The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects

CONTEXT: Hepatic lipase plays a pivotal role in the metabolism of high-density lipoprotein (HDL) and low-density lipoprotein by involvement in reverse cholesterol transport and the formation of atherogenic small dense low-density lipoprotein. OBJECTIVES: The objective was to investigate the impact of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. DESIGN: The LIPC -250G>A (rs2070895) variant was genotyped in the Inter99 study (n = 6070), the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care Denmark screening cohort of individuals with risk factors for undiagnosed type 2 diabetes (n = 8662), and in additional type 2 diabetic patients (n = 1,064) and glucose-tolerant control subjects (n = 360). RESULTS: In the Inter99 study, the A allele of rs2070895 associated with a 0.057 mmol/liter [95% confidence interval (CI) 0.039-0.075] increase in fasting serum HDL-cholesterol (HDL-c) (P = 8 x 10(-10)) supported by association in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A-allele carriers had a 0.30 mmol/liter (95% CI 0.22-0.37) increase in HDL-c compared with homozygous G-allele carriers. CONCLUSIONS: We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the -250 A allele. This interaction may have potential implications for public health and disease prevention.     

Induction of globin mRNA transcription by erythropoietin in differentiating erythroid precursor cells

The effects of erythropoietin (epo) on the proliferation of late erythroid progenitor cells (CFU-E) and on the formation of hemoglobin and of globin mRNA in these cells are described. CFU-E were isolated from thiamphenicol-pretreated anemic mice by elutriation and Percoll density gradient methods. These CFU-E are restricted in their capacity to proliferate in vitro without added epo. The epo dependence in vitro was not absolute. With no epo in the culture medium the first cell division was unimpaired, whereas the third division was only 1%-2% of the control. In the absence of epo the synthesis of hemoglobin is very low in CFU-E, but is increased significantly after about 5 h of incubation with epo present. In epo deprived cells there was considerable hemoglobin formed at about 14 h, but not earlier. The presence as detected by the Northern blot technique of globin mRNA, isolated from CFU-E, was variable, probably depending on the presence of some more mature erythroid cells. By an extrapolation method we show evidence that pure CFU-E would have virtually no detectable globin mRNA. The production of globin mRNA is rapidly (2 h) induced in cells incubated with epo. We conclude that epo, besides having a mitogenic effect on CFU-E, induces the rapid expression of the globin genes.     

The effect of growth hormone on the insulin-like growth factor system during fasting

The present study investigates the possible stimulatory effect of endogenous GH on IGF and IGF-binding protein (IGFBP) levels during fasting. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state; 2) after 40 h of fasting; 3) after 40 h of fasting with somatostatin suppression of GH; and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement. The two somatostatin experiments were identical in terms of hormone replacement (except for GH). Short-term fasting led to a 50% reduction in free IGF-I. The reduction in free IGF-I was paralleled by an increase in IGFBP-1, an increase in the complex formation of IGFBP-1 and IGF-I, and a modest reduction in IGFBP-3 proteolysis. GH deprivation during fasting led to a 35% reduction in total IGF-I and a 70% reduction in free IGF-I. GH replacement increased free and total IGF-I to levels similar to those observed during plain fasting and decreased IGFBP-1, however, without affecting IGFBP-1-bound IGF-I. Finally, IGFBP-3 proteolysis was slightly increased by GH replacement. In conclusion, the major new finding of the present study is that the GH hypersecretion seen during short-term fasting is not merely secondary to a reduction in IGF bioactivity.     

Microbiology of parapharyngeal abscesses in adults: in search of the significant pathogens

European Journal of Clinical Microbiology & Infectious Diseases - We aimed to describe the microbiology of parapharyngeal abscess (PPA) and point out the likely pathogens using the following...     

Left bundle branch block without a typical contraction pattern is associated with increased risk of ventricular arrhythmias in cardiac resynchronization therapy patients

The International Journal of Cardiovascular Imaging - Cardiac resynchronization therapy (CRT) reduces the risk of ventricular arrhythmias (VA) in heart failure (HF) patients with left bundle branch...     

