Phage K exposure generates phage-neutralizing activity in a rabbit model-humoral receptiveness may impact efficacy of phage therapy.

Phage therapy has not been established in the clinical routine, in part due to uncertainties concerning efficacy and immunogenicity. Here, three rabbits were immunized against staphylococcal phage K to assess viral potency in the presence of immunized serum. Three rabbits received weekly intramuscular injections of ~1010±1 pfu/mL phage K. Phage K-specific IgG formation was measured by an enzyme-linked immunosorbent assay (ELISA); phage inactivation was assessed by calculating K-rates. Using transmission electron microscopy (TEM) and immunogold labeling, antibody binding to phage K was visualized. This was numerically assessed by objective imaging analysis comparing the relative distances of each gold particle to the nearest phage head and tail structure. Immunization led to a strong IgG response, plateauing 7 days after the last phage injection. There was no significant correlation between K-rate and antibody titer over time. TEM showed IgG binding to the head structure of phage K. Image analysis showed a significant reduction in relative distances between antibodies and phage head structures when comparing samples from day 0 and day 28 (P < 0.0001). These results suggest that while individual serum analysis for antibodies against therapeutic phage bears consideration prior to and with prolonged therapy, during phage application, the formation of specific antibodies against phage may only partially explain decreased phage potency in the presence of immunized serum. Instead, other factors may contribute to an individual's "humoral receptiveness" to phage therapy. Future investigations should be directed toward the identification of the humoral factors that have the most significant predictive value on phage potency in vivo.

Comparing the compensatory reserve metric obtained from invasive arterial measurements and photoplethysmographic volume-clamp during simulated hemorrhage.

PURPOSE: The compensatory reserve metric (CRM) is a novel tool to predict cardiovascular decompensation during hemorrhage. The CRM is traditionally computed using waveforms obtained from photoplethysmographic volume-clamp (PPGVC), yet invasive arterial pressures may be uniquely available. We aimed to examine the level of agreement of CRM values computed from invasive arterial-derived waveforms and values computed from PPGVC-derived waveforms. METHODS: Sixty-nine participants underwent graded lower body negative pressure to simulate hemorrhage. Waveform measurements from a brachial arterial catheter and PPGVC finger-cuff were collected. A PPGVC brachial waveform was reconstructed from the PPGVC finger waveform. Thereafter, CRM values were computed using a deep one-dimensional convolutional neural network for each of the following source waveforms; (1) invasive arterial, (2) PPGVC brachial, and (3) PPGVC finger. Bland-Altman analyses were used to determine the level of agreement between invasive arterial CRM values and PPGVC CRM values, with results presented as the Mean Bias [95% Limits of Agreement]. RESULTS: The mean bias between invasive arterial- and PPGVC brachial CRM values at rest, an applied pressure of -45mmHg, and at tolerance was 6% [-17%, 29%], 1% [-28%, 30%], and 0% [-25%, 25%], respectively. Additionally, the mean bias between invasive arterial- and PPGVC finger CRM values at rest, applied pressure of -45mmHg, and tolerance was 2% [-22%, 26%], 8% [-19%, 35%], and 5% [-15%, 25%], respectively. CONCLUSION: There is generally good agreement between CRM values obtained from invasive arterial waveforms and values obtained from PPGVC waveforms. Invasive arterial waveforms may serve as an alternative for computation of the CRM.

Patient and dentist perspectives on collecting patient reported outcomes after painful dental procedures in the National Dental PBRN.

BACKGROUND: Dental Patient Reported Outcomes (PROs) relate to a dental patient's subjective experience of their oral health. How practitioners and patients value PROs influences their successful use in practice. METHODS: Semi-structured interviews were conducted with 22 practitioners and 32 patients who provided feedback on using a mobile health (mHealth) platform to collect the pain experience after dental procedures. A themes analysis was conducted to identify implementation barriers and facilitators. RESULTS: Five themes were uncovered: (1) Sense of Better Care. (2) Tailored Follow-up based on the dental procedure and patient's pain experience. (3) Effective Messaging and Alerts. (4) Usable Digital Platform. (5) Routine mHealth Integration. CONCLUSION: Frequent automated and preferably tailored follow-up messages using an mHealth platform provided a positive care experience for patients, while providers felt it saved them time and effort. Patients thought that the mHealth questionnaires were well-developed and of appropriate length. The mHealth platform itself was perceived as user-friendly by users, and most would like to continue using it. PRACTICAL IMPLICATIONS: Patients are prepared to use mobile phones to report their pain experience after dental procedures. Practitioners will be able to close the post-operative communication gap with their patients, with little interruption of their workflow.

