Ischemic toe after surgery for lesser toe deformities: An algorithm.

Ischemia after correction of lesser toe deformities is usually due to temporary vasospasm and can rarely cause gangrene. The published literature on dealing with the issue and been reviewed and used to suggest an algorithm for a logical step by step approach to a pale or white toe when encountered in the postoperative period.

Functional dystonia in the foot and ankle.

AIMS: To assess the characteristic clinical features, management, and outcome of patients who present to orthopaedic surgeons with functional dystonia affecting the foot and ankle. METHODS: We carried out a retrospective search of our records from 2000 to 2019 of patients seen in our adult tertiary referral foot and ankle unit with a diagnosis of functional dystonia. RESULTS: A total of 29 patients were seen. A majority were female (n = 25) and the mean age of onset of symptoms was 35.3 years (13 to 71). The mean delay between onset and diagnosis was 7.1 years (0.5 to 25.0). Onset was acute in 25 patients and insidious in four. Of the 29 patients, 26 had a fixed dystonia and three had a spasmodic dystonia. Pain was a major symptom in all patients, with a coexisting diagnosis of chronic regional pain syndrome (CRPS) made in nine patients. Of 20 patients treated with Botox, only one had a good response. None of the 12 patients who underwent a surgical intervention at our unit or elsewhere reported a subjective overall improvement. After a mean follow-up of 3.2 years (1 to 12), four patients had improved, 17 had remained the same, and eight reported a deterioration in their condition. CONCLUSION: Patients with functional dystonia typically presented with a rapid onset of fixed deformity after a minor injury/event and pain out of proportion to the deformity. Referral to a neurologist to rule out neurological pathology is advocated, and further management should be carried out in a movement disorder clinic. Response to treatment (including Botulinum toxin (Botox) injections) is generally poor. Surgery in this group of patients is not recommended and may worsen the condition. The overall prognosis remains poor. Cite this article: Bone Joint J 2021;103-B(6):1127-1132.

A prospective study on surgical management of foot deformities in Charcot Marie tooth disease.

Foot deformities are frequently observed in patients with Charcot Marie tooth disease (CMT) and orthopaedic surgery is often required. Currently there is no evidence-based guideline on surgical management and only a few studies which have evaluated long-term outcomes of surgical procedures. The aim of the study was to evaluate longitudinally the effect of foot surgery in a cohort of CMT patients. Twenty-five CMT adult patients were assessed using a comprehensive group of validated scales and questionnaires before and after surgery. A wide range of surgical procedures was performed by one team of dedicated foot ankle orthopaedic surgeons. Foot alignment as measured by the foot posture index, pain, quality of life and callosities significantly improved after one year and the improvement was maintained up to 4 years after surgery. There was a trend towards a reduction in the number of falls post-operatively. Surgery had no effect on fatigue, balance and CMT examination score. Our findings showed significant improvement of pain, foot alignment, callosities and quality of life after surgery and suggested that foot deformity correction in adults with CMT performed in a specialised foot and ankle unit is beneficial.

Retinal and Lens Degeneration in New Zealand White Rabbits Administered Intravitreal TSG-6 Link Domain-Rabbit FAb Fusion Proteins.

Fusion of biologic therapeutics to hyaluronic acid binding proteins, such as the link domain (LD) of Tumor necrosis factor (TNF)-Stimulated Gene-6 (TSG-6), is expected to increase vitreous residence time following intravitreal injection and provide for long-acting delivery. The toxicity of a single intravitreal dose of free TSG-6-LD and fusion proteins of TSG-6-LD and a nonbinding rabbit antibody fragment (RabFab) were assessed in New Zealand White rabbits. Animals administered free TSG-6-LD exhibited extensive lens opacities and variable retinal vascular attenuation, correlated with microscopic findings of lens and retinal degeneration. Similar but less severe findings were present in animals dosed with the RabFab-TSG-6-LD fusion proteins. In-life ocular inflammation was noted in all animals from 7-days postdose and was associated with high anti-RabFab antibody titers in animals administered fusion proteins. Inflammation and retinal degeneration were multifocally associated with evidence of retinal detachment, and hypertrophy and migration of vimentin, glial fibrillary acidic protein, and glutamine synthetase positive Müller cells to the outer nuclear layer. Further assessment of alternative hyaluronic acid binding protein fusions should consider the potential for retinal degeneration and enhanced immune responses early in development.

Charcot neuroarthropathy in patients with Charcot Marie Tooth Disease.

Charcot Marie Tooth disease (CMT) is the most common inherited neuropathy and is also called Hereditary Motor Sensory Neuropathy (HMSN). Whilst both motor and sensory deficits are present, motor deficits tend to predominate over sensory deficits. Charcot neuroarthropathic joints occur in conditions, most commonly diabetes nowadays, where joints are destroyed in association with reduced protective sensation, pain in particular. Three cases of development of Charcot joint disorders in patients with CMT are discussed and the literature is reviewed. Orthopaedic surgeons should be aware that Charcot joints can occur in CMT and surgery can be complicated by Charcot joints.

Multiplexed screening of natural humoral immunity identifies antibodies at fine specificity for complex and dynamic viral targets.

