bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bereaved families’ experiences of end-of-life decision making for general medicine patients
Authors: Moon Felicity , Mooney Christine , McDermott Fiona , Miller Alistair , Poon Peter 
Published: March 2021

BackgroundFamily involvement in decision making for hospitalised patients is associated with improved end-of-life care. Yet, these discussions can be challenging for physicians and families and associated with distress, confusion and conflict. There is a need to understand how best to support families involved in decisions regarding the transition from active to palliative treatment in hospital settings.AimTo explore bereaved families’ experiences of end-of-life decision making for general medicine patients.DesignA qualitative exploratory study framed by social constructionism using semistructured interviews and thematic analysis.Setting and participantsThe general medicine units of one large public hospital in Melbourne, Australia. We recruited 28 bereaved family members of patients who had received end-of-life care.FindingsPatients and families depended on physicians to explain clinical complexity and treatment beneficence; however, trust in medical judgement was mediated by participant’s own interpretations of clinical progress. Families sought to be respected as advocates and experienced distress if physicians disregarded their perspectives and insight concerning patient preferences. Ideally, families supported patients to express their preferences to physicians. Otherwise, families contextualised treatment decisions through their knowledge of patient’s values and quality of life. Families often felt burdened by or excluded from medical decision making and experienced distress and confusion regarding their rights to request or refuse treatment.ConclusionOur study highlights how families contribute to decision making to ensure end-of-life care treatments reflect patient preferences. Physicians can ease families’ distress around treatment withdrawal by providing a meaningful explanation of complex clinical issues, clarifying decision-making roles and acknowledge families’ desire to protect and advocate for their loved one.
Clinicopathological characteristic of ciliated muconodular papillary tumour of the lung
Authors: Yang Yong , Xie Xiaofeng , Jiang Gening , Zhang Liping , Liu Hongcheng 
Published: March 2021

AimsCiliated muconodular papillary tumour (CMPT) is a rare tumour characterised by tripartite cellular components of mucinous cells, ciliated columnar cells and basal cells with a predominantly papillary architecture. Its clinicopathological characteristics and treatment methods have not been fully elucidated.MethodsTwenty-six patients with CMPT diagnosed and treated in our hospital were retrospectively analysed.ResultsThe cohort was composed of 13 males and 13 females, with a mean age of 64.4±5.93 years. The diameter of the primary tumour ranged from 0.3 to 1.4 cm. The lesions appeared as subsolid nodules, ground-glass nodules and cavitary nodules under the CT scan. All the patients underwent surgical treatment and did not receive postoperative adjuvant therapy. All the CMPTs were diagnosed by immunohistochemistry and not by intraoperative frozen sections. Next-generation sequencing detection demonstrated EGFR, KRAS and BRAF mutations and ALK rearrangements in CMPTs. The follow-up duration ranged from 5 to 65 months, and no case of tumour recurrence was observed until the final follow-up.ConclusionsThe incidence of CMPT is low, and the prognosis is good. Immunohistochemistry is helpful for an accurate diagnosis of CMPT, while intraoperative frozen sections cannot fully guide the surgical method. Sublobectomy may be enough without adjuvant treatment. CMPTs exhibited a relatively high rate of driver gene mutations, while the mutation sites were not consistent with those in lung adenocarcinoma.
Real-world biomarker testing rate and positivity rate in NSCLC in Spain: Prospective Central Lung Cancer Biomarker Testing Registry (LungPath) from the Spanish Society of Pathology (SEAP)
Authors: Salas Clara , Martín-López Javier , Martínez-Pozo Antonio , Hernández-Iglesias Teresa , Carcedo David , Ruiz de Alda Lucia , García J Francisco , Rojo Federico 
Published: March 2021

