Health-Related Quality of Life,Treatment Efficacy,and Hemodialysis Patient Outcome

The aim of the study was to examine the influence of improved treatment of hemodialysis (HD) patients on their health-related quality of life (HrQoL) and to assess the predictive value of HrQoL dimensions on patient outcome. The prospective cohort study involved 102 HD patients, and their clinical and laboratory parameters and HD adequacy indices were followed from 2001 to 2007. HrQoL was measured using KDQOL-SF Version 1.3 in 2001, 2004, and 2007. During a six-year period, quality of HD and anemia treatment improved and resulted in significant increase of mean Kt/V (1.2–1.56) and hemoglobin levels (86.5–115.6 g/L). All four HrQoL dimensions (i.e., physical, mental health, kidney disease target issues, and patient satisfaction) remained unchanged, but significant improvement in several HrQoL physical health domains and the effects of kidney disease domain was found. Mortality rate decreased from 18.6% to 7.14% per year. Age was associated positively, but kidney disease target issue score negatively, with patient death. Improved HD adequacy and anemia treatment in HD patients were followed with maintenance of all four HrQoL dimensions unchanged over six years. Moreover, an improvement in several physical health domains and the effects of kidney disease domain was found. Age and kidney disease target issue appeared as significant predictors of patients' death.     

p21Cip restrains hippocampal neurogenesis and protects neuronal progenitors from apoptosis during acute systemic inflammation

Altered neurogenesis in adult hippocampus is implicated in cognition impairment and depression. Inflammation is a potent inhibitor of neurogenesis. The cyclin‐dependent kinase inhibitor p21^Cip1 (p21) restrains cell cycle progression and arrests the cell in the G1 phase. We recently showed that p21 is expressed in neuronal progenitors and regulates proliferation of these cells in the subgranular zone of the dentate gyrus of hippocampus where adult neurogenesis occurs. The current study suggests that p21 is induced in vivo in the hippocampus of WT mice in response to acute systemic inflammation caused by LPS injections, restrains neuronal progenitor proliferation and protects these cells from inflammation‐induced apoptosis. In intact p21^?/? hippocampus, neuronal progenitors proliferate more actively as assessed by BrdU incorporation, and give rise to increased number of DCX positive neuroblasts. However, when mice were treated with LPS, the number of neuroblasts decreased due to induced subgranular zone apoptosis. In vitro, differentiating Tuj‐1 positive neuroblasts isolated from p21^?/? hippocampus exhibited increased proliferation rate, measured by Ki‐67 staining, as compared to WT cells (p<0.05). In WT neuronal progenitors treated with IL‐6, the number of p21‐positive cells was increased (p<0.05), and this led to Tuj‐1⁺ cell proliferation restraint, whereas the number of proliferating GFAP⁺ astrocytes was increased ～ 2‐fold. Thus, when p21 is intact, inflammation might divert neuronal progenitors towards astrogliogenesis by inducing p21. At the same time, when p21 is lacking, no effects of IL‐6 on proliferation of Tuj‐1⁺ cells or GFAP⁺ cells are detected in differentiating p21^?/? neuronal progenitors. These results underscore the important role of p21 controlling hippocampal neuronal differentiation during inflammation. © 2013 Wiley Periodicals, Inc.     

Asymmetric 1,3-dipolar cycloaddition reaction of chiral 1-alkyl-1,2-diphospholes with diphenyldiazomethane

The 1,3-dipolar cycloaddition of chiral 1-alkyl-1,2-diphosphacyclopenta-2,4-dienes ((1-(−)-menthyl)oxymethyl-1,2-diphosphole and 1-(+)-neomenthyl-1,2-diphosphole) with diphenyldiazomethane leads to novel P-chiral bicyclic phosphiranes having six chiral centers. The degree of diastereoselectivity depends on the substituent at phosphorus, and dramatically increases in the case of (+)-neomenthyl group (de up to 71%). DFT calculations indicate that the cycloaddition is thermodynamically controlled.

The 1,3-dipolar cycloaddition of chiral 1-alkyl-1,2-diphosphacyclopenta-2,4-dienes with diphenyldiazomethane leads to novel P-chiral bicyclic phosphiranes having six chiral centers.     

Failure of the first step of two-stage revision due to polymicrobial prosthetic joint infection of the hip

Background

The unsuccessful treatment of prosthetic joint infection (PJI) with two-stage revision leads to infection recurrence. The objectives of the study were to assess the clinical and demographic characteristics of patients with polymicrobial PJI, and to evaluate the role of the microbial profile involved in PJI in the risk of infection recurrence after the first step of two-stage revision surgery.

