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Background: Hemodynamic assessment of untreated nonculprit lesions was not studied in the PROSPECT study (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). We developed a virtual intravascular ultrasound–derived lesion-specific fractional flow reserve (lesion-specific IVUS-FFR) algorithm to assess individual lesion-level FFR. We sought to investigate the relation between lesion-specific IVUS-FFR and major adverse cardiovascular events (MACE) arising from untreated nonculprit lesions in the PROSPECT study. Methods: In PROSPECT, 697 patients with acute coronary syndromes underwent 3-vessel grayscale and virtual histology–IVUS to correlate untreated nonculprit plaque morphology with 3-year nonculprit related MACE (composite of cardiac death, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina). Lesion-specific IVUS-FFR was calculated from volumetric IVUS lumen area measurements at 0.4 mm intervals by applying a mathematical circulation model using basic fluid dynamics equations. Results: Lesion-specific IVUS-FFR was analyzable in 3227 nonculprit lesions in 660 patients among whom 54 nonculprit MACE events (3 myocardial infarctions) occurred at median 3.4-year follow-up. By receiver-operating characteristic analysis, the best cutoff value of lesion-specific IVUS-FFR to predict nonculprit MACE was ≤0.95. After adjusting for patient and lesion characteristics, lesion-specific IVUS-FFR (hazard ratio, 4.83 [95% CI, 2.20–10.61]; P 2 , plaque burden ≥70%, and virtual histology thin-cap fibroatheroma. Conclusions: Minor reductions in lesion-specific IVUS-FFR were independently associated with future nonculprit MACE arising from untreated angiographically mild stenoses along with previously established high-risk lesion morphological characteristics. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00180466.

Post-traumatic stress disorder (PTSD) represents a global public health concern, affecting about 1 in 20 individuals. The symptoms of PTSD include intrusiveness (involuntary nightmares or flashbacks), avoidance of traumatic memories, negative alterations in cognition and mood (such as negative beliefs about oneself or social detachment), increased arousal and reactivity with irritable reckless behavior, concentration problems, and sleep disturbances. PTSD is also highly comorbid with anxiety, depression, and substance abuse. To advance the field from subjective, self-reported psychological measurements to objective molecular biomarkers while considering environmental influences, we examined a unique cohort of Israeli veterans who participated in the 1982 Lebanon war. Non-invasive oral 16S RNA sequencing was correlated with psychological phenotyping. Thus, a microbiota signature (i.e., decreased levels of the bacteria sp_HMT_914, 332 and 871 and Noxia) was correlated with PTSD severity, as exemplified by intrusiveness, arousal, and reactivity, as well as additional psychopathological symptoms, including anxiety, hostility, memory difficulties, and idiopathic pain. In contrast, education duration correlated with significantly increased levels of sp_HMT_871 and decreased levels of Bacteroidetes and Firmicutes, and presented an inverted correlation with adverse psychopathological measures. Air pollution was positively correlated with PTSD symptoms, psychopathological symptoms, and microbiota composition. Arousal and reactivity symptoms were correlated with reductions in transaldolase, an enzyme controlling a major cellular energy pathway, that potentially accelerates aging. In conclusion, the newly discovered bacterial signature, whether an outcome or a consequence of PTSD, could allow for objective soldier deployment and stratification according to decreases in sp_HMT_914, 332, 871, and Noxia levels, coupled with increases in Bacteroidetes levels. These findings also raise the possibility of microbiota pathway-related non-intrusive treatments for PTSD.

Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the Biorest Liposomal Alendronate Administration for Diabetic Patients Undergoing Drug-Eluting Stent Percutaneous Coronary Intervention trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI withDES in reducing NIH as measured by optical coherence tomography postprocedure in patients with DM.Patients with DM were randomized to a bolus infusion of LABR-312 vs placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by optical coherence tomography.From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3% ± 9.2 vs 14.6% ± 8.5, P = .35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups.Among patients with DM undergoing PCI with drug-eluting stents, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.

Severe coronary artery calcification has been associated with stent underexpansion, procedural complications, and increased rates of early and late adverse clinical events in patients undergoing percutaneous coronary intervention. To date, no lesion preparation strategy has been shown to definitively improve outcomes of percutaneous coronary intervention for calcified coronary artery lesions.ECLIPSE (NCT03108456) is a prospective, randomized, multicenter trial designed to evaluate two different vessel preparation strategies in severely calcified coronary artery lesions. The routine use of the Diamondback 360 Coronary Orbital Atherectomy System is compared with conventional balloon angioplasty prior to drug-eluting stent implantation. The trial aims to enroll approximately 2000 subjects with a primary clinical endpoint of target vessel failure, defined as the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization assessed at 1 year. The co-primary endpoint is the acute post-procedural in-stent minimal cross-sectional area as assessed by optical coherence tomography in a 500-subject cohort. Enrollment is anticipated to complete in 2022 with total clinical follow-up planned for 2 years.ECLIPSE is a large-scale, prospective randomized trial powered to demonstrate whether a vessel preparation strategy of routine orbital atherectomy system is superior to conventional balloon angioplasty prior to implantation of drug-eluting stents in severely calcified coronary artery lesions.

To examine the impact of an integrative medicine (IM) course on self-perceived IM-related communication and research skills.A 3-day mandatory "hybrid" (online and in-person) IM course was held within COVID-19 restrictions for 161 pre-clerkship medical students, with workshops facilitated by mentor healthcare professionals (IM and non-IM) and student-directed tasks. Self-perceived levels of 6 IM-related skills were scored (from 1 to 5) for history-taking; communicating with patients with "alternative" health-beliefs; referral to IM consultations; assessing risks/benefits; and working with non-medical IM practitioners.137 students (85.1%) completed pre-/post-course questionnaires, with overall scores improving from pre-course (1.98 ± 0.92) to post-course (3.31 ± 0.63; p 0.0001), for the entire group and student subgroups (with vs. without prior IM experience). Multivariate analysis found no association between age, gender, primary language or prior experience with IM and improvement in skill scores.The IM course increased self-perceived skill levels, reflecting the course curriculum and workshops. Further research needs to explore the application of these skills during clinical training.Teaching medical students about IM in a course comprising communication and research skills was shown to be feasible and effective. The application of IM-related skills needs to be evaluated during the clinical clerkship.

