tbuckley/cabot-search huggingface dataset:
Scale of NHS’s “corridor care” is revealed in Royal College of Nursing report
Authors: Jacqui Wise
Journal: BMJ (2025)

Has treating patients in corridors and cloakrooms become "normalised"? Jacqui Wise reports A nurse forced to change an incontinent patient with dementia beside a vending machine and a patient dying from a cardiac arrest who couldn't be given adequate cardiopulmonary resuscitation (CPR) because of overcrowding in the corridor are just two examples from a stark new report from the Royal College of Nursing.1 The report is based on a survey of 5408 UK nursing staff carried out from 18 December to 11 January 2025, in which more than two thirds (66.8%) said they had on a daily basis treated patients in inappropriate settings such as a corridor, bathroom, cloakroom, bereavement room, or converted cupboard. More than nine in 10 of those surveyed believed that patients' safety was being compromised. Nurses reported caring for up to 40 patients in a corridor but unable to access oxygen, cardiac monitors, and other vital equipment. The report also highlights serious concerns about infection prevention and control. One nurse reported that a patient vomited on another patient because they were so close together lined up in a corridor awaiting cubicles. The 460 page report contains many examples of patients receiving diagnoses and having discussions in public and being treated, fed, washed, and toileted with no privacy (box 1). Box 1 ### Harrowing descriptions given by nurses in RCN reportRETURN TO TEXT
Incidence and prognostic implications of PSA persistence and relapse after radical prostatectomy. Population-based study
Authors: Pietro Scilipoti, Hans Garmo, Rolf Gedeborg, David Robinson, Pär Stattin, Marcus Westerberg
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background There has been a wide range in incidence of prostate-specific antigen (PSA) persistence and relapse after radical prostatectomy (RP) for prostate cancer (PCa). We aimed to describe incidence and prognostic implications of PSA persistence and relapse. Methods Register-based cohort study in Sweden of men diagnosed with PCa between 2007 and 2020 who underwent RP. Risks were estimated using competing risk cumulative incidence curves. Treatment after persistence or relapse and risk of PCa death and other causes were stratified according to persistence, European Association of Urology relapse risk groups, time to relapse, and life expectancy based on age and comorbidities. Results Among 10,700 men, the 10-year risk of PSA persistence or relapse after RP was 34% (95% CI, 32-35%). Within 12 months of persistence/relapse, 75% of men with persistence, high-risk relapse or early relapse (&amp;lt;2 years) received treatment. The 10-year risk of PCa death ranged from 12% for men with persistence to 2% in men with low-risk relapse, while death from other causes ranged from 11% to 16%. Risk of PCa death was 8.5% after early relapse (&amp;lt;2 years) and 1.4% after late relapse (&amp;gt;5 years). Conclusions This population-based study estimated that one third of men would have PSA persistence or relapse within 10 years from RP. There was a wide range in risk of death from PCa according to cancer characteristics and time to relapse. Risk of death from other causes was substantial. These factors, along with life expectancy, should inform treatment decisions for men with persistence or relapse.
An exosome-based liquid biopsy predicts depth of response and survival outcomes to cetuximab and panitumumab in metastatic colorectal cancer: The EXONERATE Study.
Authors: Caiming Xu, Alessandro Mannucci, Francis Esposito, Helena Oliveres, Vicente Alonso Orduña, Alfonso Yubero, Carlos Fernández-Martos, Antonieta Salud, Javier Gallego, Marta Martin-Richard, Julen Fernández-Plana, Monica Guillot, Jorge Aparicio, Marwan Fakih, Scott Kopetz, Jaime Feliu, Joan Maurel, Ajay Goel
Journal: Clinical Cancer Research (2025)

