The feasibility of a randomised control trial to assess physiotherapy against surgery for recurrent patellar instability.

BACKGROUND: Patellar instability is a relatively common condition that leads to disability and restriction of activities. People with recurrent instability may be given the option of physiotherapy or surgery though this is largely driven by clinician preference rather than by a strong evidence base. We sought to determine the feasibility of conducting a definitive trial comparing physiotherapy with surgical treatment for people with recurrent patellar instability. METHODS: This was a pragmatic, open-label, two-arm feasibility randomised control trial (RCT) with an embedded interview component recruiting across three NHS sites comparing surgical treatment to a package of best conservative care; 'Personalised Knee Therapy' (PKT). The primary feasibility outcome was the recruitment rate per centre (expected rate 1 to 1.5 participants recruited each month). Secondary outcomes included the rate of follow-up (over 80% expected at 12 months) and a series of participant-reported outcomes taken at 3, 6 and 12 months following randomisation, including the Norwich Patellar Instability Score (NPIS), the Kujala Patellofemoral Disorder Score (KPDS), EuroQol-5D-5L, self-reported global assessment of change, satisfaction at each time point and resources use. RESULTS: We recruited 19 participants. Of these, 18 participants (95%) were followed-up at 12 months and 1 (5%) withdrew. One centre recruited at just over one case per month, one centre was unable to recruit, and one centre recruited at over one case per month after a change in participant screening approach. Ten participants were allocated into the PKT arm, with nine to the surgical arm. Mean Norwich Patellar Instability Score improved from 40.6 (standard deviation 22.1) to 28.2 (SD 25.4) from baseline to 12 months. CONCLUSION: This feasibility trial identified a number of challenges and required a series of changes to ensure adequate recruitment and follow-up. These changes helped achieve a sufficient recruitment and follow-up rate. The revised trial design is feasible to be conducted as a definitive trial to answer this important clinical question for people with chronic patellar instability. TRIAL REGISTRATION: The trial was prospectively registered on the International Standard Randomised Controlled Trial Number registry on the 22/12/2016 (reference number: ISRCTN14950321). http://www.isrctn.com/ISRCTN14950321.

Mapping the contact area of the patellofemoral joint: the relationship between stability and joint congruence.

AIMS: The aim of this study was to determine and compare the congruency of the articular surface contact area of the patellofemoral joint (PFJ) during both active and passive movement of the knee with the use of an MRI mapping technique in both the stable and unstable PFJ. PATIENTS AND METHODS: A prospective case-control MRI imaging study of patients with a history of PFJ instability and a control group of volunteers without knee symptoms was performed. The PFJs were imaged with the use of an MRI scan during both passive and active movement from 0° through to 40° of flexion. The congruency through measurement of the contact surface area was mapped in 5-mm intervals on axial slices. In all, 40 patients were studied. The case group included 31 patients with symptomatic patellofemoral instability and the control group of nine asymptomatic volunteers. The ages were well matched between the case and control groups. The mean age was 25 years (16 to 42; sd 6.9) in the case group and 26 years (19 to 32; sd 5.1) in the control group. There were 19 female and 12 male patients in the case group. RESULTS: The unstable PFJs were demonstrably less congruent than the stable PFJs throughout the range of knee movement. The greatest mean differences in congruency between unstable and stable PFJ's were observed between 11° and 20° flexion (1.73 cm2vs 4.00 cm2; p < 0.005). CONCLUSION: The unstable PFJ is less congruent than the stable PFJ throughout the range of knee movement studied. This approach to mapping PFJ congruency produces a measurable outcome and will allow the assessment of pre- and postoperative results following surgical intervention. This may facilitate the design of new procedures for patients with PFJ instability. If a single axial series is to be obtained on MRI scan, the authors recommend 11° to 20° of tibiofemoral flexion, as this was shown to have the greatest difference in contact surface area between the case and control groups. Cite this article: Bone Joint J 2019;101-B:552-558.

