Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study

ABSTRACT: INTRODUCTION: Acute kidney injury (AKI), which is a major complication after cardiovascular surgery, is associated with significant morbidity and mortality. Diuretic agents are frequently used to improve urine output, and to facilitate fluid management in these patients. Mannitol, an osmotic diuretic, is used in the perioperative setting in the belief that it exerts reno-protective properties. In a recent study on uncomplicated post-cardiac surgery patients with normal renal function, mannitol increased glomerular filtration rate (GFR), possibly by a de-swelling effect on tubular cells. Furthermore, experimental studies have previously shown that renal ischemia causes an endothelial cell injury and dysfunction followed by endothelial cell oedema. We studied the effects of mannitol on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and extraction (RO2Ex) in early, ischaemic AKI after cardiac surgery. METHODS: Eleven patients with AKI were studied during propofol sedation and mechanical ventilation 2-6 days after complicated cardiac surgery. All patients had severe heart failure treated with one (100%) or two (73%) inotropic agents and intra-aortic balloon pump (36%). Systemic haemodynamics were measured by a pulmonary artery catheter. RBF and renal filtration fraction (FF) were measured by the renal vein thermo-dilution technique and by renal extraction of chromium-51- ethylenediaminetetraacetic acid (51Cr-EDTA), respectively. GFR was calculated as the product of FF and renal plasma flow RBF x (1-hematocrit). RVO2 and RO2Ex were calculated from arterial and renal vein blood samples according to standard formulae. After control measurements, a bolus dose of mannitol 225 mg/kg, was given followed by an infusion at a rate of 75 mg/kg/h for two 30-minute periods. RESULTS: Mannitol did not affect cardiac index or cardiac filling pressures. Mannitol increased urine flow by 61% (P<0.001). This was accompanied by a 12% increase in RBF (P<0.05) and 13% decrease in renal vascular resistance (P<0.05). Mannitol increased the RBF/cardiac output (CO) relationship (P=0.040). Mannitol caused no significant changes in RO2Ext or renal FF. CONCLUSIONS: Mannitol treatment of postoperative AKI induces a renal vasodilation and redistributes systemic blood flow to the kidneys. Mannitol does not affect filtration fraction or renal oxygenation, suggestive of balanced increases in perfusion/filtration and oxygen demand/supply.     

Age at onset of childhood-onset type 1 diabetes and the development of end-stage renal disease: a nationwide population-based study

OBJECTIVE: To analyze the impact of age at onset on the development of end-stage renal disease (ESRD) due to diabetic nephropathy in a nationwide population-based cohort with childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: A record linkage between two nationwide registers, the Swedish Childhood Diabetes Registry, including 12,032 cases with childhood-onset diabetes, and the Swedish Registry for Active Treatment of Uraemia was performed. Log-rank test was used to test differences between cumulative risk curves of developing ESRD due to diabetic nephropathy in three different strata of age at onset (0-4, 5-9, and 10-14 years). RESULTS: At a maximum follow-up of 27 years, 33 patients had developed ESRD due to diabetic nephropathy and all had a diabetes duration >15 years. In total, 4,414 patients had diabetes duration >15 years, and thus the risk in this cohort to develop ESRD was 33 of 4,414 (0.7%). A significant difference in risk of developing ESRD was found between the youngest (0-4 years) and the two older (5-9 and 10-14 years) age-at-onset strata (P = 0.03 and P = 0.001, respectively). A significant difference in the risk of developing ESRD was also found between children with prepubertal (0-4 and 5-9 years, n = 2,424) and pubertal (10-14 years, n = 2000) onset of diabetes (P = 0.002). No patient with onset of diabetes before 5 years of age had developed ESRD. CONCLUSIONS: With a median duration of 21 years in this population-based Swedish cohort with childhood-onset diabetes, <1% of the patients had developed ESRD due to diabetic nephropathy, and a prepubertal onset of diabetes seems to prolong the time to development of ESRD.     

Association between Gm allotypes and asthma severity from childhood to young middle age

Immunoglobulin constant heavy G chain (IGHG) gene polymorphisms are associated with atopy and can be determined by the serum Gm allotypes. We studied whether certain polymorphisms are related to asthma severity and to the extent or intensity of allergic sensitization in asthmatic subjects followed from childhood to young middle age. Fifty-five subjects (28 males) with childhood asthma were all followed-up prospectively on six occasions from a mean age of 9 to 35 years in a study including asthma severity scoring, spirometry, skin prick, and specific serum IgE antibody testing. At the last visit, extended lung function tests and a cold air challenge were performed, and IGHG gene polymorphisms were identified by the alternative serum IgG subclass allotypes, employing ELISA and double immunodiffusion. The 19 subjects with the homozygous IGHG*bf/*bf genotype (originating from the IGHG3*b and the IGHG1*f alleles, which are in strong linkage disequilibrium), showed significantly higher asthma scores, lower airway function, and greater bronchodilator responses from childhood to adulthood, and in middle age greater airway hyperresponsiveness, compared to the subjects with the IGHG*bf/*ga or IGHG*ga/*ga genotypes. Among the subjects sensitized to animal danders, those with the IGHG*bf/*bf genotype showed the highest specific IgE levels. In conclusion, IGHG gene polymorphisms were associated with the severity and outcome of childhood asthma, and with the intensity of allergic sensitization.     

