auxetics, Becton-Dickinson, Boston Scientific, Contego, Crossliner, Innova Vascular, Inspire MD, Janssen/Johnson and Johnson, Magneto, Mayo Clinic, MedAlliance, Medtronic, Neptune Medical, Penumbra, Philips, Surmodics, Terumo, Thrombolex, Truvic, Vasorum, and Vumedi; and owns equity or stock options in the following entities: Access Vascular, Aerami, Althea Medical, Auxetics, Contego, Crossliner, Cruzar Systems, Endospan, Imperative Care/Truvic, Innova Vascular, InspireMD, JanaCare, Magneto, MedAlliance, Neptune Medical, Orchestra, Prosomnus, Shockwave, Skydance, Summa Therapeutics, Thrombolex, Vasorum, and Vumedi. K.R. or his institution (on his behalf) receives research grants from the following entities: NIH, Abiomed, Boston Scientific, Novo Nordisk Foundation, Penumbra, and Gettinge-Atrium. He serves as a member of the Board of Directors of the following organization: The National PERT Consortium. M.S.C. has a relationship with Abbott Vascular DSMB. The remaining authors report no conflicts., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Urinary tract infection (UTI) represents one of the most common bacterial infections in children, mainly caused by Gram-negative bacteria. Empirical antibiotic treatment is based on international and national guidelines for treating UTIs in children and is individualized with local antibiotic resistance patterns. The aim of this study is to bring a clear view of present-day particularities of UTIs in children., Methods: We analyzed 210 positive urine cultures identified in 141 pediatric patients admitted to the hospital over a 6-month period., Results: The majority of patients were females (57%) with a median age of 5 years (IQR 12), while male patients revealed a median age of 2 (IQR 7). Most patients originated from urban areas (53%). Only 18 patients (12.76%) were identified with underlying Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). Escherichia Coli was the most frequent pathogen. Increased antibiotic resistance was found in commonly-used antibiotics Ampicillin and Trimethoprim/Sulfamethoxazole, and in the case of patients with CAKUT. Suitable antibiotics for treating a Gram-negative UTI are aminoglycosides, Meropenem, third-generation Cephalosporins, and Nitrofurantoin. Vancomycin upholds efficacy in treating a Gram-positive pediatric UTI., Conclusion: Periodical analysis needs to be performed in order to constantly update clinicians on uropathogenic antibiotic resistance and optimal empirical treatment options.

Objectives: Patients undergoing revascularization for chronic limb-threatening ischemia experience a high burden of target limb reinterventions. We analyzed data from the Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) randomized trial comparing initial open bypass (OPEN) and endovascular (ENDO) treatment strategies, with a focus on reintervention-related study endpoints., Methods: In a planned secondary analysis, we examined the rates of major reintervention, any reintervention, and the composite of any reintervention, amputation, or death by intention-to-treat assignment in both trial cohorts (cohort 1 with suitable single-segment great saphenous vein [SSGSV], n = 1434; cohort 2 lacking suitable SSGSV, n = 396). We also compared the cumulative number of major and all index limb reinterventions over time. Comparisons between treatment arms within each cohort were made using univariable and multivariable Cox regression models., Results: In cohort 1, assignment to OPEN was associated with a significantly reduced hazard of a major limb reintervention (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.28-0.49; P < .001), any reintervention (HR, 0.63; 95% CI, 0.53-0.75; P < .001), or any reintervention, amputation, or death (HR, 0.68; 95% CI, 0.60-0.78; P < .001). Findings were similar in cohort 2 for major reintervention (HR, 0.53; 95% CI, 0.33-0.84; P = .007) or any reintervention (HR, 0.71; 95% CI, 0.52-0.98; P = .04). In both cohorts, early (30-day) limb reinterventions were notably higher for patients assigned to ENDO as compared with OPEN (14.7% vs 4.5% of cohort 1 subjects; 16.6% vs 5.6% of cohort 2 subjects). The mean number of major (mean events per subject ratio [MR], 0.45; 95% CI, 0.34-0.58; P < .001) or any target limb reinterventions (MR, 0.67; 95% CI, 0.57-0.80; P < .001) per year was significantly less in the OPEN arm of cohort 1. The mean number of reinterventions per limb salvaged per year was lower in the OPEN arm of cohort 1 (MR, 0.45; 95% CI, 0.35-0.57; P < .001 and MR, 0.66; 95% CI, 0.55-0.79; P < .001 for major and all, respectively). The majority of index limb reinterventions occurred during the first year following randomization, but events continued to accumulate over the duration of follow-up in the trial., Conclusions: Reintervention is common following revascularization for chronic limb-threatening ischemia. Among patients deemed suitable for either approach, initial treatment with open bypass, particularly in patients with available SSGSV conduit, is associated with a significantly lower number of major and minor target limb reinterventions., Competing Interests: Disclosures M.C. is on the DSMB for Abbott Vascular. M.M. is an advisor for Janssen. K.R. receives income as a consultant or member of a scientific advisory board for Abbott Vascular, Althea Medical, Angiodynamics, Auxetics, BectonDickinson, Boston Scientific, Contego, Crossliner, Innova Vascular, Inspire MD, Janssen/Johnson and Johnson, Magneto, Mayo Clinic, MedAlliance, Medtronic, Neptune Medical, Penumbra, Philips, Surmodics, Terumo, Thrombolex, Truvic, Vasorum, and Vumedi; owns equity or stock options in the following entities: Access Vascular, Aerami, Althea Medical, Auxetics, Contego, Crossliner, Cruzar Systems, Endospan, Imperative Care/Truvic, Innova Vascular, InspireMD, JanaCare, Magneto, MedAlliance, Neptune Medical, Orchestra, Prosomnus, Shockwave, Skydance, Summa Therapeutics, Thrombolex, Vasorum, and Vumedi; serves as a member of the board of directors of the following organization: The National PERT ConsortiumTMA; and K.R. or his institution (on his behalf) receive research grants from the following entities: NIH, Abiomed, Boston Scientific, Novo Nordisk Foundation, Penumbra, and Gettinge-Atrium. A.F. received a grant from Novo Nordisk Foundation; is a consultant with Sanifit, LeMaitre, and BioGenCell; and is on the advisory board for Dialysis-X and iThera Medical. E.A. is a consultant with Philips and is participating in clinical trials with Inari Medical. C.M. is a consultant with Cook, Abbott, Penumra, and Optum Labs; and received a research grant from Shockwave and Philips., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Congenital anomalies affecting the kidneys present significant challenges in pediatric nephrology, needing precise methods for assessing renal function and guiding therapeutic intervention. Bedside Schwartz formula with the cystatin-C-based Full Age Spectrum formula and Chronic Kidney Disease in Children (CKiD) U 25 formula used in estimating glomerular filtration rate (eGFR) and also to assess if the eGFR in association with kidney length percentiles can be a monitoring parameter for the progression of chronic kidney disease in children with congenital anomalies of the kidney and urinary tract (CAKUT). A total of 64 pediatric patients (median age at diagnostic was 12 months with an interquartile range of 2 to 60) were diagnosed with congenital anomalies in the kidney and urinary tract between June 2018 and May 2023 at "Louis Turcanu" Emergency Hospital for Children in Timisoara, Romania. Baseline characteristics, CAKUT types, associated pathologies, CKD staging, and eGFR using creatinine and cystatin C were analyzed. The mean age at the moment of examination was 116.50 months; (65, 180). Chronic kidney disease staging revealed a predominance of patients in CKD stages G1 and A1. Analysis of eGFR methods revealed a small mean difference between eGFR estimated by creatinine and cystatin C, with a moderate-strong positive correlation observed between the eGFR and ultrasound parameters. Using cystatin-C-based formulas for eGFR, in conjunction with ultrasound measurements, may offer reliable insights into renal function in pediatric patients with congenital anomalies affecting the kidney and urinary tract. However, the economic aspect must be taken into consideration because cystatin C determination is approximately eight times more expensive than that of creatinine. An interdisciplinary approach is crucial for managing patients with CAKUT.

