Chronic Gastro-Duodenal Ulcerative Disease and the Death of Father Stephan Schätzl from Viechtwang (Austria).

Stephan Schätzl was the parish priest of Viechtwang, Upper Austria. He lived in the aftermath of the Peace of Augsburg in a period of schism between Roman Catholics and Lutherans. His portrait, depicted only 6 days before his demise in 1590, shows that he had extreme ante mortem cachexia. Documentary sources detailed his life and ill-health and it is proposed that he had chronic gastro-duodenal ulcerative disease which ultimately led his to death.

Subchondral bone in osteoarthritis: association between MRI texture analysis and histomorphometry.

OBJECTIVE: Magnetic resonance imaging (MRI) texture analysis is a method of analyzing subchondral bone alterations in osteoarthritis (OA). The objective of this study was to evaluate the association between MR texture analysis and ground-truth subchondral bone histomorphometry at the tibial plateau. DESIGN: The local research ethics committee approved the study. All subjects provided written, informed consent. This was a cross-sectional study carried out at our institution between February and August 2014. Ten participants aged 57-84 with knee OA scheduled for total knee arthroplasty (TKA) underwent pre-operative MRI of the symptomatic knee at 3T using a high spatial-resolution coronal T1 weighted sequence. Tibial plateau explants obtained at the time of TKA underwent histological preparation to allow calculation of bone volume fraction (BV.TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N). Texture analysis was performed on the tibial subchondral bone of MRI images matched to the histological sections. Regression models were created to assess the association of texture analysis features with BV.TV, Tb.Th, Tb.Sp and Tb.N. RESULTS: MRI texture features were significantly associated with BV.TV (R2 = 0.76), Tb.Th (R2 = 0.47), Tb.Sp (R2 = 0.75) and Tb.N (R2 = 0.60, all P < 0.001). Simple gray-value histogram based texture features demonstrated the highest standardized regression coefficients for each model. CONCLUSION: MRI texture analysis features were significantly associated with ground-truth subchondral bone histomorphometry at the tibial plateau.

Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA.

OBJECTIVE: To use deep sequencing to identify novel microRNAs (miRNAs) in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. DESIGN: A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate miRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray and computational analysis, validated using 3'-UTR-luciferase reporter plasmids. Protein levels were assessed by western blot and functional analysis by cell adhesion. RESULTS: We identified 990 known miRNAs and 1621 potential novel miRNAs in human osteoarthritic chondrocytes, 60 of the latter were expressed in all samples assayed. MicroRNA-140-3p was the most highly expressed microRNA in osteoarthritic cartilage. Sixteen novel candidate miRNAs were analysed further, of which six remained after northern blot analysis. Three novel miRNAs were regulated across models of chondrogenesis, chondrocyte differentiation or cartilage injury. One sequence (novel #11), annotated in rodents as microRNA-3085-3p, was preferentially expressed in cartilage, dependent on chondrocyte differentiation and, in man, is located in an intron of the cartilage-expressed gene CRTAC-1. This microRNA was shown to target the ITGA5 gene directly (which encodes integrin alpha5) and inhibited adhesion to fibronectin (dependent on alpha5beta1 integrin). CONCLUSION: Deep sequencing has uncovered many potential microRNA candidates expressed in human cartilage. At least three of these show potential functional interest in cartilage homeostasis and osteoarthritis (OA). Particularly, novel #11 (microRNA-3085-3p) which has been identified for the first time in man.

MRI of asymptomatic patients with metal-on-metal and polyethylene-on-metal total hip arthroplasties.

AIMS: To define and compare magnetic resonance imaging (MRI) findings of asymptomatic patients with metal-on-metal (MOM) and polyethylene-on-metal (POM) total hip replacements (THRs). MATERIALS AND METHODS: Twenty-two THRs in 20 asymptomatic patients (seven men, 13 women, mean age 68 years, range 47-86 years) with normal hip radiographs were included in the study. These comprised 10 POM and 12 MOM bearings. Each patient underwent MRI with metal artefact reduction sequences (MARS) at a mean time of 46 months (POM) and 70 months (MOM) after surgery. Two musculoskeletal radiologists independently read each MRI examination for fluid collections, soft-tissue masses, muscle atrophy, and bone marrow signal changes. RESULTS: A pre-MRI hip radiograph showed no significant differences from the postoperative radiograph regarding acetabular inclination, femoral stem angle, and stem mantle grade. There were eight periprosthetic collections (one POM, seven MOM). The majority of THRs had normal gluteal muscles. The ipsilateral piriformis and obturator internus muscles were more frequently abnormal in the MOM group. Overall, there were no significant differences in the number of abnormalities between the two types of bearings. CONCLUSION: A range of MRI abnormalities are present in normal asymptomatic THRs but the increased frequency of these associated with MOM THR suggest that some of these changes might represent subclinical disease.

