Pre-Operative Digital Templating Aids Restoration of Leg-Length Discrepancy and Femoral Offset in Patients Undergoing Total Hip Arthroplasty for Primary Osteoarthritis.

Background Pre-operative planning and templating is a crucial pre-requisite for total hip arthroplasty (THA). Recently, the use of digital radiography has allowed templating to be digitalised instead of traditional methods involving the use of radiograph transparencies. The primary aim of this study was to compare the accuracy in correction of leg length discrepancy (LLD) and restoring femoral offset in patients undergoing THA for primary osteoarthritis with pre-operative digital templating (PDT) versus conventionalplanning without digital templating. Methods This retrospective cohort study compared two groups of patients who underwent THA for primary osteoarthritis. During the period of the year 2020, 56 patients underwent THA with pre-operative digital templating and 50 patients without digital templating. Two independent blinded observers recorded all radiological data. Results The digital templated and non-digital templated cohorts were matched for variables including age (mean = 71.8 years vs 70.9 years), pre-operative LLD (-4.9mm vs -5.2mm) and pre-operative offset (41.2mm vs 43.7mm). PDT resulted in correction of LLD to <5mm compared to the contralateral hip in 76.8% of cases, 5-10mm in 21.4% and >10mm in one case (1.8%). The non-digital templated cohort had a LLD of <5mm in 50% of cases, 5-10mm in 28% and >10mm in 22%. Chi-square testing demonstrated these results to be statistically significant (p = 0.002). The mean pre-operative offset in the digital templated group was 40mm and 46mm post-operatively. The non-digital templated cohort had a mean pre-operative offset of 42mm and 36mm post-operatively. Independent t-testing revealed statistical significance of these results (p = 0.05). Conclusion PDT leads to an increased likelihood of restoring LLD to <5mm and a significantly increased likelihood of preventing lengthening >10mm. PDT also significantly increases the chance of restoring femoral offset to match the pre-operative native hip. Decreased offset is seen predominantly in the non-digitally templated patients.

Low-Fidelity Arthroscopic Simulation Training in Trauma and Orthopaedic Surgery: A Systematic Review of Experimental Studies.

PURPOSE: To identify and appraise evidence assessing the effectiveness of low-fidelity arthroscopic simulation in the acquisition of arthroscopic surgical skills in a novice population. METHODS: Four databases were electronically searched in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) algorithm. Studies from any year that described the use of orthopaedic, low-fidelity arthroscopic training models in novice populations were included. Questionnaires, case studies, and review studies were excluded. Risk of bias assessment was conducted using the Cochrane Collaboration's Risk of Bias Tool or the Cochrane Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) checklist. RESULTS: Sixteen studies were identified. Using the PRISMA algorithm, 6 studies were included with a total of 131 novice participants. Individual studies ranged from 8 to 40 novices and were of Level I to II evidence. Outcome measurements varied between studies (total 16 different outcomes used). Various outcome measures used for assessing arthroscopic surgical skills within all 6 studies demonstrated significant improvement. A cross-study subjective outcome synthesis revealed low-fidelity arthroscopic simulators reduced time to completion outcomes (2 studies, P < .05), increased Arthroscopic Surgical Skill Evaluation Tool scores (2 studies, P < .01), and confirmed face validity (2 studies) and transfer of skills to cadavers (2 studies) or live patients (1 study). Cost data were under-reported in all studies apart from one. CONCLUSIONS: Arthroscopic training using low-fidelity simulators likely improves the performance of novice participants in completing basic arthroscopic procedures. These simulators may also be more cost effective and thus more implementable than their high-fidelity counterparts. LEVEL OF EVIDENCE: Level II, systematic review of Level I-II studies.

Does scrolling affect measurement equivalence of electronic patient-reported outcome measures (ePROM)? Results of a quantitative equivalence study.

BACKGROUND: Scrolling is a perceived barrier in the use of bring your own device (BYOD) to capture electronic patient reported outcomes (ePROs). This study explored the impact of scrolling on the measurement equivalence of electronic patient-reported outcome measures (ePROMs) in the presence and absence of scrolling. METHODS: Adult participants with a chronic condition involving daily pain completed ePROMs on four devices with different scrolling properties: a large provisioned device not requiring scrolling; two provisioned devices requiring scrolling - one with a "smart-scrolling" feature that disabled the "next" button until all information was viewed, and a second without this feature; and BYOD with smart-scrolling. The ePROMs included were the SF-12, EQ-5D-5L, and three pain measures: a visual analogue scale, a numeric response scale and a Likert scale. Participants completed English or Spanish versions according to their first language. Associations between ePROM scores were assessed using intraclass correlation coefficients (ICCs), with lower bound of 95% confidence interval (CI) > 0.7 indicating comparability. RESULTS: One hundred fifteen English- or Spanish-speaking participants (21-75y) completed all four administrations. High associations between scrolling and non-scrolling were observed (ICCs: 0.71-0.96). The equivalence threshold was met for all but one SF-12 domain score (bodily pain; lower 95% CI: 0.65) and two EQ-5D-5L item scores (pain/discomfort, usual activities; lower 95% CI: 0.64/0.67). Age, language, and device size produced insignificant differences in scores. CONCLUSIONS: The measurement properties of PROMs are preserved even in the presence of scrolling on a handheld device. Further studies that assess scrolling impact over long-term, repeated use are recommended.