Effect of Patient-Reported Preprocedural Physical and Mental Health on 10-Year Mortality After Percutaneous or Surgical Coronary Revascularization.

BACKGROUND: Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical outcomes after revascularization. METHODS: This subgroup analysis of the SYNTAXES trial (SYNTAX Extended Survival), which is the extended follow-up of the randomized SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) comparing PCI with CABG in patients with left-main CAD or 3-vessel disease, stratified patients by terciles of Physical (PCS) or Mental Component Summary (MCS) scores derived from the preprocedural 36-Item Short Form Health Survey, with higher PCS and MCS scores representing better physical and mental health, respectively. The primary end point was all-cause death at 10 years. RESULTS: A total of 1656 patients with preprocedural 36-Item Short Form Health Survey data were included in the present study. Both higher PCS and MCS were independently associated with lower 10-year mortality (10-point increase in PCS adjusted hazard ratio, 0.84 [95% CI, 0.73-0.97]; P=0.021; in MCS adjusted hazard ratio, 0.85 [95% CI, 0.76-0.95]; P=0.005). A significant survival benefit with CABG over PCI was observed in the highest PCS (>45.5) and MCS (>52.3) terciles with significant treatment-by-subgroup interactions (PCS Pinteraction=0.033, MCS Pinteraction=0.015). In patients with both high PCS (>45.5) and MCS (>52.3), 10-year mortality was significantly higher with PCI compared with CABG (30.5% versus 12.2%; hazard ratio, 2.87 [95% CI, 1.55-5.30]; P=0.001), whereas among those with low PCS (≤45.5) or low MCS (≤52.3), there were no significant differences in 10-year mortality between PCI and CABG, resulting in a significant treatment-by-subgroup interaction (Pinteraction=0.002). CONCLUSIONS: Among patients with left-main CAD or 3-vessel disease, patient-reported preprocedural physical and mental health status was strongly associated with long-term mortality and modified the relative treatment effects of PCI versus CABG. Patients with the best physical and mental health had better 10-year survival with CABG compared with PCI. Assessment of self-reported physical and mental health is important when selecting the optimal revascularization strategy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; SYNTAXES Unique identifier: NCT03417050. URL: https://www. CLINICALTRIALS: gov; SYNTAX Unique identifier: NCT00114972.

Understanding Reader Variability: A 25-Radiologist Study on Liver Metastasis Detection at CT.

Background Substantial interreader variability exists for common tasks in CT imaging, such as detection of hepatic metastases. This variability can undermine patient care by leading to misdiagnosis. Purpose To determine the impact of interreader variability associated with (a) reader experience, (b) image navigation patterns (eg, eye movements, workstation interactions), and (c) eye gaze time at missed liver metastases on contrast-enhanced abdominal CT images. Materials and Methods In a single-center prospective observational trial at an academic institution between December 2020 and February 2021, readers were recruited to examine 40 contrast-enhanced abdominal CT studies (eight normal, 32 containing 91 liver metastases). Readers circumscribed hepatic metastases and reported confidence. The workstation tracked image navigation and eye movements. Performance was quantified by using the area under the jackknife alternative free-response receiver operator characteristic (JAFROC-1) curve and per-metastasis sensitivity and was associated with reader experience and image navigation variables. Differences in area under JAFROC curve were assessed with the Kruskal-Wallis test followed by the Dunn test, and effects of image navigation were assessed by using the Wilcoxon signed-rank test. Results Twenty-five readers (median age, 38 years; IQR, 31-45 years; 19 men) were recruited and included nine subspecialized abdominal radiologists, five nonabdominal staff radiologists, and 11 senior residents or fellows. Reader experience explained differences in area under the JAFROC curve, with abdominal radiologists demonstrating greater area under the JAFROC curve (mean, 0.77; 95% CI: 0.75, 0.79) than trainees (mean, 0.71; 95% CI: 0.69, 0.73) (P = .02) or nonabdominal subspecialists (mean, 0.69; 95% CI: 0.60, 0.78) (P = .03). Sensitivity was similar within the reader experience groups (P = .96). Image navigation variables that were associated with higher sensitivity included longer interpretation time (P = .003) and greater use of coronal images (P < .001). The eye gaze time was at least 0.5 and 2.0 seconds for 71% (266 of 377) and 40% (149 of 377) of missed metastases, respectively. Conclusion Abdominal radiologists demonstrated better discrimination for the detection of liver metastases on abdominal contrast-enhanced CT images. Missed metastases frequently received at least a brief eye gaze. Higher sensitivity was associated with longer interpretation time and greater use of liver display windows and coronal images. © RSNA, 2022 Online supplemental material is available for this article.