Proprioception following partial meniscectomy in stable knees.

PURPOSE: to investigate the proprioceptive function of patients with isolated meniscal tears of the knee before and after arthroscopic partial meniscectomy. METHODS: one hundred subjects (50 patients who underwent a knee arthroscopy and 50 normal controls) were evaluated using single-leg dynamic postural stabilometry. All participants were assessed clinically and radiologically. Knee outcome scores were obtained for all subjects. RESULTS: of the 50 patients arthroscoped, 34 were found to have meniscal tears. Twenty-nine of these patients were reassessed 3 months post-operatively. There was a significant proprioceptive deficit in subjects with meniscal tears when compared to their normal contra-lateral knee (P < 0.001) and the control group (P < 0.001). Partial meniscectomy resulted in a significant improvement in knee outcome scores but not proprioception measurements (n.s.). CONCLUSION: patients with isolated meniscal tears were found to have a significant proprioceptive deficit which persisted following arthroscopic partial meniscectomy despite an otherwise successful clinical outcome.

Do the vastus medialis obliquus and vastus medialis longus really exist? A systematic review.

There remains controversy over whether the vastus medialis (VM) is a single anatomical structure or whether it is composed of two separate portions, the vastus medialis longus (VML) proximally and the vastus medialis obliquus (VMO) distally. The objective of this study was to assess the evidence base of investigations into muscle fiber orientation, presence of a fibrofascial plane, and the innervation of the VM in human cadaver specimens and subjects. In addition to a hand search of specialist journals, an electronic search of AMED, British Nursing Index, CINAHL, the Cochrane database, EMBASE, ovid Medline, Pubmed, and Zetoc were performed from their inception to September 2008. All human subject papers assessing VM fiber orientation, presence of a fibrofascial plane, and the innervation of the VM where reviewed. Twenty-six papers, assessing 699 healthy knees, and 591 specimens with patellofemoral dysfunction were reviewed. The majority of nonpathological and pathological cases presented with a substantial alteration in fiber alignment seen between proximal and distal muscle portions of VM. Both cohorts presented with either one or two nerve branches to the VM. A fibrofascial plane dividing these two muscles was seen in a small proportion of both pathological and nonpathological knees. There was, however, insufficient good quality evidence to state whether the VM is composed of two separate components, the proximal VML and the distal VMO. Further study is recommended to evaluate the pathophysiological implications of such findings and to assess whether these correlate to functional electromyographic findings between the VML and VMO muscles.

Differential Toll-like receptor-dependent collagenase expression in chondrocytes.

OBJECTIVES: To characterise the catabolic response of osteoarthritic chondrocytes to Toll-like receptor (TLR) ligands. METHODS: Induction of the collagenases, matrix metalloproteinase (MMP)1 and MMP13, by TLR ligands was assessed in chondrocytes by real-time reverse transcriptase (RT)-PCR. TLR signalling pathway activation and their involvement in collagenase induction were confirmed by immunoblotting and use of pathway inhibitors and siRNA. TLR expression was compared in the femoral head cartilage of normal controls and patients with osteoarthritis (OA) by real-time RT-PCR. RESULTS: Ligands for TLR6/2 and TLR3 showed the greatest upregulation of MMP1 and MMP13 respectively, although all TLR ligands upregulated these MMPs. MMP1 and MMP13 induction by TLR3 and TLR1/2 or TLR6/2 ligands were dependent on Trif and MyD88, respectively. These inductions were dependent upon the nuclear factor (NF)kappaB pathway, but were differentially inhibited by various mitogen-activated protein kinase inhibitors, with MMP13 induction most reliant on the extracellular signal-regulated kinase pathway. In addition, ligands for TLR1/2 and TLR6/2, but not TLR3, induced significant collagenolysis in a cartilage resorption assay. Finally, TLR2 was significantly downregulated and TLR3 upregulated in OA, compared to normal, cartilage. CONCLUSIONS: Activation of chondrocyte TLRs leads to differential collagenase gene activation. Treatment of chondrocytes with TLR1/2 or TLR6/2 ligands resulted in collagen resorption. The modulated expression of chondrocyte TLR2 and TLR3 in OA cartilage, compared to normal, may reflect a response to repair cartilage or prevent further extracellular matrix destruction. These data suggest modulation of TLR-mediated signalling as a potential therapeutic strategy for the treatment of OA.

