Long-term follow-up in a single-bundle arthroscopic acromioclavicular joint reconstruction after Rockwood III to VI dislocation.

This retrospective study presents the clinical and radiographic results of a single-bundle arthroscopic acromioclavicular joint reconstruction in 45 patients with a mean follow-up of 4.8 years. Patients with a Rockwood grade III or higher were included. Clinical results were based on satisfaction, pain and functional scores. These outcome scores were compared to coracoclavicular distance measurement on X-ray. Secondly, clinical outcome scores were compared between patients who had surgery in the first 6 weeks after trauma and patients treated after 6 weeks. Overall, X-ray showed a good reduction in 71.1% of the patients (less than 50% loss of reduction). These patients showed better clinical results than patients with radiographical failure in terms of satisfaction (p = .001), Constant (p = .001), DASH (p = .031) and SPADI (p = .005) scores. In total, 78% of the patient had surgery in the first 6 weeks after trauma. When treated later (mean time to surgery of 8.8 months), patients showed worse results for satisfaction (p = .003) and DASH score (p = .006), suggesting that treatment of chronic cases might warrant additional fixation techniques. As a conclusion, these results showed that, in the acute approach, single-bundle arthroscopic coracoclavicular fixation is a good treatment in acromioclavicular joint dislocation Rockwood grade III or higher.

Lung imaging in bronchopulmonary dysplasia: a systematic review.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a common complication of preterm birth. Both historically and in current practice, radiologic evaluation of the lungs has an important role in assessing disease severity and complications. AIM: To provide an overview of imaging techniques for detecting lung abnormalities in patients with BPD in all age ranges. METHODS: A systematic literature search was conducted in PubMed, Web of Science and the Cochrane Library. Records were screened by title and abstract and then by full text. A total of 37 records were selected and included in this qualitative literature overview. RESULTS: Computed tomography (CT) was the most commonly used imaging modality, followed by chest radiography and magnetic resonance imaging (MRI). Several qualitative and quantitative scoring systems were presented and most showed good correlation with BPD severity. The association with functional and clinical outcomes was only rarely reported, showing varying correlation with spirometry results and respiratory exacerbations. MRI is an upcoming imaging technique for BPD that is technically feasible, showing clear differences in the lung parenchyma of patients with BPD. CONCLUSION: Several imaging and scoring methods indicate that lung imaging continues to play a role in BPD care. Standardization and correlation with functional and clinical outcomes will become increasingly important for further research.

Skin thickness measurements for optimal intradermal injections in children.

BACKGROUND: In the context of precision medicine and in response to the highly needed capacity of rapid interventions towards new infectious diseases and pandemic outbreaks, intradermal immunization is gaining increased attention. However, the currently used Mantoux technique for ID injection is difficult to standardize and requires training, especially when used in children. To allow determining the maximum penetration depth and needle characteristics for the development of a platform of medical devices suited for intradermal injection, VAX-ID® and to ensure an accurate ID injection in children, the epidermal and dermal thickness at the proximal ventral and dorsal forearm (PVF & PDF) and at the deltoid region in children aged 8 weeks to 18 years were assessed. The lateral part of the upper leg was assessed as well in children aged 8 weeks to 2 years since it is a commonly used injection site in this population. MATERIALS & METHODS: Mean thickness of the PVF, PDF, lateral part of the upper leg and deltoid were measured using high-frequency ultrasound. Association with gender, age and BMI was assessed using Mann-Whitney U Test, Spearman correlation and Wilcoxon Signed Ranks Test, respectively. RESULTS: Results showed an overall mean skin thickness of 0.99 mm (SD: 0.14 mm) at the PVF, 1.20 mm (SD: 0.17) at the PDF, 1.28 mm (SD: 0.16) at the lateral part of the upper leg and increasing to 1.32 mm (0.25) at the deltoid region. Age and BMI correlated significantly (p < 0.001) with skin thickness at all investigated body sites. Gender did not affect skin thickness in the investigated population. CONCLUSION: Significant differences in skin thickness at the PVF, PDF and deltoid region were seen according to age and BMI. An optimal needle length of 0.7 mm is advised to guarantee intradermal injection in children at all investigated injection sites. (NCT02727114).

Immunogenicity and safety of intradermal delivery of hepatitis B booster vaccine using the novel drug delivery device VAX-ID™.