Trypanosoma brucei DHFR-TS Revisited: Characterisation of a Bifunctional and Highly Unstable Recombinant Dihydrofolate Reductase-Thymidylate Synthase.

Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a chemically and genetically validated target in African trypanosomes, causative agents of sleeping sickness in humans and nagana in cattle. Here we report the kinetic properties and sensitivity of recombinant enzyme to a range of lipophilic and classical antifolate drugs. The purified recombinant enzyme, expressed as a fusion protein with elongation factor Ts (Tsf) in ThyA- Escherichia coli, retains DHFR activity, but lacks any TS activity. TS activity was found to be extremely unstable (half-life of 28 s) following desalting of clarified bacterial lysates to remove small molecules. Stability could be improved 700-fold by inclusion of dUMP, but not by other pyrimidine or purine (deoxy)-nucleosides or nucleotides. Inclusion of dUMP during purification proved insufficient to prevent inactivation during the purification procedure. Methotrexate and trimetrexate were the most potent inhibitors of DHFR (Ki 0.1 and 0.6 nM, respectively) and FdUMP and nolatrexed of TS (Ki 14 and 39 nM, respectively). All inhibitors showed a marked drop-off in potency of 100- to 1,000-fold against trypanosomes grown in low folate medium lacking thymidine. The most potent inhibitors possessed a terminal glutamate moiety suggesting that transport or subsequent retention by polyglutamylation was important for biological activity. Supplementation of culture medium with folate markedly antagonised the potency of these folate-like inhibitors, as did thymidine in the case of the TS inhibitors raltitrexed and pemetrexed.

Long-term donor site morbidity after free nonvascularized toe phalangeal transfer.

PURPOSE: Free nonvascularized toe phalangeal transfer is an established surgical option for the reconstruction of hypoplastic digits. This study assessed long-term morbidity in the feet using this technique. METHODS: We reviewed 40 children treated between 1991 and 2007 by free nonvascularized toe phalangeal transfer. The diagnosis was digital hypoplasia resulting from symbrachydactyly in 33 cases, constriction ring syndrome in 3 cases, thumb hypoplasia in 3 cases, and perinatal subclavian venous thrombosis in 1 case. The patients were followed up after surgery for a mean of 10 years (range, 3-19 y). The Oxford Ankle Foot Questionnaire was administered to patients and families to assess patient symptoms and patient and parental satisfaction. We assessed toe length ratio, the presence of visible deformity, and distal hypoplasia of the donor toes clinically and radiographically. RESULTS: Emotional problems related to foot appearance were common. We also found functional problems with footwear in some patients. All patients had floppy unstable toes with visible deformity. Increasing foot deformity was seen with growth, which led to deterioration in foot aesthetics, particularly where multiple donor toes had been harvested. We identified distal and middle phalangeal and metatarsal hypoplasia in the donor toes. CONCLUSIONS: Donor site morbidity for free toe phalangeal transfer is greater than previously documented. This should be considered during surgical decision making for reconstruction of hypoplastic digits. Preoperative counseling should include discussion regarding possible consequences of phalangeal harvest on donor toes and options for donor site reconstruction. Long-term follow-up of the donor site is essential to accurately assess results. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

DNA demethylation at specific CpG sites in the IL1B promoter in response to inflammatory cytokines in human articular chondrocytes.

OBJECTIVE: To determine whether changes in the DNA methylation status in the promoter region of the gene encoding interleukin-1beta (IL-1beta) account for expression of IL1B messenger RNA (mRNA) after long-term treatment of human articular chondrocytes with inflammatory cytokines. METHODS: IL-1beta, tumor necrosis factor alpha (TNFalpha) plus oncostatin M (OSM), or 5-azadeoxycytidine (5-aza-dC) was added twice weekly for 4-5 weeks to primary cultures of normal human articular chondrocytes derived from the femoral head cartilage of patients with a fracture of the femoral neck. Expression of MMP13, IL1B, TNFA, and DNMT1 was determined by SYBR Green-based quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of genomic DNA and total RNA extracted from the same sample before and after culture. Bisulfite modification was used to identify which CpG sites in the IL1B promoter showed differential methylation between IL1B-expressing and IL1B-nonexpressing cells. The percentages of cells that were methylated at that critical CpG site (-299 bp) were quantified by a method that depended on methylation-sensitive restriction enzymes and real-time RT-PCR. Secretion of IL-1beta into the culture media was assessed by enzyme-linked immunosorbent assay. RESULTS: Healthy chondrocytes did not express IL1B mRNA, but the levels were increased 5-fold by treatment with 5-aza-dC and were increased 100-1,000-fold by treatment with TNFalpha/OSM. The percentage CpG methylation was decreased by 5-aza-dC treatment but was reduced considerably more by IL-1beta and was almost abolished by TNFalpha/OSM. The mRNA was translated into protein in cytokine-treated chondrocytes. CONCLUSION: These novel findings indicate that inflammatory cytokines can change the DNA methylation status at key CpG sites, resulting in long-term induction of IL1B in human articular chondrocytes.