Distal Limb Research Articles

Prospective Study of Acalabrutinib with Rituximab in Patients with Symptomatic Anti-MAG Mediated IgM Peripheral Neuropathy

Background: Peripheral neuropathy (PN) occurs in 20-25% of patients with an IgM paraprotein and up to 50% of these patients have an anti-myelin associated glycoprotein (MAG) antibody which is frequently associated with sensory ataxia and distal limb weakness negatively affecting function and quality of life. While rituximab is active, its activity is limited as a monotherapy and often associated with an IgM flare that can potentiate PN. BTK-inhibitors can block rituximab-associated IgM flare and are proven to markedly reduce serum IgM in Waldenström's Macroglobulinemia (WM). We therefore initiated this trial to evaluate a novel treatment for anti-MAG PN. Methods: We initiateda prospective, single-arm phase II study of acalabrutinib and rituximab (NCT05065554). Patients with an anti-MAG antibody with an IgM monoclonal gammopathy or WM; and a predominantly sensory demyelinating PN with a modified Rankin score of ≥1 with progressive symptoms or a score of ≥2 are eligible. Treatment consists of continuous oral acalabrutinib (100 mg twice daily) with rituximab weekly in cycles 1 and 4. Each cycle is 28 days. The primary endpoint is to evaluate the hematologic response rate. The key secondary endpoint is to evaluate the proportion of patients that achieve improvement or stability in PN based on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) patient-reported disability scale. Additional secondary neurologic endpoints include the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, MRC distal sum score, INCAT sensory sum score, and a neuropathy-specific quality of life scale (IN-QOL). We hypothesize that 75% of participants (H1) will have a hematologic response versus a null (H0) of 50% or lower. With 33 evaluable patients, there will be 82% power to detect a significant difference with an alpha (2-sided) of 0.04. Results: Eight patients, including 4 females, have enrolled as of July 1, 2023. The median age is 70 years (range 65-76), and median ECOG is 1. Median I-RODS score at baseline was 41 (range 23-48; 48 = no disability). All patients have an IgM kappa paraprotein with median baseline serum IgM of 975 mg/dL (range 226-2137), kappa free light chain of 28 mg/L (range 16-47), and M-spike of 0.6 g/dL (range 0.17-1.1). Anti-MAG antibody titer range is 1:70,000 to 1:819,200 IU/L. Bone marrow biopsy showed no disease in 4 patients, a clonal plasma cell population in 1 patient, and lymphoplasmacytic infiltrate in 3 patients. No adenopathy or splenomegaly were detected on baseline CT scans. Six patients (75%) are MYD88 mutated and none CXCR4 mutated. Five patients had prior rituximab therapy and two received prior IVIG. With a median time on treatment of 175 days (range 28-510), the overall response rate among 7 evaluable patients using IWWM-11 criteria was 86%. Categorical responses include 2 very good partial responses (≥90% decrease in IgM, or normalization of IgM with persistent IgM monoclonal protein); 1 partial response (≥50% but <90% decrease in IgM); 3 minor responses (≥25% but <50% decrease in IgM) and 1 stable disease. Four of 7 patients (57%) had improvement in the I-RODS score. Median improvement was 0.5 points (range -4 to 11). One patient was removed from the trial after 28 days due to grade 3 elevation in ALT. Two other reversible grade 3 adverse events occurred including rituximab related infusion reaction and syncope unrelated to treatment. Conclusions: The combination of acalabrutinib and rituximab has demonstrated activity in this first prospective study that is evaluating BTK-inhibition with CD20 directed therapy in patients with IgM related anti-MAG PN. Hematologic responses occurred in 86% of patients and 57% had an improvement in the I-RODS score. Treatment is well tolerated. Additional data from more detailed neurologic assessments are forthcoming. The trial continues to enroll patients. Our findings provide a framework to develop novel, more effective treatment options for anti-MAG PN.

