tbuckley/cabot-search huggingface dataset:
“I think that she would have wanted...”: Caregiver reflections on goal-concordant care for patients with cancer at the end of life.
Authors: Brigitte N. Durieux, Anna Berrier, Hannah Z. Catzen, Tamryn Gray, James A. Tulsky, Justin J. Sanders
Journal: Journal of Clinical Oncology (2021)

163 Background: Experts recognize goal-concordant care (GCC) as among the most important outcomes for those with advanced cancer. Despite a conceptual understanding about ways to measure goal-concordant care, we know little about what patient experiences align perceptions of goal concordance. Caregivers’ close proximity to patients give them a unique perspective on what factors contribute to perceived goal concordance. Methods: We conducted semi-structured interviews with 19 recently bereaved family caregivers of those with cancer to understand their experience of care, the extent to which they felt it was goal-concordant, and the factors of care which contextualized their experience. Caregivers were interviewed using a semi-structured guide based on the end-of-life planning module in Round 2 of the National Health and Aging Trends Survey (NHATS). We used template analysis to identify themes across the 19 interviews. Results: Most caregivers reported goal-concordant care when prompted, though many also recalled moments of goal discordance. Three high-level themes characterized their care perceptions: communication, relationships and humanistic care, and care transitions. Sub-themes of communication included clinician communication quality, prognostic communication, and information gaps. First, clear and transparent clinician communication facilitated GCC and high-quality care. Prognostic communication that did not align to patient preferences or consider patient hope was seen as harmful. Information gaps inhibited high-quality care as well as caregivers’ confidence that decisions were goal concordant. Second, relationships between patients and their clinicians enriched care, and humanistic care was seen as higher-quality. Lastly, logistical barriers, the need for relationship rebuilding, uncertain information communication, and a general lack of coordination characterized perceptions around care transitions and goal discordance. In particular, several caregivers noted issues and inter-specialty tensions around transitions specifically involving hospice. Conclusions: Caregivers consistently rated care as goal-concordant while also identifying areas of disappointing and low-quality care. Measures that capture goal-concordant care may be subject to psychological bias and may not clearly align with or predict other measures of care quality. Communication, relationships and humanistic care, and care transitions are all modifiable targets for quality improvement and deserve clear attention for patients with advanced cancer.
Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in <i>GUCY2C</i>
Authors: Vishwas Mishra, Avipsa Bose, Shashi Kiran, Sanghita Banerjee, Idrees A. Shah, Pooja Chaukimath, Mudasir M. Reshi, Swarna Srinivas, Anaxee Barman, Sandhya S. Visweswariah
Journal: The Journal of Experimental Medicine (2021)

