Processed meat intake and incidence of colorectal cancer: a systematic review and meta-analysis of prospective observational studies.

The objective was to use accumulated evidence to explore the association between processed meat intake and risk of colorectal cancer (CRC) and to investigate the reliability of associations by evaluating patterns of risk by study population characteristics and research quality parameters. We included 29 observational prospective cohort studies with relative risk estimates and 95% confidence intervals for CRC according to various levels of processed meat consumption. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Data sources were PubMed and Embase up to January 2017. The summary relative risks for high versus low processed meat consumption and risk of CRC, colon, and rectal cancer were 1.13 (95% CI: 1.01, 1.26), 1.19 (95% CI: 1.09, 1.31), and 1.21 (95% CI: 0.98, 1.49), respectively. Similar estimates were observed for the dose-response analyses. Heterogeneity across studies was detected in most analytical models. The overall judgment showed that two out of 29 studies had a moderate risk of bias, 25 had a serious risk of bias, and 2 had a critical risk of bias. The bias domains most often rated critical were bias due to risk of confounding, bias due to missing data, and selective outcome reporting bias. Although this meta-analysis indicates a modest association between processed meat intake and an increased risk of CRC, our assessment of internal validity warrants a cautious interpretation of these results, as most of the included studies were judged to have serious or critical risks of bias.

Depletion of SMC5/6 sensitizes male germ cells to DNA damage.

The structural maintenance of chromosomes complex SMC5/6 is thought to be essential for DNA repair and chromosome segregation during mitosis and meiosis. To determine the requirements of the SMC5/6 complex during mouse spermatogenesis we combined a conditional knockout allele for Smc5, with four germ cell-specific Cre-recombinase transgenes, Ddx4-Cre, Stra8-Cre, Spo11-Cre, and Hspa2-Cre, to mutate Smc5 in spermatogonia, in spermatocytes before meiotic entry, during early meiotic stages, and during midmeiotic stages, respectively. Conditional mutation of Smc5 resulted in destabilization of the SMC5/6 complex. Despite this, we observed only mild defects in spermatogenesis. Mutation of Smc5 mediated by Ddx4-Cre and Stra8-Cre resulted in partial loss of preleptotene spermatocytes; however, spermatogenesis progresses and mice are fertile. Mutation of Smc5 via Spo11-Cre or Hspa2-Cre did not result in detectable defects of spermatogenesis. Upon exposure to gamma irradiation or etoposide treatment, each conditional Smc5 mutant demonstrated an increase in the number of enlarged round spermatids with multiple acrosomes and supernumerary chromosome content. We propose that the SMC5/6 complex is not acutely required for premeiotic DNA replication and meiotic progression during mouse spermatogenesis; however, when germ cells are challenged by exogenous DNA damage, the SMC5/6 complex ensures genome integrity, and thus, fertility.

Electroencephalographic study showing that tactile stimulation by fabrics of different qualities elicit graded event-related potentials.

BACKGROUND/PURPOSE: Neurophysiologic data on reactions of the human brain towards tactile stimuli evoked by fabrics moved on the skin are scarce. Furthermore, evaluation of fabrics' pleasantness using questionnaires suffers subjective biases. That is why we used a 64-channel electroencephalography (EEG) to objectively evaluate real-time brain reactions to fabric-skin interactions. METHODS: Tactile stimuli were triggered by selected fabrics of different qualities, i.e. modal/polyamide single jersey, cotton double rib and a jute fabric, applied hidden to either the palm or forearm of 24 subjects via a custom-made fabric-to-skin applicator called SOFIA. One-way anova analysis was carried out to verify the EEG data. RESULTS: The modal/polyamide fabric applied to the forearm and palm led to slightly stronger emotional valence scores in the brain than the conventional or baseline fabric. Furthermore, the single jersey elicits significant higher event-related potential (ERP) signals in all subjects when applied to the forearm, suggesting less distraction and better cognitive resources during the fabric/skin interaction. The brain thus reacts with instantaneous ERP to tactile stimulation of fabrics and is able to discriminate different qualities via implicit preferences. CONCLUSION: The test procedure described here may be a tool to evaluate the fabric feel with the exclusion of subjective biases.

Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted approach toward peptide-based immunotherapy.

Identification of physiologically relevant peptide vaccine targets calls for the direct analysis of the entirety of naturally presented human leukocyte antigen (HLA) ligands, termed the HLA ligandome. In this study, we implemented this direct approach using immunoprecipitation and mass spectrometry to define acute myeloid leukemia (AML)-associated peptide vaccine targets. Mapping the HLA class I ligandomes of 15 AML patients and 35 healthy controls, more than 25 000 different naturally presented HLA ligands were identified. Target prioritization based on AML exclusivity and high presentation frequency in the AML cohort identified a panel of 132 LiTAAs (ligandome-derived tumor-associated antigens), and 341 corresponding HLA ligands (LiTAPs (ligandome-derived tumor-associated peptides)) represented subset independently in >20% of AML patients. Functional characterization of LiTAPs by interferon-γ ELISPOT (Enzyme-Linked ImmunoSpot) and intracellular cytokine staining confirmed AML-specific CD8(+) T-cell recognition. Of note, our platform identified HLA ligands representing several established AML-associated antigens (e.g. NPM1, MAGED1, PRTN3, MPO, WT1), but found 80% of them to be also represented in healthy control samples. Mapping of HLA class II ligandomes provided additional CD4(+) T-cell epitopes and potentially synergistic embedded HLA ligands, allowing for complementation of a multipeptide vaccine for the immunotherapy of AML.

[Denervation of the patella: influence on mid-term results after total knee arthroplasty]. / Retropatellare Denervierung : Einfluss auf die mittelfristigen Ergebnisse von Knietotalendoprothesenimplantationen.

BACKGROUND: The purpose of the study was to determine possible differences in the mid-term results of total knee arthroplasty in patients treated with and without denervation of the patella. PATIENTS AND METHODS: This study included 80 total knee replacements in 71 patients who were treated with total knee replacement, either with (n = 40) or without (n = 40) simultaneous denervation of the patella out of a total population with 122 knee replacements in 100 patients. Comparability of both groups was achieved by applying matching criteria. All patients were reviewed by isokinetic tests, physical and radiological examination. The mean follow-up time was 2.2 years. RESULTS: The mean hospital for special surgery (HSS) score revealed no statistically significant differences between both groups (with denervation 77.9 ± 11.1 and without denervation 77.8 ± 11.0, p = 0.976). The isokinetic torque measurements with low angle velocity (60°/s) indicated slightly higher values during extension (60.2 ± 32.2 Nm versus 55.8 ± 25.2 Nm, p = 0.497) and flexion (52.4 ± 28.3 Nm versus 46.1 ± 22.3 Nm, p = 0.272) movements of the affected knee joint. However, the differences did not reach statistical significance. At high angle velocity (180°/s) no differences could be found between both groups. No cases of postoperative necrosis of the patella were observed. Anterior knee pain after denervation was reported in 6 cases (15 %) compared to 10 cases (25 %) in patients who were treated without denervation (p = 0.402). CONCLUSION: No statistically significant differences could be found between patients with and without denervation of the patella for total knee arthroplasty.

New point mutation in Golga3 causes multiple defects in spermatogenesis.

Mice with repro27 exhibit fully penetrant male-specific infertility associated with a nonsense mutation in the golgin subfamily A member 3 gene (Golga3). GOLGA3 is a Golgi complex-associated protein implicated in protein trafficking, apoptosis, positioning of the Golgi and spermatogenesis. In repro27 mutant mice, a point mutation in exon 18 of the Golga3 gene that inserts a pre-mature termination codon leads to an absence of GOLGA3 protein expression. GOLGA3 protein was undetectable in the brain, heart and liver in both mutant and control mice. Although spermatogenesis in Golga3(repro27) mutant mice appears to initiate normally, development is disrupted in late meiosis during the first wave of spermatogenesis, leading to significant germ cell loss between 15 and 18 days post-partum (dpp). Terminal Deoxynucleotidyl Transferase dUTP-mediated Nick End Labeling analysis showed elevated DNA fragmentation in meiotic germ cells by 12 dpp, suggesting apoptosis as a mechanism of germ cell loss. The few surviving post-meiotic round spermatids exhibited abnormal spermiogenesis with defects in acrosome formation, head and tail development and extensive vacuolization in the seminiferous epithelium. Analysis of epididymal spermatozoa showed significantly low sperm concentration and motility and in vitro fertilization with mutant spermatozoa was unsuccessful. Golga3(repro27) mice lack GOLGA3 protein and thus provide an in vivo tool to aid in deciphering the role of GOLGA3 in Golgi complex positioning, cargo trafficking and apoptosis signalling in male germ cells.