Phenotypic and genotypic analysis of a patient with Miyoshi myopathy caused by truncated protein

Dysferlin protein deficiency can cause neuromuscular dysfunction, resulting in autosomal recessive dysferlinopathy, which is caused by DYSF gene mutation. Dysferlin proteins belongs to the Ferlin1-like protein family and are associated with muscle membrane repair and regeneration. In China, pathogenic mutations of the protein often result in two clinical phenotypes of Miyoshi muscular or limb band muscular dystrophy type 2B. It is clinically characterized by progressive muscle weakness and elevated serum creatine kinase. The data of the child were collected, blood samples of the child and his family members were collected, and whole exome sequencing (WES) was performed. The recombinant expression vector was constructed, the function of the mutation was verified by minigene, and the pathogenicity of the mutation was further analyzed by combining with biological information analysis. The patient initially presented with asymptomatic elevation of serum creatine kinase（CK）. Then progressive lower limb weakness, mainly distal limb weakness. Large amounts of scattered necrosis, myogenic lesions, and complete deletion of dysferlin protein were observed under muscle biopsy, which further improved genetic detection. Whole exome sequencing showed compound mutations (c.1397 + 1_1397 + 3del and c.1375dup p.M459Nfs*15) in DYSF gene. c.1375dup p.M459Nfs*15 have been reported. The other mutation is the deletion of c.1397 + 1_1397 + 3 in Intron15, which is an intron mutation that may affect splicing and the pathogenesis is still unknown. Minigene splicing assay verified that c.1397 + 1_1397 + 3del resulted in exon15 skipping and produced a premature termination codon. We report a novel pathogenic mutation in DYSF gene with Miyoshi myopathy and demonstrate this variant causes skipping of exon15 by minigene splicing assay. We point out the need of conducting functional analysis to verify the pathogenicity of intronic mutation. The finding enriches the mutation spectrum of DYSF gene and laid a foundation for future studies on the correlation between genotype and phenotype.

Deep-learning-based markerless tracking of distal anatomical landmarks in clinically recorded videos for assessing infant movement patterns associated with neurodevelopmental status

ABSTRACT Abnormal patterns in infants’ General Movements (GMs) are robust clinical indicators for the progression of neurodevelopmental disorders, including cerebral palsy. Availability of automated platforms for General Movements Assessments (GMA) could improve screening rate and allow identifying at-risk infants. While we have previously shown that deep-learning schemes can accurately track the longitudinal axes of infant limb movements (12 anatomical locations, 3 per limb), information about the distal limb segments’ rotational movements is important for making an accurate clinical assessment, but has not previously been captured. Here we show that training schemes that are highly successful at tracking trunk and proximal limb landmarks perform less well for the distal limb landmarks, and this problem is exacerbated when landmarks are more precisely defined in the training-set to capture rotational movements. Increasing the sample size to 26 videos using a mixture of laboratory and clinical data pre-selected for diversity of pose and video conditions in a ResNet-152 deep-net model was sufficient to permit accuracy of >85% for the distal markers, and overall accuracy of 98.28% (SD 2.29) across the 24 landmarks. This scheme is suitable to form the basis of an infant pose reconstruction algorithm that captures clinically relevant information for an automated GMA.

Association between activity in the ventral premotor cortex and spinal cord activation during force generation-A combined cortico-spinal fMRI study.

Force generation is a crucial element of dexterity and a highly relevant skill of the human motor system. How cerebral and spinal components interact and how spinal activation is associated with the activity in the cerebral primary motor and premotor areas is poorly understood. Here, we conducted combined cortico-spinal functional magnetic resonance imaging during a simple visually guided isometric force generation task in 20 healthy young subjects. Activation was localized in the right cervical spinal cord and left primary motor and premotor areas. The main finding is that spinal activation was negatively correlated with ventral premotor cortex activation. Spinal activation was furthermore significantly correlated with primary motor cortex activation, while increasing target forces led to an increase in the amount of activation. These data indicate that human premotor areas such as the ventral premotor cortex might be functionally connected to the lower cervical spinal cord contributing to distal upper limb functions, a finding that extends our understanding of human motor function beyond the animal literature.

Dose effect and duration of action of liposomal bupivacaine administered as a perineural analgesic in a reversible and adjustable frog-pressure model of equine lameness.