Activating mutations in receptor guanylyl cyclase C (GC-C), the target of gastrointestinal peptide hormones guanylin and uroguanylin, and bacterial heat-stable enterotoxins cause early-onset diarrhea and chronic inflammatory bowel disease (IBD). GC-C regulates ion and fluid secretion in the gut via cGMP production and activation of cGMP-dependent protein kinase II. We characterize a novel mouse model harboring an activating mutation in Gucy2c equivalent to that seen in an affected Norwegian family. Mutant mice demonstrated elevated intestinal cGMP levels and enhanced fecal water and sodium content. Basal and linaclotide-mediated small intestinal transit was higher in mutant mice, and they were more susceptible to DSS-induced colitis. Fecal microbiome and gene expression analyses of colonic tissue revealed dysbiosis, up-regulation of IFN-stimulated genes, and misregulation of genes associated with human IBD and animal models of colitis. This novel mouse model thus provides molecular insights into the multiple roles of intestinal epithelial cell cGMP, which culminate in dysbiosis and the induction of inflammation in the gut.
Effect of a multidisciplinary Severe Immunotherapy Complications Service on outcomes for patients receiving immune checkpoint inhibitor therapy for cancer
Authors: Leyre Zubiri, Gabriel E Molina, Meghan J Mooradian, Justine Cohen, Sienna M Durbin, Laura Petrillo, Genevieve M Boland, Dejan Juric, Michael Dougan, Molly F Thomas, Alex T Faje, Michelle Rengarajan, Amanda C Guidon, Steven T Chen, Daniel Okin, Benjamin D Medoff, Mazen Nasrallah, Minna J Kohler, Sara R Schoenfeld, Rebecca K Leaf, Meghan E Sise, Tomas G Neilan, Daniel A Zlotoff, Jocelyn R Farmer, Aditya Bardia, Ryan J Sullivan, Steven M Blum, Yevgeniy R Semenov, Alexandra-Chloé Villani, Kerry L Reynolds
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background In 2017, Massachusetts General Hospital implemented the Severe Immunotherapy Complications (SIC) Service, a multidisciplinary care team for patients hospitalized with immune-related adverse events (irAEs), a unique spectrum of toxicities associated with immune checkpoint inhibitors (ICIs). This study’s objectives were to evaluate the intervention’s (1) effect on patient outcomes and healthcare utilization, and (2) ability to collect biological samples via a central infrastructure, in order to study the mechanisms responsible for irAEs. Methods A hospital database was used to identify patients who received ICIs for a malignancy and were hospitalized with severe irAEs, before (April 2, 2016–October 3, 2017) and after (October 3, 2017–October 24, 2018) SIC Service initiation. The primary outcome was readmission rate after index hospitalization. Secondary outcomes included length of stay (LOS) for admissions, corticosteroid and non-steroidal second-line immunosuppression use, ICI discontinuation, and inpatient mortality. Results In the pre-SIC period, 127 of 1169 patients treated with ICIs were hospitalized for irAEs; in the post-SIC period, 122 of 1159. After SIC service initiation, reductions were observed in irAE readmission rate (14.8% post-SIC vs 25.9% pre-SIC; OR 0.46; 95% CI 0.22 to 0.95; p=0.036) and readmission LOS (median 6 days post-SIC vs 7 days pre-SIC; 95% CI −16.03 to –0.14; p=0.046). No significant pre-initiation and post-initiation differences were detected in corticosteroid use, second-line immunosuppression, ICI discontinuation, or inpatient mortality rates. The SIC Service collected 789 blood and tissue samples from 234 patients with suspected irAEs. Conclusions This is the first study to report that establishing a highly subspecialized care team focused on irAEs is associated with improved patient outcomes and reduced healthcare utilization. Furthermore, the SIC Service successfully integrated blood and tissue collection safety into routine care.
Overcoming barriers to data sharing with medical image generation: a comprehensive evaluation
Authors: August DuMont Schütte, Jürgen Hetzel, Sergios Gatidis, Tobias Hepp, Benedikt Dietz, Stefan Bauer, Patrick Schwab
Journal: npj Digital Medicine (2021)

Abstract Privacy concerns around sharing personally identifiable information are a major barrier to data sharing in medical research. In many cases, researchers have no interest in a particular individual’s information but rather aim to derive insights at the level of cohorts. Here, we utilise generative adversarial networks (GANs) to create medical imaging datasets consisting entirely of synthetic patient data. The synthetic images ideally have, in aggregate, similar statistical properties to those of a source dataset but do not contain sensitive personal information. We assess the quality of synthetic data generated by two GAN models for chest radiographs with 14 radiology findings and brain computed tomography (CT) scans with six types of intracranial haemorrhages. We measure the synthetic image quality by the performance difference of predictive models trained on either the synthetic or the real dataset. We find that synthetic data performance disproportionately benefits from a reduced number of classes. Our benchmark also indicates that at low numbers of samples per class, label overfitting effects start to dominate GAN training. We conducted a reader study in which trained radiologists discriminate between synthetic and real images. In accordance with our benchmark results, the classification accuracy of radiologists improves with an increasing resolution. Our study offers valuable guidelines and outlines practical conditions under which insights derived from synthetic images are similar to those that would have been derived from real data. Our results indicate that synthetic data sharing may be an attractive alternative to sharing real patient-level data in the right setting.
Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.
Authors: David J. Pinato, Sam M Murray, Alejandro Forner, Takahiro Kaneko, Petros Fessas, Pierluigi Toniutto, Beatriz Mínguez, Valentina Cacciato, Claudio Avellini, Alba Diaz, Rosemary J. Boyton, Daniel M. Altmann, Robert D Goldin, Ayse U Akarca, Teresa Marafioti, Francesco A Mauri, Edoardo Casagrande, Federica Grillo, Edoardo Giannini, Sherrie Bhoori, Vincenzo Mazzaferro
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Modulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment. Methods We profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T− (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163. Results We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p&lt;0.001) compared with T−. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T−. Conclusions TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.
Obesity in US children increased at an unprecedented rate during the pandemic
Authors: Owen Dyer
Journal: BMJ (2021)

