Search

Cooling energy demand is sensitive to urban form and socioeconomic characteristics of cities. Climate change will impact how these characteristics influence cooling demand. We use random forest machine learning methods to analyze the sensitivity of cooling demand in Chicago, IL, to weather, vegetation, building type, socioeconomic, and control variables by dividing census tracts of the city into four groups: below-Q1 income–hot days; above-Q1 income–hot days; below-Q1 income–regular days; and above-Q1 income–regular days. Below-Q1 census tracts experienced an increase in cooling demand on hot days while above-Q1 census tracts did not see an increase in demand. Weather (i.e. heat index and wind speed) and control variables (i.e. month of year, holidays and weekends) unsurprisingly had the most influence on cooling demand. Among the variables of interest, vegetation was associated with reduced cooling demand for below-Q1 income on hot days and increased cooling demand for below-Q1 income on regular days. In above-Q1 income census tracts building type was the most closely associated non-weather or control variable with cooling demand. The sensitivity of cooling demand for below-Q1 income census tracts to vegetation on hot days suggests vegetation could become more important for keeping cities cool for low-income populations as global temperatures increase. This result further highlights the importance of considering environmental justice in urban design.

EVOH (Ethylene-Vinyl Alcohol) materials are widely used in automotive applications in multi-layer fuel lines and tanks owing to their excellent barrier properties to aromatic and aliphatic hydrocarbons. These barrier materials are essential to limit environmental fuel emissions and comply with the challenging requirements of fast changing international regulations. Nevertheless, the measurement of EVOH permeability to model fuel mixtures or to their individual components is particularly difficult due to the complexity of these systems and their very low permeability, which can vary by several orders of magnitude depending on the permeating species and their relative concentrations. This paper describes the development of a new automated permeameter capable of taking up the challenge of measuring minute quantities as low as 1 mg/(m2.day) for partial fluxes for model fuel mixtures containing ethanol, i-octane and toluene at 50°C. The permeability results are discussed as a function of the model fuel composition and the importance of EVOH preconditioning is emphasized for accurate permeability measurements. The last part focuses on the influence of EVOH conditioning on its mechanical properties and its microstructure, and further illustrates the specific behavior of EVOH in presence of ethanol oxygenated fuels. The new metrology developed in this work offers a new insight in the permeability properties of a leading barrier material and will help prevent the consequences of (bio)ethanol addition in fuels on environmental emissions through fuel lines and tanks.

Objectives: To synthesize the current evidence of maternal point-of-care ultrasound (POCUS) in obstetrics. A scoping review was conducted using PubMed, Clinicaltrials.gov, and the Cochrane library from inception through October 2023., Methods: Studies were eligible for inclusion if they described the use of POCUS among obstetric or postpartum patients. Two authors independently screened all abstracts. Quantitative, qualitative, and mixed-methods studies were eligible for inclusion. Case reports of single cases, review articles, and expert opinion articles were excluded. Studies describing detailed maternal nonobstetric sonograms or maternal first trimester sonograms to confirm viability and rule out ectopic pregnancy were also excluded. Data were tabulated using Microsoft Excel and summarized using a narrative review and descriptive statistics., Results: A total of 689 publications were identified through the search strategy and 12 studies met the inclusion criteria. Nine studies evaluated the use of lung POCUS in obstetrics in different clinical scenarios. Lung ultrasound (LUS) findings in preeclampsia showed an excellent ability to detect pulmonary edema (area under the receiver operating characteristic 0.961) and findings were correlated with clinical evidence of respiratory distress (21 of 57 [37%] versus 14 of 109 [13%]; P = .001). Three studies evaluated abdominal POCUS, two of the inferior vena cava (IVC) to predict postspinal anesthesia hypotension (PSAH) and fluid receptivity and one to assess the rate of ascites in patients with preeclampsia. Patients with PSAH had higher IVC collapsibility (area under the curve = 0.950, P < .001) and, in patients with severe preeclampsia, there is a high rate of ascites (52%) associated with increased risk of adverse outcomes. There were no studies on the use of subjective cardiac POCUS., Conclusion: POCUS use in the management of high-risk obstetrics has increased. LUS has been the most studied modality and appears to have a potential role in the setting of preeclampsia complicated by pulmonary edema. Cardiac and abdominal POCUS have not been well studied. Trials are needed to evaluate its clinical applicability, reliability, and technique standardization before widespread use., (© 2024 American Institute of Ultrasound in Medicine.)