AimThe aim of this study was to describe the testing rate and frequency of molecular alterations observed in the Lung Cancer Biomarker Testing Registry (LungPath).MethodsA descriptive study of NSCLC biomarker determinations collected from March 2018 to January 2019, from 38 Spanish hospitals, was carried out. Only adenocarcinoma and not otherwise specified histologies were included for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) expression. The testing rate and the positivity rate were calculated. Multivariate logistic regression was used to explore the joint relationship between independent explanatory factors and both testing and positivity rates. Two models were adjusted: one with sample type and histology as independent factors, and the other adding the testing rate or the positivity rate of the other biomarkers.Results3226 patient samples were analysed, whereEGFR,ALK,ROS1and PD-L1 information was collected (a total of 12 904 determinations). Overall, 9118 (71.4%) determinations were finally assessed.EGFR(91.4%) andALK(80.1%) were the mainly tested biomarkers. Positivity rates forEGFR,ALK,ROS1and PD-L1 were 13.6%, 3.4%, 2.0% and 49.2%, respectively. Multivariate models showed a lower testing rate for ALK in surgical pieces, fine-needle aspiration or other types of samples versus biopsies.ConclusionsDespite the high testing rate in EGFR and ALK in NSCLC, the real-world evidence obtained from the LungPath demonstrates that ROS1 and PD-L1 were not determined in a significant portion of patients. LungPath provides crucial information to improve the coverage in molecular testing in lung cancer, to monitor the positivity rate and the introduction of new biomarker testing in clinical practice.
Secondary haemophagocytic lymphohistiocytosis in COVID-19: correlation of the autopsy findings of bone marrow haemophagocytosis with HScore
Authors: Núñez-Torrón Claudia , Ferrer-Gómez Ana , Moreno Moreno Esther , Pérez-Mies Belen , Villarrubia Jesús , Chamorro Sandra , López-Jiménez Javier , Palacios J , Piris-Villaespesa Miguel , García-Cosío Mónica 
Published: March 2021

BackgroundSecondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH.AimOur objective is to ascertain the existence of sHLH in some patients with severe COVID-19.MethodsWe report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records.ResultsEleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case.ConclusionsOur results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.
Psoriasis Does Not Worsen Outcomes in Patients Admitted for Ischemic Stroke: An Analysis of the National Inpatient Sample
Authors: Edigin Ehizogie , Kaul Subuhi , Eseaton Precious Obehi , Ojemolon Pius Ehiremen , Patel Axi , Manadan Augustine 
Published: March 2021

Psoriasis is a chronic inflammatory state associated with an increased risk of cardiometabolic diseases, stroke, and mortality. Although psoriasis increases the risk of ischemic stroke, whether outcomes, including mortality, are adversely affected is unknown. This study aims to compare inpatient mortality of patients admitted for ischemic stroke with and without psoriasis. The secondary outcome measures were hospital length of stay (LOS), total hospital charges, odds of receiving tissue plasminogen activator (TPA), and mechanical thrombectomy between both groups. Data were obtained from the National Inpatient Sample (NIS) 2016 and 2017 databases using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. Multivariable logistic and linear regression analysis were used accordingly to account for confounders of the outcomes. The combined 2016 and 2017 NIS database comprised over 71 million discharges. Of these, ischemic stroke accounted for 525,570 hospitalizations and 2425 (0.5%) had a concomitant diagnosis of psoriasis. Patients hospitalized for ischemic stroke with coexisting psoriasis did not have a difference in inpatient mortality (3.5% vs 5.5%; p=0.285) compared with those without psoriasis. However, psoriasis cohort had shorter LOS (5.0 vs 5.7 days; p=0.029) and lower total hospital charges ($60,471 vs $70,246; p=0.003) compared with the non-psoriasis cohort. The odds of receiving TPA and undergoing mechanical thrombectomy were not different in both groups. Inpatient mortality, odds of receiving TPA, and undergoing mechanical thrombectomy in patients who had an ischemic stroke with or without psoriasis were not different. However, patients with psoriasis had a significantly shorter LOS and lower hospital charges.
Designed improvement to T-cell immunotherapy by multidimensional single cell profiling
Authors: Bandey Irfan N , Adolacion Jay R T , Romain Gabrielle , Paniagua Melisa Martinez , An Xingyue , Saeedi Arash , Liadi Ivan , You Zheng , Rajanayake Rasindu B , Hwu Patrick , Singh Harjeet , Cooper Laurence JN , Varadarajan Navin 
Published: March 2021