The Avon patellofemoral joint arthroplasty: two- to 18-year results of a large single-centre cohort.

Aims: This study reports on the medium- to long-term implant survivorship and patient-reported outcomes for the Avon patellofemoral joint (PFJ) arthroplasty. Patients and Methods: A total of 558 Avon PFJ arthroplasties in 431 patients, with minimum two-year follow-up, were identified from a prospective database. Patient-reported outcomes and implant survivorship were analyzed, with follow-up of up to 18 years. Results: Outcomes were recorded for 483 implants (368 patients), representing an 86% follow-up rate. The median postoperative Oxford Knee Score (0 to 48 scale) was 35 (interquartile range (IQR) 25.5 to 43) and the median Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, 0 to 100 scale) was 35 (IQR 25 to 53) at two years. There were 105 revisions, 61 (58%) for progression of osteoarthritis. All documented revisions were to primary knee systems without augmentation. The implant survival rate was 77.3% (95% confidence interval (CI) 72.4 to 81.7, number at risk 204) at ten years and 67.4% (95% CI 72.4 to 81.7 number at risk 45) at 15 years. Regression analysis of explanatory data variable showed that cases performed in the last nine years had improved survival compared with the first nine years of the cohort, but the individual operating surgeon had the strongest effect on survivorship. Conclusion: Satisfactory long-term results can be obtained with the Avon PFJ arthroplasty, with maintenance of patient-reported outcome measures (PROMs), satisfactory survival, and low rates of loosening and wear. Cite this article: Bone Joint J 2018;100-B:1162-7.

Trochleoplasty with a flexible osteochondral flap: results from an 11-year series of 214 cases.

AIMS: The Bereiter trochleoplasty has been used in our unit for 12 years to manage recurrent patellar instability in patients with severe trochlea dysplasia. The aim of this study was to document the outcome of a large consecutive cohort of patients who have undergone this operation. PATIENTS AND METHODS: Between June 2002 and August 2013, 214 consecutive trochleoplasties were carried out in 185 patients. There were 133 women and 52 men with a mean age of 21.3 years (14 to 38). All patients were offered yearly clinical and radiological follow-up. They completed the following patient reported outcome scores (PROMs): International Knee Documentation Committee subjective scale, the Kujala score, the Western Ontario and McMaster Universities Arthritis Index score and the short-form (SF)-12. RESULTS: Outcomes were available for 199 trochleoplasties in 173 patients giving a 93% follow-up rate at a mean of 4.43 years (1 to 12). There were no infections or deep vein thromboses. In total, 16 patients reported further patella dislocation, giving an 8.3% rate of recurrence. There were 27 re-operations, giving a rate of re-operation of 14%. Overall, 88% were satisfied with the operation and 90% felt that their symptoms had been improved. CONCLUSION: All PROMs improved significantly post-operatively except for the mental component score of the SF-12. Trochleoplasty performed using a flexible osteochondral flap is an effective treatment for recurrent patellar instability in patients with severe trochlea dysplasia and gives good results in the medium term. Cite this article: Bone Joint J 2017;99-B:344-50.

Adolescent patellar instability: current concepts review.

Patellar instability most frequently presents during adolescence. Congenital and infantile dislocation of the patella is a distinct entity from adolescent instability and measurable abnormalities may be present at birth. In the normal patellofemoral joint an increase in quadriceps angle and patellar height are matched by an increase in trochlear depth as the joint matures. Adolescent instability may herald a lifelong condition leading to chronic disability and arthritis. Restoring normal anatomy by trochleoplasty, tibial tubercle transfer or medial patellofemoral ligament (MPFL) reconstruction in the young adult prevents further instability. Although these techniques are proven in the young adult, they may cause growth arrest and deformity where the physis is open. A vigorous non-operative strategy may permit delay of surgery until growth is complete. Where non-operative treatment has failed a modified MPFL reconstruction may be performed to maintain stability until physeal closure permits anatomical reconstruction. If significant growth remains an extraosseous reconstruction of the MPFL may impart the lowest risk to the physis. If minor growth remains image intensifier guided placement of femoral intraosseous fixation may impart a small, but acceptable, risk to the physis. This paper presents and discusses the literature relating to adolescent instability and provides a framework for management of these patients. Cite this article: Bone Joint J 2017;99-B:159-70.

