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1.
Foot Ankle Surg ; 30(3): 231-238, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37996295

ABSTRACT

BACKGROUND: Total ankle arthroplasty (TAA) is increasingly used to treat end-stage ankle arthritis to restore ankle functional outcomes and alleviate pain. This treatment outcome may be influenced by pre-morbid patient anxiety. METHODS: Twenty-five Infinity TAA implants were prospectively followed post-operatively with a mean follow-up time of 34.18 months. Demographic, clinical, and functional outcomes were assessed. Analysis was performed on the effect of anxiety, reported by the HADS, on patient-perceived postoperative pain, functioning, and quality of life. RESULTS: Postoperative the PROMs and Range of Motion (ROM) improved significantly. Linear regression analysis and Pearson correlation showed a significant negative effect of anxiety on the postoperative patient-reported outcome measurements (EQ-5D-5L, VAS, and MOxFQ) at the end of follow-up. CONCLUSION: Good functional, clinical, and radiographic results were observed in this prospective cohort study. Anxiety had a negative influence on the outcome of the patient-reported outcome measurements (EQ-5D-5L and MOxFQ) postoperatively. LEVEL OF EVIDENCE: Level III, prospective cohort study.


Subject(s)
Ankle , Arthroplasty, Replacement, Ankle , Humans , Ankle/surgery , Prospective Studies , Quality of Life , Arthroplasty, Replacement, Ankle/methods , Ankle Joint/diagnostic imaging , Ankle Joint/surgery , Treatment Outcome , Anxiety/etiology , Retrospective Studies
2.
Crit Rev Microbiol ; : 1-22, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37452571

ABSTRACT

The formation of bacterial biofilms in the human body and on medical devices is a serious human health concern. Infections related to bacterial biofilms are often chronic and difficult to treat. Detailed information on biofilm formation and composition over time is essential for a fundamental understanding of the underlying mechanisms of biofilm formation and its response to anti-biofilm therapy. However, information on the chemical composition, structural components of biofilms, and molecular interactions regarding metabolism- and communication pathways within the biofilm, such as uptake of administered drugs or inter-bacteria communication, remains elusive. Imaging these molecules and their distribution in the biofilm increases insight into biofilm development, growth, and response to environmental factors or drugs. This systematic review provides an overview of molecular imaging techniques used for bacterial biofilm imaging. The techniques included mass spectrometry-based techniques, fluorescence-labelling techniques, spectroscopic techniques, nuclear magnetic resonance spectroscopy (NMR), micro-computed tomography (µCT), and several multimodal approaches. Many molecules were imaged, such as proteins, lipids, metabolites, and quorum-sensing (QS) molecules, which are crucial in intercellular communication pathways. Advantages and disadvantages of each technique, including multimodal approaches, to study molecular processes in bacterial biofilms are discussed, and recommendations on which technique best suits specific research aims are provided.

3.
JOR Spine ; 6(2): e1251, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37361332

ABSTRACT

Background Context: Cervical disc replacement (CDR) aims to restore motion of the treated level to reduce the risk of adjacent segment disease (ASD) compared with spinal fusion. However, first-generation articulating devices are unable to mimic the complex deformation kinematics of a natural disc. Thus, a biomimetic artificial intervertebral CDR (bioAID), containing a hydroxyethylmethacrylate (HEMA)-sodium methacrylate (NaMA) hydrogel core representing the nucleus pulposus, an ultra-high-molecular-weight-polyethylene fiber jacket as annulus fibrosus, and titanium endplates with pins for primary mechanical fixation, was developed. Purpose: To assess the initial biomechanical effect of the bioAID on the kinematic behavior of the canine spine, an ex vivo biomechanical study in 6-degrees-of-freedom was performed. Study Design: A canine cadaveric biomechanical study. Methods: Six cadaveric canine specimens (C3-C6) were tested in flexion-extension (FE), lateral bending (LB) axial rotation (AR) using a spine tester in three conditions: intact, after C4-C5 disc replacement with bioAID, and after C4-C5 interbody fusion. A hybrid protocol was used where first the intact spines were subjected to a pure moment of ±1 Nm, whereafter the treated spines were subjected to the full range of motion (ROM) of the intact condition. 3D segmental motions at all levels were measured while recording the reaction torsion. Biomechanical parameters studied included ROM, neutral zone (NZ), and intradiscal pressure (IDP) at the adjacent cranial level (C3-C4). Results: The bioAID retained the sigmoid shape of the moment-rotation curves with a NZ similar to the intact condition in LB and FE. Additionally, the normalized ROMs at the bioAID-treated level were statistically equivalent to intact during FE and AR while slightly decreased in LB. At the two adjacent levels, ROMs showed similar values for the intact compared to the bioAID for FE and AR and an increase in LB. In contrast, levels adjacent to the fused segment showed an increased motion in FE and LB as compensation for the loss of motion at the treated level. The IDP at the adjacent C3-C4 level after implantation of bioAID was close to intact values. After fusion, increased IDP was found compared with intact but did not reach statistical significance. Conclusion: This study indicates that the bioAID can mimic the kinematic behavior of the replaced intervertebral disc and preserves that for the adjacent levels better than fusion. As a result, CDR using the novel bioAID is a promising alternative treatment for replacing severely degenerated intervertebral discs.

