Strategic testing following toxic epidermal necrolysis allows reintroduction of chemotherapy in a patient with progressive myeloma.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome belong to a family of severe cutaneous adverse reactions that can be life-threatening and carry a risk of significant morbidity and potential mortality in the event of re-exposure. Lifelong avoidance of the culprit agent is mandated, which can lead to the exclusion of multiple medications if the trigger is unclear. This can result in adverse health outcomes analogous to that of a penicillin allergy label. We present a case in which the patient would progress to fatal myeloma in the absence of treatment, however, multiple medications were administered prior to the occurrence of TEN following previous chemotherapy. Available risk stratification tools including human leucocyte antigen assessment and the algorithm of drug causality for epidermal necrolysis scoring system were utilized followed by patch testing which identified a lesser-suspected agent as possibly causative. Further evidence-based in vivo testing and subsequent challenges allowed for the reintroduction of life-saving chemotherapy.

Transcatheter Aortic Valve Replacement in Congenital Heart Disease.

Transcatheter aortic valve replacement is not widely used in patients with congenital heart disease. We describe our single-center experience of transcatheter aortic valve replacement in congenital heart disease, demonstrating short-term feasibility and safety, role in lifetime management of congenital aortic valve disease, and use as a bridge to recovery, future surgery, or transplantation.

Intermittent Ex Vivo Lung Perfusion in a Porcine Model for Prolonged Lung Preservation.

BACKGROUND: Ex vivo lung perfusion expands the lung transplant donor pool and extends preservation time beyond cold static preservation. We hypothesized that repeated regular ex vivo lung perfusion would better maintain lung grafts. METHODS: Ten pig lungs were randomized into 2 groups. The control underwent 16 h of cold ischemic time and 2 h of cellular ex vivo lung perfusion. The intermittent ex vivo lung perfusion group underwent cold ischemic time for 4 h, ex vivo lung perfusion (first) for 2 h, cold ischemic time for 10 h, and 2 h of ex vivo lung perfusion (second). Lungs were assessed, and transplant suitability was determined after 2 h of ex vivo lung perfusion. RESULTS: The second ex vivo lung perfusion was significantly associated with better oxygenation, limited extravascular water, higher adenosine triphosphate, reduced intraalveolar edema, and well-preserved mitochondria compared with the control, despite proinflammatory cytokine elevation. No significant difference was observed in the first and second perfusion regarding oxygenation and adenosine triphosphate, whereas the second was associated with lower dynamic compliance and higher extravascular lung water than the first. Transplant suitability was 100% for the first and 60% for the second ex vivo lung perfusion, and 0% for the control. CONCLUSIONS: The second ex vivo lung perfusion had a slight deterioration in graft function compared to the first. Intermittent ex vivo lung perfusion created a better condition for lung grafts than cold static preservation, despite cytokine elevation. These results suggested that intermittent ex vivo lung perfusion may help prolong lung preservation.

Clinical and laboratory features of COVID-19 illness and outcomes in immunocompromised individuals during the first pandemic wave in Sydney, Australia.

People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March-October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n = 12), secondary immunosuppression (N = 8) and those with primary or acquired immunodeficiency (i.e. HIV; N = 7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups.

Prevalence of ATTR-CA and high-risk features to guide testing in patients referred for TAVR.

PURPOSE: Transthyretin cardiac amyloidosis (ATTR-CA) is thought to be prevalent in patients with severe aortic stenosis (AS) who are referred for transcatheter aortic valve replacement (TAVR). However, prior studies were published when TAVR was only offered to elderly, inoperable, and high-risk patients. The aim of this study was to reevaluate the prevalence of ATTR-CA in a contemporary TAVR population and identify high-risk features to guide referral for technetium-99 pyrophosphate scan (99mTc-PyP scan) screening. METHODS: Patients seen in a multidisciplinary TAVR clinic for severe AS 70 years and older were referred for a 99mTc-PyP scan to evaluate for ATTR-CA. The primary outcome was the percent with a positive scan. The discriminatory ability of high-risk features was assessed to develop a more judicious screening system. RESULTS: Over the study period, 380 patients underwent screening, and 20 patients (5.3%) had a positive scan, with 17 patients having confirmed ATTR-CA, 1 patient deferring confirmatory testing (combined 4.7%), 1 having light chain amyloidosis, and 1 negative on biopsy. Compared to other patient and echocardiographic measures, elevated NT-pro BNP (> 1000 ng/L) was the best discriminator on who should be referred for 99mTc-PyP scan screening, with a sensitivity of 90% and a negative predictive value of 99%. CONCLUSION: The prevalence of ATTR-CA may be lower in a contemporary TAVR population due to its expanded indication for low-risk patients. NT-pro BNP is a simple test that can improve screening yield and more judiciously guide screening for ATTR-CA in this at-risk population. Comparison of the original versus the proposed algorithm.

