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Background:. Congenital vertical talus (CVT) and congenital oblique talus (COT) are rocker-bottom foot deformities that have similar names and no objective definitions. This has led to confusion for practitioners, as well as scientific challenges for researchers. Our goal was to provide objective radiographic criteria to define and differentiate CVT and COT. Methods:. We evaluated 62 pairs of maximum dorsiflexion and plantar flexion lateral radiographs of infant feet that had been clinically diagnosed with CVT. The dorsiflexion tibiotalar angle, the plantar flexion talus-first metatarsal angle, and the plantar flexion foot center of rotation of angulation (foot-CORA) were measured using transparent overlay tools. Freehand measurements were made on a subset of 10 pairs of radiographs to confirm clinical applicability. Nine contralateral pairs of radiographs of normal feet were measured for comparison. Results:. Specific values for the radiographic measurements were identified that, together, reliably differentiated the shapes of rocker-bottom feet with CVT, COT, and flexible flatfoot with a short tendo-Achilles (FFF-STA), as well as the shape of the normal foot. More severe and rigid rocker-bottom foot deformities were diagnosed with CVT. Less severe and more flexible deformities were diagnosed with COT. Conclusions:. CVT, COT, FFF-STA, and normal feet can be reliably differentiated using 2 angular measurements and 1 bone position measurement on dorsiflexion and plantar flexion lateral radiographs. Our data indicated that the differentiation of CVT and COT is based primarily on the rigidity of the navicular dislocation rather than the verticality of the talus. The data further supported the proposition that COT is a foot deformity along a spectrum of valgus/eversion deformities of the hindfoot that requires early treatment. Application of these diagnostic criteria should lead to clinical studies that identify a specific treatment, treatment outcome, and prognosis for each deformity. Level of Evidence:. Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

MYC is a transcription factor crucial for maintaining cellular homeostasis, and its dysregulation is associated with highly aggressive cancers. Despite being considered “undruggable” due to its unstable protein structure, MYC gains stability through its interaction with its partner protein, MAX. The MYC-MAX heterodimer orchestrates the expression of numerous genes that contribute to an oncogenic phenotype. Previous efforts to develop small molecules, disrupting the MYC-MAX interaction, have shown promise in vitro but none have gained clinical approval. Our current computer-aided study utilizes an approach to explore drug repurposing as a strategy for inhibiting the c-MYC-MAX interaction. We have focused on compounds from DrugBank library, including Food and Drug Administration-approved drugs or those under investigation for other medical conditions. First, we identified a potential druggable site on flat interface of the c-MYC protein, which served as the target for virtual screening. Using both activity-based and structure-based screening, we comprehensively assessed the entire DrugBank library. Structure-based virtual screening was performed on AutoDock Vina and Glide docking tools, while activity-based screening was performed on two independent quantitative structure-activity relationship models. We focused on the top 2% of hit molecules from all screening methods. Ultimately, we selected consensus molecules from these screenings—those that exhibited both a stable interaction with c-MYC and superior inhibitory activity against c-MYC-MAX interaction. Among the evaluated molecules, we identified a protein kinase inhibitor (tyrosine kinase inhibitor [TKI]) known as nilotinib as a promising candidate targeting c-MYC-MAX dimer. Molecular dynamic simulations demonstrated a stable interaction between MYC and nilotinib. The interaction with nilotinib led to the stabilization of a region of the MYC protein that is distorted in apo-MYC and is important for MAX binding. Further analysis of differentially expressed gene revealed that nilotinib, uniquely among the tested TKIs, induced a gene expression program in which half of the genes were known to be responsive to c-MYC. Our findings provide the foundation for subsequent in vitro and in vivo investigations aimed at evaluating the efficacy of nilotinib in managing MYC oncogenic activity.

