Early Cardiac Arrest Hemodynamics, End-Tidal C o2 , and Outcome in Pediatric Extracorporeal Cardiopulmonary Resuscitation: Secondary Analysis of the ICU-RESUScitation Project Dataset (2016-2021).

OBJECTIVES: Cannulation for extracorporeal membrane oxygenation during active extracorporeal cardiopulmonary resuscitation (ECPR) is a method to rescue patients refractory to standard resuscitation. We hypothesized that early arrest hemodynamics and end-tidal C o2 (ET co2 ) are associated with survival to hospital discharge with favorable neurologic outcome in pediatric ECPR patients. DESIGN: Preplanned, secondary analysis of pediatric Utstein, hemodynamic, and ventilatory data in ECPR patients collected during the 2016-2021 Improving Outcomes from Pediatric Cardiac Arrest study; the ICU-RESUScitation Project (ICU-RESUS; NCT02837497). SETTING: Eighteen ICUs participated in ICU-RESUS. PATIENTS: There were 97 ECPR patients with hemodynamic waveforms during cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 71 of 97 patients (73%) were younger than 1 year old, 82 of 97 (85%) had congenital heart disease, and 62 of 97 (64%) were postoperative cardiac surgical patients. Forty of 97 patients (41%) survived with favorable neurologic outcome. We failed to find differences in diastolic or systolic blood pressure, proportion achieving age-based target diastolic or systolic blood pressure, or chest compression rate during the initial 10 minutes of CPR between patients who survived with favorable neurologic outcome and those who did not. Thirty-five patients had ET co2 data; of 17 survivors with favorable neurologic outcome, four of 17 (24%) had an average ET co2 less than 10 mm Hg and two (12%) had a maximum ET co2 less than 10 mm Hg during the initial 10 minutes of resuscitation. CONCLUSIONS: We did not identify an association between early hemodynamics achieved by high-quality CPR and survival to hospital discharge with favorable neurologic outcome after pediatric ECPR. Candidates for ECPR with ET co2 less than 10 mm Hg may survive with favorable neurologic outcome.

High levels of expression of Trop-2 in thymic epithelial tumors.

BACKGROUND: Trophoblastic antigen 2 (Trop2) is a cell surface glycoprotein expressed in multiple types of cancers, including breast cancer, non-small cell lung cancer, and gastrointestinal cancers. Trop2 expression and the use of Trop2-directed therapy such as antibody-drug conjugate (ADC) have not yet been investigated in thymic epithelial tumors (TETs). METHODS: Patients with TETs treated at MedStar Georgetown University Hospital were retrospectively identified. Of the patients for whom tumor samples and normal thymus tissue were available, immunohistochemistry (IHC) membranous staining for Trop2 and PD-L1 were performed. Positivity for Trop2 required at least 10% of the tumor cells to be stained, with an intensity scored of 1+ (weak), 2+ (moderate), and 3+ (strong). Cases with CPS ≥ 5% were considered positive for PD-L1. RESULTS: 30 TET samples from 29 patients (17 patients with thymoma and 12 patients with thymic carcinoma) were identified. One patient with thymic carcinoma had two samples from different time points. From the same set of patients, 13 samples of normal thymus tissue were available. In normal thymus tissue, eight samples (62%) showed no positivity of Trop2, while five samples (38%) showed 1 + IHC staining. In the thymoma samples, four (24%) showed 0 or 1 + IHC staining, while 13 (76%) showed 2 + or 3 + staining. Of the 13 thymic carcinoma samples, three samples (23%) showed 1 + IHC staining while seven (54%) showed 2 + staining and three (23%) showed 3 + staining. There was no statistically significant correlation found between PD-L1 expression and Trop-2 expression in thymoma or thymic carcinoma. CONCLUSIONS: Trop2 is readily expressed in TETS with a higher degree of expression in thymic carcinoma. The expression of Trop-2 was lower in normal thymic tissue compared with TETs. The increased expression of Trop-2 in TETs suggests that Trop2 is an attractive therapeutic target for Trop-2 directed therapy.

Corneal oedema during reverse piggyback scleral lens wear.