Early neurophysiology and MRI in predicting neurological outcome at 9-10 years after birth asphyxia.

OBJECTIVE: To assess whether early somatosensory evoked potentials (SEP) predict long-term neurodevelopmental outcome in normothermic, full-term infants with mild to moderate neonatal encephalopathy (NE), and to compare their predictive value to already available amplitude integrated EEG (aEEG) and magnetic resonance imaging (MRI). METHODS: Fifty-six infants with post-asphyxia NE were prospectively recruited, and their SEP, aEEG and MRI data were acquired during the first five days. Follow-up continued to 9-10 years for assessment of neuromotor and neurocognitive development. We analysed SEP latency (N1 component), normality of aEEG background pattern, as well as patterns of injury on the neonatal MRI. Neurological outcome measures at 9-10 years included conventional MRI, Movement-ABC and the WISC-III NL. RESULTS: A SEP latency <50 ms during the first five days was associated with a normal neuromotor outcome (p < 0.03), and a prolonged day 3 latency was associated with lower childhood IQ (p = 0.02). The presence of multiple seizures in aEEG, as well as a moderate or severe injury on the neonatal MRI was associated with a poor neuromotor score (p = 0.03 and p < 0.01, respectively). Combination of multiple techniques improved prediction of long-term outcome compared to single modality. CONCLUSION: Early SEPs provide information that is comparable to the already available aEEG and MRI paradigms in the prediction of long-term outcome of full-term infants with mild to moderate neonatal encephalopathy. SIGNIFICANCE: The present results call for further studies using early SEP to aid early assessment of infants treated with hypothermia.

[Prosthesis loosening]. / Prothesenlockerung.

Prosthesis loosening is becoming more and more important due to increasing numbers of primary arthroplasty. Especially in patients suffering from rheumatoid arthritis this is a major topic due to younger age and multiple affected joints. A carefully performed diagnostic regimen is essential for ruling out septic loosening of the prosthesis. Preoperative planning is crucial for revision surgery. Revision implants should be available as back-up. Revision arthroplasty is a technically and economically demanding procedure. Costs for revision surgery are much higher than for primary arthroplasty due to longer hospital stay, intensive care, microbiology, histology, diagnostic imaging, implants and antibiotics. Revision arthroplasty should be performed in highly specialized centers.

Adipogenic differentiation of scaffold-bound human adipose tissue-derived stem cells (hASC) for soft tissue engineering.

Adipose tissue engineering, instead of tissue substitution, often uses autologous adipose tissue-derived stem cells (hASC). These cells are known to improve graft integration and to support neovascularization of scaffolds when seeded onto biomaterials. In this study we thought to engineer adipose tissue using scaffold-bound hASC, since they can be differentiated into the adipocyte cell lineage and used for soft tissue regeneration. We show here by microscopy and gene expression of the peroxysome proliferator-activated receptor gene (PPARγ2) that hASC growing on polypropylene fibrous scaffolds as well as on three-dimensional nonwoven scaffolds can be turned into adipose tissue within 19 days. Freshly isolated hASC displayed a higher differentiation potential than hASC cultured for eight passages. In addition, we proved a modified alginate microcapsule to directly induce adipogenic differentiation of incorporated hASC. The results may help to improve long-term success of adipose tissue regeneration, especially for large-scale soft tissue defects, and support the development of cell-scaffold combinations which can be shaped individually and directly induce the adipogenic differentiation of incorporated hASC at the site of implantation.