BACKGROUND: Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT). METHODS: ELOQUENT-1 is an open-label, multicentre, randomised, phase 3 trial conducted at 185 hospitals, oncology practices, and research centres in 19 countries. Eligible patients were aged 18 years or older with newly diagnosed, untreated, symptomatic myeloma and not candidates for high-dose therapy plus HSCT, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower. Patients were randomly assigned (1:1) to receive elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone using an interactive voice response system, stratified by the International Staging System (ISS; stage I-II vs III), age (

Percutaneous cholecystostomy (PCC) is a well-established treatment in patients with high surgical risk and those who failed conservative treatment. However, the role of cholangiography in the management of PCC patients is not clear. In our medical center, cholangiography is routinely performed before discharging patient with PCC. We aimed to evaluate the utility of this test and its effect on the patient's management.The study included all patients managed with PCC between 2015 to 2017. The patients were divided to those with positive findings and those with no findings. The two groups were compered in demographical and clinical parameters.119 patients underwent PCC during the study period. Indication for PCC were comorbidities in 73% and failure of conservative treatment in 27%. Cholangiography was performed in 95 patients. Third of the patients had positive findings in their cholangiography. 13 patients had CBD stones, 14 had obstruction of gallbladder and 6 had bile leak. All positive findings required changed in management.PCC is a safe procedure. Cholangiography, should be performed in every patient who was managed by PCC since it might change the management in third of the cases.

The purpose of this study is to determine the reliability of standard magnetic resonance imaging (MRI) evaluation of AIIS morphology compared with three-dimensional (3D) computerized tomography (CT) (reference standard).Sixty hips in 30 patients met the inclusion criteria. The images were reviewed and classified by two fellowship-trained orthopedic surgeons. A second imaging viewing session was conducted in the same manner for validation of AIIS evaluation. The agreement and accuracy indices between the two raters were calculated for each imaging modality (inter-rater agreement) as well the agreement across the imaging modality for each rater (intermethod agreement).The inter-rater agreement for the morphological evaluation of the AIIS for the first session according to 3D CT was .553 (P.05) and by means of MRI was .0163 (P.05). The inter-rater agreement for the second session by means of 3D CT was .449 (P.05) and according to MRI was 0 (P.05). The inter-method agreement for rater 1 for the first session was .04 (P0.05), while the agreement for rater 2 was .016 (P.05). The intermethod agreement for rater 1 on the second session was .35 (P0.05), while that of rater 2 was .297(P.05). The overall accuracy of MRI compared to 3D CT for rater 1 for the first session was .531, .490, and .959 for types I, II, III respectively and .551, .531, and .980 for the second session for types I, II, and III respectively. The overall accuracy of MRI compared to 3D CT for rater 2 for the first session was .551, .469, and .918 for types I, II, III respectively and .633, .592, and .918 for the second session for types I, II, and III, respectively.MRI evaluations and subsequent classifications of AIIS morphology demonstrated a poor to slight correlation compared with that of the reference standard of 3D CT.Level II, retrospective diagnostic study.

To examine and compare the medical burden of measles, influenza and COVID-19 outbreaks in the city of Bnei Brak, Israel.The study was conducted during 2018-2021. The numbers of hospitalisations for these infections and their complications were recorded. Hospitalisation rates were determined by using the number of children residing in Bnei Brak and hospitalised with these infections during the study period as the numerators. The denominators were the estimated paediatric cases of measles, influenza and COVID-19 in Bnei Brak and were calculated under both pragmatic and conservative assumptions.A total of 247, 65 and 32 children were hospitalised with influenza, COVID-19 and measles respectively. Complication rates were higher following measles than after influenza and SARS-CoV-2 infections. Hospitalisation rates were 10% for measles, 0.6%-1.2% for influenza and 0.15% - 0.25% for COVID-19 infections. Relative risks (RR) with 95% confidence intervals (CI) for hospitalisation following measles compared with COVID-19 ranged from 42 (26.3-67.3) to 70.1 (43.8-112.1), while the relative risks for influenza hospitalisation ranged from 2.5 (1.83-3.41) to 8.2 (6.0-11.2), compared with COVID-19 infection.Hospitalisation rates and direct medical burdens of measles and influenza were significantly higher than those of COVID-19 infection in children.

OBJECTIVES Incidence and prognosis of ST-segment elevation myocardial infarction (STEMI) vary according to ambient temperature and season. We sought to assess whether season and temperature on the day of STEMI are associated with infarct size, microvascular obstruction (MVO), left ventricular ejection fraction (LVEF) and clinical outcomes after primary percutaneous coronary intervention (PCI). METHODS Individual patient data from 1598 patients undergoing primary PCI in six randomized clinical trials were pooled. Infarct size was evaluated by cardiac magnetic resonance within 30 days in all trials. Patients were categorized either by whether they presented on a day of temperature extremes (minimum temperature 25 °C) or according to season. RESULTS A total of 558/1598 (34.9%) patients presented with STEMI on a day of temperature extremes, and 395 (24.7%), 374 (23.4%), 481 (30.1%) and 348 (21.8%) presented in the spring, summer, fall and winter. After multivariable adjustment, temperature extremes were independently associated with larger infarct size (adjusted difference 2.8%; 95% CI, 1.3-4.3; P

Background Aging and type 2 diabetes (T2DM) are associated with an increased risk of sarcopenia. Diagnosis of sarcopenia is commonly done using dual-energy X-ray absorptiometry (DXA) in specialized settings. Another available method for assessing body composition is direct segmental multi-frequency bioelectrical impedance analysis (DSMF-BIA). Here, we examine the accuracy of a DSMF-BIA (InBody-770) for assessing body composition in older adults with T2DM when compared to DXA. Methods Eighty-four obese/overweight older adults (49 women, 71 ± 5 years) with T2DM who were recruited for the CEV-65 study and had both DSMF-BIA and DXA assessments at baseline were included. The analysis included Bland–Altman plots and intra class correlation coefficients. Sub-analyses were performed according to gender and following 10 weeks of interventions (diet, circuit training, and Empagliflozin). Results The leg lean mass results according to DSMF-BIA and DXA were 14.76 ± 3.62 kg and 15.19 ± 3.52 kg, respectively, with no difference between devices according to Bland–Altman analyses (p = 0.353). Assessment of appendicular skeletal mass index did not differ between DSMF-BIA and DXA (7.43 vs. 7.47 kg/m2; p = 0.84; ICC = 0.965, p p = 0.595). Gender and treatment interventions did not modify the accuracy of the DSMF-BIA when compared to DXA. Conclusions In older adults with T2DM the degree of agreement between DSMF-BIA and DXA, was high, supporting the use of DSMF-BIA to measure muscle mass.

