Is hospital volume associated with length of stay, re-admissions and reoperations for total hip replacement? A population-based register analysis of 78 hospitals and 54,505 replacements

Introduction

Hospital volume has been suggested to be a significant determinant of the outcome of joint replacement surgery. We updated previously published data on the effect of hospital volume on length of stay, re-admissions, and reoperations for total hip replacement (THR) at the population level in Finland.

Materials and methods

A total of 54,505 THRs for primary osteoarthritis performed between 1998 and 2010 were identified from the Hospital Discharge Register and the Finnish Arthroplasty Register. Hospitals were classified into four groups according to the number of primary and revision total hip and knee arthroplasties performed on an annual basis over the whole study period: 1–199 (group 1), 200–499 (group 2), 500–899 (group 3), and >900 (group 4). We analyzed the association between hospital procedure volume and length of stay (LOS), length of uninterrupted institutional care (LUIC), re-admissions and reoperations.

Results

The larger the volume group, the shorter were LOS and LUIC (p < 0.01). According to the adjusted data, risk for re-admission in 42 days was greater in group 1 than in group 4 (OR = 1.14; 95 % CI: 1.05–1.23). There was no difference in the risk for reoperation.

Conclusion

LOS and LUIC ought to be shortened in lower volume hospitals.     

Psychophysiological responses to eye contact in a live interaction and in video call

Another person's gaze directed to oneself elicits autonomic arousal and facial reactions indicating positive affect in its observer. These effects have only been found to occur with mutual, live eye contact and not in response to direct gaze pictures or when the observer believes that the live person cannot see them. The question remains whether the physical presence of the other person is necessary for these effects. We measured psychophysiological responses to another person's direct versus averted gaze in three conditions: live interaction, bidirectional video call, and watching a mere video. Autonomic arousal was measured with skin conductance responses and facial reactions with facial electromyography. In the live and video call conditions, but not in the mere video condition, direct gaze increased autonomic arousal in comparison to averted gaze. In all three conditions, however, direct gaze elicited positive affective facial reactions. Therefore, an experience of being seen is essential for the autonomic reactions but not for the facial responses that are elicited by another person's direct gaze. Most importantly, the results suggest that the physical presence or proximity of the other person is not necessary for these psychophysiological responses to eye contact.     

Heart rate variability associates with asymptomatic coronary atherosclerosis

Purpose

Heart rate variability (HRV) becomes impaired in symptomatic coronary artery disease (CAD), particularly, after myocardial infarction. The mechanism how CAD results in impairment of cardiac autonomic regulation is not known. Whether it results rather from coronary atherosclerosis itself than myocardial ischemia and myocardial injury has remained elusive.

Methods

Quantitative coronary angiography was performed in 30 subjects without history of myocardial ischemia, but with high familial risk for CAD. HRV was measured from 24-h ambulatory ECG recordings in time and frequency domain and also non-linear HRV variables SD1 and SD2 in Poincare plot were calculated. Myocardial ischemia was excluded by Tc-99m sestamibi scintigraphy at rest and during exercise.

Results

Coronary angiography revealed mean diameter stenosis of 32 ± 19 % in left anterior descending coronary artery, 26 ± 16 % in left circumflex coronary artery and 25 ± 20 % in right coronary artery. An inverse correlation was found between pNN50 and global severity of coronary artery diameter stenosis (r = ?0.415, p < 0.05). Correspondingly, power of HF spectral component correlated negatively with global extent of coronary atherosclerosis (r = ?0.366, p < 0.05). In Poincare plot, SD1/SD2 ratio correlated with global extent (r = ?0.394, p < 0.05) and global burden (r = ?0.388, p < 0.05) of coronary arteries.

Conclusions

The severity and extent of coronary atherosclerosis were related to a shift of cardiac autonomic regulation towards sympathetic predominance in asymptomatic subjects without evidence of myocardial ischemia.     

Extracellular prolyl oligopeptidase derived from activated microglia is a potential neuroprotection target

Prolyl oligopeptidase (PREP) is an abundant peptidase in the brain and periphery, but its physiological functions are still largely unknown. Recent findings point to a role for PREP in inflammatory processes. This study assessed the cellular and extracellular PREP activities in cultures of mouse primary cortical neurons, microglial cells and astrocytes, and immortalized microglial BV‐2 cells under neuroinflammatory conditions induced by lipopolysaccharide (LPS) and interferon gamma (IFNγ). Furthermore, we evaluated the neuroprotective effect of a specific PREP inhibitor, KYP‐2047, in a neuroinflammation model based on a coculture of primary cortical neurons and activated BV‐2 cells. The inflammatory insult reduced intracellular and increased extracellular PREP activity specifically in microglial cells, suggesting that activated microglia excretes active PREP. A targeted proteomics approach revealed up‐regulation in PREP protein levels in BV‐2 cell growth medium but down‐regulation in crude membrane‐bound PREP after LPS+IFNγ. In the coculture of BV‐2 cells and primary neurons, an increase in extracellular PREP activity was also detected after inflammation. KYP‐2047 (10 μmol/L) significantly protected neurons against microglial toxicity and reduced the levels of the pro‐inflammatory cytokine tumour necrosis factor alpha. In conclusion, these data point to an extracellular role for microglial PREP in the inflammatory process. Inhibition of PREP during neuroinflammation is a potential target for neuroprotection. Thus, PREP inhibitors may offer a novel therapeutic approach for the treatment of neurodegenerative disorders with an inflammatory component including Parkinson's and Alzheimer's diseases.     

