Search

PURPOSE Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia ( P ≤ .001); febrile neutropenia ( P = .002); and alopecia ( P < .001) were significantly lower, whereas grade 3 or 4 nausea ( P = .004) was more common. CONCLUSION In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Tracheobronchoplasty (TBP) is the gold-standard treatment for severe symptomatic excessive central airway collapse; however outcomes among obese patients are unknown.A retrospective, single-center analysis was conducted on consecutive patients undergoing TBP for severe symptomatic excessive central airway collapse from 2003 to 2020. Demographics, comorbidities, functional status, and perioperative complications were collected. Functional status was assessed with a 6-minute walk test (6MWT). Health-related quality of life (HRQOL) was assessed with the St George's Respiratory Questionnaire (SGRQ), Cough-specific Quality of Life Questionnaire, and modified Medical Research Council dyspnea scale (mMRC) at baseline and postoperatively. Wilcoxon rank-sum and χ2 tests were used to compare outcomes between groups. A mixed-effects regression model compared 6MWT and HRQOL over time.One hundred three patients underwent TBP with complete follow-up data. Thirty-four patients (33%) were obese (body mass index ≥ 35 kg/m2). Baseline demographics were similar between obese and nonobese groups, but obese patients had worse preoperative SGRQ and mMRC scores. Overall complication rates were similar (52.9% vs 43.5%, P = .36). At 3 months there was no significant difference in SGRQ, Cough-specific Quality of Life Questionnaire, or 6MWT scores; however mMRC scores were higher in obese patients (P = .04). At 12 months there was no significant difference in SGRQ, Cough-specific Quality of Life Questionnaire, mMRC, or 6MWT scores. Correcting for age, sex, and Charlson Comorbidity Index a mixed-effects regression model demonstrated obesity was not an independent predictor for lower 6MWT scores or HRQOL.Obese patients achieve similar improvement in HRQOL and functional capacity with comparable morbidity after TBP as nonobese patients. Obesity should not preclude patients with severe symptomatic excessive central airway collapse from TBP.

Subglottic concretion is a rare and perilous condition usually presenting with existing or impending airway obstruction. Due to long-standing nature of the condition, slow progression of symptoms and rarity of occurrence, the condition is either missed or misdiagnosed. Its resemblance in presentation and symptoms to that of foreign body (FB) bronchus can lead to a diagnostic misadventure. Detailed history, chronology of symptoms and radiological imaging in conjunction with fiberoptic evaluation are keys for establishing correct diagnosis. Treatment outcomes in such cases depend on appropriate management approach with backup plan in tandem. We describe a child with β thalassemia major with subglottic concretion, which was erroneously diagnosed and managed as a case of subglottic FB due to its classical history and presentation. The aim is to highlight the circumstances leading to this diagnostic misadventure with emphasis on airway management, problems faced and lessons learnt during the same.

Brown tumours of bone are highly vascular osteolytic lesions that depict a reparative cellular process instead of a neoplastic process in hyperparathyroidism (HPT) patients. These tumours have the potential to be aggressive and destructive. We report a case of a 30-year-old woman who presented with left thigh and lower back pain. The radiological evaluation showed multiple bony lesions in the pelvis and the spine, which mimicked multiple metastatic tumours. However, on biochemistry evaluation, serum calcium, alkaline phosphatase, and parathyroid hormone were all high, while serum phosphate was low, indicating primary HPT (PHPT), which was confirmed by parathyroid scintigraphy showing left parathyroid adenoma. Hence, the bony lesions were diagnosed as brown tumours secondary to PHPT. The patient underwent parathyroidectomy and developed severe hungry bone syndrome requiring parenteral calcium infusion along with oral calcium and active vitamin D supplementation. The clinical symptoms of bone pain improved after surgery.

Purpose: To examine the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in neovascular age-related macular degeneration (nvAMD). Design: Retrospective cohort study. Methods: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. Anti-VEGF agent selection for the first four injections and at one year were examined in both the sample and control groups. Results: Adherence to the initial agent was high between first and subsequent injections (2nd, 3rd, 4th injection, and 1 year) in both sample (96.2%, 95.9%, 91.9%, 93.4%, respectively) and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p

Background In 2019, the total National Healthcare Expenditure (NHE) reached $3.8 trillion, or nearly 20% of the total Gross Domestic Product. This represents a 4-fold increase in its Gross Domestic Product share since 1960. Given the magnitude and growth of such expenditures, healthcare cost containment is central to the country's financial sustainability. Moreover, as Medicare represents nearly 20% of the total NHE, it is a primary target for piloting, implementing and scaling initiatives that reduce expenditures. Objective To assess trends in Medicare Physician Fee Schedule for Service (Part B) payments and utilization for Imaging relative to other services from 2009 through 2019. Materials and methods We conducted a retrospective observational study of annual expenditures and utilization of imaging services using data from Centers for Medicare and Medicaid Services Medicare Part B. Data was grouped according to the Berenson-Eggers Type of Service Classification. The values were adjusted for inflation and we calculated the annual changes and the compound annual growth rates and the price elasticity of supply. Results For the 10-year period, Imaging represented on average 8% of the total Medicare Part B expenditures, an equivalent of 1.4% of total Medicare expenditures or 0.05% of the NHE. While NHE, overall Medicare and overall Part B had positive growth rates of total expenditures, Imaging did not. Moreover, Imaging had the most negative CAGR compared to all other categories, including Drugs, Procedures, Evaluation and Management and Durable Medical Equipment. Conclusion Imaging did not contribute to the increase in Medicare Part B expenditures, and it might have been disproportionately affected by cost containment policies.

