Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions-International Pediatric Low-Grade Glioma Coalition.

Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morbidities. The majority of pLGGs have an underlying activation of the RAS/MAPK pathway due to mutational events, leading to the use of molecularly targeted therapies in clinical trials, with recent regulatory approval for the combination of BRAF and MEK inhibition for BRAFV600E mutated pLGG. Despite encouraging activity, tumor regrowth can occur during therapy due to drug resistance, off treatment as tumor recurrence, or as reported in some patients as a rapid rebound growth within 3 months of discontinuing targeted therapy. Definitions of these patterns of regrowth have not been well described in pLGG. For this reason, the International Pediatric Low-Grade Glioma Coalition, a global group of physicians and scientists, formed the Resistance, Rebound, and Recurrence (R3) working group to study resistance, rebound, and recurrence. A modified Delphi approach was undertaken to produce consensus-based definitions and recommendations for regrowth patterns in pLGG with specific reference to targeted therapies.

Transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation (ALIGN-AR): a prospective, multicentre, single-arm study.

BACKGROUND: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve. METHODS: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing. FINDINGS: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (pnon-inferiority<0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (pnon-inferiority<0·0001). INTERPRETATION: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary. FUNDING: JenaValve Technology.

Patient-Prosthesis Mismatch After Surgical Aortic Valve Replacement: Analysis of the PARTNER Trials.

BACKGROUND: Our objective was to compare the impact of patient-prosthesis mismatch (PPM) for 2 years after surgical aortic valve replacement within the prospective, randomized Placement of Aortic Transcatheter Valves (PARTNER) trials. METHODS: Surgical aortic valve replacement patients from the PARTNER 1, 2, and 3 trials were included. PPM was classified as moderate (indexed effective orifice area ≤0.85 cm2/m2) or severe (indexed effective orifice area ≤0.65 cm2/m2). The primary endpoint was the composite of all-cause death and heart failure rehospitalization at 2 years. RESULTS: By the predicted PPM method (PPMP), 59.1% had no PPM, 38.8% moderate PPM, and 2.1% severe PPM; whereas by the measured PPM method (PPMM), 42.4% had no PPM, 36.0% moderate, and 21.6% severe. Patients with no PPMP (23.6%) had a lower rate of the primary endpoint compared with patients with moderate (28.2%, P = .03) or severe PPMP (38.8%, P = .02). Using the PPMM method, there was no difference between the no (17.7%) and moderate PPMM groups (21.1%) in the primary outcome (P = .16). However, those with no PPMM or moderate PPMM were improved compared with severe PPMM (27.4%, P < .001 and P = .02, respectively). CONCLUSIONS: Severe PPM analyzed by PPMP was only 2.1% for surgical aortic valve replacement patients. The PPMM method overestimated the incidence of severe PPM relative to PPMP, but was also associated with worse outcome. There was higher all-cause mortality in patients with severe PPM, thus surgical techniques to minimize PPM remain critical.

Management of long-term complications from immunosuppression.

This review discusses long-term complications from immunosuppressants after liver transplantation and the management of these complications. Common complications of calcineurin inhibitors include nephrotoxicity and metabolic diseases. Nephrotoxicity can be managed by targeting a lower drug level and/or adding an immunosuppressant of a different class. Metabolic disorders can be managed by treating the underlying condition and targeting a lower drug level. Gastrointestinal adverse effects and myelosuppression are common complications of antimetabolites that are initially managed with dose reduction or discontinuation if adverse events persist. Mammalian targets of rapamycin inhibitors are associated with myelosuppression, proteinuria, impaired wound healing, and stomatitis, which may require dose reduction or discontinuation. Induction agents and agents used for steroid-refractory rejection or antibody-mediated rejection are reviewed. Other rare complications of immunosuppressants are discussed as well.

Minimally invasive approach associated with lower resource utilization after aortic and mitral valve surgery.