To determine the dose effect of peri-neural liposomal bupivacaine (LB) in an induced forelimb lameness model. 12 clinically normal adult horses. A randomized cross-over design was performed with 1 limb receiving saline and the other LB: low dose (6), high dose (6). Lameness was induced in 1 forelimb using a frog-pressure model. In the lame limb, peri-neural injection of the palmar nerves at the proximal sesamoid bones was performed using saline, low dose LB (0.25 mg/kg) (LDLB), or high dose LB (0.5mg/kg) (HDLB) in random order with a 1-week washout period between treatments. Distal limb swelling, mechanical nociceptive thresholds (MNT), and objective lameness data were collected before and up to 72 hours after peri-neural anesthesia. Data analysis was performed with mixed model ANOVA, equality of medians test, and Kaplan Meier survival analysis. Compared with baseline, horses treated with LDLB and HDLB had improvements in MNT and lameness (P < .001). In the LDLB group, the median duration of analgesia was 4.5 hours (range = 3-6 hours) and the median return to lameness was 7 hours (range = 4-24 hours). In the HDLB group, the median duration of analgesia was 12 hours (range = 4-48 hours) and the median return to lameness was 9 hours (range = 3-48 hours). Mild to moderate swelling was identified in 11/12 (92%) LB limbs. Both LDLB and HDLB resulted in loss of skin sensation and improvement of lameness. There was high variability among horses in duration of action for both doses.

Arthrocentesis approaches to the phalangeal joints of the one humped camel (Camelus dromedarius)

Irrespective of the exceptional adaptation of dromedaries to harsh environmental conditions, they remain highly susceptible to joint lameness resulting from a range of diverse factors and conditions. The joints most often affected by traumatic osteoarthritis in dromedaries are the metacarpophalangeal and metatarsophalangeal joints. A comprehensive understanding of joint anatomy and topography of the dromedary is required to perform arthrocentesis correctly on affected joints. Forty-two distal limbs were taken from 28 camels and studied by gross dissection, casting, ultrasonography, and computed tomography (CT). Representative three-dimensional models of the joint cavities, recesses, and pouches were obtained using different casting agents. This study provides a detailed description of dorsally, axially, and abaxially positioned joint recesses, as well as palmar/plantar positioned joint pouches. The safety and feasibility of the different arthrocentesis approaches were evaluated. The traditional dorsal arthrocentesis approach of the metacarpophalangeal, metatarsophalangeal, proximal interphalangeal, and distal interphalangeal joints, has limitations due to the risk of damaging the tendon structures and articular cartilage, which can lead to joint degeneration. A lateral arthrocentesis approach via the proximal palmar/plantar pouches of the metacarpophalangeal/metatarsophalangeal and proximal interphalangeal joints is recommended. This approach eliminates the potential needle injury to the articulating joint cartilage and other surrounding joint structures, such as tendons, blood vessels, and nerves.

Low-Field Magnetic Resonance Imaging Findings of the Fetlock Region of Nonracehorses

Low-field, magnetic resonance imaging (MRI) is an advanced imaging modality widely used to diagnose distal limb pathology in horses, but there are limited data regarding lesion distribution within the metacarpo/metatarsophalangeal joint (MCP/MTPJ) region in lame nonracehorses. The aim of this study was to describe the low-field MRI findings and lesion distribution in nonracehorses with MCP/MTPJ region pain. Clinical records from horses undergoing MRI of the MCP/MTPJ region between July 2016 and March 2023 were reviewed. Horses were included if pain causing lameness was localized to this region and conventional imaging failed to provide a definitive diagnosis. Eighty-four horses met the inclusion criteria. Soft tissues were affected in 76 (90.5%) horses, with suspensory ligament branch injuries being the most frequent (60.7%) soft tissue pathology identified. Osseous pathology was diagnosed in 51 horses. The subchondral bone (SCB) of the distal third metacarpal/metatarsal bone (MC3/MT3) was the osseous structure most frequently affected (40.5%), with 79.4% of these horses having lesions on the dorsal aspect of the bone. Osteoarthritis was present in 48 (57.1%) horses. The main limitations of the study were the lack of a standardized diagnostic analgesia pattern due to varying veterinary surgeon involvement, and the absence of bilateral magnetic resonance (MR) sequences in all limbs. MRI is a useful diagnostic tool to assess soft tissue structures in the MCP/MTP region, especially in horses with thick skin, which may make ultrasonographic imaging unreliable.