BACKGROUND Spontaneous hemopericardium, associated with direct oral anticoagulant (DOAC) use, is one of the uncommon complications with high morbidity that has not been extensively studied We aimed to determine demographic characteristics, clinical features, lab evaluation, management, and outcomes of the studies focusing on hemopericardium as a DOAC use. METHODS PubMed, Web of Science, Google Scholar, and CINAHL databases were searched for relevant articles using MeSH key-words and imported into referencing/review software. The data regarding demographics, clinical characteristics, cardiac investigations, and management were analyzed in IBM Statistics SPSS 21. t-Test and Chi-square test were used. A P score of

Introduction Hospital quality improvement and hospital performance are commonly evaluated using parameters such as average length of stay (LOS), patient safety measures and rates of hospital readmission. Thirty-day readmission (30-DR) rates are widely used as a quality indicator and a quantifiable metric for hospitals since patients are often readmitted for the exacerbation of conditions from index admission. The quality of patient education and postdischarge care can influence readmission rates. We report the 30-DR rates of patients with asthma using a national dataset for the year 2013. Objectives The aim of our study was to assess the 30- day readmission (30-DR) rate as well as, the causes and predictors of readmissions. Study designs/methods Using the Nationwide Readmission Database (NRD) (2013), we identified primary discharge diagnoses of asthma by using International Classification of Diseases, Ninth Revision, Clinical Modification code ‘493’. Categorical and continuous variables were assessed by a χ2 test and a Student's t-test, respectively. The independent predictors of unplanned 30-DR were detected by multivariate analysis. We used sampling weights, which are provided in the NRD, to generate the national estimates. Results There were 130 490 (weighted N=311 173) inpatient asthma admissions during 2013. The overall 30-DR for asthma was 11.9%. The associated factors for 30-DR were age 45–84 years (40.32% vs 29.05%; p Conclusions We found that the overall 30-DR rate for asthma was 11.9% all-cause readmission. Major causes of 30-DR were asthma exacerbation (36.74%), chronic obstructive pulmonary disease (11.47%), respiratory failure (6.46%), non-specific pneumonia (6.19%), septicaemia (3.61%) and congestive heart failure (3.32%). One-fourth of the revisits occurred in the first week, while half of the revisits took place in the first 2 weeks. Education regarding illness and the importance of medicine compliance could play a significant role in preventing asthma-related readmission.

Objective: Glomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D). Research Design and Methods: Blood and urine samples were collected from 40 children with DKA (52% boys, mean age 11 ± 4 years, venous pH7.2 ± 0.1, glucose 451 ± 163 mg/dL) at three timepoints: 0–8 and 12–24 h after starting insulin, and 3 months after discharge. Mixed-effects models evaluated the changes in tubular injury markers over time (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1 [KIM-1], and interleukin 18 [IL-18]). We also evaluated the relationships among the tubular injury biomarkers, copeptin, a vasopressin surrogate, and serum uric acid (SUA). Results: Serum NGAL, KIM-1, and IL-18 were highest at 0–8h (306.5 ± 45.9ng/mL, 128.9 ± 10.1pg/mL, and 564.3 ± 39.2pg/mL, respectively) and significantly decreased over 3 months (p=0.03, p=0.01, and p < 0.001, respectively). There were strong relationships among increases in copeptin and SUA and rises in tubular injury biomarkers. At 0–8h, participants with acute kidney injury (AKI) [17%] showed significantly higher concentrations of tubular injury markers, copeptin, and SUA. Conclusions: DKA was characterized by tubular injury, and the degree of injury associated with elevated copeptin and SUA. Tubular injury biomarkers, copeptin and SUA may be able to predict AKI in DKA.

Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

Cirrhosis is the terminal stage of progressive liver fibrosis, affecting 1%-2% of the global population and accounting for 1.3 million deaths annually.1,2 Median survival for persons with compensated cirrhosis is approximately 12 years, compared with only 2 years for those with hepatic decompensation. Accurate prediction of hepatic decompensation is an unmet need to enable identification of patients with cirrhosis who could benefit from close monitoring and timely medical interventions. Besides, risk stratification of patients with cirrhosis could help inform patient selection for trials evaluating therapies to prevent hepatic decompensation. Although various clinical scores, such as the albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4) indices (ALBI-FIB4 score) have been proposed to predict long-term risk of hepatic decompensation,3 external validation has often shown suboptimal prognostic capability and revealed room for improvement.4.

PURPOSE: Given the perioperative morbidity and intensity of multimodality treatment, patients with resected pancreatic ductal adenocarcinoma (PDAC) spend a substantial amount of time in clinical care. The primary aim was to determine total time spent in multimodality care for patients with locoregional PDAC. METHODS: A cohort study of all patients who underwent curative-intent resection for PDAC at a single-institution, tertiary care center was performed (2015-2019). Exact times for all relevant visits were abstracted from the primary medical record, and travel time was calculated. Care time was divided into preoperative, surgical, radiation, and systemic therapy phases of care. Primary outcome measures were the percentage of total survival time (TST) and percentage of overall survival (OS) days spent in receipt of care. RESULTS: One hundred seven patients were included. Patients spent a median of 5.0% (interquartile range [IQR] 2.4%-10.1%) of TST and 11.0% (IQR, 5.7%-20.4%) of OS days in receipt of clinical care. Preoperative, surgical, radiation, and systemic therapy phases of care comprised a median of 0.9% (IQR, 0.4%-2.2%), 3.0% (IQR, 1.9%-6.8%), 4.4% (IQR, 3.6%-6.3%), and 10.0% (IQR, 6.2%-14.1%) of OS days. The median per-visit travel time was 60 minutes (IQR, 32-120), and the median cumulative travel time was 22.0 hours (IQR, 12.0-51.5). 12.1% (n = 13) and 7.8% (n = 4) of patients spent > 10% of TST in receipt of surgical and systemic therapy care, respectively. CONCLUSION: Patients with locoregional pancreatic cancer spend a considerable percentage of their survival time in receipt of oncologic care. Further research to determine predictors of increased time burden is warranted to better inform shared decision making.

Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF.The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach.A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P.001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone.In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

PURPOSE: Serious Illness Conversations (SICs) are structured conversations between clinicians and patients about prognosis, treatment goals, and end-of-life preferences. Although behavioral interventions may prompt earlier or more frequent SICs, their impact on the quality of SICs is unclear. METHODS: This was a secondary analysis of a randomized clinical trial ( NCT03984773 ) among 78 clinicians and 14,607 patients with cancer testing the impact of an automated mortality prediction with behavioral nudges to clinicians to prompt more SICs. We analyzed 318 randomly selected SICs matched 1:1 by clinicians (159 control and 159 intervention) to compare the quality of intervention vs. control conversations using a validated codebook. Comprehensiveness of SIC documentation was used as a measure of quality, with higher integer numbers of documented conversation domains corresponding to higher quality conversations. A conversation was classified as high-quality if its score was ≥ 8 of a maximum of 10. Using a noninferiority design, mixed effects regression models with clinician-level random effects were used to assess SIC quality in intervention vs. control groups, concluding noninferiority if the adjusted odds ratio (aOR) was not significantly < 0.9. RESULTS: Baseline characteristics of the control and intervention groups were similar. Intervention SICs were noninferior to control conversations (aOR 0.99; 95% CI, 0.91 to 1.09). The intervention increased the likelihood of addressing patient-clinician relationship (aOR = 1.99; 95% CI, 1.23 to 3.27; P < .01) and decreased the likelihood of addressing family involvement (aOR = 0.56; 95% CI, 0.34 to 0.90; P < .05). CONCLUSION: A behavioral intervention that increased SIC frequency did not decrease their quality. Behavioral prompts may increase SIC frequency without sacrificing quality.

Blocking the complement system as a therapeutic strategy has been proposed for numerous glomerular diseases but presents a myriad of questions and challenges, not the least of which is demonstrating efficacy and safety. In light of these potential issues and because there are an increasing number of anti-complement therapy trials either planned or underway, the National Kidney Foundation (NKF) facilitated an all-virtual format scientific workshop entitled, "Improving Clinical Trials for Anti-complement Therapies in Complement-mediated Glomerulopathies." Attended by patient representatives and experts in glomerular diseases, complement physiology, and clinical trial design, the aim of this workshop was to develop standards applicable for designing and conducting clinical trials for anti-complement therapies across a wide spectrum of complement-mediated glomerulopathies. Discussions focused on study design, subject risk assessment and mitigation, laboratory measurements and biomarkers to support these studies, and identification of optimal outcome measures to detect benefit, specifically for trials in complement-mediated diseases. This report summarizes the discussions from this workshop and outlines consensus recommendations.

Our purpose was to evaluate the accuracy of LI-RADS Treatment Response Algorithm (LR-TRA) for assessing the viability of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT), using explant pathology as the gold standard.This retrospective study included patients who underwent SBRT for locoregional treatment of HCC between 2008 and 2019 with subsequent liver transplantation. Five radiologists independently assessed all treated lesions by using the LR-TRA. Imaging and posttransplant histopathology were compared. Lesions were categorized as either completely (100%) or incompletely (100%) necrotic, and performance characteristics and predictive values for the LR-TR viable and nonviable categories were calculated for each reader. Interreader reliability was calculated using the Fleiss kappa test.A total of 40 treated lesions in 26 patients (median age, 63 years [interquartile range, 59.4-65.5]; 23 men) were included. For lesions treated with SBRT, sensitivity for incomplete tumor necrosis across readers ranged between 71% and 86%, specificity between 85% and 96%, and positive predictive value between 86% and 92%, when the LR-TR equivocal category was treated as nonviable, accounting for subject clustering. When the LR-TR equivocal category was treated as viable, sensitivity of complete tumor necrosis for lesions treated with SBRT ranged from 88% to 96%, specificity from 71% to 93%, and negative predictive value from 85% to 96%. Interreader reliability was fair (k = 0.22; 95% confidence interval, 0.13-0.33). Although a loss of arterial phase hyperenhancement (APHE) was highly correlated with pathologically nonviable tumor on explant, almost half of the patients with APHE had pathologically nonviable tumor on explant.LR-TRA v2018 performs well for predicting complete and incomplete necrosis in HCC treated with SBRT. In contrast to other locoregional therapies, the presence of APHE after SBRT does not always indicate viable tumor and suggests that observation may be an appropriate strategy for these patients.

Development of novel materials with desirable properties remains at the forefront of modern scientific research. Machine learning (ML), a branch of artificial intelligence, has recently emerged as a powerful technology in optoelectronic devices for the prediction of various properties and rational design of materials. Metal halide perovskites (MHPs) have been at the centre of attraction owing to their outstanding photophysical properties and rapid development in solar cell application. Therefore, the application of ML in the field of MHPs is also getting much attention to optimize the fabrication process and reduce the cost of processing. Here, we comprehensively reviewed different applications of ML in the designing of both MHP absorber layers as well as complete perovskite solar cells (PSCs). At the end, the challenges of ML along with the possible future direction of research are discussed. We believe that this review becomes an indispensable roadmap for optimizing materials composition and predicting design strategies in the field of perovskite technology in the future.

Summary Background The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. Methods In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT04351152 , and is completed. Findings Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41–137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79–89) participants in the lenzilumab group and in 190 (78%; 72–83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. Interpretation Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. Funding Humanigen.

Background: Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities. Results: Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59–76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%–61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67–0.79]) after accounting for differences in demographics and smoking-related comorbidities. Conclusions: There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.

Mixed epithelial mesenchymal (MEM) hepatoblastoma with teratoid features is rare histological variant of hepatoblastoma and described in case reports. Growing teratoma syndrome (GTS) is a rare and often unrecognised phenomenon generally associated with less than 5% of germ cell tumour. It is defined by enlarging tumour mass which is generally mature teratoma with normal or significantly decreasing tumour markers during chemotherapy. The treatment outcomes in GTS are dependent on early recognition and complete surgical excision. We describe a rare case of MEM hepatoblastoma with teratoid features with GTS in an infant who had a delay in definitive management due to late diagnosis of GTS.

Introduction: Fine-needle aspiration cytology (FNAC) can be challenging to provide a precise diagnosis in salivary gland cytopathology due to diversity of lesions and cytomorphological convergence between the tumors and within the same tumor of salivary gland. The recently proposed Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a risk stratication-based classication system with an intrinsic risk of malignancy (ROM) for each diagnostic category, which aims to furnish useful information to the clinicians. This study was undertaken to evaluate the diagnostic utility and validity of MSRSGC. A 4-year retrospective Materials and Methods: study was conducted at a tertiary care hospital in Central Gujarat in Western India. A total of 90 cases of FNAC of salivary gland lesions for the period of January 2018 to March 2021 were reviewed. Patient clinical details, FNAC smears and histological slides where available were retrieved from the departmental records. Results: The cases belong to following categories: non-diagnostic (4.4%), non-neoplastic (10%), atypia of undetermined signicance (1.1%), benign neoplasm (68.9%), salivary gland neoplasm of uncertain malignant potential (8.9%), suspicious for malignancy (2.2%), and malignant (4.4%). Out of 90 cases, 62 cases (68.8%) had follow-up. The ROM were 7.6% for category IV—A and 50% for category IV-B. The sensitivity, specicity, positive predictive value, negative predictive value, and likelihood ratio for differentiating between benign and malignant lesions were recorded as 98.1%, 42.9%, 92.8%, 75.0%, and 1.750, respectively. Conclusion: Application of MSRSGC has immense value for standardization of reporting of salivary gland FNAC. The Milan system of reporting is a risk stratication system which can improve the overall effectiveness of reporting and care of patients.