4.
Foot Ankle Surg ; 28(8): 1183-1193, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35872118

ABSTRACT

BACKGROUND: Total ankle arthroplasty (TAA) is increasingly used as a treatment for end-stage ankle arthropathy. However, TAA may be more sensitive to complications, failure and subsequent re-operations compared to ankle arthrodesis. The aim of this systematic review and meta-analysis is to generate an overview of complications of TAA surgery. METHODS: PubMed, EMBASE and the Cochrane library were searched between 2000 and 2020 to identify all papers reporting on complications in TAA surgery. Meta-analysis was conducted based on type of complication in TAA surgery. Pooled estimates of complications were calculated using a random effects model. Risk of bias and quality was assessed using the Cochrane risk of bias and ROBINS-I tools. The confidence in estimates was rated and described according to the recommendations of the GRADE working group. RESULTS: One hundred twenty-seven studies were included in this systematic review. All combined, they reported on 16.964 TAAs with an average follow-up of 47.99 ± 29.18 months. Complications with highest reported pooled incidence were intra-operative fracture 0.06 (95 %CI 0.04-0.08) (GRADE Very low) and impingement 0.06 (95 %CI 0.04-0.08) (GRADE low) respectively. CONCLUSION: Reported complication incidence of TAA surgery is still high and remains a significant clinical problem that can be severely hampering long-term clinical survival of the prosthesis. The results of this systematic review and meta-analysis can help guide surgeons in informing their patient about complication risks. Implementation of more stringent patient selection criteria might contribute to diminishing TAA complication rates.


Subject(s)
Arthroplasty, Replacement, Ankle , Humans , Retrospective Studies , Arthroplasty, Replacement, Ankle/adverse effects , Arthroplasty, Replacement, Ankle/methods , Arthrodesis/adverse effects , Arthrodesis/methods , Ankle Joint/surgery , Reoperation , Treatment Outcome
5.
Acta Gastroenterol Belg ; 85(2): 360-382, 2022.
Article in English | MEDLINE | ID: mdl-35709780

ABSTRACT

BACKGROUND: Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS: A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS: Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS: A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.


Subject(s)
Irritable Bowel Syndrome , Humans , Belgium/epidemiology , Consensus , Constipation/drug therapy , Diarrhea , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/etiology
6.
Foot Ankle Surg ; 28(7): 883-886, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34949541