Viral entry targets with therapeutic neutralizing potential are subject to multiple escape mechanisms, including antigenic drift, immune dominance of functionally irrelevant epitopes, and subtle variations in host cell mechanisms. A surprising finding of recent years is that potent neutralizing antibodies to viral epitopes independent of strain exist, but are poorly represented across the diverse human population. Identifying these antibodies and understanding the biology mediating the specific immune response is thus difficult. An effective strategy for meeting this challenge is to incorporate multiplexed antigen screening into a high throughput survey of the memory B cell repertoire from immune individuals. We used this approach to discover suites of cross-clade antibodies directed to conformational epitopes in the stalk region of the influenza A hemagglutinin (HA) protein and to select high-affinity anti-peptide antibodies to the glycoprotein B (gB) of human cytomegalovirus. In each case, our screens revealed a restricted VH and VL germline usage, including published and previously unidentified gene families. The in vivo evolution of paratope specificity with optimal neutralizing activity was understandable after correlating biological activities with kinetic binding and epitope recognition. Iterative feedback between antigen probe design based on structure and function information with high throughput multiplexed screening demonstrated a generally applicable strategy for efficient identification of safe, native, finely tuned antibodies with the potential for high genetic barriers to viral escape.

Two case study evaluations of an arts-based social skills intervention for adolescents with childhood brain disorder.

OBJECTIVE: Arts-based programmes have been shown to be useful for individuals with disturbances in cognitive and behavioural functioning. The current case studies examined the feasibility and effectiveness of a theatre skills training programme to facilitate social skills and participation for adolescents with childhood brain disorder. METHODS: A case study approach was used with two adolescent participants. Focus groups were conducted immediately post-intervention, while a battery of quantitative measures were administered pre- and post-treatment, as well as 8 months post-treatment. RESULTS: Perceived and documented improvements in social skills and participation were observed from pre- to post-intervention and at follow-up. CONCLUSION: Results support the use of an arts-based intervention for youth with brain injuries to facilitate social skills and participation. Findings also highlight the need for more sensitive measures of these skills for youth with childhood brain disorder, who may have impaired awareness of their abilities and/or impairments in memory and language comprehension.

BMP signaling and podocyte markers are decreased in human diabetic nephropathy in association with CTGF overexpression.

Diabetic nephropathy is characterized by decreased expression of bone morphogenetic protein-7 (BMP-7) and decreased podocyte number and differentiation. Extracellular antagonists such as connective tissue growth factor (CTGF; CCN-2) and sclerostin domain-containing-1 (SOSTDC1; USAG-1) are important determinants of BMP signaling activity in glomeruli. We studied BMP signaling activity in glomeruli from diabetic patients and non-diabetic individuals and from control and diabetic CTGF(+/+) and CTGF(+/-) mice. BMP signaling activity was visualized by phosphorylated Smad1, -5, and -8 (pSmad1/5/8) immunostaining, and related to expression of CTGF, SOSTDC1, and the podocyte differentiation markers WT1, synaptopodin, and nephrin. In control and diabetic glomeruli, pSmad1/5/8 was mainly localized in podocytes, but both number of positive cells and staining intensity were decreased in diabetes. Nephrin and synaptopodin were decreased in diabetic glomeruli. Decrease of pSmad1/5/8 was only partially explained by decrease in podocyte number. SOSTDC1 and CTGF were expressed exclusively in podocytes. In diabetic glomeruli, SOSTDC1 decreased in parallel with podocyte number, whereas CTGF was strongly increased. In diabetic CTGF(+/-) mice, pSmad1/5/8 was preserved, compared with diabetic CTGF(+/+) mice. In conclusion, in human diabetic nephropathy, BMP signaling activity is diminished, together with reduction of podocyte markers. This might relate to concomitant overexpression of CTGF but not SOSTDC1.

Connective tissue growth factor and its regulation in the peritoneal cavity of peritoneal dialysis patients.

BACKGROUND: Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is highly expressed in wound healing and fibrotic lesions. The role of transforming growth factor-beta (TGF-beta) in fibrosis is well documented, and the emerging understanding that its fibrogenic actions are mediated through CTGF has provided an attractive target molecule for the modulation of matrix overproduction in fibrotic disease. The involvement of CTGF in the pathogenesis of peritoneal membrane fibrosis in peritoneal dialysis (PD) patients has not been investigated, and so the aim of this study was to ascertain whether CTGF is produced in the peritoneal cavity of PD patients and to investigate its regulation by cytokines. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), Northern blotting, and Western blotting were used to study CTGF expression by cultured human peritoneal mesothelial cells (HPMC) from peritoneal dialysis patients. Western blotting was used to detect CTGF expression in spent peritoneal dialysate from patients with and without peritonitis. RESULTS: RT-PCR analysis demonstrated the expression of CTGF mRNA in cultured primay HPMCs isolated from spent peritoneal effluent. The production of the major 36 to 38 kD CTGF protein doublet by HPMC in addition to a 23 to 25 kD proteolytically processed form was confirmed by Western blotting. Several molecular weight forms of CTGF (18 to 38 kD) were also detected by Western blotting in peritoneal dialysate, with levels markedly elevated during episodes of peritonitis. Northern and Western blot analysis revealed that CTGF mRNA and protein production by HPMC was up-regulated by TGF-beta, with mRNA levels significantly increasing above the control (P < 0.01). In contrast, platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and tumor necrosis factor-alpha (TNF-alpha) had no measurable effects on CTGF mRNA expression. CONCLUSION: These results are the first to demonstrate the production of CTGF by HPMC and its presence in the peritoneal cavity of PD patients. The marked increase in CTGF levels by factors implicated in the development of peritoneal membrane fibrosis suggests its involvement in the underlying pathophysiologic mechanism(s).