Background Evidence of the cardiovascular benefits of adherence to quality indicators in diabetes care over a period of years is lacking. Methods and Results We conducted a population‐based, historical cohort study of 105 656 people aged 45 to 80 with pharmacologically treated diabetes and who were free of cardiac disease in 2010. Data were retrieved from electronic medical records of the 4 Israeli health maintenance organizations. The association between level of adherence to national quality indicators (2006–2010: adherence assessment) and incidence of cardiac outcome; ischemic heart disease or heart failure (2011–2016: outcome assessment) was estimated using Cox proportional hazards models. During 529 551 person‐years of follow‐up, 19 246 patients experienced cardiac disease. An inverse dose–response association between the level of adherence and risk of cardiac morbidity was shown for most of the quality indicators. The associations were modified by age, with stronger associations among younger patients ( Conclusions Longitudinal adherence to quality indicators in diabetes care is associated with reduced risk of cardiac morbidity. Implementation of programs that measure and enhance quality of care may improve the health outcomes of people with diabetes.

Acute septic arthritis of the knee joint is an orthopedic emergency, potentially devastating, which can lead to high morbidity and may even be life-threatening. While any synovial joint can be infected, the knee is the most often affected joint and is involved in about 50 % of the cases. The infection is usually caused by a gram-positive bacteria. The diagnosis is made by synovial fluid aspiration, microbiological analysis and hematological investigations of inflammatory measures. Treatment requires emergency irrigation and debridement of the joint, and intravenous antibiotics. Surgical debridement can be performed either arthroscopically or via open arthrotomy. In recent years, arthroscopic treatment demonstrated more favorable outcomes with better functional outcomes, shorter operative time and hospital stays.

Background: There is a paucity of data regarding the effect of inhibition of the renin-angiotensin system on outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to examine long-term outcomes of patients with left main coronary disease (LMCAD) randomized to PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents or CABG according to treatment at discharge with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in the large-scale, multicenter, randomized EXCEL trial. Methods: EXCEL randomized 1905 patients with LMCAD of low and intermediate anatomical complexity (visually-assessed SYNTAX score ≤32) to PCI (n = 948) versus CABG (n = 957). Patients were categorized according to whether they were treated with ACEI/ARB at discharge; their outcomes from discharge to 5 years were examined using multivariable logistic regression with an offset for follow-up time. Results: Among 1775 patients discharged alive with known ACEI/ARB treatment status, 896 (50.5%) were treated with one of these agents. Among those treated with ACEI/ARB, the 5-year rate of all-cause death was similar after PCI or CABG (10.7% versus 9.8% respectively, adjOR, 0.94; 95% CI, 0.56-1.57) in contrast to patients not treated with ACEI/ARB (15.0% versus 7.8%, respectively, adjOR, 2.20; 95% CI, 1.32-3.67) (Pinteraction = 0.02). Significant interactions between treatment arm (PCI versus CABG) and ACEI/ARB treatment status were also found for cardiovascular death (Pinteraction = 0.03), ischemia-driven revascularization (Pinteraction = 0.03), target vessel revascularization (Pinteraction = 0.007) and target vessel failure (Pinteraction = 0.0009). Conclusion: In the EXCEL trial, the postdischarge rates of death and revascularization after 5 years were similar after PCI and CABG in patients with LMCAD treated with ACEI/ARB at discharge. In contrast, event rates were higher after PCI versus CABG in those not so treated.

Childhood adversity (CA) may alter reactivity to stress throughout life, increasing risk for psychiatric and medical morbidity, yet long-term correlates of milder CA levels among high functioning healthy adolescents are less studied. The current study examined the prevalence and impact of CA exposure among a cohort of healthy motivated elite parachute unit volunteers, prospectively assessed at rest and at the height of an intensive combat-simulation exposure. We found significantly reduced gene expression levels in resting mononuclear cell nuclear receptor, subfamily 3, member 1 (NR3C1), and its transactivator spindle and kinetochore-associated protein 2 (SKA2), that predict blunted cortisol reactivity to combat-simulation stress among CA exposed adolescents. Long-term alterations in endocrine immune indices, subjective distress, and executive functions persist among healthy high functioning adolescents following milder CA exposure, and may promote resilience or vulnerability to later real-life combat exposure.

Background During 2020, Israel experienced two COVID-19-related lockdowns that impacted the provision of primary and secondary preventive care. Methods We examined the month-by-month performance of selected preventive care services using data from Israel’s national Quality Indicators in Community Healthcare program. Process of care measures included hemoglobin A1c (HbA1c) testing, cholesterol testing, colon cancer screening and mammography. Intermediate outcome measures included low-density lipoprotein control and HbA1c control. Measures were stratified by sex and by area-level socioeconomic position (SEP). Diabetes and mammography are presented in this abstract due to space limitations. Results Annual HbA1c testing among persons with diabetes decreased from 90.9% in 2019 to 88.0% in 2020. Performance of HbA1c tests during lockdown months was as low as half the usual amount. There were compensatory increases in testing during post-lockdown months that did not quite make up for the missed tests. In 2019, 9.0% of Israelis with diabetes had poor glycemic control (HbA1c ≥ 9.0); in 2020, it was 8.8%. In total, 4.5% fewer mammograms were performed in 2020 compared with 2019. Women in the lowest SEP level performed 10.4% fewer mammograms in 2020 than in 2019, while women in the highest SEP level performed 3.1% more mammograms. Conclusions Prolonged COVID lockdowns in 2020 were associated with marked decreases in the performance of preventive health services during those months. Compensatory spikes following the end of lockdowns partly, but did not completely, make up for the missed care. COVID lockdowns may have exacerbated socioeconomic disparities in some preventive health services.

In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient-reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaires. Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (CIs) derived from a mixed-effects model. PRO assessment compliance rates were high and similar in both D-Rd and Rd groups through cycle 40 (week 156). In this on-treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ-C30 global health status, physical functioning, and pain scores in the D-Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D-Rd treatment. These findings complement the sustained and significant improvement in progression-free survival observed with D-Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009.