Randomised controlled trials of immediate weight-bearing mobilisation for rupture of the tendo Achillis.

We performed two independent, randomised, controlled trials in order to assess the potential benefits of immediate weight-bearing mobilisation after rupture of the tendo Achillis. The first trial, on operatively-treated patients showed an improved functional outcome for patients mobilised fully weight-bearing after surgical repair. Two cases of re-rupture in the treatment group suggested that careful patient selection is required as patients need to follow a structured rehabilitation regimen. The second trial, on conservatively-treated patients, provided no evidence of a functional benefit from immediate weight-bearing mobilisation. However, the practical advantages of immediate weight-bearing did not predispose the patients to a higher complication rate. In particular, there was no evidence of tendon lengthening or a higher re-rupture rate. We would advocate immediate weight-bearing mobilisation for the rehabilitation of all patients with rupture of the tendo Achillis.

The Norwich Patellar Instability Score: Validity, internal consistency and responsiveness for people conservatively-managed following first-time patellar dislocation.

BACKGROUND: This paper assessed the validity, internal consistency, responsiveness and floor-ceiling effects of the Norwich Patellar Instability (NPI) Score for a cohort of conservatively managed people following first-time patellar dislocation (FTPD). METHODS: Fifty patients were recruited, providing 130 completed datasets over 12 months. The NPI Score, Lysholm Knee Score, Tegner Level of Activity Score and isometric knee extension strength were assessed at baseline, six weeks, six and 12 months post-injury. RESULTS: There was high convergent validity with a statistically significant correlation between the NPI Score and the Lysholm Knee Score (p<0.001), Tegner Level of Activity Score (p<0.001) and isometric knee extension strength (p<0.002). Principal component analysis revealed that the NPI Score demonstrated good concurrent validity with four components account for 70.4% of the variability. Whilst the NPI Score demonstrated a flooring-effect for 13 of the 19 items, no ceiling effect was reported. There was high internal consistency with a Cronbach Alpha value of 0.93 (95% CI: 0.91 to 0.93). The NPI Score was responsive to change over the 12 months period with an effect size of 1.04 from baseline to 12 months post-injury. CONCLUSIONS: The NPI Score is a valid tool to assess patellar instability symptoms in people conservatively managed following FTPD. LEVEL OF EVIDENCE: Level II.

Gait abnormalities following rupture of the tendo Achillis: a pedobarographic assessment.

One of the factors that influence the outcome after rupture of the tendo Achillis is abnormality of gait. We prospectively assessed 14 patients and 15 normal control subjects using an in-shoe plantar pressure measurement system. There was a significant reduction in peak mean forefoot pressure in the early period of rehabilitation (p < 0.001). There was a concomitant rise in heel pressure on the injured side (p = 0.05). However, there was no difference in cadence, as determined by the duration of the terminal stance and pre-swing phases as a proportion of total stance. The forefoot pressure deficit in the group with tendon ruptures was smaller when assessed six months after the injury but was still significant (p = 0.029). Pedobarographic assessment confirms that there are marked abnormalities within the gait cycle. Rehabilitation programmes which address these abnormalities may improve outcome.

The Elite Plus total hip arthroplasty: the need for radiological surveillance.

We prospectively studied 217 patients who underwent 234 Elite Plus total hip arthroplasties. At a mean of 6.4 (SD 0.7) years post-operatively, 39 patients had died and 22 were either lost to follow-up or had no radiographs available. Clinical (Oxford hip score) and radiological assessments were performed on 156 patients (168 hip arthroplasties) who had a mean age of 67.7 (SD 9.7) years at operation. In the assessed group, 26 of 159 (16.4%) of femoral stems which had not already been revised and 19 of 159 (11.9%) of acetabular cups were definitely loose. In total, 52 of 168 (31%) of hips had either been revised or had definite evidence of loosening of a component. We could not establish any relationship between clinical and radiological outcomes. Despite the fact that the clinical outcome and rate of revision for the Elite Plus appeared to meet international standards, our findings give us cause for concern. We believe that joint registries should include radiological surveillance in order to provide reliable information about medium-term outcomes for hip prostheses.

The surgical treatment of anterior knee pain due to infrapatellar fat pad pathology: A systematic review.