The impact of moderate aortic stenosis in acute myocardial infarction: A multicenter retrospective study.

BACKGROUND: Aortic stenosis (AS) is associated with myocardial ischemia through different mechanisms and may impair coronary arterial flow. However, data on the impact of moderate AS in patients with acute myocardial infarction (MI) is limited. AIMS: This study aimed to investigate the impact of moderate AS in patients presenting with acute myocardial infarction (MI). METHODS: We conducted a retrospective analysis of all patients who presented with acute MI to all Mayo Clinic hospitals, using the Enterprise Mayo PCI Database from 2005 to 2016. Patients were stratified into two groups: moderate AS and mild/no AS. The primary outcome was all cause mortality. RESULTS: The moderate AS group included 183 (13.3%) patients, and the mild/no AS group included 1190 (86.7%) patients. During hospitalization, there was no difference between both groups in mortality. Patients with moderate AS had higher in-hospital congestive heart failure (CHF) (8.2% vs. 4.4%, p = 0.025) compared with mild/no AS patients. At 1-year follow-up, patients with moderate AS had higher mortality (23.9% vs. 8.1%, p < 0.001) and higher CHF hospitalization (8.3% vs. 3.7%, p = 0.028). In multivariate analysis, moderate AS was associated with higher mortality at 1-year (odds ratio 2.4, 95% confidence interval [1.4-4.1], p = 0.002). In subgroup analyses, moderate AS increased all-cause mortality in STEMI and NSTEMI patients. CONCLUSION: The presence of moderate AS in acute MI patients was associated with worse clinical outcomes during hospitalization and at 1-year follow-up. These unfavorable outcomes highlight the need for a close follow-up of these patients and for timely therapeutic strategies to best manage these coexisting conditions.

Outcomes of Wilms tumor therapy in Lilongwe, Malawi, 2016-2021: Successes and ongoing research priorities.

INTRODUCTION: Wilms tumor therapy in low- and middle-income countries (LMICs) relies on treatment protocols adapted to resource limitations, but these protocols have rarely been evaluated in real-world settings. Such evaluations are necessary to identify high-impact research priorities for clinical and implementation trials in LMICs. The purpose of this study was to identify highest priority targets for future clinical and implementation trials in sub-Saharan Africa by assessing outcomes of a resource-adapted treatment protocol in Malawi. METHODS: We conducted a retrospective cohort study of children treated for Wilms tumor with an adapted SIOP-backbone protocol in Lilongwe, Malawi between 2016 and 2021. Survival analysis assessed variables associated with poor outcome with high potential for future research and intervention. RESULTS: We identified 136 patients, most commonly with stage III (n = 35; 25.7%) or IV disease (n = 35; 25.7%). Two-year event-free survival (EFS) was 54% for stage I/II, 51% for stage III, and 13% for stage IV. A single patient with stage V disease survived to 1 year. Treatment abandonment occurred in 36 (26.5%) patients. Radiotherapy was indicated for 55 (40.4%), among whom three received it. Of these 55 patients, 2-year EFS was 31%. Of 14 patients with persistent metastatic pulmonary disease at the time of nephrectomy, none survived to 2 years. Notable variables independently associated with survival were severe acute malnutrition (hazard ratio [HR]: 1.9), increasing tumor stage (HR: 1.5), and vena cava involvement (HR: 3.1). CONCLUSION: High-impact targets for clinical and implementation trials in low-resource settings include treatment abandonment, late presentation, and approaches optimized for healthcare systems with persistently unavailable radiotherapy.

Bilateral lunotriquetral coalition: a dynamic four-dimensional computed tomography technical case report.