Objective: To investigate the effect of minimally invasive cardiac surgery (MICS) on resource utilization, cost, and postoperative outcomes in patients undergoing left-heart valve operations. Methods: Data were retrospectively reviewed for patients undergoing single-valve surgery (eg, aortic valve replacement, mitral valve replacement, or mitral valve repair) at a single center from 2018 to 2021, stratified by surgical approach: MICS vs full sternotomy (FS). Baseline characteristics and postoperative outcomes were compared. Primary outcome was high resource utilization, defined as direct procedure cost higher than the third quartile or either postoperative LOS ≥7 days or 30-day readmission. Secondary outcomes were direct cost, length of stay, 30-day readmission, in-hospital and 30-day mortality, and major morbidity. Multiple regression analysis was conducted, controlling for baseline characteristics, operative approach, valve operation, and lead surgeon to assess high resource utilization. Results: MICS was correlated with a significantly lower rate of high resource utilization (MICS, 31.25% [n = 115] vs FS 61.29% [n = 76]; P < .001). Median postoperative length of stay (MICS, 4 days [range, 3-6 days] vs FS, 6 days [range, 4 to 9 days]; P < .001) and direct cost (MICS, $22,900 [$19,500-$28,600] vs FS, $31,900 [$25,900-$50,000]; P < .001) were lower in the MICS group. FS patients were more likely to experience postoperative atrial fibrillation (P = .040) and renal failure (P = .027). Other outcomes did not differ between groups. Controlling for stratified Society of Thoracic Surgeons predicted risk of mortality, cardiac valve operation, and lead surgeon, FS demonstrated increased likelihood of high resource utilization (P < .001). Conclusions: MICS for left-heart valve pathology demonstrated improved postoperative outcomes and resource utilization.

Transcatheter Aortic-Valve Replacement in Low-Risk Patients at Five Years.

BACKGROUND: A previous analysis in this trial showed that among patients with severe, symptomatic aortic stenosis who were at low surgical risk, the rate of the composite end point of death, stroke, or rehospitalization at 1 year was significantly lower with transcatheter aortic-valve replacement (TAVR) than with surgical aortic-valve replacement. Longer-term outcomes are unknown. METHODS: We randomly assigned patients with severe, symptomatic aortic stenosis and low surgical risk to undergo either TAVR or surgery. The first primary end point was a composite of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure. The second primary end point was a hierarchical composite that included death, disabling stroke, nondisabling stroke, and the number of rehospitalization days, analyzed with the use of a win ratio analysis. Clinical, echocardiographic, and health-status outcomes were assessed through 5 years. RESULTS: A total of 1000 patients underwent randomization: 503 patients were assigned to undergo TAVR, and 497 to undergo surgery. A component of the first primary end point occurred in 111 of 496 patients in the TAVR group and in 117 of 454 patients in the surgery group (Kaplan-Meier estimates, 22.8% in the TAVR group and 27.2% in the surgery group; difference, -4.3 percentage points; 95% confidence interval [CI], -9.9 to 1.3; P = 0.07). The win ratio for the second primary end point was 1.17 (95% CI, 0.90 to 1.51; P = 0.25). The Kaplan-Meier estimates for the components of the first primary end point were as follows: death, 10.0% in the TAVR group and 8.2% in the surgery group; stroke, 5.8% and 6.4%, respectively; and rehospitalization, 13.7% and 17.4%. The hemodynamic performance of the valve, assessed according to the mean (±SD) valve gradient, was 12.8±6.5 mm Hg in the TAVR group and 11.7±5.6 mm Hg in the surgery group. Bioprosthetic-valve failure occurred in 3.3% of the patients in the TAVR group and in 3.8% of those in the surgery group. CONCLUSIONS: Among low-risk patients with severe, symptomatic aortic stenosis who underwent TAVR or surgery, there was no significant between-group difference in the two primary composite outcomes. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).

Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations.