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

BACKGROUND AND PURPOSE: Microstructural white matter abnormalities on DTI using Tract-Based Spatial Statistics at term-equivalent age are associated with cognitive and motor outcomes at 2 years of age or younger. However, neurodevelopmental tests administered at such early time points are insufficiently predictive of mild-moderate motor and cognitive impairment at school age. Our objective was to evaluate the microstructural antecedents of cognitive and motor outcomes at 3 years' corrected age in a cohort of very preterm infants. MATERIALS AND METHODS: We prospectively recruited 101 very preterm infants (

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.

Iatrogenic complications may manifest in a variety of ways. We present the case of an 86-year-old woman who underwent a percutaneous coronary intervention with a drug-eluting stent for non–ST-segment elevation myocardial infarction followed by leadless pacemaker placement through a femoral approach. Her post-procedure course was complicated by new onset high-output heart failure secondary to iatrogenic arteriovenous fistula formation, requiring covered stent placement. (Level of Difficulty: Advanced.), Graphical abstract

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.1%, 8.9%, and 23.9% of patients experienced nodal, metastatic, and overall upstaging, respectively, without histologic confirmation. On multivariable analysis, Gleason grade group (GG) and percent positive core (PPC) on systematic biopsy significantly predict overall upstaging (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.33-3.45; p = 0.002; and OR 1.03, 95% CI 1.01-1.04; p

Purpose This analysis of the pivotal phase 3 HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials. Design Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER. Participants Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis. Methods Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures. Main Outcome Measures Incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes, and brolucizumab treatment after the first IOI-related AE. Results Seventy IOI-related AEs were reported in 49 eyes. Before the onset of first IOI-related AE, eyes received a mean ± standard deviation (SD) of 3.9 ± 2.2 brolucizumab injections. Median time to first IOI-related AE from the last administered brolucizumab injection was 18.0 days (interquartile range, 4.0–29.0 days). Of the 70 AEs, 61 (87.1%) were treated, most with topical corticosteroids; systemic and intraocular corticosteroids were used for 3 AEs each. Overall, inflammation resolved completely in 39 eyes (79.6%), resolved with sequelae in 5 eyes (10.2%), and did not resolve in 5 eyes (10.2%) by end-of-study (EOS). Overall, the mean ± SD best-corrected visual acuity (BCVA) change from baseline to EOS, before AE to the lowest BCVA in 3 months after AE, and from before AE to EOS were −0.84 ± 20.6 , −16.31 ± 17.6, and −0.22 ± 18.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively. Of the 36 eyes (73.5%) that continued with brolucizumab therapy after the first IOI-related AE, 24 completed the trials and 12 discontinued; mean ± SD BCVA change in these eyes was 2.6 ± 17.6, 7.8 ± 13.2, and −7.7 ± 21.3 ETDRS letters, respectively, from baseline to EOS. The remaining 13 eyes (26.5%) were not treated with brolucizumab after first IOI-related AE and showed a mean ± SD BCVA change of −10.4 ± 25.5 ETDRS letters from baseline to EOS. Conclusions Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.

Background Endovascular revascularization (ER) via percutaneous transluminal angioplasty (PTA) and stenting are viable options for revascularization in below-the-knee (BTK) peripheral arterial disease . Two-dimensional angiography has been the standard of practice for estimating vessel size and selecting treatment devices during ER. However, in other vascular territories, intravascular ultrasound (IVUS) offers better visualization of the lumen dimensions. Purpose To compare angiographic and intravascular ultrasound reference vessel (lumen) measurements in below-the-knee peripheral artery interventions. Methods 20 consecutive patients were enrolled in the BTK Calibration study from 2 sites in the United States and Australia. Patients with at least one diseased segment in a native infra-popliteal artery (below-the-knee) and a clinical indication for endovascular therapy (EVT) were included with no limitations with regards to vessel diameter or lesion length. Digital subtraction angiography and intravascular ultrasound imaging were collected pre-and post-percutaneous transluminal angioplasty and images were sent to an independent Core lab for standardized quantitative analysis of the normal-looking reference vessel dimensions when available. The results were presented as least square means with 95% confidence intervals and a p-value of Results The overall (N = 19) mean reference vessel diameter for QVA was 2.98 ± 1.24 vs. 3.47 ± 0.72 for IVUS (mean difference was −0.50, (95% CI: −0.80, −0.20; p = 0.14). As expected in the proximal segments (N = 12), the mean reference vessel diameters were larger: for QVA was 3.17 ± 1.34 vs. 3.55 ± 0.76 in IVUS, (mean difference was −0.38, (95% CI:-0.79,0.03; p = 0.40); while in the distal segments (N = 7), mean reference vessel diameters were smaller: for QVA was 2.64 ± 1.06 vs. 3.33 ± 0.67 in IVUS, (mean difference was −0.69, (95% CI:-1.04,-0.34; p = 0.17). We observed a greater degree of acute gain in cases where the treatment balloon size correlated with the IVUS measured reference size. Conclusion Angiography underestimates infrapopliteal reference vessel lumen size even when quantitatively assessed. Adjunctive IVUS imaging use in guiding BTK procedures could help ensure adequate sizing and possibly impact immediate post-procedure indices.

Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity. Despite an improved understanding of genetic defects in pES, the underlying immunobiology of pES is poorly defined, and characteristic diagnostic immune parameters are lacking. We describe the immune characteristics of 24 patients with pES and compared them with 22 patients with chronic immune thrombocytopenia (cITP) and 24 healthy controls (HCs). Compared with patients with cITP and HC, patients with pES had increased circulating T-follicular helper cells (cTfh), increased T-cell activation, and decreased naïve CD4+ T cells for age. Despite normal or high immunoglobulin G (IgG) in most pES at presentation, class-switched memory B cells were decreased. Within the cTfh subset, we noted features of postactivation exhaustion with upregulation of several canonical checkpoint inhibitors. T-cell receptor β chain (TCR-β) repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HCs. Among patients with pES, those without a known gene defect had a similar characteristic immune abnormality as patients with defined genetic defects. Similarly, patients with pES with normal IgG had similar T-cell abnormalities as patients with low IgG. Because genetic defects have been identified in less than half of patients with pES, our findings of similar immune abnormalities across all patients with pES help establish a common characteristic immunopathology in pES, irrespective of the underlying genetic etiology.

Hepatocellular carcinoma (HCC) continues to have a dismal prognosis, with 5-year survival below 20%. This poor prognosis can be in part attributed to failures along the cancer screening process continuum such as underuse of screening in at risk patients and appropriate treatments for patients with HCC. Better understanding these process failures, and how they compare to those seen in other cancer types, can help inform potential intervention targets and strategies to reduce HCC-related mortality. Herein, we outline a conceptual model with several discrete steps in the HCC screening process continuum including risk assessment, screening initiation, follow-up of screening results, diagnostic evaluation, and treatment evaluation. The conceptual model illustrates how each step in the screening process is prone to delays or failure, resulting in worse outcomes such as late stage diagnosis or poor survival, and how factors at the patient, provider, and health care system levels can contribute to these failures. We compare cancer screening processes for HCC with those employed in breast and colorectal cancer screening to identify opportunities for improvement. The Translational Liver Cancer consortium was recently established by the National Cancer Institute with the goal of improving early detection of HCC. Studies designed to address failures in the HCC screening process continuum will help accomplish this goal.

Trackers on variable terrain can incur electric mismatch losses from row-to-row shading even with backtracking. Tracker terrain loss is the difference between the performance of trackers on horizontal ground and that on variable terrain. SolarFarmer was used to study tracker terrain loss by simulating the Hopewell Friends Solar power plant, which has an average 4% southwest slope. The results yielded a tracker terrain loss of −2% with standard backtracking and slope-aware backtracking completely recovered the 2% loss. By subdividing the site from one to three layouts, the tracker terrain loss decreased 0.5%. The 1-h versus 5-min input data did not significantly affect the tracker terrain loss. This study is a continuation of a previous study that prompted improvements in SolarFarmer’s 3-D tracker shading algorithm. The results of this study demonstrate that SolarFarmer can now be used to calculate tracker terrain loss. A comparison of the SolarFarmer results with a separate uneven terrain model developed by DNV using PVsyst produced similar results.

Background Rotator cuff repair (RCR) is one of the most common elective orthopedic procedures with predictable indications, technique, and outcomes. As a result, this surgery is an ideal choice for studying value. The purpose of this study was to utilize Patient-level value-analysis (PLVA) within the setting of RCR over the one-year episode-of-care. Methods Included patients (n=396) underwent RCR between 2009 and 2016 at a single outpatient orthopedic surgery center. The episode-of-care was defined as one-year following surgery. The Western Ontario Rotator Cuff (WORC) index was collected at both the initial preoperative baseline and the one-year postoperative mark. The total cost-of-care was determined using time-driven activity-based costing (TDABC). Both patient (PLVA) and provider-level value-analysis (pLVA) were performed. Results The average TDABC cost-of-care was derived at $5413.78 ± $727.41 [$5341.92, $5485.64]. At the patient-level, arthroscopic isolated supraspinatus tears yielded the highest value coefficient, 0.82 (ANOVA F-Test, p=0.01). There was a poor correlation between the change in one-year WORC score and the TDABC cost-of-care (r2=0.03). Provider-level value demonstrated significant variation between the 8 evaluated providers (p Conclusion RCR is one of the most common orthopedic procedures, yet the correlations between cost-of-care and patient outcomes is unknown. PLVA quantifies the ratio of functional improvement to the TDABC estimated cost-of-care at the patient-level. This is the first study to apply patient-level value analysis over the first-year episode-of-care. With healthcare transitioning towards value-based delivery, PLVA offers a quantitative tool to measure the value of individual patient care delivery over the entire episode-of-care.

Introduction:Private equity firms have recently acquired several large urology practices in the United States. As little is known about these acquisitions, we sought to characterize trends ...

Background: Semaphorins and plexins are ligands and cell surface receptors that regulate multiple neurodevelopmental processes such as axonal growth and guidance. PLXNA3 is a plexin gene located on the X chromosome that encodes the most widely expressed plexin receptor in fetal brain, plexin-A3. Plexin-A3 knockout mice demonstrate its role in semaphorin signaling in vivo. The clinical manifestations of semaphorin/plexin neurodevelopmental disorders have been less widely explored. This study describes the neurological and neurodevelopmental phenotypes of boys with maternally inherited hemizygous PLXNA3 variants. Methods: Data-sharing through GeneDx and GeneMatcher allowed identification of individuals with autism or intellectual disabilities (autism/ID) and hemizygous PLXNA3 variants in collaboration with their physicians and genetic counselors, who completed questionnaires about their patients. In silico analyses predicted pathogenicity for each PLXNA3 variant. Results: We assessed 14 boys (mean age, 10.7 [range 2 to 25] years) with maternally inherited hemizygous PLXNA3 variants and autism/ID ranging from mild to severe. Other findings included fine motor dyspraxia (92%), attention-deficit/hyperactivity traits, and aggressive behaviors (63%). Six patients (43%) had seizures. Thirteen boys (93%) with PLXNA3 variants showed novel or very low allele frequencies and probable damaging/disease-causing pathogenicity in one or more predictors. We found a genotype-phenotype correlation between PLXNA3 cytoplasmic domain variants (exons 22 to 32) and more severe neurodevelopmental disorder phenotypes (P < 0.05). Conclusions: We report 14 boys with maternally inherited, hemizygous PLXNA3 variants and a range of neurodevelopmental disorders suggesting a novel X-linked intellectual disability syndrome. Greater understanding of PLXNA3 variant pathogenicity in humans will require additional clinical, computational, and experimental validation.