ABSTRACT

BACKGROUND: Studies concerning total ankle arthroplasty could be influenced by several forms of bias. Independent national arthroplasty registries represent objective data on survival and patient reported outcomes. The aim of this study was to determine survival and identify risk factors for early failure in a nationwide series of total ankle arthroplasties from the Dutch Arthroplasty Register (LROI). PATIENTS AND METHODS: Data of 810 patients, who received 836 total ankle arthroplasties between 2014 and 2020 were obtained from the Dutch Arthroplasty Register (LROI) with a median follow-up of 38 months (range 1-84 months). Survival was expressed in Kaplan-Meier analysis and associated hazard ratios for implant failure were determined. Implant failure was defined as the need for revision surgery for any reason or (pan)arthrodesis. RESULTS: During follow-up, we recorded 39 failures (4.7%) resulting in a implant survival of 95.3% with a median follow-up of 38 months (range 1-84 months). Medial malleolus osteotomy (HR = 2.27), previous surgery (HR = 1.83), previous osteotomy (HR = 2.82) and previous ligament reconstruction (HR = 2.83) all showed potentially clinically meaningful associations with a higher incidence of implant failure, yet only previous OCD treatment (HR = 6.21), BMI (HR = 1.09) and age (HR = 0.71) were statistically significant. INTERPRETATION: Excellent short-term survival (95.3%) with a median follow-up of 38 months was reported for TAA patients from the Dutch Arthroplasty Register. Patients with a lower age, a higher BMI or who had a prior surgical OCD treatment before TAA surgery appear to have a higher risk for revision after short-term clinical follow-up. Thorough patient selection with emphasis on risk factors associated with early implant failure might be essential to improve TAA survivorship.


Subject(s)
Ankle , Arthroplasty, Replacement, Ankle , Arthroplasty, Replacement, Ankle/adverse effects , Humans , Prosthesis Failure , Reoperation , Retrospective Studies , Risk Factors
7.
PLoS One ; 16(3): e0248483, 2021.
Article in English | MEDLINE | ID: mdl-33711061

ABSTRACT

AIMS: Previous studies have already shown early proximal ingrowth, fast osseous integration, and a stable fit of the uncemented Symax hip stem, with excellent clinical and radiographic performance. Aims were to evaluate cumulative revision rates and reasons for revision of the Symax hip stem using Dutch Arthroplasty Register (LROI) data and to assess possible associations between patient characteristics and revision rate of the Symax hip stem. PATIENTS AND METHODS: All total hip arthroplasties with the uncemented Symax hip stem registered in the LROI between 2007 and 2017 were included (n = 5,013). Kaplan-Meier survival analysis was performed to assess the cumulative 1, 5 and 7-year revision percentages. Cox proportional hazard regression analysis was performed to assess the association between patient and procedural characteristics, and revision arthroplasty of the stem. RESULTS: Cumulative 1, 5, and 7-year revision rates (with 95% confidence interval (CI)) for revision of any component were 1.5% (CI 1.2%-1.8%), 3.2% (CI 2.7%-3.7%), and 3.8% (CI 3.1%-4.4%) respectively. Cumulative 1, 5, and 7-year stem revision rates of the Symax hip stem were 0.9% (CI 0.6%-1.1%), 1.5% (CI 1.1%-1.9%), and 1.7% (CI 1.3%-2.1%) respectively. Periprosthetic fractures (n = 35) and loosening of the stem (n = 30) were the most common reasons for revision of the stem. Revision of the stem was associated with acute fracture as primary diagnosis (Hazard Ratio (HR) 2.4 (CI 1.3-4.3)), or history of a previous surgery to the affected hip (HR 2.7 (CI 1.4-5.2)). CONCLUSION: This population-based registry study shows revision rates for the Symax hip stem comparable to those for best performing uncemented total hip arthroplasties in the Netherlands. Primary diagnosis of an acute fracture, and history of previous surgery on the affected hip, were significantly associated risk factors for revision of the Symax hip stem, and we discourage the use of the Symax hip stem in these patients.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Periprosthetic Fractures , Prosthesis Failure/etiology , Registries , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Periprosthetic Fractures/etiology , Periprosthetic Fractures/mortality
8.
Build Environ ; 193: 107659, 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33568882