BACKGROUND: Although intramuscular (IM) injection is still the most preferred method for vaccination, intradermal (ID) delivery may have several advantages over intramuscular and subcutaneous (SC), including an improved immune response and antigen dose sparing effect. However it is currently limited due to the difficulty in standardizing the injection technique often based on the Mantoux technique. Difficulties encountered using the Mantoux technique could be overcome by the use of alternative ID delivery systems that confer more uniform and standardized procedures. The aim of this study was to evaluate the performance of a newly developed intradermal injection device, VAX-ID™, via a proof-of-concept to assess the immunogenicity of a commercially available hepatitis B booster vaccination in healthy hepatitis B pre-immunised subjects. Additionally, device safety and tolerability was evaluated. MATERIALS AND METHODS: Three different routes of administration were compared over 4 groups, each receiving hepatitis B vaccine antigen: (1) standard IM injection in the deltoid region (HBVAXPRO® 10 µg/1 ml), (2) ID injection in the proximal posterior area of the forearm according to the Mantoux technique, (3) with VAX-ID™ in one forearm, or (4) with VAX-ID™ in both forearms. For ID injections 0.11 cc, of which 0.01 cc is overfill, was drawn from a vial containing HBVAXPRO® 40 µg/1 ml. Immunogenicity and safety were followed-up at day 0, 14, 30 and 210. RESULTS: A total of 48 subjects were included. All subjects showed an anamnestic response at 14 days post booster vaccination. Elevated titres persisted until end of follow-up at day 210. For the ID groups a 3 fold higher immune response at day 14 and day 30 was recorded compared to IM group. Local adverse events were more reported for ID compared to IM. CONCLUSIONS: The investigated ID injection device VAX-ID™ proves to be a good alternative to offer ID vaccination.

Treatment of non-idiopathic clubfeet with the Ponseti method: a systematic review.

PURPOSE: Although non-idiopathic clubfeet were long thought to be resistant to non-surgical treatment methods, more studies documenting results on treatment of these feet with the Ponseti method are being published. The goal of this systematic review is to summarize current evidence on treatment of non-idiopathic clubfeet using the Ponseti method. METHODS: PubMed and Limo were searched, reference lists of eligible studies were screened and studies that met the inclusion criteria were included. Data on average number of casts, Achilles tendon tenotomy (ATT), initial correction, recurrence, successful treatment at final follow-up and complications were pooled. The Methodological Index for Non-Randomized Studies was used to assess the methodological quality of the selected studies. RESULTS: In all, 11 studies were included, yielding a total of 374 non-idiopathic and 801 idiopathic clubfeet. Non-idiopathic clubfeet required more casts (7.2 versus 5.4) and had a higher rate of ATT (89.4% versus 75.7%). Furthermore, these feet had a higher recurrence rate (43.3% versus 11.5%) and a lower rate of successful treatment at final follow-up (69.3% versus 95.0%). Complications were found in 20.3% of the non--idiopathic cohort. When comparing results between clubfeet associated with myelomeningocele and arthrogryposis, the first group presented with a lower number of casts (5.4 -versus 7.2) and a higher rate of successful treatment at final follow-up (81.8% versus 58.2%). CONCLUSION: The Ponseti method is a valuable and non-invasive option in the primary treatment of non-idiopathic clubfeet in young children. Studies with longer follow-up are necessary to evaluate its long-term effect. LEVEL OF EVIDENCE: Level III - systematic review of Level-III studies.This work meets the requirements of the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and -Meta-Analyses).

Oral Tobramycin Prophylaxis Prior to Colorectal Surgery Is Not Associated with Systemic Uptake.

Preoperative oral prophylaxis with nonabsorbable antibiotics has been reported to reduce the risk of surgical site infections after colorectal surgery. This prospective study was conducted to evaluate the risk of toxic side effects by measuring postoperative serum tobramycin levels in patients who received a 3-day prophylaxis with tobramycin and colistin prior to colorectal surgery. In all patients, serum tobramycin concentrations were below the detection limit (0.3 mg/liter), implying a low risk of toxicity.

Selection and transfer of an IncI1-tet(A) plasmid of Escherichia coli in an ex vivo model of the porcine caecum at doxycycline concentrations caused by crosscontaminated feed.

