Clinical Characteristics and Whole Exome Sequencing Analysis in Serbian Cases of Clubfoot Deformity-Single Center Study.

BACKGROUND: Recognized as one of the most serious musculoskeletal deformities, occurring in 1-2 per 1000 newborns, 80% of clubfeet are idiopathic while 20% present with associated malformations. The etiopathogenesis of clubfoot is described as multifactorial, including both genetic and environmental risk factors. The aim of this study was to analyze possible genetic causes of isolated and syndromic clubfoot in Serbian children, as well as to correlate clinical and genetic characteristics that would provide insight into clubfoot etiopathogenesis and possibly contribute to global knowledge about clinical features of different genetically defined disorders. METHODS: We evaluated 50 randomly selected, eligible children with clubfoot aged 3 to 16 years that were initially hospitalized and treated at University Children's Hospital between November 2006 and November 2022. The tested parameters were gender, age, dominant foot, affected foot, degree of deformity, treatment, neuromuscular disorders, positive family history, and maternal smoking. According to the presence of defined genetic mutation/s by whole exome sequencing (WES), patients were separated into two groups: positive (with genetic mutation/s) and negative (without genetic mutation/s). RESULTS: Seven patients were found to be positive, i.e., with genetic mutation/s. A statistically significant difference between categorical variables was found for families with a history of clubfoot, where more than half (57.14%) of patients with confirmed genetic mutation/s also had a family history of genetic mutation/s (p = 0.023). CONCLUSIONS: The results from this study further expand the genetic epidemiology of clubfoot. This study contributes to the establishment of genetic diagnostic strategies in pediatric patients with this condition, which can lead to more efficient genetic diagnosis.

An Eastern Europe and Middle East multinational expert Delphi consensus study on the prevention, diagnosis, and treatment of developmental dysplasia of the hip before walking age.

PURPOSE: The incidence of developmental dysplasia of the hip (DDH) is higher in Eastern Europeans and Middle Easterners. This study aimed to establish consensus among experts in this geographical area on the management of DDH before walking age. METHODS: Fourteen experienced orthopedic surgeons agreed to participate in a four-round online consensus panel by the Delphi method. The questionnaire included 31 statements concerning the prevention, diagnosis, and treatment of DDH before walking age. RESULTS: Consensus was established for 26 (84%) of 31 statements. Hip ultrasonography is the proper diagnostic tool under six months in DDH; universal newborn hip screening between three and six weeks is necessary; positive family history, breech presentation, female gender, and postnatal swaddling are the most important risk factors; Ortolani, Barlow tests, and limitation of abduction are the most important clinical findings; Pavlik harness is the first bracing preference; some Graf type IIa hips and all Graf type IIb and worse hips need abduction bracing treatment; the uppermost age limit for closed and open reductions is 12 months and 12-24 months, respectively; anatomic reduction is essential in closed and open reductions, postoperative MRI or CT is not always indicated; anterior approach open reduction is better than medial approach open reduction; forceful reduction and extreme positioning of the hips (> 60° hip abduction) are the two significant risk factors for osteonecrosis of the femoral head. CONCLUSION: The findings of the present study may be useful for clinicians because a practical reference, based on the opinions of the multinational expert panel, but may not be applicable to all settings is provided.

The Magnetic Resonance Imaging Pattern of the Lesions Caused by Knee Overuse in the Pediatric Population.