Pacing-Related Differences After SAPIEN-3 TAVI: Clinical and Echocardiographic Correlates.

Data regarding the impact of pacing on outcomes after transcatheter aortic valve implantation (TAVI) is evolving especially with regards to pre-existing permanent pacemaker (PPM). We examined the impact of new and previous PPM on the clinical and hemodynamic outcomes after SAPIEN-3 TAVI. We included all consecutive patients who underwent transfemoral TAVI using SAPIEN-3 valve from 2015 to 2018 at our institution. Among 1,028 patients, 10.2% required a new PPM within 30 days, whereas 14% had a pre-existing PPM. The presence of either previous or new PPM had no impact on the 3-year mortality (log-rank p = 0.6) or 1-year major adverse cardiac and cerebrovascular events (log-rank p = 0.65). New PPM was associated with lower left ventricular (LV) ejection fraction (LVEF) at both 30 days (54.4 ± 11.3% vs 58.4 ± 10.1%, p = 0.001) and 1 year (54.2 ± 12% vs 59.1 ± 9.9%, p = 0.009) than no PPM. Similarly, previous PPM was associated with worse LVEF at 30 days (53.6 ± 12.3%, p <0.001) and 1 year (55.5 ± 12.1%, p = 0.006) than no PPM. Interestingly, new PPM was associated with lower 1-year mean gradient (11.4 ± 3.8 vs 12.6 ± 5.6 mm Hg, p = 0.04) and peak gradient (21.3 ± 6.5 vs 24.1 ± 10.4 mm Hg, p = 0.01), despite no baseline differences. Previous PPM was also associated with lower 1-year mean gradient (10.3 ± 4.4 mm Hg, p = 0.001) and peak gradient (19.4 ± 8 mm Hg, p <0.001) and higher Doppler velocity index (0.51 ± 0.12 vs 0.47 ± 0.13, p = 0.039). Moreover, 1-year LV end-systolic volume index was higher with new (23.2 ± 16.1 vs 20 ± 10.8 ml/m2, p = 0.038) and previous PPM (24.5 ± 19.7, p = 0.038) than no PPM. Previous PPM was associated with higher moderate-to-severe tricuspid regurgitation (35.3% vs 17.7%, p <0.001). There were no differences regarding the rest of the studied echocardiographic outcomes at 1 year. In conclusion, new and previous PPM did not affect 3-year mortality or 1-year major adverse cardiac and cerebrovascular events; however, they were associated with worse LVEF, higher 1-year LV end-systolic volume index, and lower mean and peak gradients on follow-up than no PPM.

Intracaval Leiomyoma with Intracardiac Extension.

The objective of this study was to explain step by step how to achieve a complete resection of an intravascular leiomyoma. A 48-year-old woman was referred to our institution with progressive dyspnea on exertion, lightheadedness, and previous history of total abdominal hysterectomy and bilateral salpingo-oophorectomy for a uterine leiomyoma echocardiography, computed tomography, and magnetic resonance imaging of the heart and abdomen/pelvis were performed and an intracaval mass with extension into the right heart and pulmonary artery was identified. After multidisciplinary review, a single-stage sternotomy-laparotomy procedure on cardiopulmonary bypass (with beating heart, mild hypothermia, and no deep hypothermic circulatory arrest) ensured complete resection of a giant intravenous leiomyoma (IVL). Multidisciplinary approach, multimodality imaging, and single-stage sternotomy-laparotomy procedure on cardiopulmonary bypass (with heart beating and mild hypothermia) ensure complete resection of IVL.

Successful treatment of pulmonary mucormycosis (Lichtheimia spp.) in a post-partum patient with COVID-19 ARDS requiring extra-corporeal membrane oxygenation using salvage therapy.

Case Summary: A 31-year-old female presented to a regional hospital at 27 weeks pregnant and was found to have COVID-19 ARDS. She underwent intubation and caesarian section for worsening hypoxia and non-reassuring fetal heart tones. Hypoxemia was refractory to proning requiring ECMO and transfer to a tertiary care center. Admission chest radiography showed a new right lower lobe cavitating lesion with computed tomography scan revealing a large multi-loculated cavity in the right lung and extensive bilateral ground-glass opacities. The patient was started on amphotericin and posaconazole, with final respiratory cultures growing Lichtheimia spp. Source control was discussed via possible open thoracostomy, but medical management alone was continued. Total ECMO support was 3 weeks. At the time of discharge to acute rehab, 1 month of amphotericin and posaconazole had been completed, with continuation of posaconazole. At last update, she had been discharged from rehab and was back home with her infant. Conclusion: Pulmonary mucormycosis, even in the non-ECLS population, carries a high mortality. Treatment in pulmonary disease with surgery improves mortality but is not always feasible. Salvage therapy with extended course antifungal medications may be an option for those not amendable.