PURPOSE EXONERATE (EXOsome and cell-free micro-RNAs of anti-EGFR ResistAnce) was an open-label, biomarker interventional study designed to develop, test, and validate a liquid biopsy predictive of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for first-line EGFR inhibitors in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with newly diagnosed RAS-WT, chemotherapy-naïve mCRC, both right- and left-sided, were enrolled in 2-nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The primary endpoint was 12-month PFS, which was hierarchically tested in left- and right-sided mCRC to predict PFS, OS, and ORR. RESULTS Genome-wide small-RNA sequencing identified 12 cell-free and 14 exosomal candidates that were differentially expressed in both plasma and tumor tissue of good vs. poor responders (based on PFS <12 months). The 8 and 9 best-performing candidates, respectively, were used to generate the EXONERATE assay. In left-sided mCRC, 65% were EXONERATE-high, correlating with shorter mPFS (9.5 vs. 18.5 months, p<0.001). In the independent right-sided mCRC cohort, 80.8% were EXONERATE-high and experienced a similarly shorter mPFS (8.6 vs. 41.2 months, p=0.0004). In the right-sided group, EXONERATE predicted PFS≥12 months with 100% sensitivity. A linear relationship existed between EXONERATE values and response depth. Multivariate analysis revealed that EXONERATE predicts PFS and OS independently of tumor-sidedness. CONCLUSION The EXONERATE assay robustly predicted PFS and OS outcomes in patients with mCRC, both right- and left-sided, before they received either panitumumab or cetuximab. It stratified PFS, OS, and ORR better than a right vs. left approach.
Tremelimumab plus durvalumab prior to chemoradiotherapy in unresectable, locally advanced non-small cell lung cancer: the Induction trial.
Authors: Michiel M. Smeenk, Judi N.A. van Diessen, Thierry N. Boellaard, Koen J. Hartemink, Jeltje F. de Vries, Vincent van der Noort, Sushil K. Badrising, Emilia C. Owers, Kim Monkhorst, Michel M. van den Heuvel, Willemijn S.M.E. Theelen
Journal: Clinical Cancer Research (2025)

Abstract Background: The phase I Induction trial (NCT04287894) assessed the feasibility and safety of induction immunotherapy (IIT) prior to concurrent chemoradiotherapy (cCRT) in patients with locally advanced non-small cell lung cancer (NSCLC). Methods: Patients with unresectable stage II/III NSCLC were eligible for inclusion. Patients received either one cycle of tremelimumab (75mg) with two cycles of durvalumab (1500mg) in cohort I, one cycle of tremelimumab (300mg) with two cycles of durvalumab in cohort II or one cycle of tremelimumab (300mg) with one cycle of durvalumab in cohort III. After IIT, a comprehensive radiological and pathological restaging was performed followed by cCRT. The combined primary endpoint was feasibility and safety of IIT-cCRT. Results: Fifteen of seventeen included patients were treated per-protocol. IIT-cCRT was completed in 13/15 of the patients within the predefined feasibility criteria. Grade ≥3 immune-related adverse events (irAEs) occurred in 7/15 patients, of which 6 were treated in the high-dose tremelimumab cohorts, thereby violating the safety criteria in cohorts II and III. The low-dose tremelimumab cohort (I) complied with safety criteria. Eleven patients had multilevel N2 or N3 disease at baseline, eight of these patients were downstaged to either N0/1 or single level N2 after IIT. Multiparametric MRI accurately identified nodal downstaging in 7/7 patients. Conclusion: Induction with high-dose tremelimumab plus durvalumab prior to cCRT in unresectable locally advanced NSCLC was associated with unacceptable toxicity, although ITT resulted in clinically relevant nodal downstaging in 8/11 of patients with baseline multilevel N2 or N3 disease. Multiparametric MRI showed potential evaluating treatment response.
Phase I study of adavosertib with radiation therapy and temozolomide in newly diagnosed glioblastoma and intratumoral drug levels in recurrent glioblastoma
Authors: Eudocia Q. Lee, Brian M. Alexander, Carlos G. Romo, Jeffrey G. Supko, Nathalie Y.R. Agar, Zahra Talebi, Manmeet S. Ahluwalia, Arati S. Desai, Jorg Dietrich, Thomas J. Kaley, David M. Peereboom, Jennifer Gantchev, Gerard Baquer, Sandro Santagata, Naoko Takebe, Serena Desideri, Joy D. Fisher, Megan Sims, Xiaobu Ye, Keith L. Ligon, Louis B. Nabors, Stuart A. Grossman, Patrick Y. Wen
Journal: Clinical Cancer Research (2025)

