Sequential bilateral total ankle replacements: No difference in patient-reported outcomes between the first and second ankle.

BACKGROUND: Total ankle replacement is an established treatment for end-stage arthritis. However, there is little data examining outcomes in sequential bilateral replacements. This study aimed to compare outcomes between first and second ankles in sequential replacement. METHODS: Patients were retrospectively contacted to complete a follow-up questionnaire including the Manchester-Oxford Foot Questionnaire (MOXFQ), EQ-5D-3 L, and a question assessing satisfaction. Electronic records identified demographics, procedural details, and complications. RESULTS: Twenty patients underwent sequential bilateral ankle replacement over the study period. At a mean follow-up of four years, 18 patients completed the follow-up questionnaire. There was no statistically significant difference between first and second ankles in terms of MOXFQ score, EQ-5D-3 L or satisfaction. Eleven complications were noted. CONCLUSIONS: We report excellent outcomes after sequential bilateral ankle replacement with no difference in outcomes between first and second ankles. These results can be used to counsel patients in the future and manage expectations. LEVEL OF EVIDENCE: IV.

Treatments for Morton's neuroma.

BACKGROUND: Morton's neuroma (MN) is a painful neuropathy resulting from a benign enlargement of the common plantar digital nerve that occurs commonly in the third webspace and, less often, in the second webspace of the foot. Symptoms include burning or shooting pain in the webspace that extends to the toes, or the sensation of walking on a pebble. These impact on weight-bearing activities and quality of life. OBJECTIVES: To assess the benefits and harms of interventions for MN. SEARCH METHODS: On 11 July 2022, we searched CENTRAL, CINAHL Plus EBSCOhost, ClinicalTrials.gov, Cochrane Neuromuscular Specialised Register, Embase Ovid, MEDLINE Ovid, and WHO ICTRP. We checked the bibliographies of identified randomised trials and systematic reviews and contacted trial authors as needed. SELECTION CRITERIA: We included all randomised, parallel-group trials (RCTs) of any intervention compared with placebo, control, or another intervention for MN. We included trials where allocation occurred at the level of the individual or the foot (clustered data). We included trials that confirmed MN through symptoms, a clinical test, and an ultrasound scan (USS) or magnetic resonance imaging (MRI). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We assessed bias using Cochrane's risk of bias 2 tool (RoB 2) and assessed the certainty of the evidence using the GRADE framework. MAIN RESULTS: We included six RCTs involving 373 participants with MN. We judged risk of bias as having 'some concerns' across most outcomes. No studies had a low risk of bias across all domains. Post-intervention time points reported were: three months to less than 12 months from baseline (nonsurgical outcomes), and 12 months or longer from baseline (surgical outcomes). The primary outcome was pain, and secondary outcomes were function, satisfaction or health-related quality of life (HRQoL), and adverse events (AE). Nonsurgical treatments Corticosteroid and local anaesthetic injection (CS+LA) versus local anaesthetic injection (LA) Two RCTs compared CS+LA versus LA. At three to six months: • CS+LA may result in little to no difference in pain (mean difference (MD) -6.31 mm, 95% confidence interval (CI) -14.23 to 1.61; P = 0.12, I2 = 0%; 2 studies, 157 participants; low-certainty evidence). (Assessed via a pain visual analogue scale (VAS; 0 to 100 mm); a lower score indicated less pain.) • CS+LA may result in little to no difference in function when compared with LA (standardised mean difference (SMD) -0.30, 95% CI -0.61 to 0.02; P = 0.06, I2 = 0%; 2 studies, 157 participants; low-certainty evidence). (Function was measured using: the American Orthopaedic Foot and Ankle Society Lesser Toe Metatarsophalangeal-lnterphalangeal Scale (AOFAS; 0 to 100 points) - we transformed the scale so that a lower score indicated improved function - and the Manchester Foot Pain and Disability Schedule (MFPDS; 0 to 100 points), where a lower score indicated improved function.) • CS+LA probably results in little to no difference in HRQoL