Intraspecific anatomical variations of the extensor tendons of the carpus and digits with a reexamination of their insertion sites in the domestic dog (Canis lupus familiaris): a cadaveric study

BackgroundThe aim of the current study was to investigate the frequency of variations of the extensor tendons of the carpus and digits in the domestic dog (Canis lupus familiaris) with a reexamination of their insertions as well as the morphometric measurements of the tendons and the brachioradialis muscle. In total, we investigated 68 paired thoracic limbs of the domestic dog (16 females and 18 males) which were fixed in a 10% formalin solution.ResultsThe extensor carpi radialis (ECR) tendons showed striking variations in both splitting and insertion sites. In 4.4% of dissections, ECR had three tendons. Of these tendons, the extra tendon either attached independently on the fourth metacarpal bone (one right) or joined its counterpart tendon at the distal end (cross-connections) (one bilateral). It is worth mentioning that one of the ECR tendons split into two or three slips which inserted on the first, second, third, or fourth metacarpal bone in 11 (16.2%) of the specimens. In addition, we found a long tendinous slip originating from the ECR tendons to digit II or III in 7.4% of the distal limbs. The most common type of contribution to digit III was a third tendon of the extensor digiti I et II (ED III) joining the extensor digitorum lateralis (EDL III) with a frequency of 17.6%. In other types of variations, the contribution to digit III was incomplete. A part of the abductor pollicis longus (APL) deep to the superficial part of the flexor retinaculum seemed to continue up to the flexor digitorum superficialis (FDS) tendon.ConclusionsThe rare intraspecific variations of the extensor tendons of the manus described in the current research are valuable from both clinical and phylogenetic perspectives. Nonetheless, their functional importance needs more studies.

Anakinra and hepatotoxicity in pediatric rheumatology: a case series

BackgroundAnakinra is a recombinant interleukin-1 (IL-1) receptor antagonist used in systemic juvenile idiopathic arthritis (sJIA), refractory Kawasaki disease (KD) and cryopyrin-associated autoinflammatory syndrome (CAPS). Anakinra associated hepatotoxicity, while rare, has been described in several cases in daily practice. ​In this case series the authors describe three pediatric patients with this side effect in the setting of severe macrophage activation syndrome (MAS) in KD and sJIA.Case presentationThe first patient was a 12-year-old boy who presented with fever, maculo-papular exanthema and polyarthralgia. Tonsillitis, distal limb induration and tender cervical lymph nodes were observed. Erythrocyte-sedimentation rate (ESR), C-reactive protein (CRP), ferritin (11,975 ng/mL), D-dimers (5,98 mg/L FEU) and soluble CD25 (3645 pg/mL) levels were elevated. Exclusion of sepsis / toxic shock syndrome warranted introduction of IV methylprednisolone and immunoglobulin (IG IV), with partial response. A MAS secondary to KD was assumed, and anakinra 2 mg/kg/day was introduced. Twenty days later he developed new-onset nausea and severe cyto-cholestasis, normalizing after 2 months of drug discontinuation. Posterior onset of polyarthritis and evanescent lead to a final diagnosis of sJIA. The second patient was a 2-year-old boy with a 10-day history of fevers, generalized rash, hepatosplenomegaly and strawberry tongue. Leucocytosis with neutrophilia and elevated CRP were observed. Initial treatment with IVIG in the setting of incomplete KD was ineffective. Mild anaemia, leukopenia and very high serum ferritin (maximum 26,128 ng/mL) ensued. Presumptive sJIA associated MAS was treated with IV methylprednisolone and anakinra 2 mg/kg/day, with prompt response. Four weeks later transaminitis was detected, and temporary anakinra suspension led to normalisation of laboratorial values. The third case related to a 4-year-old boy presenting with fever, maculopapular rash and cervical lymphadenopathy. CRP and ESR were elevated, and KD was diagnosed. IVIG and methylprednisolone were initiated with clinical worsening, warranting for anakinra introduction at 2 mg/kg/day. After three weeks, liver enzymes progressively elevated, resolving on 2 weeks of anakinra discontinuation.ConclusionsTo the best of our knowledge, this is the first case series describing anakinra associated hepatotoxicity in pediatric patients with rheumatic diseases other than sJIA, bringing additional insight to therapeutic monitoring in patients undergoing this treatment.