PURPOSE: One clinical approach to address poor front surface wettability during scleral lens wear is the use of a "reverse piggyback" system (a soft contact lens applied to the anterior surface of a scleral lens). The aim of this study was to compare the magnitude of corneal oedema induced following short-term reverse piggyback scleral lens wear and standard scleral lens wear. METHODS: Ten young (mean age 22 ± 6 years) healthy participants with normal corneas were recruited. On separate days, central corneal thickness and fluid reservoir thickness were measured using optical coherence tomography before and after 90 min of standard scleral lens wear (Kerectasia Alignment Tangent Torus diagnostic lenses, hexafocon A, Dk 100 × 10-11 (cm2 /s)(ml O2 /ml × mmHg), Capricornia Contact Lenses, capcl.com.au) and reverse piggyback scleral lens wear (the same scleral lens with a Dailies Total 1®, delefilcon A, Dk 140 × 10-11 (cm2 /s)(ml O2 /ml × mmHg), Alcon, alcon.com, applied to the anterior scleral lens surface). RESULTS: After correcting for small variations in the initial central fluid reservoir thickness, central corneal oedema was similar between the reverse piggyback (2.32 ± 1.15%) and standard scleral lens conditions (2.02 ± 0.76%; p = 0.45). CONCLUSIONS: Following 90 min of lens wear, the highly oxygen-permeable reverse piggyback system did not induce a clinically or statistically greater magnitude of central corneal oedema compared with standard scleral lens wear in young adults with healthy corneas. This approach may be suitable to address poor front surface scleral lens wettability or to correct residual refractive error during diagnostic scleral lens fitting.

An Unusual Combination of Arthrogryposis, Gastroschisis, Cecal Volvulus, and Malignant Hyperthermia in a Young Woman: A Case Report.

BACKGROUND The purpose of this study is to discuss a patient with a history of conditions, including arthrogryposis, gastroschisis, and malignant hyperthermia, who presented with cecal volvulus requiring urgent surgical intervention. CASE REPORT A 29-year-old woman with a history of arthrogryposis, gastroschisis, malignant hyperthermia, and multiple childhood abdominal surgeries presents to the Emergency Department (ED) with 2 days of abdominal pain and bloody diarrhea. A CT abdomen/pelvis revealed findings concerning for a cecal volvulus. The patient was premedicated and monitored closely by the anesthesia team due to her history of malignant hyperthermia. She underwent an exploratory laparotomy, where a dilated cecum and proximal ascending colon were found to be completely volvulized around the mesentery. Manual bowel detorsion was performed, which resulted in reperfusion of the ischemic-appearing bowel, which then appeared viable. She recovered well after the procedure and was discharged on postoperative day 5. CONCLUSIONS This case highlights a patient who presented with a combination of 4 findings: arthrogryposis, gastroschisis, malignant hyperthermia, and cecal volvulus. With arthrogryposis reported to be associated with gastroschisis and malignant hyperthermia, this report not only corroborates this association, but also aims to draw attention to the fact that these conditions have potential to occur jointly with cecal volvulus. Given the patient's history of gastroschisis requiring extensive abdominal surgeries that contribute as risk factors for cecal volvulus, it is possible there may be other arthrogryposis patients who present with cecal volvulus similar to that seen in this patient.

Measuring Critical Care Unit Performance Using a Postoperative Mechanical Ventilation Quality Metric.