Background: There is limited data on the organisation of paediatric echocardiography laboratories in Europe., Methods: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs., Results: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%)., Conclusion: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.

The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the "Victor Babes" Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control ( n = 114) and the Post-COVID group ( n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m 2 vs. 91.2 mL/min/1.73 m 2 , p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study's findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function., Competing Interests: The authors declare no conflict of interest.

Objectives: There has been significant variability in practice patterns and equipoise regarding treatment approach for chronic limb-threatening ischemia (CLTI). We aimed to assess treatment preferences of Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) investigators prior to and following the trial., Methods: An electronic 60-question survey was sent to 1180 BEST-CLI investigators in 2022, after trial conclusion and before announcement of results. Investigators' preferences were assessed across clinical scenarios for both open (OPEN) and endovascular (ENDO) revascularization strategies. Vascular surgeon (VS) surgical and ENDO preferences were compared with a 2010 survey administered to prospective investigators before trial funding., Results: For the 2022 survey, the response rate was 20.2% and was comprised of VSs (76.3%), interventional cardiologists (11.4%) and interventional radiologists (11.6%). The majority (72.6%) were in academic practice and 39.1% were in practice for >20 years. During initial CLTI work-up, 65.8%, 42.6%, and 55.9% of respondents always or usually ordered an arterial duplex, computed tomography angiography, and vein mapping, respectively. The most common practice distribution between ENDO and OPEN procedures was 70/30. Postoperatively, a majority reported performing routine duplex surveillance of vein bypass (99%), prosthetic bypass (81.9%), and ENDO interventions (86%). A minority reported always or usually using the wound, ischemia, and foot infection (WIfI) criteria (25.8%), GLASS (8.3%), and a risk calculator (14.8%). More than one-half (52.9%) agreed that the statement "no bridges are burned with an ENDO-first approach" was false. Intervention choice was influenced by availability of the operating room or ENDO suite, personal schedule, and personal skill set in 30.1%, 18.0%, and 45.9% of respondents, respectively. Most respondents reported routinely using paclitaxel-coated balloons (88.1%) and stents (67.5%); however, 73.3% altered practice when safety concerns were raised. Among surgeons, 17.8%, 2.9%, and 10.3% reported performing >10 annual alternative autogenous vein bypasses, composite vein composite vein bypasses, and bypasses to pedal targets, respectively. Among all interventionalists, 8%, 24%, and 8% reported performing >10 annual radial access procedures, pedal or tibial access procedures, and pedal loop revascularizations. The majority (89.1%) of respondents felt that CLTI teams improved care; however, only 23.2% had a defined team. The effectiveness of the teamwork at institutions was characterized as highly effective in 42.5%. When comparing responses by VSs to the 2010 survey, there were no changes in preferred treatment based on Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) II classification or conduit preference. In 2022, OPEN surgery was preferred more for a popliteal occlusion. For clinical scenarios, there were no differences except a decreased proportion of respondents who felt there was equipoise for major tissue loss for major tissue loss (43.8% vs 31.2%) and increased ENDO choice for minor tissue loss (17.6% vs 30.8%) (P < .05)., Conclusions: There is a wide range of practice patterns among vascular specialists treating CLTI. The majority of investigators in BEST-CLI had experience in both advanced OPEN and ENDO techniques and represent a real-world sample of technical expertise. Over the course of the decade of the BEST-CLI trial, there was overall similar equipoise among VSs., Competing Interests: Disclosures A.F. has received a grant from the Novo Nordisk Foundation; is a consultant for Sanifit, LeMaitre, and BioGenCell; and is on the advisory board of Dialysis-X and iThera Medical. M.M. is an advisor for Janssen. K.G. is an advisory board member for Boston Scientific. K.R. receives income as a consultant or member of a scientific advisory board for the following entities: Abbott Vascular; Althea Medical; Angiodynamics; Auxetics; Becton-Dickinson; Boston Scientific; Contego; Crossliner; Innova Vascular; Inspire MD; Janssen/Johnson and Johnson; Magneto; Mayo Clinic; MedAlliance; Medtronic; Neptune Medical; Penumbra; Philips; Surmodics; Terumo; Thrombolex; Truvic; Vasorum; Vumedi. KR owns equity or stock options in the following entities: Access Vascular; Aerami; Althea Medical; Auxetics; Contego; Crossliner; Cruzar Systems; Endospan; Imperative Care/Truvic; Innova Vascular; InspireMD; JanaCare; Magneto; MedAlliance; Neptune Medical; Orchestra; Prosomnus; Shockwave; Skydance; Summa Therapeutics; Thrombolex; Vasorum; Vumedi. K.R. or his institution (on my behalf) receive research grants from the following entities: NIH; Abiomed; Boston Scientific; Novo Nordisk Foundation; Penumbra; Gettinge-Atrium. K.R. serves as a member of the Board of Directors of the following organization: The National PERT ConsortiumTM., (Copyright © 2024. Published by Elsevier Inc.)

Systemic Bartonella henselae infection, also known as cat-scratch disease (CSD), presents a diagnostic challenge due to the variability of clinical manifestations and the potential for serological cross-reactivity with other organisms. This study aimed to retrospectively analyze the epidemiological, clinical, laboratory, and imaging characteristics of pediatric patients diagnosed with systemic B. henselae infection, to improve understanding and facilitate timely diagnosis and treatment. We conducted a 10-year retrospective study at the "Louis Turcanu" Children's Emergency Hospital and private clinics in Timisoara, Romania, reviewing records for confirmed cases of B. henselae infection from January 2014 to January 2024. The study adhered to the Declaration of Helsinki and received approval from the Institutional Review Board. Diagnostic criteria included contact with animals, prolonged fever, hematological and/or hepatosplenic manifestations, and positive serological tests for B. henselae . Nineteen pediatric patients were identified with a median age of 8.1 years. The majority were exposed to felines (94.7%), reflecting the disease's epidemiological profile. Clinical findings highlighted fever (47.4%), lymphadenopathy (78.9%), and less frequently, abdominal pain and headache (both 10.5%). Laboratory analyses revealed a mean hemoglobin of 12.6 mg/dL, WBC count of 13.1 × 10 3 cells/microliter, and platelet count of 340.6 × 10 3 per microliter. Significant findings included elevation in ESR and CRP in 47.4% and 21.1% of patients, respectively, and high seropositivity rates for B. henselae IgM (63.2%) and IgG (94.7%). Imaging studies demonstrated widespread lymphadenopathy and occasional splenomegaly and hepatic microabscesses. All patients received antibiotic therapy, with azithromycin being the most commonly used (94.7%). Co-infections with Epstein-Barr Virus, Cytomegalovirus, and Toxoplasma gondii were documented, indicating the complex infectious status of the patients. Systemic B. henselae infection in children predominantly manifests with fever and lymphadenopathy, with a significant history of exposure to felines. Laboratory and imaging findings support the diagnosis, which is further complicated by potential co-infections. Effective antibiotic therapy, primarily with azithromycin, underscores the need for comprehensive diagnostic and treatment strategies. This study emphasizes the importance of considering systemic B. henselae infection in pediatric patients with prolonged fever and contact with cats, to ensure timely and appropriate treatment.

