Introducing mathematical modelling of kinetics into the therapeutic decision

Background Evolution of metastatic melanoma (MM) under B-RAF inhibitors (BRAFi) is unpredictable, but anticipation is crucial for therapeutic decision. Kinetics changes in metastatic growth are driven by molecular and immune events, and thus we hypothesized that they convey relevant information for decision making. Patients and methods We used a retrospective cohort of 37 MM patients treated by BRAFi only with at least 2 close CT-scans available before BRAFi, as a model to study kinetics of metastatic growth before, under and after BRAFi. All metastases (mets) were individually measured at each CT- scan. From these measurements, different measures of growth kinetics of each met and total tumor volume were computed at different time points. A historical cohort permitted to build a reference model for the expected spontaneous disease kinetics without BRAFi. All variables were included in Cox and multistate regression models for survival, to select best candidates for predicting overall survival. Results Before starting BRAFi, fast kinetics and moreover a wide range of kinetics (fast and slow growing mets in a same patient) were pejorative markers. At the first assessment after BRAFi introduction, high heterogeneity of kinetics predicted short survival, and added independent information over RECIST progression in multivariate analysis. Metastatic growth rates after BRAFi discontinuation was usually not faster than before BRAFi introduction, but they were often more heterogeneous than before. Conclusions Monitoring kinetics of different mets before and under BRAFi by repeated CT-scan provides information for predictive mathematical modelling. Disease kinetics deserves more interes

Prevalence and predictors for 72-h mortality after transfer to acute palliative care unit

PURPOSE Accurate prediction of survival is important to facilitate clinical decision-making and improve quality of care at the end of life. While it is well documented that survival prediction poses a challenge for treating physicians, the need for clinically valuable predictive factors has not been met. This study aims to quantify the prevalence of patient transfer 72 h before death onto the acute palliative care unit in a tertiary care center in Switzerland, and to identify factors predictive of 72-h mortality. METHODS All patients hospitalized between January and December 2020 on the acute palliative care unit of the Competence Center Palliative Care of the Department of Radiation Oncology at the University Hospital Zurich were assessed. Variables were retrieved from the electronic medical records. Univariable and multivariable logistic regressions were used to identify predictors of mortality. RESULTS A total of 398 patients were screened, of which 188 were assessed. Every fifth patient spent less than 72 h on the acute palliative care unit before death. In multivariable logistic regression analysis, predictors for 72-h mortality after transfer were no prior palliative care consult (p = 0.011), no advance care directive (p = 0.044), lower performance status (p = 0.035), lower self-care index (p = 0.003), and lower blood albumin level (p = 0.026). CONCLUSION Late transfer to the acute palliative care unit is not uncommon, which can cause additional distress to patients and caretakers. Though clinically practical short-term survival predictors remain largely unidentified, early integration of palliative care should be practiced more regularly in patients with life-limiting illness

Tm4sf1-marked Endothelial Subpopulation Is Dysregulated in Pulmonary Arterial Hypertension.

The identification and role of endothelial progenitor cells in pulmonary arterial hypertension (PAH) remain controversial. Single-cell omics analysis can shed light on endothelial progenitor cells and their potential contribution to PAH pathobiology. We aim to identify endothelial cells that may have stem/progenitor potential in rat lungs and assess their relevance to PAH. Differential expression, gene set enrichment, cell-cell communication, and trajectory reconstruction analyses were performed on lung endothelial cells from single-cell RNA sequencing of Sugen-hypoxia, monocrotaline, and control rats. Relevance to human PAH was assessed in multiple independent blood and lung transcriptomic data sets. Rat lung endothelial cells were visualized by immunofluorescence in situ, analyzed by flow cytometry, and assessed for tubulogenesis in vitro. A subpopulation of endothelial cells (endothelial arterial type 2 [EA2]) marked by Tm4sf1 (transmembrane 4 L six family member 1), a gene strongly implicated in cancer, harbored a distinct transcriptomic signature enriched for angiogenesis and CXCL12 signaling. Trajectory analysis predicted that EA2 has a less differentiated state compared with other endothelial subpopulations. Analysis of independent data sets revealed that TM4SF1 is downregulated in lungs and endothelial cells from patients and PAH models, is a marker for hematopoietic stem cells, and is upregulated in PAH circulation. TM4SF1+CD31+ rat lung endothelial cells were visualized in distal pulmonary arteries, expressed hematopoietic marker CD45, and formed tubules in coculture with lung fibroblasts. Our study uncovered a novel Tm4sf1-marked subpopulation of rat lung endothelial cells that may have stem/progenitor potential and demonstrated its relevance to PAH. Future studies are warranted to further elucidate the role of EA2 and Tm4sf1 in PAH