BACKGROUND: Detection of the BRAF V600E mutation in pediatric low-grade glioma has been associated with a lower response to standard chemotherapy. In previous trials, dabrafenib (both as monotherapy and in combination with trametinib) has shown efficacy in recurrent pediatric low-grade glioma with BRAF V600 mutations, findings that warrant further evaluation of this combination as first-line therapy. METHODS: In this phase 2 trial, patients with pediatric low-grade glioma with BRAF V600 mutations who were scheduled to receive first-line therapy were randomly assigned in a 2:1 ratio to receive dabrafenib plus trametinib or standard chemotherapy (carboplatin plus vincristine). The primary outcome was the independently assessed overall response (complete or partial response) according to the Response Assessment in Neuro-Oncology criteria. Also assessed were the clinical benefit (complete or partial response or stable disease for ≥24 weeks) and progression-free survival. RESULTS: A total of 110 patients underwent randomization (73 to receive dabrafenib plus trametinib and 37 to receive standard chemotherapy). At a median follow-up of 18.9 months, an overall response occurred in 47% of the patients treated with dabrafenib plus trametinib and in 11% of those treated with chemotherapy (risk ratio, 4.31; 95% confidence interval [CI], 1.7 to 11.2; P<0.001). Clinical benefit was observed in 86% of the patients receiving dabrafenib plus trametinib and in 46% receiving chemotherapy (risk ratio, 1.88; 95% CI, 1.3 to 2.7). The median progression-free survival was significantly longer with dabrafenib plus trametinib than with chemotherapy (20.1 months vs. 7.4 months; hazard ratio, 0.31; 95% CI, 0.17 to 0.55; P<0.001). Grade 3 or higher adverse events occurred in 47% of the patients receiving dabrafenib plus trametinib and in 94% of those receiving chemotherapy. CONCLUSIONS: Among pediatric patients with low-grade glioma with BRAF V600 mutations, dabrafenib plus trametinib resulted in significantly more responses, longer progression-free survival, and a better safety profile than standard chemotherapy as first-line therapy. (Funded by Novartis; ClinicalTrials.gov number, NCT02684058.).

Ambulatory Electrocardiography Monitoring for Early Discharge After Minimally Invasive Valve Surgery.

INTRODUCTION: We sought to compare outcomes after early discharge in patients with and without predischarge diagnosis of arrhythmia following minimally invasive valve surgery (MIVS). MATERIALS AND METHODS: We retrospectively reviewed ambulatory electrocardiography (AECG) datasheets and medical records of patients discharged with 14-d AECG monitoring from our facility between October 2019 and March 2022 ≤ 3 d after MIVS. Baseline and clinical characteristics, arrhythmias during AECG monitoring, and 30-d adverse outcomes were reported for the population and stratified by presence or absence of predischarge arrhythmia. RESULTS: Of 41 patients discharged ≤3 d postoperatively of MIVS, 17 (41.5%) experienced predischarge arrhythmias and 24 (58.5%) did not. The population was predominantly male and White with a median age of 62 y [57, 70]. Baseline and clinical characteristics did not differ between subgroups. Most patients (92.7% [n = 38]) experienced one or more tachyarrhythmias during the AECG monitoring period. There were similar proportions of patients experiencing atrial fibrillation in both groups, but patients with predischarge arrhythmias had higher burden of atrial fibrillation on AECG monitoring (27.60% [6.57%, 100%] versus 1.65% [0.76%, 4.32%]; P = 0.004). The predischarge arrhythmia subgroup had higher proportions of patients experiencing nonsustained ventricular tachycardia but lower proportions experiencing supraventricular tachycardia. There were no mortalities within 30 d of surgery. Six (14.6%) patients were readmitted within 30 d with equal proportions of readmissions between subgroups (P = 0.662). CONCLUSIONS: Early discharge timelines and noninvasive monitoring techniques can allow patients to return to their normal activities quicker in the comfort of their own home with no increased risk of morbidity or mortality.

Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600-Mutant Pediatric High-Grade Glioma.

PURPOSE: BRAF V600 mutation is detected in 5%-10% of pediatric high-grade gliomas (pHGGs), and effective treatments are limited. In previous trials, dabrafenib as monotherapy or in combination with trametinib demonstrated activity in children and adults with relapsed/refractory BRAF V600-mutant HGG. METHODS: This phase II study evaluated dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600-mutant pHGG. The primary objective was overall response rate (ORR) by independent review by Response Assessment in Neuro-Oncology criteria. Secondary objectives included ORR by investigator determination, duration of response (DOR), progression-free survival, overall survival (OS), and safety. RESULTS: A total of 41 pediatric patients with previously treated BRAF V600-mutant HGG were enrolled. At primary analysis, median follow-up was 25.1 months, and 51% of patients remained on treatment. Sixteen of 20 discontinuations were due to progressive disease in this relapsed/refractory pHGG population. Independently assessed ORR was 56% (95% CI, 40 to 72). Median DOR was 22.2 months (95% CI, 7.6 months to not reached [NR]). Fourteen deaths were reported. Median OS was 32.8 months (95% CI, 19.2 months to NR). The most common all-cause adverse events (AEs) were pyrexia (51%), headache (34%), and dry skin (32%). Two patients (5%) had AEs (both rash) leading to discontinuation. CONCLUSION: In relapsed/refractory BRAF V600-mutant pHGG, dabrafenib plus trametinib improved ORR versus previous trials of chemotherapy in molecularly unselected patients with pHGG and was associated with durable responses and encouraging survival. These findings suggest that dabrafenib plus trametinib is a promising targeted therapy option for children and adolescents with relapsed/refractory BRAF V600-mutant HGG.

Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare, heterogenous, neoplastic disorder primarily affecting children. BRAF mutations have been reported in >50% of patients with LCH. The selective BRAF inhibitor, dabrafenib, in combination with the MEK1/2 inhibitor, trametinib, has been approved in select BRAF V600-mutant solid tumors. Two open-label phase 1/2 studies were conducted in pediatric patients with BRAF V600-mutant, recurrent/refractory malignancies treated with dabrafenib monotherapy (CDRB436A2102; NCT01677741) or dabrafenib plus trametinib (CTMT212X2101; NCT02124772). The primary objectives of both studies were to determine safe and tolerable doses that achieve similar exposure to the approved doses for adults. Secondary objectives included safety, tolerability, and preliminary antitumor activity. Thirteen and 12 patients with BRAF V600-mutant LCH received dabrafenib monotherapy and in combination with trametinib, respectively. Investigator-assessed objective response rates per Histiocyte Society criteria were 76.9% (95% confidence interval [CI], 46.2-95.0) and 58.3% (95% CI, 27.7-84.8) in the monotherapy and combination studies, respectively. More than 90% of responses were ongoing at study completion. The most common treatment-related adverse events (AEs) were vomiting and increased blood creatinine with monotherapy and pyrexia, diarrhea, dry skin, decreased neutrophil count, and vomiting with combination therapy. Two patients each discontinued treatment with monotherapy and combination therapy because of AEs. Overall, dabrafenib monotherapy or in combination with trametinib demonstrated clinical efficacy and manageable toxicity in relapsed/refractory BRAF V600-mutant pediatric LCH, with most responses ongoing. Safety was consistent with that reported in other pediatric and adult conditions treated with dabrafenib plus trametinib.

Telephone-Only Visits Preserved Hepatocellular Cancer Screening Rates in Patients with Cirrhosis Early in the COVID-19 Pandemic.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic required an immediate and large-scale transition to telemedicine. Telemedicine includes phone visits and video visits. Studies suggest that hepatocellular cancer (HCC) screening rates fell at the beginning of the COVID-19 pandemic. If left unaddressed, HCC morbidity/mortality may increase following the pandemic due to inadequate screening. AIMS: To assess the impact of phone-only visits on HCC screening rates in patients with cirrhosis. METHODS: Utilizing ICD-10 codes, 2 cohorts of patients with cirrhosis were identified. The pre-pandemic cohort had index visit between 1/1/2019 and 6/30/2019 (n = 290). The pandemic cohort (n = 112) was evaluated between 4/7/2020 and 6/7/2020. Each cohort was followed for 6 months from their index visit to determine HCC screening rate. Demographics and socioeconomic data from the American Community Survey database were compiled and compared between the cohorts. RESULTS: HCC screening rates in the pre-pandemic and pandemic cohorts were 72.4% and 69.6%, respectively, p = 0.67. No differences in HCC screening rates were observed between the two cohorts when stratified by demographic and socioeconomic factors. CONCLUSIONS: Use of phone-only visits was associated with adherence to HCC screening similar to that seen with in-person visits. The lack of influence on screening rates by racial/socioeconomic factors suggest telephone-only visits do not exacerbate healthcare disparities. In times of public health of crisis, telephone-only visits may provide the necessary access to hepatology care to ensure HCC screening regimens remain in-place for at-risk patients.

Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric BRAF V600-Mutant Low-Grade Glioma.