The Defecation Index as a Measure of Emotionality: Questions Raised by HPA Axis and Prolactin Response to Stress in the Maudsley Model.

The Maudsley Reactive and Maudsley Non-Reactive strains have been selectively bred for differences in open-field defecation (OFD), a putative index of stress. We investigated whether variations in the hypothalamic-pituitary-adrenal (HPA) axis are correlated with strain differences in OFD in the Maudsley model. Exposure to the open-field test did not result in increases in ACTH in male rats of either strain and there were no strain differences in the large increases in ACTH and corticosteroid that occurred in response to intermittent footshock. Parallel studies of prolactin showed that Maudsley Reactive rats had greater response to the open-field and to footshock than Maudsley Non-Reactive rats. The lack of correlation between strain differences in OFD and reactivity of the HPA axis is consistent with the idea that HPA response to stress and OFD reflect the output of different neural systems and that individual differences in emotionality, as indexed by OFD do not influence other measures of stress-reactivity in a simple manner, if at all. The reactivity of the prolactin system to the open-field test and lack of response of ACTH to the same situation is consistent with the idea that the prolactin system is sensitive to lower levels of stress than the HPA axis, a finding at variance with the presumed extreme sensitivity of the latter system. Earlier comparisons of the HPA axis in these strains implicate local factors such as neuropeptide-Y peptide in the adrenal in attenuating the response of the adrenal cortex to ACTH and hints at the complexity of regulation of the HPA axis.

The effects of nutrition-induced abnormal food metabolism in the Southern Plains woodrat (Neotoma micropus): comparisons of variations of the Western diet.

We investigated the effects of several modifications of the Western diet on a medium-sized rodent, Neotoma micropus, that lives in the area of the wildland-urban interface. We conducted a laboratory study of the response of N. micropus to high fat-high fructose (HFHF), high fat-high sucrose (HFHS), high fat-low sugar (HFLSu) and control (low fat-low sugar) diets. We found a significant increase in hepatic lipid deposition and a significant decrease in podocytes in those animals that consumed the HFHF and HFLSu diets compared to those on the HFHS and control diets. We found no significant differences in Bowman's space or hepatic collagen formation. We predict that N. micropus in the wild, with access to anthropogenic resources, will show similar effects as a result of the consumption of anthropogenic resources.

Bristol index of patellar width to thickness (BIPWiT): a reproducible measure of patellar thickness from adult MRI.

BACKGROUND: The restoration of an adequate patellar thickness is a key to the successful outcome of knee arthroplasty. This study investigated the relationship between the thickness of the native patellar and medial-lateral patellar width using magnetic resonance imaging (MRI). METHODS: 75 MRI scans of young adults, with an average age of 27 (range 16-40) were studied. Exclusion criteria included a diagnosis of degenerative joint disease, patello-femoral pathology or age under 16/over 40 (170 patients). The bony thickness of the patellar, the chondral thickness and patellar width were measured, as was the location of maximal patellar thickness. Inter/intraobserver variability was calculated and correlation analysis was performed. RESULTS: We found a strong correlation between patellar width and thickness (bone plus cartilage) (Pearson 0.75, P<0.001). The mean width to thickness ratio was 1.8:1 (standard deviation 0.1, 95% confidence interval 1.78-1.83). Without cartilage the ratio was 2.16:1 (SD 0.15, 95% CI 2.11-2.21), correlation was moderate (Pearson 0.59, P<0.001). The average maximal patellar cartilage thickness was 4.1mm (SD 1.3). CONCLUSION: The strong correlation and narrow confidence intervals for the ratio of patellar width to thickness, suggest that patellar width might be used as a guide for accurate restoration of patellar thickness during total knee or patello-femoral replacement. After removing osteophytes we would recommend a ratio of 1.8:1. Further work is required to establish whether there is a relationship between anterior knee pain post total knee arthroplasty and an abnormal patellar width:thickness ratio. LEVEL OF EVIDENCE: Level III.