BACKGROUND: Safely minimizing postoperative mechanical ventilation duration after congenital heart surgery could be a cardiac intensive care unit (CICU) quality measure. We aimed to measure CICU performance using duration of postoperative mechanical ventilation and identify organizational factors associated with this metric. METHODS: Observational analysis of 16,848 surgical hospitalizations of patients invasively ventilated on admission from the operating room from 26 Pediatric Cardiac Critical Care Consortium CICUs. We fitted a multivariable model to predict duration of postoperative mechanical ventilation adjusting for pre- and postoperative factors to measure CICU performance accounting for postoperative illness severity. We used our model to calculate observed-to-expected (adjusted) ventilation duration ratios for each CICU, describe variation across CICUs, and characterize outliers based on bias-corrected bootstrap 95% CIs. We explored associations between organizational characteristics and patient-level adjusted ventilation duration by adding these as independent variables to the model. RESULTS: We observed wide variation across CICUs in adjusted ventilation duration ratios, ranging from 0.7 to 1.7. Nine of 26 CICUs had statistically better than expected ventilation duration, while 10 were significantly worse than expected. Organizational characteristics associated with shorter adjusted ventilation duration included mixed (60%-90%) staffing by critical care or anesthesia-trained attendings, lower average attending-to-patient ratio, average CICU daily occupancy 80% to 90%, and greater nurse staffing ratios and experience. CONCLUSIONS: CICU performance in postoperative duration of mechanical ventilation varies widely across Pediatric Cardiac Critical Care Consortium centers. Several potentially modifiable organizational factors are associated with this metric. Taken together, these findings could spur efforts to improve ventilation duration at outlier hospitals.

Remarkable Intracranial Response to Sotorasib in a Patient With KRAS G12C-Mutated Lung Adenocarcinoma and Untreated Brain Metastases: A Case Report.

Sotorasib is a KRAS G12C inhibitor that recently received approval for use in locally advanced or metastatic KRAS G12C-mutated NSCLC. CodeBreaK100, the phase 2 clinical trial leading to the approval of sotorasib, excluded patients with untreated brain metastases; there have been no reports describing efficacy of sotorasib on untreated brain metastases. We present a case of a patient with active untreated brain metastases with resulting disorientation and weakness who has radiographic response and complete resolution of neurologic symptoms with sotorasib. Our case illustrates the intracranial activity of sotorasib, but additional studies are needed to characterize the intracranial response rate and duration of response in these patients.

Standardized Training for Physicians Practicing Pediatric Cardiac Critical Care.

OBJECTIVES: In the vast majority of Children's Hospitals, the critically ill patient can be found in one of three locations: the PICU, the neonatal ICU, and the cardiac ICU. Training, certification, and maintenance of certification for neonatology and critical care medicine are over seen by the Accreditation Council for Graduate Medical Education and American Board of Pediatrics. There is no standardization of training or oversight of certification and maintenance of certification for pediatric cardiac critical care. DATA SOURCES: The curricula from the twenty 4th year pediatric cardiac critical care training programs were collated, along with the learning objectives from the Pediatric Cardiac Intensive Care Society published "Curriculum for Pediatric Cardiac Critical Care Medicine." STUDY SELECTION: This initiative is endorsed by the Pediatric Cardiac Intensive Care Society as a first step toward Accreditation Council for Graduate Medical Education oversight of training and American Board of Pediatrics oversight of maintenance of certification. DATA EXTRACTION: A taskforce was established of cardiac intensivists, including the directors of all 4th year pediatric cardiac critical care training programs. DATA SYNTHESIS: Using modified Delphi methodology, learning objectives, rotational requirements, and institutional requirements for providing training were developed. CONCLUSIONS: In the current era of increasing specialized care in pediatric cardiac critical care, standardized training for pediatric cardiac critical care is paramount to optimizing outcomes.

Postoperative outcomes of total knee arthroplasty across varying levels of multimodal pain management protocol adherence.

We examined the effect of varying multimodal pain management (MMPM) combinations on oral morphine milligram equivalents (OMME) and length of stay (LOS) after total knee arthroplasty (TKA). Five groups were compared based on the combination of multimodal analgesics ranging from no MMPM to full MMPM with acetaminophen, gabapentinoids, and celecoxib. After risk adjustment, MMPM was associated with decreased odds of LOS ≥2 days and OMME ≥75th percentile. MMPM protocols are effective at reducing LOS and postoperative narcotic requirements post-TKA. Patients appear to derive similar benefit from receiving all three medications, as well as various combinations of these drugs.

Unequal allotment of patients in phase III oncology clinical trials.