Prior studies in patients with noncomplex coronary artery disease have demonstrated the safety of percutaneous coronary intervention (PCI) in the outpatient setting. We sought to examine the outcomes of outpatient PCI in patients with unprotected left main coronary artery disease (LMCAD). In the EXCEL trial, 1905 patients with LMCAD and site-assessed low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus coronary artery bypass grafting. The primary end point was major adverse cardiovascular events (MACE; the composite of death, stroke, or myocardial infarction). In this sub-analysis, outcomes at 30 days and 5 years were analyzed according to whether PCI was performed in the outpatient versus inpatient setting. Among 948 patients with LMCAD assigned to PCI, 935 patients underwent PCI as their first procedure, including 100 (10.7%) performed in the outpatient setting. Patients who underwent outpatient compared with inpatient PCI were less likely to have experienced recent myocardial infarction. Distal left main bifurcation disease involvement and SYNTAX scores were similar between the groups. Comparing outpatient to inpatient PCI, there were no significant differences in MACE at 30 days (4.0% vs 5.0% respectively, adjusted OR 0.52 95% CI 0.12 to 2.22; p = 0.38) or 5 years (20.6% vs 22.1% respectively, adjusted OR 0.72, 95% CI 0.40 to 1.29; p = 0.27). Similar results were observed in patients with distal left main bifurcation lesions. In conclusion, in the EXCEL trial, outpatient PCI of patients with LMCAD was not associated with an excess early or late hazard of MACE. These data suggest that outpatient PCI may be safely performed in select patients with LMCAD.

Background Whether the time of day of primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI) is associated with infarct size, microvascular obstruction (MVO), and prognosis is uncertain. We compared infarct size assessed by cardiac MRI (CMR) and clinical outcomes in STEMI patients according to the pPCI time of day from a large, individual patient-data pooled database. Methods We pooled patient-level data from five randomized pPCI trials in which infarct size was measured within 1 month by CMR. Patients were categorized according to the pPCI time of day. Results Among 1519 patients with STEMI, 794 (52.2%) underwent pPCI between 8:00 h and 15:59 h, 431 (28.4%) between 16:00 h and 23:59 h, and 294 (19.4%) between 24:00 h and 7:59 h. Infarct size was assessed in 1331 patients at a median of 3.0 days (interquartile range 2.0-5.0) after pPCI. Compared with patients who underwent PCI between 8:00 h and 15:59 h, infarct size was not significantly different for patients undergoing PCI from 16:00 h to 23:59 h [adjusted difference -0.7%, 95% confidence interval (CI) -3.1 to 1.7%, P = 0.46] or 24:00 h to 7:59 h (adjusted difference 0.9%, 95% CI -1.2 to 3.1%, P = 0.29). The time of day of pPCI was also unrelated to MVO and the 1-year risks of death or heart failure hospitalization. Conclusion In this large-scale, individual patient data pooled analysis, no association was found between the time of day of pPCI and infarct size, MVO, or prognosis after STEMI.

Aims In the ILUMIEN III trial, among 450 randomised patients with non-complex lesions undergoing percutaneous coronary intervention (PCI), optical coherence tomography (OCT) guidance led to greater stent expansion than angiography guidance, similar minimal stent area compared to both intravascular ultrasound (IVUS) guidance and angiography guidance, and lower rates of uncorrected dissection and malapposition than both IVUS guidance and angiography guidance. Whether these differences impact on clinical outcomes is unknown. The aim of the present study was to report the 12-month clinical follow-up data from the ILUMIEN III study. Methods and results OCT-guided PCI, using an external elastic lamina-based protocol, was compared to operator-directed IVUS-guided or angiography-guided PCI. Target lesion failure (TLF) and major adverse cardiovascular events (MACE) at 12 months were adjudicated by a blinded clinical events committee. There were no significant differences in the rates of TLF (2.0% OCT, 3.7% IVUS, 1.4% angiography), MACE (9.8% OCT, 9.1% IVUS, 7.9% angiography), or any of the individual components of these outcomes among the groups. No independent predictors of 12-month stent-related clinical events were identified from final OCT. Conclusions In this underpowered study, OCT-guided PCI of non-complex lesions did not show a statistical difference in clinical outcomes at 12 months compared with IVUS or angiography guidance. An appropriately powered trial, including only complex patients and lesions, is underway to substantiate the potential clinical benefit of OCT-guided PCI. Trial registration NCT02471586.

Background We investigated the association of insulin resistance (IR) with coronary plaque morphology and the risk of cardiovascular events in patients enrolled in the Providing Regional Observations to Study Predictors of Events in Coronary Tree (PROSPECT) study. Methods Patients with acute coronary syndromes (ACS) were divided based on DM status. Non-DM patients were further stratified according to homeostasis-model-assessment IR (HOMA-IR) index as insulin sensitive (IS; HOMA-IR ≤ 2), likely-IR (LIR; 2 Results Among non-diabetic patients, 109 patients (21.5%) were categorized as LIR, and 65 patients (12.8%) as DIR. Patients with DIR or DM had significantly higher rates of echolucent plaque compared with LIR and IS. In addition, DIR and DM were independently associated with increased risk of MACE compared with IS (adjusted hazard ratio [aHR] 2.29, 95% confidence interval [CI] 1.22–4.29, p = 0.01 and aHR 2.12, 95% CI 1.19–3.75, p = 0.009, respectively). Conclusions IR is common among patients with ACS. DM and advanced but not early stages of IR are independently associated with increased risk of adverse cardiovascular events. Trial Registration ClinicalTrials.gov Identifier: NCT00180466.

BACKGROUND: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild.OBJECTIVES: We sought to examine the outcomes of percutaneous coronary intervention (PCI) of non-flow-limiting vulnerable plaques.METHODS: Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically non-obstructive stenosis not intended for PCI but with IVUS plaque burden ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) vs. GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (non-powered) safety endpoint was randomized target lesion failure (TLF; cardiac death, target vessel-related MI or clinically-driven target lesion revascularization) at 24 months. The secondary (non-powered) clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (MACE; cardiac death, MI, unstable angina, or progressive angina) at latest follow-up.RESULTS: A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by NIRS-IVUS median plaque burden was 73.7%, median MLA was 2.9 mm2, and median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9±2.6 mm2 compared with 3.0±1.0 mm2 in GDMT alone-treated lesions (least square means difference 3.9 mm2, 95% CI 3.3-4.5, PCONCLUSIONS: PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial.