Materials and methods

A retrospective analysis of 189 cases of culture-positive PJI following total hip replacement over a 5-year period was performed. The demographic characteristics of patients, clinical symptoms, microbiology cultures of intraoperative biopsies, laboratory values of C-reactive protein (CRP), white blood cell count and erythrocyte sedimentation rate were analyzed. Patients were divided into two groups—135 with monomicrobial and 54 with polymicrobial infection.

Results

Of all patients, 68.9 % in the monomicrobial and 83.3 % in the polymicrobial group had a body mass index >25 kg/m² (p = 0.05). The median CRP values were 5.7 mg/L (IQR 4.0–10.0 mg/L) in the monomicrobial compared to 8.8 mg/L (IQR 5.0–27 mg/L) in the polymicrobial group (p = 0.01). The percentage of successful outcomes was 27.8 % in patients with microbial associations (p < 0.0001). Gram-negative pathogens caused polymicrobial PJI in 61.5 % of cases with infection recurrence (OR 4.4; 95 % CI 1.18–16.37; p = 0.03).

Conclusions

Overweight and obese patients or those with elevated CRP had a greater risk of polymicrobial PJI. They were predisposed to recurrence of infection after the first step of two-stage revision. An unsuccessful outcome was more likely in cases with polymicrobial infection compared to those with monomicrobial infection. In addition, the presence of multidrug-resistant strains of Gram-negative bacteria substantially increased the risk of PJI treatment being unsuccessful.

Level of evidence

Level III, therapeutic study.

     

Altered performance of reelin-receptor ApoER2 deficient mice on spatial tasks using the Barnes maze

The apolipoprotein E receptor 2 (ApoER2), expressed predominantly in forebrain regions including the hippocampus, is 1 of 2 receptors for the extracellular matrix protein reelin, which is critical for cortical development. Previous studies of ApoER2 mutant mice have indicated deficits in synaptic plasticity and learning. The current authors assessed learning and memory of ApoER2 knockout and wild-type mice on the Barnes circular maze. Mice were trained in this task for 22 days, followed by memory recall and reversal tests. ApoER2 knockout mice were initially slower to complete the task, but by Day 22 they were more accurate than wild-type mice on several indices. There were no differences in memory assessed by the recall task, but ApoER2 knockout mice performed significantly worse on the memory reversal task. ApoER2 knockout mice also displayed altered use of specific search strategies and relationship of these strategies to errors made on the maze.     

Aetiological risk factors are associated with distinct imaging findings in patients with chronic pancreatitis: A study of 959 cases from the Scandinavian Baltic Pancreatic Club (SBPC) imaging database

ObjectivesThe relation between aetiology and structural changes of the pancreas in patients with chronic pancreatitis (CP) is not fully understood. Earlier studies are limited by focusing on selected factors in studies of limited sample size. We aimed to use a large dataset to explore associations between aetiology and pancreatic morphology in CP.MethodsSubjects with definite or probable CP according to the M-ANNHEIM diagnostic criteria were included in this multicentre cross-sectional observational study and assessed using a standardized and validated CP imaging system. We performed multivariate logistic regression to analyse if aetiological factors adjusted for covariates were independently associated with morphological pancreatic features.ResultsWe included 959 patients (66% males). Mean (SD) age was 55 (14) years. Pancreatic structural changes were found in 94% of the subjects: 67% had calcifications, 59% main pancreatic duct dilatation, 33% pseudo-cysts and 22% pancreatic atrophy. Alcohol abuse was independently associated with pancreatic calcifications (odds ratio (OR, [95% CI]); 1.61, [1.09, 2.37]) and focal acute pancreatitis (OR; 2.13, [1.27, 3.56]), whereas smoking was independently associated with more severe calcifications (OR; 2.09, [1.34, 3.27]) and involvement of the whole gland (OR; 2.29, [1.61, 3.28]). Disease duration was positively associated with calcifications (OR; (per year) 1.05 [1.02, 1.08]) and pancreatic atrophy (OR; 1.05 [1.02, 1.08]) and negatively associated with focal acute pancreatitis (OR 0.91, [0.87, 0.95] and pseudo cysts (OR; 0.96, [0.93, 0.98]).ConclusionIn this large-scale study, etiological risk factors and disease duration in CP were independently associated with specific structural pancreatic imaging changes.