Disparities exist in access to a multitude of screening and diagnostic imaging examinations and procedures. To address these disparities within radiology, emphasis so far has been placed upon diversifying the workforce and formally educating trainees on healthcare disparities. Currently, there is no organized and nationally accepted educational program or content for practicing radiologists specific to diversity and healthcare disparity. This void can be addressed by providing an educational curriculum framework for practicing radiologists based on three key factors: individual efforts, calling for institutional change, and national collaboration. Individual efforts should focus on acknowledging the existence of disparities, understanding the contribution of one's implicit bias in perpetuating disparities, understanding and highlighting issues related to insurance coverage of radiology examinations, and participating in radiology political action committees. These efforts can be facilitated by a consolidated web-based training program for practicing radiologists. To pave the way for meaningful systemic change, the implementation of institutional change like that initiated by the Culture of Safety movement in 2002 is needed. A national collaborative effort initiated by radiology organizations to empower radiologists and recognize positive changes would further provide support. Summary A three-pronged educational framework combining individual radiologist education, institutional change, and national collaboration will enable radiologists to play a role in addressing imaging-related disparities in healthcare.

This report describes the Ion Endoluminal System (Intuitive Surgical, Inc, Sunnyvale, CA) and practices for safe and effective use in patients with small peripheral pulmonary nodules (PPNs).This shape-sensing robotic-assisted bronchoscopy system allows airway visualization and navigation to reach and biopsy small PPNs through a stable platform. The system provides 3-dimensional mapping and visualization of the airways, a flexible and fully articulating 3.5-mm (outer diameter) catheter, a peripheral vision probe, and system-specific biopsy needles.The Ion Endoluminal System was evaluated in an ongoing prospective, multicenter trial including 241 patients with 270 PPNs (largest mean cardinal measurement, 18.8 ± 6.5 mm). Mean time to register and navigate decreased from 10 minutes in the first 10 cases to 7 minutes in the subsequent cases. Asymptomatic pneumothorax occurred in 8 patients (3.3%), 1 (0.4%) with pigtail catheter placement. Two patients (0.8%) experienced airway bleeding; both cases of bleeding resolved within 5 minutes of tamponade.The Ion Endoluminal System's unique shape-sensing technology can be leveraged to facilitate localization and sampling of PPNs and potentially improve diagnostic accuracy.

Background and aims The burden of hepatocellular carcinoma (HCC) is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes along the HCC care continuum. Approach and results We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate patient-reported outcomes (PRO) based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. Conclusions The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population.

Adolescents and young adults (AYAs, 15-39 years) are the largest uninsured population in the Unites States, increasing the likelihood of late-stage cancer diagnosis and poor survival. We evaluated the associations between the Affordable Care Act (ACA), insurance coverage, stage at diagnosis and survival among AYAs with lymphoma. We used data from the California Cancer Registry linked to Medicaid enrollment files on AYAs diagnosed with a primary non-Hodgkin (NHL; n=5959) or Hodgkin (n=5378) lymphoma pre-ACA and in the early and full ACA eras. Health insurance was categorized as continuous Medicaid, discontinuous Medicaid, Medicaid enrollment at diagnosis/uninsurance, other public and private. We used multivariable regression models for statistical analyses. The proportion of AYAs uninsured/Medicaid enrolled at diagnosis decreased from 13.4% pre-ACA to 9.7% with full ACA implementation, while continuous Medicaid increased from 9.3% to 29.6% during this time (P

Introduction Electromagnetic interference (EMI) from left ventricular assist devices (LVADs) can cause implantable cardioverter-defibrillator (ICD) oversensing. We sought to assess the frequency of inappropriate shocks/oversensing due to LVAD-related EMI and prospectively compare integrated (IB) versus dedicated bipolar (DB) sensing in patients with LVADs. Methods Single-center study in LVAD patients with Medtronic or Abbott ICDs between September 2017 and March 2020. We excluded patients that were pacemaker dependent. Measurements were obtained of IB and DB sensing and noise to calculate a signal-to-noise ratio (SNR). Device checks were reviewed to assess appropriate and inappropriate sensing events. Results Forty patients (age 52 ± 14 years, 75% men, 38% ischemic cardiomyopathy) were included with the median time between LVAD implantation and enrollment of 6.7 months [2.3, 11.4 months]. LVAD subtypes included: HeartWare (n=22, 55%), Heartmate II (n=10, 25%), and Heartmate III (n=8, 20%). Over a follow-up duration of 21.6 ± 12.9 months after LVAD implantation, 5% of patients (n=2) had oversensing of EMI from the LVAD (both with HeartWare LVADs and Abbott ICDs) at 4 days and 10.8 months after LVAD implantation. Both patients underwent adjustment of ventricular sensing with resolution of oversensing and no further events over 5 and 15 months of further follow-up. The SNR was similar between IB and DB sensing (50 [29-67] and 57 [41-69], p=0.89). Conclusion ICD oversensing of EMI from LVADs is infrequent and can be managed with reprogramming the sensitivity. There was no significant difference in the R-wave SNR with IB versus DB ICD leads. This article is protected by copyright. All rights reserved.