Background IDH1 mutations are common in many cancers, however, their role in promoting the Warburg effect remains elusive. This study elucidates the putative involvement of mutant-IDH1 in regulating hypoxia-inducible factor (HIF1-α) and Sine-Oculis Homeobox-1 (SIX-1) expression. Methodology Genetic screening was performed using the ARMS-PCR in acute myeloid leukemia (AML), brain, and breast cancer (BC) cohorts, while transcript expression was determined using qPCR. Further, a meta-analysis of risk factors associated with the R132 mutation was performed. Results Approximately 32% of AML and ∼60% of glioma cases were mutants, while no mutation was found in the BC cohort. ‘AA’ and TT’ were associated with higher disease risk (OR = 12.18 & 4.68) in AML and had significantly upregulated IDH1 expression. Moreover, downregulated HIF1-α and upregulated SIX-1 expression was also observed in these patients, suggesting that mutant-IDH1 may alter glucose metabolism. Perturbed IDH1 and HIF-α levels exhibited poor prognosis in univariate and multivariate analysis, while age and gender were found to be contributory factors as well. Based on the ROC model, these had a good potential to be used as prognostic markers. A significant variation in frequencies of R132 mutations in AML among different populations was observed. Cytogenesis ( R 2 = 12.2%), NMP1 mutation status ( R 2 = 18.5%), and ethnic contributions ( R 2 = 73.21%) were critical moderators underlying these mutations. Women had a higher risk of R132 mutation (HR = 1.3, P < 0.04). The pooled prevalence was calculated to be 0.29 (95% CI 0.26-0.33, P < 0.01), indicating that IDH1 mutations are a significant prognostic factor in AML. Conclusion IDH1 and HIF1-α profiles are linked to poor survival and prognosis, while high SIX-1 expression in IDH1 mutants suggests a role in leukemic transformation and therapy response in AML.

ABSTRACT: Hip Arthroscopy in the pediatric and adolescent hip has evolved from its role as a diagnostic tool to a primary modality of management of variety of hip pathologies in children and adolescents. This article reviews current concepts and advances in hip arthroscopy in this population. We discuss the indications, techniques, outcomes, and complications of hip arthroscopy in children and adolescents. We explore the newer indications of hip arthroscopy in the treatment of SCFE (Slipped Capital Femoral Epiphysis) deformity correction, borderline hip dysplasia, septic arthritis, infantile developmental dysplasia, Perthes disease, and the existing and developing evidence. Finally, we address the challenges and future directions in research, education, and training, unique to the pediatric and adolescent population. Key Concepts: (1) Hip arthroscopy has significant surgical applications in the pediatric and adolescent population, and can be used to help address several intra-articular as well as extra-articular pathologies. (2) The indications and potential for arthroscopic interventions and associated arthroscopic techniques is growing and developing rapidly, along with improving technology, techniques, and training. (3) FAI (Femoro Acetabular Impingement) and labral pathology are the most common indications for surgery in the adolescent, and clinical outcome studies show excellent results. However, nonoperative optimization should be strongly emphasized before surgical consideration. (4) Hip arthroscopy is minimally invasive and relatively low risk, though main risks and complications to be aware of is the potential need for revision or further surgery, transient neuropraxia of the pudendal nerve, surgical site infection, implant/tool-related breakage or failure, failed surgery, and venous thromboembolism. (5) Continued research and innovation in the field of pediatric hip arthroscopy are essential for further improving outcomes and expanding treatment options for young patients with hip disorders, and more pediatric-specific clinical research is needed.