Two-year outcomes after transcatheter aortic valve-in-valve implantation in degenerated surgical valves.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has emerged in recent years as a safe alternative to redo surgery in high-risk patients. Although early results are encouraging, data beyond short-term outcomes are lacking. Herein, we aimed to assess the 2-year outcomes after ViV-TAVI. METHODS: Patients undergoing ViV-TAVI for degenerated surgical valves between 2013 and 2019 at the Cleveland Clinic were reviewed. The coprimary endpoints were all-cause mortality and congestive heart failure (CHF) hospitalizations. We used time-to-event analyses to assess the primary outcomes. Further, we measured the changes in transvalvular gradients and the incidence of structural valve deterioration (SVD). RESULTS: One hundred and eighty-eight patients were studied (mean age = 76 years; 65% males). At 2 years of follow-up, all-cause mortality and CHF hospitalizations occurred in 15 (8%) and 28 (14.9%) patients, respectively. On multivariable analysis, the postprocedural length of stay was a significant predictor for both all-cause mortality (hazard ratio [HR] = 1.1; 95% confidence interval [CI]: 1.01, 1.19) and CHF hospitalization (HR = 1.16; 95% CI: 1.07, 1.27). However, the internal diameter of the surgical valve was not associated with significant differences in both primary endpoints. For hemodynamic outcomes, nine patients (4.8%) developed SVD. The mean and peak transvalvular pressure gradients remained stable over the follow-up period. CONCLUSION: ViV-TAVI for degenerated surgical valves was associated with favorable 2-year clinical and hemodynamic outcomes. Further studies are needed to better understand the role of ViV-TAVI as a treatment option in the life management of aortic valve disease.

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR).

INTRODUCTION: Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand. METHODS AND ANALYSIS: Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12619000241134).

Prone ex vivo lung perfusion protects human lungs from reperfusion injury.

BACKGROUND: We previously reported beneficial effects of prone positioning during ex vivo lung perfusion (EVLP) using porcine lungs. In this study, we sought to determine if prone positioning during EVLP was beneficial in human donor lungs rejected for clinical use. METHODS: Human double lung blocs were randomized to prone EVLP (n = 5) or supine EVLP (n = 5). Following 16 h of cold storage at 4°C and 2 h of cellular EVLP in either the prone or supine position. Lung function, compliance, and weight were evaluated and transplant suitability determined after 2 h of EVLP. RESULTS: Human lungs treated with prone EVLP had significantly higher partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio [348 (291-402) vs. 199 (191-257) mm Hg, p = 0.022] and significantly lower lung weight [926(864-1078) vs. 1277(1029-1483) g, p = 0.037] after EVLP. 3/5 cases in the prone group were judged suitable for transplant after EVLP, while 0/5 cases in the supine group were suitable. When function of upper vs. lower lobes was evaluated, prone EVLP lungs showed similar P/F ratios and inflammatory cytokine levels in lower vs. upper lobes. In contrast, supine EVLP lungs showed significantly lower P/F ratios [68(59-150) vs. 467(407-515) mm Hg, p = 0.012] and higher tissue tumor necrosis factor alpha levels [100.5 (46.9-108.3) vs. 39.9 (17.0-61.0) ng/ml, p = 0.036] in lower vs. upper lobes. CONCLUSIONS: Prone lung positioning during EVLP may optimize the outcome of EVLP in human donor lungs, possibly by improving lower lobe function.

ProPACC: Protocol for a Trial of Integrated Specialty Palliative Care for Critically Ill Older Adults.

