In situ cross-linkable hyaluronan hydrogel enhances chondrogenesis

The present work describes the feasibility of a cross-linkable injectable hyaluronan hydrogel for cartilage repair. The hydrogel used is a two-component system based on aldehyde-modified hyaluronan and hydrazide-modified polyvinyl alcohol, which are rapidly cross-linked in situ upon mixing. The in vitro study showed that chondrocytes and mesenchymal cells cultured in the gel form cartilage-like tissue, rich in glycosaminoglycans, collagen type II and aggrecan. In a rabbit animal model the injection of the hydrogel improved the healing of a full-thickness cartilage defect created in the knee as compared to non-treated controls. This rabbit study showed that the regenerated cartilage defects stained more intensely for type II collagen upon treatment with the hydrogel. The hyaluronan-based hydrogel may be used as a delivery vehicle for both growth factors and/or cells for cartilage repair. The in vivo study also indicated that the hydrogel alone has a beneficial effect on cartilage regeneration.     

A nationwide cohort study of resection rates and short-term outcomes in open and laparoscopic distal pancreatectomy

BackgroundDistal pancreatectomy (DP) is increasingly done by laparoscopy but data from routine practise are scarce. We describe practise in a national cohort.MethodsData from the Norwegian Patient Register of all patients undergoing DP from 2012 to 2016. National resection rates were analysed. Short-term outcomes include length of stay, reoperation, readmissions and 90-day mortality. Risk is reported as odds ratio (OR) with 95% confidence interval (c.i.).ResultsOf 554 procedures, 327 (59%) were laparoscopic. Median age was 66 years (iqr 55–72) and 52% were women. Resection rates increased during the period for all DP (from 1.76 to 2.39 per 100.000/yr), and significantly for laparoscopic DP (adjusted R-square 0.858; P = 0.015). Elderly patients had more resection (r₂ = 0.11; P = 0.019). Splenectomy (n = 427; 77%) was less likely with laparoscopy (laparoscopy 72% vs open 84%, respectively; OR 0.64, 95% c.i. 0.42–0.97; P = 0.035). Multivisceral resections occurred more often in open DP (5.3% vs 1.2% for laparoscopy, OR 4.51, 1.44–14.2; P = 0.008). Reoperation occurred in 34 (6%), readmission in 109 (20%), and mortality in 8 (1.4%). Hospital stay was shorter for laparoscopic DP.ConclusionUse of DP increases in the population, particularly in the elderly, with use of laparoscopic access and an association with a reduced hospital stay.     

Single nucleotide polymorphisms in inflammatory genes and the risk of early onset of lone atrial fibrillation

Background  

Systemic low-grade inflammation is a prognostic risk factor of atrial fibrillation (AF).     

IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-alpha-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) > or = 25 kg/m2 (P = .004) and with baseline viral load > or = 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P < .05), higher viral load (P = .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.     

A Physiological Model of the Effect of Hypoglycemia on Plasma Potassium

Background

Adrenaline release and excess insulin during hypoglycemia stimulate the uptake of potassium from the bloodstream, causing low plasma potassium (hypokalemia). Hypokalemia has a profound effect on the heart and is associated with an increased risk of malignant cardiac arrhythmias. It is the aim of this study to develop a physiological model of potassium changes during hypoglycemia to better understand the effect of hypoglycemia on plasma potassium.

Method

Potassium counterregulation to hypokalemia was modeled as a linear function dependent on the absolute potassium level. An insulin-induced uptake of potassium was modeled using a negative exponential function, and an adrenaline-induced uptake of potassium was modeled as a linear function. Functional expressions for the three components were found using published data.

Results

The performance of the model was evaluated by simulating plasma potassium from three published studies. Simulations were done using measured levels of adrenaline and insulin. The mean root mean squared error (RMSE) of simulating plasma potassium from the three studies was 0.09 mmol/liter, and the mean normalized RMSE was 14%. The mean difference between nadirs in simulated and measured potassium was 0.12 mmol/liter.

Conclusions

The presented model simulated plasma potassium with good accuracy in a wide range of clinical settings. The limited number of hypoglycemic episodes in the test set necessitates further tests to substantiate the ability of the model to simulate potassium during hypoglycemia. In conclusion, the model is a good first step toward better understanding of changes in plasma potassium during hypoglycemia.     

