Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson's disease in an Egyptian cohort.

Introduction: Parkinson's disease (PD) is the most common motor neurodegenerative disease worldwide. Given the complexity of PD etiology and the different metabolic derangements correlated to the disease, metabolomics profiling of patients is a helpful tool to identify patho-mechanistic pathways for the disease development. Dopamine metabolism has been the target of several previous studies, of which some have reported lower phenylalanine and tyrosine levels in PD patients compared to controls. Methods: In this study, we have collected plasma from 27 PD patients, 18 reference controls, and 8 high-risk controls to perform a metabolomic study using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Results: Our findings revealed higher intensities of trans-cinnamate, a phenylalanine metabolite, in patients compared to reference controls. Thus, we hypothesize that phenylalanine metabolism has been shifted to produce trans-cinnamate via L-phenylalanine ammonia lyase (PAL), instead of producing tyrosine, a dopamine precursor, via phenylalanine hydroxylase (PAH). Discussion: Given that these metabolites are precursors to several other metabolic pathways, the intensities of many metabolites such as dopamine, norepinephrine, and 3-hydroxyanthranilic acid, which connects phenylalanine metabolism to that of tryptophan, have been altered. Consequently, and in respect to Metabolic Control Analysis (MCA) theory, the levels of tryptophan metabolites have also been altered. Some of these metabolites are tryptamine, melatonin, and nicotinamide. Thus, we assume that these alterations could contribute to the dopaminergic, adrenergic, and serotonergic neurodegeneration that happen in the disease.

Prognostic value of arterial lactate index in ST-elevation myocardial infarction treated with primary percutaneous coronary intervention: a prospective cohort study.

Aim: Limited knowledge exists on the pathophysiological cascade beyond serum lactate's association with myocardial injury. Method: Assessed the prognostic value of lactate index on periprocedural variables and its impact on 30-day major adverse cardiovascular events (MACE) in 300 prospective ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). Results: Significant correlations were observed between admission lactate and Killip class, periprocedural time intervals, postprocedure thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade (MBG; p < 0.01). Lactate levels correlated with diminished ST-deviation resolution, cardiac enzymes (CK-MB, troponin; p < 0.001; 0.004), and lower ejection fraction (p < 0.001). This relationship impacted 30-day MACE (p < 0.001). Conclusion: Hyperlactatemia in STEMI patients undergoing pPCI is associated with worse Killip class, unsatisfactory TIMI flow, MBG, larger infarct size and higher 30-day MACE. Serum lactate aids risk stratification in pPCI for STEMI patients.

Harnessing role of sesamol and its nanoformulations against neurodegenerative diseases.

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.

Pelvis reconstruction by proximal femur upshifting and total hip arthroplasty after radical resection of an adolescent patient pelvic Ewing's sarcoma, a case report, and literature review.

INTRODUCTION AND IMPORTANCE: Pelvis reconstruction after tumor resection poses a challenge, especially in younger patients where preserving the patient's function and mobility is paramount. CASE PRESENTATION: A 16 years old female presented in March 2019 with vague right iliac area pain, diagnosed as pelvic Ewing's sarcoma after imaging studies (MRI and MSCT scan) and obtaining an incisional biopsy. After initial chemotherapy cycles, the tumor decreased in size, and surgical intervention in two stages was performed. The first stage was in October 2019 and consisted of pelvic resection type I and II according to Enneking and Dunham classification, proximal femur upshifting to compensate for the pelvic bone defect, and a cement spacer to fill the space of the resected proximal femur. The second stage was performed after two months and consisted of implanting a total hip arthroplasty using Megaprostheses and a cementless dual mobility acetabular cup. No local recurrence or distant metastases were detected during follow-ups. At the final follow up after 36 months, the patient showed acceptable functional outcomes (HHS score 83, and MSTS score 23 (76.7 %) points), and the radiographs showed proper implant positioning and stability. CLINICAL DISCUSSION: Treating pelvic Ewing's sarcoma requires a multidisciplinary team. After surgical resection, the pelvic reconstruction options include using allografts or autografts, femur upshifting, and hemipelvis prostheses, which should be chosen considering patients and tumor characteristics as well as surgical team efficiency. CONCLUSION: Reconstructing the pelvic defect after bone tumor resection by proximal femoral upshifting is a valid biological option with acceptable outcomes.