Obesity in US children increased at an unprecedented rate during the pandemic Owen DyerThe proportion of US children who are overweight or obese, which has climbed steadily for years, surged to unprecedented levels during the pandemic, according to new figures from the Centers for Disease Control and Prevention (CDC). 1 Among a cohort of 432 302 people aged 2-19 years, the rate of body mass index (BMI) increase roughly doubled during the pandemic compared with the period preceding it.The greatest increases were seen in children aged 6-11 and in those already overweight before the pandemic.
Sixty seconds on . . . Nicki Minaj
Authors: Mun-Keat Looi
Journal: BMJ (2021)

The US rap superstar, of course. Last week, Minaj found herself in an unlikely war of words with England’s chief medical officer Chris Whitty and the prime minister Boris Johnson after suggesting covid vaccination could cause impotency.

After it emerged that guests at the Met Gala in New York had to be covid vaccinated to attend, Minaj refused on the grounds that her cousin in Trinidad turned down an invitation to get vaccinated “cuz his …
Printability during projection-based 3D bioprinting
Authors: Kang Yu, Xinjie Zhang, Yuan Sun, Qing Gao, Jianzhong Fu, Xiujun Cai, Yong He
Journal: Bioactive Materials (2021)

Since projection-based 3D bioprinting (PBP) could provide high resolution, it is well suited for printing delicate structures for tissue regeneration. However, the low crosslinking density and low photo-crosslinking rate of photocurable bioink make it difficult to print fine structures. Currently, an in-depth understanding of the is lacking. Here, a research framework is established for the analysis of printability during PBP. The gelatin methacryloyl (GelMA)-based bioink is used as an example, and the printability is systematically investigated. We analyze the photo-crosslinking reactions during the PBP process and summarize the specific requirements of bioinks for PBP. Two standard quantized models are established to evaluate 2D and 3D printing errors. Finally, the better strategies for bioprinting five typical structures, including solid organs, vascular structures, nerve conduits, thin-wall scaffolds, and micro needles, are presented.
Smoke-free vehicles: impact of legislation on child smoke exposure across three countries
Authors: Anthony A. Laverty, Filippos T. Filippidis, Jasper V. Been, Frances Campbell, Hazel Cheeseman, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2021)

Second-hand tobacco smoke is a significant threat to the health of children [1]. Across Europe, 12% of children are regularly exposed, a percentage that has stalled in the last decade [2]. In addition to placing children at greater risk of health complications, such as asthma attacks and respiratory tract infections [1], exposure to smoking behaviour by family and peers increases the likelihood of tobacco smoking uptake [3]. Legislation to require no tobacco smoking in vehicles with children is effective in reducing exposure to second-hand smoke <https://bit.ly/3z8fZRa> Action on Smoking and Health commission and fund the annual youth survey, which is conducted by YouGov.
U2af1 is a haplo-essential gene required for hematopoietic cancer cell survival in mice
Authors: Brian A. Wadugu, Sridhar Nonavinkere Srivatsan, Amanda Heard, Michael O. Alberti, Matthew Ndonwi, Jie Liu, Sarah Grieb, Joseph Bradley, Jin Shao, Tanzir Ahmed, Cara L. Shirai, Ajay Khanna, Dennis L. Fei, Christopher A. Miller, Timothy A. Graubert, Matthew J. Walter
Journal: Journal of Clinical Investigation (2021)