Objectives: Patients with diabetes mellitus (DM) undergoing coronary artery bypass grafting (CABG) have been repeatedly demonstrated to have worse clinical outcomes compared to patients without DM. The objective of this study was to evaluate the impact of DM on 1-year clinical outcomes after isolated CABG., Methods: The European DuraGraft registry included 1130 patients (44.6%) with and 1402 (55.4%) patients without DM undergoing isolated CABG. Intra-operatively, all free venous and arterial grafts were treated with an endothelial damage inhibitor. Primary end point in this analysis was the incidence of a major adverse cardiac event (MACE), a composite of all-cause death, repeat revascularization or myocardial infarction at 1 year post-CABG. To balance between differences in baseline characteristics (n = 1072 patients in each group), propensity score matching was used. Multivariable Cox proportional hazards regression was performed to identify independent predictors of MACE., Results: Diabetic patients had a higher cardiovascular risk profile and EuroSCORE II with overall more comorbidities. Patients were comparable in regard to surgical techniques and completeness of revascularization. At 1 year, diabetics had a higher MACE rate {7.9% vs 5.5%, hazard ratio (HR) 1.43 [95% confidence interval (CI) 1.05-1.95], P = 0.02}, driven by increased rates of death [5.6% vs 3.5%, HR 1.61 (95% CI 1.10-2.36), P = 0.01] and myocardial infarction [2.8% vs 1.4%, HR 1.99 (95% CI 1.12-3.53) P = 0.02]. Following propensity matching, no statistically significant difference was found for MACE [7.1% vs 5.7%, HR 1.23 (95% CI 0.87-1.74) P = 0.23] or its components. Age, critical operative state, extracardiac arteriopathy, ejection fraction ≤50% and left main disease but not DM were identified as independent predictors for MACE., Conclusions: In this study, 1-year outcomes in diabetics undergoing isolated CABG were comparable to patients without DM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: This study aimed to determine the status of training of adult congenital heart disease (ACHD) cardiologists in Europe., Methods: A questionnaire was sent to ACHD cardiologists from 34 European countries., Results: Representatives from 31 of 34 countries (91%) responded. ACHD cardiology was recognised by the respective ministry of Health in two countries (7%) as a subspecialty. Two countries (7%) have formally recognised ACHD training programmes, 15 (48%) have informal (neither accredited nor certified) training and 14 (45%) have very limited or no programme. Twenty-five countries (81%) described training ACHD doctors 'on the job'. The median number of ACHD centres per country was 4 (range 0-28), median number of ACHD surgical centres was 3 (0-26) and the median number of ACHD training centres was 2 (range 0-28). An established exit examination in ACHD was conducted in only one country (3%) and formal certification provided by two countries (7%). ACHD cardiologist number versus gross domestic product Pearson correlation coefficient=0.789 (p<0.001)., Conclusion: Formal or accredited training in ACHD is rare among European countries. Many countries have very limited or no training and resort to 'train people on the job'. Few countries provide either an exit examination or certification. Efforts to harmonise training and establish standards in exit examination and certification may improve training and consequently promote the alignment of high-quality patient care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with systemic light chain (AL) amyloidosis undergoing treatment with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) may develop renal and cardiac toxicities potentially exacerbated by the co-solvent propylene glycol in conventional melphalan formulations. We investigated the safety and efficacy of propylene glycol-free melphalan (PGF-Mel) during HDM/SCT in patients with AL amyloidosis (ClinicalTrials.gov identifier NCT02994784). The primary objective of this phase II, open-label study was evaluation for renal dysfunction, new cardiac arrhythmias, and postural hypotension related to autonomic dysfunction. Secondary objectives included time to neutrophil and platelet engraftment, treatment-related mortality (TRM), overall hematologic response, organ response, and number of peritransplantation hospitalizations. Twenty-eight patients with AL amyloidosis enrolled, of whom 27 underwent HDM/SCT. PGF-Mel at 140 to 200 mg/m 2 was administered i.v. in 2 equally divided doses. Patients were monitored for up to 30 days after the last administration of PGF-Mel to assess for treatment-related toxicity. Patients were followed for 12 months from the time of treatment with HDM/SCT for evaluation of hematologic and organ responses. Kaplan-Meier analysis was used to estimate progression-free survival. Two patients (7%) developed renal dysfunction, 5 (19%) experienced new cardiac arrhythmias, and 3 (11%) developed orthostatic hypotension. All patients achieved neutrophil and platelet engraftment, at a median of 10 days and 17 days post-HDM/SCT, respectively. TRM on day +100 was 0%. Peritransplantation hospitalization was required for 23 patients (85%). The most common nonhematologic adverse events were diarrhea (93%), fatigue (82%), and nausea (74%). At 6 months post-HDM/SCT, hematologic complete response or very good partial response occurred in 66% of the patients. At 12 months post-HDM/SCT, renal response occurred in 12 of 23 (52%) patients with renal involvement, and cardiac response occurred in 3 of 11 (27%) patients with evaluable cardiac involvement. Our data indicate that PGF-Mel is safe and efficacious as a high-dose conditioning regimen for autologous SCT in patients with AL amyloidosis., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: Anticipated perioperative morbidity is an important factor for choosing a revascularization method for chronic limb-threatening ischemia (CLTI). Our goal was to assess systemic perioperative complications of patients treated with surgical and endovascular revascularization in the Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial., Methods: BEST-CLI was a prospective randomized trial comparing open (OPEN) and endovascular (ENDO) revascularization strategies for patients with CLTI. Two parallel cohorts were studied: Cohort 1 included patients with adequate single-segment great saphenous vein (SSGSV), whereas Cohort 2 included those without SSGSV. Data were queried for major adverse cardiovascular events (MACE-composite myocardial infarction, stroke, death), non-serious (non-SAEs) and serious adverse events (SAEs) (criteria-death/life-threatening/requiring hospitalization or prolongation of hospitalization/significant disability/incapacitation/affecting subject safety in trial) 30 days after the procedure. Per protocol analysis was used (intervention received without crossover), and risk-adjusted analysis was performed., Results: There were 1367 patients (662 OPEN, 705 ENDO) in Cohort 1 and 379 patients (188 OPEN, 191 ENDO) in Cohort 2. Thirty-day mortality in Cohort 1 was 1.5% (OPEN 1.8%; ENDO 1.3%) and in Cohort 2 was 1.3% (2.7% OPEN; 0% ENDO). MACE in Cohort 1 was 4.7% for OPEN vs 3.13% for ENDO (P = .14), and in Cohort 2, was 4.28% for OPEN and 1.05% for ENDO (P = .15). On risk-adjusted analysis, there was no difference in 30-day MACE for OPEN vs ENDO for Cohort 1 (hazard ratio [HR] 1.5; 95% confidence interval [CI], 0.85-2.64; P = .16) or Cohort 2 (HR, 2.17; 95% CI, 0.48-9.88; P = .31). The incidence of acute renal failure was similar across interventions; in Cohort 1 it was 3.6% for OPEN vs 2.1% for ENDO (HR, 1.6; 95% CI, 0.85-3.12; P = .14), and in Cohort 2, it was 4.2% OPEN vs 1.6% ENDO (HR, 2.86; 95% CI, 0.75-10.8; P = .12). The occurrence of venous thromboembolism was low overall and was similar between groups in Cohort 1 (OPEN 0.9%; ENDO 0.4%) and Cohort 2 (OPEN 0.5%; ENDO 0%). Rates of any non-SAEs in Cohort 1 were 23.4% in OPEN and 17.9% in ENDO (P = .013); in Cohort 2, they were 21.8% for OPEN and 19.9% for ENDO (P = .7). Rates for any SAEs in Cohort 1 were 35.3% for OPEN and 31.6% for ENDO (P = .15); in Cohort 2, they were 25.5% for OPEN and 23.6% for ENDO (P = .72). The most common types of non-SAEs and SAEs were infection, procedural complications, and cardiovascular events., Conclusions: In BEST-CLI, patients with CLTI who were deemed suitable candidates for open lower extremity bypass surgery had similar peri-procedural complications following either OPEN or ENDO revascularization: In such patients, concern about risk of peri-procedure complications should not be a deterrent in deciding revascularization strategy. Rather, other factors, including effectiveness in restoring perfusion and patient preference, are more relevant., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Pediatric hemato-oncology patients undergoing anthracycline therapy are at risk of cardiotoxicity, with disease type and treatment intensity potentially affecting cardiac function. Novel echocardiographic measures like speckle tracking echocardiography (STE), global longitudinal strain (GLS), and the myocardial performance index (MPI) may predict early changes in cardiac function not detected by traditional methods. This study aimed to assess the impact of cancer type and treatment protocol on these parameters and their potential in predicting long-term cardiac complications. We conducted a single-center, retrospective cohort study of 99 pediatric oncology patients and 46 controls that were assessed at 3, 6, and 12 months. The median age was 10.7 ± 4.4 years for cases and 10.2 ± 3.6 years for controls. STE, GLS, and MPI were measured, and statistical analyses were performed to determine any significant correlations with cardiotoxicity. Significant variations were observed in traditional cardiac function measurements between the patient and control groups, with a lower average ejection fraction (EF) of 62.8 ± 5.7% in patients vs. 66.4 ± 6.1% in controls ( p < 0.001), poorer GLS of -16.3 ± 5.1 in patients compared to -19.0 ± 5.4 in controls ( p = 0.004), and higher MPI values of 0.37 ± 0.06 in patients compared to 0.55 ± 0.10 in controls, indicating worse overall cardiac function ( p < 0.001). However, differences in cardiac function measurements by cancer histology or treatment protocol were not statistically significant. Regression analyses showed that the combination of GLS, SMOD, and MPI increased the odds of cardiac toxicity with an odds ratio of 7.30 (95% CI: 2.65-12.81, p < 0.001). The study underscores the predictive value of the combined GLS, SMOD, and MPI measurements in pediatric oncology patients undergoing anthracycline treatment for cardiotoxicity. Although variations across cancer types and treatment protocols were not significant, the study emphasizes the potential utility of these novel echocardiographic measures in early detection and long-term prediction of anthracycline-induced cardiotoxicity. Further studies in larger, multi-center cohorts are required for validation.