Despite successful primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI), myocardial salvage is often suboptimal, resulting in large infarct size and increased rates of heart failure and mortality. Unloading of the left ventricle (LV) before primary PCI may reduce infarct size and improve prognosis.STEMI-DTU (NCT03947619) is a prospective, randomized, multicenter trial designed to compare mechanical LV unloading with the Impella CP device for 30 minutes prior to primary PCI to primary PCI alone without LV unloading. The trial aims to enroll approximately 668 subjects, with a potential sample size adaptation, with anterior STEMI with a primary end point of infarct size as a percent of LV mass evaluated by cardiac magnetic resonance at 3-5 days after PCI. The key secondary efficacy end point is a hierarchical composite of the 1-year rates of cardiovascular mortality, cardiogenic shock ≥24 hours after PCI, use of a surgical left ventricular assist device or heart transplant, heart failure, intra-cardiac defibrillator or chronic resynchronization therapy placement, and infarct size at 3 to 5 days post-PCI. The key secondary safety end point is Impella CP-related major bleeding or major vascular complications within 30 days. Clinical follow-up is planned for 5 years.STEMI-DTU is a large-scale, prospective, randomized trial evaluating whether mechanical unloading of the LV by the Impella CP prior to primary PCI reduces infarct size and improves prognosis in patients with STEMI compared to primary PCI alone without LV unloading.

Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079). Dr Farkouh has received research grants from Amgen, Novo Nordisk, and Novartis. Dr Stone has received speaker honoraria from Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Miracor, Neovasc, Abiomed, Ancora, Vectorious, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, and Amgen; and has equity/ options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Godoy is supported by the Frederick Banting and Charles Best Canada Graduate Scholarship (Doctoral Research Award) from the Canadian Institutes of Health Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

IMPORTANCE: The outcome and interpretation of noninferiority trials depend on the magnitude of the noninferiority margin and whether a relative or absolute noninferiority margin is used and may be affected by imprecision in event rate estimation. OBJECTIVE: To assess the consequence of imprecise event rate estimations on interpretation of peer-reviewed randomized clinical trials. DATA SOURCES: PubMed/MEDLINE was searched for articles published between January 1, 2015, and April 30, 2021. STUDY SELECTION: Noninferiority randomized clinical trials of coronary stents published in selected journals with clinical events as the primary end point. DATA EXTRACTION AND SYNTHESIS: Two reviewers (M.S. and F.V.) independently extracted data on trial characteristics, noninferiority assumptions, primary end point clinical outcomes, and study conclusions. Overestimation or underestimation of the control event rate was evaluated by dividing the assumed control event rate by the observed control event rate. For noninferiority end points with absolute margins, the assumed corresponding relative margin was defined as the ratio of the absolute margin and the assumed event rate, and the observed corresponding relative margin as the ratio between the absolute margin and the observed event rate in the control arm. Noninferiority comparisons with absolute margins were reanalyzed using the assumed corresponding relative margin and the Farrington-Manning score test for relative risk. MAIN OUTCOMES AND MEASURES: Overestimation or underestimation, assumed and observed corresponding relative margins, and relative reanalysis of the primary end points of trials with absolute margins. RESULTS: A total of 106 989 patients from 58 trials were included. The event rate in the control arms was overestimated by a median (IQR) of 28% (2%-74%). Most noninferiority trials used absolute rather than relative margins (55 of 58 trials [94.8%]). Owing to overestimation, absolute noninferiority margins became more permissive than originally assumed (median [IQR] of observed relative noninferiority margin, 1.62 [1.50-1.80] vs assumed relative noninferiority margin, 1.47 [1.39-1.55]; P

BackgroundPersonality disorders are prevalent in 6–10% of the population, but their risk for cause-specific mortality is unclear. The aim of the study was to assess the association between personality disorders diagnosed in late adolescence and all-cause as well as cause-specific (cardiovascular-related, external-related) mortality.MethodsWe performed a longitudinal study on a historical prospective cohort based on nationwide screening prior to recruitment to the Israeli army. The study participants were 16–19-year-old persons who attended the army screening (medical and cognitive, including screening for psychiatric disorders) between 1967 and 2006. Participants were followed from 1967 till 2011.ResultsThe study included 2 051 606 subjects, of whom 1 229 252 (59.9%) were men and 822 354 (40.1%) were women, mean age 17.36 years. There were 55 508 (4.5%) men and 8237 (1.0%) women diagnosed with personality disorders. The adjusted hazard ratio (HRs) for coronary, stroke, cardiovascular, external-related causes and all-cause mortality among men with personality disorders were 1.34 (1.03–1.74), 1.82 (1.20–2.76), 1.45 (1.23–1.71), 1.41 (1.30–1.53) and 1.44 (1.36–1.51), respectively. The absolute rate difference for all-cause mortality was 56.07 and 13.19 per 105 person-years among men and women, respectively. Among women with personality disorders, the adjusted HRs for external-related causes and all-cause mortality were 2.74 (1.87–4.00) and 2.01 (1.56–2.58). Associations were already evident within 10 years of follow-up.ConclusionsPersonality disorder in late adolescence is associated with increased risk of cardiovascular, external- and all-cause mortality. Increased cardiovascular mortality is evident before the age of 40 years and may point to the importance of lifestyle education already in youth.

The win ratio was introduced in 2012 as a new method for examining composite endpoints and has since been widely adopted in cardiovascular (CV) trials. Improving upon conventional methods for analysing composite endpoints, the win ratio accounts for relative priorities of the components and allows the components to be different types of outcomes. For example, the win ratio can combine the time to death with the number of occurrences of a non-fatal outcome such as CV-related hospitalizations (CVHs) in a single hierarchical composite endpoint. The win ratio can provide greater statistical power to detect and quantify a treatment difference by using all available information contained in the component outcomes. The win ratio can also incorporate quantitative outcomes such as exercise tests or quality-of-life scores. There is a need for more practical guidance on how best to design trials using the win ratio approach. This manuscript provides an overview of the principles behind the win ratio and provides insights into how to implement the win ratio in CV trial design and reporting, including how to determine trial size.

