Pecksnyder7653

Discussions about goals of care with patients who are seriously ill typically occur infrequently and late in the illness trajectory, are of low quality, and focus narrowly on the patient's resuscitation preferences (ie, code status), risking provision of care that is inconsistent with patients' values. The Serious Illness Care Program (SICP) is a multifaceted communication intervention that builds capacity for clinicians to have earlier, more frequent, and more person-centered conversations.

To explore clinicians' experiences with the SICP 1 year after implementation.

This qualitative study was conducted at 2 tertiary care hospitals in Canada. The SICP was implemented at Hamilton General Hospital (Hamilton, Ontario) from March 1, 2017, to January 19, 2018, and at Foothills Medical Centre (Calgary, Alberta) from March 1, 2018, to December 31, 2020. A total of 45 clinicians were invited to participate in the study, and 23 clinicians (51.1%) were enrolled and interviewed. Semistructured interviews of cliniacilitating meaningful patient interactions that shifted the focus of goals-of-care conversations beyond discussion of code status. The perceived benefits of SICP implementation stimulated uptake within the medical units. These findings suggest that the SICP may prompt hospital culture changes in goals-of-care dialogue with patients and the care of hospitalized patients with serious illness.Metabolic diseases including type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS) are alarming health burdens around the world, while therapies for these diseases are far from satisfying as their etiologies are not completely clear yet. T2DM, NAFLD, and MetS are all complex and multifactorial metabolic disorders based on the interactions between genetics and environment. Omics studies such as genetics, transcriptomics, epigenetics, proteomics, and metabolomics are all promising approaches in accurately characterizing these diseases. And the most effective treatments for individuals can be achieved via omics pathways, which is the theme of precision medicine. In this review, we summarized the multi-omics studies of T2DM, NAFLD, and MetS in recent years, provided a theoretical basis for their pathogenesis and the effective prevention and treatment, and highlighted the biomarkers and future strategies for precision medicine.

Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear.

To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories.

We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020.

The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories.

Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those <50 to 35% for those >80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in <50 years and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, P < 0.001), but adjusted HR for diabetes was significant only in patients younger than age 50 years (HR 1.81 [1.14-2.87]).

Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.

Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.

Impaired incretin secretion may contribute to the defective insulin secretion and abnormal glucose tolerance (AGT) that associate with worse clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF). The study objective was to test the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitor-induced increases in intact incretin hormone [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] concentrations augment insulin secretion and glucagon suppression and lower postprandial glycemia in PI-CF with AGT.

26 adults from Children's Hospital of Philadelphia and University of Pennsylvania CF Center with PI-CF and AGT [defined by oral glucose tolerance test glucose (mg/dL) early glucose intolerance (1-h ≥ 155 and 2-h < 140), impaired glucose tolerance (2-h ≥ 140 and < 200 mg/dL), or diabetes (2-h ≥ 200)] were randomized to a 6-month double-blind trial of DPP-4 inhibitor sitagliptin 100 mg daily or matched placebo; 24 completed the trial (n = 12 sitagliptin; n ecting postprandial glycemia.Until recently, weight loss in older obese people was feared because of ensuing muscle loss and frailty. Facing overall increasing longevity, high rates of obesity in older individuals (age ≥ 65 years) and a growing recognition of the health and functional cost of the number of obesity years, abetted by evidence that intentional weight loss in older obese people is safe, this approach is gradually, but not unanimously, being replaced by more active principles. Lifestyle interventions that include reduced but sufficient energy intake, age-adequate protein and micronutrient intake, coupled with aerobic and resistance exercise tailored to personal limitations, can induce weight loss with improvement in frailty indices. Sustained weight loss at this age can prevent or ameliorate diabetes. More active steps are controversial. The use of weight loss medications, particularly glucagon-like peptide-1 analogs (liraglutide as the first example), provides an additional treatment tier. Its safety and cardiovascular health benefits have been convincingly shown in older obese patients with type 2 diabetes mellitus. In our opinion, this option should not be denied to obese individuals with prediabetes or other obesity-related comorbidities based on age. Finally, many reports now provide evidence that bariatric surgery can be safely performed in older people as the last treatment tier. Risk-benefit issues should be considered with extreme care and disclosed to candidates. The selection process requires good presurgical functional status, individualized consideration of the sequels of obesity, and reliance on centers that are highly experienced in the surgical procedure as well as short-term and long-term subsequent comprehensive care and support.