Speckle tracking-echocardiography (STE) is a novel non-invasive imaging tool capable of quantifying myocardial deformation, and thus holds promise in detecting early subclinical myocardial injury. This study aimed to evaluate the correlation of STE with traditional biomarkers in predicting anthracycline-induced cardiotoxicity in the context of varying dosages and treatment protocols in pediatric hemato-oncology patients. We conducted a retrospective study involving pediatric hemato-oncology patients undergoing anthracycline-based chemotherapy. A total of 99 patients were included in the final analysis, with 82 receiving Doxorubicin, of which 58.5% were males, and 17 receiving Epirubicin, of which 70.6% were males, with a median of 10 years old. Traditional biomarkers, such as Troponin I (cTnI) and B-type natriuretic peptide (BNP), were compared with STE parameters, including the global longitudinal strain (GLS), Simpson method of discs (SMOD), and myocardial performance index (MPI). A comprehensive evaluation was conducted based on different dosages of anthracyclines and different treatment protocols, with a follow-up period of one year post-chemotherapy. It was observed that the cTnI levels in the Doxorubicin group were significantly higher (3.2 ng/mL, p = 0.002) than in the Epirubicin group (2.7 ng/mL). However, BNP and NT-proBNP levels were not significantly different between the two groups ( p = 0.096 and p = 0.172, respectively). Regarding STE parameters, a significant negative correlation was observed between the anthracycline dose and GLS (Rho = -0.411, p = 0.001), indicating increased cardiotoxicity with dose elevation. The SMOD and MPI gave significantly better values in the Epirubicin group (59.2 and 0.41 vs. 54.4 and 0.36, respectively). However, the ROC analysis did not find GLS, SMOD, or MPI to be significant independent predictors of cardiotoxicity ( p > 0.05). There was also considerable variation in cardiotoxicity between the Doxorubicin and Epirubicin study groups, suggesting that the risk of cardiotoxicity is not solely determined by dose. Our study underlines the potential of STE as a sensitive tool for the early detection and prediction of anthracycline-induced cardiotoxicity in pediatric hemato-oncology patients, but only in association with the clinical findings and cardiac biomarkers. While traditional biomarkers still play a role, STE can offer a more accurate prediction of cardiac risk, potentially leading to better management and outcomes for these patients.

Aims: Residual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result., Methods and Results: EVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm 3 vs. an increase of 41 mm 3 , p  = 0.008), widening at 18 months (6 mm 3 vs. 58 mm 3 increase, p  = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p  < 0.01 (sustained at 18 months), generalizing well to a validation cohort., Conclusion: Plaques in the IPE-treated patients acquired more characteristics of stability. Reliable assessment using histologically validated analysis of individual response is possible at 9 months, with sustained stabilization at 18 months, providing a quantitative basis to elucidate drug mechanism and assess individual patient response., Competing Interests: MB receives grant support from Amarin, participates in its speaker's bureau, and receives grant support from General Electric. AB is the founder and shareholder of Elucid Bioimaging, Inc. PL is an unpaid consultant to or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, MedImmune, Merck, Novo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron. PL is a member of the scientific advisory board for Amgen, Caristo, Cartesian, CSL Behring, DalCor Pharmaceuticals, Dewpoint, Kowa Pharmaceuticals, Olatec Therapeutics, MedImmune, Novartis, PlaqueTec, and XBiotech, Inc. PL's laboratory has received research funding from Novartis, Genentech, and Novo Nordisk in the last 2 years. PL is on the Board of Directors of XBiotech, Inc. PL has a financial interest in Xbiotech, a company developing therapeutic human antibodies. DB discloses the following relationships—Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: Angiowave (stock options), Boston VA Research Institute, Bristol-Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures, Hims; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald's Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. JN discloses the following: Amarin, Amgen, Boehringer Ingelheim, and Boston Heart Diagnostic speaker bureaus. Consultant and advisor to and stock shareholder of Amarin Pharma and Amgen. AN was employed by Elucid Bioimaging Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Buckler, Doros, Kinninger, Lakshmanan, Le, Libby, May, Muhlestein, Nelson, Nicolaou, Roy, Shaikh, Shekar, Tayek, Zheng, Bhatt and Budoff.)

The aftermath of severe COVID-19 frequently involves considerable cardiopulmonary damage, necessitating rehabilitation. This study aimed to evaluate the impact of COVID-19 on cardiopulmonary health and assess the effectiveness of various rehabilitative interventions. Conducted between September 2021 and September 2022, this prospective study included patients who had been diagnosed with severe COVID-19 and admitted at the "Victor Babes" Infectious Diseases and Pulmonology Hospital, Timisoara, Romania. The patients were stratified into low- and high-intensity rehabilitation groups. The rehabilitation protocols were individually tailored, and the patient recovery was closely monitored over a 3-month period. Our cohort comprised 84 patients, with a mean age of 56.3 years for the low-intensity group ( n = 42) and 53.1 years for the high-intensity group ( n = 42). Both groups showed significant improvements in the lung injury area, need for oxygen supplementation, ejection fraction, systolic pulmonary artery pressure, and forced vital capacity. Additionally, considerable enhancements were observed in maximal voluntary ventilation, FEV1, FEV1/FVC ratio, peak expiratory flow, and forced expiratory flow at 25-75%. The work intensity also demonstrated substantial improvements from the initial testing to the 3-month mark in both groups. This study provides evidence that personalized, targeted rehabilitation strategies can improve long-term cardiopulmonary health in patients recovering from severe COVID-19, proving both low-intensity and high-intensity training as sufficient to improve heart and lung function if performed correctly and over a relatively short duration of 3 months. The study findings underscore the importance of implementing comprehensive cardiopulmonary rehabilitation protocols in the care of post-COVID-19 patients and highlight the value of stratified rehabilitation intensity based on individual patient dynamics and recovery features.