PURPOSE: BRAF V600 mutations occur in many childhood cancers, including approximately 20% of low-grade gliomas (LGGs). Here, we describe a phase I/II study establishing pediatric dosing and pharmacokinetics of trametinib with or without dabrafenib, as well as efficacy and safety in a disease-specific cohort with BRAF V600-mutant LGG; other cohorts will be reported elsewhere. METHODS: This is a four-part, phase I/II study (ClinicalTrials.gov identifier: NCT02124772) in patients age < 18 years with relapsed/refractory malignancies: trametinib monotherapy dose finding (part A) and disease-specific expansion (part B), and dabrafenib + trametinib dose finding (part C) and disease-specific expansion (part D). The primary objective assessed in all patients in parts A and C was to determine pediatric dosing on the basis of steady-state pharmacokinetics. Disease-specific efficacy and safety (across parts A-D) were secondary objectives. RESULTS: Overall, 139 patients received trametinib (n = 91) or dabrafenib + trametinib (n = 48). Trametinib dose-limiting toxicities in > 1 patient (part A) included mucosal inflammation (n = 3) and hyponatremia (n = 2). There were no dose-limiting toxicities with combination therapy (part C). The recommended phase II dose of trametinib, with or without dabrafenib, was 0.032 mg/kg once daily for patients age < 6 years and 0.025 mg/kg once daily for patients age ≥ 6 years; dabrafenib dosing in the combination was as previously identified for monotherapy. In 49 patients with BRAF V600-mutant glioma (LGG, n = 47) across all four study parts, independently assessed objective response rates were 15% (95% CI, 1.9 to 45.4) for monotherapy (n = 13) and 25% (95% CI, 12.1 to 42.2) for combination (n = 36). Adverse event-related treatment discontinuations were more common with monotherapy (54% v 22%). CONCLUSION: The trial design provided efficient evaluation of pediatric dosing, safety, and efficacy of single-agent and combination targeted therapy. Age-based and weight-based dosing of trametinib with or without dabrafenib achieved target concentrations with manageable safety and demonstrated clinical efficacy and tolerability in BRAF V600-mutant LGG.

Paediatric Strategy Forum for medicinal product development in mitogen-activated protein kinase pathway inhibitors: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

As the mitogen-activated protein kinase (MAPK) signalling pathway is activated in many paediatric cancers, it is an important therapeutic target. Currently, a range of targeted MAPK pathway inhibitors are being developed in adults. However, MAPK signals through many cascades and feedback loops and perturbing the MAPK pathway may have substantial influence on other pathways as well as normal development. In view of these issues, the ninth Paediatric Strategy Forum focused on MAPK inhibitors. Development of MAPK pathway inhibitors to date has been predominantly driven by adult indications such as malignant melanoma. However, these inhibitors may also target unmet needs in paediatric low-grade gliomas, high-grade gliomas, Langerhans cell histiocytosis, juvenile myelomonocytic leukaemia and several other paediatric conditions. Although MAPK inhibitors have demonstrated activity in paediatric cancer, the response rates and duration of responses needs improvement and better documentation. The rapid development and evaluation of combination approaches, based on a deep understanding of biology, is required to optimise responses and to avoid paradoxical tumour growth and other unintended consequences including severe toxicity. Better inhibitors with higher central nervous systempenetration for primary brain tumours and cancers with a propensity for central nervous system metastases need to be studied to determine if they are more effective than agents currently being used, and the optimum duration of therapy with MAPK inhibition needs to be determined. Systematic and coordinated clinical investigations to inform future treatment strategies with MAPK inhibitors, rather than use outside of clinical trials, are needed to fully assess the risks and benefits of these single agents and combination strategies in both front-line and in the refractory/relapse settings. Platform trials could address the investigation of multiple similar products and combinations. Accelerating the introduction of MAPK inhibitors into front-line paediatric studies is a priority, as is ensuring that these studies generate data appropriate for scientific and regulatory purposes. Early discussions with regulators are crucial, particularly if external controls are considered as randomised control trials in small patient populations can be challenging. Functional end-points specific to the populations in which they are studied, such as visual acuity, motor and neuro psychological function are important, as these outcomes are often more reflective of benefit for lower grade tumours (such as paediatric low-grade glioma and plexiform neurofibroma) and should be included in initial study designs for paediatric low-grade glioma. Early prospective discussions and agreements with regulators are necessary. Long-term follow-up of patients receiving MAPK inhibitors is crucial in view of their prolonged administration and the important involvement of this pathway in normal development. Further rational development, with a detailed understanding of biology of this class of products, is crucial to ensure they provide optimal benefit while minimising toxicity to children and adolescents with cancer.

Primary Care Evaluation of a Hepatitis C Virus (HCV) Screening Education Intervention.