BACKGROUND: Although immune checkpoint inhibitor-based therapy has improved the outcomes of many patients with metastatic renal cell carcinoma (mRCC), most eventually develop disease progression. Newer agents that modulate immune response can possibly potentiate checkpoint inhibitor therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate immunotherapy. We conducted an investigator-initiated trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC patients, particularly in those previously exposed to immune checkpoint inhibitors. METHODS: Eligible patients had mRCC of any histologic subtype, completed at least one line of prior systemic therapy which could have included prior immunotherapy, and had acceptable end-organ function with ECOG performance status of 0–2. Treatment consisted of nivolumab 240 mg intravenously every 2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade 3 or higher adverse event (AE) attributable to therapy. After identification of the recommended phase 2 dose (RP2D), up to 19 patients were enrolled to an expansion cohort to further evaluate toxicities and any early evidence of efficacy. The primary endpoints of the trial were establishment of RP2D and progression-free survival (PFS). RESULTS: A total of 31 patients were enrolled, 6 to dose level 0, 7 (of which one was not evaluable for DLT) in dose level -1, and 18 in the expansion cohort. Median age was 60 years (range, 36–90), most had clear cell histology (n = 27; 87%), and most had prior immune checkpoint inhibitor therapy (n = 28; 90%). Three patients experienced one DLT each, all in dose level 0 (all Grade 3), namely elevated lipase, hypoalbuminemia, and nausea. No DLTs were seen in dose level –1 which was declared the RP2D. The most common Grade 3 or higher AEs include anemia (n = 5), lymphocyte count decrease (4), nausea (2), and hypotension (2). Of 28 patients evaluable for response, one patient (3.6%) had a complete response, 2 (7.1%) had a partial response, and 11 (39.2%) had stable disease, for an objective response rate of 10.7%(95%CI: 3.7%–27.2%) and a disease control rate of 50%(95%CI: 32.6%–67.4%). All responders had received prior immune checkpoint inhibitor therapy. Median PFS was 2.5 months (95%CI, 1.9 –4.8) while median OS was 9.1 months (95%CI, 6.6 –19.0). CONCLUSIONS: Ibrutinib at a dose of 420 mg orally once daily in combination with nivolumab 240 mg IV every 2 weeks is feasible and tolerable in mRCC patients. No unique immune-related AEs were observed. Anti-tumor activity was seen in patients previously exposed to PD-1 targeted therapy.

Context Many children with advanced cancer are not referred to palliative care despite both professional recommendations to do so and bereaved parental preference for earlier support from sub-specialty palliative care. Objectives To assess the feasibility, acceptability, and impact of an adaptive intervention to address individual and team-level barriers to specialty palliative care referrals. Methods A multiple-method approach assessed feasibility and acceptability among clinicians from pediatric oncology teams at a single institution. Quantitative measures of comfort with palliative care consultations, team cohesion, and team collaboration were conducted before and after the intervention. Number of palliative care consults were examined before, during, and after sessions. Intervention satisfaction surveys and qualitative interviews were conducted after the intervention. Results Twenty-six team members (90% of consented) attended at least one intervention session with 20 (69%) participants completing 75% or more sessions. The intervention was modified in response to participant feedback. After the intervention, participants reported greater team cohesion, comfort discussing palliative care consultation, team collaboration, process satisfaction, and decision satisfaction. Participants agreed that the training was useful, effective, helpful, and worthwhile, that they would use the skills, and that they would recommend the training to other providers. The numbers of palliative care consults increased before intervention sessions were conducted, but did not significantly change during or after the sessions. In the interviews, participants reported overall favorably regarding the intervention with some participants reporting changes in practice. Conclusion An adaptive intervention to reduce barriers to initiating palliative care for pediatric oncology teams is feasible and acceptable.

The upheaval created by a merger can precipitate voluntary employee turnover, causing merging organizations to lose valuable knowledge-based resources and competencies precisely when they are needed most to achieve the merger's integration goals. While prior research has shown that employees' connections to coworkers reduce their likelihood of leaving, we know little about how personal social networks should change to increase the likelihood of staying through the disruptive post-merger integration period. In a pre-post study of social network change, we investigate over 15 million email communications between employees within two large merging consumer goods firms over 2 years. We use insights from network activation theory to posit and find that employees with high formal power (rank) and high informal status (indegree centrality) react to the merger's general uncertainty and threat by developing new social connections in a manner indicative of a network widening response: reaching out and connecting with those in the counterpart legacy organization. We also investigate whether increased personally felt threat in the form of merger-related job insecurity strengthens these relationships, finding it does in the case of high formal power. We also find that employees increasing their cross-legacy social connections is key in reducing those employees' turnover after a merger. Our study suggests that network activation theory can be extended to explain network changes and not simply network cognition. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A retained intracardiac catheter fragment left in situ for 2 years was incidentally found in a patient presenting with worsening heart failure and atrial fibrillation. This case describes the diagnostic evaluation of this rare event, with successful endovascular retrieval and resolution of his symptoms. (Level of Difficulty: Advanced.), Central Illustration

PURPOSE: Colorectal cancer (CRC) incidence in patients younger than 50 years of age, commonly defined as early-onset (EO-CRC), is rising. EO-CRC often presents with distinct clinicopathologic features. However, data on prognosis are conflicting and outcomes with modern treatment approaches for metastatic disease are still limited. MATERIALS AND METHODS: We prospectively enrolled patients with metastatic CRC (mCRC) to a biobanking and clinical data collection protocol from 2014 to 2018. We grouped the cohort based on age at initial diagnosis: < 40 years, 40-49 years, and ≥ 50 years. We used regression models to examine associations among age at initial diagnosis, treatments, clinicopathologic features, and survival. RESULTS: We identified 466 patients with mCRC (45 [10%] age < 40 years, 109 [23%] age 40-49 years, and 312 [67%] age ≥ 50 years). Patients < 40 years of age were more likely to have received multiple metastatic resections (odds ratio [OR], 3.533; P = .0066) than their older counterparts. Patients with EO-CRC were more likely to receive triplet therapy than patients > 50 years of age (age < 40 years: OR, 6.738; P = .0002; age 40-49 years: OR, 2.949; P = .0166). Patients 40-49 years of age were more likely to have received anti-EGFR therapy (OR, 2.633; P = .0016). Despite differences in care patterns, age did not predict overall survival. CONCLUSION: Despite patients with EO-CRC receiving more intensive treatments, survival was similar to the older counterpart. However, EO-CRC had clinical and molecular features associated with worse prognoses. Improved biologic understanding is needed to optimize clinical management of EO-CRC. The cost-benefit ratio of exposing patients with EO-CRC to more intensive treatments has to be carefully evaluated.

