Aims/hypothesis The UK Prospective Diabetes Study (UKPDS) risk engine has become a standard for cardiovascular risk assessment in type 2 diabetes mellitus. Skin autofluorescence was recently ...introduced as an alternative tool for cardiovascular risk assessment in diabetes. We investigated the prognostic value of skin autofluorescence for cardiovascular events in combination with the UKPDS risk engine in a cohort of patients with type 2 diabetes managed in primary care. Methods Clinical, UKPDS risk engine and skin autofluorescence data were obtained at baseline in 2001-2002 in the type 2 diabetes group (n = 973). Follow-up data concerning fatal and non-fatal cardiovascular events (primary endpoint) were obtained till 2005. Patients were classified as 'low risk' when their 10 year UKPDS risk score for fatal cardiovascular events was <10%, and 'high risk' if >10%. Skin autofluorescence was measured non-invasively with an autofluorescence reader. Skin autofluorescence was classified by the median (i.e. low risk < median, high risk > median). Results The incidence of cardiovascular events was 119 (44 fatal, 75 non-fatal). In multivariate analysis, skin autofluorescence, age, sex and diabetes duration were predictors for the primary endpoint. Addition of skin autofluorescence information to that from the UKPDS risk engine resulted in re-classification of 55 of 203 patients from the low-risk to the high-risk group. The 10 year cardiovascular event rate was higher in patients with a UKPDS score >10% when skin autofluorescence was above the median (55.8% vs 38.9%). Conclusions/interpretation Skin autofluorescence provides additional information to the UKPDS risk engine which can result in risk re-classification of a substantial number of patients. It furthermore identifies patients who have a particularly high risk for developing cardiovascular events.
Despite intense investigation, acute respiratory distress syndrome (ARDS) remains an enormous clinical problem for which no specific therapies currently exist. In this study, we used intratracheal ...lipopolysaccharide or Pseudomonas bacteria administration to model experimental acute lung injury (ALI) and to further understand mediators of the resolution phase of ARDS. Recent work demonstrates macrophages transition from a predominant proinflammatory M1 phenotype during acute inflammation to an anti-inflammatory M2 phenotype with ALI resolution. We tested the hypothesis that IL-4, a potent inducer of M2-specific protein expression, would accelerate ALI resolution and lung repair through reprogramming of endogenous inflammatory macrophages. In fact, IL-4 treatment was found to offer dramatic benefits following delayed administration to mice subjected to experimental ALI, including increased survival, accelerated resolution of lung injury, and improved lung function. Expression of the M2 proteins Arg1, FIZZ1, and Ym1 was increased in lung tissues following IL-4 treatment, and among macrophages, FIZZ1 was most prominently upregulated in the interstitial subpopulation. A similar trend was observed for the expression of macrophage mannose receptor (MMR) and Dectin-1 on the surface of alveolar macrophages following IL-4 administration. Macrophage depletion or STAT6 deficiency abrogated the therapeutic effect of IL-4. Collectively, these data demonstrate that IL-4-mediated therapeutic macrophage reprogramming can accelerate resolution and lung repair despite delayed use following experimental ALI. IL-4 or other therapies that target late-phase, proresolution pathways may hold promise for the treatment of human ARDS.
Summary
Continuous intraperitoneal insulin infusion (CIPII) is a treatment option for patients with type 1 diabetes mellitus who fail to reach adequate glycaemic control despite intensive ...subcutaneous (SC) insulin therapy. CIPII has clear advantages over SC insulin administration in terms of pharmacokinetic and pharmacodynamic properties and has been shown to improve glycaemic regulation. Due to the delivery of insulin predominantly in the portal vein, as opposed to systemically, CIPII offers a unique research model to investigate the effects of insulin on endocrine and metabolic parameters in vivo. The aim of the present article is to provide an overview of the literature with respect to the effects of CIPII on glucose management, quality of life, complications and costs, with additional focus on metabolic and endocrine aspects. Finally, future use and research objectives are discussed.
Aims/hypothesis Homozygosity for a five leucine repeat (5L-5L) in the carnosinase gene (CNDP1) has been found to be cross-sectionally associated with a low frequency of diabetic nephropathy (DN), ...mainly in type 2 diabetes. We prospectively investigated in patients with type 1 diabetes whether: (1) 5L-5L is associated with mortality; (2) there is an interaction of 5L-5L with DN or sex for prediction of mortality; and (3) 5L-5L is associated with progression to end-stage renal disease (ESRD). Methods In this prospective study in white European patients with type 1 diabetes, individuals with DN were defined by persistent albuminuria ≥300 mg/24 h. Controls without nephropathy were defined by persistent (>15 years) normoalbuminuria <30 mg/24 h. Leucine repeats were assessed with a fluorescent DNA analysis system. Onset of ESRD was defined by need to start chronic dialysis or kidney transplantation. Results The study involved 916 patients with DN and 1,170 controls. During follow-up for 8.8 years, 107 patients (14%) with 5L-5L died compared with 182 patients (13.8%) with other genotypes (p = 0.99). There was no significant interaction of 5L-5L with DN for prediction of mortality (p = 0.57), but a trend towards interaction with sex (p = 0.08). In patients with DN, HR for ESRD in 5L-5L vs other genotypes was not constant over time, with increased risk for 5L-5L beyond 8 years of follow-up (p = 0.03). Conclusions/interpretation CNDP1 polymorphism was not associated with mortality, and nor was there an interaction of this polymorphism with DN for prediction of mortality in patients with type 1 diabetes. CNDP1 polymorphism predicts progression to ESRD in patients with DN, but only late after baseline measurements.