[The oncofetal gene survivin - a possible target gene for regenerative therapy concepts in cartilaginous tissue]. / Das "onkofetale" Gen Survivin - ein mögliches Ziel-Gen regenerativer Therapiekonzepte im Gelenkknorpel.

Survivin, the smallest member of the inhibitor of the apoptosis protein gene family (IAP) is a key molecule for mammalian cell cycle regulation and cellular survival. Of note these functions have been thought to be limited to embryonic and malignant tissues. However, a growing body of evidence indicates a limited expression of survivin in some highly specific adult tissues and cells. In the present study it has been demonstrated that the antiapoptotic protein survivin is re-expressed in osteoarthritic human cartilage and primary human chondrocytes. Furthermore, the data indicated that survivin significantly affects cell cycle regulation and cellular survival. The modulation of survivin expression and function in cartilaginous tissues might be important for understanding osteoarthritis and the development of regenerative strategies.

[Patient satisfaction and muscle torque after total knee replacement in dependence on body mass index]. / Patientenzufriedenheit und Muskelkraft nach Knietotalendoprothese in Abhängigkeit vom Body-Mass-Index.

AIM: In a monocentric study, we investigated patient satisfaction, clinical outcome and isokinetic muscle torque in dependence on the body mass index (BMI) in the mid-term outcome after total knee arthroplasty. PATIENTS AND METHODS: A group-matched study with two groups (each 40 knee arthroplasties in 40 patients) with a normal body mass index (BMI 20-25) and above 25 was conducted. The groups were matched for sex, diagnosis and age. Satisfaction, HSS score and isokinetic torque parameters with the Cybex 340 system were measured. RESULTS: There were no differences in the demographic data except for BMI. The HSS score was significantly lower in the overweight group (p = 0.04). Also there were more patients with an HSS score below 60 (bad result) in the group with the higher BMI (0 vs. 9, p = 0.002). Only one patient was not satisfied in the normal weight group, whereas 9 patients in the group BMI > 25 were not satisfied (p = 0.014). No differences between the groups could be found in maximum torque, work and power. CONCLUSION: The patient satisfaction was much lower in patients with BMI higher than 25. There were no differences between the groups in isokinetic torque parameters.

[Hallux rigidus]. / Hallux rigidus.

Osteoarthritis of the first metatarsophalangeal joint is termed hallux rigidus. Clinical symptoms are expressed by a painful limitation of range of motion, finally leading to an eponymous total stiffness of the joint. Conservative treatment includes drug therapy, physical therapy and orthotic devices like insoles and footwear modification. After making use of the whole range of conservative treatment options, several surgical techniques are available, which should be considered depending on stage, patient's activity level and possible comorbid diseases. Open and arthroscopic techniques addressing the cartilage and cheilectomy can be chosen in early stages of hallux rigidus. Osteoarthritis at a higher stage requires further reaching techniques, e.g. Bonney-Kessel procedure or Watermann-Green procedure. When the complete clinical picture of hallux rigidus is present, arthrodesis is the gold standard. Nevertheless, alternative surgical treatments like arthroplasty and resection arthroplasty are being discussed.

Prospective single-arm, multi-center trial of a patient-specific interpositional knee implant: early clinical results.

BACKGROUND: The treatment of unicompartmental arthritis in younger patients is challenging. The aim of this study is to report final safety and efficacy analysis results for the iForma patient-specific interpositional device, which is designed for the treatment of isolated medial or lateral compartment arthritis of the knee. METHODS: From June 2005 to June 2008 78 subjects (42 men, 36 women) received an iForma implant. The mean age was 53 years, the mean Body Mass Index 29.0. We surveyed the WOMAC scores, the visual analog pain scale and the Knee Society Scores. RESULTS: The mean follow up was 16.4 months. The mean WOMAC knee scores increased from 48.3 before surgery to 71.3 after 24 months. A reduction in pain was achieved for all five pain measures using a standard visual analog scale (VAS). Knee Society Knee Score improved from 39.2 before to 61.9 24 month after surgery. The Knee Society Function Scores improved form preoperative 64.5 to 82.5 2 years postoperative. The preoperative range of motion could be restored. The overall revision rate was 24%. 15 implants were removed early, 4 knees were revised without implant removal. CONCLUSION: Within narrow indication of patients with unicompartmental disease, the iForma device can provide improvement in knee function and reduction in pain, however, with a significant higher risk of early revision compared to traditional arthroplasty. Respecting this limitation it may be an alternative option for arthritic patients with unicompartmental disease who have contraindications to High Tibial Osteotomy or are too young for knee replacement; the iForma device further has the distinct advantage of time and cost saving compared to those procedures.