Streptococcus pneumoniae contains 3 rlrA pilus variants that are clonally related

BACKGROUND: Pilus components of Streptococcus pneumoniae encoded by rlrA were recently shown to elicit protection in an animal model of infection. Limited data are available on the prevalence of the rlrA operon in pneumococci; therefore, we investigated its distribution and its antigenic variation among disease-causing strains. METHODS: The prevalence of rlrA and its association with serotype and genotype were evaluated in a global panel of 424 pneumococci isolates (including the 26 drug-resistant clones described by the Pneumococcal Molecular Epidemiology Network). RESULTS: The rlrA islet was found in 130 isolates (30.6%) of the defined collection. Sequence alignment of 15 rlrA islets defined the presence of 3 clade types, with an overall homology of 88%-92%. The presence or absence of a pilus-encoding operon correlated with S. pneumoniae genotype (P < .001), as determined by multilocus sequence typing, and not with serotype. Further investigation identified a positive trend of rlrA occurrence among antimicrobial-resistant pneumococci. CONCLUSIONS: On the basis of S. pneumoniae genotype, it is possible to predict the incidence of the rlrA pilus operon in a collection of pneumococcal isolates. This will facilitate the development of a protein vaccine.     

Risk factors for falls in people with and without a diagnose of dementia living in residential care facilities: a prospective study

People with dementia are at increased risk of falling. The purpose of this study was to identify predisposing risk factors for falls in older people with and without a diagnose of dementia living in residential care facilities, and to compare the results. Eighty-three residents without dementia (mean age ± S.D.; 83.5 ± 7.1 years) and 103 with dementia (83.6 ± 6.3 years) in Umeå, Sweden, participated. The baseline assessment included probable risk factors like walking ability, diagnoses and treatment with drugs. The follow-up period was 6 months. In people with dementia, the fall rate was higher (crude incidence rate ratio 2.55, 95% CI 1.60–4.08) and a larger proportion experienced falls (62% versus 41%). In the group without dementia 54.8% of the variation in falls was explained by a model including orthostatism, “women walking with aid”, and treatment with Angiotensin Converting Enzyme (ACE) inhibitors. In the group with dementia 25.5% of the variation in falls was explained by a model including “man walking with aid”. Our results show that with the same set of common risk factors for falls a considerably lower proportion of the variation in falls can be explained in the group of people with dementia.     

Model-based predictions on health benefits and budget impact of implementing empagliflozin in people with type 2 diabetes and established cardiovascular disease

Aim

To perform a model-based analysis of the short- and long-term health benefits and costs of further increased implementation of empagliflozin for people with type 2 diabetes and established cardiovascular disease (eCVD) in Sweden.

Materials and Methods

The validated Institute for Health Economics Diabetes Cohort Model (IHE-DCM) was used to estimate health benefits and a 3-year budget impact, and lifetime costs per quality-adjusted life years (QALY) gained of increased implementation of adding empagliflozin to standard of care (SoC) for people with type 2 diabetes and eCVD in a Swedish setting. Scenarios with 100%/75%/50% implementation were explored. Analyses were based on 30 model cohorts with type 2 diabetes and eCVD (n = 131 412 at baseline) from national health data registers. Sensitivity analyses explored the robustness of results.

Results

Over 3 years, SoC with empagliflozin (100% implementation) versus SoC before empagliflozin resulted in 7700 total life years gained and reductions in cumulative incidence of cardiovascular deaths by 30% and heart failures by 28%. Annual costs increased by 15% from higher treatment costs and increased survival. Half of these benefits and costs are not yet reached with current implementation below 50%. SoC with empagliflozin yielded 0.37 QALYs per person, with an incremental cost-effectiveness ratio of 16 000 EUR per QALY versus SoC before empagliflozin.

Conclusions

Model simulations using real-world data and trial treatment effects indicated that a broader implementation of empagliflozin, in line with current guidelines for treatment of people with type 2 diabetes and eCVD, would lead to further benefits even from a short-term perspective.     