ABSTRACT

SARS-CoV-2 can spread by close contact through large droplet spray and indirect contact via contaminated objects. There is mounting evidence that it can also be transmitted by inhalation of infected saliva aerosol particles. These particles are generated when breathing, talking, laughing, coughing or sneezing. It can be assumed that aerosol particle concentrations should be kept low in order to minimize the potential risk of airborne virus transmission. This paper presents measurements of aerosol particle concentrations in a gym, where saliva aerosol production is pronounced. 35 test persons performed physical exercise and aerosol particle concentrations, CO2 concentrations, air temperature and relative humidity were obtained in the room of 886 m³. A separate test was used to discriminate between human endogenous and exogenous aerosol particles. Aerosol particle removal by mechanical ventilation and mobile air cleaning units was measured. The gym test showed that ventilation with air-change rate ACH = 2.2 h-1, i.e. 4.5 times the minimum of the Dutch Building Code, was insufficient to stop the significant aerosol concentration rise over 30 min. Air cleaning alone with ACH = 1.39 h-1 had a similar effect as ventilation alone. Simplified mathematical models were engaged to provide further insight into ventilation, air cleaning and deposition. It was shown that combining the above-mentioned ventilation and air cleaning can reduce aerosol particle concentrations with 80 to 90% , depending on aerosol size. This combination of existing ventilation supplemented with air cleaning is energy efficient and can also be applied for other indoor environments.

9.
Qual Life Res ; 30(3): 703-711, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33098493

ABSTRACT

PURPOSE: To identify the life domains that are most frequently reported to be affected in scoliosis patients undergoing brace treatment. METHODS: A search within the PubMed database was conducted and a total of 60 publications were selected. We classified the studies based on the methods used to measure patients' quality of life (QoL) and categorized the life domains reported to be affected. RESULTS: Self-image/body configuration was the most reported affected domain of patients' QoL, identified in 32 papers, whilst mental health/stress was the second most reported affected domain. Mental health was identified in 11 papers, and 11 papers using the BSSQ questionnaire reported medium stress amongst their participants. Vitality was the third most reported affected domain, identified in 12 papers. CONCLUSIONS: Our review indicates that scoliotic adolescents treated with bracing suffer in their quality of life most from psychological burdens. To improve these patients' life quality, more attention should be focussed on supporting their mental health.


Subject(s)
Braces/standards , Quality of Life/psychology , Scoliosis/psychology , Adolescent , Female , Humans , Male
10.
Article in English | MEDLINE | ID: mdl-32676498

ABSTRACT

The one-stage treatment of chronic osteomyelitis with S53P4 bioactive glass (BAG) granules has shown excellent results. However, these granules possess suboptimal handling properties. Therefore, new injectable S53P4 putty materials have been developed by the incorporation of a synthetic binder to contain glass granules. The goal of the current study was to assess their potential to eradicate five clinically relevant pathogens: methicillin sensitive Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), Enterococcus coli (E. coli), Enterococcus faecalis (E. faecalis), and Pseudomonas aeruginosa (P. aeruginosa). As a control, S53P4 granules (500-800 µm) and S66 glass (< 45 µm) were used. To evaluate the antimicrobial properties, the materials were cultured with the pathogens in a Müller-Hinton II broth for a week with daily colony forming unit (CFU) counting. One of the tested putty formulations was observed to reduce the number of CFU/mL compared to a negative control (no material, only pathogen in broth) for E. coli, E. faecalis and P. aeruginosa. However, none of the tested putty formulations was able to completely eradicate the pathogens in the broths, which would be needed for safe infection treatment. The results obtained for the control materials were unexpected. S66 glass showed full eradication of P. aeruginosa and reduced the number of CFUs of other pathogens, while the S53P4 granules did not show eradication. The observations on the loose S53P4 granules in this study contradict available literature, which needs further investigation. The results obtained in this study also stretch the importance for a better understanding of the underlying antimicrobial mechanism of S53P4 BAG and how this is related to the dosage. In addition, it should be elucidated how these antimicrobial properties are affected by changes in the material formulation, for example by addition of binders to improve the handling properties or by changing the surface area.