BACKGROUND: Each year, approximately one million older adults die in American intensive care units (ICUs) or survive with significant functional impairment. Inadequate symptom management, surrogates' psychological distress and inappropriate healthcare use are major concerns. Pioneering work by Dr. J. Randall Curtis paved the way for integrating palliative care (PC) specialists to address these needs, but convincing proof of efficacy has not yet been demonstrated. DESIGN: We will conduct a multicenter patient-randomized efficacy trial of integrated specialty PC (SPC) vs. usual care for 500 high-risk ICU patients over age 60 and their surrogate decision-makers from five hospitals in Pennsylvania. INTERVENTION: The intervention will follow recommended best practices for inpatient PC consultation. Patients will receive care from a multidisciplinary SPC team within 24 hours of enrollment that continues until hospital discharge or death. SPC clinicians will meet with patients, families, and the ICU team every weekday. SPC and ICU clinicians will jointly participate in proactive family meetings according to a predefined schedule. Patients in the control arm will receive routine ICU care. OUTCOMES: Our primary outcome is patient-centeredness of care, measured using the modified Patient Perceived Patient-Centeredness of Care scale. Secondary outcomes include surrogates' psychological symptom burden and health resource utilization. Other outcomes include patient survival, as well as interprofessional collaboration. We will also conduct prespecified subgroup analyses using variables such as PC needs, measured by the Needs of Social Nature, Existential Concerns, Symptoms, and Therapeutic Interaction scale. CONCLUSIONS: This trial will provide robust evidence about the impact of integrating SPC with critical care on patient, family, and health system outcomes.

Concomitant Redo Transcatheter Aortic Valve Replacement and Valve-in-Mitral Annular Calcification.

Contemporary challenges in structural heart intervention include redo transcatheter aortic valve replacement and transcatheter mitral valve replacement in severe mitral annular calcification. We report a case of concomitant redo transcatheter aortic valve replacement and transcatheter mitral valve replacement in mitral annular calcification in a patient with radiation heart disease. (Level of Difficulty: Advanced.).

Surgical versus medical management of infective endocarditis after TAVR.

We assessed the incidence of aortic valve surgery intervention in the treatment of infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) and compared the characteristics and outcomes of surgical intervention versus medical management alone in this cohort using a nationwide data set. We identified all the hospitalizations in patients undergoing TAVR who developed IE within 1-year (i.e., early IE) of the procedure from 2014 to 2017 using the Nationwide Readmission Database (NRD). The primary outcomes of the study were in-hospital mortality. A total of 906 hospitalizations were identified for IE amongst the TAVR patients from 2014 to 2017 of which 20 (2.21%) underwent aortic valve surgery during the hospitalization. Patients undergoing surgery were younger, more likely to have Staphylococcus aureus endocarditis, cardiogenic shock, and acute kidney injury (AKI) during the hospitalization. There were no significant differences in in-hospital mortality (9.9% vs. 12.4%, p = 0.824; adjusted odds ratio (aOR): 0.26 (0.01-1.58), p = 0.223) and 30-day readmissions. However, the length of stay and hospitalization costs were higher in surgical intervention group. The important predictors of in-hospital mortality in TAVR-related IE patients were dialysis during IE hospitalization, AKI, cardiogenic shock, Staphylococcus aureus endocarditis, stroke, and female sex. The utilization of surgical management for IE post-TAVR during the index hospitalization is low, and there is no significant mortality benefit with surgical intervention as compared with the medical management.

Cardiac Operations After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is now frequently performed for severe aortic stenosis. Data regarding cardiac operations after TAVR are limited, however. Therefore, we investigated patient characteristics, operative timing and indications, and outcomes of these operations in a single-center experience. METHODS: From January 2012 to July 2020, 59 patients (median age, 70 years) underwent cardiac operations after TAVR, 38 (64%) of which were performed in other centers. The Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) was calculated at the time of prior TAVRs and at applicable index cardiac operations. RESULTS: From 2012 to 2018, fewer than 10 operations were performed after TAVR, but 18 were performed in 2019. The interval between prior TAVR and cardiac surgery decreased exponentially from 7 years to less than 1 year over the experience. In applicable cases (19 of 59 operations [32%]), the median STS-PROM was 5.5% (15th-85th percentiles, 3.1%-25%), and 40 (68%) were complex operations with no calculable STS-PROM. The TAVR valve was explanted in 46 (78%); 5 were isolated surgical aortic valve replacements. TAVR valve stenosis/regurgitation (34 [58%]) was the leading indication, followed by paravalvular leak in 14 (24%) and endocarditis in 10 (17%). When the TAVR valve was not explanted, mitral regurgitation was the leading indication for operation. Operative death occurred in 5 (8.5%), postoperative stroke in 2 (3.4%), and postoperative dialysis in 6 (10%). CONCLUSIONS: Cardiac operations after TAVR are increasing, and the interval between TAVR and operation is decreasing. Most cardiac operations are complex, high-risk reoperations, and isolated aortic valve replacement is rare. These findings should be considered when TAVR is selected for low- to intermediate-risk patients, particularly with multiple cardiac pathologies not addressed by TAVR.