Background and Objectives: Excessive use of the knee in patients with immature locomotor systems leads to a whole spectrum of morphological changes with possible consequences in adulthood. This study aimed to examine the morphological pattern in magnetic resonance imaging (MRI) that is associated with recurrent pain due to increased physical activity in children. Materials and Methods: This was a retrospective study conducted among pediatric patients treated at the University Children's Hospital in Belgrade in 2018 and 2019. MRI findings of patients who reported recurrent pain in the knee joint during physical activity and who were without any pathological findings on both clinical examination and knee radiographs were included in the study. Results: MRI findings of 168 patients (73 boys and 95 girls, mean age 14.07 ± 3.34 years) were assessed. Meniscus and cartilage lesions were the most commonly detected morphological findings: meniscus lesions in 49.4%, cartilage ruptures in 44.6%, and cartilage edema in 26.2% of patients. The medial meniscus was more often injured in girls (p = 0.030), while boys were more prone to other joint injuries (p = 0.016), re-injury of the same joint (p = 0.036), bone bruises (p < 0.001), and ligament injuries (p = 0.001). In children older than 15 years, tibial plateau cartilage edema (p = 0.016), chondromalacia patellae (p = 0.005), and retropatellar effusion (p = 0.011) were detected more frequently compared to younger children. Conclusions: Children reporting recurrent knee pain due to increased physical activity, without any detected pathological findings on clinical examination and knee radiography, may have morphological changes that can be detected on MRI. Timely diagnosis of joint lesions should play a significant role in preventing permanent joint dysfunction in the pediatric population as well as in preventing the development of musculoskeletal diseases in adulthood.

Computational analysis of MRIs predicts osteosarcoma chemoresponsiveness.

Aim: This study aimed to improve osteosarcoma chemoresponsiveness prediction by optimization of computational analysis of MRIs. Patients & methods: Our retrospective predictive model involved osteosarcoma patients with MRI scans performed before OsteoSa MAP neoadjuvant cytotoxic chemotherapy. Results: We found that several monofractal and multifractal algorithms were able to classify tumors according to their chemoresponsiveness. The predictive clues were defined as morphological complexity, homogeneity and fractality. The monofractal feature CV for Λ'(G) provided the best predictive association (area under the ROC curve = 0.88; p <0.001), followed by   Y-axis intersection of the regression line  for â€Šbox fractal dimension, r²â€Š for  FDM and tumor circularity. Conclusion: This is the first full-scale study to indicate that computational analysis of pretreatment MRIs could provide imaging biomarkers for the classification of osteosarcoma according to their chemoresponsiveness.

Combined technique with hydroxyapatite coated intramedullary nails in treatment of anterolateral bowing of congenital pseudarthrosis of tibia.

PURPOSE: The goal of this study is to evaluate the treatment outcomes of anterolateral bowing and residual deformities of distal tibia in patients with CPT using circular external fixation and hydroxyapatite coated flexible intramedullary nailing without excision of affected part of tibia. PATIENTS AND METHODS: Six patients (4 boys and 2 girls, mean age 12.4 ±â€¯4.1 years) were included in the study. Mean follow-up is 2.1 years. In 4 patients with early onset of disease initial surgical treatment (at age of 5-8 years) was dysplastic zone or pseudarthrosis resection with proximal metaphyseal osteotomy for bone transport. Children with unbroken bowed tibia (2 cases of type II according to Crawford classification) had no previous surgery. Neurofibromatosis type I was diagnosed in 4 cases. Surgical technique for residual deformity correction consisted of percutaneous osteotomy, application of circular external frame and composite hydroxyapatite-coated intramedullary nailing. RESULTS: Mean external fixation time was 95.3 ±â€¯17.5 days. All patients never get fractured after frame removal. At the present time, they are considered to be healed, in 2.1 years, in average, without fractures or deformity recurrence. Mean lower limb length discrepancy varied from 2 to 10 mm at the latest follow-up control. After realignment procedure, patients didn't require additional surgery but one. Intramedullary nails were removed in two years after deformity correction for individual reason. CONCLUSION: Correction of anterolateral bowing or residual deformity in children with CPT is indicated. Association of external fixation with intramedullary nailing/rodding left in situ after frame removal ensure stability and accuracy of deformity correction. Biological methods of stimulation of bone formation in dysplastic zone are obligatory to ensure bone union. Intramedullary nailing with composite hydroxyapatite-coated surface provides mechanical and biological advantages in patients with CPT.

Outcomes and special techniques for treatment of penile amputation injury.