Objective: To characterize the development and performance of a cataract surgery episode-based cost measure for the Medicare Quality Payment Program. Design: Claims-based analysis. Participants: Medicare clinicians with cataract surgery claims between June 1, 2016, and May 31, 2017. Methods: We limited the analysis to claims with procedure code 66984 (routine cataract surgery), excluding cases with relevant ocular comorbidities. We divided episodes into subgroups by surgery location (Ambulatory Surgery Center [ASC] or Hospital Outpatient Department [HOPD]) and laterality (bilateral when surgeries were within 30 days apart). For the episode-based cost measure, we calculated costs occurring between 60 days before surgery and 90 days after surgery, limited to services identified by an expert committee as related to cataract surgery and under the influence of the cataract surgeon. We attributed costs to the clinician submitting the cataract surgery claim, categorized costs into clinical themes, and calculated episode cost distribution, reliability in detecting clinician-dependent cost variation, and costs with versus without complications. We compared episode-based cost scores with hypothetical “nonselective” cost scores (total Medicare beneficiary costs between 60 days before surgery and 90 days after surgery). Main Outcome Measures: Episode costs with and without complications, clinician-dependent variation (proportion of total cost variance), and proportion of costs from cataract surgery-related clinical themes. Results: We identified 583 356 cataract surgery episodes attributed to 10 790 clinicians and 8189 with ≥ 10 episodes during the measurement period. Most surgeries were performed in an ASC (71%) and unilateral (66%). The mean episode cost was $2876. The HOPD surgeries had higher costs; geography and episodes per clinician did not substantially affect costs. The proportion of cost variation from clinician-dependent factors was higher in episode-based compared with nonselective cost measures (94% vs. 39%), and cataract surgery-related clinical themes represented a higher proportion of total costs for episode-based measures. Episodes with complications had higher costs than episodes without complications ($3738 vs. $2276). Conclusions: The cataract surgery episode-based cost measure performs better than a comparable nonselective measure based on cost distribution, clinician-dependent variance, association with cataract surgery-related clinical themes, and quality alignment (higher costs in episodes with complications). Cost measure maintenance and refinement will be important to maintain clinical validity and reliability. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background: Although the classic open Latarjet has a low recurrence rate in unstable shoulders, this advantage may be offset by the higher number of complications. We aimed to report the safety-driven nuanced steps and the resulting short-term complications of the Latarjet-Walch technique. Methods: Between 2016 and 2022, 150 patients who underwent the Latarjet procedure following the key safety-driven technical steps were retrospectively evaluated for intraoperative and short-term (3 months) complications. The complications were divided into 3 types: Any adverse event that did not need a change in the treatment protocol was a type 1 complication. An event that resulted in a prolongation of rehabilitation protocol or an additional medical line of treatment was classified as type 2, and an event that resulted in readmission, a resurgery, or one that affected the outcome was classified as a type 3 complication. Results: There were 12 (8%) short-term complications in 9 patients. Neurological complications were noted in 3 (2%) patients (1 axillary nerve injury, 1 suprascapular nerve injury, and 1 musculocutaneous nerve injury). Type 1 complications were noted in 2 patients: 2 patients had hematoma that was detected as superficial swelling, but no surgical drainage was needed, and both resolved at their 1-month follow-up. Type 2 complications were noted in 4 patients. One patient had surgical site infection and a second patient had superficial wound dehiscence in the lower part of the wound. The third patient had suprascapular nerve paresis and the fourth had musculocutaneous nerve paresis and shoulder stiffness. Both nerve injuries recovered completely after 6 months of rehabilitation. Type 3 complications were noted in 3 patients. One patient had axillary nerve paresis and shoulder stiffness. The axillary nerve palsy had recovered partially by 8 months. One patient had an intraoperative graft fracture and postoperative shoulder stiffness, and the third patient had shoulder stiffness. Conclusion: Following the safety-driven nuanced steps in the Latarjet-Walch procedure, the short-term complication rate was 8%, and the neurological complication was 2% (n = 3). The musculocutaneous and suprascapular nerves completely recovered, and the axillary nerve had partially recovered.

Background. Kidneys from potential deceased donors with brain cancer are often foregone due to concerns of cancer transmission risk to recipients. There may be uncertainty around donors’ medical history and their absolute transmission risk or risk-averse decision-making among clinicians. However, brain cancer transmissions are rare, and prolonging waiting time for recipients is harmful. Methods. We assessed the cost-effectiveness of increasing utilization of potential deceased donors with brain cancer using a Markov model simulation of 1500 patients waitlisted for a kidney transplant, based on linked transplant registry data and with a payer perspective (Australian government). We estimated costs and quality-adjusted life-years (QALYs) for three interventions: decision support for clinicians in assessing donor risk, improved cancer classification accuracy with real-time data-linkage to hospital records and cancer registries, and increased risk tolerance to allow intermediate-risk donors (up to 6.4% potential transmission risk). Results. Compared with current practice, decision support provided 0.3% more donors with an average transmission risk of 2%. Real-time data-linkage provided 0.6% more donors (1.1% average transmission risk) and increasing risk tolerance (accepting intermediate-risk 6.4%) provided 2.1% more donors (4.9% average transmission risk). Interventions were dominant (improved QALYs and saved costs) in 78%, 80%, and 87% of simulations, respectively. The largest benefit was from increasing risk tolerance (mean +18.6 QALYs and AU$2.2 million [US$1.6 million] cost-savings). Conclusions. Despite the additional risk of cancer transmission, accepting intermediate-risk donors with brain cancer is likely to increase the number of donor kidneys available for transplant, improve patient outcomes, and reduce overall healthcare expenditure.