Combining Habitat Analysis and Autoencoder Neural Network for Feature Extraction to Predict COVID 19 Infection in CT Images

https://openworks.mdanderson.org/sumexp21/1254/thumbnail.jp

Recent developments in frailty identification, management, risk factors and prevention : A narrative review of leading journals in geriatrics and gerontology

Funding The Frailty Epidemiology Research Network (EPI-FRAIL) is an international collaborative project aimed at filling knowledge gaps in the field of frailty epidemiology. The network was established as part of a NWO/ZonMw Veni fellowship awarded to E.O. Hoogendijk (Grant no. 91618067). P. Hanlon is funded through a Clinical Research Training Fellowship from the Medical Research Council (Grant reference: MR/S021949/1). Z. Liu was supported by the Soft Science Research Program of Zhejiang Province (2023KXCX-KT011). J. Jylhävä has received grant support from the Swedish Research Council (grant no. 2018-02077), the Academy of Finland (grant no. 349335), the Sigrid Jusélius Foundation, the Yrjö Jahnsson Foundation and the Instrumentarium Science Foundation. M. Sim is supported by a Royal Perth Hospital Research Foundation Career Advancement Fellowship and an Emerging Leader Fellowship from the Future Health Research and Innovation Fund (Department of Health, Western Australia). R. Ambagtsheer receives funding from the Australian Medical Research Future Fund (grant #MRF2016140). D. L. Vetrano receives financial support from the Swedish Research Council (2021-03324). S. Shi reports funding from the National Institute of Aging, R03AG078894-01. None of the funding agencies had any role in the conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.Peer reviewedPublisher PD

Camellia sinensis extract delays microbiological and oxidative changes in striped catfish fillets during frozen storage

peer reviewedThis study investigated the effects of tea leaf (Camellia sinensis) extract on the quality of striped catfish (Pangasianodon hypophthalmus) fillets during 18-months of frozen storage (-20 ± 2 °C). Fillet samples were submitted to the treatments Control (cold tap water), CS 7.63 (C. sinensis extract solution 7.63 µg/mL) and CS 625 (C. sinensis extract 625 µg/mL) and stored for 18 months, with collections performed at 0, 1, 3, 6, 9, 12 and 18 months. Total viable count, physicochemical parameters (water holding capacity, total volatile basic nitrogen, peroxide value, thiobarbituric acid reactive substances, moisture and pH), sensory properties and color measurement were evaluated. Results showed that fillets treated with C.a sinensis extracts slightly reduced lipid oxidation, inhibited bacterial growth and improved sensory properties compared to untreated samples, without causing significant changes in the other quality indicators. The findings indicated that the green tea leaf extract immersion treatments, contributed to the improved quality preservation of striped catfish fillets during frozen storage

Single-Cell Study of Two Rat Models of Pulmonary Arterial Hypertension Reveals Connections to Human Pathobiology and Drug Repositioning.

Rationale: The cellular and molecular landscape and translational value of commonly used models of pulmonary arterial hypertension (PAH) are poorly understood. Single-cell transcriptomics can enhance molecular understanding of preclinical models and facilitate their rational use and interpretation.Objectives: To determine and prioritize dysregulated genes, pathways, and cell types in lungs of PAH rat models to assess relevance to human PAH and identify drug repositioning candidates.Methods: Single-cell RNA sequencing was performed on the lungs of monocrotaline (MCT), Sugen-hypoxia (SuHx), and control rats to identify altered genes and cell types, followed by validation using flow-sorted cells, RNA in situ hybridization, and immunofluorescence. Relevance to human PAH was assessed by histology of lungs from patients and via integration with human PAH genetic loci and known disease genes. Candidate drugs were predicted using Connectivity Map.Measurements and Main Results: Distinct changes in genes and pathways in numerous cell types were identified in SuHx and MCT lungs. Widespread upregulation of NF-κB signaling and downregulation of IFN signaling was observed across cell types. SuHx nonclassical monocytes and MCT conventional dendritic cells showed particularly strong NF-κB pathway activation. Genes altered in SuHx nonclassical monocytes were significantly enriched for PAH-associated genes and genetic variants, and candidate drugs predicted to reverse the changes were identified. An open-access online platform was developed to share single-cell data and drug candidates (http://mergeomics.research.idre.ucla.edu/PVDSingleCell/).Conclusions: Our study revealed the distinct and shared dysregulation of genes and pathways in two commonly used PAH models for the first time at single-cell resolution and demonstrated their relevance to human PAH and utility for drug repositioning