Individuals with monogenic diabetes due to inactivating glucokinase (GCK) variants typically do not require treatment, except potentially during pregnancy. In pregnancy, fetal GCK genotype determines whether treatment is indicated, but noninvasive methods are not clinically available.

This work aims to develop a method to determine fetal GCK genotype noninvasively using maternal cell-free fetal DNA.

This was a proof-of-concept study involving 3 pregnant women with a causal GCK variant that used information from 1) massive parallel sequencing of maternal plasma cell-free DNA, 2) direct haplotype sequences of maternal genomic DNA, and 3) the paternal genotypes to estimate relative haplotype dosage of the pathogenic variant-linked haplotype. Statistical testing of variant inheritance was performed using a sequential probability ratio test (SPRT).

In each of the 3 cases, plasma cell-free DNA was extracted once between gestational weeks 24 and 36. Taurocholic acid The fetal fraction of cell-free DNA ranged from 21.8% to 23.0%. Paternal homozygous alleles that were identical to the maternal GCK variant-linked allele were not overrepresented in the cell-free DNA. Paternal homozygous alleles that were identical to the maternal wild-type-linked allele were significantly overrepresented. Based on the SPRT, we predicted that all 3 cases did not inherit the GCK variant. Postnatal infant genotyping confirmed our prediction in each case.

We have successfully implemented a noninvasive method to predict fetal GCK genotype using cell-free DNA in 3 pregnant women carrying an inactivating GCK variant. This method could guide tailoring of hyperglycemia treatment in pregnancies of women with GCK monogenic diabetes.

We have successfully implemented a noninvasive method to predict fetal GCK genotype using cell-free DNA in 3 pregnant women carrying an inactivating GCK variant. This method could guide tailoring of hyperglycemia treatment in pregnancies of women with GCK monogenic diabetes.

Animal studies suggested that vitamin D might decrease insulin resistance. Estrogen increased insulin sensitivity and glucose tolerance in rodents. However, sex-specific association of vitamin D with insulin resistance in humans remains unclear.

To investigate the sex-dependency of the association of insulin resistance and 25-hydroxyvitamin D [25(OH)D] in a large Caucasian population.

Cross-sectional study from out-patients' blood samples with measurements of 25(OH)D and homeostatic model assessment of insulin resistance (HOMA-IR) drawn at exactly the same day (n = 1887). This cohort was divided into 3 groups (1) group with vitamin D deficiency (n = 1190), (2) group with vitamin D sufficiency (n = 686), and (3) vitamin D excess groups (n = 11); the vitamin D excess group was excluded from further analysis due to the small size.

Analysis of the entire study population showed that serum 25(OH)D was inversely associated with HOMA-IR [Spearman correlation coefficient (rs) = -0.19, P < 0.0001]. When conmin D deficient women might benefit from vitamin D substitution by improving insulin resistance. This, however, needs to be proven in adequately designed double-blind placebo-controlled clinical studies.WNT signalling is important for development in all metazoans and is associated with various human diseases. The ubiquitin-proteasome system (UPS) and regulatory endoplasmic reticulum-associated degradation (ERAD) have been implicated in the production of WNT proteins. Here, we investigated how the WNT secretory factor EVI (also known as WLS) is ubiquitylated, recognised by ERAD components and subsequently removed from the secretory pathway. We performed a focused immunoblot-based RNAi screen for factors that influence EVI/WLS protein stability. We identified the VCP-binding proteins FAF2 and UBXN4 as novel interaction partners of EVI/WLS and showed that ERLIN2 links EVI/WLS to the ubiquitylation machinery. Interestingly, we also found that EVI/WLS is ubiquitylated and degraded in cells irrespective of their level of WNT production. This K11, K48 and K63-linked ubiquitylation is mediated by the E2 ubiquitin-conjugating enzymes UBE2J2, UBE2K and UBE2N, but is independent of the E3 ubiquitin ligases HRD1 (also known as SYVN1) and GP78 (also known as AMFR).