The immunodetection of NUT protein is a reliable tool to identify NUT carcinoma, a rare and still underdiagnosed tumor entity. The technique was implemented in 2017 in our department, a tertiary reference center with a large recruitment in all tumor types, including head and neck and thoracic tumors. We evaluated its use over a 6-year period (2017-2022) to (a) describe the indications for the technique, (b) determine the number of NUT carcinomas detected and confirmed by Fluorescence in situ hybridization, and (c) describe briefly the characteristics of these tumors. Over the study period, 382 NUT immunodetections were performed; the annual number of requests varied from 45 to 83. All 21 pathologists of the department made at least one request (range: 1 to 94; annual mean: 18.2). 54.7% of immunodetections were performed for internal cases, 37% for cases submitted for consultation, and 8.3% for cases submitted for confirmation of a suspected diagnosis. The main indications were poorly differentiated tumors of the head and neck region (39%) and the thorax (19.6%), and difficult-to-classify soft tissue tumors (11.8%). Twelve cases of NUT carcinoma were detected by immunohistochemistry and confirmed by Fluorescence in situ hybridization. Seven were from the head and neck region (4.7% of the tumors tested), 4 from lung or mediastinum (5.3%), 1 from an unknown primary at the time of diagnosis. In conclusion, the implementation of NUT immunodetection in the daily workflow of a pathology department improves the detection of NUT carcinoma. This becomes essential with the emergence of potential targeted therapies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to assess the effectiveness of prophylactic ureteral stent placement for the prevention of genitourinary tract injury at the time of cesarean hysterectomy for placenta accreta spectrum. The secondary objectives were to assess mean blood loss, operative time, number of packed red blood cells transfused, and rates of urinary tract infection among patients undergoing cesarean hysterectomy for placenta accreta spectrum with and without prophylactic ureteral stent placement., Data Sources: The search was performed using PubMed, Cochrane Library, and ClinicalTrials.gov from inception to February 2022 to December 2022. The protocol for this review was registered with the International Prospective Register of Systematic Reviews before data collection (registration number: CRD42022372817)., Study Eligibility Criteria: All studies that examined differences in the rate of genitourinary tract injury among women undergoing cesarean hysterectomy for prenatally suspected placenta accreta spectrum with and without placement of prophylactic ureteral stents were included. Genitourinary injury was defined as cystotomy, ureteral injury, and/or bladder fistula. Cases of both intentional and unintentional genitourinary injuries were included in the analysis., Methods: For all studies meeting the inclusion criteria, the following data were extracted: number of included patients, maternal demographic information, obstetrical history, type of invasive placentation, placement of stents (yes or no), type of stent placed, blood loss, operative time, genitourinary tract injury, and urinary tract infection. Pooled data analysis was completed using the Review Manager (version 5.3; Nordic Cochrane Centre, Copenhagen, Denmark; Cochrane Collaboration, 2014). The summary measures were reported as summary relative risk or as summary mean difference. The quality and risk of biases of the included studies were assessed according to the Newcastle-Ottawa Scale., Results: Overall, 9 studies, including 848 patients, fulfilled our inclusion criteria and were included in our analysis. Moreover, 523 patients (61.7%) had prophylactic ureteral stents placed, and 325 patients (38.3%) did not. Genitourinary injury occurred in 138 of 523 patients (26.4%) in the ureteral stent group vs 83 of 325 patients (25.5%) in the no ureteral stent group (relative risk, 0.94; 95% confidence interval, 0.74-1.20). The mean number of packed red blood cells transfused did not differ between the 2 groups. The pooled analysis demonstrated decreased blood loss among patients who received prophylactic ureteral stents, with a mean difference of 392 mL (95% confidence interval, 52.74-738.13)., Conclusion: Our systematic review and meta-analysis demonstrated no difference in the rates of genitourinary tract injury with the use of prophylactic ureteral stent placement among cases of prenatally suspected placenta accreta spectrum undergoing cesarean hysterectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Computed tomography angiography (CTA) and invasive coronary angiography (ICA) are routinely performed before transcatheter aortic valve replacement (TAVR) to assess aortic root anatomy and screen for coronary artery disease (CAD), respectively., Objectives: This study explored the efficacy of CTA as a screening tool for significant proximal CAD before TAVR., Methods: With proper ethical oversight, patients undergoing TAVR at Cleveland Clinic with a preprocedural CTA and invasive coronary angiography (ICA), and no prior percutaneous intervention, were identified from 2015 to 2021. Blinded to ICA results, the authors reviewed the left main, proximal left anterior descending coronary artery, proximal left circumflex coronary artery, and proximal right coronary artery by CTA coronary reconstruction to assess for nonsignificant stenosis (0% to 49%), moderate stenosis (50% to 69%), and severe stenosis (≥70%). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen Kappa statistic were analyzed., Results: 2,217 patients (53.4% male, age 79.2 ± 8.5 years) met inclusion criteria. CTA evaluation revealed a sensitivity of 90%, specificity of 92%, PPV of 74%, and NPV of 97% for detecting ≥50% stenosis. Using a ≥70% stenosis cutoff, evaluation revealed a sensitivity of 91%, specificity of 97%, PPV of 83%, and NPV of 99%. Assessment of bypass graft patency revealed a sensitivity of 86%, specificity of 97%, PPV of 84%, and NPV of 98%. Cohen Kappa analysis indicated substantial to near perfect agreement between pre-TAVR CTA and ICA., Conclusions: Pre-TAVR CTA has a high NPV for high-grade proximal stenosis of each coronary artery. As a result, CTA can be used as a screening tool to rule out significant proximal CAD in patients undergoing TAVR., Competing Interests: Funding Support and Author Disclosures This study was supported by the Department of Cardiovascular Medicine and the Heart, Vascular, and Thoracic Institute at Cleveland Clinic. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Key molecular alterations (MA) of neuroendocrine neoplasm (NEN) of various grade/primaries have been described but the applicability of molecular profiling (MP) for precision medicine in NEN remains to be demonstrated., Methods: We conducted a retrospective study of all patients with metastatic NEN who had MP on tumour tissue at Gustave Roussy. The primary objective was to assess the clinical applicability of MP by evaluating the growth modulator index (GMI) as the primary end-point., Results: MPs were obtained in 114 out of 156 eligible patients, including 12% NET-G1, 42% NET-G2, 13% NET-G3 and 35% neuroendocrine carcinoma (NEC). Primary sites were lung/thymus (40%), pancreas (19%), gastro-intestinal (16%), head&neck (10%), unknown (10%) and others (10%) with synchronous metastases in 61% of the patients. Most frequent MA were: MEN1 (25%), PTEN (13%), TP53 (11%) and TSC2 (9%), in neuroendocrine tumour (NET), and TP53 (50%) and RB1 (18%) in NEC. ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) classification of these MA were: I(5%), III(20%), IV(23%), X(27%); a putative actionable MA was identified in 48% patients. Median TMB was 5.7 Mut/Mb, with 3 TMB > 10 and 1 MSI NET. No MA was found in 26% patients. Molecularly matched treatment was administered to 19 patients (4 NEC, 15 NET): immunotherapy (n = 3), tipifarnib (n = 1), NOTCHi (n = 1), EGFRi (n = 2), HER2i (n = 1) and everolimus (n = 11). Overall, 67% of patients had a clinical benefit defined as a GMI over 1.3 with a 78% disease control rate., Conclusion: We report 48% of NEN with a putative actionable MA of which 35% received molecularly matched treatment, with a clinical benefit in 67% of the cases., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EB received honorarium for board participation and grants from HRA. TSL: consultant: GE, Terumo, quantum surgical (none related to this paper) AI: Research grant (AstraZeneca, Bayer, BMS, Merck, MSD, Pharmamar) DP: reports receiving consulting, advisory role, or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Janssen, and AbbVie; reports receiving honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Janssen, and AbbVie; clinical trial research as principal or co-investigator (institutional financial interests) for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, Janssen, and AbbVie; and travel, accommodations, and expenses from AstraZeneca, Roche, Novartis, and Pfizer. ARB: Personal: Advisory board: Sanofi, Janssen. As part of the Drug Development Department (DITEP) = Principal/sub-Investigator of Clinical Trials for Abbvie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Astex Pharmaceuticals, Astra Zeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Casi Pharmaceuticals, Inc, Celgene Corporation, Cellcentric, Chugai Pharmaceutical Co, Cullinan-Apollo, Curevarc, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Incyte Corporation, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Janssen R&D LLC, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Genomics, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre Medicament, Relay Therapeutics, Inc, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Transgene S.A, Turning Point Therapeutics, XencorResearch Grants from Astrazeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi Non-financial support (drug supplied) from Astrazeneca, BMS, Boringher Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche MD: declares conflicts of interest with Merck Serono, MSD, AMGEN, Roche, Bayer, Ipsen, Pfizer, Servier, Pierre Fabre, HalioDx, Lilly, Sanofi, BMS. JH: declares grant/research support from Novartis and consultant for IPSEN, Lilly, Roche, Pharma Mar and Eisai Other authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: Little data exist about the natural history and disease progression of secondary mitral regurgitation (SMR). We sought to study the temporal progression of left-sided volumes and functions in patients who progress to develop severe SMR., Methods and Results: We screened patients with chronic severe SMR who had at least one previous transthoracic echocardiography showing non-severe MR. Unsupervised phenotypic clustering based on baseline and rate of change in left ventricular (LV) and left atrial (LA) volumes, ejection fraction (EF), and MR severity progression identified two different phenotypes. We then compared them in terms of clinical characteristics, mechanistic and anatomical features, management, and outcomes. A total of 257 patients were included. Cluster 1 started with lower EF and LA strain and higher LV and LA volumes compared with Cluster 2, with a slower progression into severe SMR. At the onset of severe MR, Cluster 2 still had higher EF, lower LV volumes, but similar LA volumes and strain, and less proportionate SMR, compared with Cluster 1. They also had higher tenting height and more compensatory leaflet growth. On follow-up, Cluster 1 had more ventricular-directed therapies, whereas Cluster 2 received more mitral valve interventions. While the heart failure burden was higher in Cluster 1, there was no difference in mortality rates., Conclusion: Based on disease progression, two distinct progression patterns of SMR exist, having different anatomical and mechanistic features with variation in management and outcomes., Competing Interests: Conflict of interest: There are no conflicts of interest to disclose for all of the authors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

"Juvenile-like (hyperplastic/inflammatory) mucosal polyp" is a term proposed for rare benign mesenchymal lesions of the gastro-intestinal tract so far reported only in patients with type 1 neurofibromatosis (NF1). We report here a first sporadic case of NF1 -associated mucosal inflammatory polyp of the colon. The diagnosis was made in a 53-year old female patient with a large polypoid tumor of the cecum. The lesion was predominantly mucosal, made of fibroblast-like cells associated with inflammatory infiltrates rich in eosinophils and containing entrapped, distorted epithelial glands, responsible for the juvenile-like appearance. Whole exome sequencing showed a pathogenic variant of NF1 . The patient had no evidence of NF1; no NF1 mutation was detected in normal tissues. Our observation may support the existence of juvenile-like inflammatory polyps associated with NF1 alterations, either germline or somatic. This justifies to test NF1 in difficult-to-classify gastrointestinal mesenchymal tumors.

Neuroendocrine carcinomas (NEC) are aggressive malignant diseases. Etoposide-based rechallenge (EBR) and the prognostic role of RB transcriptional corepressor 1 (RB1) status in second-line chemotherapy (2L) have not been studied. The objectives of this study were to report the results of 2L including EBR as well as prognostic factors in a national retrospective multicentre study. NEC patients treated with 2L and further, with tissue samples available, were included. RB1 status and morphological classification were reviewed centrally. Among the 121 NEC patients (40% female, median age 61 years) included, there were 73 small-cell NEC (60%), 34 large-cell NEC (28%) and 14 NEC (not otherwise specified, 12%). Primary sites were lung (39%), gastroenteropancreatic (36%), other (13%) and unknown (12%). Median Ki-67 index was 80%. Median progression-free survival (PFS) and overall survival (OS) under 2L were 2.1 and 6.2 months, respectively. No difference was observed between patients who received an 'adenocarcinoma-like' or a 'neuroendocrine-like' 2L or according to the RB1 status. Thoracic NEC primary was the only adverse prognostic factor for OS. EBR, administered to 31 patients, resulted in a 62% disease control rate with a median PFS and OS of 3.2 and 11.7 months, respectively. In the 94 patients with a relapse-free interval of ≥3 months after first-line platinum-etoposide chemotherapy, the median OS was 12 months in patients who received EBR as compared to 5.9 months in patients who did not (P = 0.043). EBR could be the best 2L option for patient with initial response to first-line platinum-etoposide lasting at least 3 months. RB1 status does not provide prognostic information in this setting.