AIMS: The aim of this study was to investigate the effect of subtherapeutic intestinal doxycycline (DOX) concentrations (4 and 1 mg l-1 ), caused by cross-contamination of feed, on the enrichment of a DOX-resistant commensal Escherichia coli and its resistance plasmid in an ex vivo model of the porcine caecum. METHODS AND RESULTS: A DOX-resistant, tet(A)-carrying, porcine commensal E. coli strain (EC 682) was cultivated for 6 days in the porcine caecum model under different conditions (0, 1 and 4 mg l-1 DOX). EC 682, other coliforms and anaerobic bacteria were enumerated daily. A selection of isolated DOX-resistant coliforms (n = 454) was characterized by rep-PCR clustering, PCR assays (Inc1 and tet(A)) and micro broth dilution susceptibility tests (Sensititre). Both 1 and 4 mg l-1 DOX-enriched medium had a significantly higher selective effect on EC 682 and other resistant coliforms than medium without DOX. Transconjugants of EC 682 were isolated more frequently in the presence of 1 and 4 mg l-1 DOX compared to medium without DOX. CONCLUSIONS: Subtherapeutic intestinal DOX concentrations have the potential to select for DOX-resistant E. coli, and promote the selection of transconjugants in a porcine caecum model. SIGNIFICANCE AND IMPACT OF THE STUDY: Cross-contamination of feed with antimicrobials such as DOX likely promotes the spread of antimicrobial resistance. Therefore, it is important to develop or fine-tune guidelines for the safe use of antimicrobials in animal feed and its storage.

High frequency ultrasound to assess skin thickness in healthy adults.

BACKGROUND: Intradermal immunization is gaining increased attention due to multiple factors: (1) intradermal (ID) vaccination has been shown to induce improved immunogenicity compared to intramuscular (IM) vaccination; (2) ID vaccination has been shown to have a dose-sparing potential over IM leading to a reduced vaccine cost and an increased availability of vaccines worldwide. However, the currently used Mantoux technique for ID injection is difficult to standardize and requires training. The aim of the study was (1) to assess the epidermal and dermal thickness at the proximal ventral and dorsal forearm (PVF & PDF) and deltoid in adults aged 18-65years (2) to determine the maximum penetration depth and needle characteristics for the development of a platform of medical devices suited for intradermal injection, VAX-ID™. MATERIALS AND METHODS: Mean thickness of the PVF, PDF and deltoid were measured using high-frequency ultrasound of healthy adults aged 18-65years. Correlation with gender, age and BMI was assessed using Mann-Whitney U Test, Spearman correlation and Wilcoxon Signed Ranks Test, respectively. RESULTS: Results showed an overall mean skin thickness of 1.19mm (0.65-1.55mm) at the PVF, 1.44mm (0.78-1.84mm) at the PDF, and 2.12mm (1,16-3.19mm) at the deltoid. Thickness of PVF & PDF and deltoid were significantly different for men vs women (pmean<0.001, <0.001, <0.001, and pmin<0.001, 0.012, <0.001, respectively). A significant association was found for age at the deltoid region (p<0.001). Skin thickness for PVF, PDF & deltoid was significantly associated to BMI (p<0.001). CONCLUSION: Significant differences in skin thickness were seen for the PVF, PDF and deltoid region for gender, and BMI. Age only influenced the skin thickness at deltoid region. A needle length of 1.0mm is best option for intradermal injection at the dorsal forearm (NCT02363465).

In vitro colonisation of the distal colon by Akkermansia muciniphila is largely mucin and pH dependent.

Host mucin is the main constituent of the mucus layer that covers the gut epithelium of the host, and an important source of glycans for the bacteria colonising the intestine. Akkermansia muciniphila is a mucin-degrading bacterium, abundant in the human gut, that is able to produce acetate and propionate during this degradation process. A. muciniphila has been correlated with human health in previous studies, but a mechanistic explanation is lacking. In this study, the main site of colonisation was characterised alongside additional conditions, such as differences in colon pH, prebiotic supplementation and variable mucin supply. To overcome the limitations of in vivo studies concerning variations in mucin availability and difficult access to proximal regions of the colon, a dynamic in vitro gut model (SHIME) was used. In this model, A. muciniphila was found to colonise the distal colon compartment more abundantly than the proximal colon ((±8 log copies/ml compared to ±4 log copies/ml) and the preference for the distal compartment was found to be pH-dependent. The addition of mucin caused a specific increase of A. muciniphila (±4.5 log increase over two days), far exceeding the response of other bacteria present, together with an increase in propionate. These findings suggest that colonisation and mucin degradation by A. muciniphila is dependent on pH and the concentration of mucin. Our results revealed the preference of A. muciniphila for the distal colon environment due to its higher pH and uncovered the quick and stable response of A. muciniphila to mucin supplementation.