Systematic approach to localisation of lameness in the distal limb of horses

Background: Lameness examination is commonly required in equine veterinary practice, whether it's to investigate a lameness already identified by the owner, or as part of the investigation of poor performance.Aim of the article: This article outlines a systematic approach to adopt when presented with a lame horse. Although it focuses on examination of the distal limb, the same principles apply when examining the proximal limb.

Fascial plane mapping for superficial tumor resection in dogs. Part III: Hindlimb and pelvis.

To categorize the fascial planes and the intersections of these fascial planes in the hindlimb of the dog to facilitate preoperative planning for superficial cancers. Qualitative anatomical study. Four male and five female mixed breed dogs, weighing ~15-35 kg. Skin and subcutaneous fat were removed, and fascial planes were explored to determine borders and quality. Fascia was categorized as type I (discrete sheets), type II (adhered to thin muscles), type III (adhered to thick muscles), or type IV (associated with periosteum). Digital modification of specimen photographs was performed to map tissues. Differences in dogs were noted due to either size or sex but were sufficiently minor to allow mapping. Fasciae of the hindlimb were predominantly type II or III, with type I fascia primarily at the lateral gluteal region, fascia lata, and lateral crus. Type IV fascia was seen at the iliac wing, ischium, patella, tibial tuberosity, medial tibia, distal crus, and pes. Fascia for surgical use was thin or absent at the ischiorectal fossa, femoral triangle, extensor mechanism, medial and distal crus, and pes. Intersections and tissues at the ventral perineum may also pose challenges for maintenance of a deep margin. Fascial types and integrity of the hindlimb varied with location, with the perineum, cranial stifle, and distal limb presenting the greatest challenges. These images may be used to guide both therapeutic decision-making and intraoperative excision of superficial tumors of the hindlimb and pelvis.

Distal muscle cross-sectional area is correlated with shot put performance

Shot putters throw a heavy shot by “pushing”. Pushing involves the coordinated extension of multiple joints and is a common motor task for both upper and lower limbs. In lower limb musculature, proximal-specific development and association with motor performance have been shown in athletes. However, as the upper limb is not mechanically loaded to support the body during daily locomotion, it may develop differently from the lower limb. We investigated the cross-sectional area of the prime movers of the upper limb and upper trunk (pectoralis major, deltoid, triceps brachii, and palmar flexors) in eleven male shot put athletes and fourteen untrained males by obtaining magnetic resonance images and manually tracing the muscles on the images. All target muscles were significantly larger in athletes than non-athletes (p < 0.01), with “huge” effect sizes for the pectoralis major and palmar flexors (d = 2.74, 2.04). All target muscle cross-sectional areas were positively correlated with season best record (r ≥ 0.62, p ≤ 0.04), with a particularly strong correlation for the palmar flexors (r = 0.96). These results suggest that the distal muscles of the upper limb are also expected to develop and are strongly associated with motor performance. This is especially true for the distal upper limb muscles (palmar flexors) in shot putters. These findings provide insight into potential training interventions for athletic performance in forceful upper limb movements.