Aims: Icosapent ethyl (IPE) significantly reduced ischaemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides in REDUCE-IT, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization. However, the mechanisms driving this clinical benefit are not fully known. The EVAPORATE trial demonstrated that IPE significantly reduced plaque burden. No study to date has assessed the impact of IPE on coronary physiology. Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) data sets (FFRCT) applies computational fluid dynamics to calculate FFR values in epicardial coronary arteries. Our objective was to assess the impact of IPE on coronary physiology assessed by FFRCT using imaging data from EVAPORATE., Methods and Results: A total of 47 patients and of 507 coronary lesions at baseline, 9 months, and 18 months with coronary CTA and FFRCT were studied in a blinded core lab. The pre-specified primary endpoint was the FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using IPE compared with placebo. The pre-specified secondary endpoint was the change in translesional FFRCT (ΔFFRCT) across the most severe (minimum 30% diameter stenosis) coronary lesion per vessel. Baseline FFRCT was similar for IPE compared with placebo (0.83 ± 0.08 vs. 0.84 ± 0.08, P = 0.55). There was significant improvement in the primary endpoint, as IPE improved mean distal segment FFRCT at 9- and 18-month follow-up compared with placebo (0.01 ± 0.05 vs. -0.05 ± 0.09, P = 0.02, and -0.01 ± 0.09 vs. -0.09 ± 0.12, P = 0.03, respectively). ΔFFRCT in 140 coronary lesions was improved, although not statistically significant, with IPE compared with placebo (-0.06 ± 0.08 vs. -0.09 ± 0.1, P = 0.054)., Conclusion: Icosapent ethyl demonstrated significant benefits in coronary physiology compared with placebo. This early and sustained improvement in FFRCT at 9- and 18-month follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial. Furthermore, this is the first assessment of FFRCT to determine drug effect., Competing Interests: Conflict of interest: M.G.R. discloses the following—consultant: HeartFlow. D.L.B. discloses the following relationships—advisory board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; board of directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; chair: inaugural chair, American Heart Association Quality Oversight Committee; consultant: Broadview Ventures; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor and associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (deputy editor), NCDR-ACTION Registry Steering Committee (chair), VA CART Research and Publications Committee (chair); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; unfunded research: FlowCo and Takeda. M.J.B. discloses the following—Amarin grant support and speakers bureau, and General Electric grant support., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: The underuse of oral anticoagulation in patients with nonvalvular atrial fibrillation (AF) is a major issue that is not well understood., Objective: To understand the lack of anticoagulation by assessing the perceptions of patients with AF who are not receiving anticoagulation and their physician's about the risk of stroke and the benefits and risks of anticoagulation., Design, Setting, and Participants: This cohort study included patients with nonvalvular AF and a CHA2DS2-VASc score of 2 or more (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) who were not receiving anticoagulation and were enrolled from 19 sites within the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence Registry (PINNACLE Registry) between January 18, 2017, and May 7, 2018. Data were collected from January 18, 2017, to September 30, 2019, and analyzed from April 2022 to March 2023., Exposure: Each patient enrolled in the study completed a survey, and their treating physician then conducted a clinical review of their care., Main Outcomes and Measures: Assessment of willingness for anticoagulation treatment and its appropriateness after central review by a panel of 4 cardiologists. Use of anticoagulation at 1 year follow-up was compared vs similar patients at other centers in the PINNACLE Registry., Results: Of the 817 patients enrolled, the median (IQR) age was 76.0 (69.0-83.0) years, 369 (45.2%) were women, and the median (IQR) CHA2DS2-VASc score was 4.0 (3.0-6.0). The top 5 reasons physicians cited for no anticoagulation were low AF burden or successful rhythm control (278 [34.0%]), patient refusal (272 [33.3%]), perceived low risk of stroke (206 [25.2%]), fall risk (175 [21.4%]), and high bleeding risk (167 [20.4%]). After rereview, 221 physicians (27.1%) would reconsider prescribing oral anticoagulation as compared with 311 patients (38.1%), including 67 (24.6%) whose physician cited patient refusal. Of 647 patients (79.2%) adjudicated as appropriate or may be appropriate for anticoagulation, physicians would reconsider anticoagulation for only 177 patients (21.2%), while 527 patients (64.5%) would either agree to starting anticoagulation (311 [38.1%]) or were neutral (216 [27.3%]) to starting anticoagulation. Upon follow-up, 119 patients (14.6%) in the BOAT-AF study were prescribed anticoagulation, as compared with 55 879 of 387 975 similar patients (14.4%) at other centers in the PINNACLE Registry., Conclusions and Relevance: The findings of this cohort study suggest that patients with AF who are not receiving anticoagulation are more willing to consider anticoagulation than their physicians. These data emphasize the need to revisit any prior decision against anticoagulation in a shared decision-making manner.

Objectives: The objective of the European Multicenter Registry to Assess Outcomes in coronary artery bypass grafting (CABG) patients (DuraGraft Registry) was to determine clinical outcomes and quality of life (QoL) after contemporary CABG that included isolated CABG and combined CABG/valve procedures, using an endothelial damage inhibitor (DuraGraft) intraoperatively for conduit preservation. Here, we report outcomes in the patient cohort undergoing isolated CABG., Methods: The primary outcome was the composite of all-cause death, myocardial infarction (MI), or repeat revascularization (RR) [major adverse cardiac events (MACE)] at 1 year. Secondary outcomes included the composite of all-cause death, MI, RR, or stroke [major adverse cardiac and cerebrovascular events (MACCE)], and QoL. QoL was assessed with the EuroQol-5 Dimension questionnaire. Independent risk factors for MACE at 1 year were determined using Cox regression analysis., Results: A total of 2532 patients (mean age, 67.4±9.2 years; 82.5% male) underwent isolated CABG. The median EuroScore II was 1.4 [interquartile range (IQR), 0.9-2.3]. MACE and MACCE rates at 1 year were 6.6% and 7.8%, respectively. The rates of all-cause death, MI, RR, and stroke were 4.4, 2.0, 2.2, and 1.9%, respectively. The 30-day mortality rate was 2.3%. Age, extracardiac arteriopathy, left ventricular ejection fraction less than 50%, critical operative state, and left main disease were independent risk factors for MACE. QoL index values improved from 0.84 [IQR, 0.72-0.92] at baseline to 0.92 [IQR, 0.82-1.00] at 1 year ( P <0.0001)., Conclusion: Contemporary European patients undergoing isolated CABG have a low 1-year clinical event rate and an improved QoL., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Human immunodeficiency virus (HIV) is a lentivirus that is transmissible through blood and other body fluids. During the late 1980s and early 1990s, an estimated 10,000 Romanian children were infected with HIV-1 subtype F nosocomially through contaminated needles and untested blood transfusions. Romania was a special case in the global acquired immunodeficiency syndrome (AIDS) pandemic, displaying the largest population of HIV-infected children by parental transmission between 1987-1990. In total, 205 HIV-infected patients from the western part of Romania were analyzed in this retrospective study. Over 70% of them had experienced horizontal transmission from an unknown source, while vertical transmission was identified in only five cases. Most patients had a moderate to severe clinical manifestation of HIV infection, 77.56% had undergone antiretroviral (ARV) treatment, most of them (71.21%) had experienced no adverse reactions and many of those with HIV (90.73%) had an undetectable viral load. Renal impairment was detected in one third of patients (34.63%). Patients born before 1990, male patients, patients diagnosed with HIV before the age of 10, and those undernourished or with renal impairment had a shorter average survival time than the group born after 1990, female patients, patients receiving ARV treatment, patients with a normal body mass index (BMI) and those without renal impairment. Periodical monitoring of the estimated glomerular filtration rate (eGFR) level, as well as the detection of protein excretion, should be taken into consideration worldwide when monitoring HIV-positive patients; this in order to detect even asymptomatic chronic kidney disease (CKD), and to manage these patients and prolong their lives.

Background: Limited data exist on training of European paediatric and adult congenital cardiologists., Methods: A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries., Results: Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87-9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63-10.72 million), and one training centre per 4.29 million population (range 1.63-10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1-17), and duration of training was 3 years (range 2-5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R 2 = 0.41)., Conclusion: Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.

Background: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear., Research Question: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19?, Study Design and Methods: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated., Results: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm., Interpretation: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04344587; URL: www., Clinicaltrials: gov., (Copyright © 2022 American College of Chest Physicians. All rights reserved.)