Patient enrollment in cancer clinical trials has traditionally been limited to an equal distribution between cases and controls, however recently some clinical trials have utilized an unequal distribution between the case and control arms. Trends and proportion of phase 3 cancer clinical trials that have an unequal allocation between the years 2010 and 2019 were studied from data extracted from clinicaltrials.gov. 323 trials with two arms and 35 trials with 3 arms were identified as randomized control trials with the primary purpose of a cancer-related treatment that provided allocation data. Amongst the trials with two arms, 238 trials had equal allocation and 85 trials had unequal allocation. Therefore, cancer clinical trials with unequal allocation represent about one in four 2-arm phase 3 trials. Amongst the eligible trials with three arms, 26 trials had equal allocation and 9 trials had unequal allocation. There was no significant difference in the annual proportion of trials with unequal allocation from 2010 to 2019. The categories of cancer which had the highest number of unequally allotted two-arm clinical trials were: gastrointestinal, breast, and genitourinary malignancies. This shift may represent a new trend in clinical trial design to help enhance closer monitoring of adverse events despite higher costs and lower statistical power attached to this method.

Cangrelor PK/PD analysis in post-operative neonatal cardiac patients at risk for thrombosis.

Essentials An optimal therapeutic strategy has yet to be established to prevent early shunt thrombosis. A phase 1 study of cangrelor was performed in neonates after palliation of congenital heart disease. PD endpoint of >90% platelet inhibition in 60% of patients was achieved at 0.5 µg/kg/min dosing. No serious adverse events related to drug administration were observed, including bleeding. ABSTRACT: Background Systemic-to-pulmonary artery shunt thrombosis is a significant cause of early postoperative mortality in neonates after palliation of congenital heart disease. In the context of thromboprophylaxis, an optimal therapeutic strategy has yet to be established before aspirin administration. Cangrelor, a fast-acting, reversible P2Y12 inhibitor, may fill this unmet need. Objectives To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of cangrelor in neonates undergoing stage 1 palliation. Methods This prospective, open-label, single-arm study evaluated two cangrelor dosing cohorts following placement of a systemic-to-pulmonary artery shunt, right ventricle-to-pulmonary artery shunt, or ductal stent. Drug concentrations and platelet reactivity, assessed by light transmission aggregometry and in microfluidic assays (MF), were measured. Results Twenty-two patients were consented and 15 received a 1-hour infusion of cangrelor at either 0.5 µg/kg/min (cohort 1) or 0.25 µg/kg/min (cohort 2). Whereas the primary PD endpoint was achieved at the higher dose (ie, reduction in maximal platelet aggregation by ≥90% in 60% of participants), only 29% of those in cohort 2 attained this goal. Comparable and statistically significant results were obtained in MF assays (P < .0001 vs. baseline). Drug levels during infusion were 3-fold higher in cohort 1 vs. cohort 2 (P < .001). Most participants (70%) had undetectable drug levels by 10 minutes postinfusion with full recovery in platelet function at 1 hour. No drug-related bleeding events occurred. Conclusions Favorable PK/PD properties of cangrelor 0.5 µg/kg/min dosing and safety profile warrant further evaluation in neonates following palliative cardiac procedures.

Relationship Between Gestational Age and Outcomes After Congenital Heart Surgery.

BACKGROUND: Previous studies suggest that birth before 39 weeks' gestational age (GA) is associated with higher perioperative mortality and morbidity after congenital heart surgery. The optimal approach to timing of cardiac operation in premature infants remains unclear. We investigated the impact of GA at birth and corrected GA at surgery on postoperative outcomes using the Pediatric Cardiac Critical Care Consortium (PC4) database. METHODS: Infants undergoing selected index cardiac operations before the end of the neonatal period were included (n = 2298). GA at birth and corrected GA at the time of the index cardiac operation were used as categorical predictors and fitted as a cubic spline to assess nonlinear relationships. The primary outcome was hospital mortality. Multivariable logistic regression models assessed the association between predictors and outcomes while adjusting for confounders. RESULTS: Late-preterm (34-36 weeks) birth was associated with increased odds of mortality compared with full-term (39-40 weeks) birth, while early-term (37-38 weeks) birth was not associated with increased mortality. Corrected GA at surgery of 34 to 37 weeks compared with 40 to 44 weeks was associated with increased mortality. When analyzing corrected GA at surgery as a continuous predictor of outcome, odds of survival improve as patients approach 39 weeks corrected GA. CONCLUSIONS: Contrary to previous literature, we did not find an association between early-term birth and hospital mortality at PC4 hospitals. Our analysis of the relationship between corrected GA and mortality suggests that operating closer to full-term corrected GA may improve survival.