The decision by pulmonary embolism response teams (PERTs) to utilize anticoagulation (AC) with or without systemic thrombolysis (ST) or catheter-directed therapies (CDT) for pulmonary embolism (PE) is a balance between the desire for a positive outcome and safety. Our primary aim was to develop a predictive model of in-hospital mortality for patients with high- or intermediate-risk PE managed by PERT while externally validating this model. Our secondary aim was to compare the relative safety and efficacy of ST and CDT in this cohort. Consecutive patients hospitalized between June 2014 and January 2020 at the Cleveland Clinic Foundation and The University of Rochester with acute high- or intermediate-risk PE managed by PERT were retrospectively evaluated. Groups were stratified by treatment strategy. The primary outcome was in-hospital mortality, and secondary outcome was major bleeding. A logistic regression model to predict the primary outcome was built using the derivation cohort, with 100-fold bootstrapping for internal validation. External validation was performed and the area under the receiver operating curve (AUC) was calculated. Of 549 included patients, 421 received AC alone, 71 received ST, and 64 received CDT. Predictors of major bleeding include ESC risk category, PESI score, hypoxia, hemodynamic instability, and serum lactate. CDT trended towards lower mortality but with an increased risk of bleeding relative to ST (OR = 0.42; 95% CI [0.15, 1.17] and OR = 2.14; 95% CI [0.9, 5.06] respectively). In the multivariable logistic regression model in the derivation institution cohort, predictors of in-hospital mortality were age, cancer, hemodynamic instability requiring vasopressors, and elevated NT-proBNP (AUC = 0.86). This model was validated using the validation institution cohort (AUC = 0.88). We report an externally-validated model for predicting in-hospital mortality in patients with PE managed by PERT. The decision by PERT to initiate CDT or ST for these patients had no impact on mortality or major bleeding, yet the long-term efficacy of these interventions needs to be elucidated., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Atrial dilation is known to be a poor prognostic indicator. However, its clinical, functional and prognostic implications have not been thoroughly explored in secondary mitral regurgitation (SMR). We sought to describe the implications of severe atrial dilation (SAD) in SMR., Methods: We included all adult patients with severe SMR due to left ventricle dysfunction (with no organic mitral valve disease) who underwent transthoracic echocardiography between January 2012 and March 2021 at our institution. The concomitant presence of severe left atrial (LA) dilation (>48 mL/m 2 ) defined SADMR (SAD in SMR), and these patients were compared with those without SAD., Results: A total of 2011 patients were included (mean age 70% and 41% females), with 71% having SADMR. MR severity and ejection fraction were similar between both groups. Patients with SADMR were older, less females and had more diabetes, but similar rates of atrial fibrillation. Mechanistically, they had lower A wave velocity (0.61 vs 0.72 cm/sec, p<0.001) and more impaired LA reservoir strain (9.7% vs 15.5%, p<0.001). Geometrically, SADMR had shallower leaflets' angulations, lower tenting height, larger annuli and smaller leaflet length/annular diameter ratios (all p<0.001). They underwent fewer MV interventions, although these were associated with better outcomes (log-rank p<0.001). Over the study period, SAD was an independent predictor of mortality (HR 1.26, p=0.04)., Conclusion: SADMR is associated with specific mechanistic and functional alterations and confers a worse prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aortic pseudoaneurysms can commonly be caused by previous thoracic surgery, trauma, and infection, quickly becoming life-threatening if ruptured. This pathology is typically asymptomatic and incidentally found on imaging; however, few cases have outlined hemoptysis as a presenting symptom for aortic pseudoaneurysms. Traditionally, management of these patients included surgical correction; however, percutaneous approaches have emerged as a safe alternative, helping to reduce the risk of morbidity and mortality associated with surgical correction. This report seeks to describe a case in which hemoptysis was the symptom unveiling the finding of a thoracic ascending aortic pseudoaneurysm and the use of an Amplatzer atrial septal defect (ASD) occlusion device as a viable option to safely resolve the disease process., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Nicholas P. Kondoleon et al.)