Spontaneous spinal epidural hematoma is a rare predominantly idiopathic entity which can prompt acute neurologic symptoms and if not managed in time can lead to devastating outcomes. High index of suspicion is required for early diagnosis on MRI for a prompt management of patients showing sudden neurologic deficits. Our patient was 42-year-old female who presented with sudden onset of numbness followed by weakness in both lower limbs and urinary retention without any comorbidity or any medication. MRI whole spine done within 14 hours of symptom onset showed ventral epidural hematoma without any vascular malformation. Immediate decompressive laminectomy with evacuation of hematoma improved power in both lower limbs with regaining bowel and bladder function. The key here is timely surgical decompression of the hematoma for a favorable neurosurgical outcome. Although there is a recent development towards non–surgical treatment, it needs to be well established yet and require such approach on case-to-case basis.

Background:. Collagen nerve wraps (CNWs) theoretically allow for improved nerve gliding and decreased perineural scarring, and create a secluded environment to allow for nerve myelination and axonal healing. The goal of this study was to investigate the effect of CNWs on nerve gliding as assessed by pull-out strength and nerve changes in a rabbit model of peripheral neuropathy. Methods:. Ten New Zealand rabbits were included. Sham surgery (control) was performed on left hindlimbs. To simulate compressive neuropathy, right sciatic nerves were freed of the mesoneurium, and the epineurium was sutured to the wound bed. Five rabbits were euthanized at 6 weeks [scarred nerve (SN); n = 5]. Neurolysis with CNW was performed in the remaining rabbits at 6 weeks (CNW; n = 5), which were euthanized at 22 weeks. Outcomes included peak pull-out force and histopathological markers of nerve recovery (axonal and Schwann cell counts). Results:. The CNW group demonstrated significantly higher pull-out forces compared with the CNW sham control group (median: 4.40N versus 0.37N, P = 0.043) and a trend toward greater peak pull-out forces compared with the SN group (median: 4.40N versus 2.01N, P = 0.076). The CNW group had a significantly higher median Schwann cell density compared with the CNW control group (CNW: 1.30 × 10−3 cells/μm2 versus CNW control: 7.781 × 10−4 cells/μm2, P = 0.0431) and SN group (CNW: 1.30 × 10−3 cells/μm2 versus SN: 7.31 × 10−4 cells/μm2, P = 0.009). No significant difference in axonal density was observed between groups. Conclusion:. Our findings suggest using a CNW does not improve nerve gliding, but may instead play a role in recruiting and/or supporting Schwann cells and their proliferation.

Background: There remains a paucity of data regarding long-term patient-reported outcomes following Lisfranc injuries. We sought to collect long-term clinical outcome data following Lisfranc injuries using PROMIS Physical Function (PROMIS-PF) and visual analog scale–foot and ankle (VAS-FA). Methods: A chart review was performed to identify all patients who had surgical treatment of an acute Lisfranc injury at our institution from 2005 to 2014. Of the 45 patients identified, we were able to recruit 19 for a follow-up clinic visit consisting of physical examination, administration of questionnaires addressing pain and medication usage, radiographs, and completion of outcome surveys including PROMIS-Physical Function and visual analog scale–foot and ankle. Results: There were 14 female and 5 male patients enrolled in the study with a mean time of 6.25 years from the time of injury. Within this cohort, the mean PROMIS-PF score was 52.4±8.2 and the mean VAS–foot and ankle score was 76.6±22.3. Conclusion: We report satisfactory long-term patient-reported outcomes using PROMIS-PF and VAS-FA. Level of Evidence: Level III, retrospective cohort study.