Purpose To assess the accuracy of template-guided implant surgery for edentulous arches. Materials and methods The stone master casts of 25 edentulous arches treated with either 4 or 6 implants with CBCT generated template-guided surgery were included in this observational cohort study. The stone casts generated from the surgical templates (group one) prior to implant placement were digitized into Standard Tesselation (STL) files with a reference scanner. For comparison, the stone master casts derived from intraoral complete-arch impressions after implant placement (group two) were also digitized. The resultant STL files were superimposed and best-fit-alignment algorithm was used to quantify the 3D deviations present between the two groups. Descriptive statistics were computed for all categorical variables. Due to the presence of nonindependent samples between maxillary and mandibular casts, a mixed-effects model was used. Results Deviations between the implant analogs of the stone casts representing digitally planned versus actually placed implants were found. The mean root-mean-square error (RMSE) between all 25 arches was found to be 0.2 mm (SD ± 0.15). The mean RMSE between presurgical and postsurgical maxillary stone casts were 0.19 ± 0.15 mm, while between mandibular stone casts were 0.21 ± 0.16 mm and were not significant (p = 0.67). The mean RMSE between presurgical and postsurgical stone casts arches with 4 versus 6 implants were found to be significant (p = 0.01). Conclusions According to the results of the study and based on the amount of 3D deviations between the digitally planned implant positions and the actually placed implants, template-guided surgery is a safe treatment modality for implant placement in edentulous arches.

Individuals who witness team members exhibiting symptoms of an acute stress reaction (ASR) in the middle of a high-stress operational event may be negatively affected; ASR-related training may moderate this impact. In the present study, 560 Israeli soldiers were surveyed about ASR exposure, posttraumatic stress disorder (PTSD) symptoms, public stigma, and whether they had received ASR-related training. This training, called YaHaLOM, is a Hebrew acronym that outlines steps for managing ASR in team members. Controlling for combat exposure, greater exposure to ASR symptoms was associated with more overall PTSD symptoms, PTSD cluster symptoms, and public stigma. YaHaLOM training buffered these relationships for PTSD, intrusion and avoidance symptoms, and public stigma. The findings suggest that such training may help teams in high-risk occupations better manage ASR exposure.

Japanese patients have shown improved outcomes after treatment with drug eluting stents compared with Western patients. Outcomes with the ridaforolimus-eluting EluNIR stent in Japanese patients are unknown. This was a multi-center trial in Japanese patients undergoing PCI with the ridaforolimus eluting EluNIR stent. A propensity-score matched analysis was performed with the EluNIR arm of the BIONICS trial. The matched cohort was compared with the Japanese patients for the primary endpoint of target lesion failure (TLF) in a non-inferiority study. 104 Japanese patients were compared with 410 matched patients from BIONICS. Baseline characteristics were similar except for more frequent multi-vessel disease in the BIONICS cohort. Post dilation was more likely in Japanese patients (90.4% vs. 64.6%, p

Aims Heart failure (HF) hospitalization prior to transcatheter aortic valve replacement (TAVR) is associated with increased post-procedural mortality. We sought to assess the association between recent (≤6 months) HF hospitalization and long-term adverse outcomes in patients with symptomatic, severe aortic stenosis, undergoing TAVR in the PARTNER 2 trial and registries. Methods and results Intermediate to high or even prohibitive risk patients who underwent TAVR in the PARTNER 2 trial and registries were included in the analysis. Clinical outcomes at 30 days and 2 years were compared between patients according to whether they were recently hospitalized for HF, using Kaplan-Meier event rates and study-stratified multivariable Cox proportional hazards regression models. A sensitivity analysis was conducted using propensity score matching. Of 3988 patients (99.8%) with available information on recent HF hospitalization, 1622 patients (40.7%) were hospitalized for HF symptoms during the 6 months prior to TAVR. After multivariable adjustments, recent HF hospitalization was associated with increased all-cause mortality at 30 days [adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.07-2.48, P = 0.02] and 2 years (adjusted HR 1.30, 95% CI 1.13-1.49, P = 0.0003), which was driven by increased cardiovascular mortality. Infective endocarditis rate at 2 years was also higher in patients with recent HF hospitalization (adjusted HR 2.35, 95% CI 1.38-4.01, P = 0.002). These results remained consistent when propensity score matching was used. Conclusion In a large cohort of patients with severe symptomatic aortic stenosis from the PARTNER 2 trial and registries, all-cause and cardiovascular mortality as well as infective endocarditis rates at 2 years were higher in patients with recent HF hospitalization.

Under conditions of profound stress, individuals in high-risk occupations may experience an acute stress reaction (ASR). Given that ASRs may interfere with functioning, placing the team in danger, the Israel Defense Forces developed YaHaLOM training to teach service members how to manage ASRs in team members. YaHaLOM is a novel, rapid, peer-based intervention specifically designed for use in the midst of a high-stress event. In all, 904 Israeli combat soldiers participated in the study; 76% reported having received YaHaLOM, and 24% reported that they had not. In addition to measures of knowledge about managing ASRs, confidence in managing ASRs, and stigma-related attitudes toward ASRs, questions also addressed training approach, including the use of a video and instructor type. Participants who reported receiving YaHaLOM also reported more knowledge about managing an ASR, more confidence in managing an ASR, less external stigma, and more normative views of ASRs. Being trained with a video was associated with more confidence and less self-stigma than being trained without a video. Instructor type was not associated with differences in knowledge, confidence, or stigma-related attitudes. The study is limited by cross-sectional self-report data. Nevertheless, results suggest YaHaLOM may prepare soldiers to manage ASRs in team members; future studies are needed to assess intervention efficacy and to expand this research to other high-risk occupational contexts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background Ethiopian soldiers in the IDF comprise an at-risk group for suicide. The study investigated the unique characteristics of these soldiers, compared with other suicides in the Israel Defense Forces (IDF). Method The research group included all (n = 36) male soldiers born an Ethiopian family, who died by suicide during their compulsory military service in the years 1990-2017. The control group included all (n = 55) non-Ethiopian soldiers who died by suicide during their military service in the years 2009-2013. Socio-demographic, military-service, and suicide-related variables were examined. Results Logistic regression analysis revealed that risk for suicide among Ethiopian soldiers were being incarcerated in a military prison, belonging to a bereaved family, seniority in the military service, and avoidance of help-seeking (explaining 87.8% of the variance). Discussion Ethiopian suicide soldiers have endured heavy environmental pressure, such as financial problems and family bereavement. These circumstances could lead to conflict with the soldier's military service, resulting in absence from service or even imprisonment. When the Ethiopian soldier's distress goes un-expressed in words or actions with others, the psychological crisis signs remain unapparent to those around him, and the risk for eventual suicide is high. Limitations The case analysis did not include retrieving information from family and relatives outside the military but was derived from archived material, collected primarily for legal purposes. This limitation was addressed by assembling objective variables and information collected prior to the suicide, along with post-mortem information collected by mental health personnel in their assessments.