Problems of motor activity in cows with orthopaedic pathology

The relevance of the study is conditioned by the fact that diseases that manifest various degrees of lameness in cows are widespread (50-70%) among livestock. Milk productivity and body weight gain decrease in sick animals, which causes their culling. It is important to establish nosological forms of such pathologies and determine the effectiveness of their treatment. The purpose of the study is to analyse the problems of motor activity in cows with orthopaedic pathology. The study included an assessment of herd mobility before entering the milking parlour, which allowed comprehensively considering the rhythm and length of steps and the load on the cows’ limbs. It was found that the development of purulent-necrotic processes is accompanied by severe lameness in 66.6% of animals. A smaller number of animals (16.6%) were diagnosed with mild lameness. It was found that in 100% of cases, pathological processes were localised in the pelvic extremities. In the vast majority of animals, more than 3/4 of the lateral hooves were affected. There were no differences in the development of pathological processes on the right or left pelvic limb. The results of the examination of cows proved that the surgical pathology was accompanied by the development of local purulent inflammation. The most common pathology of the distal limbs in cows was purulent pododermatitis, which accounted for 66.6% of surgical diseases. Phlegmon in the area of the corolla and interdigital ulcers were diagnosed less frequently, with their respective shares in the pathology structure being 16.6%. It is proved that for the treatment of lame cows with the use of Levomekol ointment, clinical recovery was established with the disappearance of symptoms of lameness for purulent pododermatitis up to 24 days, and for phlegmonic processes in the corolla area and lesions of the finger arch – up to 22 days. The proposed therapy regimens will help to reduce the duration of treatment of purulent pododermatitis, phlegmon in the corolla area and lesions of the finger arch compared to conventional methods

Biostimulation effect of platelet-rich fibrin augmented with decellularized bovine pericardium on full-thickness cutaneous wound healing in Donkeys (Equus asinus)

AimThe current research aimed to evaluate the potential effect of adding platelet-rich fibrin (PRF) to the decellularized bovine pericardium (DBP) on the distal limb of donkeys’ full-thickness cutaneous wounds healing (Equus asinus).Materials and MethodsHealthy male donkeys (n = 12) were used in this study. Under general anesthesia, 6 cm2 full-thickness incisions were made on the middle dorsolateral surface of both forelimbs’ metacarpi. The left forelimbs were control wounds, while the right wounds were treated with PRF/DBP. Control wounds were bandaged with a standard dressing after saline irrigation and were evaluated at days 4, 7, 10, 13, 16, 19, 22, 25, and 28 post-wounding. PRF/DBP-treated wounds were dressed with a combination of PRF/DBP at the first, second, and third weeks post-wounding. Clinical and histopathological examinations of the wounds were performed to assess the healing process. Additionally, the immunohistochemical evaluation and gene expression profiles of myofibroblastic and angiogenic genes (transforming growth factor-β1, vascular endothelial growth factor-A, fibroblast growth factor 7 (FGF-7), and collagen type 3α1) were analyzed.ResultsPRF/DBP wounds had a significantly faster healing process (61.3 ± 2.6 days) than control wounds (90.3 ± 1.4 days) (p < 0.05). The immunohistochemical examination and gene expression profile revealed significant enrichment in PRF/DBP wounds compared to control wounds.ConclusionPRF/DBP dressing can be considered a natural and cost-effective biomaterial for enhancing the recovery of donkeys’ distal limb injuries.

The Effect of the COVID-19 Pandemic on Early Adolescent Fractures in the Republic of Korea.

Background and Objectives: Restrictions on daily activities to slow down the propagation of COVID-19 have changed the epidemiological pattern of pediatric fractures in many countries. However, the effect of the pandemic on pediatric fractures has not been fully studied. In this study, we investigated the impact of COVID-19 on early adolescent fractures in Korea. Materials and methods: We conducted a retrospective follow-up on a nationwide cohort of Korean early adolescents born between 2006 and 2009. The prevalence and incidence of pediatric fractures and the frequency of surgical treatment were compared between two different eras. Results: The prevalence and incidence of fractures during the pandemic have both shown a significant decrease: prevalence reduced from 34,626 to 24,789 (p < 0.001), while incidence decreased from 29,804 to 18,898 (p < 0.001). Considering sex, the shift in fracture prevalence was statistically significant (p = 0.020), whereas the incidence was not (p = 0.862). The decline in both fracture prevalence and incidence exhibited significant variation across birth year groups (prevalence, p < 0.001; incidence, p < 0.001), with a more pronounced reduction observed in the older age groups. While the proportion of patients who required surgeries has increased, the mean frequency of surgical treatment per patient remained at a similar level (by prevalence, p = 0.181; by incidence, p = 0.735). The decline in both fracture prevalence and incidence has shown significant variation in relation to fracture sites (prevalence, p < 0.001; incidence, p < 0.001), with a decrease in distal limb fractures and an increase in forearm and axial body fractures. Conclusions: The pediatric fracture pattern in Korea has been notably influenced by the COVID-19 pandemic, warranting further investigation into causal factors. Our findings should help predict epidemiology in the post-pandemic period and thus aid policymaking and patient management.