Purpose: Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC., Patients and Methods: Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm 2 , Ki67 proliferative index ≥ 5%, or tumor necrosis., Results: Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; P < .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; P = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; P = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers., Conclusion: This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis., Competing Interests: Eric BaudinConsulting or Advisory Role: Ipsen, Novartis, AAA HealthCare, Pfizer, Hutchison MediPharmaResearch Funding: Pfizer (Inst), Novartis (Inst), HRA Pharma (Inst) James A. FaginConsulting or Advisory Role: Loxo OncologyPatents, Royalties, Other Intellectual Property: 3. MSK Ref. SK 2014-024-03 Title: Treatment of H-RAS-Driven Tumors. Application Number: 15/305,788 Dana HartlConsulting or Advisory Role: Medtronic Fedaa NajdawiEmployment: PathAINo other potential conflicts of interest were reported.

Introduction and Aim: Neuroendocrine carcinomas (NECs) are aggressive malignant diseases. Platinum-etoposide (PE) combination is the standard first-line treatment, whatever the primary location. The NEC score and also retinoblastoma protein (Rb) status have been suggested to be predictive/prognostic factors in NEC. The primary objective of our multicentric retrospective study was to evaluate the prognostic relevance of the NEC score and Rb status, assessed by immunohistochemistry in PE-treated patients with metastatic NEC., Methods: Seven centres participated. The inclusion criteria were NEC, whatever the primary site, metastatic stage, first-line treatment with PE and tissue samples available. Rb status was determined centrally., Results: We report multicentric data from 185 metastatic patients (37% women, median age 63). There were 108 small-cell NECs (SCNECs, 58.4%), 50 large-cell NECs (LCNECs, 27%) and 27 not otherwise specified NECs (nosNECs, 14.6%). The primary sites were the thorax (37%), gastroenteropancreatic sites (38%), unknown (15%) and other (9%). The mean Ki-67 index was 76% (range 20-100). Rb status was interpretable in 122 cases. Rb expression was lost in 74% of the cases: 84% of SCNEC vs. 60% and 63% of LCNEC and nosNEC, respectively (p = 0.016). Objective response was seen in 70% of SCNEC, 45% of LCNEC and 48% of nosNEC (p < 0.001) and in 62% of Rb-negative tumours vs. 46% of Rb-positive tumours (p = 0.3). There was no difference in median progression-free survival or overall survival (OS) as per Rb status. Age, NEC score and response to chemotherapy were the main factors associated with OS in our cohort., Conclusion: In our series, Rb status had no prognostic impact in PE-treated metastatic patients with NEC, whereas age, NEC score and response to chemotherapy were the main factors associated with OS., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Sarcoma with EWSR1-PATZ1 gene fusion is an exceedingly rare and newly described Ewing-like sarcoma harboring EWSR1 rearrangements involving fusion partners other than ETS family genes. The clinical, histopathologic and immunophenotypic features of cases reported in literature are fairly diverse and not specific. We report a new case report posing real challenges for histological and molecular diagnosis., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Few data are available concerning human papillomavirus (HPV) in early esophageal squamous cell carcinoma (ESCC) in Western population. Our study intended to determine the prevalence of HPV infection and the histological characteristics in such early tumors. A monocentric and retrospective study was conducted including 86 patients with early ESCC treated by endoscopic resection or esophagectomy, from 2012 to 2018. Histopathological prognostic criteria were evaluated. Immunohistochemistry for p16 and p53 and an HPV mRNA in situ hybridization were performed. The tumors were composed of 25 (29%) in situ carcinomas, 21 (24%) intramucosal carcinomas, and 40 (47%) submucosal carcinomas, of which 34 had a deep infiltration (> 200 μm). Emboli, present in 12 cases, were associated with deep infiltration. P16-positive ESCC accounted for 21% of the patients. It was not correlated with active HPV infection as no cases were found to be positive in RISH analysis for RNA detection of this virus. However, there was a correlation between p16 expression and alcohol or tobacco consumption. The only histopathological criterion correlated with p16 positivity was marked inflammatory infiltrate. Local or distant neoplastic recurrence occurred in 25% of patients. Overall survival was 95.8% and local or metastatic recurrence-free survival was 75%. There was a correlation between positive resection margins and tumor recurrence. In contrast to oropharynx carcinoma, our study showed that ESCC were not associated with an active HPV infection, highlighting the negligible role of this virus in early ESCC carcinogenesis in the Western world.