11.
Int J Spine Surg ; 14(2): 182-188, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32355624

ABSTRACT

BACKGROUND: To avoid early fusion and allow residual growth of the spine in early onset scoliosis (EOS) treatment, growth-guided scoliosis surgery can be performed. Four patients with EOS are presented in which a growth-guidance instrumentation is used with sliding titanium (Ti) sublaminar cables. Residual growth of the spine can be preserved using metal sublaminar wiring; however, several drawbacks of this technique and type of material are illustrated. METHODS: Four patients with progressive neuromuscular scoliosis were treated with a posterior stabilization. A fusionless growth-guidance instrumentation was used consisting of a combination of lumbar pedicle screws and sliding Ti sublaminar cables along cobalt chrome rods. RESULTS: In 2 cases, the described growth-guidance technique provided sufficient stability and correction of the curvature with preservation of growth. In 2 patients, the instrumentation failed due to upper thoracic sublaminar wire breakage. The ongoing abrasion of the rod-wire interface caused severe metallosis. In these cases, a debridement and revision surgery was performed with partial fusion of the spine. CONCLUSIONS: Growth-guidance techniques with sliding metal sublaminar wires seem to be a valuable solution for the preservation of spinal growth in EOS surgery. High curvatures, however, have a higher chance of failure and demand for more corrective strength and support of the instrumentation. The use of metal sublaminar wires in a "sliding" instrumentation can lead to early breakage and metallosis. LEVEL OF EVIDENCE: 4, case series. CLINICAL RELEVANCE: Surgeons should be aware of possible complications associated with the use of metal laminar wires in spinal fusion and growth-guidance scoliosis surgery. The implementation of materials containing higher fatigue strength and lower friction properties (eg, UHMWPE wires) may avoid these potential complication risks.

12.
Bone ; 127: 510-516, 2019 10.
Article in English | MEDLINE | ID: mdl-31226529

ABSTRACT

Identifying determinants of long-term functional outcome after a distal radius fracture is challenging. Previously, we reported on the association between early HR-pQCT measurements and clinical outcome 12 weeks after a conservatively treated distal radius fracture. We extended the follow-up and assessed functional outcome after two years in relation to early HR-pQCT derived bone parameters. HR-pQCT scans of the fracture region were performed in 15 postmenopausal women with a distal radius fracture at 1-2 (baseline), 3-4 weeks and 26 months post-fracture. Additionally, the contralateral distal radius was scanned at baseline. Bone density, micro-architecture parameters and bone stiffness using micro-finite element analysis (µFEA) were evaluated. During all visits, wrist pain and function were assessed using the patient-rated wrist evaluation questionnaire (PRWE), quantifying functional outcome with a score between 0 and 100. Two-year PRWE was associated with torsional and bending stiffness 3-4 weeks post-fracture (R2: 0.49, p = 0.006 and R2: 0.54, p = 0.003, respectively). In contrast, early micro-architecture parameters of the fracture region or contralateral bone parameters did not show any association with long-term outcome. This exploratory study indicates that HR-pQCT with µFEA performed within four weeks after a distal radius fracture captures biomechanical fracture characteristics that are associated with long-term functional outcome and therefore could be a valuable early outcome measure in clinical trials and clinical practice.


Subject(s)
Radius Fractures/diagnostic imaging , Radius Fractures/physiopathology , Radius/diagnostic imaging , Radius/physiopathology , Tomography, X-Ray Computed , Aged , Biomechanical Phenomena , Disability Evaluation , Female , Humans , Middle Aged , Pain/etiology , Radius Fractures/complications , Time Factors
13.
Dev Comp Immunol ; 93: 45-57, 2019 04.
Article in English | MEDLINE | ID: mdl-30579935

ABSTRACT

Keyhole limpet hemocyanin (KLH)-binding natural antibody (NAb) titers in chickens are heritable, and higher levels have previously been associated with a higher survival. This suggests that selective breeding for higher NAb levels might increase survival by means of improved general disease resistance. Chickens were divergently selected and bred for total NAb levels binding KLH at 16 weeks of age for six generations, resulting in a High NAb selection line and a Low NAb selection line. To for test differences in disease resistance, chickens were challenged with avian pathogenic Escherichia coli (APEC) in two separate experiments. Chickens at 8 days of age received one of four intratracheal inoculations of 0.2 mL phosphate buffered saline (PBS): 1) mock inoculate, 2) with 0.2 mL PBS containing 108.20 colony-forming units (CFU)/mL APEC, 3) with 0.2 mL PBS containing 106.64 CFU/mL APEC, and 4) with 0.2 mL PBS containing 107.55 CFU/mL APEC. Mortality was recorded during 7 days post inoculation. Overall, 50-60% reduced mortality was observed in the High line compared to the Low line for all APEC doses. In addition, morbidity was determined of the surviving chickens at 15 days of age. The High line had lower morbidity scores compared to the Low line. We conclude that selective breeding for high KLH-binding NAb levels at 16 weeks of age increase APEC resistance in early life. This study and previous studies support the hypothesis that KLH-binding NAb might be used as an indicator trait for to selective breed for general disease resistance in an antigen non-specific fashion.