Somatic mutations in the spliceosome gene U2AF1 are common in patients with myelodysplastic syndromes. U2AF1 mutations that code for the most common amino acid substitutions are always heterozygous, and the retained WT allele is expressed, suggesting that mutant hematopoietic cells may require the residual WT allele to be viable. We show that hematopoiesis and RNA splicing in U2af1 heterozygous knockout mice were similar to those in control mice, but that deletion of the WT allele in U2AF1(S34F) heterozygous mutant-expressing hematopoietic cells (i.e., hemizygous mutant) was lethal. These results confirm that U2AF1 mutant hematopoietic cells are dependent on the expression of WT U2AF1 for survival in vivo and that U2AF1 is a haplo-essential cancer gene. Mutant U2AF1(S34F)-expressing cells were also more sensitive to reduced expression of WT U2AF1 than nonmutant cells. Furthermore, mice transplanted with leukemia cells expressing mutant U2AF1 had significantly reduced tumor burden and improved survival after the WT U2af1 allele was deleted compared with when it was not deleted. These results suggest that selectively targeting the WT U2AF1 allele in heterozygous mutant cells could induce cancer cell death and be a therapeutic strategy for patients harboring U2AF1 mutations.
P04.14 Sporadic wild-type multiple meningiomas harbor distinct driver mutations
Authors: T Juratli, I Prilop, F Saalfeld, M Meinhardt, G Schackert, T Pinzer
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Multiple meningiomas (MM) are rare and present a unique management challenge. While the mutational landscape of single meningiomas has been extensively studied, understanding of the molecular pathogenesis of sporadic MM remains incomplete. The objective of this study is to elucidate the genetic features of sporadic MM. MATERIAL AND METHODS We identified eight patients with MM (n=17) defined as ≥2 spatially separated synchronous or metachronous meningiomas. We profiled genetic changes in these tumors using a next generation sequencing (NGS) assay that covers a large number of targetable and frequently mutated genes in meningiomas including AKT1, KLF4, NF2, PIK3CA/PIK3R1, POLR2A, SMARCB1, SMO, SUFU, TRAF7, and the TERT promoter. RESULTS Most of MM were WHO grade 1 (n= 14, 82.3%). Within individual patients, no driver mutation was shared between separate tumors. All but two cases harbored different hot spot mutations in known meningioma-driver genes like TRAF7 (n= 5), PIK3CA (n= 3), AKT1 (n= 3) and SMO (n= 1). Moreover, individual tumors differed in histologic subtype in 7/8 patients. The low frequency of NF2 mutations in our series stands in contrast to previous studies that included hereditary cases arising in the setting of neurofibromatosis type 2 (NF2). CONCLUSION Our findings provide evidence for genomic inter-tumor heterogeneity and an independent molecular origin of sporadic NF2 wild-type MM. Furthermore, these findings suggest that genetic characterization of each lesion is warranted in sporadic MM.
Intercrypt sentinel macrophages tune antibacterial NF-κB responses in gut epithelial cells via TNF
Authors: Annika Hausmann, Boas Felmy, Leo Kunz, Sanne Kroon, Dorothée Lisa Berthold, Giverny Ganz, Ioana Sandu, Toshihiro Nakamura, Nathan Sébastien Zangger, Yang Zhang, Tamas Dolowschiak, Stefan Alexander Fattinger, Markus Furter, Anna Angelika Müller-Hauser, Manja Barthel, Katerina Vlantis, Laurens Wachsmuth, Jan Kisielow, Luigi Tortola, Danijela Heide, Mathias Heikenwälder, Annette Oxenius, Manfred Kopf, Timm Schroeder, Manolis Pasparakis, Mikael Erik Sellin, Wolf-Dietrich Hardt
Journal: The Journal of Experimental Medicine (2021)