Adavosertib is an oral small molecular inhibitor of Wee1. The Adult Brain Tumor Consortium performed a phase I study of adavosertib, radiation (RT) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) as well as a surgical window of opportunity study in recurrent GBM. The maximum tolerated dose (MTD) of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in 2 separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ. A combination cohort with both concurrent and adjuvant adavosertib at MTD followed. We also performed intratumoral drug distribution studies in recurrent GBM patients undergoing surgery. As separate cohorts, MTD for concurrent adavosertib with RT/TMZ was 200 mg daily M-F x 6 weeks during RT and for adjuvant adavosertib with TMZ was 425 mg daily for 5 days of each 28-day cycle. However, 6/12 patients experienced DLTs in the combination cohort. The mean ratio of the intratumoral-to-plasma concentration of adavosertib was 4.18 ± 3.36 for contrast-enhancing tissue and 0.74 ± 0.63 in non-enhancing tissue. Adavosertib 200 mg daily M-F x 6 weeks with RT/TMZ and 425 mg daily on a 5d/28d cycle with TMZ had an unacceptable DLT rate. Additional dose levels in combination cohorts resulted in DLTs and we deemed concurrent adavosertib too toxic for further examination. Adavosertib 425 mg daily on a 5d/28d cycle with adjuvant TMZ is the recommended phase II dose. Tissue PK in tissue homogenates and by microdialysis provided complementary information about drug penetration.
Genomic Profiling of Cardiac Angiosarcoma Reveals Novel Targetable KDR Variants, Recurrent MED12 Mutations and a High Burden of Germline POT1Alterations
Authors: Igor Odintsov, David J. Papke, Suzanne George, Robert F. Padera, Jason L. Hornick, Stephanie E. Siegmund
Journal: Clinical Cancer Research (2025)

Cardiac angiosarcoma (CAS) is a rare, aggressive malignancy with limited treatment options. Both sporadic and familial cases occur, with recent links to germline POT1 mutations. The genomic landscape of this disease is poorly understood. We conducted comprehensive genomic profiling of CAS to assess the burden of germline predisposition and identify other recurrent genomic alterations of clinical significance. Six patients were female and four were male. The median age at presentation was 40 years (range 21- 69 years). All cases with available follow up exhibited an aggressive clinical course (6/8 patients died of disease). KDR alterations, including novel structural variants, were found in 9/11 cases, at a rate significantly higher than in non-cardiac angiosarcomas. POT1 mutations were present in 45.5% of CAS cases. In three of five POT1-mutant cases, the germline status was confirmed through testing of normal tissue and in one additional case, the germline status was inferred with high probability through allele frequency analysis. Additionally, we identified novel recurrent MED12 exon 2 mutations in POT1-wild type CAS, suggesting an alternative path to CAS oncogenesis. CAS demonstrate unique genetic profile, distinct from non-cardiac angiosarcoma. This study highlights the role of germline POT1 burden on CAS development and demonstrates recurrent MED12 alterations for the first time. The reported KDR variants provide a potential avenue for treatment of this aggressive disease. Given the prevalence of germline POT1 mutations reported herein, germline genetic testing should be considered in patients diagnosed with CAS.
pDCs, type 1 IFN, and the female predileXion of SSc
Authors: Nikhil Jiwrajka, Montserrat C. Anguera
Journal: The Journal of Experimental Medicine (2025)