INTRODUCTION: Increased screening efforts and the development of effective antiviral treatments have led to marked improvement in Hepatitis C (HCV) patient outcomes. However, many people in the US are believed to have undiagnosed HCV. Successful screening strategies and access to a coordinated system of care are critical for HCV affected adults. The objective of this study was to evaluate a primary care HCV screening education intervention that took place 2018 to 2019 to improve primary care training and management of patients after the implementation of the electronic medical record (EMR) screening alert. METHODS: Using 15 primary care practices located in vicinity of neighborhoods at-risk for higher rates of HCV infections, a stepped wedge randomized control study design was utilized to deliver an educational screening intervention. The education intervention was implemented sequentially with 5 practices being presented to every 3 months. Number of patients within the Baby Boomer cohort (birth years 1945-1965) were collected 3 months before the first practice receiving the intervention to 3 months after the last practice receiving the education intervention. The main outcome collected was the HCV screening. Generalized linear mixed models were used to test the hypothesis of improved screening rates after intervention implementation. RESULTS: There were a total of 85,697 patients within the Baby Boomer cohort seen at the 15 practices. Practices receiving the intervention had patients who were more likely to be screened for HCV (ß = 0.259, P < .001; Odds Ratio [OR] [95%CI] 1.296 [1.098-1.529]).In terms of demographics, results showed that females are less likely to be screened than males (ß = -0.141, P < .001; OR [95%CI] 0.868[0.813 to 0.927]), Baby Boomer patients aged less than 65 were more likely to be screened than Baby Boomer patients aged 65 and older (ß = 0.293, P < .001; OR [95%CI] 1.340[1.251 to 1.436]). DISCUSSION: This study looked at screening rates before and after an educational intervention which happened subsequent to the activation of an EMR alert. Whereas HCV EMR alerts showed an increase in HCV screenings before the education intervention, the addition of the education showed a modest increase in HCV screening rates for Baby Boomer patients.

Is cardiopulmonary bypass standby still required for laser lead extractions?

OBJECTIVE: Over the last two decades there has been an increase in the number of cardiac implantable electronic devices and consequently, there has also been an increased need for lead extractions. Fibrotic attachments develop between the lead and the venous and cardiac structures that may require the use of a laser to mobilize the lead. Cardiothoracic surgeons (CTS) have traditionally provided backup for surgical emergencies for these extractions. This study evaluates the surgical outcomes of patients undergoing transvenous laser lead extractions (TLE) and determines if CTS are still needed for backup. METHODS: A retrospective review of consecutive patients undergoing laser lead extractions at a single academic center. Lead extractions using only laser sheaths were analyzed. The clinical characteristics, complications, and mortality of the patients were evaluated. RESULTS: One hundred and twenty-one patients underwent TLEs from January 1st, 2014 to December 31st, 2018. The majority were male (N = 80, 66.1%), and the average age was 66.48 ± 14 years. The indication for removal was either laser lead malfunction or infection. A total of 30 patients (24.8%) had complications postoperatively including wound hematomas, superficial infections, and arrhythmias. The average length of stay was 9 ± 12 for all the patients in the study. 2 patients (1.6%) had injuries that required emergency surgical repair with injuries to the posterior superior vena cava and right ventricle. Both patients survived the initial injury with one patient was discharged home on day 4 and the other succumbing to his injuries on postoperative day 20. CONCLUSION: Although the incidence of surgical emergencies is rare the morbidity and mortality for TLE require that surgical backup be available.

TAVR in an XXXL annulus (1057 mm2 ) with type I bicuspid aortic valve.

We report the largest annulus (>1000 m2 ) treated with transcatheter aortic valve replacement to date. It highlights the unique challenges in planning, sizing, and deployment considerations in the setting of a very large and altered geometry of a bicuspid aortic valve.

Migrating Foreign Body in the Heart.

Foreign bodies in the heart are a rare condition and an exact mechanism for this occurrence has not been well described. These objects can reach the heart by direct penetration due to local trauma or through intravenous migration or may remain in the heart after medical procedures. The most common foreign bodies that reach the heart are bullets and shrapnel. The purpose of this study is to review a case where a patient injected himself with recreational drugs. The needle subsequently dislodged from the syringe and migrated into the heart.

Single center first year experience and outcomes with Impella 5.5 left ventricular assist device.