Interactions between Humans and Dogs during the COVID-19 Pandemic: Recent Updates and Future Perspectives.

COVID-19 is one of the deadliest epidemics. This pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the role of dogs in spreading the disease in human society is poorly understood. This review sheds light on the limited susceptibility of dogs to COVID-19 infections which is likely attributed to the relatively low levels of angiotensin-converting enzyme 2 (ACE2) in the respiratory tract and the phylogenetic distance of ACE2 in dogs from the human ACE2 receptor. The low levels of ACE2 affect the binding affinity between spike and ACE2 proteins resulting in it being uncommon for dogs to spread the disease. To demonstrate the role of dogs in spreading COVID-19, we reviewed the epidemiological studies and prevalence of SARS-CoV-2 in dogs. Additionally, we discussed the use of detection dogs as a rapid and reliable method for effectively discriminating between SARS-CoV-2 infected and non-infected individuals using different types of samples (secretions, saliva, and sweat). We considered the available information on COVID-19 in the human-dog interfaces involving the possibility of transmission of COVID-19 to dogs by infected individuals and vice versa, the human-dog behavior changes, and the importance of preventive measures because the risk of transmission by domestic dogs remains a concern.

Epigenetics and the role of nutraceuticals in health and disease.

In the post-genomic era, the data provided by complete genome sequencing could not answer several fundamental questions about the causes of many noninfectious diseases, diagnostic biomarkers, and novel therapeutic approaches. The rapidly expanding understanding of epigenetic mechanisms, as well as widespread acceptance of their hypothesized role in disease induction, facilitated the development of a number of novel diagnostic markers and therapeutic concepts. Epigenetic aberrations are reversible in nature, which enables the treatment of serious incurable diseases. Therefore, the interest in epigenetic modulatory effects has increased over the last decade, so about 60,000 publications discussing the expression of epigenetics could be detected in the PubMed database. Out of these, 58,442 were published alone in the last 10 years, including 17,672 reviews (69 historical articles), 314 clinical trials, 202 case reports, 197 meta-analyses, 156 letters to the editor, 108 randomized controlled trials, 87 observation studies, 40 book chapters, 22 published lectures, and 2 clinical trial protocols. The remaining publications are either miscellaneous or a mixture of the previously mentioned items. According to the species and gender, the publications included 44,589 human studies (17,106 females, 14,509 males, and the gender is not mentioned in the remaining papers) and 30,253 animal studies. In the present work, the role of epigenetic modulations in health and disease and the influencing factors in epigenetics are discussed.

Future regenerative medicine developments and their therapeutic applications.

Although the currently available pharmacological assays can cure most pathological disorders, they have limited therapeutic value in relieving certain disorders like myocardial infarct, peripheral vascular disease, amputated limbs, or organ failure (e.g. renal failure). Pilot studies to overcome such problems using regenerative medicine (RM) delivered promising data. Comprehensive investigations of RM in zebrafish or reptilians are necessary for better understanding. However, the precise mechanisms remain poorly understood despite the tremendous amount of data obtained using the zebrafish model investigating the exact mechanisms behind their regenerative capability. Indeed, understanding such mechanisms and their application to humans can save millions of lives from dying due to potentially life-threatening events. Recent studies have launched a revolution in replacing damaged human organs via different approaches in the last few decades. The newly established branch of medicine (known as Regenerative Medicine aims to enhance natural repair mechanisms. This can be done through the application of several advanced broad-spectrum technologies such as organ transplantation, tissue engineering, and application of Scaffolds technology (support vascularization using an extracellular matrix), stem cell therapy, miRNA treatment, development of 3D mini-organs (organoids), and the construction of artificial tissues using nanomedicine and 3D bio-printers. Moreover, in the next few decades, revolutionary approaches in regenerative medicine will be applied based on artificial intelligence and wireless data exchange, soft intelligence biomaterials, nanorobotics, and even living robotics capable of self-repair. The present work presents a comprehensive overview that summarizes the new and future advances in the field of RM.