when compared to LA (MD 0.07, 95% CI -0.03 to 0.17; P = 0.19; 1 study, 122 participants; moderate-certainty evidence), and CS+LA may not increase satisfaction (risk ratio (RR) 1.08, 95% CI 0.63 to 1.85; P = 0.78; 1 study, 35 participants; low-certainty evidence). (Assessed using the EuroQol five dimension instrument (EQ-5D; 0-1 point); a higher score indicated improved HRQoL.) • The evidence is very uncertain about the effects of CS+LA on AE when compared with LA (RR 9.84, 95% CI 1.28 to 75.56; P = 0.03, I2 = 0%; 2 studies, 157 participants; very low-certainty evidence). Adverse events for CS+LA included mild skin atrophy (3.9%), hypopigmentation of the skin (3.9%) and plantar fat pad atrophy (2.6%); no adverse events were observed with LA. Ultrasound-guided (UG) CS+LA versus non-ultrasound-guided (NUG) CS+LA Two RCTs compared UG CS+LA versus NUG CS+LA. At six months: • UG CS+LA probably reduces pain when compared with NUG CS+LA (MD -15.01 mm, 95% CI -27.88 to -2.14; P = 0.02, I2 = 0%; 2 studies, 116 feet; moderate-certainty evidence). (Assessed with a pain VAS.) • UG CS+LA probably increases function when compared with NUG CS+LA (SMD -0.47, 95% CI -0.84 to -0.10; P = 0.01, I2 = 0%; 2 studies, 116 feet; moderate-certainty evidence). We do not know of any established minimum clinical important difference (MCID) for the scales that assessed function, specifically, the MFPDS and the Manchester-Oxford Foot Questionnaire (MOXFQ; 0 to 100 points; a lower score indicated improved function.) • UG CS+LA may increase satisfaction compared with NUG CS+LA (risk ratio (RR) 1.71, 95% CI 1.19 to 2.44; P = 0.003, I2 = 15%; 2 studies, 114 feet; low-certainty evidence). • HRQoL was not measured. • UG CS+LA may result in little to no difference in AE when compared with NUG CS+LA (RR 0.42, 95% CI 0.12 to 1.39; P = 0.15, I2 = 0%; 2 studies, 116 feet; low-certainty evidence). AE included depigmentation or fat atrophy for UG CS+LA (4.9%) and NUG CS+LA (12.7%). Surgical treatments Plantar incision neurectomy (PN) versus dorsal incision neurectomy (DN) One study compared PN versus DN. At 34 months (mean; range 28 to 42 months), PN may result in little to no difference for satisfaction (RR 1.06, 95% CI 0.87 to 1.28; P = 0.58; 1 study, 73 participants; low-certainty evidence), or for AE (RR 0.95, 95% CI 0.32 to 2.85; P = 0.93; 1 study, 75 participants; low-certainty evidence) compared with DN. AE for PN included hypertrophic scaring (11.4%), foreign body reaction (2.9%); AE for DN included missed nerve (2.5%), artery resected (2.5%), wound infection (2.5%), postoperative dehiscence (2.5%), deep vein thrombosis (2.5%) and reoperation with plantar incision due to intolerable pain (5%). The data reported for pain and function were not suitable for analysis. HRQoL was not measured. AUTHORS' CONCLUSIONS: Although there are many interventions for MN, few have been assessed in RCTs. There is low-certainty evidence that CS+LA may result in little to no difference in pain or function, and moderate-certainty evidence that UG CS+LA probably reduces pain and increases function for people with MN. Future trials should improve methodology to increase certainty of the evidence, and use optimal sample sizes to decrease imprecision.

Two to Five-Year Outcomes of Total Ankle Arthroplasty with the Infinity Fixed-Bearing Implant: A Concise Follow-up of a Previous Report.

LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen.

This study investigates the predicting factors of the biochemical response and survival of patients with advanced metastatic prostate cancer who underwent therapy with radioligand lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA), often referred to as [177Lu]Lu-PSMA. This study is a review of the previous literature. This study included articles published in the last 10 years in the English language. According to the literature review, treatment with [177Lu]Lu-PSMA has a positive impact on prostate-specific antigen (PSA) within the first cycle and a negative impact on lymph node metastasis. There is a plausible positive impact on PSA after multiple cycles and performance status and a negative impact on visceral metastasis. In conclusion, the reviews show that treatment with [177Lu]Lu-PSMA in patients with castration-resistant prostate cancer is beneficial in reducing PSA and metastasis.