Intestinal epithelial cell (IEC) NF-κB signaling regulates the balance between mucosal homeostasis and inflammation. It is not fully understood which signals tune this balance and how bacterial exposure elicits the process. Pure LPS induces epithelial NF-κB activation in vivo. However, we found that in mice, IECs do not respond directly to LPS. Instead, tissue-resident lamina propria intercrypt macrophages sense LPS via TLR4 and rapidly secrete TNF to elicit epithelial NF-κB signaling in their immediate neighborhood. This response pattern is relevant also during oral enteropathogen infection. The macrophage-TNF-IEC axis avoids responses to luminal microbiota LPS but enables crypt- or tissue-scale epithelial NF-κB responses in proportion to the microbial threat. Thereby, intercrypt macrophages fulfill important sentinel functions as first responders to Gram-negative microbes breaching the epithelial barrier. The tunability of this crypt response allows the induction of defense mechanisms at an appropriate scale according to the localization and intensity of microbial triggers.
COVID-19 outbreak investigation and response in a penitentiary setting: the experience of a prison in Italy, February to April 2020
Authors: Ruggero Giuliani, Cristina Cairone, Lara Tavoschi, Laura Ciaffi, Teresa Sebastiani, Raffaella Bartolotti, Silvia Mancini, Laura Cremonini, Roberto Ranieri
Journal: Eurosurveillance (2021)

Prisons are high-risk settings for COVID-19 and present specific challenges for prevention and control. We describe a COVID-19 outbreak in a large prison in Milan between 20 February and 30 April 2020. We performed a retrospective analysis of routine data collected during the COVID-19 emergency in prison. We analysed the spatial distribution of cases and calculated global and specific attack rates (AR). We assessed prevention and control measures. By 30 April 2020, 57 confirmed COVID-19 cases and 66 clinically probable cases were recorded among a population of 1,480. Global AR was 8.3%. The index case was a custodial officer. Two clusters were detected among custodial staff and healthcare workers. On 31 March, a confirmed case was identified among detained individuals. COVID-19 spread by physical proximity or among subgroups with cultural affinity, resulting in a cluster of 22 confirmed cases. Following index case identification, specific measures were taken including creation of a multidisciplinary task-force, increasing diagnostic capacity, contact tracing and dedicated isolation areas. Expanded use of personal protective equipment, environmental disinfection and health promotion activities were also implemented. Outbreaks of COVID-19 in prison require heightened attention and stringent comprehensive measures.
Social toxicity among patients with cancer diagnosis in Saudi Arabia: A descriptive phenomenological qualitative study.
Authors: Abdul-Rahman Jazieh, Hoda Jradi, Omar B. Da'ar, Mohammad Alkaiyat, Ashwaq Alolayan
Journal: Journal of Clinical Oncology (2021)

151 Background: The objective of this study was to describe the social and financial experience of cancer patients throughout the continuum of their disease. Methods: A descriptive phenomenological qualitative study was conducted in the Oncology Department in King Abdulaziz Medical City in Saudi Arabia. Four focus groups, including 15 cancer patients (9 women and 6 men) and 11 care givers (5 females and 6 males), and face-to-face interviews among 29 healthcare workers including physicians, nurses, social workers, and health educators were conducted. All discussions were transcribed verbatim and entered into NVIVO software and themes were extracted and examined. Results: Focus group discussions and interviews revealed a range of social and financial themes such as experiencing fear of spousal abandonment, concerns of becoming a social and financial burden to the family, poor physical appearance, and hair loss for females. Experiencing depression, social isolation, fear of infertility, and fear of job loss for both genders. Males were mostly affected by facial hair loss and sexual dysfunction. An emerging theme regarding the elderly patient was neglect by family members and isolation from society with the intention of protecting them. Acceptability of disease and submission as an act of religiosity was a general positive feeling. Conclusions: This descriptive phenomenological qualitative study characterized the significant social and financial toxicities among patients with cancer diagnosis in Saudi Arabia. Such phenomena and context are expected to enable a deeper understanding of oncology professionals’ experiences in order to better deliver patient-centered care as a component of a holistic approach.
Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity
Authors: Enyuan Cao, Matthew J. Watt, Cameron J. Nowell, Tim Quach, Jamie S. Simpson, Vilena De Melo Ferreira, Sonya Agarwal, Hannah Chu, Anubhav Srivastava, Dovile Anderson, Gracia Gracia, Alina Lam, Gabriela Segal, Jiwon Hong, Luojuan Hu, Kian Liun Phang, Alistair B. J. Escott, John A. Windsor, Anthony R. J. Phillips, Darren J. Creek, Natasha L. Harvey, Christopher J. H. Porter, Natalie L. Trevaskis
Journal: Nature Metabolism (2021)