INTRODUCTION: Management of severe penile trauma presents great challenges for reconstructive urologists since these injuries vary from abrasions to total emasculation. A review of our case experience with penile amputation is presented, emphasizing techniques used to salvage or reconstruct the most difficult of penile injury cases. MATERIALS AND METHODS: A total of 13 patients with penile amputation injury referred to us between 2007 and 2016 were analyzed. Mean age at surgery was 16 years (ranged from 4 to 29 years). Etiology of penile amputation (partial or total) combined with management and outcomes were evaluated. Management included different surgical procedures with the aim to achieve good functional and esthetical outcomes. Postoperative questionnaire was used for assessment of patient's overall satisfaction. RESULTS: Follow-up ranged from 13 to 182 months (mean 53). Causes of penile injury were iatrogenic trauma (8), self-amputation (2), electrocution (1), intentional sexual assault (1) and mother's hair strangulation (1). Outcome criteria including aesthetic appearance, urinary function and ability to engage in satisfactory coitus, were noted in 11 cases (85%). Two cases with ensuing complications relating to the total phalloplasty required additional treatment due to urethral fistula. CONCLUSIONS: Severe penile injuries should be treated on a case by case basis utilizing the most propitious techniques. We respectfully propose that the needs of such patients are best served by referral centers with extensive experience.

Limb lengthening and deformity correction in children with abnormal bone.

Flexible intramedullary nailing (FIN) provides multiple advantages in limb lengthening and progressive deformity correction in combination with external fixation. The article presents brief literature review and authors' experience in limb lengthening of abnormal bone (Ollier's disease, fibrous dysplasia, osteogenesis imperfecta). Titanium and, especially, hydroxyapatite-coated bent elastic nails in combination with external fixator are appropriate in limb lengthening of abnormal bone in children. FIN left in situ after lengthening procedure and external frame removal should be applied for long-term reinforcement of lengthened bone in patients with abnormal bone (metabolic bone disorders, skeletal dysplasias with compromised bone tissue development). The FIN respects bone biology, which is mandatory for good bone consolidation. Osteoactive properties of intramedullary elastic implants are favorable for bone formation and as well as for stable position of nails without risks of migration in long-term follow-up.

TREATMENT OF UNICAMERAL BONE CYSTS IN CHILDREN: A COMPARATIVE STUDY.

Unicameral bone cysts (UBC) are benign bone tumor-like lesions. Mostly they are located in the metaphyseal-diaphyseal region of long bones in children and adolescents. The etiology of UBC is still unclear. There is no consensus about the protocol of UBC treatment. The aim of this study was to evaluate the effectiveness of three different techniques for the treatment of UBC. This study included 129 pediatric patients with UBC treated at University Children's Hospital in Belgrade during the 8-year period. The mean follow up was 7.14 years. The following parameters were observed: gender, age, site, length of cyst, cyst index, cortical thickness, presentation of pathologic fracture, healing of cyst, treatment complications and length of hospitalization. These parameters were correlated to three treatment modalities, i.e. intracystic methylprednisolone acetate injection (group 1), curettage with bone grafting (group 2) and osteoinductive procedure using demineralized bone matrix (group 3). We found statistically significant differences in healing of the cysts and length of hospital treatment between groups 1 and 2, and between groups 2 and 3. In conclusion, complete healing of UBC can be achieved only using open surgery procedure. Intracystic methylprednisolone acetate instillation can be considered a good option for initial treatment of UBC.

A prospective randomised non-blinded comparison of conventional and Dorgan's crossed pins for paediatric supracondylar humeral fractures.