BACKGROUND: Anterior knee pain (AKP) encompasses a range of pathologies. As a result, there are a number of therapeutic options used to treat AKP. The non-operative treatments have been analysed in a number of randomised controlled trials and systematic reviews. There is however a scarcity of such publications covering the surgical management of AKP. There are no systematic reviews that have investigated surgical interventions for AKP due to pathology of the infrapatellar fat pad (IFP). The aims of this study were to review the literature systematically, to establish which surgical procedures have been used to treat IFP disease and to determine their efficacy. METHODS: The review was conducted in accordance with the PRISMA reporting guidelines. A search of the literature was performed on 1st January 2014 using multiple databases including CENTRAL, MEDLINE, EMBASE, PubMed, and Google Scholar. The quality of the studies was assessed using Oxford Evidence-Based Medicine Levels of Evidence guidelines and the GRADE approach. RESULTS: Twenty-four eligible studies were found and included. The critical appraisal identified that the current evidence-base has low methodology quality. The clinical findings indicated that there is a positive trend towards the surgical management of IFP disease for AKP symptoms. Excision of IFP tumours and resection of the IFP in Hoffa's disease can lead to improvements in symptoms and function. CONCLUSIONS: Truly robust evidence to support the surgical management of IFP pathology requires randomised controlled trials; however the expenses involved to design such trials means that they are unlikely to be undertaken for this uncommon disorder. Consequently well-designed and well-reported case series need to be undertaken to improve our current understanding that includes recording quantitative measures such as range of knee motion, VAS Pain scores and a validated scoring system.

Rehabilitation following first-time patellar dislocation: a randomised controlled trial of purported vastus medialis obliquus muscle versus general quadriceps strengthening exercises.

BACKGROUND: We aimed to define whether distal vastus medialis (VM) muscle strengthening improves functional outcomes compared to general quadriceps muscle strengthening following first-time patellar dislocation (FTPD). METHODS: Fifty patients post-FTPD were randomised to either a general quadriceps exercise or rehabilitation programme (n=25) or a specific-VM exercise and rehabilitation regime (n=25). The primary outcome was the Lysholm knee score, and secondary outcomes included the Tegner Level of Activity score, the Norwich Patellar Instability (NPI) score, and isometric knee extension strength at various knee flexion ranges of motion. Outcomes were assessed at baseline, six weeks, six months and 12months. RESULTS: There were statistically significant differences in functional outcome and activity levels with the Lysholm knee score and Tegner Level of Activity score at 12months in the general quadriceps exercise group compared to the VM group (p=0.05; 95% confidence interval (CI): -14.0 to 0.0/p=0.04; 95% CI: -3.0 to 0.0). This did not reach a clinically important difference. There was no statistically significant difference between the groups for the NPI score and isometric strength at any follow-up interval. The trial experienced substantial participant attrition (52% at 12months). CONCLUSIONS: Whilst there was a statistical difference in the Lysholm knee score and Tegner Level of Activity score between general quadriceps and VM exercise groups at 12months, this may not have necessarily been clinically important. This trial highlights that participant recruitment and retention are challenges which should be considered when designing future trials in this population. LEVEL OF EVIDENCE: Therapeutic study, Level I.

Partial meniscectomy and anterior cruciate ligament rupture in soccer players. A study with a minimum 20-year followup.

A retrospective review of 77 soccer players with 91 affected knees that had undergone the same operation, a rim-preserving meniscectomy, was made with a minimum followup of 20 years and an average followup of 27 years. The patients were divided into groups based on the presence of an intact (Group 1) or ruptured (Group 2) anterior cruciate ligament. At 5 years after meniscectomy, 75% of Group 1 and 52% of Group 2 were still playing soccer, and 13% in Group 1 as opposed to 28% in Group 2 had given up sports. The sporting class assessment was good in 80% of the Group 1 knees and 62% in the Group 2 knees. By followup, 5% of Group 1 and 32% of Group 2 required further meniscectomies, and 2% of Group 1 and 16% of Group 2 required operations for osteoarthritis. Radiologically diagnosed osteoarthritis was present in 24% of Group 1 knees compared with 77% of Group 2. Functionally, 60% of the Group 1 knees were excellent at followup as opposed to 9% in Group 2 knees. In Group 1, 49% were still involved in sports compared with 22% in Group 2. However, 97% of Group 1 were satisfied with their knees compared with 74% of Group 2. All of these differences were statistically significant.