Surgical Management of Jones Fractures in Athletes: Orthobiologic Augmentation: A Systematic Review and Meta-analysis of 718 Fractures.

BACKGROUND: The use of orthobiologics is expanding. However, the use of orthobiologic augmentation in primary fracture fixation surgery remains limited. Primary fracture fixation of the fifth metatarsal (Jones) in athletes is one of the rare situations where primary orthobiologic augmentation has been advocated. PURPOSE: To determine the effect of orthobiologic augmentation on the outcome of surgically managed Jones fractures in athletes. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, 2 independent team members searched several databases including PubMed, MEDLINE, Embase, Google Scholar, Web of Science, Cochrane Library, and ClinicalTrials.gov through March 2021 to identify studies reporting on surgically managed Jones fractures of the fifth metatarsal exclusively in athletes. The primary outcomes were the return to play (RTP) rate and time to RTP, whereas the secondary outcomes were time to union, union rate, and refractures. Data were presented by type of treatment (biologically augmented fixation or fixation alone). RESULTS: In the biologically augmented fixation group, successful RTP was reported in 195 (98.98%) of 197 fractures (odds ratio [OR], 97.5%; 95% CI, 95.8%-100%; I2 = 0), with a mean time to RTP of 10.3 weeks (95% CI, 9.5-11.1 weeks; I2 = 99%). In the group that received fixation without biological augmentation, successful RTP was reported in 516 (99.04%) of 521 fractures (OR, 98.7%; 95% CI, 97.8%-99.7%; I2 = 0], with a mean time to RTP of 9.7 weeks (95% CI, 7.84-11.53 weeks; I2 = 98.64%]. In the biologically augmented fixation group, fracture union was achieved in 194 (98.48%) of 197 fractures (OR, 97.6%; 95% CI, 95.5%-99.7%; I2 = 0%), with a mean time to fracture union of 9.28 weeks (95% CI, 7.23-11.34 weeks; I2 = 98.18%). In the group that received fixation without biological augmentation, fracture union was achieved in 407 (93.78%) of 434 fractures (OR, 97.4%; 95% CI, 96%-98.9%; I2 = 0%), with a mean time to fracture union of 8.57 weeks (95% CI, 6.82-10.32 weeks; I2 = 98.81%). CONCLUSION: Orthobiologically augmented surgical fixation of Jones fractures in athletes is becoming increasingly common, despite the lack of comparative studies to support this practice. Biologically augmented fixation of Jones fractures results in higher fracture union rates than fixation alone but similar rates of RTP and time to RTP. Although the current evidence recommends primary surgical fixation for the management of Jones fractures in athletes, further high quality comparative studies are required to establish the indication for orthobiologic augmentation.

Primary total ankle replacement surgery is a cost-effective intervention.

AIMS: The primary aim was to assess the cost-effectiveness of primary total ankle replacements (PTAR) in the UK. Secondary aim was to identify predictors associated with increased cost-effectiveness of PTAR. METHODS: Pre-operative and six-month post-operative data was obtained over a 90-month period across the two centres receiving adult referrals in the UK. The EuroQol general health questionnaire (EQ-5D-3L) measured health-related Quality of Life (HRQoL) and the Manchester-Oxford Foot Questionnaire (MOXFQ) measured joint function. Predictors, tested for significance with QALYs gained, were pre-operative scores and demographic data including age, gender, BMI and socioeconomic status. A cost per QALY of less than £20,000 was defined as cost effective. RESULTS: The 51-patient cohort [mean age 67.70 (SD 8.91), 58.8% male] had 47.7% classed as obese or higher. Cost per QALY gained was £1669, rising to £4466 when annual (3.5%) reduction in health gains and revision rates and discounting were included. Lower pre-operative EQ-5D-3L index correlated significantly with increased QALYs gained (p < 0.01), all other predictors were not significantly (p > 0.05) associated with QALYs gained. CONCLUSIONS: PTAR is a cost-effective intervention for treating end-stage ankle arthritis. Pre-operative EQ-5D-3L was associated with QALYs gained. A pre-operative EQ-5D-3L score of 0.57 or more was not cost effective to operate on.

Assessing risk of damage to posterior ankle structures during total ankle arthroplasty.

