Objectives:
To determine if heart rate (HR) is associated with desaturation indexes as HR is associated with arrhythmia and sudden death.
Study design:
A community based cross-sectional study of 1214 ...Alaskan Inuit.
Methods:
Data of FA concentrations from plasma and red blood cell membranes from those ≥35 years of age (n = 819) were compared to basal HR at the time of examination. Multiple linear regression with backward stepwise selection was employed to analyze the effect of the desaturase indexes on HR, after adjustment for relevant covariates.
Results:
The Δ
5
desaturase index (Δ
5
-DI) measured in serum has recently been associated with a protective role for cardiovascular disease. This index measured here in plasma and red blood cells showed a negative correlation with HR. The plasma stearoyl-CoA-desaturase (SCD) index, previously determined to be related to cardiovascular disease (CVD) mortality, on the other hand, was positively associated with HR, while the Δ
6
desaturase index (Δ
6
-DI) had no significant effect on HR.
Conclusion:
Endogenous FA desaturation is associated with HR and thereby, in the case of SCD, possibly with arrhythmia and sudden death, which would at least partially explain the previously observed association between cardiovascular mortality and desaturase activity.
To describe first episodes of bacterial cholangitis complicating autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD) and to identify risk ...factors for cholangitis episodes among patients with ADPKD-associated polycystic liver disease (PLD).
We searched the electronic medical records at our tertiary referral center for episodes of cholangitis in patients with ADPKD or ADPLD from January 1, 1996, through June 30, 2017. Cases were categorized as suspected or definite cholangitis by expert review. Clinical, laboratory, and radiologic data were manually abstracted. A nested case-control study was conducted to investigate risk factors for cholangitis in patients with ADPKD.
We identified 29 cases of definite or suspected cholangitis complicating PLD (24 with ADPKD-associated PLD and 5 with ADPLD). Among patients with definite cholangitis in ADPKD-associated PLD (n=19) vs ADPLD (n=4), the mean ± SD age was 62.4±12.2 vs 55.1±8.6 years, and 9 (47.4%) vs 0 (0%), respectively, were male. The odds of gallstones (odds ratio OR, 21.6; 95% CI, 3.17-927; P<.001), prior cholecystectomy (OR, 12.2; 95% CI, 1.59-552; P=.008), duodenal diverticulum (OR, 13.5; 95% CI, 2.44 to not estimable; P=.004), type 2 diabetes mellitus (OR, 6.41; 95% CI, 1.01 to not estimable; P=.05), prior endoscopic retrograde cholangiopancreatography (OR, 14.0; 95% CI, 1.80-631; P=.005), and prior kidney transplant (OR, 8.06; 95% CI, 1.72-76.0; P=.004) were higher in patients with ADPKD-associated PLD with definite cholangitis compared to controls.
Gallstones, prior cholecystectomy, duodenal diverticulosis, type 2 diabetes mellitus, prior endoscopic retrograde cholangiopancreatography, and prior kidney transplant constituted risk factors for cholangitis among patients with ADPKD-associated PLD.
Academic, industry, regulatory leaders and patient advocates in cancer clinical research met in November 2018 at the Innovation and Biomarkers in Cancer Drug Development meeting in Brussels to ...address the existing dichotomy between increasing calls for personalised oncology approaches based on individual molecular profiles and the need to make resource and regulatory decisions at the societal level in differing health-care delivery systems around the globe. Novel clinical trial designs, the utility and limitations of real-world evidence (RWE) and emerging technologies for profiling patient tumours and tumour-derived DNA in plasma were discussed. While randomised clinical trials remain the gold standard approach to defining clinical utility of local and systemic therapeutic interventions, the broader adoption of comprehensive tumour profiling and novel trial designs coupled with RWE may allow patient and physician autonomy to be appropriately balanced with broader assessments of safety and overall societal benefit.
•Develop biomarkers using rigorous methodology, rationality in clinical context, not limited to drug development.•Standardise biomarker testing seeking equivalence between Companion Diagnostics and Laboratory-Developed Tests.•Improve clinical study designs to include patient-centred end-points and core outcome sets.•Bridge the gap between individualised and population-based oncology using real-world evidence.
Epidermal growth factor receptor tyrosine kinase inhibition is not protective in PCK rats.
Advances in the understanding of cystogenesis, identification of the PKHD1 gene and availability of a rat ...model (the PCK rat) caused by a Pkhd1 mutation facilitate testing of therapies for autosomal-recessive polycystic kidney disease (ARPKD). Considerable support exists for the importance of the epidermal growth factor (EGF)/transforming growth factor-alpha (TGF-α)/EGF receptor (EGFR) axis and of the adenylyl cyclase-adenosine 3′,5′-cyclic monophosphate (cAMP) pathway in the pathogenesis of cyst formation and progressive enlargement.
To determine whether EGFR tyrosine kinase inhibition is protective in the PCK rat, male and female animals were treated with EKI-785 or EKB-569 or with vehicle alone between 3 and 10 weeks of age. Biochemical and histomorphometric analysis, immunohistochemistry, immunoblotting, enzyme immunoassay, and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to ascertain the effects of treatment.
Contrary to other murine models of ARPKD, overexpression and apical mislocalization of EGFR were not detected in the PCK rats. Consistent with these expression results, EKI-785 or EKB-569 administration had no effect or worsened PKD, and had no effect on the development of fibrocystic liver disease. Increased renal cAMP and vasopressin V2 receptor expression were observed in the EKI-785–treated animals.
EGFR tyrosine kinase inhibition did not protect PCK rats from the development of PKD. This may be due to effects on collecting duct cAMP that counteract possible beneficial effects on the extracellular-regulated protein kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway, particularly in the absence of EGFR overexpression or mislocalization. The relevance of these observations to the treatment of human cystic kidney diseases deserves further study.
ObjectiveIdentify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19.DesignMulticentre prospective observational cohort study ...using questionnaire data at visit 1 (2–7 months post discharge) and visit 2 (10–14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations.Setting64 UK acute hospital Trusts.ParticipantsAdults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19.Main outcome measuresSelf-reported swallow, communication, voice and cognitive compromise.ResultsCompromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001).ConclusionSwallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.
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