Author(s): Parikh-Patel, Arti; Morris, Cyllene R; Kizer, Kenneth W; Wun, Ted; Keegan, Theresa HM | Abstract: IntroductionPrevious research suggests cancer patients living in rural areas have lower quality of care, but population-based studies have yielded inconsistent results. This study examines the impact of rurality on care quality for 7 cancer types in California.MethodsBreast, ovarian, endometrial, cervix, colon, lung, and gastric cancer patients diagnosed from 2004 to 2017 were identified in the California Cancer Registry. Multivariable logistic regression and proportional hazards models were used to assess effects of residential location on quality of care and survival. Stratified models examined the impact of treatment at National Cancer Institute designated cancer centers (NCICCs). Quality of care was evaluated using Commission on Cancer measures. Medical Service Study Areas were used to assess urban/rural status. Data were collected in 2004-2019 and analyzed in 2020.Results989,747 cancer patients were evaluated, with 14% living in rural areas. Rural patients had lower odds of receiving radiation after breast conserving surgery compared to urban residents. Colon and gastric cancer patients had 20% and 16% lower odds, respectively, of having optimal surgery. Rural patients treated at NCICCs had greater odds of recommended surgery for most cancer types. Survival was similar among urban and rural subgroups.ConclusionsRural residence was inversely associated with receipt of recommended surgery for gastric and colon cancer patients not treated at NCICCs, and for receiving recommended radiotherapy after breast conserving surgery regardless of treatment location. Further studies investigating the impact of care location and availability of supportive services on urban-rural differences in quality of care are warranted.

Background Recent evidence suggests an increased incidence of venous thromboembolism among cancer patients of Black race. This study aimed to determine whether Black patients undergoing major oncologic resection experience increased rates of postoperative venous thromboembolism. Methods A cohort study of patients who underwent major oncologic resection was performed using American College of Surgeons National Surgical Quality Improvement Program (2016−2018). Primary outcome was venous thromboembolism within 30 days of surgery. Multivariable logistic regression was performed to evaluate the independent association of race and venous thromboembolism. Results Of 91,707 patients, 67.7% were White, 9.5% Black, and 22.9% other race. Venous thromboembolism rates differed slightly by race: 2.2% among Whites, 2.4% Blacks, and 1.8% other (P = .002). Black patients were older, with higher rates of obesity, diabetes, and smoking. By multivariable logistic regression, risk of venous thromboembolism was lower among patients of other compared with White race (odds ratio 0.83; 95% confidence interval, 0.74–0.94). There was no difference in odds of venous thromboembolism among Black relative to White patients (odds ratio 1.08; 95% confidence interval, 0.93–1.26). When stratified by age, rates of venous thromboembolism were >50% higher among Black patients older than 75 years compared with White patients (odds ratio 1.54; 95% confidence interval, 1.17–2.03). Conclusion Despite evidence that Black patients with cancer experience higher rates of venous thromboembolism, they do not appear to have an increased risk in the postoperative period.

Purpose: We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal cancer. Patients and Methods: The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX × 8 followed by chemoradiation. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of circulating tumor DNA (ctDNA) to treatment response. Results: From October 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all eight planned cycles, and 88% completed chemoradiation. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% intention to treat). Tumor-specific mutations were identified in 21 (84%) patients, of whom 4 and 17 patients had undetectable and detectable ctDNA at baseline, respectively. Presence of detectable post-chemoradiation ctDNA (P = 0.004) and/or postoperative ctDNA (P = 0.045) were associated with disease recurrence. Conclusions: Here we show neoadjuvant FOLFIRINOX followed by chemoradiation for locally advanced gastroesophageal cancer is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence. See related commentary by Catenacci, p. 6281

PURPOSE Machine learning models developed from electronic health records data have been increasingly used to predict risk of mortality for general oncology patients. But these models may have suboptimal performance because of patient heterogeneity. The objective of this work is to develop a new modeling approach to predicting short-term mortality that accounts for heterogeneity across multiple subgroups in the presence of a large number of electronic health record predictors. METHODS We proposed a two-stage approach to addressing heterogeneity among oncology patients of different cancer types for predicting their risk of mortality. Structured data were extracted from the University of Pennsylvania Health System for 20,723 patients of 11 cancer types, where 1,340 (6.5%) patients were deceased. We first modeled the overall risk for all patients without differentiating cancer types, as is done in the current practice. We then developed cancer type–specific models using the overall risk score as a predictor along with preselected type-specific predictors. The overall and type-specific models were compared with respect to discrimination using the area under the precision-recall curve (AUPRC) and calibration using the calibration slope. We also proposed metrics that characterize the degree of risk heterogeneity by comparing risk predictors in the overall and type-specific models. RESULTS The two-stage modeling resulted in improved calibration and discrimination across all 11 cancer types. The improvement in AUPRC was significant for hematologic malignancies including leukemia, lymphoma, and myeloma. For instance, the AUPRC increased from 0.358 to 0.519 (∆ = 0.161; 95% CI, 0.102 to 0.224) and from 0.299 to 0.354 (∆ = 0.055; 95% CI, 0.009 to 0.107) for leukemia and lymphoma, respectively. For all 11 cancer types, the two-stage approach generated well-calibrated risks. A high degree of heterogeneity between type-specific and overall risk predictors was observed for most cancer types. CONCLUSION Our two-stage modeling approach that accounts for cancer type–specific risk heterogeneity has improved calibration and discrimination than a model agnostic to cancer types.

Introduction: Lymphnodes are common site of metastases for different cancers. Thus, clinical recognition and urgent diagnosis of palpable lymphadenopathy is of paramount importance; specially to differentiate between inflammatory lesions from neoplastic lesions. Fine needle aspiration cytology (FNAC) of the lymph node is a simple diagnostic tool to diagnose suspected and unsuspected lymph node malignancy.Aims–To find out the role of FNAC in the diagnosis of metastatic lesions of lymphnode and whenever possible, for typing of tumor.Material &Method– A total 900 patients, who presented with lymphadenopathy were studied at AMC MET medical College and L.G hospital, Ahmedabad, Gujarat for a period of 2 years. FNAC of enlarged lymphnode was performed and stain with hematoxylin and eosin.Results- Out of total 900 cases studied, 785 were benign and 95 were malignant lesions. Twenty cases were inconclusive. Among the malignant lesions, 80 cases were found to be metastatic lesions. Maximum numbers of metastatic lesions were found in cervical lymphnodes and metastatic squamous cell carcinoma was the most common lesion followed by metastatic adenocarcinoma.Conclusion- FNAC is a simple, rapid, accurate and non-expensive diagnostic technique which can be used for the initial diagnosis of metastatic lymphadenopathy. It can give significant clue to detect the primary site of the tumor in cases with hidden malignancy, who are presented with metastatic lymphadenopathy as an initial sign. Therefore, FNAC is a useful tool in diagnosing metastatic lesion of lymphnodes.