Long-Term Results of Microsurgical Brachial Plexus Reconstruction in Late-Presenting Cases of Brachial Plexus Birth Injury.

PURPOSE: The role of primary surgery in delayed presenting cases of brachial plexus birth injury is still debated. The purpose of this study was to evaluate the results of brachial plexus reconstruction performed at the age of ≥12 months. METHODS: Twenty-nine cases were included. Five cases had upper (C5-6) palsy, 4 had upper/middle (C5-7), and 20 had total (C5-8 and T1) palsy. RESULTS: The age at the time of primary surgery was an average of 15.6 months. The brachial plexus was formally explored and neurolysis, grafting, and neurotization were used in different combinations. Exploration revealed that 27% of the roots were avulsed and 32% were ruptured. The follow-up was an average of 7.9 years. Generally, the best functional recovery was elbow flexion followed by shoulder external rotation. Satisfactory shoulder abduction (≥6 on the Toronto Active Movement Scale [TAMS]) was achieved in 31% of cases. The abduction range was an average of 79° ± 35°; 50° in upper palsy, 103° in upper/middle palsy, and 82° in total palsy. Shoulder external rotation ≥6 on the TAMS was achieved in 62% of cases. External rotation range was an average of 58° ± 29°; 78° in upper palsy, 68° in upper/middle palsy, and 52° in total palsy. Elbow flexion and extension of ≥6 on the TAMS were achieved in 69% and 58% of cases, respectively. Wrist flexion and finger flexion of ≥6 on the TAMS were achieved in 35% and 12.5%, whereas wrist and finger extension of >6 on the TAMS were achieved in 25% and 4% of cases, respectively. CONCLUSION: In the delayed presentation of brachial plexus birth injury, brachial plexus reconstruction results in good functional recovery of elbow flexion and shoulder external rotation but modest functional recovery of finger flexion and wrist extension. The rate of functional recovery of the elbow flexion was similar following nerve grafting and transfer. Nerve transfer for shoulder external rotation should be considered even in infants with available roots for grafting. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Selective IgA Deficiency a Probable Risk of Recurrent Chest Infections in Asthmatics.

BACKGROUND: Selective immunoglobulin A (IgA) deficiency is characterized by a high incidence of both recurrent infections and atopic diseases. Asthma is one of the most common lung diseases affecting around 300 million people worldwide and is associated with risk of serious pneumococcal disease and microbial infections. Multiple studies have attributed this to impaired innate and adaptive immunity in asthmatics. An additional probable hypothesis is the existence of an underlying primary immunodeficiency (PID), such as selective IgA deficiency (sIgAD). AIM: To assess the prevalence of selective IgA deficiency and its correlation to recurrent infections in asthmatic patients. METHODS: A case-control study was conducted on 80 subjects who were divided into 3 groups: 20 Asthmatic patients with recurrent chest infections (Group A), 20 asthmatic patients without recurrent chest infections (Group B) and 40 healthy controls (Group C). RESULTS: On comparing the 3 studied groups, there was a statistically significant difference between the three groups (p = ˂0.001) concerning serum IgA. The mean serum IgA was statistically significantly lower in Group A&B than in Group C. Furthermore, it was significantly lower in Group A than in Group B and C (p1,2 <0.002 and <0.001*, respectively). The percentage of selective IgA deficiency or partial IgA deficiency in asthmatic patients was 56% (26 patients). Group A showed a statistically significant higher percentage of selective/partial IgA deficiency.

Association of interleukin-2, interleukin-21 and interleukin-23 with hyperlipidemia in pediatric type 1 diabetes.