The Minimum Clinically Important Difference of the Patient-rated Wrist Evaluation Score for Patients With Distal Radius Fractures

Background

The Patient-rated Wrist Evaluation (PRWE) is a commonly used instrument in upper extremity surgery and in research. However, to recognize a treatment effect expressed as a change in PRWE, it is important to be aware of the minimum clinically important difference (MCID) and the minimum detectable change (MDC). The MCID of an outcome tool like the PRWE is defined as the smallest change in a score that is likely to be appreciated by a patient as an important change, while the MDC is defined as the smallest amount of change that can be detected by an outcome measure. A numerical change in score that is less than the MCID, even when statistically significant, does not represent a true clinically relevant change. To our knowledge, the MCID and MDC of the PRWE have not been determined in patients with distal radius fractures.

Questions/Purposes

We asked: (1) What is the MCID of the PRWE score for patients with distal radius fractures? (2) What is the MDC of the PRWE?

Methods

Our prospective cohort study included 102 patients with a distal radius fracture and a median age of 59 years (interquartile range [IQR], 48–66 years). All patients completed the PRWE questionnaire during each of two separate visits. At the second visit, patients were asked to indicate the degree of clinical change they appreciated since the previous visit. Accordingly, patients were categorized in two groups: (1) minimally improved or (2) no change. The groups were used to anchor the changes observed in the PRWE score to patients’ perspectives of what was clinically important. We determined the MCID using an anchor-based receiver operator characteristic method. In this context, the change in the PRWE score was considered a diagnostic test, and the anchor (minimally improved or no change as noted by the patients from visit to visit) was the gold standard. The optimal receiver operator characteristic cutoff point calculated with the Youden index reflected the value of the MCID.

Results

In our study, the MCID of the PRWE was 11.5 points. The area under the curve was 0.54 (95% CI, 0.37–0.70) for the pain subscale and 0.71 (95% CI, 0.57−0.85) for the function subscale. We determined the MDC to be 11.0 points.

Conclusions

We determined the MCID of the PRWE score for patients with distal radius fractures using the anchor-based approach and verified that the MDC of the PRWE was sufficiently small to detect our MCID.

Clinical Relevance

We recommend using an improvement on the PRWE of more than 11.5 points as the smallest clinically relevant difference when evaluating the effects of treatments and when performing sample-size calculations on studies of distal radius fractures.     

Good Functional Recovery of Complex Elbow Dislocations Treated With Hinged External Fixation: A Multicenter Prospective Study