Background Studies examining sex-related outcomes following percutaneous coronary intervention (PCI) have reported conflicting results. Objectives The purpose of this study was to examine the sex-related risk of 5-year cardiovascular outcomes after PCI. Methods The authors pooled patient-level data from 21 randomized PCI trials and assessed the association between sex and major adverse cardiac events (MACE) (cardiac death, myocardial infarction [MI], or ischemia-driven target lesion revascularization [ID-TLR]) as well as its individual components at 5 years. Results Among 32,877 patients, 9,141 (27.8%) were women. Women were older and had higher body mass index, more frequent hypertension and diabetes, and less frequent history of surgical or percutaneous revascularization compared with men. By angiographic core laboratory analysis, lesions in women had smaller reference vessel diameter and shorter lesion length. At 5 years, women had a higher unadjusted rate of MACE (18.9% vs. 17.7%; p = 0.003), all-cause death (10.4% vs. 8.7%; p = 0.0008), cardiac death (4.9% vs. 4.0%; p = 0.003) and ID-TLR (10.9% vs. 10.2%; p = 0.02) compared with men. By multivariable analysis, female sex was an independent predictor of MACE (hazard ratio [HR:]: 1.14; 95% confidence interval [CI:]: 1.01 to 1.30; p = 0.04) and ID-TLR (HR: 1.23; 95% CI: 1.05 to 1.44; p = 0.009) but not all-cause death (HR: 0.91; 95% CI: 0.75 to 1.09; p = 0.30) or cardiac death (HR: 0.97; 95% CI: 0.73 to 1.29; p = 0.85). Conclusions In the present large-scale, individual patient data pooled analysis of contemporary PCI trials, women had a higher risk of MACE and ID-TLR compared with men at 5 years following PCI.

Elderly patients may have increased platelet reactivity and adverse events after percutaneous coronary intervention. Whether age is an independent predictor of worse outcomes after accounting for platelet reactivity is unknown. We sought to determine the relation between age and platelet reactivity on 2-year outcomes after percutaneous coronary intervention with drug-eluting stents (DES). ADAPT-DES was a prospective observational registry comprising 8,582 DES-treated patients. Patients were categorized with an age cutoff of 75 years. On-clopidogrel platelet reactivity was evaluated with VerifyNow P2Y12 testing. Multivariable Cox proportional hazards regression models were used to describe the relation between increasing age and 2-year clinical outcomes. Patients ≥75 old were more likely to be women and had more cardiovascular risk factors and more extensive coronary artery disease than younger patients. Residual platelet reactivity on-clopidogrel increased slightly with age (adjusted r = 0.05, p0.0001). Age ≥75 years was associated with greater all-cause mortality (adjusted HR 1.64, 95% CI 1.25 to 2.15, p0.001), myocardial infarction (adjusted HR 1.33, 95% CI 1.01 to 1.74, p = 0.04) and clinically relevant bleeding (adjusted HR 1.33, 95% CI 1.10 to 1.61 p = 0.003). In contrast, the risk of stent thrombosis was independent of age (adjusted HR 0.83, 95% CI 0.46 to 1.52, and p = 0.55). Considered as a continuous variable, age was directly related to clinically relevant bleeding, cardiac and all-cause mortality, was inversely related to stent thrombosis, and was not related to myocardial infarction. There was no significant interaction between age and on-treatment platelet reactivity for the risk of 2-year clinical outcomes. In conclusion, increasing age had a stronger association with the risk of death and bleeding than of thrombotic events. Despite being associated with older age, higher residual platelet reactivity did not modify the adjusted relative risks of ischemic and bleeding events associated with age.

The incidence, recurrence rate, and prognostic significance of atrial fibrillation or flutter (AF) following hospital discharge after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD) are unknown. We sought to determine the 3-year incidence and clinical impact of postdischarge AF in patients with LMCAD treated with PCI or CABG. In the EXCEL trial, 1,905 patients with LMCAD were randomized to PCI versus CABG. We analyzed the occurrence of postdischarge AF through 3 years and its time-adjusted association with adverse outcomes. A total of 1,802 patients without AF at baseline comprised the study cohort. Within 3 years, 227 episodes of AF occurred (29 [12.8%] in the PCI arm and 198 [87.2%] in the CABG arm, p

The majority of stent-related major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) are believed to occur within the first year. Very-late (1-year) stent-related MACE have not been well described.The purpose of this study was to assess the frequency and predictors of very-late stent-related events or MACE by stent type.Individual patient data from 19 prospective, randomized metallic stent trials maintained at a leading academic research organization were pooled. Very-late MACE (a composite of cardiac death, myocardial infarction [MI], or ischemia-driven target lesion revascularization [ID-TLR]), and target lesion failure (cardiac death, target-vessel MI, or ID-TLR) were assessed within year 1 and between 1 and 5 years after PCI with bare-metal stents (BMS), first-generation drug-eluting stents (DES1) and second-generation drug-eluting stents (DES2). A network meta-analysis was performed to evaluate direct and indirect comparisons.Among 25,032 total patients, 3,718, 7,934, and 13,380 were treated with BMS, DES1, and DES2, respectively. MACE rates within 1 year after PCI were progressively lower after treatment with BMS versus DES1 versus DES2 (17.9% vs. 8.2% vs. 5.1%, respectively, p 0.0001). Between years 1 and 5, very-late MACE occurred in 9.4% of patients (including 2.9% cardiac death, 3.1% MI, and 5.1% ID-TLR). Very-late MACE occurred in 9.7%, 11.0%, and 8.3% of patients treated with BMS, DES1, and DES2, respectively (p 0.0001), linearly increasing between 1 and 5 years. Similar findings were observed for target lesion failure in 19,578 patients from 12 trials. Findings were confirmed in the network meta-analysis.In this large-scale, individual patient data pooled study, very-late stent-related events occurred between 1 and 5 years after PCI at a rate of ∼2%/year with all stent types, with no plateau evident. New approaches are required to improve long-term outcomes after PCI.