Comparison of two accelerated clinical pathways--after total knee replacement how fast can we really go?

OBJECTIVE: To evaluate whether a further optimization of an existing accelerated clinical pathway protocol after total knee replacement is feasible and improves postoperative outcome. DESIGN: Prospective, parallel group design. SETTING: Orthopaedic University Medical Centre. PATIENTS: A total of 143 patients, scheduled for unilateral primary total knee replacement under perioperative regional analgesia. INTERVENTION: Sixty-seven patients received an optimized accelerated clinical pathway including patient-controlled regional analgesia pumps, ultra-early/doubled physiotherapy and motor-driven continuous passive motion machine units. Seventy-six patients received a standard accelerated clinical pathway. MAIN MEASURES: Feasibility was defined as the proportion of patients successfully completing the assigned pathway. Early postoperative pain on a visual analogue scale, consumption of regional anaesthetics, knee range of motion, time out of bed, non-stop walking distance/stair climbing, circumference measurement and Knee Society Score on the operated leg. Possible discharge according to an own discharge checklist. RESULTS: All patients assigned to both groups successfully completed this pathway. Patients in the optimized pathway showed significant benefits regarding stair climbing/walking distance/time out of bed/circumference measurements of the thigh/Knee Society function score on the fifth postoperative day and stair climbing/ circumference measurements of the thigh on the eighth postoperative day, and reduction of the consumption of regional anaesthetics. No significant reduction in length of stay was observed. CONCLUSIONS: Early postoperative functional process indicators tended to be higher within the optimized pathway group, but the main effects flattened over the course of the first eight postoperative days.

[Toxicity of antiseptics on chondrocytes in vitro]. / Toxizität lokaler Antiseptika auf Chondrozyten in vitro.

AIM: Local antiseptics are commonly used for perioperative skin and wound disinfection and as solutions for joint lavage. Therefore, we examined if an intra-articular use of these antiseptics is possible by using an IN VITRO chondrocyte model. MATERIAL AND METHODS: Articular chondrocytes harvested from 7 patients were cultured. After reaching 80% confluency different concentrations (0%, 1%, 10%, 50%, 100%) of polyhexanide, hydrogen peroxide and povidone-iodine were added for 5 minutes. Afterwards, the solution was removed and the chondrocytes were cultured for 24 hours. Subsequently the vitality and proliferation rate (DNA synthesis) were analysed with the WST-1 and BrdU tests. RESULTS: 1% povidone-iodine and 1% hydrogen peroxide solutions significantly (p=0.001) decreased the chondrocyte vitality as compared to our control group. There was no significant difference (p=0.71) after the application of 1% polyhexanide in the vitality ratios. A significant decrease in vitality was also observed after the application of 10% polyhexanide solution (p=0.001). Application of 1% povidone-iodine solution, 1% hydrogen peroxide solution and 10% polyhexanide revealed a decrease in the metabolic cell activity of 80% compared to our control group, whereas the activity was 65% (p=0.026) compared to the control group after application of 1% polyhexanide solution. CONCLUSION: Our results demonstrate the chondrotoxic effect of the tested antiseptic solutions in clinical used concentrations within short time points. Polyhexanide in a low concentrated solution (1%) was the antiseptic with the lowest influence on the vitality and the DNA synthesis of chondrocytes. Thus, this antiseptic solution seemed to be the best choice for intra-articular application. But overall, our study showed general limitations for the intra-articular use of local antiseptics.

