• Mcconnell Hickman opublikował 5 miesięcy, 1 tydzień temu

    Immune checkpoint inhibitors, medications that boost host immune response to tumor cells, are now at the forefront of anti-cancer therapy. While efficacious in the treatment of patients with advanced cancer, immune checkpoint inhibitors can lead to serious autoimmune side effects involving any organ in the body. Immune checkpoint inhibitor nephrotoxicity is an increasingly recognized cause of acute kidney injury in patients with cancer. This review discusses the clinical and histopathologic diagnosis of immune checkpoint inhibitor nephrotoxicity, highlighting the need for more reliable non-invasive diagnostic testing. We focus on the controversy surrounding the role of kidney biopsy in diagnosis and management of suspected immune checkpoint inhibitor toxicity with inclination toward pursuing kidney biopsy in certain outlined circumstances. Finally, we briefly discuss treatment of immune checkpoint inhibitor nephrotoxicity and the decision to re-challenge immunotherapy in patients who experience these adverse events.

    Intravascular (IV) catheters are the most invasive medical device in healthcare. Localized priority-setting related to IV catheter quality surveillance is a key objective of recent healthcare reform in Australia. We sought to determine the plausibility of using electronic health record (EHR) data for catheter surveillance by mapping currently available data across state-wide platforms. This work has identified barriers and facilitators to a state-wide EHR surveillance initiative.

    Data variables were generated and mapped from routinely used EHR sources across Queensland, Australia through a systematic search of gray literature and expert consultation with clinical information specialists. EHR systems were eligible for inclusion if they collected data related to IV catheter insertion, care, or outcomes of hospitalized patients. Generated variables were mapped against international recommendations for IV catheter surveillance, with data linkage and data export capacity narratively summarized.

    We identifiednd transform health surveillance.

    Current data linkage across EHR systems limits the development of an IV catheter quality surveillance system to provide timely data related to catheter complications and harm. To facilitate reliable and timely surveillance of catheter outcomes using clinical informatics, substantial work is needed to overcome existing barriers and transform health surveillance.

    To improve the fidelity of the cellular transcriptome of disaggregated synovial tissue for applications such as single-cell RNA sequencing (scRNAseq) by modifying the disaggregation technique.

    Osteoarthritis (OA) and rheumatoid arthritis (RA) synovia were collected at arthroplasty. RNA was extracted from intact or disaggregated replicate pools of tissue fragments. Disaggregation was performed with either a proprietary protease, Liberase TL (Lib) as a reference method, Liberase TL with an RNA polymerase inhibitor flavopyridol (Flavo), or a cold digestion with subtilisin A (SubA). qPCR on selected markers and RNAseq were used to compare disaggregation methods using the original intact tissue as reference.

    Disaggregated cell yield and viability were similar for all three methods with some viability improved (SubA). Candidate gene analysis showed that Lib alone dramatically increased expression of several genes involved in inflammation and immunity compared with intact tissue and was unable to differentiates on the transcriptome. We found that disaggregation with an RNA polymerase inhibitor or using a cold enzyme tended to limit induction of some relevant transcripts during tissue processing. The resultant data in the disaggregated transcriptome better represented the in situ transcriptome. The specific method chosen can be tailored to the genes of interest and the hypotheses being tested in order to optimize the fidelity of technique for applications based on cell suspensions such as sorted populations or scRNAseq.The need for innovative payment models for health technologies with high upfront costs has emerged due to affordability concerns across the world. Early technology adopter countries have been experimenting with delayed payment schemes. Our objective included listing potential barriers for implementing delayed payment models and recommendations on how to address these barriers in lower income countries of Central and Eastern Europe (CEE) and the Middle East (ME). We conducted a survey, an exploratory literature review and an iterative brainstorming about potential barriers and solutions to implement delayed payment models in these two regions. A draft list of recommendations was validated in a virtual workshop with payer experts from the two regions. Eight barriers were identified in 4 areas, including transaction costs and administrative burden, payment schedule, information technology and data infrastructure, and governance. Fifteen practical recommendations were prepared to address these barriers, including recommendations that are specific to lower income countries, and recommendations that can be applied more universally, but are more crucial in countries with severe budget constraints. Conclusions of this policy research can be considered as an initial step in a multistakeholder dialogue about implementing delayed payment schemes in CEE and ME countries.

    Early identification and treatment are paramount for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). Unfortunately, there is no single crucial biomarker to identify these patients in a timely manner, which makes KD the most common cause of acquired heart disease in children in developed countries. Recently, many studies have focused on the association between serum ferritin (SF), IVIG resistance, and CALs in KD. We thus performed a systematic review and meta-analysis to ascertain the diagnostic and prognostic values of SF in predicting IVIG resistance and CALs in KD in the acute phase.