Structural Reorganization of the Third Metatarsal Bone Shaft After Autogenous Plasty of the Tibial Portion of the Sciatic Nerve

Background. Previous research has shown that neurectomy of the sciatic nerve leads to a reduction in bone density in the femur and tibia of laboratory mice and rats. However, the impact of surgeries aimed at restoring nerve innervation on the bones of distal limb parts has not been studied.&#x0D; Aim of the study to identify structural changes in the shaft of the third metatarsal bone after primary autogenous plasty of the resection defect of the tibial portion of the sciatic nerve in rats.&#x0D; Methods. Autologous neuroplasty of the tibial portion of the sciatic nerve was performed on 16 Wistar rats (aged 8-10 months). The animals were euthanized at 4 and 6 months after the surgery, and a control group of 7 intact rats of similar age was included. Histomorphometric analysis was conducted on a dissected fragment of the forefoot at the level of the metatarsal bones. The ratio of fuchsinophilic and anilinophilic structures of the cortical plate was determined using point-count volumetry on Masson-stained images of transverse sections of the third metatarsal bone shaft. The thickness of the cortical plate, numerical density, area, and diameter of osteons and Haversian canals were measured.&#x0D; Results. After 4 months, compared to the control group, a 15% decrease (p = 0.0001) in the proportion of mineralized structures of the cortical plate and a 12.7% reduction (p = 0.0184) in its thickness were observed. Osteolysis signs were present in the osteonal layer, along with decreased numerical density and dimensional characteristics of osteons, and the presence of osteons with dilated Haversian canals. At 6 months, the thickness of the cortical plate did not significantly differ from the norm (p = 0.2067), but there was a progressive 33.6% decrease (p = 0.0001) in the proportion of mineralized structures. Reduced values of numerical density, area, and diameter of osteons persisted in the osteonal layer, while the diameters of Haversian canals in osteons increased over time.&#x0D; Conclusion. From 4 to 6 months, the thickness of the cortical layer in the compact bone of the third metatarsal bone shaft was restored. However, changes in the numerical and dimensional composition of osteons, along with decreased mineralization of the extracellular matrix and erosion of the subperiosteal bone layer, continued to progress. The developed experimental 2D model can be used to assess denervation osteopenia in distal limb parts and further explore rehabilitation interventions that enhance and improve reinnervation.

Modulation of ipsilateral motor evoked potentials during bimanual coordination tasks.

Ipsilateral motor evoked potentials (iMEPs) are difficult to obtain in distal upper limb muscles of healthy participants but give a direct insight into the role of ipsilateral motor control. We tested a new high-intensity double pulse transcranial magnetic stimulation (TMS) protocol to elicit iMEPs in wrist extensor and flexor muscles during four different bimanual movements (cooperative-asymmetric, cooperative-symmetric, non-cooperative-asymmetric and non-cooperative-symmetric) in 16 participants. Nine participants showed an iMEP in the wrist extensor in at least 20% of the trials in each of the conditions and were classified as iMEP+ participants. iMEP persistence was greater for cooperative (50.5 ± 28.8%) compared to non-cooperative (31.6 ± 22.1%) tasks but did not differ between asymmetric and symmetric tasks. Area and amplitude of iMEPs were also increased during cooperative (area = 5.41 ± 3.4 mV × ms; amplitude = 1.60 ± 1.09 mV) compared to non-cooperative (area = 3.89 ± 2.0 mV × ms; amplitude = 1.12 ± 0.56 mV) tasks and unaffected by task-symmetry. The upregulation of iMEPs during common-goal cooperative tasks shows a functional relevance of ipsilateral motor control in bimanual movements. The paired-pulse TMS protocol is a reliable method to elicit iMEPs in healthy participants and can give new information about neural control of upper limb movements. With this work we contribute to the research field in two main aspects. First, we describe a reliable method to elicit ipsilateral motor evoked potentials in healthy participants which will be useful in further advancing research in the area of upper limb movements. Second, we add new insight into the motor control of bimanual movements. We were able to show an upregulation of bilateral control represented by increased ipsilateral motor evoked potentials in cooperative, object-oriented movements compared to separate bimanual tasks. This result might also have an impact on neurorehabilitation after stroke.