Systemic sclerosis (SSc) is a debilitating autoimmune disease that preferentially afflicts women. The molecular origins of this female bias are unclear. A new study of plasmacytoid dendritic cells from SSc patients by Du et al. (https://doi.org/10.1084/jem.20231809) suggests the X chromosome may play a key role.
Clinical significance of the estimation of pulmonary-right ventricular uncoupling in patients with transthyretin amyloid cardiomyopathy
Authors: Hiroki Usuku, Eiichiro Yamamoto, Kasumi Miyazaki, Ryudai Higashi, Atsushi Nozuhara, Fumi Oike, Naoto Kuyama, Noriaki Tabata, Masanobu Ishii, Shinsuke Hanatani, Tadashi Hoshiyama, Hisanori Kanazawa, Daisuke Sueta, Yuichiro Arima, Seitaro Oda, Hiroaki Kawano, Yasushi Matsuzawa, Yasuhiro Izumiya, Mitsuharu Ueda, Yasuhito Tanaka, Kenichi Tsujita
Journal:  (2025)

Abstract Aims There are few data on the prognostic impact of pulmonary-right ventricular (RV) uncoupling in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Methods and results Among the 174 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from 2002 to 2021, 143 patients who met the current Japanese guideline and had sufficient information for two-dimensional speckle tracking echocardiography were retrospectively analysed. During a median follow-up of 1209 days, 39 cardiac deaths occurred. Compared with patients in the non-event group, those in the cardiac death group were significantly older (79.3 ± 6.7 vs. 76.4 ± 6.2, respectively; P &amp;lt; 0.05). Additionally, RV global longitudinal strain (RV-GLS)/systolic pulmonary artery pressure (sPAP), an index of pulmonary-RV uncoupling, was significantly lower in patients in the cardiac death group vs. the non-event group [0.29 (0.18–0.35) vs. 0.40 (0.29–0.57), P &amp;lt; 0.01]. Multivariate Cox proportional hazards regression analysis demonstrated that RV-GLS/sPAP was significantly associated with cardiac death after adjusting for tricuspid annular plane systolic excursion/sPAP (P &amp;lt; 0.01), sPAP (P &amp;lt; 0.05), and conventional prognostic factors including age and hospitalization for heart failure (&amp;lt;0.01), laboratory finding including high-sensitivity cardiac troponin T, and B-type natriuretic peptide (P &amp;lt; 0.01). Receiver operating characteristic analysis showed that the area under the curve for RV-GLS/sPAP for cardiac death was 0.72 and that the best cut off value for RV-GLS/sPAP was 0.34 (sensitivity, 76%; specificity, 65%). In the Kaplan–Meier analysis, patients with ATTRwt-CM who had low vs. high RV-GLS/sPAP (cut-off value 0.34) had a significantly higher probability of cardiac death (P &amp;lt; 0.01). Conclusion Pulmonary-RV uncoupling has significantly higher prognostic value compared with conventional prognostic factors in ATTRwt-CM.
Development, review, and activation of thoracic oncology investigator-initiated trials
Authors: David E. Gerber, Claire R. Wynters, Tanushree Prasad, Ronny K. Schnel, Song Zhang, Thomas E. Stinchcombe, Liza C. Villaruz, Joshua M. Bauml, Wade T. Iams, Tejas Patil, Stephen V. Liu, Leora Horn, John M. Hudak, D. Ross. Camidge
Journal: Clinical Cancer Research (2025)