Lunotriquetral coalitions are the most common form of carpal coalition wherein the cartilage between the lunate and triquetrum ossification centers failed to undergo apoptosis. This technical case report examines the arthrokinematics of bilateral lunotriquetral coalitions with dissimilar Minnaar types in one participant with one asymptomatic wrist and one wrist with suspected distal radioulnar joint injury. Static and dynamic (four-dimensional) CT images during pronosupination were captured using a photon-counting detector CT scanner. Interosseous proximity distributions were calculated between the lunotriquetral coalition and adjacent bones in both wrists to quantify arthrokinematics. Interosseous proximity distributions at joints adjacent to the lunotriquetral coalition demonstrate differences in median and minimum interosseous proximities between the asymptomatic and injured wrists during resisted pronosupination. Altered kinematics from lunotriquetral coalitions may be a source of ulnar-sided wrist pain and discomfort, limiting the functional range of motion. This case report highlights potential alterations to wrist arthrokinematics in the setting of lunotriquetral coalitions and possible associations with ulnar-sided wrist pain, highlighting anatomy to examine in radiographic follow-up. Furthermore, this case report demonstrates the technical feasibility of four-dimensional CT using photon-counting detector technology in assessing arthrokinematics in the setting of variant wrist anatomy.

Single or multiple arterial bypass graft surgery vs. percutaneous coronary intervention in patients with three-vessel or left main coronary artery disease.

AIM: The aim of this study was to compare long-term all-cause mortality between patients receiving percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) using multiple (MAG) or single arterial grafting (SAG). METHODS AND RESULTS: The current study is a post hoc analysis of the SYNTAX Extended Survival Study, which compared PCI with CABG in patients with three-vessel (3VD) and/or left main coronary artery disease (LMCAD) and evaluated survival with ≥10 years of follow-up. The primary endpoint was all-cause mortality at maximum follow-up (median 11.9 years) assessed in the as-treated population. Of the 1743 patients, 901 (51.7%) underwent PCI, 532 (30.5%) received SAG, and 310 (17.8%) had MAG. At maximum follow-up, all-cause death occurred in 305 (33.9%), 175 (32.9%), and 70 (22.6%) patients in the PCI, SAG, and MAG groups, respectively (P < 0.001). Multiple arterial grafting [adjusted hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.49-0.89], but not SAG (adjusted HR 0.83, 95% CI 0.67-1.03), was associated with significantly lower all-cause mortality compared with PCI. In patients with 3VD, both MAG (adjusted HR 0.55, 95% CI 0.37-0.81) and SAG (adjusted HR 0.68, 95% CI 0.50-0.91) were associated with significantly lower mortality than PCI, whereas in LMCAD patients, no significant differences between PCI and MAG (adjusted HR 0.90, 95% CI 0.56-1.46) or SAG (adjusted HR 1.11, 95% CI 0.81-1.53) were observed. In patients with revascularization of all three major myocardial territories, a positive correlation was observed between the number of myocardial territories receiving arterial grafts and survival (Ptrend = 0.003). CONCLUSION: Our findings suggest that MAG might be the more desirable configuration for CABG to achieve lower long-term all-cause mortality than PCI in patients with 3VD and/or LMCAD. TRIAL REGISTRATION: Registered on clinicaltrial.gov. SYNTAXES: NCT03417050 (https://clinicaltrials.gov/ct2/show/NCT03417050); SYNTAX: NCT00114972 (https://www.clinicaltrials.gov/ct2/show/NCT00114972).

Primary Outcome Evaluation of a Next-Generation Left Atrial Appendage Closure Device: Results From the PINNACLE FLX Trial.

BACKGROUND: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. METHODS: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. RESULTS: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA2DS2-VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% (P<0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% (P<0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. CONCLUSIONS: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02702271.

Ten-Year All-Cause Death According to Completeness of Revascularization in Patients With Three-Vessel Disease or Left Main Coronary Artery Disease: Insights From the SYNTAX Extended Survival Study.