The 2015 VESPA voyage (Volcanic Evolution of South Pacific Arcs) was a seismic and rock dredging expedition to the Loyalty and Three Kings Ridges and South Fiji Basin. In this paper we present 33 ...40Ar/39Ar, 22 micropaleontological, and two U/Pb ages for igneous and sedimentary rocks from 33 dredge sites in this little‐studied part of the southwest Pacific Ocean. Igneous rocks include basalts, dolerites, basaltic andesites, trachyandesites, and a granite. Successful Ar/Ar dating of altered and/or low‐K basalts was achieved through careful sample selection and processing, detailed petrographic and element mapping of groundmass, and incremental heating experiments on both phenocryst and groundmass separates to interpret the complex spectra produced by samples having multiple K reservoirs. The 40Ar/39Ar ages of most of the sampled lavas, irrespective of composition, are latest Oligocene to earliest Miocene (25–22 Ma); two are Eocene (39–36 Ma). The granite has a U/Pb zircon age of 23.6 ± 0.3 Ma. 40Ar/39Ar lava ages are corroborated by microfossil ages from associated sedimentary rocks. The VESPA lavas are part of a >3,000 km long disrupted belt of Eocene to Miocene subduction‐related volcanic rocks. The belt includes arc rocks in Northland New Zealand, Northland Plateau, Three Kings Ridge, and Loyalty Ridge and, speculatively, D’Entrecasteaux Ridge. This belt is the product of superimposed Eocene and Oligocene‐Miocene remnant volcanic arcs that were stranded along and near the edge of Zealandia while still‐active arc belts migrated east with the Pacific trench.
Plain Language Summary
Samples of lava from the seabed between New Zealand and New Caledonia have been dated using atomic clocks and fossils. Most lavas erupted in a big pulse of volcanic activity between 25 and 22 million years ago. They are part of a belt of now‐extinct undersea volcanoes that stretches for more than 3,000 km between New Zealand and the Solomon Islands. These volcanoes were formed by subduction of the Pacific Plate under the Australian Plate.
Key Points
A major pulse of 25–22 Ma volcanism is documented on the Loyalty and Three Kings Ridges, southwest Pacific Ocean
The ridges are part of a more than 3,000 km long belt of Eocene to Miocene remnant volcanic arcs, stranded along the edge of Zealandia
With care in sample selection, and petrological work, meaningful Ar/Ar ages can be obtained from altered and/or very low‐K submarine basalts
Purpose
Although thyroid hormones are irrefutably implicated in cardiovascular physiology, the impact of within-reference range variations of thyroid function on cardiovascular disease (CVD) remains ...unclear. Elucidating this is important, since it could foster preventive treatment and reduce global CVD burden. We therefore investigated the impact of within-reference range variations of thyroid function on all-cause and cardiovascular mortality.
Methods
We included community-dwelling individuals aged 28–75 years from a prospective cohort study, without known use of thyroid-affecting therapy and with thyrotropin within reference range. Associations of thyroid function with mortality were quantified using Cox models and adjusted for sociodemographic and cardiovascular risk factors.
Results
Mean (SD) age of the 6,054 participants (52.0% male) was 53.3 (12.0) years. During 47,594 person-years of follow-up, we observed 380 deaths from all causes and 103 from CVDs. Although higher thyrotropin was not associated with all-cause mortality (adjusted HR 1.02, 95% CI 0.92–1.14), point estimates for cardiovascular mortality diverged toward increased risk in younger (<72 years) participants (1.31, 1.00–1.72) and decreased risk in elderly (≥72 years) (0.77, 0.56–1.06). Higher free thyroxine (FT
4
) was associated with all-cause mortality (1.18, 1.07–1.30) and with cardiovascular mortality only in elderly (1.61, 1.19–2.18), but not in younger participants (1.03, 0.78–1.34). Higher free triiodothyronine (FT
3
) was associated with all-cause mortality in females only (1.18, 1.02–1.35). FT
3
was not associated with cardiovascular mortality (0.91, 0.70–1.18).
Conclusions
Community-dwelling elderly individuals with high-normal thyroid function are at increased risk of all-cause and cardiovascular mortality, reinforcing the need of redefining the current reference ranges of thyroid function.
Abstract
Background
Circulating desphospho-uncarboxylated matrix γ-carboxyglutamate (Gla) protein (dp-ucMGP), a marker of vitamin K status, is associated with renal function and may serve as a ...potentially modifiable risk factor for incident chronic kidney disease (CKD). We aimed to assess the association between circulating dp-ucMGP and incident CKD.