Subject(s)
Antibodies/blood , Chickens/immunology , Disease Resistance/immunology , Escherichia coli Infections/immunology , Escherichia coli/immunology , Hemocyanins/immunology , Selective Breeding , Animals , Disease Resistance/genetics , Poultry Diseases/immunology
14.
J Bone Joint Surg Am ; 100(24): 2153-2161, 2018 Dec 19.
Article in English | MEDLINE | ID: mdl-30562296

ABSTRACT

BACKGROUND: Chronic osteomyelitis is caused by bacterial infection of the bone and is a major problem in orthopaedic surgery. Treatment of chronic osteomyelitis requires surgical debridement accompanied by local and systemic administration of antibiotics. A widely established biodegradable local antibiotic carrier is antibiotic-loaded collagen sponges (fleeces). These sponges are commonly used in the treatment of chronic osteomyelitis, but a systematic review of their clinical efficacy and assessment of the quality of evidence have not been conducted, to our knowledge. METHODS: This systematic review, performed according to the PRISMA statement, examined the clinical efficacy of and quality of evidence regarding different antibiotic-loaded collagen sponges in the clinical treatment of chronic osteomyelitis. Clinical efficacy was defined as eradication of infection with bone and wound-healing. In addition, the in vivo pharmacokinetics of the various collagen sponges were evaluated. Quality was based on the Level of Evidence, methodological quality, and risks of bias. RESULTS: A total of 813 articles were screened, and 10 were included. Gentamicin-sulfate sponges and gentamicin-sulfate/gentamicin-crobefate sponges were studied. A total of 413 patients were treated, with a success rate of 91%. Reported complications were fistulas, prolonged wound drainage, and wound-healing problems. In vivo pharmacokinetic profiles showed an average local antibiotic concentration that was above the minimum inhibitory concentration for only 5 days. The general quality of the included studies was low to moderate, and there was a moderate to high risk of bias. CONCLUSIONS: The evidence quality and Level of Evidence of the included studies were low, and the risk of bias in these studies was high. This makes the evidence regarding these sponges inconclusive, and no clinical decision-making can be based on these studies. Utilization of antibiotic-loaded collagen sponges in the treatment of chronic osteomyelitis should only be carried out with caution; studies with high-level evidence are needed. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Gentamicins/administration & dosage , Osteomyelitis/drug therapy , Absorbable Implants , Adult , Anti-Bacterial Agents/pharmacokinetics , Chronic Disease , Collagen , Female , Gentamicins/pharmacokinetics , Humans , Male , Middle Aged , Research Design , Surgical Sponges , Treatment Outcome
15.
Ann Oncol ; 29(10): 2061-2067, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30412224

ABSTRACT

Background: Gene expression-based profiling of colorectal cancer (CRC) can be used to identify four molecularly homogeneous consensus molecular subtype (CMS) groups with unique biologic features. However, its applicability to colorectal premalignant lesions remains unknown. Patients and methods: We assembled the largest transcriptomic premalignancy dataset by integrating different public and proprietary cohorts of adenomatous and serrated polyps from sporadic (N = 311) and hereditary (N = 78) patient populations and carried out a comprehensive analysis of carcinogenesis pathways using the CMS random forest (RF) classifier. Results: Overall, transcriptomic subtyping of sporadic and hereditary polyps revealed CMS2 and CMS1 subgroups as the predominant molecular subtypes in premalignancy. Pathway enrichment analysis showed that adenomatous polyps from sporadic or hereditary cases (including Lynch syndrome) displayed a CMS2-like phenotype with WNT and MYC activation, whereas hyperplastic and serrated polyps with CMS1-like phenotype harbored prominent immune activation. Rare adenomas with CMS4-like phenotype showed significant enrichment for stromal signatures along with transforming growth factor-ß activation. There was a strong association of CMS1-like polyps with serrated pathology, right-sided anatomic location and BRAF mutations. Conclusions: Based on our observations made in premalignancy, we propose a model of pathway activation associated with CMS classification in colorectal carcinogenesis. Specifically, while adenomatous polyps are largely CMS2, most hyperplastic and serrated polyps are CMS1 and may transition into other CMS groups during evolution into carcinomas. Our findings shed light on the transcriptional landscape of premalignant colonic polyps and may help guide the development of future biomarkers or preventive treatments for CRC.