Malaria and Fetal Growth Alterations in the 3(rd) Trimester of Pregnancy: A Longitudinal Ultrasound Study.

Pregnancy associated malaria is associated with decreased birth weight, but in-utero evaluation of fetal growth alterations is rarely performed. The objective of this study was to investigate malaria induced changes in fetal growth during the 3(rd) trimester using trans-abdominal ultrasound. An observational study of 876 pregnant women (398 primi- and secundigravidae and 478 multigravidae) was conducted in Tanzania. Fetal growth was monitored with ultrasound and screening for malaria was performed regularly. Birth weight and fetal weight were converted to z-scores, and fetal growth evaluated as fetal weight gain from the 26th week of pregnancy. Malaria infection only affected birth weight and fetal growth among primi- and secundigravid women. Forty-eight of the 398 primi- and secundigravid women had malaria during pregnancy causing a reduction in the newborns z-score of -0.50 (95% CI: -0.86, -0.13, P = 0.008, multiple linear regression). Fifty-eight percent (28/48) of the primi- and secundigravidae had malaria in the first half of pregnancy, but an effect on fetal growth was observed in the 3(rd) trimester with an OR of 4.89 for the fetal growth rate belonging to the lowest 25% in the population (95%CI: 2.03-11.79, P<0.001, multiple logistic regression). At an individual level, among the primi- and secundigravidae, 27% experienced alterations of fetal growth immediately after exposure but only for a short interval, 27% only late in pregnancy, 16.2% persistently from exposure until the end of pregnancy, and 29.7% had no alterations of fetal growth. The effect of malaria infections was observed during the 3(rd) trimester, despite infections occurring much earlier in pregnancy, and different mechanisms might operate leading to different patterns of growth alterations. This study highlights the need for protection against malaria throughout pregnancy and the recognition that observed changes in fetal growth might be a consequence of an infection much earlier in pregnancy.\u

Challenges to access and provision of palliative care for people who are homeless : a systematic review of qualitative research

Background: People who are homeless or vulnerably housed are a marginalized group who often experience high rates of morbidity and die young as a result of complex problems. Access to health care and support can be challenging, with access to palliative care even more so. This review presents a synthesis of published qualitative research exploring from the perspective of homeless people and those working to support them, current challenges to palliative care access and provision, in addition to suggestions for what may improve palliative care for this population. Methods: Systematic review of qualitative research analysed using thematic synthesis. PsycINFO, Medline, Sociological Abstracts, Social Services Abstracts, Science citations index and CINAHL were searched up to September 2016. Thematic synthesis involved a three-step inductive process to develop a deeper understanding of the challenges to and suggestions for the access and provision of palliative care for homeless people. Results: Thirteen qualitative articles, reporting nine studies were identified. The challenges to access and provision to palliative care were drawn from the data covering three broad areas, namely “the chaotic lifestyles sometimes associated with being homeless”, “the delivery of palliative care within a hostel for homeless people” and provision within “mainstream health care systems”. Obstacles were related to homeless persons competing day-to-day priorities, their experience of stigma in mainstream settings, the high burden on hostel staff in supporting residents at the end of life and inflexibility in mainstream health care systems. Suggestions for improving access to palliative care include building trust between homeless persons and health professionals, increasing collaboration between and flexibility within services, and providing more training and support for all professionals. Conclusions: The provision of palliative care can be complicated for all populations, however delivering palliative care for people who are homeless is influenced by a potentially greater and more varied range of factors, on both individual and systemic levels, than providing palliative care for the housed population. Careful consideration and potentially great changes will be needed within health care systems to ensure homeless populations have equitable access to palliative care