Trends in the crossover of patients in phase III oncology clinical trials in the USA.

BACKGROUND: The incorporation of crossover in randomised controlled trials is accepted as an ethical obligation, especially in cancer clinical trials. The more common type of crossover is crossover allowance, which allows patients assigned to one arm to switch to another arm if there is an established benefit in the crossover arm. In contrast, crossover-designed studies involve switching patients from all arms to a different arm as part of the study design. Crossover allowance may have advantages in patient recruitment and incorporating crossover after initial positive results fulfil ethical requirements. However, crossover can also contribute to confounding major endpoints of studies, such as overall survival or the second progression-free survival interval. For this reason, it is important to investigate and identify potential trends of crossover in clinical trials testing novel therapies. METHODS: Data about cancer clinical trials were extracted from clinicaltrials.gov. The search query was limited to completed phase III studies in adult populations. Location was limited to the USA. Date range extended from 1990 to 2019. Search query included the terms: cancer; completed- recruitment status; age: 18-65+ years; sex: all; location: USA; and study phase: phase 3. Studies were then excluded if they were not randomised controlled trials (RCTs) with the primary purpose of treatment and if they did not test cancer-related interventions. RESULTS: A total of 744 clinical trials were identified. There were 459 RCTs aimed at treatment, and of those, 35 utilised crossover. The start dates of these crossover trials ranged from 1997 to 2012. Thirty studies utilised crossover allowance. Prostate, breast and gastrointestinal stromal tumour cancers were the most represented cancer types in crossover studies. Among the 30 studies, the median proportion of patients who crossed over relative to the original arm assignment ranged from 2% to 88%, with a median of 57.5%. CONCLUSIONS: The proportion of identified clinical trials with crossover compared to those without is extremely small. Crossover in clinical trials studying cancer treatment does not appear to be a widespread practice. Even though statistical approaches to mitigate confounding exist, crossover can still skew accurate reporting of the impact of experimental therapies on overall survival.

Locally Advanced Osteosarcoma of the Ethmoid Sinus: A Report of Successful Management.

Osteosarcoma of the skull has poor outcomes. This case report describes the presentation and clinical course of a patient who was diagnosed with osteosarcoma of the skull involving the cribriform plate. After her initial diagnosis, she developed esotropia with severe unremitting headaches. She received palliative radiation, followed by chemotherapy, and responded well. Her initial symptoms involving the cranial nerves subsided, and her response was sustained. This report illustrates the need to effectively treat osteosarcoma of the skull despite its reported poor outcomes.

Cost-effectiveness analysis of nivolumab compared to pembrolizumab in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck.

Pembrolizumab and nivolumab are anti-PD-1 immunotherapy agents approved for the treatment of metastatic or recurrent head and neck squamous cell carcinoma (HNSCC) with demonstrated benefit as shown by the CheckMate 141 and KEYNOTE-040 clinical trials. Increasing costs of anticancer drugs in particular may influence the choice of treatment. There are limited data and mixed results on the cost-effectiveness of these immunotherapy agents when used in the setting of recurrent or metastatic HNSCC. This study compares the cost-effectiveness of pembrolizumab and nivolumab in this setting. Data published from the CheckMate 141 and KEYNOTE-040 studies were used to generate a model estimating treatment costs and overall survival benefit. Cost of treatment of toxicity-related events were obtained from previous literature and incorporated into calculated costs. Data from both experimental arms and both standard of care arms in the two studies were used for cost estimation in the model. An adjusted standard of care arm was derived from existing data as a common comparator for nivolumab and pembrolizumab. The initial incremental cost-effectiveness ratio (ICER) for nivolumab was $409,000 per quality-adjusted life year (QALY). The initial ICER for pembrolizumab was $1,137,595/QALY. Comparison to adjusted standard of care arm resulted in ICERs of $484,000/QALY and $856,173/QALY, for nivolumab and pembrolizumab, respectively. Nivolumab appears to have a lower cost per QALY and may be more cost-effective than pembrolizumab. Neither drug would be considered a cost-effective treatment option at a threshold of $100,000/QALY for patients in this setting. Outcomes of improved long-term survival have yet to be reported as these agents are relatively new; incorporation of this future data would likely improve the cost-effectiveness of these drugs.