The correct rotation of the femoral component in patellofemoral replacement: a laboratory assessment of a surgical technique.

Ensuring correct rotation of the femoral component is a challenging aspect of patellofemoral replacement surgery. Rotation equal to the epicondylar axis or marginally more external rotation is acceptable. Internal rotation is associated with poor outcomes. This paper comprises two studies evaluating the use of the medial malleolus as a landmark to guide rotation. We used 100 lower-leg anteroposterior radiographs to evaluate the reliability of the medial malleolus as a landmark. Assessment was made of the angle between the tibial shaft and a line from the intramedullary rod entry site to the medial malleolus. The femoral cut was made in ten cadaver knees using the inferior tip of the medial malleolus as a landmark for rotation. Rotation of the cut relative to the anatomical epicondylar axis was assessed using CT. The study of radiographs found the position of the medial malleolus relative to the tibial axis is consistent. Using the inferior tip of the medial malleolus in the cadaver study produced a mean external rotation of 1.6° (0.1° to 3.7°) from the anatomical epicondylar axis. Using the inferior tip of the medial malleolus to guide the femoral cutting jig avoids internal rotation and introduces an acceptable amount of external rotation of the femoral component.

Medial patellofemoral ligament reconstruction for patellar instability in patients with hypermobility: a case control study.

Hypermobility is an acknowledged risk factor for patellar instability. In this case control study the influence of hypermobility on clinical outcome following medial patellofemoral ligament (MPFL) reconstruction for patellar instability was studied. A total of 25 patients with hypermobility as determined by the Beighton criteria were assessed and compared with a control group of 50 patients who were matched for age, gender, indication for surgery and degree of trochlear dysplasia. The patients with hypermobility had a Beighton Score of ≥ 6; the control patients had a score of < 4. All patients underwent MPFL reconstruction performed using semitendinosus autograft and a standardised arthroscopically controlled technique. The mean age of the patients was 25 years (17 to 49) and the mean follow-up was 15 months (6 to 30). Patients with hypermobility had a significant improvement in function following surgery, with reasonable rates of satisfaction, perceived improvement, willingness to repeat and likelihood of recommendation. Functional improvements were significantly less than in control patients (p < 0.01). Joint hypermobility is not a contraindication to MPFL reconstruction although caution is recommended in managing the expectations of patients with hypermobility before consideration of surgery.

Medial patellofemoral ligament reconstruction: a prospective outcome assessment of a large single centre series.

We report a prospective analysis of clinical outcome in patients treated with medial patellofemoral ligament (MPFL) reconstruction using an autologous semitendinosus graft. The technique includes superolateral portal arthroscopic assessment before and after graft placement to ensure correct graft tension and patellar tracking before fixation. Between October 2005 and October 2010, a total of 201 consecutive patients underwent 219 procedures. Follow-up is presented for 211 procedures in 193 patients with a mean age of 26 years (16 to 49), and mean follow-up of 16 months (6 to 42). Indications were atraumatic recurrent patellar dislocation in 141 patients, traumatic recurrent dislocation in 50, pain with subluxation in 14 and a single dislocation with persistent instability in six. There have been no recurrent dislocations/subluxations. There was a statistically significant improvement between available pre- and post-operative outcome scores for 193 patients (all p < 0.001). Female patients with a history of atraumatic recurrent dislocation and all patients with history of previous surgery had a significantly worse outcome (all p < 0.05). The indication for surgery, degree of dysplasia, associated patella alta, time from primary dislocation to surgery and evidence of associated cartilage damage at operation did not result in any significant difference in outcome. This series adds considerably to existing evidence that MPFL reconstruction is an effective surgical procedure for selected patients with patellofemoral instability.