BACKGROUND: Closed reduction and percutaneous pinning are the preferred treatment of displaced supracondylar humeral fractures in children. The purpose of this study is to evaluate the non-standard Dorgan's method and compare its results with those of the standard percutaneous cross pinning method in treatment of unstable or irreducible Gartland type II and III supracondylar humeral fractures in children. PATIENTS AND METHODS: This was a prospective evaluation of 138 consecutive patients with Gartland type II or III extension supracondylar humeral fractures referred to University Children's Hospital during a four-year period. The patients were randomized into two groups: the first group, comprised of 71 patients, was treated with standard pin configuration and the second group, comprised of 67 patients, underwent Dorgan's method. The study included 88 boys and 50 girls aged 1.5-11.4 years (mean 6.5±2). At initial presentation 8.7% (n-12) fractures were classified as Gartland type IIa, 25.4% (n-35) as Gartland type IIb and 65.9% (n-91) as Gartland type III. RESULTS: Flynn's criteria were used to evaluate the results. An excellent clinical outcome was reported in about 90% of patients (n-90) treated with standard pin configuration and 89.5% (n-60) of patients treated with Dorgan's method. There were no statistically significant differences in outcomes between the groups in terms of their gender, age, fracture types, function and cosmetics. Neurological lesions were observed in 9.9% of patients (n=7) who were treated using the standard configuration Kirschner pins, while in those treated by Dorgan's method neurological complications were not observed. However, the procedure time was longer (mean 36.54±5.65min) and radiation exposure significantly higher (mean 10.19±2.70 exposures) in the group that was treated using Dorgan's method, compared to the conventional method (mean 28.66±3.76min and 7.54±1.63 exposures). CONCLUSION: Two laterally inserted crossed pins provide adequate stability with good functional and cosmetic outcome for most unstable paediatric supracondylar humeral fractures with no risk of iatrogenic ulnar nerve injury.

(Un)importance of physical therapy in treatment of displaced supracondylar humerus fractures in children.

Elbow joint stiffness is a common complication following supracondylar humerus fractures. In prospective study, dynamics of establishing a full range of motion in the elbow joint following the treatment of supracondylar humerus fractures were assessed, together with the effects of physical therapy on improvement in the range of motion. Two groups of patients were observed. Physical therapy was administered to the first group, comprised of 25 patients. The second group, comprised of 28 patients, underwent no physical therapy. In the first few months following treatment, the range of motion was significantly greater in the patients who had undergone physical therapy, but after 12 months, the range of motion was almost equal in the two groups. This study has shown that it takes about 12 months to establish a full range of motion after the injury, and that it is not necessary to apply physical therapy in patients with elbow fractures.

Pseudoachondroplasia: a case report.

INTRODUCTION: Pseudoachondroplasia (PSACH) is an autosomal dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein. It is characterized by rhizomelic dwarfism, limb and vertebral deformity, joint laxity and early onset osteoarthrosis. We present the girl with the early expressed and severe PSACH born to clinically and radiographically unaffected parents. CASE OUTLINE: A 6.5-year-old girl presented with short-limbed dwarfism (body height 79.5 cm, < P5;-32%) and normal craniofacial appearance and intelligence. The girl was normal until 3 months of age when she expressed growth retardation with apparently shorter extremities in relation to the torso. With age, her rhizomelic dwarfism became increasingly visible, and since completed 15 months of age, when she started to walk, the disease was complicated with genu varum, lumbar lordosis and abnormal gait. Beside visibly short forearms, short, broad and ulnar deviation of the hands, brachydactyly and joint hyperlaxity, the radiographic picture showed markedly flared metaphyses, small and irregular epiphyses and poorly formed acetabulum. CONCLUSION: PSACH is an achondroplasia-like rhizomelic dwarfism recognized by the absence of abnormality at birth, normal craniofacial appearance, characteristic epiphyseal and metaphyseal radiographic finding and joint hyperlaxity.

Combined external fixation and intramedullary alignment in correction of limb length discrepancies.