Attributions of adolescents with type 1 diabetes in social situations: relationship with expected adherence, diabetes stress, and metabolic control

OBJECTIVE: To examine the relationships among negative attributions of friend reactions (NAFRs) within a social context, anticipated adherence difficulties, diabetes stress, and metabolic control. RESEARCH DESIGN AND METHODS: A sample of 104 adolescents with type 1 diabetes completed instruments measuring demographics, attribution of friend reactions, anticipated adherence, and diabetes stress. Metabolic control was measured by HbA(1c) obtained during the clinic visit. RESULTS: Path analysis demonstrated an excellent fit of a model depicting an indirect relationship between NAFRs and metabolic control through the mechanisms of expected adherence difficulties and diabetes stress. CONCLUSIONS: Adolescents who make NAFRs are likely to find adherence difficult in social situations and have increased feelings of stress, with the latter associated with poorer metabolic control. Intervention efforts to address negative attributions may impact adherence behavior and feelings of stress, especially if specific contexts of self-care behavior are taken into account.     

PI3K/Akt-dependent Epo-induced signalling and target genes in human early erythroid progenitor cells

Erythropoietin (Epo) is the major regulator of differentiation, proliferation and survival of erythroid progenitors, but the Epo-induced changes in gene expression that lead to these effects are not fully understood. The aim of this study was to examine how Epo, via activation of phosphatidylinositol 3-kinase (PI3K)/Akt, exerts its role in the development of erythroid progenitors from CD34+ cells, and to identify early Epo target genes in human erythroid progenitors. In CD34+ progenitor cells, Epo alone was able to induce cell cycle progression as demonstrated by upregulation of cyclin D3, E and A leading to hyperphosphorylation of the retinoblastoma protein (RB). These effects were completely counteracted by the PI3K inhibitor LY294002. Furthermore, enforced expression of an activated form of Akt kinase highly augmented Epo-induced erythropoiesis. Fluorescent-activated cell sorting (FACS)-sorted CD34+CD71+CD45RA-GPA- erythroid progenitors stimulated with Epo in the presence or absence of LY294002 were subjected to gene expression profiling. Several novel target genes of Epo were identified, and the majority were regulated in a PI3K-dependent manner, including KIT (CD117) and CDH1 (E-cadherin). FACS analysis of Epo-stimulated erythroid progenitors showed that the increased mRNA expression of KIT and CDH1 was accompanied by an induction of the corresponding proteins CD117 and E-cadherin.     

Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial

The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.     

Non-white noise in fMRI: Does modelling have an impact?

The sources of non-white noise in Blood Oxygenation Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) are many. Familiar sources include low-frequency drift due to hardware imperfections, oscillatory noise due to respiration and cardiac pulsation and residual movement artefacts not accounted for by rigid body registration. These contributions give rise to temporal autocorrelation in the residuals of the fMRI signal and invalidate the statistical analysis as the errors are no longer independent. The low-frequency drift is often removed by high-pass filtering, and other effects are typically modelled as an autoregressive (AR) process. In this paper, we propose an alternative approach: Nuisance Variable Regression (NVR). By inclusion of confounding effects in a general linear model (GLM), we first confirm that the spatial distribution of the various fMRI noise sources is similar to what has already been described in the literature. Subsequently, we demonstrate, using diagnostic statistics, that removal of these contributions reduces first and higher order autocorrelation as well as non-normality in the residuals, thereby improving the validity of the drawn inferences. In addition, we also compare the performance of the NVR method to the whitening approach implemented in SPM2.     

Gas within the liver and polymicrobial bacteraemia due to colovenous fistula: two cases in one month

Two cases presented at our hospital within 1 month with polymicrobial bacteraemia and gas within the liver shown on CT scan. Both transpired to have colovenous fistula due to diverticulitis. Because of our awareness of the first case, the colovenous fistula of the second case was identified rapidly. As surgical treatment is probably essential for this condition, the possibility of colovenous fistula should be borne in mind in patients with gas within the liver, especially if they have bacteraemia.