Subject(s)
Adenoma/diagnosis , Biomarkers, Tumor/genetics , Colonic Polyps/diagnosis , Colorectal Neoplasms/classification , Colorectal Neoplasms/diagnosis , Mutation , Precancerous Conditions/diagnosis , Adenoma/genetics , Colonic Polyps/genetics , Colorectal Neoplasms/genetics , Female , Follow-Up Studies , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Neoplasm Staging , Phenotype , Precancerous Conditions/genetics , Predictive Value of Tests , Prognosis , Transcriptome
16.
Aliment Pharmacol Ther ; 47(12): 1661-1672, 2018 06.
Article in English | MEDLINE | ID: mdl-29696671

ABSTRACT

BACKGROUND: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. AIM: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. METHODS: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant. RESULTS: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). CONCLUSION: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.


Subject(s)
Dumping Syndrome/drug therapy , Quality of Life , Somatostatin/analogs & derivatives , Adult , Aged , Diarrhea/chemically induced , Female , Humans , Male , Middle Aged , Nausea/chemically induced , Somatostatin/therapeutic use
17.
Vaccine ; 36(11): 1444-1452, 2018 03 07.
Article in English | MEDLINE | ID: mdl-29409681

ABSTRACT

NAb are defined as antigen binding antibodies present without a known previous exposure to this antigen. NAb are suggested to enhance specific antibody (SpAb) responses, but consequences of different NAb levels on immunization are largely unknown. Layer chickens were divergently selected and bred for keyhole limpet hemocyanin (KLH)-binding NAb titers, resulting in a High line and a Low line. In this study, we investigated: (1) the relation of NAb levels with SpAb titers; and (2) the effect of immunization on NAb titers. The 50 highest females of the High line and the 50 lowest females of the Low line of generation 2 were intramuscularly immunized at 33 weeks of age with 1 mL phosphate buffered saline (PBS) containing one of four treatments: (1) negative control (no antigen), (2) 500 µg KLH, (3) 100 µg avian tuberculin purified protein derivative of Mycobacterium avium (PPD), or (4) 250 µg human serum albumin (HuSA). IgM and IgG titers of NAb and SpAb in plasma were determined prior to immunization and weekly for 5 weeks post immunization by indirect ELISA. In addition, antibody affinity was investigated. No differences in SpAb and NAb response against KLH and PPD were observed as a consequence of different NAb titers, but increased and prolonged SpAb and NAb titer responses against HuSA were observed for the High line compared to the Low line. Different natural antibody titers did not impair SpAb dynamics and SpAb affinity. NAb titers were not, or for only short-term, affected by immunization. We show here that NAb may enhance SpAb responses, but that this effect is antigen-dependent. We hypothesize that NAb play a role in general disease resistance through enhancement of the humoral adaptive immune response.


Subject(s)
Antibody Formation/immunology , Antigens/immunology , Chickens/immunology , Immunity, Innate , Selective Breeding , Animals , Antibody Specificity/immunology , Chickens/genetics , Epitopes/immunology , Humans
18.
Eur J Clin Microbiol Infect Dis ; 37(2): 187-208, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28871407