Investigator-initiated trials (IITs) may address important biological and clinical questions that may not be prioritized by pharmaceutical sponsors. However, little is known about the process by which IIT proposals are evaluated and activated. We performed a retrospective study of IIT concepts submitted through the Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC), which comprises 13 institutions in the U.S. and Canada, from 2014 (consortium inception) to 2024. We compared approved and disapproved concepts using chi-squared tests, Fisher's exact tests, and Wilcoxon Rank-Sum tests. Among a total of 68 presented IIT concepts, 60 (88%) received consortium approval a median of 30 days (interquartile range [IQR] 31-59 days) after submission. Concepts submitted by junior faculty were more likely to be approved than those from full professors (P=0.003). Of the 60 concepts subsequently submitted to pharmaceutical sponsors, 15 (25%) were approved, 43 (72%) were disapproved, and 2 (3%) remain under review. The median time between concept submission to a sponsor and the sponsor's decision was 61 days (IQR 31-183 days). Concepts with shorter projected durations were more likely to be approved by the pharmaceutical sponsor (P=0.05). For sponsor-approved IIT concepts, median overall time from initial submission to trial activation was 18 months. Only a small proportion of proposed investigator-initiated cancer clinical trials are successfully activated following a prolonged development process. Given the importance of IITs in addressing real-world, practical questions and the growing professional challenges facing clinical research physician faculty, further attention to IIT development facilitators and barriers is warranted.
Human neuroinvasive Toscana virus infections in Italy from 2016 to 2023: Increased incidence in 2022 and 2023
Authors: Emmanouil Alexandros Fotakis, Elisa Di Maggio, Martina Del Manso, Alberto Mateo-Urdiales, Daniele Petrone, Massimo Fabiani, Giulia Perego, Antonino Bella, Gioia Bongiorno, Ilaria Bernardini, Marco Di Luca, Giulietta Venturi, Claudia Fortuna, Stefania Giannitelli, Federica Ferraro, Francesco Maraglino, Patrizio Pezzotti, Anna Teresa Palamara, Flavia Riccardo
Journal: Eurosurveillance (2025)

Background Toscana virus (TOSV) is transmitted to humans through bites of infected sand flies. Neuroinvasive TOSV infections are leading causes of meningitis/encephalitis in southern Europe and notifiable in Italy since 2016. In 2022–23, Italy experienced extreme climate anomalies and a concomitant increase in mosquito and tick-borne disease transmission. Aim To identify the spatiotemporal distribution and risk groups of neuroinvasive TOSV infections in Italy in 2022–23 vs 2016–21. Methods We retrospectively described all autochthonous, laboratory-confirmed neuroinvasive TOSV cases notified to the national surveillance system in 2016–23 using frequencies, proportions, incidences and incidence risk ratios (IRRs) with 95% CIs, stratified by year, sex, age, region/autonomous province (AP) of infection/exposure and infection/exposure municipality by urbanisation level. Results In 2022–23, 276 cases were notified (average annual incidence: 2.34/1,000,000 population) vs 331 cases in 2016–21 (0.92/1,000,000), with increased incidence extending into September. In 2022–23, infections were acquired in 12/21 regions/APs, predominantly in Emilia Romagna (57.6%; 159/276) as in 2016–21, including four regions/APs with no local infections in 2016–21. Similar to 2016–21, during 2022–23 residence in rural municipalities (vs urban), male sex, working age (19–67 years) and age &gt; 67 years (vs ≤ 18 years) were identified as risk factors with IRRs of 2.89 (95% CI: 2.01–4.17), 2.17 (95% CI: 1.66–2.84), 5.31 (95% CI: 2.81–10.0) and 5.06 (95% CI: 2.59–9.86), respectively. Conclusion Italy experienced a nearly 2.6-fold increase in neuroinvasive TOSV incidence in 2022–23 vs 2016–21. Raising public awareness on risk factors and personal protection measures may enhance prevention efforts.
Trends in human parainfluenza virus in Scotland before and after the peak of the COVID-19 pandemic, January 2017 to October 2023
Authors: Tonje Sande Laird, Mark Hamilton, Naoma William, Shivani Karanwal, Kimberly Marsh, Josie Evans
Journal: Eurosurveillance (2025)