AIMS: Arthroplasty has become increasingly popular to treat end-stage ankle arthritis. Iatrogenic posterior neurovascular and tendinous injury have been described from saw cuts. However, it is hypothesized that posterior ankle structures could be damaged by inserting tibial guide pins too deeply and be a potential cause of residual hindfoot pain. METHODS: The preparation steps for ankle arthroplasty were performed using the Infinity total ankle system in five right-sided cadaveric ankles. All tibial guide pins were intentionally inserted past the posterior tibial cortex for assessment. All posterior ankles were subsequently dissected, with the primary endpoint being the presence of direct contact between the structure and pin. RESULTS: All pin locations confer a risk of damaging posterior ankle structures, with all posterior ankle structures except the flexor hallucis longus tendon being contacted by at least one pin. Centrally-aligned transcortical pins were more likely to contact posteromedial neurovascular structures. CONCLUSION: These findings support our hypothesis that tibial guide pins pose a considerable risk of contacting and potentially damaging posterior ankle structures during ankle arthroplasty. This study is the first of its kind to assess this risk in the Infinity total ankle system. Cite this article: Bone Jt Open 2021;2(7):503-508.

On the Emergence of Tremor in Prodromal Parkinson's Disease.

Clinical, neuropathological and neuroimaging research suggests that pathological changes in Parkinson's disease (PD) start many years before the emergence of motor signs. Since disease-modifying treatments are likely to be most effective when initiated early in the disease process, there has been significant interest in characterizing prodromal PD. Some people with PD describe autonomic symptoms at the time of diagnosis suggesting that autonomic dysfunction is a common feature of prodromal PD. Furthermore, subtle motor signs may be present and emerge prior to the time of diagnosis. We present a series of patients who, in the prodromal phase of PD, experienced the emergence of tremor initially only while yawning or straining at stool and discuss how early involvement of autonomic brainstem nuclei could lead to these previously unreported phenomena. The hypothalamic paraventricular nucleus (PVN) plays a central role in autonomic control including bowel/bladder function, cardiovascular homeostasis and yawning and innervates multiple brainstem nuclei involved in autonomic functions (including brainstem reticular formation, locus ceruleus, dorsal raphe nucleus and motor nucleus of the vagus). The PVN is affected in PD and evidence from related phenomena suggest that the PVN could increase tremor either by increasing downstream cholinergic activity on brainstem nuclei such as the reticular formation or by stimulating the locus ceruleus to activate the cerebellothalamocortical network via the ventrolateral nucleus of the thalamus. Aberrant cholinergic/noradrenergic transmission between these brainstem nuclei early in PD couldlead to tremor before the emergence of other parkinsonian signs, representing an early clinical clue to prodromal PD.

Consent in forefoot surgery; What does it mean to the patient?

AIMS: This study aimed to assess patient risk recall and find risk thresholds for patients undergoing elective forefoot procedures. METHODS: Patients were interviewed in the pre-assessment clinic (PAC) or on day of surgery (DOS); some in both settings. A standardised questionnaire was used for all interviews, regardless of setting. Patients were tested on which risks they recalled from their consent process, asked for thresholds for five pre-chosen risks and asked about a sham risk. RESULTS: Across all interviews, risk recall on DOS (2.34 risks/patient interview) was significantly lower (p=.05) than in PAC (2.95 risks/patient interview) - this was repeated when comparing results from patients interviewed in both settings only with PAC mean recall of 2.93 risks/patient interview and DOS mean recall of 2.57 risks/patient interview. The mean reported risk thresholds greatly exceeded NHS Lothian's observed complication rates for forefoot procedures. The five risks tested for thresholds produced the same order in each interview setting, suggesting a patient-perceived severity ranking. Patients answering the sham risk question incorrectly tended to recall fewer risks across all interviews. CONCLUSIONS: This study shows that patient risk recall is poor, as previous literature outlines, reinforcing that consent process improvements could be made. It also illustrates the value of PAC visits in patient education, as shown by higher levels of recall when compared to DOS.

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification.

Measurement of temperature induced in bone during drilling in minimally invasive foot surgery.