Background: Drug-coated balloons (DCB) are frequently used to treat femoropopliteal artery disease. However, patency loss occurs in ≥10% of patients within 12 months posttreatment with poor understanding of the underlying mechanisms., Objectives: The authors sought to investigate the determinants of DCB failure in femoropopliteal disease., Methods: Data from randomized clinical trials (IN.PACT SFA, MDT-2113 SFA Japan) and 2 prespecified imaging cohorts of the IN.PACT Global Clinical Study were included. Influential procedural characteristics were evaluated by an independent angiographic core laboratory. The primary endpoint was DCB failure (patency loss during follow-up). Additional endpoints were binary restenosis and clinically driven target lesion revascularization. Multivariable analyses evaluated the clinical, anatomical, and procedural predictors of DCB failure., Results: Included were 557 participants with single lesions and 12-month core laboratory-adjudicated duplex ultrasonography. Key clinical characteristics were as follows: mean age 68.8 years, 67.5% male, 87.6% with hypertension, 76.9% with hyperlipidemia, 40.5% with diabetes mellitus, 90.5% in Rutherford Classification Category (RCC) 2 to 3, and 9.5% in RCC 4 to 5. Average length and reference vessel diameter (RVD) were 16.37 cm and 4.66 mm, respectively; 49.7% of lesions were totally occluded. In multivariable analysis, only residual stenosis >30% was associated with patency loss, whereas residual stenosis >30% and smaller preprocedure RVD were associated with increased binary restenosis risk. RCC >3 and residual stenosis >30% were associated with increased 12-month clinically driven target lesion revascularization risk., Conclusions: Patency loss after DCB treatment was influenced by procedural and clinical factors. Residual stenosis >30%, smaller preprocedure RVD, and higher RCC may be considered predictors of increased risk of DCB failure and its components in femoropopliteal artery disease. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II]; NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA]; NCT01947478; IN.PACT Global Clinical Study; NCT01609296)., Competing Interests: Funding Support and Author Disclosures The clinical studies included in this analysis were sponsored and funded by Medtronic. Data were transferred for independent analysis to the Baim Institute for Clinical Research, and the analysis was funded by Medtronic. Dr Krishnan has served as a consultant to Abbott and Medtronic. Dr Schneider has served as a member of the advisory board for Philips, Boston Scientific, and Medtronic; and has served as a consultant for Cagent, Cardiovascular Systems, Inc, Intact Vascular, Medtronic, Profusa, Silk Road Medical, and Surmodics. Dr Brodmann has received speaker honoraria from Bard Peripheral Vascular, Biotronik, Medtronic, Spectranetics, and VIVA Physicians; and is a consultant for Bard Peripheral Vascular, Biotronik, Medtronic, and Spectranetics. Dr Micari is a compensated consultant for Medtronic and Boston Scientific. Dr Sachar has served as a consultant for, an advisory board member for, and has received compensation for educational programs from Boston Scientific and Medtronic; has received funds for research or clinical trials from Abbott Vascular, Bard Peripheral Vascular, Cook Medical, W.L. Gore and Associates, Medtronic, Terumo, and Veryan; and is a major shareholder of Contego Medical. Dr Scheinert is a compensated consultant for Abbott, Acotec, Alvimedica, Bayer, Boston Scientific, Cook Medical, Cardionovum, CR Baird, Gardia Medical/Allium, Medtronic, Phillips, and Upstream Peripheral Technologies. Dr Doros is an employee of the Baim Institute for Clinical Research, which was funded by Medtronic to conduct the present analysis. Dr Tepe has received research grants from Medtronic; and is a compensated advisory board member for Medtronic. Dr Laird is an employee of Medtronic; has served on the advisory board for Abbott Vascular and Boston Scientific; has served as a consultant for Abbott Vascular, Bard/Becton Dickinson, Boston Scientific, Medtronic, and Philips; and has received speaker fees from Medtronic. Dr Zeller has received speaking honoraria from Abbott Vascular, Bard Peripheral Vascular, Biotronik, Boston Scientific, Cook Medical, Cordis, GLG, W.L. Gore & Associates, Medtronic, Philips, Spectranetics, Straub Medical, TriReme, Veryan, and VIVA Physicians; is a consultant for Abbott Vascular, Bard Peripheral Vascular, Boston Scientific, Cook Medical, W.L. Gore & Associates, Medtronic, and Spectranetics; and his clinic has received study funds or funds for research or clinical trials from 480 Biomedical, Abbott Vascular, B. Braun, Bard Peripheral Vascular, Bayer Pharma, Biotronik, Caveo Med, Contego Medical, Cook Medical, CSI, W.L. Gore & Associates, Innora, Intact Vascular, Medtronic, Mercator, Philips, Pluristem, Shockwave, Spectranetics, Terumo, TriReme, and Veryan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Randomized trials have demonstrated the superiority of ultrathin strut drug-eluting stents compared with alternative stent designs. Whether these differences persist over late-term follow-up is uncertain., Objectives: This study sought to compare late-term (5-year) clinical outcomes among patients treated with ultrathin strut (60 µm) bioresorbable polymer sirolimus-eluting stents (BP SES) and thin strut (81 µm) durable polymer everolimus-eluting stents (DP EES)., Methods: BIOFLOW V (Biotronik Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in the Treatment of Subjects with Up to Three De Novo or Restenotic Coronary Artery Lesions V) was an international, 2:1 randomized trial comparing percutaneous coronary intervention with ultrathin strut BP SES versus thin strut DP EES regarding the primary endpoint of 12-month target lesion failure (TLF). Prespecified outcomes through 5 years were assessed., Results: Among 1,334 patients randomized to treatment with BP SES (n = 884) or DP EES (n = 450), the 5-year rates of TLF were 12.3% for BP SES and 15.3% for DP EES (P = 0.108). Revascularization with BP SES was associated with a significantly lower target vessel-related myocardial infarction (6.6% vs 10.3%, P = 0.015) and late/very late definite/probable stent thrombosis (0.3% vs 1.6%, P = 0.021). Ischemia-driven target lesion revascularization was numerically but not significantly lower with BP SES (5.9% vs 7.7%, P = 0.202). Cardiac death rates were 2.6% versus 1.9% (P = 0.495) for BP SES and DP EES, respectively., Conclusions: In a large, randomized trial, TLF and the individual outcomes of cardiac death and target lesion revascularization at 5 years were similar among patients treated with BP SES versus DP EES. Both target vessel-related myocardial infarction and late/very late definite/probable stent thrombosis were significantly lower with BP SES. These results confirm the durability of safety and the effectiveness of percutaneous coronary intervention with ultrathin BP SES., Competing Interests: Funding Support and Author Disclosures This study was funded by BIOTRONIK AG, Bülach, Switzerland. Dr Kandzari has received institutional research/grant support from Biotronik, Boston Scientific, Cardiovascular Systems, Inc, Medtronic, Orbus Neich, and Teleflex; and has received personal consulting honoraria from Cardiovascular Systems, Inc, Medtronic, and Terumo. Dr Koolen has received lecturer and consultant fees from Medtronic; and has been a proctor for Biotronik. Dr Doros has been a consultant for Pfizer, Sarepta, Novartis, Softworld, and Lipocine. Drs Garcia-Garcia and Bennett have received research grants from Abbott Vascular and Biotronik AG; and have received speaker fees from Abbott Vascular, Biotronik AG, Boston Scientific, and Terumo. Dr Cutlip has received salary support from Baim Institute. Dr Waksman has received consultant fees from Abbott Vascular, Biotronik, Boston Scientific, MeAlliance, SIS Medical, Medtronic, and Philips Volcano; is on the advisory board for Abbott Vascular, Boston Scientific, Medtronic, and Philips Volcano; has received grant support from Abbott Vascular, Biotronik, and Boston Scientific; and is on the Speakers Bureau for AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments., Methods and Results: LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001)., Conclusion: Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment., Competing Interests: Conflict of interest: R.W., C.D.M., H.M.G.-G., and R.T. were Principal Investigator, European Principal Investigator, Responsible Officer Core Laboratory NIRS-IVUS and angiographic analysis, Worldwide Study Coordinator of the Lipid Rich Trial, sponsored by Infraredx-Nipro, Bedford, MA, USA. H.M.G.-G. reports the following institutional grant support: Biotronik, Boston Scientific, Medtronic, Abbott, Neovasc, Shockwave, Phillips, and Corflow. C.D.M. is the recipient of research grants (through the Department of Clinical and Experimental Medicine of the University of Florence) from AMGEN, Behring, Chiesi, Daiichi Sankyo, Edwards, Medtronic, and Shockwave. Z.A.A. reports grants from NIH/NHLBI, Abbott Vascular, and Cardiovascular Systems Inc.; personal fees from Amgen, Astra Zeneca, and Boston Scientific; and equity from Shockwave Medical. G.S.M. reports honoraria from Boston Scientific and Philips. R.W. reports serving on the advisory boards of Abbott Vascular, Amgen, Boston Scientific, Cardioset, Cardiovascular Systems Inc., Medtronic, Philips, and Pi-Cardia Ltd.; being a consultant for Abbott Vascular, Amgen, Biotronik, Boston Scientific, Cardioset, Cardiovascular Systems Inc., Medtronic, Philips, Pi-Cardia Ltd., and Transmural Systems; receiving grant support from AstraZeneca, Biotronik, Boston Scientific, and Chiesi; serving on the speakers bureaus of AstraZeneca and Chiesi, and being an investor in MedAlliance and Transmural Systems. All other authors declared no conflict of interest., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Effective systemic therapies suppress toxic light chain production leading to an increased proportion of patients with light chain (AL) amyloidosis who survive longer albeit with end-stage renal disease. There is a critical need to identify patients in this population who benefit from renal transplantation. This multicenter, observational study from five countries includes 237 patients with AL amyloidosis who underwent renal transplantation between 1987 and 2020. With a median follow-up of 8.5 years, the median overall survival from renal transplantation was 8.6 years and was significantly longer in patients with complete and very good partial hematologic responses (CR + VGPR) compared to less than VGPR (9 versus 6.8 years; HR: 1.5, P = 0.04 [95% CI: 1-2.1]) at renal transplantation. Median graft survival was 7.8 years and was better in the CR + VGPR group (8.3 vs 5.7 years, HR: 1.4, P = 0.05 [95% CI: 1-2]). The frequency and time to amyloid recurrence in the graft was also lower (16% vs 37%, p = 0.01) and longer (median time not achieved vs 10 years, p = 0.001) in the CR + VGPR group. Comparing CR vs. VGPR there was no difference in overall or graft survival. Although 69 patients (29%) experienced hematologic relapse, treatment effectively prevented graft loss in the majority (87%). Renal transplantation in selected AL amyloidosis patients is associated with extended overall and renal graft survival. Patients with hematologic CR or VGPR have the most favorable outcomes, and these patients should be considered for renal transplantation., (© 2022. The Author(s).)