BACKGROUND: Ten-year all-cause death according to incomplete (IR) versus complete revascularization (CR) has not been fully investigated in patients with 3-vessel disease and left main coronary artery disease undergoing percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). METHODS: The SYNTAX Extended Survival study (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]) evaluated vital status up to 10 years in patients who were originally enrolled in the SYNTAX trial. In the present substudy, outcomes of the CABG CR group were compared with the CABG IR, PCI CR, and PCI IR groups. In addition, in the PCI cohort, the residual SYNTAX score (rSS) was used to quantify the extent of IR and to assess its association with fatal late outcome. The rSS of 0 suggests CR, whereas a rSS>0 identifies the degree of IR. RESULTS: IR was more frequently observed in patients with PCI versus CABG (56.6% versus 36.8%) and more common in those with 3-vessel disease than left main coronary artery disease in both the PCI arm (58.5% versus 53.8%) and the CABG arm (42.8% versus 27.5%). Patients undergoing PCI with CR had no significant difference in 10-year all-cause death compared with those undergoing CABG (22.2% for PCI with CR versus 24.3% for CABG with IR versus 23.8% for CABG with CR). In contrast, those with PCI and IR had a significantly higher risk of all-cause death at 10 years compared with CABG and CR (33.5% versus 23.7%; adjusted hazard ratio, 1.48 [95% CI, 1.15-1.91]). When patients with PCI were stratified according to the rSS, those with a rSS≤8 had no significant difference in all-cause death at 10 years as the other terciles (22.2% for rSS=0 versus 23.9% for rSS>0-4 versus 28.9% for rSS>4-8), whereas a rSS>8 had a significantly higher risk of 10-year all-cause death than those undergoing PCI with CR (50.1% versus 22.2%; adjusted hazard ratio, 3.40 [95% CI, 2.13-5.43]). CONCLUSIONS: IR is common after PCI, and the degree of incompleteness was associated with 10-year mortality. If it is unlikely that complete (or nearly complete; rSS<8) revascularization can be achieved with PCI in patients with 3-vessel disease, CABG should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00114972. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03417050.

Antithrombotic Therapy in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Undergoing Percutaneous Coronary Intervention: A North American Perspective: 2021 Update.

A growing number of patients undergoing percutaneous coronary intervention (PCI) with stent implantation also have atrial fibrillation. This poses challenges for their optimal antithrombotic management because patients with atrial fibrillation undergoing PCI require oral anticoagulation for the prevention of cardiac thromboembolism and dual antiplatelet therapy for the prevention of coronary thrombotic complications. The combination of oral anticoagulation and dual antiplatelet therapy substantially increases the risk of bleeding. Over the last decade, a series of North American Consensus Statements on the Management of Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention have been reported. Since the last update in 2018, several pivotal clinical trials in the field have been published. This document provides a focused updated of the 2018 recommendations. The group recommends that in patients with atrial fibrillation undergoing PCI, a non-vitamin K antagonist oral anticoagulant is the oral anticoagulation of choice. Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor should be given to all patients during the peri-PCI period (during inpatient stay, until time of discharge, up to 1 week after PCI, at the discretion of the treating physician), after which the default strategy is to stop aspirin and continue treatment with a P2Y12 inhibitor, preferably clopidogrel, in combination with a non-vitamin K antagonist oral anticoagulant (ie, double therapy). In patients at increased thrombotic risk who have an acceptable risk of bleeding, it is reasonable to continue aspirin (ie, triple therapy) for up to 1 month. Double therapy should be given for 6 to 12 months with the actual duration depending on the ischemic and bleeding risk profile of the patient, after which patients should discontinue antiplatelet therapy and receive oral anticoagulation alone.

Cardiogenic shock complicating non-ST-segment elevation myocardial infarction: An 18-year study.

OBJECTIVE: To evaluate the epidemiology and outcomes of non-ST-segment-elevation myocardial infarction-cardiogenic shock (NSTEMI-CS) in the United States. METHODS: Adult (>18 years) NSTEMI-CS admissions were identified using the National Inpatient Sample (2000-2017) and classified by tertiles of admission year (2000-2005, 2006-2011 and 2012-2017). Outcomes of interest included temporal trends of prevalence and in-hospital mortality, use of cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay. RESULTS: In over 7.3 million NSTEMI admissions, CS was noted in 189,155 (2.6%). NSTEMI-CS increased from 1.5% in 2000 to 3.6% in 2017 (adjusted odds ratio 2.03 [95% confidence interval 1.97-2.09]; P < .001). Rates of non-cardiac organ failure and cardiac arrest increased during the study period. Between 2000 and 2017, coronary angiography (43.9%-63.9%), early coronary angiography (13.6%-25.6%), percutaneous coronary intervention (14.8%-31.6%), and coronary artery bypass grafting use (19.0%-25.8%) increased (P < .001). Over the study period, the use of intra-aortic balloon pump remained stable (28.6%-28.8%), and both percutaneous left ventricular assist devices (0%-9.1%) and extra-corporeal membrane oxygenation (0.1%-1.6%) increased (all P < .001). In hospital mortality decreased from 50.2% in 2000 to 32.3% in 2017 (adjusted odds ratio 0.27 [95% confidence interval 0.25-0.29]; P < .001). During the 18-year period, hospital lengths of stay decreased, and hospitalization costs increased. CONCLUSIONS: In the United States, prevalence of CS in NSTEMI has increased 2-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and percutaneous coronary intervention increased during the study period.