Objectives: Although life-threatening emergencies for cancer patients are relatively rare, cancer patients often seek care in the emergency department. The use of emergency medical service (EMS) by these patients is not well studied. The aim of this study was to investigate the characteristics of cancer patients who present to the emergency department (ED) for care and compare characteristics of patients transported by EMS vs. those transported by private vehicle. Methods : Our retrospective cohort study was conducted in an EMS system with 21,070 annual transports and an academic ED with 129,263 annual visits. Our study consisted of patients with a new diagnosis of cancer between January 1 and July 1, 2015 who subsequently presented to the ED between January 1, 2015 and July 1, 2017. Study variables included patient demographics, mode of ED arrival, cancer type and treatment, patient clinical characteristics, and disposition. To describe differences in patient characteristics of EMS vs. private vehicle transport, we report variable frequencies and stratified them by mode of transport. Results: Of the 2,727 patients with a new diagnosis of cancer, 1,303 (47.8%) presented to the ED with a total of 3,590 visits in 30 months. EMS transported 22% of cancer patients to the ED vs. 78% transported by private vehicle. Thus, cancer patients would make up approximately 1.5% (781/52,675) of all EMS transports during the study period. For those transported by EMS, the most common chief complaints were respiratory distress (16.0%), pain (15.4%), and neurological symptoms (12.6%). Patients with cancer of the lung/respiratory tract (21.5%), upper GI (12.4%), and central nervous system (CNS) (11.0%) were most frequently transported by EMS. Older age, presence of CNS cancer, presentation with neurological or cardiovascular complaints, and higher acuity were significantly associated with EMS transport to ED, while gender and pain severity were not. Patients transported by EMS were more likely to be hospitalized and for greater than 2 days ( p  < 0.0001). Conclusions: Cancer patients frequently seek emergency care after initial diagnosis, most commonly present for symptom relief, and are often admitted. Patients transported by EMS are more likely to be admitted and for longer periods of time.

The thyroid is an unusual site for metastasis, and metastases in a preexisting primary thyroid tumor are exceedingly rare. We report the first case of a patient with colon cancer who was diagnosed with a thyroid metastasis in a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). A 55-year-old male patient presented with a 19 mm thyroid nodule in the inferior left lobe. It was EU-TIRADS 5 on echography and suspicious of papillary thyroid carcinoma (Bethesda V) on cytology. Macroscopically, the nodule was fleshy and completely encapsulated. At frozen section examination, it demonstrated follicular architecture with mild atypia. Inside the nodule was a focus of tumor with glandular architecture, marked cellular atypia, and necrosis. These findings suggested a secondary malignancy. The patient's medical history was significant for metastatic colon cancer. The definitive histology showed features of metastatic colorectal adenocarcinoma within a NIFTP. Immunohistochemical studies were confirmatory with expression of CDX2 and CK20 localized to the metastatic focus. PAX8, TG, and TTF were negative in the metastasis but expressed in the surrounding NIFTP lesion. The possibility of a metastasis to the thyroid may be considered in patients presenting with a solitary thyroid nodule with a previous history of cancer. Metastatic colorectal adenocarcinoma occurring in a NIFTP has never been reported before now, although metastases to the thyroid are documented in the literature. In cases of a secondary malignancy to the thyroid, treatment is controversial.

Objective: This study was aimed to evaluate the prevalence of sonographic markers for placenta accreta spectrum (PAS) in pregnancies at low-risk for PAS., Study Design: Pregnant women at low-risk for PAS presenting for routine second trimester ultrasound who enrolled in the study were evaluated prospectively for sonographic markers of PAS during two ultrasounds at 18 to 24 and 28 to 34 weeks. Frequencies of PAS markers were compared between the second and third trimester and between those with and without prior cesarean deliveries (CD)., Results: Overall, 174 women were included. Several markers were seen frequently in the second trimester: vascular cervical invasion (57%), lacunae (46%), subplacental hypervascularity (37%), and irregularity of the posterior bladder wall (37%). Other markers were seen infrequently or not at all: loss of the retroplacental clear zone, uterovesical interface < 1 mm, bridging vessels, placental bulge or focal exophytic mass. Frequencies of markers did not differ between women with and without prior CD. Lacunae were larger and more numerous in the third trimester. Two or more PAS markers were observed in 98% of second trimester ultrasounds., Conclusion: Several PAS sonographic markers occur commonly in low-risk pregnancies. In the absence of risk factors, the independent predictive value of these markers is questionable., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

This overview presents nomenclature and serology information on human leucocyte antigens, or HLA molecules, which are encoded by a cluster of genes linked on the short arm of chromosome 6. This region is known as the major histocompatibility complex and codes for class I and class II molecules, which are distinguished from each other based upon their structure, tissue distribution, and source of peptide antigen, as well as upon their interactions with T cell subsets. © 2017 by John Wiley & Sons, Inc., (Copyright © 2017 John Wiley & Sons, Inc.)