Aims: Diabetes mellitus (DM) is associated with increased cardiovascular morbidity and mortality. The multicentre, prospective Lipid-Rich Plaque trial (LRP) examined non-culprit (NC) non-obstructive coronary segments with a combined near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) catheter. This study assessed the differences in NC plaque characteristics and their influence on major adverse cardiac events (MACE) in diabetic and non-diabetic patients., Methods and Results: Patients with known DM status were divided into no diabetes, diabetes not treated with insulin (non-ITDM), and insulin-treated diabetes (ITDM). The association between presence and type of DM and NC-MACE was assessed at both the patient and coronary segment levels by Cox proportional regression modelling. Out of 1552 patients enrolled, 1266 who had their diabetes status recorded were followed through 24 months. Female sex, hypertension, chronic kidney disease, peripheral vascular disease, and high body mass index were significantly more frequent in diabetic patients. The ITDM group had more diseased vessels, at least one NC segment with a maxLCBI4 mm ≥400 in 46.2% of patients, and maxLCBI4 mm ≥400 in nearly one out of six Ware segments (15.2%, 125/824 segments). The average maxLCBI4 mm significantly increased from non-diabetic patients (NoDM) to non-insulin-treated diabetic patients (non-ITDM) to insulin-treated diabetic patients (ITDM; 137.7 ± 161.9, 154.8 ± 173.6, 182.9 ± 193.2, P < 0.001, respectively). In patients assigned to follow-up (692 ± 129 days), ITDM doubled the incidence of NC-MACE compared with the absence of diabetes (15.7% vs. 6.9%, P = 0.0008). The presence of maxLCBI4 mm>400 further increased the NC-MACE rate to 21.6% (Kaplan-Meier estimate)., Conclusion: Cholesterol-rich NC plaques detected by NIRS-IVUS were significantly more frequent in diabetic patients, especially those who were insulin-treated, and were associated with an increased NC-MACE during follow-up., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Acute kidney injury (AKI) is a common complication after high-dose melphalan and autologous stem cell transplantation (HDM/SCT) in patients with light chain (AL) amyloidosis. However, its incidence, predictors and outcomes are not well known., Methods: This observational study included 223 patients with AL amyloidosis who underwent HDM/SCT. AKI was defined as an increase in serum creatinine to ≥1.5 times the baseline occurring within the first 30 days of HDM/SCT., Results: The median age was 58 years (range: 30-77). Kidney and cardiac involvement were present in 86.1% and 56.8%, respectively. The median estimated glomerular filtration rate (eGFR) was 83.5 mL/min/1.73 m2 (range: 9-213) and proteinuria was 2899 mg/day (range: 0-19 966). AKI occurred in 29.1% of patients. Dialysis was initiated in 15 patients (6.7%) and of these 12 (80%) were able to discontinue dialysis. Most of the episodes of AKI occurred within the first 2 weeks; with a median follow-up of 4.5 years (range: 0.1-16.5), AKI was associated with increased overall mortality [hazard rato (HR) = 4.53, 95% confidence interval (CI) 2-10.23]. The 10-year overall survival was 87.1% without AKI, versus 56.9% with AKI. AKI was also associated with an increased risk for end-stage kidney disease (ESKD) (HR = 4.6, 95% CI 1.44-14.38). The risk of developing ESKD at 10 years was 18.9% with AKI, versus 8.1% without AKI. Several risk factors were found and using multivariate logistic regression, a prediction model was developed that included three readily available variables: eGFR <60 mL/min/1.73 m2, interventricular septal thickness in diastole >12 mm and albumin <3 g/dL. This model was able to predict AKI development with an area under the curve of 0.8., Conclusions: AKI is common in the post-HDM/SCT period and it leads to increased risk for ESKD and death. Our prediction model is an easily deployable tool in clinical settings as part of the discussion with patients who are being prepared for HDM/SCT., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Diflunisal is a non-steroidal anti-inflammatory drug that stabilises transthyretin (TTR) and reduces neurologic deterioration in patients with polyneuropathy caused by hereditary transthyretin amyloidosis (ATTRv)., Methods: We conducted a retrospective cohort study of patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) treated with diflunisal for at least one year between 2009 and 2016 at the Boston University Amyloidosis Centre. Baseline and one year follow up characteristics were measured, including plasma chemistries and echocardiography. Cox proportional hazards analysis assessed the primary outcome of all-cause mortality., Results: A total of 104 ATTRwt-CM patients were evaluated with 35 patients receiving diflunisal. Patients in the diflunisal group were younger (73.8 vs 76.8 years, p  = 0.034), with lower B-type natriuretic peptide (BNP, 335 +/- 67 vs. 520 +/- 296 pg/mL, p  = 0.006), similar troponin I (0.1 +/- 0.1 vs 0.2 +/- 0.3 ng/mL, p  = 0.09), and better renal function (eGFR 67 +/- 17 vs 53 +/- 18 mL/min/1.73m2, p  = 0.0002) at baseline. Over a median follow-up of 3.2 years, 52 deaths occurred. Diflunisal administration was associated with improved survival in unadjusted analysis (HR 0.13, 95% CI 0.05 - 0.36, p  < 0.001) that persisted after adjustment for age, baseline BNP, eGFR, troponin I, interventricular septal thickness, and left ventricular ejection fraction (HR 0.18, 95% CI 0.06 - 0.51, p  = 0.0006). Over the observation period, no significant changes in BNP, troponin I, interventricular septal thickness or left ventricular ejection fraction were observed with diflunisal treatment. A total of 14 patients (40%) discontinued diflunisal in this study, but only 3 within the first year. Mean eGFR in treated patients was 59 ml/min/1.73m 2 at 1 year (change from baseline p  = 0.03)., Conclusion: Diflunisal administration in ATTRwt-CM was associated with improved survival and overall stability in clinical and echocardiographic markers of disease with decrement renal function.