BACKGROUND: The Impella 5.5® was approved by the FDA for use for mechanical circulatory support up to 14 days in late 2019 at limited centers in the United States. Our single center's experience with Impella 5.5® can expand the overall understanding for achieving successful patient outcomes as well as provide support for the expansion of its FDA-approved use. METHODS: This study is an IRB-approved single-center retrospective cohort analysis of hospitalized adult patient characteristics and outcomes in cases where the Impella 5.5® was utilized for mechanical circulatory support. RESULTS: A total of 26 implanted Impella 5.5® devices were identified in 24 hospitalized patients at our institution from January 2020 to January 2021. The overall survival rate during index hospitalization was 75%. Eleven Impella 5.5® devices were identified in 10 patients with an average device implantation greater than 14 days. Average device implantation for this subgroup was 27 days with a range of 15-80 days. Survival rate for Impella 5.5® use greater than 14 days was 67%. In the entire cohort and subgroup of device implantation > 14 days, evidence of end organ damage improved with Impella 5.5® use. Complications in our cohort and subgroup of device implantation > 14 days were similar to previously reported complication incidence of axillary inserted LVAD devices. CONCLUSIONS: Our institution's experience with the Impella 5.5® has been strongly positive with favorable outcomes and helps to establish the Impella 5.5® as a viable option for mechanical circulatory support beyond 14 days.

Contemporary trends and in-hospital outcomes of mechanical and bioprosthetic surgical aortic valve replacement in the United States.

INTRODUCTION: The choice between a mechanical versus a bioprosthetic valve in aortic valve replacement (AVR) is based on life expectancy, bleeding risk and comorbidities, since bioprosthetic AVR (bAVR) are associated with a more rapid structural deterioration compared to mechanical AVR (mAVR). The impact of widespread transcatheter valve replacements, on the decision to use bAVR versus mAVR, in the contemporary era and subsequent outcomes remain to be determined. METHODS: The National Inpatient database (2009-2018) was used to study trends in admissions for bAVR and mAVR and in-hospital mortality and outcomes over time. Survey estimation commands were used to determine weighted national estimates. RESULTS: There were 700,896 ± 18,285 inpatient visits for AVR with 70.1% (95% CI 69.2%-71.1%) and 29.9% (95% CI 28.9%-30.8%) visits for bAVR and mAVR, respectively. Those undergoing bAVR were significantly older (bAVR [69.8 years] vs. mAVR [62.7 years] p < .001]. The rates of mAVR decreased across all age groups during the study period (ptrend < .001), including patients ≤50 years (ptrend < .001). In-hospital mortality for mAVR recipients was higher, both after multivariable adjustment (OR 1.35 95% CI 1.26-1.45 p < .001) and propensity matching (mean difference 0.846% ± 0.19%). CONCLUSION: In the contemporary era, the utilization of mAVR has decreased across all age groups, including those younger than 50 years old. Although mAVR recipients were healthier with less comorbidities, inpatient mortality was higher after mAVR compared to bAVR. In addition to understanding causes for higher in-hospital mortality after mAVR, future research should focus on developing transcatheter valve replacement friendly bAVR.

Thirty-Year Trends in Graft Survival After Heart Transplant: Modeled Analyses of a Transplant Registry.

BACKGROUND: Heart failure is an epidemic in the United States, and transplantation remains the most definitive therapy. We describe multidecade trends in posttransplant graft survival, adjusted for concurrent changes in the population, over the 30 years antecedent to the most recent heart allocation policy change. METHODS: Scientific Registry of Transplant Recipients data were used to identify all primary adult heart recipients from 1989 to 2017. We described temporal changes in population characteristics (recipient and donor demographics and comorbidities, pretransplant interventions, clinical transplant measures, and providers). The primary outcome was graft survival, defined as freedom from all-cause death and graft failure, within 6 months posttransplant. Modified Poisson logistic regression estimated relative changes in risk of outcomes compared with 1989, with and without adjustment for changing population characteristics. We identified risk factors, quantified by associated risk ratios. RESULTS: Among 56,488 primary adult heart recipients, we observed 5529 (9.8%) all-cause deaths and 1933 (3.4%) graft failure events within 6 months posttransplant. Prevalence of known recipient risk factors increased over time. Unadjusted modeling demonstrated a significant 30-year improvement in graft survival, averaging 2.6% per year (95% confidence interval, 2.4-2.9; P for trend < .001). After adjusting for population changes the 30-year trend remained significant and graft survival improved on average 3.0% per year (95% confidence interval, 2.6-3.3). Regression modeling identified multiple predictors of graft survival. Modeling 2 additional outcomes of 6-month mortality and 6-month graft failure produced similar results. CONCLUSIONS: Short-term graft survival after heart transplantation has improved significantly leading up to the 2018 heart allocation policy change, despite concurrent increase in prevalence of higher risk population characteristics.