ABSTRACT

In the field of orthopaedic surgery, bacterial invasion of implants and the resulting periprosthetic infections are a common and unresolved problem. Antimicrobial susceptibility testing methods help to define the optimal treatment and identify antimicrobial resistance. This review discusses proven gold-standard techniques and recently developed models for antimicrobial susceptibility testing, while also providing a future outlook. Conventional, gold-standard methods, such as broth microdilution, are still widely applied in clinical settings. Although recently developed methods based on microfluidics and microdroplets have shown advantages over conventional methods in terms of testing speed, safety and the potential to provide a deeper insight into resistance mechanisms, extensive validation is required to translate this research to clinical practice. Recent optical and mechanical methods are complex and expensive and, therefore, not immediately clinically applicable. Novel osteoblast infection and tissue models best resemble infections in vivo. However, the integration of biomaterials into these models remains challenging and they require a long tissue culture, making their rapid clinical implementation unlikely. A method applicable for both clinical and research environments is difficult to realise. With a continuous increase in antimicrobial resistance, there is an urgent need for methods that analyse recurrent infections to identify the optimal treatment approaches. Graphical abstract Timeline of published and partly applied antimicrobial susceptibility testing methods, listed according to their underlying mechanism, complexity and application in research or clinics.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Microbial Sensitivity Tests/methods , Drug Resistance, Bacterial , Humans , Orthopedic Procedures/adverse effects , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/microbiology
19.
BMC Musculoskelet Disord ; 18(1): 279, 2017 Jun 29.
Article in English | MEDLINE | ID: mdl-28662692

ABSTRACT

BACKGROUND: Despite growing evidence in the literature, there is still a lack of consensus regarding the use of the mobile-bearing (MB) design total knee arthroplasty (TKA). METHODS: In a prospective, comparative, randomised, single centre trial, 106 patients with end-stage osteoarthritis of the knee were randomised to either an MB or fixed-bearing (FB) group to receive posterior stabilised (PS)-TKA using a standard medial parapatellar approach and patellar resurfacing with follow-up (FU) for 5 years. The primary outcome was anterior knee pain (AKP) during the chair rise test and the stair climb test 5 years after surgery. The secondary outcome was the ability to rise from a chair and to climb stairs, range of motion (ROM), Knee Society Score (KSS), RAND-36 scores and radiological analysis of the patellar tilt. RESULTS: No statistically significant difference was found between the two groups at 5 years FU in terms of median AKP during the chair rise test and the stair climb test (p = 0.5 and p = 0.8, respectively). There was no significant difference in any of the other secondary outcome parameters between the groups at 5 years FU. CONCLUSION: A mobile-bearing TKA does not decrease AKP compared to fixed bearings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02892838 . LEVEL OF EVIDENCE: II.


Subject(s)
Arthroplasty, Replacement, Knee/instrumentation , Knee Prosthesis/adverse effects , Pain, Postoperative/etiology , Humans , Prospective Studies
20.
Bone Joint Res ; 6(7): 423-432, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28733366

ABSTRACT

OBJECTIVES: The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery. METHODS: A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included. RESULTS: The literature search resulted in 823 manuscripts of which 64 manuscripts met the final inclusion criteria. The included manuscripts consisted of four randomised controlled trials (level I), eight cohort studies (level III) and 49 case-series (level IV). No clinical studies were found for ten DBM products, and most DBM products were only used in combination with other grafting materials. DBM products were most extensively investigated in spinal surgery, showing limited level I evidence that supports the use Grafton DBM (Osteotech, Eatontown, New Jersey) as a bone graft extender in posterolateral lumbar fusion surgery. DBM products are not thoroughly investigated in trauma surgery, showing mainly level IV evidence that supports the use of Allomatrix (Wright Medical, London, United Kingdom), DBX (DePuy Synthes, Zuchwil, Switzerland), Grafton DBM, or OrthoBlast (Citagenix Laval, Canada) as bone graft extenders. CONCLUSIONS: The clinical level of evidence that supports the use of DBM in trauma and orthopaedic surgery is limited and consists mainly of poor quality and retrospective case-series. More prospective, randomised controlled trials are needed to understand the clinical effect and impact of DBM in trauma and orthopaedic surgery.Cite this article: J. van der Stok, K. A. Hartholt, D. A. L. Schoenmakers, J. J. C. Arts. The available evidence on demineralised bone matrix in trauma and orthopaedic surgery: A systemati c review. Bone Joint Res 2017;6:423-432. DOI: 10.1302/2046-3758.67.BJR-2017-0027.R1.

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