Methods
We included 3969 participants with a mean age of 52.3 ± 11.6 years, of whom 48.0% were male, enrolled in the general population–based Prevention of REnal and Vascular ENd-stage Disease study. Study outcomes were incident CKD, defined as either development of an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or microalbuminuria. Associations of dp-ucMGP with these outcomes were quantified using Cox proportional hazards models and were adjusted for potential confounders.
Results
Median plasma dp-ucMGP was 363 interquartile range (IQR) 219–532 pmol/L and mean serum creatinine- and serum cystatin C-based eGFR (eGFRSCr-SCys) was 95.4 ± 21.8 mL/min/1.73 m2. During 7.1 years of follow-up, 205 (5.4%) participants developed incident CKD and 303 (8.4%) developed microalbuminuria. For every doubling of plasma dp-ucMGP, hazard ratios for the development of incident CKD and microalbuminuria were 1.85 95% confidence interval (CI) 1.59–2.16; P < 0.001 and 1.19 (95% CI 1.07–1.32; P = 0.001), respectively. These associations lost significance after adjustment for baseline eGFRSCr-SCys 0.99 (95% CI 0.88–1.12; P = 0.86) and baseline age 1.03 (95% CI 0.94–1.14; P = 0.50), respectively.
Conclusions
The associations of plasma dp-ucMGP with incident CKD and microalbuminuria were driven by the respective baseline effects of renal function and age.
Abstract
Background
The management and care of older patients with multiple health problems is demanding and complex. Interprofessional and intraprofessional collaboration has the potential to ...improve both the efficiency and the quality of care for these patients. However, it has proven difficult to demonstrate the efficacy of this approach in terms of objective patient-related outcomes. Recently, a care model with interprofessional and intraprofessional care was started, the Intensive Collaboration Ward (ICW). This ward combines
inter
professional care and
intra
professional care for older patients with multiple health problems. The aim of this study was to evaluate the effects of ICW care in older patients with multiple health problems.
Methods
This retrospective cohort study evaluated the effects on patients outcomes. This was done by comparing patients of the new model, the ICW (ICW group), to a historical cohort of comparable patients who would have been eligible for the ICW (control group). Outcomes were medical consultations, allied health professional consultations, radiological procedures, waiting time for radiological procedures, change in primary treating specialty, length of hospital stay, readmission rate, and mortality rate. Linear and logistic regression analyses were performed, adjusted for baseline differences.
Results
The ICW group required significantly fewer medical consultations than the control group. Calls to specialists from the emergency room decreased significantly, but there was no change in in-person consultations on the ER. 51% of control patients had ≥ 1 in-hospital consultation compared to 21% of ICW patients (
p
< 0.05). Patients in the ICW group received significantly more consultations with allied health professionals and more often had a change in primary treating specialty.
Conclusions
Interprofessional and intraprofessional clinical collaboration on the ICW reduced in-hospital consultations and increased allied health professionals’ consultations. This approach may decrease fragmentation of care and provide more integrated, efficient and patient centered care. This may improve the overall care of older patients with multiple health problems.
Galectin-3 may play a causal role in kidney inflammation and fibrosis, which may also be involved in the development of kidney graft failure. With novel galectin-3-targeted pharmacological therapies ...increasingly coming available, we aimed to investigate whether galectin-3 is associated with risk of late graft failure in kidney transplant recipients (KTR).
We studied adult KTR who participated in TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study, recruited in a university setting (2001-2003). Follow-up was performed for a median of 9.5 (interquartile range, 6.2-10.2) years. Overall and stratified (Pinteraction < 0.05) multivariable-adjusted Cox proportional-hazards regression analyses were performed to study the association of galectin-3 with risk of graft failure (restart of dialysis or retransplantation).
Among 561 KTR (age 52 ± 12 y; 54% males), baseline median galectin-3 was 21.1 (interquartile range, 17.0-27.2) ng/mL. During follow-up, 72 KTR developed graft failure (13, 18, and 44 events over increasing tertiles of galectin-3). Independent of adjustment for donor, recipient, and transplant characteristics, galectin-3-associated with increased risk of graft failure (hazard ratios HR per 1 SD change, 2.12; 95% confidence interval CI, 1.63-2.75; P < 0.001), particularly among KTR with systolic blood pressure ≥140 mmHg (HR, 2.29; 95% CI, 1.80-2.92; P < 0.001; Pinteraction = 0.01) or smoking history (HR, 2.56; 95% CI, 1.95-3.37; P < 0.001; Pinteraction = 0.03). Similarly, patients in the highest tertile of galectin-3 were consistently at increased risk of graft failure.
Serum galectin-3 levels are elevated in KTR, and independently associated with increased risk of late graft failure. Whether galectin-3-targeted therapies may represent novel opportunities to decrease the long-standing high burden of late graft failure in stable KTR warrants further studies.
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