    The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) were extracted from the data to evaluate the SF levels in KD. The hazard ratios (HRs) of related risk factors and their corresponding 95% confidence intervalsd as a workable and critical biomarker for the diagnosis and prognosis of IVIG resistance and CALs in patients with KD. We also propose that maintaining the dynamic balance between iron, SF, and ferroptosis will be an important therapeutic strategy to reduce the morbidity of CALs.

    [https//www.crd.york.ac.uk/prospero/], identifier [CRD42022279157].

    [https//www.crd.york.ac.uk/prospero/], identifier [CRD42022279157].

    Chemotherapy-induced polyneuropathy (CIPN) and post-chemotherapy cognitive impairment (PCCI) are frequent side effects of paclitaxel treatment. CIPN/PCCI are potentially irreversible, reduce quality of life and often lead to treatment limitations, which affect patients’ outcome. We previously demonstrated that paclitaxel enhances an interaction of the Neuronal calcium sensor-1 protein (NCS-1) with the Inositol-1,4,5-trisphosphate receptor (InsP

    R), which disrupts calcium homeostasis and triggers neuronal cell death via the calcium-dependent protease calpain in dorsal root ganglia neurons and neuronal precursor cells. Prophylactic treatment of rodents with lithium inhibits the NCS1-InsP

    R interaction and ameliorates paclitaxel-induced polyneuropathy and cognitive impairment, which is in part supported by limited retrospective clinical data in patients treated with lithium carbonate at the time of chemotherapy. Currently no data are available from a prospective clinical trial to demonstrate its efficacy.

    and (7) serum Neurofilament light chain protein concentrations.

    The study protocol was approved by the Berlin ethics committee (reference 21/232 – IV E 10) and the respective federal agency (Bundesinstitut für Arzneimittel und Medizinprodukte, reference 61-3910-4044771). The results of the study will be published in peer-reviewed medical journals as well as presented at relevant (inter)national conferences.

    [https//www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027165], identifier [DRKS00027165].

    [https//www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027165], identifier [DRKS00027165].

    To describe the time-dependent impact of granulomatosis with polyangiitis (GPA) on the risk of mortality and end-stage kidney disease (ESKD). The results would provide valuable insight regarding the most vulnerable period for patients with GPA.

    We conducted a retrospective cohort study using a nationally representative database in Taiwan. Patients with incident GPA without prior ESKD were identified, and non-GPA control cohorts were selected and matched to GPA cohorts based on sex, age, entry time and comorbidities in a 14 ratio. Cox regression model was used to estimate hazard ratios (HR) for mortality and ESKD stratified by the follow-up period.

    We identified a total of 142 GPA patients and 568 matched controls. Of those, 52 GPA patients died during follow-up, 48.1% of whom did so within the first 6 months after diagnosis. The 1-, 3-, 5-, and 10-year survival rates of GPA were 78.2, 71.2, 62.6, and 54.7%, respectively. Patients with GPA exhibited the greatest risk of mortality within the first 6 months after follow-up compared with non-GPA cohorts (HR 21.9, 95% CI 8.41-57.5). The mortality risk diminished after 1 year and to a marginally significant level during the follow-up period of 5-10 years (HR 2.71, 95% CI 0.97-7.62). Ten (7.1%) of the GPA patients experienced ESKD, and these cases occurred exclusively in the first 3 years following diagnosis.

    Our findings suggest that physicians should closely monitor the treatment response and complications of patients with GPA in the first critical 6-month period after diagnosis to improve long-term survival outcome.

    Our findings suggest that physicians should closely monitor the treatment response and complications of patients with GPA in the first critical 6-month period after diagnosis to improve long-term survival outcome.

    The Quick Sequential Organ Failure Assessment (qSOFA) score proposed by Sepsis-3 as a sepsis screening tool has shown suboptimal accuracy. Heparin-binding protein (HBP) has been shown to identify early sepsis with high accuracy. Herein, we aim to investigate whether or not HBP improves the model performance of qSOFA.

    We conducted a multicenter prospective observational study of 794 adult patients who presented to the emergency department (ED) with presumed sepsis between 2018 and 2019. For each participant, serum HBP levels were measured and the hospital course was followed. The qSOFA score was used as the comparator. The data was split into a training dataset (

    = 556) and a validation dataset (

    = 238). The primary endpoint was 30-day all-cause mortality.

    Compared with survivors, non-survivors had significantly higher serum HBP levels (median 71.5 ng/mL vs 209.5 ng/mL,

    < 0.001). Serum level of HBP weakly correlated with qSOFA class (

    = 0.240,

    < 0.001). Compared with the qSOFA model alone, the addition of admission HBP level to the qSOFA model significantly improved 30-day mortality discrimination (AUC, 0.

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