BACKGROUND: In type 1 diabetes mellitus (T1DM), cytokines have a central role in orchestrating multicellular relations between ß-cells and immune cells. This study aims to investigate the role of interleukin (IL)-21, IL-23, and IL-2, and their association with dyslipidemia in T1DM children. METHODS: The sample population consisted of 30 healthy controls and 70 children with T1DM, the latter of which were split into two groups according to the duration of their T1DM diagnosis: recent (≤ 1 year; n = 21) and older (> 1 year; n = 49) diagnoses. RESULTS: Fasting blood sugar and glycated hemoglobin levels in all diabetic children were significantly (P < 0.001) higher, whereas levels of plasma C-peptide were markedly (P < 0.001) lower in children with T1DM compared to healthy controls. In older T1DM diagnosis children, the levels of creatinine were noticeably (P < 0.05) increased relative to healthy controls. In all diabetic children, levels of total triglyceride, cholesterol, and low-density lipoprotein were increased significantly (P < 0.001) than those of healthy controls. Furthermore, the IL-21 and IL-23 mRNA expressions of all children with T1DM were elevated significantly (P < 0.001) relative to healthy controls, whereas IL-2 levels revealed a significant (P < 0.001) decrease in all diabetic children. CONCLUSION: There was a synergistic interplay between IL-21 and IL-23 with an antagonistic action of IL-2 in T1DM patients, and all three interleukins were associated with dyslipidemia in diabetic children. Importantly, therapies targeting IL-21 and IL-23 are promising targets for preventive strategies against the development of T1DM and its complications.

Microbiota and epigenetics: promising therapeutic approaches?

The direct/indirect responsibility of the gut microbiome in disease induction in and outside the digestive tract is well studied. These results are usually from the overpopulation of certain species on the cost of others, interaction with beneficial microflora, interference with normal epigenetic control mechanisms, or suppression of the immune system. Consequently, it is theoretically possible to cure such disorders by rebalancing the microbiome inside our bodies. This can be achieved by changing the lifestyle pattern and diet or by supplementation with beneficial bacteria or their metabolites. Various approaches have been explored to manipulate the normal microbial inhabitants, including nutraceutical, supplementations with prebiotics, probiotics, postbiotics, synbiotics, and antibiotics, or through microbiome transplantation (fecal, skin, or vaginal microbiome transplantation). In the present review, the interaction between the microbiome and epigenetics and their role in disease induction is discussed. Possible future therapeutic approaches via the reestablishment of equilibrium in our internal micro-ecosystem are also highlighted.

Microbiota's role in health and diseases.

The microbiome is a term that usually refers to the community of various microorganisms that inhabit/live inside human/animal bodies or on their skin. It forms a complex ecosystem that includes trillions of commensals, symbiotics, and even pathogenic microorganisms. The external environment, diet, and lifestyle are the major determinants influencing the microbiome's composition and vitality. Recent studies have indicated the tremendous influence of the microbiome on health and disease. Their number, constitution, variation, and viability are dynamic. All these elements are responsible for the induction, development, and treatment of many health disorders. Serious diseases such as cancer, metabolic disorders, cardiovascular diseases, and even psychological disorders such as schizophrenia are influenced directly or indirectly by microbiota. In addition, in the last few weeks, accumulating data about the link between COVID-19 and the microbiota were published. In the present work, the role of the microbiome in health and disease is discussed. A deep understanding of the exact role of microbiota in disease induction enables the prevention of diseases and the development of new therapeutic concepts for most diseases through the correction of diet and lifestyle. The present review brings together evidence from the most recent works and discusses suggested nutraceutical approaches for the management of COVID-19 pandemic.

The link among microbiota, epigenetics, and disease development.

The microbiome is a community of various microorganisms that inhabit or live on the skin of humans/animals, sharing the body space with their hosts. It is a sort of complex ecosystem of trillions of commensals, symbiotic, and pathogenic microorganisms, including trillions of bacteria, archaea, protozoa, fungi, and viruses. The microbiota plays a role in the health and disease status of the host. Their number, species dominance, and viability are dynamic. Their long-term disturbance is usually accompanied by serious diseases such as metabolic disorders, cardiovascular diseases, or even cancer. While epigenetics is a term that refers to different stimuli that induce modifications in gene expression patterns without structural changes in the inherited DNA sequence, these changes can be reversible or even persist for several generations. Epigenetics can be described as cell memory that stores experience against internal and external factors. Results from multiple institutions have contributed to the role and close interaction of both microbiota and epigenetics in disease induction. Understanding the mechanisms of both players enables a better understanding of disease induction and development and also opens the horizon to revolutionary therapeutic approaches. The present review illustrates the roles of diet, microbiome, and epigenetics in the induction of several chronic diseases. In addition, it discusses the application of epigenetic data to develop diagnostic biomarkers and therapeutics and evaluate their safety for patients. Understanding the interaction among all these elements enables the development of innovative preventive/therapeutic approaches for disease control.