Characteristics associated with falls in patients with dementia in a psychogeriatric ward

BACKGROUND AND AIMS: Few studies have reported fall-risk factors for persons with dementia, and no successful randomized fall prevention studies have been published. The aim of this study was to identify characteristics associated with falls in patients with dementia in a psychogeriatric ward. METHODS: This prospective study comprised 204 patients with any diagnosis of dementia. It was carried out in a psychogeriatric ward specializing in the assessment and treatment of behavioral and psychological symptoms in patients with dementia (BPSD). Baseline patient data were collected from medical records, and covered physical, behavioral and cognitive areas. Falls were recorded during time spent in the ward and median follow-up time was 52.5 days. RESULTS: Eighty-two patients fell a total of 251 times. Factors significantly and independently associated with an increased risk of falling were male sex (IRR 3.36, 95% CI 2.02-5.61), failed "copy design" activity (decreased visual perception) (IRR 2.37, 95% CI 1.24-4.52), and any walking difficulty on level ground (IRR 1.84, 95% CI 1.10-3.08). Statins were associated with a decreased risk of falling (IRR 0.29, 95% CI 0.10-0.86). Twenty-seven percent of the variation in falls was explained. CONCLUSIONS: Male sex, decreased visual perception, and walking difficulties were all associated with an increased number of falls, and the model explained 1/4 of the variation in falls. Well-planned furnishing and use of color to achieve a plain, clearly defined environment, as well as training in walking ability, may decrease the risk of falling in people with dementia.     

The Smoker’s Paradox Revisited: A Patient-Level Pooled Analysis of 18 Randomized Controlled Trials

ObjectivesThis study examined the smoker’s paradox using patient-level data from 18 prospective, randomized trials of patients undergoing percutaneous coronary intervention (PCI) with stent implantation.BackgroundStudies on the effects of smoking and outcomes among patients undergoing PCI have reported conflicting results.MethodsData from the RAVEL, E-SIRIUS, SIRIUS, C-SIRIUS, TAXUS IV and V, ENDEAVOR II to IV, SPIRIT II to IV, HORIZONS-AMI, COMPARE I and II, PLATINUM, and TWENTE I and II randomized trials were pooled. Patients were stratified by smoking status at time of enrollment. The 1- and 5-year ischemic outcomes were compared.ResultsAmong 24,354 patients with available data on smoking status, 6,722 (27.6%) were current smokers. Smokers were younger and less likely to have diabetes mellitus; hypertension; hyperlipidemia; or prior myocardial infarction (MI), PCI, or coronary artery bypass grafting. Angiographically, smokers had longer lesions, more complex lesions, and more occlusions, but were less likely to have moderate or severe calcification or tortuosity. At 5 years, smokers had significantly higher rates of MI (7.8% vs. 5.6%; p < 0.0001) and definite or probable stent thrombosis (3.5% vs. 1.8%; p < 0.0001); however, there were no differences in the rates of death, cardiac death, target lesion revascularization, or composite endpoints (cardiac death, target vessel MI, or ischemic target lesion revascularization). After multivariable adjustment for potential confounders, smoking was a strong independent predictor of death (hazard ratio [HR]: 1.86; 95% confidence interval [CI]: 1.63 to 2.12; p < 0.0001), cardiac death (HR: 1.68; 95% CI: 1.38 to 2.05; p < 0.0001), MI (HR: 1.38; 95% CI: 1.20 to 1.58; p < 0.0001), stent thrombosis (HR: 1.60; 95% CI: 1.28 to 1.99; p < 0.0001), and target lesion failure (HR: 1.17; 95% CI: 1.05 to 1.30; p = 0.005).ConclusionsThe present large, patient-level, pooled analysis with 5-year follow-up clearly demonstrates smoking to be an important predictor of adverse outcomes after PCI.     

Takotsubo triggered by acute myocardial infarction：a common but overlooked syndrome？

Takotsubo cardiomyopathy （TCM） is an acute cardiac syndrome characterized by extensive, but potentially reversible, left ventricular dysfunction in the absence of an explanatory coronary obstruction. Thus, TCM is distinct from coronary artery disease （CAD） and acute myocardial infarction （AMI）. However, substantial evidence for co-existing CAD in some TCM patients exist. Herein, we take this associa-tion one step further and present a case in which the patient simultaneously suffered from AMI and TCM, and in which we believe that a primary coronary event triggered TCM. An 88-year-old female presented with chest pain. Echocardiography revealed apical akinesia with hypercontractile bases. An occluded diagonal branch with suspected acute plaque rupture was identified on the angiogram, but could not explain the extent of akinesia. Cardiac function recovered completely. Thus, this patient adhered to current diagnostic criteria for TCM. TCM is a well-known complication for other conditions associated with somatic stress. It is therefore intuitive to assume that AMI, which also associates with somatic stress and elevated catecholamine, can cause TCM. Our case illustrates that TCM and AMI may occur simulta-neously. Although causality cannot be conclusively inferred from this association, the somatic stress associated with AMI may have caused TCM in this patient.     

Occupational implications of the chlorofluorocarbon ban in Sweden

Limitations on the use of full halogenated chlorofluorocarbons (CFCs) may create occupational environmental problems. These are currently largely unknown, because the toxicology of most CFC substitutes is unknown. Therefore, toxicity testing of CFC substitutes is necessary, and this can best be done before their use commences. Destruction of CFC and materials containing CFC could generate new chemical compounds, especially during incineration. In addition, problems with higher noise and vibration levels may occur when CFC substitutes are employed, and we should keep in mind that occupational environment problems could also develop when new routines are introduced for transporting, storing, and handling new materials.