BackgroundAdoptive cell therapy based on the infusion of chimeric antigen receptor (CAR) T cells has shown remarkable efficacy for the treatment of hematologic malignancies. The primary mechanism of action of these infused T cells is the direct killing of tumor cells expressing the cognate antigen. However, understanding why only some T cells are capable of killing, and identifying mechanisms that can improve killing has remained elusive.MethodsTo identify molecular and cellular mechanisms that can improve T-cell killing, we utilized integrated high-throughput single-cell functional profiling by microscopy, followed by robotic retrieval and transcriptional profiling.ResultsWith the aid of mathematical modeling we demonstrate that non-killer CAR T cells comprise a heterogeneous population that arise from failure in each of the discrete steps leading to the killing. Differential transcriptional single-cell profiling of killers and non-killers identified CD137 as an inducible costimulatory molecule upregulated on killer T cells. Our single-cell profiling results directly demonstrate that inducible CD137 is feature of killer (and serial killer) T cells and this marks a different subset compared with the CD107apos(degranulating) subset of CAR T cells. Ligation of the induced CD137 with CD137 ligand (CD137L) leads to younger CD19 CAR T cells with sustained killing and lower exhaustion. We genetically modified CAR T cells to co-express CD137L, in trans, and this lead to a profound improvement in anti-tumor efficacy in leukemia and refractory ovarian cancer models in mice.ConclusionsBroadly, our results illustrate that while non-killer T cells are reflective of population heterogeneity, integrated single-cell profiling can enable identification of mechanisms that can enhance the function/proliferation of killer T cells leading to direct anti-tumor benefit.
MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia
Authors: Manera Ana L , Dadar Mahsa , Van Swieten John Cornelis , Borroni Barbara , Sanchez-Valle Raquel , Moreno Fermin , Laforce Jr Robert , Graff Caroline , Synofzik Matthis , Galimberti Daniela , Rowe James Benedict , Masellis Mario , Tartaglia Maria Carmela , Finger Elizabeth , Vandenberghe Rik , de Mendonca Alexandre , Tagliavini Fabrizio , Santana Isabel , Butler Christopher R , Gerhard Alex , Danek Adrian , Levin Johannes , Otto Markus , Frisoni Giovanni , Ghidoni Roberta , Sorbi Sandro , Rohrer Jonathan Daniel , Ducharme Simon , Collins D Louis ,   FTLDNI investigators
Published: March 2021

IntroductionStructural brain imaging is paramount for the diagnosis of behavioural variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis.MethodsA total of 515 subjects from two different bvFTD cohorts (training and independent validation cohorts) were used to perform voxel-wise morphometric analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from deformation-based morphometry differences in isolation and together with semantic fluency. Tenfold cross validation was used to assess the performance of the classifier within the training cohort. A second held-out cohort of genetically confirmed bvFTD cases was used for additional validation.ResultsAverage 10-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In the separate validation cohort of definite bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added semantic fluency scores.ConclusionOur results show that structural MRI and semantic fluency can accurately predict bvFTD at the individual subject level within a completely independent validation cohort coming from a different and independent database.
Evaluation of stroke thrombectomy including patients where IV
thrombolysis is contraindicated or has failed: a randomized trial of two
novel thrombectomy devices
Authors: White Philip M , Gregson Barbara , Cora Elena Adela , Dixit Anand , Subramanian Ganesh , Joshi Yogish , Simister Robert , Lakey Rachel , Maiter Ahmed , Ford Gary A 
Published: March 2021

Background
Study was a PROBE design phase II randomized controlled trial (RCT).
We assessed trial feasibility and technical efficacy and safety of two
novel thrombectomy devices – ERIC (a retriever device) and SOFIA (a
distal access catheter) – used alone or in combination depending on
operator preference.

Methods
Four UK neuroscience centers enrolled adults with proximal large
artery occlusion (LAO) stroke on imaging where arterial puncture was
achievable within 5.5 hours (8.5 hours for posterior circulation) of
symptom onset; National Institutes of Health Stroke Scale (NIHSS) ≥6
with limited ischemic change on CT imaging. Randomization was 2:1 into
intervention arm (ERIC and/or SOFIA). Patients and core lab were blinded
to allocation. Primary outcome was independent core lab adjudication of
reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI)
scale). Secondary outcomes were modified Rankin score (mRS) at 90 and
365 days (independence and shift analysis), 30-day mortality,
symptomatic intracranial hemorrhage (sICH), procedural complications and
NIHSS change.