Purpose: Postoperative radiation therapy (RT) is commonly used for World Health Organization grade II-III intracranial ependymoma. Clinicians generally aim to begin RT ≤5 weeks after surgery, but postoperative recovery and need for second look surgery can delay the initiation of adjuvant therapy. On ACNS 0831, patients were required to enroll ≤8 weeks after initial surgery and begin adjuvant therapy within 3 weeks after enrollment. The purpose of this study was to determine the optimal timing of RT after surgery. Methods and Materials: The National Cancer Database was queried for patients (aged 1-39 years) with localized World Health Organization grade II-III intracranial ependymoma treated with surgery and postoperative RT. Overall survival (OS) curves were plotted based on RT timing (≤5 weeks, 5-8 weeks, and >8 weeks after surgery) and were compared by log-rank test. Factors associated with OS were identified by multivariate analysis. After 2009, complete data were available on whether patients underwent gross total resection or subtotal resection. Planned subset analysis was performed to examine the effect of RT timing on OS in patients with known extent of resection. Results: In the final analytical data set of 1043 patients, no difference in 3-year OS was observed in patients who initiated RT ≤5 weeks, 5 to 8 weeks, and >8 weeks after surgery (89.8% vs 89.1% vs 88.4%; P = .796). On multivariate analysis, grade III tumors (hazard ratio, 2.752; 95% confidence interval, 1.969-3.846, P < .001) and subtotal resection (hazard ratio, 2.253; 95% confidence interval, 1.405-3.611, P < .001) were significantly associated with reduced OS. Timing of RT, total RT dose, age, and other factors were not significant. These findings were affirmed in the subset of patients treated between 2010 and 2016, when extent of resection was routinely recorded. Conclusions: Delayed postoperative RT was not associated with inferior survival in patients with intracranial ependymoma. Delayed RT initiation may be acceptable in patients who require longer postoperative recovery or referral to an appropriate RT center, but should be minimized whenever practical.

Category: Hindfoot Introduction/Purpose: Tibiotalocalcaneal (TTC) fusion is a salvage procedure for post-traumatic as well as neuropathic cases. Many of these cases are characterised by some or other form of loss of talus resulting in a defect. At TTC fusion, prevention of shortening following such a defect is a challenge. Though allografts have helped solve this issue, they may not be easily available in developing countries. A retrospective analysis of prospectively collected data of 14 cases of TTC fusion with loss of talus is presented here. Cases were managed with innovative defect bridging ‘Bamboo Hut’ technique. Methods: Cases with either preoperative or perioperative loss of talus who required bridging of defect were included in the present study. Resultant defect following excision of the talus was bridged with two or three vertically placed fibular strut grafts. Grafts were snugly tied with each other with sutures to prepare a construct like a hut supported with wooden steaks (Bamboo). Fixation was carried out with indigenous TTC nail with a built-in compression device to generate compression of grafts between tibia and calcaneus. Results: Present series comprised of 6 post-traumatic cases, 7 cases of diabetic Charcot neuroarthropathy and 1 case of neuroarthropathy following operated meningomyelocele. Cases were followed up for an average period of 36 months with the average time to union being six months. All posttraumatic cases went on to the bony union but two out of eight neuropathy cases ended up in fibrous union with collapse & loss of fixation. Wound healing issues were noticed in two cases. None of the cases required amputation. Conclusion: With non-availability of allografts, prevention of shortening at TTC fusion is a challenge. This issue can be successfully managed with innovative ‘Bamboo Hut’ grafting technique, supported with in-built compression of the fusion site with the use of an indigenous nail.

Category: Trauma Introduction/Purpose: Primary subtalar fusion for Sander IV calcaneus fractures was considered to be the standard of care till recent past. Presently debate is on whether to manage Sander IV calcaneus fracture cases with primary subtalar fusion or with open reduction and internal fixation. Bilateral Sander IV calcaneus fractures are seen in cases with fall from height. No study has ever been conducted till date to compare the results of primary fusion of a Sander IV calcaneus fracture on one side and open reduction and internal fixation on another side in cases with bilateral Sander IV calcaneus fractures. We present a study comparing the results of primary fusion versus open reduction and internal fixation for bilateral sander IV calcaneus fracture cases. Methods: Twelve cases with bilateral closed Sander IV calcaneus fractures where included in the present study. Cases were operated between four to six weeks by a single surgeon after the appearance of wrinkles. All right sided fractures underwent open reduction and internal fixation with proximal tibia grafting. While all left-sided fractures underwent subtalar fusion with the use of ipsilateral anterior iliac crest grafts. Cases were followed up for 24 months. Results: Though operative time was more in the fusion group wound problems were equal in both the groups. Four months of average time to union was the same in both the groups and so was time to return to work. At two years, the AOFAS score was slightly better in the fusion group but it was not statistically significant. Conclusion: Primary subtalar fusion is with almost similar results as those with open reduction and internal fixation in bilateral Sander IV at 24 months. Long term follow up with more number of cases is required to prove the benefit of one over other.