Assessment of SRM, MRM(3) , and DIA for the targeted analysis of phosphorylation dynamics in non-small cell lung cancer.

Hypothesis-driven MS-based targeted proteomics has gained great popularity in a relatively short timespan. Next to the widely established selected reaction monitoring (SRM) workflow, data-independent acquisition (DIA), also referred to as sequential window acquisition of all theoretical spectra (SWATH) was introduced as a high-throughput targeted proteomics method. DIA facilitates increased proteome coverage, however, does not yet reach the sensitivity obtained with SRM. Therefore, a well-informed method selection is crucial for designing a successful targeted proteomics experiment. This is especially the case when targeting less conventional peptides such as those that contain PTMs, as these peptides do not always adhere to the optimal fragmentation considerations for targeted assays. Here, we provide insight into the performance of DIA, SRM, and MRM cubed (MRM(3) ) in the analysis of phosphorylation dynamics throughout the phosphoinositide 3-kinase mechanistic target of rapamycin (PI3K-mTOR) and mitogen-activated protein kinase (MAPK) signaling network. We observe indeed that DIA is less sensitive when compared to SRM, however demonstrates increased flexibility, by postanalysis selection of alternative phosphopeptide precursors. Additionally, we demonstrate the added benefit of MRM(3) , allowing the quantification of two poorly accessible phosphosites. In total, targeted proteomics enabled the quantification of 42 PI3K-mTOR and MAPK phosphosites, gaining a so far unachieved in-depth view mTOR signaling events linked to tyrosine kinase inhibitor resistance in non-small cell lung cancer.

Does pre-surgical central modulation of pain influence outcome after total knee replacement? A systematic review.

The aim of this study is to systematically review whether the presence of altered central pain modulation pre-surgical influences outcome after total knee replacement (TKR) in patients with knee osteoarthritis (OA), and if so which indices of central pain modulation predict poor outcome after TKR. To identify relevant articles, PubMed and Web of Science were searched. The search strategy was a combination of key words related to "Knee Osteoarthritis and Total Knee Replacement", "Central Pain Modulation" and "Post-Surgical Outcome Measures". Articles fulfilling the inclusion criteria were screened for methodological quality and results were analyzed and summarized. Sixteen prospective cohort studies were included. Strong evidence is available that presence of catastrophic thinking and poor coping strategies predict more pain after TKR and that there is no association between fear of movement and post-surgical pain or function. Evidence on other psychosocial influences is limited or conflicting. Literature on the influence of other signs of altered central pain modulation on post-surgical outcome is scarce. It is plausible that pre-surgical signs of altered central pain modulation, such as joint pain at rest or widespread pain sensitization, predict more post-surgical pain. Surgeons should be attentive for patients with signs of altered central pain modulation before surgery as they might be at risk for unfavorable outcome. A broader therapeutic approach aiming to desensitize the central nervous system can be adapted in these patients. Further research is however needed to identify the influence of central pain modulation pre-surgical in predicting outcome after TKR.

Risk assessment and shared care planning in out-patient forensic psychiatry: cluster randomised controlled trial.

BACKGROUND: Forensic psychiatry aims to reduce recidivism and makes use of risk assessment tools to achieve this goal. Various studies have reported on the predictive qualities of these instruments, but it remains unclear whether their use is associated with actual prevention of recidivism in clinical care. AIMS: To test whether an intervention combining risk assessment and shared care planning is associated with a reduction in violent and criminal behaviour. METHOD: A cluster randomised controlled trial (Netherlands Trial Register number NTR1042) was conducted in three out-patient forensic psychiatric clinics. The intervention comprised risk assessment with the Short Term Assessment of Risk and Treatability (START) and a shared care planning protocol formulated according to shared decision-making principles. The control group received usual care. The outcome consisted of the proportion of clients with violent or criminal incidents at follow-up. RESULTS: In total 58 case managers and 632 of their clients were included. In the intervention group (n = 310), 65% received the intervention at least once. Findings showed a general treatment effect (22% of clients with an incident at baseline v. 15% at follow-up, P<0.01) but no significant difference between the two treatment conditions (odds ratio (OR) = 1.46, 95% CI 0.89-2.44, P = 0.15). CONCLUSIONS: Although risk assessment is common practice in forensic psychiatry, our results indicate that the primary goal of preventing recidivism was not reached through risk assessment embedded in shared decision-making.