Team-Based Intervention to Reduce the Impact of Nonactionable Alarms in an Adult Intensive Care Unit.

BACKGROUND: Nonactionable alarms comprise over 70% of alarms and contribute a threat to patient safety. Few studies have reported approaches to translate and sustain these interventions in clinical settings. PURPOSE: This study tested whether an interprofessional team-based approach can translate and implement effective alarm reduction interventions in the adult intensive care unit. METHODS: The study was a prospective, cohort, pre- and postdesign with repeated measures at baseline (preintervention) and post-phase I and II intervention periods. The settings for the most prevalent nonactionable arrhythmia and bedside parameter alarms were adjusted during phases I and II, respectively. RESULTS: The number of total alarms was reduced by 40% over a 14-day period after both intervention phases were implemented. The most prevalent nonactionable parameter alarms decreased by 47% and arrhythmia alarms decreased by 46%. CONCLUSIONS: It is feasible to translate and sustain system-level alarm management interventions addressing alarm fatigue using an interprofessional team-based approach.

Differential Gamma-Synuclein Expression in Acute and Chronic Retinal Ganglion Cell Death in the Retina and Optic Nerve.

We used genetic naturally occurring glaucoma (DBA/2J) and experimentally induced optic nerve crush (ONC) as models to study gamma-synuclein expression change in retinal ganglion cells and optic nerves. Gene chip microarray analysis demonstrated downregulated expression of the gamma-synuclein gene in DBA/2J mice as they developed age-associated glaucoma with concomitant with retinal ganglion cell loss. Real-time PCR, Western blot, and immunostaining results confirmed that the expression of gamma-synuclein at the mRNA and protein level was significantly reduced in the retinas and optic nerves of aged DBA/2J mice. We also observed similar reduced expression of gamma-synuclein in the retinas from mice after optic nerve crush. Surprisingly, the expression of gamma-synuclein was increased in optic nerves after crush. This is the first study demonstrating gamma-synuclein-expressing cells accumulate in the optic nerve crush site. Gamma-synuclein was found in axons colocalizing largely with neurofilaments in control mice without injury but was found inside cells within the scar in the crush site. Gamma-synuclein expression is predominantly expressed at the optic nerve crush site associated with CD68+ macrophage-like cells, not GFAP-expressing astroglial cells, suggesting gamma-synuclein expression is associated with glial scar formation inhibitory to optic nerve regeneration. We propose gamma-synuclein labels macrophage-like cells recruited to the site of acute optic nerve injury.

Differences in the early stage gene expression profiles of lung adenocarcinoma and lung squamous cell carcinoma.

The discovery of lung carcinoma subtype-specific gene expression changes has the potential to elucidate the molecular differences and provide personalized therapeutic targets for these pathologies. The aim of the present study was to characterize the genetic profiles of the early stages (IA/IB) of two non-small cell lung cancer subtypes, adenocarcinoma (AD) and squamous cell carcinoma (SC). RNA-Seq gene expression data from The Cancer Genome Atlas was analyzed to compare the gene expression differences between AD and SC. The gene sets specific to each subtype were further analyzed to identify the enriched Gene Ontology terms, Kyoto Encyclopedia of Genes and Genomes pathways and biological functions. The results demonstrated that a unique set of genes (145 upregulated and 27 downregulated) was altered in AD, but not in SC; another set of genes (146 upregulated and 103 downregulated) was significantly altered in SC, but not in AD. Genes highly upregulated specifically in AD included albumin (1,732-fold), protein lin-28 homolog A, which is a positive regulator of cyclin-dependent kinase 2 (150-fold) and gastric lipase (81-fold). Genes highly upregulated specifically in SC included amelotin (618-fold), alcohol dehydrogenase 7 (57-fold), aclerosteosis (55-fold) and claudin-22 (54-fold). Several cancer/testis antigen family genes were notably upregulated in SC, but not in AD, whereas mucins were upregulated only in AD. Functional pathway analysis demonstrated that the dysregulation of genes associated with retinoid X receptors was common in AD and SC, genes associated with 'lipid metabolism' and 'drug metabolism' were dysregulated only in SC, whereas genes associated with 'molecular transport' and 'cellular growth and proliferation' were significantly enriched in AD specifically. These results reveal fundamental differences in the gene expression profiles of early-stage AD and SC. In addition, the present study identified molecular pathways that are uniquely associated with the pathogenesis of these subtypes.