The aim of this study was to evaluate the influence of intramedullary (IM) alignment used in combination with external fixation on the healing index (HI) and lengthening index (LI) in the treatment of congenital and acquired leg length discrepancies (LLD). We compared duration of the external fixator application, LLD, HI and LI between two groups of children: children in Group I underwent limb lengthening by the conventional llizarov technique, and children in Group II underwent a combination of Ilizarov technique and intramedullary alignment with Kirschner wires. Two types of LLDs were treated: congenital and acquired. We found significant differences between the two groups for duration of external fixator application and HI. Significant differences were also noted in the duration of the external fixator application, HI and LI, between patients with congenital and acquired LLDs. We also noted significant differences between Group I and Group II regarding duration of external fixator application for patients with congenital LLD and also regarding HI for both congenital and acquired types of LLD.

Fast-track surgery concepts for congenital urogenital anomalies.

AIM: To investigate the possibility of fast-track surgery concepts in pediatric urology department as a single center study model of a developing country. MATERIAL OF STUDY: The study included 1620 patients surgically treated at the pediatric urology department, from 2009 to 2011. According to the congenital anomalies, all patients were classified in one of four groups: I - testicular anomalies (197 patients); II - external genital anomalies (453); III - upper urinary tract anomalies (801) and IV - associated anomalies (169). We analyzed the total duration of stay in the hospital of all patients among all treating doctors concerning the anomaly. RESULTS: Statistically significant difference in total length of hospitalization of all patients in Group I was noted in Doctors 1 and 5 (F=10.36** for F0.05;5;12=3.11 and F0.01;5;12=5.06), as well as in the Group II (F=17.01** for F0.05;5;12=3.11 and F0.01;5;12=5.06). Statistical analysis was not possible to be performed in groups III and IV because of lack of the patients. DISCUSSION: Analyzing the length of hospitalization of the patients treated at the urology department, all doctors showed the tendency to shorten the total length of hospitalization in patients of all groups. Majority of the studies carried out on pediatric urology departments in developed countries, showed that over 50% of children were successfully treated using fast-track surgery concept. CONCLUSIONS: Modern methods of surgical management and anesthesia allow decrease of hospitalization length, financial savings to the healthcare system and better comfort for patients.

Evaluation of inflammatory markers after orthopedic surgical intervention in children.

OBJECTIVE: The study aim was to evaluate inflammation markers values (C-reactive protein (CRP), Erythrocite sedimentation (ES), White blood cells count (WBC)) in surgically treated pediatric patients with diagnosed developmental displasia of the hip or Perthes disease before and after operation. METHODS: We have evaluated 43 children (20 patients were with diagnosed unilateral developmental displasia of the hip while 23 had Perthes disease). Blood samples were drown at the admission and 5 days after admission, and further inflammatory parameters were analyzed: ES (mm/hour), CRP (mg/L) and WBC (x1000/mm3) count. RESULTS: Elevated erythrocite sedimentation (ESR) was significantly frequent than elevated CRP (p<0.01) and elevated WBC as well (p<0.01). Values of ESR and WBC do not correlate closely with age (FESR= 1.805; FWBC= 0.130; p>0.05) while CRP values correlate significantly with the age of the patients (FCRP= 4.948; p<0.05). The most frequently isolated marker was ESR (34.88%). The most frequent elevated two markers were ESR and CRP (44.19%). CONCLUSION: Surgical procedure could alter the values of inflammatory markers leading to the increasement even though there is no other clinical signs of infection. For estimation of the possible presence of the infection, clinical signs and patients intensive clinical follow-up after the surgery, should be done along with the evaluation of inflammatory markers.

Correlation of ABO and Rh blood groups with transfusion administration and fever onset after hip surgery in children.