Objectives: This study aims to validate the feasibility and accuracy of a new standardized six-step approach to the performance of the focused basic obstetric ultrasound examination, and compare the new approach to the regular approach performed in the scheduled obstetric ultrasound examination., Study Design: A new standardized six-step approach to the performance of the focused basic obstetric ultrasound examination, to evaluate fetal presentation, fetal cardiac activity, presence of multiple pregnancy, placental localization, amniotic fluid volume evaluation, and biometric measurements, was prospectively performed on 100 pregnant women between 18(+0) and 27(+6) weeks of gestation and another 100 pregnant women between 28(+0) and 36(+6) weeks of gestation. The agreement of findings for each of the six steps of the standardized six-step approach was evaluated against the regular approach., Results: In all ultrasound examinations performed, substantial to perfect agreement (Kappa value between 0.64 and 1.00) was observed between the new standardized six-step approach and the regular approach., Conclusion: The new standardized six-step approach to the focused basic obstetric ultrasound examination can be performed successfully and accurately between 18(+0) and 36(+6) weeks of gestation. This standardized approach can be of significant benefit to limited resource settings and in point of care obstetric ultrasound applications., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Left and bilateral cardiac sympathetic denervation (CSD) have been shown to reduce burden of ventricular arrhythmias acutely in a small number of patients with ventricular tachyarrhythmia (VT) storm. The effects of this procedure beyond the acute setting are unknown., Objective: The purpose of this study was to evaluate the intermediate and long-term effects of left and bilateral CSD in patients with cardiomyopathy and refractory VT or VT storm., Methods: Retrospective analysis of medical records for patients who underwent either left or bilateral CSD for VT storm or refractory VT between April 2009 and December 2012 was performed., Results: Forty-one patients underwent CSD (14 left CSD, 27 bilateral CSD). There was a significant reduction in the burden of implantable cardioverter-defibrillator (ICD) shocks during follow-up compared to the 12 months before the procedure. The number of ICD shocks was reduced from a mean of 19.6 ± 19 preprocedure to 2.3 ± 2.9 postprocedure (P < .001), with 90% of patients experiencing a reduction in ICD shocks. At mean follow-up of 367 ± 251 days postprocedure, survival free of ICD shock was 30% in the left CSD group and 48% in the bilateral CSD group. Shock-free survival was greater in the bilateral group than in the left CSD group (P = .04)., Conclusion: In patients with VT storm, bilateral CSD is more beneficial than left CSD. The beneficial effects of bilateral CSD extend beyond the acute postsympathectomy period, with continued freedom from ICD shocks in 48% of patients and a significant reduction in ICD shocks in 90% of patients., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine gender variations in the association of self-rated health (SRH) with social capital, social support, and economic security among older adults from three deprived communities in the suburbs of metropolitan Beirut., Methods: A population-based cross-sectional study using the Older Adult Component of the Urban Health Survey. Face-to-face interviews were conducted with 328 older men and 412 older women aged 60 years and above. SRH was assessed by a single question and treated as a dichotomous outcome, and several indicators of social capital, social support, and economic security were examined as independent variables., Results: Women were significantly more likely to report poor SRH compared to men (37.2 vs. 25.9 %, respectively). Better social capital indicators decreased significantly the odds of poor SRH among both men (OR = 0.76, 95 % CI: 0.65-0.89) and women (OR = 0.71, 95 % CI: 0.62-0.82). Social support was strongly associated with SRH among women (OR = 0.56), but not among men (OR = 0.94). The reverse situation was observed for economic security (OR = 0.57 among men, OR = 0.80 among women)., Conclusions: In these deprived neighborhoods, social and economic factors may have gender-specific effects on the promotion of well-being among older adults, with social support being more salient to women's SRH and economic security being more salient to men's SRH. In health studies among older people, SRH captures not only social and physical health but also broader economic well-being.