Traumatic Brachial Plexus Palsy in Children: Long-Term Outcome and Strategy of Reconstruction.

BACKGROUND: Traumatic brachial plexus injuries in children represent a definite spectrum of injuries between adult and neonatal brachial plexus injuries. Their characteristics have been scarcely reported in the literature. The priority of functional restoration is not clear. METHODS: In total, 52 children with surgically treated traumatic brachial plexus injuries, excluding Erb's palsy, were reviewed after a minimum follow-up of 2 years. All children except nine were males, with an average age at surgery of 8 years. Forty-five children had exclusive supraclavicular plexus injuries. Twenty-one of them (46%) had two or more root avulsions. Seven children (13.5%) had infraclavicular plexus injuries. Time from trauma to surgery varied from 1 to 15 months (mean = 4.7 months). Extraplexal neurotization was the most common surgical technique used. RESULTS: Shoulder abduction and external rotation were restored to an average of 83 and 26 degrees, respectively. Elbow flexion and extension were restored to grade ≥3 in 96 and 91.5% of cases, respectively. Finger flexion and extension were restored to grade ≥4 in 29 and 32% of cases, respectively. Wrist flexion and extension were restored to grade ≥4 in 21 and 27% of cases, respectively. Results of neurotization were superior to those of neurolysis and nerve grafting. Among the 24 children with insensate hands, 20 (83.3%) recovered S3 sensation, 3 recovered S2, and 1 recovered S1. No case complained of neuropathic pain. Functional recovery correlated negatively but insignificantly with the age at surgery and time from injury to surgery. CONCLUSION: Brachial plexus injuries in children are associated with a high incidence root avulsions and no pain. Neurotization is frequently required and the outcome is not significantly affected by the delay in surgery. In total plexus injuries, some useful hand function can be restored, and management should follow that of obstetric palsy and be focused on innervating the medial cord.

Coronaviruses in humans and animals: the role of bats in viral evolution.

Bats act as a natural reservoir for many viruses, including coronaviruses, and have played a crucial epidemiological role in the emergence of many viral diseases. Coronaviruses have been known for 60 years. They are usually responsible for the induction of mild respiratory signs in humans. However, since 2002, the bat-borne virus started to induce fatal epidemics according to WHO reports. In this year, the first serious human coronavirus epidemic (severe acute respiratory syndrome; SARS) occurred (China, 8098 cases, 774 deaths [9.5% of the cases] in 17 countries). The case fatality was higher in elderly patients above 60 years and reached 50% of the cases. SARS epidemic was followed 10 years later by the emergence of the middle east respiratory syndrome (MERS) in Saudi Arabia (in 2012, 2260 cases, 803 deaths [35.5% of the cases] in 27 countries). Finally, in December 2019, a new epidemic in Wuhan, China, (corona virus disease 2019, COVID-19) emerged and could spread to 217 countries infecting more than 86,255,226 cases and killing 1,863,973 people by the end of 2020. There are many reasons why bats are ideal reservoir hosts for viral diseases such as the tolerance of their immune system to the invading viruses for several months. They can actively shed the viruses, although they develop no clinical signs (will be discussed in details later in the review). Bats were directly or indirectly involved in the three previous coronavirus epidemics. The indirect transmission takes place via intermediate hosts including civet cats for SARS and dromedary camels in the case of MERS. Although bats are believed to be the source of COVID-19 pandemic, direct pieces of evidence are still lacking. Therefore, coronaviruses' role in epidemics induction and the epidemiological role of bats are discussed. The current work also presents different evidence (phylogenetic data, animal experiments, bats artificial infection studies, and computerized models of SARS-CoV2 evolution) that underline the involvement of bats in the epidemiology of the pandemic.

Bovine mastitis prevention and control in the post-antibiotic era.