OBJECTIVE: Aim of our study was to evaluate distribution of ABO and Rh blood type groups in children after hip surgery regarding transfusion administration and fever presence. METHODS: Four types of ABO blood groups (A; B; AB; O) and 2 types of Rh blood groups (Rh+; Rh-) were evaluated in group with administered transfusion (tr+) and without given transfusion (tr-); and in group with fever (fev+) and without fever (fev-), in 146 children after hip surgery. Tr+ and fev+ groups were divided into 3 groups (0-24h; 25-48h; 49-72h): for tr+ group (Group 1, Group 2, Group 3), and for fev+ group (Group A, Group B, Group C). RESULTS: AB blood group significantly decreased in Group 1 (χ2= 6.44; p<0.05) and A blood group in Group 3 in tr+ group (χ2= 7.68; p<0.01). O blood group significantly increased in Group 3 in tr+ group (χ2= 9.96; p<0.01). AB blood group significantly decreased in Groups B (χ2= 12.2; p<0.01) and C (χ2= 4.2; p<0.05) in fev+ versus fevgroup. B blood group significantly increased in Group C (χ2= 34.4; p<0.01) in fev+group. CONCLUSION: Administration of transfusion and fever onset in pediatric patients undergoing surgical correction of the hip is not influenced by the ABO and Rh blood groups system in humans. There is correlation between distribution of ABO blood groups with the time of transfusion administration and fever onset in children after hip surgery.

Minimally invasive inguinal technique for the management of duplex ureteric anomaly.

OBJECTIVE: To present outcomes of a minimally invasive inguinal technique for the separation of the distal part of ureters in duplex systems and for the extravesical ureteroneocystostomy of only the pathologically involved ureter. MATERIALS AND METHODS: From November 2001 to February 2007, we performed extravesical reimplantation of only the involved ureter in 21 duplex systems, of which 14 were refluxing (megaureters) and seven had obstruction of the ureterovesical junction. The mean (range) age of the patients was 39 (17-59) months. In seven patients, ureterocutaneostomy (of the involved ureter only) was performed first, with reimplantation 3-6 months later, after the diameter of the ureter had decreased, to ensure safe reimplantation. The mean (range) postoperative follow-up was 28 (12-47) months. RESULTS: Postoperative voiding cysto-urethrograms (VCUGs) and magnetic resonance imaging (MRI), showed an absence of vesico-ureteric reflux (VUR) or obstruction in the ureters of the first 10 patients. In the remaining 11 patients, there was no ultrasound detectable dilatation, but symptomatic urinary tract infection developed in two of these patients. Subsequent VCUG and MRI results showed no obstructions or VURs. CONCLUSION: Our results showed that the minimally invasive inguinal approach to separation of ureters in duplex systems and single ureteroneocystostomy of only the pathologically involved ureter represents a viable treatment option.

Sacrospinous ligament fixation for neovaginal prolapse prevention in male-to-female surgery.

OBJECTIVES: To report our experiences of vaginal sacrospinous ligament fixation after vaginoplasty in male transsexual patients with the aim of preventing its postoperative prolapse. METHODS: From August 1997 through November 2005, a total of 62 male transsexual patients (mean age 26 years, range 18 to 58) underwent sacrospinous ligament fixation for neovaginal prolapse during male-to-female sex reassignment surgery. The neovagina was created from a penile skin tube flap combined with a urethral flap. A deep and wide perineal cavity between the urethra, bladder, and rectum was created by dissection of the tendineous center and rectourethral muscle. The right pararectal space was opened by penetrating the right pararectal fascia (rectal pillar) and right ischial spine was palpated. Using the ischial spine as a prominent landmark, the sacrospinous ligament was palpated. Long-handled Deschamps ligature was used to pierce the ligament medially to the ischial spine. Vaginopexy to the sacrospinous ligament was performed, and the neovagina was placed deep in the perineal cavity. RESULTS: The median follow-up was 32 months (range 7 to 102). Sacrospinous ligament fixation was successfully performed in all patients. The mean vaginal length was 10.7 cm (range 9.5 to 16). Of the 62 patients, 42 (76%) were able to have normal sexual intercourse. The appearance of the neovagina was aesthetically acceptable in 52 patients. In 3 cases, a minor bulge of the anterior vaginal wall was easily resolved by simple excision. CONCLUSIONS: Vaginal sacrospinous fixation is feasible in male transsexuals for neovaginal prolapse prevention. However, extensive experience with male pelvic surgery is required to avoid possible complications.