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Hyperthermia produces profound redistribution of blood and circulatory reflex function. We investigated the potential for lower body positive pressure (LBPP) to maintain or restore haemodynamics during graded hyperthermia. Eight healthy adults rested supine in a custom-made LBPP box, sealed distal to the iliac crest. Following 5 min of normothermic rest, 20 mmHg of LBPP was applied and repeated when core temperature (Tcore ) had increased passively by +0.5 and +1°C. Primary dependent variables included mean middle cerebral artery blood velocity (MCAvmean , transcranial Doppler), mean arterial blood pressure (MAP, finger photoplethysmography), heart rate (HR) and partial pressure of end-tidal carbon dioxide (PET CO2 ). The absolute increase in MAP during LBPP was lower at Tcore +1°C (2 ± 3 mmHg), compared with normothermia (7 ± 3 p = .01). The modest increase in MCAvmean was unchanged by Tcore (normothermia, 2 ± 3 cm/s; +0.5°C, 3 ± 3 cm/s and +1°C, 3 ± 4 cm/s, p = .74). By design, PET CO2 was unchanged in all conditions from normothermic baseline (42 ± 1, p = .81). LBPP-induced changes in HR were greater at +0.5°C (-13 ± 4 b/min) and +1°C (-12 ± 6 b/min) compared with normothermia (-3 ± 3 b/min, p = .01 and p = .01, respectively). These data indicate that despite a significant attenuation in MAP to LBPP with moderate hyperthermia, MCAvmean dynamics were unchanged among the thermal manipulations.
The optimal choice between sorafenib (SOR) or lenvatinib (LEN) as the first-line treatment for unresectable hepatocellular carcinoma (u-HCC) remains debatable. Using propensity score matching, this study compares the outcomes of SOR and LEN in the molecular-targeted agent (MTA) sequential treatment of u-HCC patients.
This retrospective, multicenter, observational study recruited 137 u-HCC patients who underwent primary treatment with LEN (n=52) or SOR (n=85) between June 2017 and June 2020 after regorafenib was approved as the secondary treatment for u-HCC. Propensity score matching was used to reduce confounding, resulting in the selection of 104 patients (n=52 for the SOR and LEN cohorts).
The median overall survival was 21.8months for LEN and 20.4months for SOR. LEN exhibited significantly greater therapeutic efficacy as compared to SOR (objective response rate 3.8% [SOR] vs. 42.3% [LEN], p<0.01; progression-free survival 10months [LEN] vs. 5.1months [SOR], p<0.01). No significant intergroup differences were noted in the rate of transition to secondary MTA treatments (SOR 58.7%; LEN 48.4%), adverse events (SOR 86%; LEN 95%), and maintenance of the Child-Pugh (CP) score during treatment. Compared to non-MTA treatments, secondary MTA treatment achieved a greater improvement in survival (4.3 vs. 2.8months, p=0.0047). Multivariate analysis demonstrated that the CP score (p<0.01) and alpha-fetoprotein level (p<0.01) were independent prognostic factors.
Both SOR and LEN treatments showed a clinically comparable therapeutic efficacy as the first-line treatments for u-HCC patients in an MTA sequential therapy.
Both SOR and LEN treatments showed a clinically comparable therapeutic efficacy as the first-line treatments for u-HCC patients in an MTA sequential therapy.Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Selleck MEK162 Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.Genomic medicine in pediatric acute care is showing great promise, with rapid results from exome and genome sequencing returned within days providing critically important information for treatment and management of seriously ill children. Many have suggested that rapid acute care genomics presents novel genetic counseling issues. This is due to the need for rapid response to referrals, the immense emotional distress that parents are likely to experience when their child is in acute care, and the unfamiliar environment of the acute care setting. To explore the practice of genetic counselors in this setting, we conducted qualitative interviews with 16 genetic counselors (GCs), representing a large proportion of GCs at the frontline of providing genetic counseling in acute care settings in Australia. Interviews revealed themes describing genetic counseling in acute care, including practical challenges of counseling within a rapid turnaround time, similarities with other contexts such as prenatal counseling, and the need for education of other health professionals. Interestingly, GCs did not raise concerns in the interviews for parents' ability to provide informed consent for rapid genomic sequencing. GCs also encountered practical and organizational challenges with counseling in this setting where 24-hr care is provided, at odds with traditional '9 to 5' Genetics service delivery. Working closely in a multidisciplinary team was common and participants believed that GCs are well positioned to take a leading role in the education of other health professionals as rapid acute care genomics becomes routine clinical practice. Despite views that genetic counseling practice in rapid acute care genomics is unique, these exploratory data suggest that GCs are flexible, adaptable, and sufficiently skilled to deliver patient-centered counseling in this setting. Our work indicates GCs are ready and willing to contribute at an early stage of adoption of genomic investigations in acute care.
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