Changes in speed of information processing in the brain following tendon repair.

The objective of this study was to measure the "preparation time" that is the speed of information processing in the brain, and discuss the relevance of this parameter in the restoration of hand function following flexor tendon repair. The preparation time of 48 healthy adult participants was measured twice at a 6-week interval and compared with that of 12 patients after flexor tendon repair. There was no difference between the left and right hands of the healthy participants. The correlation between repeated measurements was high, although healthy participants performed 2.6% faster 6 weeks after the first measurement. After 6 weeks of immobilisation, patients showed a significant deterioration with respect to the speed of information processing by the brain on both the injured and uninjured sides compared with healthy participants, who had improved between the first and the second measurements. The results indicate that a period of lack of normal use of the hand leads to a change in cerebral control of hand movements.

Are the take-off and landing phase dynamics of the volleyball spike jump related to patellar tendinopathy?

OBJECTIVE: The causal mechanism of the chronic sports injury patellar tendinopathy is not well understood. The aim of the present study was to compare ankle and knee joint dynamics during the performance of the volleyball spike jump between healthy volleyball players (n = 8) and asymptomatic volleyball players with previous patellar tendinopathy (n = 7). DESIGN: Cross-sectional. METHODS: Inverse dynamics were used to estimate ankle and knee joint dynamics. From these multiple biomechanical variables, a logistic regression was performed to estimate the probability of the presence or absence of previous patellar tendinopathy among the volleyball players studied. RESULTS: Several biomechanical variables improved the prediction of the presence or absence of previous patellar tendinopathy. For landing, ankle plantar flexion at the time of touch-down, and knee range of motion during the first part of impact, and for take-off, loading rate of the knee extensor moment during the eccentric countermovement phase of take-off were predictive. As interaction effects, the presence or absence of previous patellar tendinopathy were correctly predicted by ankle and knee range of motion during the first part of impact, by loading rate of the knee extensor moment during the eccentric phases of take-off and landing, and by knee angular velocity during the eccentric phases of take-off and landing. CONCLUSION: Smaller joint flexion during the first part of landing impact , and higher rate of knee moment development during the eccentric phases of the spike-jump landing sequence, together with higher knee angular velocities, might be risk factors in the development of patellar tendinopathy in volleyball players.

The effect of high load training on psychomotor speed.

The purpose of the present study was to investigate whether overreached athletes show psychomotor slowness after a period of high load training. Fourteen well-trained cyclists (10 male, 4 female, mean age 25.3 [SD = 4.1] years, mean maximal oxygen consumption 65.5 [SD = 8.1] ml/kg.min) performed a maximal graded exercise test on a cycle ergometer, filled out two questionnaires and performed two tests of psychomotor speed before and after high load training and after two weeks of recovery training. A control group performed the two tests of psychomotor speed on the same occasions without changing physical activity levels. Five cyclists were classified as functional overreached, seven cyclists were classified as well-trained and two cyclists were excluded from analysis. Results showed no significant differences in psychomotor speed between the control, well-trained and functional overreached groups on the three measurements. A trend towards psychomotor slowness was found for the functional overreached compared to the control group after high load training. Additional research with more subjects and a greater degree of overload training is necessary to more conclusively determine if psychomotor speed can be used as an early marker for overtraining.

Older women strongly prefer stride lengthening to shortening in avoiding obstacles.

In the present study the obstacle avoidance strategy during treadmill walking was investigated in ten young (aged 19-32) and ten older females (aged 65-78). Minimisation of displacement of the foot from its original landing position has been proposed to be the main criterion for the selection of alternate foot placement. Each participant performed 60 obstacle avoidance trials. Foot-obstacle configurations were varied in order to obtain both lengthening and shortening avoidance reactions. For each trial it was calculated how much lengthening and how much shortening of the stride was required minimally for successful avoidance. The difference between required lengthening and required shortening was expressed as a percentage of the control stride length and was used as a measure of minimal displacement. The behavior of young females was in agreement with the minimal displacement criterion. The older females, however, exhibited a strong preference for stride lengthening, even in situations in which stride shortening would be highly favorable. The explanation for the long step strategy preference of the older females is discussed in terms of age-related changes in decision-making, differences between young and older persons in the unobstructed gait pattern, and safety considerations.