Results
Sixty-six patients were enrolled. TICI 2B/3 reperfusion was achieved
in 72% in intervention compared with 90% in control arm on intention to
treat (ITT) analysis (P=0.2) and 78% compared with 86% on per protocol
analysis (P=0.7). Functional independence at 90 days was 40%
(intervention) compared with 43% (control) on ITT analysis (P=1.0). sICH
rates were low at 0% and 5%, respectively (P=0.3). The 30-day mortality
was 9% intervention compared with 14% control (P=0.7).

Conclusions
Study indicated feasibility of a phase II RCT trial approach for
assessing new thrombectomy devices. In a broad LAO stroke population
ERIC and SOFIA were not statistically different from control devices.
Larger trials are needed.
Age-adjusted infarct volume cut-off points improve stroke outcome prognostication beyond modeling with age and infarct volume
Authors: Bouslama Mehdi , Haussen Diogo C , Rodrigues Gabriel Martins , Barreira Clara M , Dehkharghani Seena , Frankel Michael R , Nogueira Raul G 
Published: March 2021

BackgroundAge and infarct volume are among the most powerful predictors of outcome after large vessel occlusion acute strokes (LVOS).ObjectiveTo study the impact of age-adjusted final infarct volume (FIV) on functional outcomes.MethodsReview of a prospectively collected thrombectomy database at a tertiary care center between September 2010 and February 2018. Consecutive patients with anterior circulation LVOS who achieved full reperfusion (modified Thrombolysis in Cerebral Infarction 3) were categorized into four age groups: (G1) <60 years, (G2) 60–69, (G3) 70–79, (G4) ≥80 years. The Youden Index was used to identify the optimal FIV cut-off point for good outcome (modified Rankin Scale score 0–2) discrimination in each group and the overall population. The predictive ability of these specific thresholds was evaluated using binary logistic regressions and compared with the non-age-adjusted cut-off point.Results516 patients were analyzed (G1: n=171, G2: n=130, G3: n=103, G4: n=112). Patients with poor outcome had a larger FIV in each group (p<0.01 for all). The target FIV cut-off point decreased with increased age: G1: 45.7 mL (sensitivity 56%, specificity 80%); G2: 30.4 mL (sensitivity 63%, specificity 75%); G3: 20.2 mL (sensitivity 76%, specificity 65%); G4: 16.9 mL (sensitivity 68%, specificity 70%). The non-age-adjusted cut-off point was 19.2 mL (sensitivity 70%, specificity 59%).In multivariate analysis, adjusting for confounders including age and FIV, achieving a FIV less than the age-adjusted threshold was an independent predictor of good outcome (aOR=2.72, 95% CI 1.41 to 5.24, p<0.001). In contrast, a similar model including the non-age-adjusted target cut-off point failed to reveal an association with good outcome (aOR=1.72, 95% CI 0.93 to 3.19, p<0.085). Furthermore, the latter model had a weaker outcome predictive ability as assessed by the Akaike information criterion (409 vs 403).ConclusionsAge-adjusted infarct volume represents a strong outcome discriminator beyond age and infarct volume in isolation and might help to refine patient selection and improve outcome prognostication in stroke thrombectomy.
Definition and time course of pericavity edema after minimally invasive endoscopic intracerebral hemorrhage evacuation
Authors: Horowitz Maxwell E , Ali Muhammad , Chartrain Alexander G , Allen Olivia S , Scaggiante Jacopo , Glassberg Brittany , Sakai Yu , Turkheimer Lena , Song Rui , Martini Michael L , Zhang Xiangnan , Mocco J , Kellner Christopher P 
Published: March 2021