The hemodynamic spectrum of pulmonary vein stenosis from fibrosing mediastinitis.

A 63-year-old man presented with hemoptysis and progressive dyspnea. His echocardiogram was concerning for pulmonary hypertension (PH) and CT chest showed fibrosing mediastinitis with possible cardiac involvement. Right heart catheterization revealed PH at rest and worsened with exercise. CT findings and simultaneous measurement of pulmonary capillary wedge pressure (PCWP), left atrial pressure, and left ventricular pressure helped diagnose pulmonary vein (PV) stenosis as the etiology of his PH. Both upper pulmonary veins were stented, and repeat exercise hemodynamic study revealed a substantial reduction in pulmonary arterial pressure with improvement in subjective dyspnea, cardiac output reserve, mechanical efficiency, and ventilatory efficiency. Repeat right upper PCWP normalized, consistent with resolution of the PV stenosis.

Regulatory strategies for early device development and approval.

The development of new technology to treat unmet clinical needs is an important component of modern cardiovascular disease. The need for this has been emphasized in the past several years beginning with the Food and Drug Administration (FDA) guidance document on Early Feasibility Studies in 2012 and then the 21st Century Cures legislation. A number of steps need to be considered in this process by the stakeholders involved including physician innovators and scientists, professional societies such as Society for Cardiovascular Angiography & Interventions, regulatory agencies, and medical device companies. This article focuses on the early iterative steps required to optimize the process and achieve the goal of timely efficient innovation and device development in cardiovascular disease.

Influence of intra-aortic balloon pump on mortality as a function of cardiogenic shock severity.

BACKGROUND: Randomized studies of intra-aortic balloon pump (IABP) in cardiogenic shock (CS) have only included on patients with acute coronary syndromes (ACS) without stratification according to shock severity. We examined the association between IABP and mortality in CS patients across the Society for Cardiovascular Angiography and Intervention (SCAI) shock stages. METHODS: We included cardiac intensive care unit patients admitted from 2007 to 2015 with CS from any etiology. In-hospital mortality associated with IABP was examined in each SCAI shock stage. Multivariable logistic regression was performed using inverse probability of treatment weighting (IPTW) to determine the association between IABP and in-hospital mortality. RESULTS: We included 934 patients, with a mean age of 68 ± 14 years; 60% had ACS. The distribution of SCAI shock stages was: B, 41%; C, 13%; D, 38%; E, 8%. In-hospital mortality was lower in the 39% of patients who received IABP (27% vs. 43%, adjusted OR with IABP after IPTW 0.53, 95% CI 0.40-0.72, p < .0001). IABP use was associated with lower crude in-hospital mortality in each SCAI shock stage (all p < .05, except p = .08 in SCAI shock stage E). We did not observe any significant heterogeneity in the association between IABP use and in-hospital mortality as a function of SCAI shock stage. CONCLUSIONS: Patients with CS who were selected to receive an IABP had lower in-hospital mortality, without differences in this effect across the SCAI shock stages. Future studies should account for the severity and etiology of shock when evaluating the efficacy of IABP for CS.

Leak closure following left atrial appendage exclusion procedures: A multicenter registry.

BACKGROUND: Though infrequent, incomplete left atrial appendage closure (LAAC) may result from residual leaks. Percutaneous closure has been described though data is limited. METHODS: We compiled a registry from four centers of patients undergoing percutaneous closure of residual leaks following LAAC via surgical means or with the Watchman device. Leak severity was classified as none (no leak), mild (1-2 mm), moderate (3-4 mm), or severe (≥5 mm). Procedural and clinical success was defined as the elimination of leak or mild residual leak at the conclusion of the procedure or follow-up, respectively. RESULTS: Of 72 (age 72.2 ± 9.2 years; 67% male) patients, 53 had undergone prior LAAC using the Watchman device and 19 patients surgical LAAC. Mean CHADS2 -VA2 Sc score was 4.0 ± 1.8. The median leak size was 5 mm, range: 2-13). A total of 13 received Amplatzer Vascular Plug-II, 18 received Amplatzer Duct Occluder-II and 40 patients received coils. One underwent closure using a 21 mm-Watchman. Procedural success was 94%. Zero surgical and nine Watchman patients (13%) had a residual leak at procedural-end (five mild, three moderate, and one severe)-only one patient had no reduction in leak size. Overall leak size reduction was 94%. Two (3%) had intraoperative pericardial effusion. There were no device embolizations, device-related thrombi, or procedural deaths. Clinical success was maintained at 94%. Two had cerebrovascular accidents-at 2 days (transient ischemic attack) and 10 months postprocedure. Two had major bleeding outside the 30-day periprocedural window. CONCLUSION: Percutaneous closure of residual leaks following left atrial appendage closure is feasible and associated with good outcomes. The procedural risk appears to be satisfactory.