Mastitis is the most important disease in the dairy industry. Antibiotics are considered to be the first choice in the treatment of the disease. However, the problem of antibiotic residue and antimicrobial resistance, in addition to the impact of antibiotic abuse on public health, leads to many restrictions on uncontrolled antibiotic therapy in the dairy sector worldwide. Researchers have investigated novel therapeutic approaches to replace the use of antibiotics in mastitis control. These efforts, supported by the revolutionary development of nanotechnology, stem cell assays, molecular biological tools, and genomics, enabled the development of new approaches for mastitis-treatment and control. The present review discusses recent concepts to control mastitis such as breeding of mastitis-resistant dairy cows, the development of novel diagnostic and therapeutic tools, the application of communication technology as an educational and epidemiological tool, application of modern mastitis vaccines, cow drying protocols, teat disinfection, housing, and nutrition. These include the application of nanotechnology, stem cell technology, photodynamic and laser therapy or the use of traditional herbal medical plants, nutraceuticals, antibacterial peptides, bacteriocins, antibodies therapy, bacteriophages, phage lysins, and probiotics as alternatives to antibiotics.

COVID-19: a new emerging respiratory disease from the neurological perspective.

Coronavirus disease 2019 (COVID-19) has become a challenging public health catastrophe worldwide. The newly emerged disease spread in almost all countries and infected 100 million persons worldwide. The infection is not limited to the respiratory system but involves various body systems and may lead to multiple organ failure. Tissue degenerative changes result from direct viral invasion, indirect consequences, or through an uncontrolled immune response. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads to the brain via hematogenous and neural routes accompanied with dysfunction of the blood-brain barrier. The involvement of the central nervous system is now suspected to be among the main causes of death. The present review discusses the historical background of coronaviruses, their role in previous and ongoing pandemics, the way they escape the immune system, why they are able to spread despite all undertaken measures, in addition to the neurological manifestations, long-term consequences of the disease, and various routes of viral introduction to the CNS.

Crawford Type IV Congenital Pseudarthrosis of the Tibia: Treatment With Vascularized Fibular Grafting and Outcome at Skeletal Maturity.

BACKGROUND: Vascularized fibular grafting (VFG) is currently accepted as one of the best treatments for congenital tibial pseudoarthrosis (CPT). However, with longer follow-up, functional results deteriorate, and some problems become evident. METHODS: Thirty-nine patients with CPT were treated with VFG. Their age at surgery averaged 5.2 years. Twenty-one cases aged 3 years or less at the time of surgery. All cases were Crawford type IV affected by neurofibromatosis-1. Fourteen patients had 1 to 7 previous surgeries with an average of 4.2 procedures. The length of the fibula used averaged 9.9 cm, and the fibula was fixed by intramedullary wires in 26 cases, and transfixion screws in 11 cases. RESULTS: Follow-up averaged 8.1 years. Seventeen cases (43.6%) reached skeletal maturity before the final follow-up. Primary bone union was achieved in 37 cases (96%) after an average of 3.2 months. Stress fracture occurred in 21 cases (51.3%) and was recurrent in 11 cases. Twenty-one cases (53.8%) developed tibial shaft deformities with an average valgus angle of 13.8 degrees and procurvatum angle of 18.8 degrees. The overall final limb length discrepancy (LLD) averaged 2.2 cm. Ipsilateral ankle valgus deformity occurred in 21 cases (53.8%) and averaged 10 degrees. A total of 17 cases required an average of 2 secondary procedures. The tibial deformity did not appear to remodel with age, but the LLD and the angle of ipsilateral ankle valgus deformity continued to significantly increase until skeletal maturity. CONCLUSION: This study reports the largest single center experience of CPT cases treated with VFG. Free VFG is an excellent treatment option for CPT. Best results are achieved when the procedure is performed at or before the age of 3 years, in the absence of previous surgeries, and with the use of intramedullary fixation. The resulting LLD and the degree of ipsilateral ankle valgus increase with age until skeletal maturity, however, tibial deformity does not remodel and should be corrected at any age if it is excessive. Donor side mild ankle valgus may occur despite sound tibiofibular synostosis. LEVEL OF EVIDENCE: Level IV.