Radiographic landmarks for tunnel placement in reconstruction of the medial patellofemoral ligament.

PURPOSE: To verify the findings of previous studies in confirming radiographic landmarks for the femoral attachment of the medial patellofemoral ligament (MPFL), but also to define radiographic landmarks for the patellar attachment. Assess the effect of limb rotation upon these radiographic landmarks. METHODS: The medial patellofemoral ligament was identified in ten fresh-frozen human cadaveric knees. A headed pin was used to mark the centre of the femoral and patellar attachments. True lateral radiographs were performed followed by lateral radiographs in 10° and 20° of internal and external rotation. Posterior-anterior and proximal-distal position of the headed pin was evaluated. RESULTS: The femoral attachment averaged 3.8 ± 5.0 mm anterior to the posterior femoral cortical line and 0.9 ± 2.4 mm distal to the perpendicular line intersecting the posterior aspect of Blumensaat's line. The patellar attachment averaged 7.4 ± 3.5 mm anterior to the posterior patellar cortical line, 5.4 ± 2.6 mm distal to the perpendicular line intersecting the proximal margin of the patellar articular surface. There was a significant relationship between limb rotation and distance of femoral and patellar attachment from the posterior cortical line (P < 0.0001 and P < 0.0002 respectively). CONCLUSION: Radiographic landmarks for the femoral attachment of the MPFL identified in this study are comparable with other recent work. This study describes new radiographic landmarks for the patellar attachment of the MPFL and highlights that it is essential to acquire true lateral radiographs if these radiographic landmarks are to be interpreted accurately.

Atrazine and breast cancer: a framework assessment of the toxicological and epidemiological evidence.

The causal relationship between atrazine exposure and the occurrence of breast cancer in women was evaluated using the framework developed by Adami et al. (2011) wherein biological plausibility and epidemiological evidence were combined to conclude that a causal relationship between atrazine exposure and breast cancer is "unlikely". Carcinogenicity studies in female Sprague-Dawley (SD) but not Fischer-344 rats indicate that high doses of atrazine caused a decreased latency and an increased incidence of combined adenocarcinoma and fibroadenoma mammary tumors. There were no effects of atrazine on any other tumor type in male or female SD or Fischer-344 rats or in three strains of mice. Seven key events that precede tumor expression in female SD rats were identified. Atrazine induces mammary tumors in aging female SD rats by suppressing the luteinizing hormone surge, thereby supporting a state of persistent estrus and prolonged exposure to endogenous estrogen and prolactin. This endocrine mode of action has low biological plausibility for women because women who undergo reproductive senescence have low rather than elevated levels of estrogen and prolactin. Four alternative modes of action (genotoxicity, estrogenicity, upregulation of aromatase gene expression or delayed mammary gland development) were considered and none could account for the tumor response in SD rats. Epidemiological studies provide no support for a causal relationship between atrazine exposure and breast cancer. This conclusion is consistent with International Agency for Research on Cancer's classification of atrazine as "unclassifiable as to carcinogenicity" and the United States Environmental Protection Agency's classification of atrazine as "not likely to be carcinogenic."

Developing a problem-based learning (PBL) curriculum for professionalism and scientific integrity training for biomedical graduate students.