BackgroundPerihematomal edema (PHE) volume correlates with intracerebral hemorrhage (ICH) volume and is associated with functional outcome. Minimally invasive surgery (MIS) for ICH decreases clot burden and PHE. MIS may therefore alter the time course of PHE, mitigating a critical source of secondary injury.ObjectiveTo describe a new method for the quantitative measurement of cerebral edema surrounding the evacuated hematoma cavity, termed pericavity edema (PCE), and obtain details of its time course following MIS for ICH.MethodsThe study included 48 consecutive patients presenting with ICH who underwent MIS evacuation. Preoperative and postoperative CT scans were assessed by two independent raters. Hematoma, edema, cavity, and pneumocephalus volumes were calculated using semi-automatic, threshold-guided volume segmentation software (AnalyzePro). Follow-up CT scans at variable delayed time points were available for 36 patients and were used to describe the time course of PCE.ResultsMean preoperative, postoperative, and delayed PCE were 21.0 mL (SD 15.5), 18.6 mL (SD 11.4), and 18.4 mL (SD 15.5), respectively. The percentage of ICH evacuated correlated significantly with a decrease in postoperative PCE (r=−0.46, p<0.01). Linear regression analysis revealed a significant relation between preoperative hematoma volume and both postoperative PCE (p<0.001) and postoperative relative PCE (p<0.001). The mean peak PCE was 26.4 mL (SD 15.6) and occurred at 6.5 days (SD 4.8) post-ictus. The 2-week postoperative time course of relative PCE did not fluctuate, suggesting stability in edema during the perioperative period surrounding evacuation and up to 2 weeks after the initial bleed.ConclusionsWe present a detailed and accurate method for measuring PCE volume with semi-automatic, threshold-guided segmentation software in the postoperative patient with ICH. Decrease in PCE after MIS evacuation correlated with evacuation percentage, and relative PCE remained stable after minimally invasive endoscopic ICH evacuation.
Pivotal trial of the Neuroform Atlas stent for treatment of posterior circulation aneurysms: one-year outcomes
Authors: Jankowitz Brian T , Jadhav Ashutosh P , Gross Bradley , Jovin Tudor G , Alhajeri Abdulnasser A , Fraser Justin F , Hanel Ricardo A , Sauvageau Eric , Aghaebrahim Amin , Frei Donald , Bellon Richard , Loy David , Puri Ajit S , Malek Adel M , Thomas Ajith , Toth Gabor , Lopes Demetrius Klee , Crowley R Webster , Arthur Adam S , Reavey-Cantwell John , Lin Eugene , Siddiqui Adnan H , Alexander Michael J , Khaldi Ahmad , Colby Geoffrey P , Caplan Justin M , Satti Sudhakar R , Turk Aquilla S , Spiotta Alejandro M , Klucznik Richard , Hallam Danial K , Kung David , Froehler Michael T , Callison R Charles , Kan Peter , Hetts Steven W , Zaidat Osama O 
Published: March 2021

BackgroundStent-assisted coiling of wide-necked intracranial aneurysms (IAs) using the Neuroform Atlas Stent System (Atlas) has shown promising results.ObjectiveTo present the primary efficacy and safety results of the ATLAS Investigational Device Exemption (IDE) trial in a cohort of patients with posterior circulation IAs.MethodsThe ATLAS trial is a prospective, multicenter, single-arm, open-label study of unruptured, wide-necked, IAs treated with the Atlas stent and adjunctive coiling. This study reports the results of patients with posterior circulation IAs. The primary efficacy endpoint was complete aneurysm occlusion (Raymond-Roy (RR) class I) on 12-month angiography, in the absence of re-treatment or parent artery stenosis >50%. The primary safety endpoint was any major ipsilateral stroke or neurological death within 12 months. Adjudication of the primary endpoints was performed by an imaging core laboratory and a Clinical Events Committee.ResultsThe ATLAS trial enrolled and treated 116 patients at 25 medical centers with unruptured, wide-necked, posterior circulation IAs (mean age 60.2±10.5 years, 81.0% (94/116) female). Stents were placed in all patients with 100% technical success rate. A total of 95/116 (81.9%) patients had complete angiographic follow-up at 12 months, of whom 81 (85.3%) had complete aneurysm occlusion (RR class I). The primary effectiveness outcome was achieved in 76.7% (95% CI 67.0% to 86.5%) of patients. Overall, major ipsilateral stroke and secondary persistent neurological deficit occurred in 4.3% (5/116) and 1.7% (2/116) of patients, respectively.ConclusionsIn the ATLAS IDE posterior circulation cohort, the Neuroform Atlas Stent System with adjunctive coiling demonstrated high rates of technical and safety performance.Trial registration numberhttps://clinicaltrials.gov/ct2/show/NCT02340585.