Neoadjuvant and consolidation immuno-oncology therapy in stage III non-small cell lung cancer.

Lung cancer continues to be the leading cause of cancer death worldwide. Recently, immunotherapy for non-small cell lung cancer (NSCLC) has emerged as a powerful treatment option for advanced lung cancer. The relative success of programmed death 1 (PD-1) and/or programmed death ligand 1 (PD-L1) antibodies in metastatic disease have increased interest in expanding their use to earlier stage NSCLC. The complex and diverse nature of stage III disease also invites the incorporation of immunotherapy into treatment plans in both the neoadjuvant and consolidation settings. Currently available data of anti-PD-(L)1 therapies in stage III NSCLC are limited. However, interim results from two studies are encouraging: a phase II neoadjuvant nivolumab trial demonstrated early signals of efficacy, and the phase III PACIFIC trial of durvalumab recently showed significant improvement in progression-free survival (PFS). Preliminary results for the phase II DETERRED trial of durvalumab have also been reported. Many studies are testing anti-PD-(L)1 therapies in the neoadjuvant and consolidation settings for stage III NSCLC, and will be discussed. As these studies mature they may provide further treatment options in management of stage III NSCLC.

HeartWare HVAD for Biventricular Support in Children and Adolescents: The Stanford Experience.

Despite increasing use of mechanical circulatory support in children, experience with biventricular device implantation remains limited. We describe our experience using the HeartWare HVAD to provide biventricular support to three patients and compare these patients with five patients supported with HeartWare left ventricular assist device (LVAD). At the end of the study period, all three biventricular assist device (BiVAD) patients had been transplanted and were alive. LVAD patients were out of bed and ambulating a median of 10.5 days postimplantation. The BiVAD patients were out of bed a median of 31 days postimplantation. Pediatric patients with both left ventricular and biventricular heart failure can be successfully bridged to transplantation with the HeartWare HVAD. Rapid improvement in functional status following HVAD implantation for isolated left ventricular support is seen. Patients supported with BiVAD also demonstrate functional recovery, albeit more modestly. In the absence of infection, systemic inflammatory response raises concern for inadequate support.

Ventricular assist devices in a contemporary pediatric cohort: Morbidity, functional recovery, and survival.

BACKGROUND: Limited availability of donor organs has led to the use of ventricular assist devices (VADs) to treat heart failure in pediatric patients, primarily as bridge to transplantation. How effective VAD therapy is in promoting functional recovery in children is currently not known. METHODS: We report morbidity and mortality as defined by the Interagency Registry for Mechanically Assisted Circulatory Support Modified for Pediatrics (PediMACS) and the use of the Treatment Intensity Score to assess functional status for 50 VAD patients supported at a single pediatric program from 2004 to 2013. RESULTS: In this cohort, 30-day survival on VAD was 98%, and 180-day survival was 83%. Stroke occurred in 11 patients (22%), with 8 (16%) resulting in persistent neurologic deficit or death. The adverse event rate was 2-fold to 3-fold higher in the first 7 days of support compared with the subsequent support period. Functional status, as measured by the Treatment Intensity Score, improved with duration of support. Successful bridge to transplantation was associated with fewer adverse events during support and greater improvement in the Treatment Intensity Score during the period of support. CONCLUSIONS: Overall survival in this cohort is excellent. The risk of serious adverse events decreases over the first month of support. However, a clinically significant risk of morbidity and mortality persists for the duration of pediatric VAD support. Measures of functional status improve with duration of support and are associated with survival to transplantation.