[Persisting pain after open articulosynovectomy--gossypiboma]. / Persistierende Schmerzen nach offener Artikulosynovektomie am Kniegelenk--die vergessene Kompresse.

We report about a 44-year-old woman who presented at our Orthopaedic Department suffering from persisting pain and a tumor of the right knee after open articulosynovectomy. MRI did not clarify the entity at all. The X-ray examination could identify an inlying compress after a synovectomy in 1999. The intra-articular foreign body could be removed by open revision surgery.

[Loosening of a total hip arthroplasty due to metastasis]. / Metastatisch bedingte Lockerung einer Hüfttotalendoprothese.

A case report of a metastatic caused loosening of a total hip arthroplasty one year after primary implantation is presented. A primary cancer was unknown at surgery. Due to suspected low-grade infection, a revision surgery was performed and the diagnosis of a metastatically caused loosening could be made. A bronchial carcinoma was identified as primary cancer. In spite of the rare incidence of the described metastatic loosening, the significance of a differential diagnostic strategy and the importance of a histological examination in revision surgery is depicted.

Effect of health-promoting posters placed on the platforms of two train stations in Copenhagen, Denmark, on the choice between taking the stairs or the escalators: a secondary publication.

OBJECTIVE: The purpose of this study was to determine whether posters placed on the platforms of two train stations in Copenhagen, promoting use of the stairs, would encourage people to use the stairs rather than the adjacent escalator. An additional purpose was to see if the effect of the intervention was maintained for a week after the poster was removed. MEASUREMENTS: The number of people using stairs and escalators at Copenhagen Central Station and Østerport Train Station in Copenhagen was recorded before and during posters promoting stair use were placed on the platforms, and a week after the posters were removed. Two years after the posters were removed, data were collected for 1 week at Østerport Train Station (long-term post-intervention). RESULTS: At Copenhagen Central Station, the overall stair use increased from 12% before the intervention to 16% (P<0.0001) during the intervention, giving an odds ratio (OR) of 1.5 for stair use. At Østerport Train Station in Copenhagen, the overall stair use increased from 23 to 31% during the intervention (P<0.0001), and dropped to 27% (P<0.0001) after the intervention (during the intervention, OR=1.5 (P<0.0001); after the intervention, OR=1.2 (P<0.0001)). At the long-term post-intervention recording, the overall stair use was 25%, which was not significantly different from the stair use found before the intervention. DISCUSSION: Posters promoting stair use placed on the platforms of train stations can result in increased stair use, during and after 1 week of intervention, and thereby seem useful only when up and immediately following intervention in changing health-promoting behavior among Danish men and women. These results agree well with results from other countries.

Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases. OBJECTIVE: The study evaluated the efficacy of intranasal treatment with an adenosine A(2A) receptor agonist/adenosine A(3) receptor antagonist (50 micro g), administered twice daily for 7 days, to reduce nasal symptoms and release of inflammatory mediators following intranasal allergen challenge in patients with allergic rhinitis (AR). The compound was compared with twice-daily treatment with intranasal fluticasone proprionate nasal spray (FPANS) for 7 days. METHODS: A randomized, double-blind, double-dummy, placebo-controlled, three-way balanced, incomplete block, crossover study was conducted on 48 males with verified AR. Following intranasal challenge with either an extract from the house dust mite (HDM), Dermatophagoides pteronyssinus, rye grass or cat dander, nasal responses and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic cationic protein, epithelial neutrophil-activating protein-78 (ENA-78), IL-5 and IL-8 in nasal secretions were measured and treatment groups were compared. RESULTS: Drug improved nasal blockage but had no significant effect on rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when compared with placebo. Drug reduced tryptase release after EAR but did not significantly reduce the levels of other mediators. CONCLUSION: A novel agonist/antagonist of adenosine A(2A) and A(3) receptors appears to have limited clinical benefit in both the early-phase and the late-phase response to intranasal allergen challenge. However, reduction of some pro-inflammatory mediators suggests that comparable, more selective compounds may have additional benefits meriting further investigation.