In clinical trials, placebo response is considered a beneficial effect arising from multiple factors, including the patient's expectations for the treatment. Its presence makes the classical parallel study design suboptimal and can bias the inference. The sequential parallel comparison design (SPCD), a two-stage design where the first stage is a classical parallel study design, followed by another parallel design among placebo subjects from the first stage, was proposed to address the shortcomings of the classical design. In SPCD, in lieu of treatment effect, a weighted average of the mean treatment difference in Stage I among all randomized subjects and the mean treatment difference in Stage II among placebo non-responders was proposed as the efficacy measure. However, by linking two possibly different populations, this weighted average lacks interpretability, and the choice of weight remains controversial. In this work, under the principal stratification framework, we propose a causal estimand for the treatment effect under each of three clinically important principal strata: Always Responders, Never Responders, and Drug-only Responders. To make the stratum treatment effect identifiable, we introduce a set of assumptions and two sensitivity parameters. By further considering the strata as latent characteristics, the sensitivity parameters can be estimated. An extensive simulation study is conducted to evaluate the operating characteristics of the proposed method. Finally, we apply our method on the ADAPT-A study data to assess the benefit of low-dose aripiprazole adjunctive to antidepressant therapy treatment., (© 2022 John Wiley & Sons Ltd.)

Background: The Lipid Rich Plaque (LRP) study demonstrated that near-infrared spectroscopy imaging of non-obstructive lesions identified patients and segments at higher risk for subsequent non-culprit major adverse cardiac events (NC-MACE). Whether this is true for both men and women is not known. In this post hoc analysis of the LRP study, we sought to investigate whether the maximum 4-mm Lipid Core Burden Index (maxLCBI 4mm ) was of similar predictive value in men and women for NC-MACE., Methods: Patients with an evaluable maxLCBI 4mm were stratified on the basis of sex at birth. A Cox proportional-hazards model was used to assess the predictive value of maxLCBI 4mm on future NC-MACE at the patient and plaque levels. The primary endpoint was cumulative incidence of NC-MACE at 24 months., Results: Among 1271 patients, 388 (30.5%) were women. Women were older and had a higher cardiovascular risk profile. Cumulative incidence of NC-MACE at 24 months was 10.3% for women and 7.6% for men (log-rank p = 0.11). When comparing maxLCBI 4mm  > 400 to maxLCBI 4mm  ≤ 400, the hazard ratio (HR) for future NC-MACE was not significantly different between sexes: 2.10 (95% confidence interval [CI]: 1.28-3.44; p = 0.003) for men and 2.24 (95% CI: 1.18-4.28; p = 0.014) for women (p = 0.87). At the plaque level, the HR comparing maxLCBI 4mm  > 400 to maxLCBI 4mm  ≤ 400 was 3.49 (95% CI: 1.60-7.60, p = 0.002) for men and 4.79 (95% CI: 2.02-11.38, p < 0.001) for women, which was not significantly different (p = 0.57)., Conclusions: The maxLCBI 4mm was of similar predictive value for NC-MACE within 24 months in men and women., (© 2022 The Authors. Published by Elsevier B.V.)

Background: Ticagrelor is often administered to patients with acute coronary syndromes. However, when these patients require urgent or emergent cardiothoracic (CT) surgery the presence of ticagrelor significantly increases surgical bleeding. The goal of the current trial is to evaluate the effectiveness and safety of the DrugSorb-ATR hemoadsorption device for the intraoperative removal of ticagrelor to reduce postoperative bleeding in the above patient population. The Safe and Timely Antithrombotic Removal - Ticagrelor (STAR-T) Trial is a multi-center, double-blind, randomized, controlled trial enrolling patients who require cardiothoracic surgery on cardiopulmonary bypass (CPB) within 48 hours of last ticagrelor dose., Methods: Subjects will be randomized 1:1 to receive either the DrugSorb-ATR device or an identical sham device during CPB. The study will enroll up to 120 subjects at 20 U.S centers, and the primary outcome is the composite of fatal perioperative bleeding, moderate/severe/massive bleeding according to the Universal Definition of Perioperative Bleeding in Cardiac Surgery (UDPB), and 24 hours chest tube drainage. The components of the composite are hierarchically ranked according to clinical significance and the primary analysis will utilize the Win Ratio method. Percent change in ticagrelor levels before and after CPB (drug removal) will be the key secondary endpoint. An independent Clinical Events Committee will adjudicate all clinical endpoints including safety endpoints relating to postoperative thrombotic events. Subjects will be followed through 30 days after the index operation., Conclusions: The results from STAR-T, if positive, will potentially support FDA market approval for DrugSorb-ATR, and provide a solution to an important unmet clinical need., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated., Methods: The AVATAR trial (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis) is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm 2 with aortic jet velocity >4 m/s or a mean transaortic gradient ≥40 mm Hg), and with normal left ventricular function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite end point of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries., Results: Between June 2015 and September 2020, 157 patients (mean age, 67 years; 57% men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in the conservative treatment group. In the early surgery group, 72 patients (92.3%) underwent SAVR with operative mortality of 1.4%. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite end point than those in the conservative arm (hazard ratio, 0.46 [95% CI, 0.23-0.90]; P =0.02). There was no statistical difference in secondary end points, including all-cause mortality, first heart failure hospitalizations, major bleeding, or thromboembolic complications, but trends were consistent with the primary outcome., Conclusions: In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02436655.

Importance and Objective: The aim of this pragmatic, embedded, adaptive trial was to measure the effectiveness of the subcutaneous anti-IL-6R antibody sarilumab, when added to an evolving standard of care (SOC), for clinical management of inpatients with moderate to severe COVID-19 disease., Design: Two-arm, randomized, open-label controlled trial comparing SOC alone to SOC plus sarilumab. The trial used a randomized play-the-winner design and was fully embedded within the electronic health record (EHR) system., Setting: 5 VA Medical Centers., Participants: Hospitalized patients with clinical criteria for moderate to severe COVID-19 but not requiring mechanical ventilation, and a diagnostic test positive for SARS-CoV-2., Interventions: Sarilumab, 200 or 400 mg subcutaneous injection. SOC was not pre-specified and could vary over time, e.g., to include antiviral or other anti-inflammatory drugs., Main Outcomes and Measures: The primary outcome was intubation or death within 14 days of randomization. All data were extracted remotely from the EHR., Results: Among 162 eligible patients, 53 consented, and 50 were evaluated for the primary endpoint of intubation or death. This occurred in 5/20 and 1/30 of participants in the sarilumab and SOC arms respectively, with the majority occurring in the initial 9 participants (3/4 in the sarilumab and 1/5 in the SOC) before the sarilumab dose was increased to 400 mg and before remdesivir and dexamethasone were widely adopted. After interim review, the unblinded Data Monitoring Committee recommended that the study be stopped due to concern for safety: a high probability that rates of intubation or death were higher with addition of sarilumab to SOC (92.6%), and a very low probability (3.4%) that sarilumab would be found to be superior., Conclusions and Relevance: This randomized trial of patients hospitalized due to respiratory compromise from COVID-19 but not mechanical ventilation found no benefit from subcutaneous sarilumab when added to an evolving SOC. The numbers of patients and events were too low to allow definitive conclusions to be drawn, but this study contributes valuable information about the role of subcutaneous IL-6R inhibition in the treatment of hospitalized COVID-19 patients. Methods developed and piloted during this trial will be useful in conducting future studies more efficiently., Trial Registration: Clinicaltrials.gov-NCT04359901; https://clinicaltrials.gov/ct2/show/NCT04359901?cond=NCT04359901&draw=2&rank=1., Competing Interests: WBE, PM, and JMS were site investigators for a study funded by Gilead Sciences (funds to institution). WBE was supported by NIH NHLBI 1K12HL138049-01. All other authors report no conflicts of interest to report. This does not alter our adherence to PLOS ONE policies on sharing data and materials.