Background Human parainfluenza viruses (HPIV) commonly cause upper respiratory tract infections, with potential for severe lower respiratory complications. Understanding seasonal increases informs strategies to prevent HPIV spreading. Aim We examined the impact of COVID-19 on HPIV epidemiological and clinical patterns in Scotland using non-sentinel and sentinel surveillance data. Methods Information on HPIV swab positivity (January 2017–October 2023) and demographic data was obtained from the Electronic Communication of Surveillance in Scotland (ECOSS) non-sentinel surveillance sources (laboratory-based data from hospital and community) and the Community Acute Respiratory Infection (CARI) sentinel surveillance programme (enhanced surveillance and symptom data). Results In 2020 during early COVID-19 waves, HPIV detection decreased aligning with lockdowns and preventive measures. In summer 2021, HPIV positivity increased, with HPIV-3 possibly reverting to pre-pandemic seasonality, but HPIV-1 not yet re-establishing alternate-year peaks. Most positive results from non-sentinel sources came from hospital tests. Sentinel surveillance (CARI) complemented non-sentinel data, offering community-level insights. There was no significant difference in CARI swab positivity by sex in any age group. Consistent with historical trends, children under five years exhibited highest test positivity: 9.3% (95% CI: 7.6–11.2) in females and 8.5% (95% CI 7.0–10.2) in males. Conclusion The COVID-19 pandemic impacted HPIV detection in Scotland. The decline during the pandemic peak and subsequent partial resurgence underscores the complex interplay between viral epidemiology and public health measures. Combining diverse surveillance systems provides a comprehensive understanding of HPIV dynamics. Insights into age-specific and symptom-associated patterns contribute to understanding HPIV epidemiology and refining public health strategies.
Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity
Authors: Jiaxin Liang, Tevis Vitale, Xixi Zhang, Thomas D. Jackson, Deyang Yu, Mark Jedrychowski, Steve P. Gygi, Hans R. Widlund, Kai W. Wucherpfennig, Pere Puigserver
Journal: Nature Cancer (2025)
Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial
Authors: Alicia F. C. Okines, Giuseppe Curigliano, Nobumasa Mizuno, Do-Youn Oh, Andree Rorive, Hatem Soliman, Shunji Takahashi, Tanios Bekaii-Saab, Mark E. Burkard, Ki Y. Chung, Philip R. Debruyne, Jenny R. Fox, Valentina Gambardella, Marta Gil-Martin, Erika P. Hamilton, Bradley J. Monk, Yoshiaki Nakamura, Danny Nguyen, David M. O’Malley, Alexander B. Olawaiye, Bhavana Pothuri, Martin Reck, Kazuki Sudo, Yu Sunakawa, Cedric Van Marcke, Evan Y. Yu, Jorge Ramos, Sherry Tan, Mark Bieda, Thomas E. Stinchcombe, Paula R. Pohlmann
Journal: Nature Medicine (2025)

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated. SGNTUC-019 is an open-label, phase 2 basket study evaluating tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2-altered solid tumors. The study included a cohort of 31 heavily pretreated female patients with HER2-mutated metastatic breast cancer who were also HER2 negative per local testing. Hormone receptor (HR)-positive patients also received fulvestrant. The overall response rate (primary endpoint) was 41.9% (90% confidence interval (CI): 26.9-58.2). Secondary endpoints of duration of response and progression-free survival were 12.6 months (90% CI: 4.7 to not estimable) and 9.5 months (90% CI: 5.4-13.8), respectively. No new safety signals were detected. Responses were observed across various HER2 mutations, including mutations in the tyrosine kinase and extracellular domains. The chemotherapy-free regimen of tucatinib and trastuzumab showed clinically meaningful antitumor activity with durable responses and favorable tolerability in heavily pretreated patients with HER2 mutations. These data support further investigation of HER2-targeted therapies in this patient population. ClinicalTrials.gov registration: NCT04579380 .