ALK fusion and its association with other driver gene mutations in Finnish non‐small cell lung cancer patients

Screening of anaplastic lymphoma tyrosine kinase (ALK) gene fusions in non‐small cell lung cancer (NSCLC) patients enables the identification of the patients likely to benefit from ALK‐targeted therapy. Our aim was to assess the prevalence of ALK fusion in Finnish NSCLC patients, which has not been reported earlier, and to study the presence of ALK fusion in relation to clinicopathological characteristics and other driver gene mutations. A total of 469 formalin‐fixed paraffin‐embedded tumor tissue specimens from Finnish NSCLC patients were screened for ALK fusion by immunohistochemistry (IHC). For confirmation of IHC results, fluorescence in situ hybridization (FISH) was conducted for 171 specimens. Next‐generation sequencing was performed for all ALK‐positive specimens to characterize the association of ALK fusion with mutations in targeted regions of 22 driver genes. Of the 469 tumors screened, 11 (2.3%) harbored an ALK fusion, including nine adenocarcinomas and two large cell carcinomas. The IHC results for all 11 ALK‐positive and 160 random ALK‐negative specimens were confirmed by FISH. ALK fusion was significantly associated with never/ex‐light smoking history (P < 0.001) and younger age (P = 0.004). Seven ALK‐positive tumors showed additional mutations; three in MET, one in MET and CTNNB1, two in TP53, and one in PIK3CA. Our results show that ALK fusion is an infrequent alteration in Finnish NSCLC patients. Although the majority of ALK‐positive cases were adenocarcinomas, the fusion was also seen in large cell carcinomas. Further studies are needed to elucidate the clinical significance of the coexistence of ALK fusion with MET, TP53, CTNNB1, and PIK3CA mutations. © 2014 Wiley Periodicals, Inc.     

Critical-sized cartilage defects in the equine carpus

Aim: The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Material and Methods: Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, with MR and µCT imaging, polarized light microscopy, standard histology, and immunohistochemistry at 12 months. Results: Filling of 2 mm chondral defects was good (77.8 ± 8.5%), but proteoglycan depletion was evident in Safranin-O staining and gadolinium-enhanced MRI (T_1Gd). Larger chondral defects showed poor filling (50.6 ± 2.7% in 4 mm and 31.9 ± 7.3% in 8 mm defects). Lesion filling in 2, 4, and 8 mm osteochondral defects was 82.3 ± 3.0%, 68.0 ± 4.6% and 70.8 ± 15.4%, respectively. Type II collagen staining was seen in 9/15 osteochondral defects but only in 1/15 chondral defects. Subchondral bone pathologies were evident in 14/15 osteochondral samples but only in 5/15 chondral samples. Although osteochondral lesions showed better neotissue quality than chondral lesions, the overall repair was deemed unsatisfactory because of the subchondral bone pathologies. Conclusion: We recommend classifying 4 mm as critical osteochondral lesion size and 2 mm as critical chondral lesion size for cartilage repair research in the equine carpal joint model.     

Mutated Ephrin Receptor Genes in Non‐Small Cell Lung Carcinoma and Their Occurrence with Driver Mutations—Targeted Resequencing Study on Formalin‐Fixed,Paraffin‐Embedded Tumor Material of 81 Patients

Non‐small cell lung carcinoma (NSCLC) is the most common subtype of lung cancer. The oncogenic potential of receptor tyrosine kinases (RTKs) is widely known and they are potential targets for tailored therapy. Ephrin receptors (Ephs) form the largest group of RTKs. Nevertheless, Ephs are not widely studied in NSCLC so far. The aim of our study was to investigate novel mutations of Eph genes (EPHA1–8, EPHB1–4, EPHB6) and their association with clinically relevant mutations in BRAF, EML4‐ALK, EGFR, INSR, KDR, KRAS, MET, PDGFRA, PDGFRB, PIK3, PTEN, RET, and TP53 in NSCLC patients. Targeted resequencing was conducted on 81 formalin‐fixed, paraffin‐embedded NSCLC tumor specimens. We analyzed missense and nonsense mutations harbored in the coding regions of the selected genes. We found 18 novel mutations of Ephs in 20% (16 of 81) of the patients. Nearly half of these mutations occurred in the protein kinase domain. The mutations were not mutually exclusive with other clinically relevant mutations. Our study shows that Ephs are frequently mutated in NSCLC patients, and occur together with other known mutations relevant to the pathogenicity of NSCLC. © 2013 Wiley Periodicals, Inc.     

Cervical squamous carcinoma cells are resistant to the combined action of tumor necrosis factor-α and histamine whereas normal keratinocytes undergo cytolysis

Background  

Previous reports showed that mast cells can typically be found in the peritumoral stroma of cervix carcinomas as well as in many other cancers. Both histamine and TNF-α are potent preformed mast cell mediators and they can act simultaneously after release from mast cells. Thus, the effect of TNF-α and histamine on cervical carcinoma cell lines was studied.