INTRODUCTION: There has been growing interest in minimally invasive foot surgery due to the benefits it delivers in post-operative outcomes in comparison to conventional open methods of surgery. One of the major factors determining the protocol in minimally invasive surgery is to prevent iatrogenic thermal osteonecrosis. The aim of the study is to look at various drilling parameters in a minimally invasive surgery setting that would reduce the risk of iatrogenic thermal osteonecrosis. METHOD: Sixteen fresh-frozen tarsal bones and two metatarsal bones were retrieved from three individuals and drilled using various settings. The parameters considered were drilling speed, drill diameter, and inter-individual cortical variability. Temperature measurements of heat generated at the drilling site were collected using two methods; thermocouple probe and infrared thermography. The data obtained were quantitatively analysed. RESULTS: There was a significant difference in the temperatures generated with different drilling speeds (p<0.05). However, there was no significant difference in temperatures recorded between the bones of different individuals and in bones drilled using different drill diameters. Thermocouple showed significantly more sensitive tool in measuring temperature compared to infrared thermography. CONCLUSION: Drilling at an optimal speed significantly reduced the risk of iatrogenic thermal osteonecrosis by maintaining temperature below the threshold level. Although different drilling diameters did not produce significant differences in temperature generation, there is a need for further study on the mechanical impact of using different drill diameters.

A Rare Cause of Myoclonus: A Cupric Conundrum.

A woman aged 22 years presented with a 3-year history of jerks when brushing her teeth and a tremor when carrying drinks. Examination revealed a bilateral jerky tremor, stimulus-sensitive myoclonus, and difficulty with tandem gait. Thyroid and liver function test results were normal, but she had rapidly progressive renal failure. Serum copper, ceruloplasmin, and manganese levels were normal, but her urinary copper level was elevated on 2 occasions. Pathological findings on organ biopsy prompted genetic testing to confirm the diagnosis. The differential diagnosis, tissue biopsy findings, and final genetic diagnosis are discussed.

'Sorry, I meant the patient's left side': impact of distraction on left-right discrimination.

CONTEXT: Medical students can have difficulty in distinguishing left from right. Many infamous medical errors have occurred when a procedure has been performed on the wrong side, such as in the removal of the wrong kidney. Clinicians encounter many distractions during their work. There is limited information on how these affect performance. OBJECTIVES: Using a neuropsychological paradigm, we aim to elucidate the impacts of different types of distraction on left-right (LR) discrimination ability. METHODS: Medical students were recruited to a study with four arms: (i) control arm (no distraction); (ii) auditory distraction arm (continuous ambient ward noise); (iii) cognitive distraction arm (interruptions with clinical cognitive tasks), and (iv) auditory and cognitive distraction arm. Participants' LR discrimination ability was measured using the validated Bergen Left-Right Discrimination Test (BLRDT). Multivariate analysis of variance was used to analyse the impacts of the different forms of distraction on participants' performance on the BLRDT. Additional analyses looked at effects of demographics on performance and correlated participants' self-perceived LR discrimination ability and their actual performance. RESULTS: A total of 234 students were recruited. Cognitive distraction had a greater negative impact on BLRDT performance than auditory distraction. Combined auditory and cognitive distraction had a negative impact on performance, but only in the most difficult LR task was this negative impact found to be significantly greater than that of cognitive distraction alone. There was a significant medium-sized correlation between perceived LR discrimination ability and actual overall BLRDT performance. CONCLUSIONS: Distraction has a significant impact on performance and multifaceted approaches are required to reduce LR errors. Educationally, greater emphasis on the linking of theory and clinical application is required to support patient safety and human factor training in medical school curricula. Distraction has the potential to impair an individual's ability to make accurate LR decisions and students should be trained from undergraduate level to be mindful of this.

Soft tissue swellings in the foot: rheumatoid nodulosis.

Background rheumatoid nodulosis is a rare disease characterised by multiple subcutaneous nodules, a high titre of rheumatoid factor, radiologically detectable cystic bone lesions, but with none or few of the systemic manifestations or joint activity of rheumatoid disease. Histopathologically, nodulosis is the same as the nodules found in rheumatoid arthritis. It is considered to be a benign variant of rheumatoid arthritis. A 69 year old male presents with multiple subcutaneous nodules on the feet. This case study highlights the benefits of ultrasound in establishing a correct diagnosis and management. Although rare, rheumatoid nodulosis is a consideration in the differential diagnoses of soft tissue swellings in the feet.