BackgroundAfter a complex dislocation, some elbows remain unstable after closed reduction or fracture treatment. Function after treatment with a hinged external fixator theoretically allows collateral ligaments to heal without surgical reconstruction. However, there is a lack of prospective studies that assess functional outcome, pain, and ROM.Questions/purposesWe asked: (1) In complex elbow fracture-dislocations, does treatment with a hinged external fixator result in reduction of disability and pain, and in improvement in ROM, function, and quality of life? (2) Does delayed treatment (7 days or later) have a negative effect on ROM after 1 year? (3) What are the complications seen after external fixator treatment?MethodsDuring a 2-year period, 11 centers recruited 27 patients 18 years or older who were included and evaluated at 2 and 6 weeks and at 3, 6, and 12 months after surgery as part of this prospective case series. During the study period, the participating centers agreed on general indications for use of the hinged external fixator, which included persistent instability after closed reduction alone or closed reduction combined with surgical treatment of associated fracture(s), when indicated. Functional outcome was evaluated using the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH; primary outcome) score, the Mayo Elbow Performance Index (MEPI), the Oxford Elbow Score, and the level of pain (VAS). ROM, adverse events, secondary interventions, and radiographs also were evaluated. A total of 26 of the 27 patients (96%) were available for followup at 1 year.ResultsAll functional and pain scores improved. The median QuickDASH score decreased from 30 (25^th–75^th percentiles [P₂₅–P₇₅], 23–40) at 6 weeks to 7 (P₂₅–P₇₅, 2–12) at 1 year with a median difference of −25 (p < 0.001). The median MEPI score increased from 80 (P₂₅–P₇₅, 64–85) at 6 weeks to 100 (P₂₅–P₇₅, 85–100) at 1 year with a median difference of 15 (p < 0.001). The median Oxford Elbow Score increased from 60 (P₂₅–P₇₅, 44–68) at 6 weeks to 90 (P₂₅–P₇₅, 73–96) at 1 year with a median difference of 29 (p < 0.001). The median VAS decreased from 2.8 (P₂₅–P₇₅, 1.0–5.0) at 2 weeks to 0.5 (P₂₅–P₇₅, 0.0–1.9) at 1 year with a median difference of −2.1 (p = 0.001). ROM also improved. The median flexion-extension arc improved from 50° (P₂₅–P₇₅, 33°–80°) at 2 weeks to 118° (P₂₅–P₇₅, 105°–138°) at 1 year with a median difference of 63° (p < 0.001). Similarly, the median pronation-supination arc improved from 90° (P₂₅–P₇₅, 63°–124°) to 160° (P₂₅–P₇₅, 138°–170°) with a median difference of 75° (p < 0.001). At 1 year, the median residual deficit compared with the uninjured side was 30° (P₂₅–P₇₅, 5°–35°) for the flexion-extension arc, and 3° (P₂₅–P₇₅, 0°–25°) for the pronation-supination arc. Ten patients (37%) experienced a fixator-related complication, and seven patients required secondary surgery (26%). One patient reported recurrent instability.ConclusionsA hinged external elbow fixator provides enough stability to start early mobilization after an acute complex elbow dislocation and residual instability. This was reflected in good functional outcome scores and only slight disability despite a relatively high complication rate.

Level of Evidence

Level IV, therapeutic study.     

Expression of hypoxia‐inducible factor‐1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

Late renal graft loss is associated with interstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) is thought to facilitate fibrosis through interaction with TGF‐β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate the expression of HIF‐1α and HGF in protocol biopsies as possible prognostic biomarkers for renal fibrosis. Thirty‐nine renal transplant recipients were included in the study. Protocol biopsies performed 1 and 2 years after transplantation were used for immunohistochemistry analysis. The correlation between HIF‐1α/HGF and the Banff score was analysed. In addition, progression in renal fibrosis and graft survival among recipients with high or low expression of HIF‐1α/HGF after transplantation was compared. There was no significant correlation between fibrosis and the HIF‐1α expression 1 and 2 years after transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival was not significantly correlated to HIF‐1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1‐10‐72‐318‐13)     

More than a decade after live donor nephrectomy: a prospective cohort study

Previously reported short‐term results after live kidney donation show no negative consequences for the donor. The incidence of new‐onset morbidity takes years to emerge, making it highly likely that this will be missed during short‐term follow‐up. Therefore, evidence on long‐term outcome is essential. A 10‐year follow‐up on renal function, hypertension, quality of life (QOL), fatigue, and survival was performed of a prospective cohort of 100 donors. After a median follow‐up time of 10 years, clinical data were available for 97 donors and QOL data for 74 donors. Nine donors died during follow‐up of unrelated causes to donation, and one donor was lost to follow‐up. There was a significant decrease in kidney function of 12.9 ml/min (P < 0.001) at follow‐up. QOL showed significant clinically relevant decreases of 10‐year follow‐up scores in SF‐36 dimensions of physical function (P < 0.001), bodily pain (P = 0.001), and general health (P < 0.001). MFI‐20 scores were significantly higher for general fatigue (P < 0.001), physical fatigue (P < 0.001), reduced activity (P = 0.019), and reduced motivation (P = 0.030). New‐onset hypertension was present in 25.6% of the donors. Donor outcomes are excellent 10 years post‐donation. Kidney function appears stable, and hypertension does not seem to occur more frequently compared to the general population.