A multidisciplinary faculty committee designed a curriculum to shape biomedical graduate students into researchers with a high commitment to professionalism and social responsibility and to provide students with tools to navigate complex, rapidly evolving academic and societal environments with a strong ethical commitment. The curriculum used problem-based learning (PBL), because it is active and learner-centred and focuses on skill and process development. Two courses were developed: Scientific Professionalism: Scientific Integrity addressed discipline-specific and broad professional norms and obligations for the ethical practice of science and responsible conduct of research (RCR). Scientific Professionalism: Bioethics and Social Responsibility focused on current ethical and bioethical issues within the scientific profession, and implications of research for society. Each small-group session examined case scenarios that included: (1) learning objectives for professional norms and obligations; (2) key ethical issues and philosophies within each topic area; (3) one or more of the RCR instructional areas; and (4) at least one type of moral reflection. Cases emphasised professional standards, obligations and underlying philosophies for the ethical practice of science, competing interests of stakeholders and oversight of science (internal and external). To our knowledge, this is the first use of a longitudinal, multi-semester PBL course to teach scientific integrity and professionalism. Both faculty and students endorsed the active learning approach for these topics, in contrast to a compliance-based approach that emphasises learning rules and regulations.

Problem-based learning for professionalism and scientific integrity training of biomedical graduate students: process evaluation.

OBJECTIVE: We conducted a process evaluation to (a) assess the effectiveness of a new problem-based learning curriculum designed to teach professionalism and scientific integrity to biomedical graduate students and (b) modify the course to enhance its relevance and effectiveness. The content presented realistic cases and issues in the practice of science, to promote skill development and to acculturate students to professional norms of science. METHOD: We used 5-step Likert-scaled questions, open-ended questions, and interviews of students and facilitators to assess curricular effectiveness. RESULTS: Both facilitators and students perceived course objectives were achieved. For example, respondents preferred active learning over lectures; both faculty and students perceived that the curriculum increased their understanding of norms, role obligations and responsibilities of professional scientists. They also reported an increased ability to identify ethical situations and felt that they had developed skills in moral reasoning and effective group work. CONCLUSIONS: These data helped to improve course implementation and instructional material. For example, to correct a negative perception that this was an 'ethics' course, we redesigned case debriefing activities to reinforce learning objectives and important skills. We refined cases to be more engaging and relevant for students, and gave facilitators more specific training and resources for each case. The problem-based learning small group strategy can stimulate an environment whereby participants are more aware of ethical implications of science, and increase their socialisation and open communication about professional behaviour.

Acute hypotension associated with leucocyte depletion filters during cell salvaged blood transfusion.

Summary Intra-operative cell salvage is used in more than 75% of NHS hospitals in the United Kingdom and is a safe and cost effective alternative to allogenic blood transfusion. We report a case of acute hypotension during reinfusion of cell salvaged blood through a leucocyte depletion filter that occurred during a caesarean section. We review the literature of hypotension associated with the use of bedside leucocyte depletion filters.

Prime-boost vaccination with recombinant mumps virus and recombinant vesicular stomatitis virus vectors elicits an enhanced human immunodeficiency virus type 1 Gag-specific cellular immune response in rhesus macaques.

Intramuscular inoculation of rhesus macaques with one or more doses of recombinant vesicular stomatitis virus (rVSV) expressing human immunodeficiency virus type 1 (HIV-1) Gag (rVSVgag) typically elicits peak cellular immune responses of 500 to 1,000 gamma interferon (IFN-gamma) enzyme-linked immunospots (ELISPOTS)/10(6) peripheral blood lymphocytes (PBL). Here, we describe the generation of a novel recombinant mumps virus (rMuV) expressing HIV-1 Gag (rMuVgag) and measure the Gag-specific cellular immune responses detected in rhesus macaques following vaccination with a highly attenuated form of rVSV expressing HIV-1 Gag (rVSVN4CT1gag1) and rMuVgag in various prime-boost combinations. Notably, peak Gag-specific cellular immune responses of 3,000 to 3,500 ELISPOTS/10(6) PBL were detected in macaques that were primed with rMuVgag and boosted with rVSVN4CT1gag1. Lower peak cellular immune responses were detected in macaques that were primed with rVSVN4CT1gag1 and boosted with rMuVgag, although longer-term gag-specific responses appeared to remain higher in this group of macaques. These findings indicate that rMuVgag may significantly enhance Gag-specific cellular immune responses when administered with rVSVN4CT1gag1 in heterologous prime-boost regimens.