Comparative study of 2-year outcomes for Hydrus or iStent inject microinvasive glaucoma surgery implants with cataract surgery.

BACKGROUND: To compare real-world 24-month outcomes of phacoemulsification combined with either iStent inject or Hydrus Microstent. METHODS: Analysis of data from the Fight Glaucoma Blindness (FGB) international registry. Anonymized data from 344 eyes with mild-to-moderate open-angle glaucoma, normal-tension glaucoma or ocular hypertension that underwent phacoemulsification combined with either iStent inject (224) or Hydrus Microstent (120) were included. Data were adjusted for baseline characteristics using linear regression and propensity score matching. The primary endpoint was a comparison of mean intraocular pressure (IOP) at 24 months. RESULTS: At 24 months, there was no significant difference in IOP reduction between the two groups, consistent across all analyses. The matched cohort showed iStent inject achieved 3.1 mmHg reduction and Hydrus a 2.3 mmHg reduction (p = 0.530) and a mean medication reduction of 1.0 for iStent inject versus 0.5 for Hydrus (p = 0.081). 5.4% of eyes in the iStent inject group and 7.5% of eyes in the Hydrus group required subsequent procedures to improve IOP control within 24 months. Complications were rare with no significant differences between the groups. CONCLUSIONS: Twenty-four-month outcomes showed sustained IOP reduction with a good safety profile for both groups. There was no significant difference in IOP outcomes between the groups. There may be a small additional reduction in glaucoma medication usage following cataract surgery with iStent inject compared to Hydrus.

Ten-year all-cause death after percutaneous or surgical revascularization in diabetic patients with complex coronary artery disease.

AIMS: The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes. METHODS AND RESULTS: The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: -7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: -6.5%, 22.5%, P = 0.227). CONCLUSIONS: The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials. TRIAL REGISTRATION: SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Study protocol: understanding pain after dental procedures, an observational study within the National Dental PBRN.

BACKGROUND: Patient-reported outcome measures provide an essential perspective on the quality of health care provided. However, how data are collected, how providers value and make sense of the data, and, ultimately, use the data to create meaningful impact all influence the success of using patient-reported outcomes. OBJECTIVES: The primary objective is to assess post-operative pain experiences by dental procedure type through 21 days post-procedure as reported by patients following dental procedures and assess patients' satisfaction with pain management following dental surgical procedures. Secondary objectives are to: 1) assess post-operative pain management strategies 1 week following dental surgical procedures, as recommended by practitioners and reported by patients, and 2) evaluate practitioner and patient acceptance of the FollowApp.Care post visit patient monitoring technology (FollowApp.Care). We will evaluate FollowApp.Care usage, perceived usefulness, ease of use, and impact on clinical workload. DESIGN AND METHODS: We describe the protocol for an observational study involving the use of the FollowApp.Care platform, an innovative mobile application that collects dental patients' assessments of their post-operative symptoms (e.g., pain). The study will be conducted in collaboration with the National Dental Practice-based Research Network, a collective Network of dental practices that include private and group practices, public health clinics, community health centers and Federal Qualified Health Centers, academic institutional settings, and special patient populations. We will recruit a minimum of 150 and up to 215 dental providers and up to 3147 patients who will receive push notifications through text messages FollowApp.Care on their mobile phones at designated time intervals following dental procedures. This innovative approach of implementing an existing and tested mobile health system technology into the real-world dental office setting will actively track pain and other complications following dental procedures. Through patients' use of their mobile phones, we expect to promptly and precisely identify specific pain levels and other issues after surgical dental procedures. The study's primary outcome will be the patients' reported pain experiences. Secondary outcomes include pain management strategies and medications implemented by the patient and provider and perceptions of usefulness and ease of use by patients and providers.