The prognostic impact of resting heart rate (RHR) following revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with left main coronary artery disease (LMCAD) is unknown. We aimed to assess the effect of RHR at discharge on 3-year cardiovascular outcomes following PCI and CABG for LMCAD. In the EXCEL trial, 1,905 patients with LMCAD were randomized to PCI with everolimus-eluting stents versus CABG. RHR was measured at discharge following the index hospitalization. The principal outcome measure was the composite endpoint of death, myocardial infarction (MI) or stroke at 3 years. Among 1,303 patients in sinus rhythm with available ECGs, the median (IQR) discharge RHR was 72 (62to 81) bpm. Median discharge RHR was higher after CABG versus PCI (78 [IQR 70 to 86] versus 65 [IQR 59 to 74] bpm, p0.0001). At 3 years, 107 patients (8.2%) had a primary composite endpoint event including 61 patients (4.7%) who died. By multivariable analysis, discharge RHR assessed as a continuous variable (per 5 bpm) was an independent predictor at 3 years of the primary composite endpoint of death, MI, or stroke (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.06 to 1.25, p = 0.0006); the secondary composite endpoint of death, MI, stroke, or ischemia-driven revascularization at 3 years (HR 1.12, 95% CI 1.05 to 1.19, p = 0.0007); all-cause mortality (HR 1.18, 95% CI 1.07 to 1.31, p = 0.002); and cardiovascular death (HR 1.16, 95% CI 1.00 to 1.33, p = 0.046). No significant interactions were present between RHR and treatment with PCI versus CABG for the primary (p

We aimed to characterise the response of locally advanced basal cell carcinoma (BCC) to systemic treatment with Vismodegib, a Hedgehog pathway inhibitor, by changes in the expression levels of Hedgehog pathway genes. Data were collected prospectively on 12 patients treated systemically for locally advanced BCC. Biopsy samples taken on admission and after treatment cessation were analysed pathologically and with the NanoString nCounter system to quantify the expression of 40 Hedgehog signaling pathway genes. Findings were compared before and after treatment, between complete and partial responders, and with localised BCC samples from 22 patients. Sixteen Hedgehog pathway genes changed significantly from before to after treatment. GAS1 was the only gene with a significantly different expression at baseline between complete responders (6 patients) and partial responders (4 patients) to Vismodegib (P = 0.014). GAS, GLIS2 and PRKACG1 showed different expression before treatment between the locally advanced and localised BCCs. The baseline expression level of GAS1 appears to be predictive of the response of locally advanced BCC to systemic Vismodegib treatment. A change in expression of many Hedgehog pathway genes, albeit expected by the known activity of Vismodegib, may nevertheless serve as an indicator of the response potential of the tumour.

Item does not contain fulltext Research has not adequately addressed a possible mutual co-regulatory influence of prosocial and aggressive behaviors in adolescents' daily lives. This study explored bidirectional within-person associations between prosocial and aggressive behaviors in the daily school lives of early adolescents. The sample included 242 sixth-graders [Mage = 11.96 (SD = 0.18), 50% girls] and their teachers. Adolescents reported on daily prosocial behavior and reactive and proactive aggression for ten consecutive days. Teachers and adolescents reported on adolescents' overall prosocial behaviors. Across-day prosocial behaviors increased after days when adolescents exhibited more reactive aggression but not among self-reported low-prosocial adolescents. Increased prosocial behaviors did not mitigate aggression the next day. The findings suggest prosocial behaviors are a plausible compensatory strategy after daily aggressive reactions. 17 p.

Background: Prior studies have reported an association between elevated white blood cell count (WBCc) and worse clinical outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). We assessed the prognostic impact of WBCc in patients undergoing revascularization for left main coronary artery disease (LMCAD). Methods: In Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL), 1905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. The 1895 patients with baseline WBCc available were grouped in tertiles of WBCc (mean 5.6 ± 0.8, 7.5 ± 0.5, and 10.1 ± 1.6 × 109/L). Results: Five-year rates of the primary endpoint (death, myocardial infarction or stroke) were similar across increasing WBCc tertiles (21.2, 18.9, and 21.6%; P = 0.46). Individual components of the primary endpoint, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, stent thrombosis or graft occlusion and ischemia-driven revascularization were all similar across WBCc tertiles. By multivariable analysis, WBCc as a continuous variable was not an independent predictor of adverse events (hazard radio per 1 × 109/L: 1.02; 95% CI, 0.97-1.08; P = 0.43). Results were consistent in the PCI and CABG arms individually. Conclusion: There was no association between baseline WBCc and 30-day or 5-year clinical outcomes after PCI or CABG. The absence of a clear incremental increase in events with increasing WBCc in the current analysis indicates that WBCc should not routinely be used as a prognostic marker or to guide revascularization decisions in patients with LMCAD.

OBJECTIVES We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD. BACKGROUND Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI. METHODS Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208. RESULTS Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p

Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).

The present study aimed to explore attitudes of medical students following a course in integrative medicine (IM) focused on palliative and supportive cancer.Attitudes to IM among pre-clerkship medical students were assessed following a 3-day required course, which included interviews with international experts in IM and "hands-on" workshops mentored by IM and non-IM healthcare professionals. Student reflections were analyzed qualitatively, and written narratives were examined thematically.Of 161 students, 102 (63.4%) provided post-course reflections. The main narrative themes included pre-course attitudes, attitude changes and influencing factors, and insights on implementing IM in clinical practice. Pre-course attitudes were predominantly skeptical, with post-course attitudes more open and non-judgmental, addressing research on IM effectiveness and safety. Students looked favorably on the implementation of IM in clinical practice and felt the course enhanced communication with patients.Student attitudes to IM shifted following the course, from a skeptical to a more non-judgmental and accepting approach. IM course may facilitate a better understanding of the limitations and risks of IM practices, particularly in the supportive cancer care setting, as well as implications regarding students' own resilience and professional growth.