ion was associated with postintubation hypotension. (ClinicalTrials.gov registration NCT0388430.).About 30% of approved drugs are cleared predominantly by renal clearance (CLr). Of these, many are secreted by transporters. For these drugs, in vitro-to-in vivo extrapolation of transporter-mediated renal secretory clearance (CLsec,plasma) is important to prospectively predict their renal clearance and to assess the impact of drug-drug interactions and pharmacogenetics on their pharmacokinetics. Here we compared the ability of the relative expression factor (REF) and the relative activity factor (RAF) approaches to quantitatively predict the in vivo CLsec,plasma of 26 organic anion transporter (OAT) substrates assuming that OAT-mediated uptake is the rate-determining step in the CLsec,plasma of the drugs. The REF approach requires protein quantification of each transporter in the tissue (e.g., kidney) and transporter-expressing cells, whereas the RAF approach requires the use of a transporter-selective probe substrate (both in vitro and in vivo) for each transporter of interest. For the REF approach, 50% and and RAF approach for organic anion transporter-mediated CLr, the REF approach should be explored further to assess its ability to predict CLr when basolateral uptake is not the sole rate-determining step.
  Oncogenic fusions involving the 
  (
  ) gene are found in approximately 0.2% of cancers of diverse histologies. The resulting chimeric NRG1 proteins bind predominantly to HER3, leading to HER3-HER2 dimerization and activation of downstream growth and survival pathways. HER3 is, therefore, a rational target for therapy in NRG1 fusion-driven cancers.
 
  We developed novel patient-derived and isogenic models of NRG1-rearranged cancers and examined the effect of the anti-HER3 antibody, seribantumab, on growth and activation of signaling networks 
  and 
  .
 
  Seribantumab inhibited NRG1-stimulated growth of MCF-7 cells and growth of patient-derived breast (MDA-MB-175-VII, 
  fusion) and lung (LUAD-0061AS3, 
  fusion) cancer cells harboring 
  fusions or 
  amplification (HCC-95). In addition, seribantumab inhibited growth of isogenic HBEC cells expressing a 
  fusion (HBECp53-CD74-NRG1) and induced apoptosis in MDA-MB-175-VII and LUAD-0061AS3 cells. Induction of proapoptotic proteins and reduced expression of thedels.To evaluate feasibility and efficacy, checkpoint inhibitor atezolizumab was added to neoadjuvant chemoradiotherapy prior to surgery for esophagogastric adenocarcinoma. The approach was deemed feasible, and while it did not demonstrate better clinical outcome to propensity-matched patients, biomarker investigation demonstrated that high inflammation in the sample at baseline predicted therapeutic benefit.See related article by van den Ende et al., p. 3351.
  Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.
 
  To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.
 
  Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).
 
  Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.
 
  A total of 3137 participants were included in the study, and median follow-up post-surgery was hat patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.
  The complexity of general practice consultations may be increasing and varies in different settings. A measure of complexity is required to test these hypotheses.
 
  To develop a valid measure of general practice consultation complexity applicable to routine medical records.
 
  Delphi study to select potential indicators of complexity followed by a cross-sectional study in English general practices to develop and validate a complexity measure.
 
  The online Delphi study over two rounds identified potential indicators of consultation complexity.  https://www.selleckchem.com/products/PHA-793887.html  The cross-sectional study used an age-sex stratified random sample of patients and general practice face-to-face consultations from 2013/2014 in the Clinical Practice Research Datalink. The authors explored independent relationships between each indicator and consultation duration using mixed-effects regression models, and revalidated findings using data from 2017/2018. The proportion of complex consultations in different age-sex groups was assessed.
 
  A total of 32 GPsforming decisions about the range of resources needed in different practices.
  Patients with myeloma experience substantial delays in their diagnosis, which can adversely affect their prognosis.
 
  To generate a clinical prediction rule to identify primary care patients who are at highest risk of myeloma.
 
  Retrospective open cohort study using electronic health records data from the UK's Clinical Practice Research Datalink (CPRD) between 1 January 2000 and 1 January 2014.
 
  Patients from the CPRD were included in the study if they were aged ≥40 years, had two full blood counts within a year, and had no previous diagnosis of myeloma. Cases of myeloma were identified in the following 2 years. Derivation and external validation datasets were created based on geographical region. Prediction equations were estimated using Cox proportional hazards models including patient characteristics, symptoms, and blood test results. Calibration, discrimination, and clinical utility were evaluated in the validation set.
 
  Of 1 281 926 eligible patients, 737 (0.06%) were diagnosed with myeloma within 2 years.