Indications and Outcomes of a Tibial Turn-up Procedure: A Case Series and Review of the Literature

Background: Treatment options for distal femoral bone loss resulting from malignancy, infection, or trauma can be grouped into limb salvage techniques versus amputation. A vascularized osteomyocutaneous flap using the ipsilateral tibia—a tibial turn-up procedure—can be used to restore femoral length for high above-knee amputations in both the primary and revision setting. We report 3 patients treated with this procedure. Purpose: To describe the treatment algorithm and functional outcomes of patients who have undergone a tibial turn-up procedure and to highlight its viability when considering surgical options for the treatment of distal femoral primary bone and soft tissue malignancy and in cases of severe trauma, infection, or implant failure. Patients and Methods: Three patients ages 21 to 56 years old treated with tibial turn-up as a salvage procedure for failed limb sparing techniques were followed for 1.5 to 3.5 years postoperatively. One was treated for recalcitrant chronic distal femur osteomyelitis, 1 for aseptic loosening of distal femoral replacement, and 1 for infected distal femoral replacement. Radiographic and functional outcomes including prosthetic use, ambulatory status, and current activity level were reported. Results: At a minimum 1.5-year follow-up, all 3 patients achieved bony union and were ambulatory with prosthetics without the use of additional gait aids. Conclusions: Tibial turn-up is an effective treatment option in the setting of distal femoral bone loss and/or limb salvage complications, providing good functional outcomes with a single durable surgery.

Workshop (Clinical/Best Practice Implementation) ID 1983439

Objective Participants of this workshop will be able to identify and recommend multimodal treatment options in managing challenging cases in spasticity management of lower limbs in spinal cord injury (SCI). Methods The complexities of spasticity management will be identified through case-based presentations, including assessment and treatment directed by patient-oriented goals. Facilitated interactive discussion on these cases will engage participants for input, debate and critique. Procedural techniques for neurolysis will be discussed. Results Goals of spasticity management in SCI often include both proximal and distal lower limb problems. Therapies include oral medications, chemodenervation with neuromuscular junction blockade with botulinum toxin or neurolysis with phenol, intrathecal baclofen, bracing, and surgery. Many patients require multiple of these therapeutic options during their course of spasticity management. Discussion Multimodal therapy as part of the clinician toolbox is essential in tone management. Patient-oriented goals are important guideposts in spasticity management. SCI is a lifespan condition, and often patient goals and health conditions change over the years, requiring different tools to address such longitudinal needs.

46. THORACOSCOPIC REPAIR OF IATROGENIC INJURY TO THE THORACIC AORTA DURING MINIMALLY INVASIVE ESOPHAGECTOMY

Abstract Description of video: Background We present the case of a 75-year-old male patient with locally advanced Siewert Type 2 gastroesophageal adenocarcinoma post neoadjuvant chemotherapy. Inadvertent through-and-through piercing of the lower thoracic aorta with the tip of an energy device just above the diaphragm was sustained during the thoracoscopic esophageal dissection phase of the three-field minimally-invasive McKeown approach. Methods The procedure proceed thoracoscopically. The lower thoracic aorta was dissected and mobilized proximally and distally, and clamped on both ends with the introduction of Debakey clamps directly through separate small incisions in the chest wall. Primary repair of both anterior and posterior defects was then performed with monofilament non-absorbable sutures. Total clamp time was 30 minutes (in 15-minute intervals). Results Post-repair, perfusion status to the distal viscera and lower limbs were verified and intact. The rest of the operation then proceeded uneventfully. A Computed Tomography scan of the thoracic aorta on postoperative day 14 showed a patent thoracic aorta with no intraluminal narrowing or thrombosis. Conclusion Thoracoscopic repair of aortic injury sustained during the thoracoscopic dissection phase of a minimally invasive esophagectomy can be performed safely in well-selected, haemodynamically stable patients. Drpbox link to video: https://www.dropbox.com/s/xbwt6ge23iywr3m/aorta3mus1.mp4?dl&amp;#x003D;0.