Notes

To be, or otherwise to get: determining PNPLA3 p.I148M function.
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) improved multiple proatherogenic risk factors and reduced cardiovascular events in recent clinical trials, suggesting that they may slow progression of atherosclerosis. We tested whether exenatide once weekly reduces carotid plaque progression in individuals with type 2 diabetes.

In a double-blind, pragmatic trial, 163 participants were randomized (21) to exenatide (
= 109) or placebo (
= 54). Changes in carotid plaque volume and composition were measured at 9 and 18 months by multicontrast 3 Tesla MRI. Fasting and post-high-fat meal plasma glucose and lipids, and endothelial function responses, were measured at 3, 9, and 18 months.

Exenatide reduced hemoglobin A
(HbA
) (estimated difference vs. placebo 0.55%,
= 0.0007) and fasting and postmeal plasma glucose (19 mg/dL,
= 0.0002, and 25 mg/dL,
< 0.0001, respectively). Mean (SD) change in plaque volume in the exenatide group (0.3% [2%]) was not different from that in the placebo group (-2.2% [8%]) (
= 0.4). The change in plaque volume in the exenatide group was associated with changes in HbA
(
= 0.38,
= 0.0004), body weight, and overall plasma glucose (
= 0.29,
= 0.007 both). There were no differences in changes in plaque composition, body weight, blood pressure, fasting and postmeal plasma triglycerides, and endothelial function between the groups.

Exenatide once weekly for up to 18 months improved fasting and postprandial glycemic control but did not modify change in carotid plaque volume or composition. This study raises the possibility that short-term antiatherosclerotic effects may not play a central role in the cardiovascular benefits of GLP-1RAs.
Exenatide once weekly for up to 18 months improved fasting and postprandial glycemic control but did not modify change in carotid plaque volume or composition. This study raises the possibility that short-term antiatherosclerotic effects may not play a central role in the cardiovascular benefits of GLP-1RAs.
The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA
, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes.

One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA
, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks' gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit).

HbA
, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal olycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR).
Experiencing adversities in childhood may increase the risk of type 1 diabetes through hyperactivation of the stress response system, but the empirical evidence is conflicting. We aim to describe the age-specific incidence of type 1 diabetes for males and females separately in five predefined groups covering the most common trajectories of adversity among Danish children.

We included all 1,081,993 children without parental type 1 diabetes born in Denmark from 1980 to 1998. We used register data to estimate age-specific incidence rates of type 1 diabetes in five trajectory groups of adversity characterized by
) low adversity,
) early life material deprivation,
) persistent material deprivation,
) loss or threat of loss in the family, and
) cumulative high adversity. All analyses were stratified by sex.

In total, 5,619 people developed type 1 diabetes before 2016. MMP-9-IN-1 ic50 We found only minor differences when comparing the incidence rates of type 1 diabetes between the trajectory groups. The only clear exceptions were in the high versus low adversity group, in which males had a higher incidence of type 1 diabetes in childhood (<11 years [incidence rate ratio (IRR) 1.78 (95% CI 1.31-2.42)]) and females had a higher incidence in early adulthood (≥16 years [IRR 2.19 (95% CI 1.57-3.07)]).

Childhood adversities were generally not associated with age-specific incidence of type 1 diabetes except among those exposed to a very high and increasing annual rate of childhood adversities. Differences between highly exposed males and females seem to depend on age at onset of type 1 diabetes.
Childhood adversities were generally not associated with age-specific incidence of type 1 diabetes except among those exposed to a very high and increasing annual rate of childhood adversities. Differences between highly exposed males and females seem to depend on age at onset of type 1 diabetes.
Panel reactive antibody informs the likelihood of finding an HLA-compatible donor for transplant candidates, but has historically been associated with acute rejection and allograft survival because testing methods could not exclude the presence of concomitant donor-specific antibodies. Despite new methods to exclude donor-specific antibodies, panel reactive antibody continues to be used to determine the choice of induction and maintenance immunosuppression. The study objective was to determine the clinical relevance of panel reactive antibody in the absence of donor-specific antibodies.

Retrospective observational study of kidney allograft survival among 4058 zero HLA-A-, B-, DR-, and DQB1-mismatched transplant recipients without antibodies to donor kidney antigens encoded by these HLA gene loci.

Among 4058 first and repeat transplant recipients, patients with calculated panel reactive antibody (cPRA) 1%-97% were not at higher risk of transplant failure, compared with patients with cPRA of 0% (death censored graft loss hazard ratio, 1.07; 95% confidence interval, 0.82 to 1.41). Patients with cPRA ≥98% had a higher risk of graft loss from any cause including death (hazard ratio, 1.39; 95% confidence interval, 1.08 to 1.79) and death censored allograft failure (hazard ratio, 1.78; 95% confidence interval, 1.27 to 2.49). In stratified analyses, the higher risk of graft loss among patients with cPRA ≥98% was only observed among repeat, but not first, transplant recipients. In subgroup analysis, there was no association between cPRA and graft loss among living related transplant recipients.

Calculated panel reactive antibody is poorly associated with post-transplant immune reactivity to the allograft in the absence of donor-specific antibody.

This article contains a podcast at https//www.asn-online.org/media/podcast/CJASN/2021_01_25_CJN13640820_final.mp3.
This article contains a podcast at https//www.asn-online.org/media/podcast/CJASN/2021_01_25_CJN13640820_final.mp3.CKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). β-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine 20 ml/min per 1.73 m2). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.
Intrahospital transfers have become more common as hospital staff balance patient needs with bed availability. However, this may leave patients more vulnerable to potential pathogen transmission routes via increased exposure to contaminated surfaces and contacts with individuals.

This study aimed to quantify the association between the number of intrahospital transfers undergone during a hospital spell and the development of a hospital-acquired infection (HAI).

A retrospective case-control study was conducted using data extracted from electronic health records and microbiology cultures of non-elective, medical admissions to a large urban hospital network which consists of three hospital sites between 2015 and 2018 (n=24 240). As elderly patients comprise a large proportion of hospital users and are a high-risk population for HAIs, the analysis focused on those aged 65 years or over. Logistic regression was conducted to obtain the OR for developing an HAI as a function of intrahospital transfers until onld be considered, and further research is needed to identify unnecessary transfers. Their reduction may diminish spread of contagious pathogens in the hospital environment.
Travel time to comprehensive emergency obstetric care (CEmOC) facilities in low-resource settings is commonly estimated using modelling approaches. Our objective was to derive and compare estimates of travel time to reach CEmOC in an African megacity using models and web-based platforms against actual replication of travel.

We extracted data from patient files of all 732 pregnant women who presented in emergency in the four publicly owned tertiary CEmOC facilities in Lagos, Nigeria, between August 2018 and August 2019. For a systematically selected subsample of 385, we estimated travel time from their homes to the facility using the cost-friction surface approach, Open Source Routing Machine (OSRM) and Google Maps, and compared them to travel time by two independent drivers replicating women's journeys. We estimated the percentage of women who reached the facilities within 60 and 120 min.

The median travel time for 385 women from the cost-friction surface approach, OSRM and Google Maps was 5, 11 and 40 rce megacities. Significant gaps in geographical access to life-saving health services like CEmOC must be urgently addressed, including in urban areas. Leveraging tools that generate 'closer-to-reality' estimates will be vital for service planning if universal health coverage targets are to be realised by 2030.
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