Milan Kokavec’s research while affiliated with Comenius University Bratislava and other places

Background: Developmental dysplasia of the hip (DDH) is a developmental disorder which is reported to be associated with hip instability. When untreated, it can lead to irreversible joint damage. DDH is known to be a multifactorial disease involving genetic, mechanical and environmental factors. The greatest causative potential is attributed to the genetic component. Growth Differentiation Factor 5 (GDF5) is among the most studied genes associated with processes of regeneration and maintenance of joints. The aim of this work was to analyse the association of SNP rs143383 in the GDF5 gene and the occurrence of DDH, along with association with various contributing factors in the Caucasian population. Material and methods: A total of 118 samples were analysed for the presence of the mutation. DNA was isolated from all individuals from peripheral blood. SNP rs143383 in the GDF5 gene was genotyped using the TaqMan assay. A standard chi-square test was used to compare allele and genotype distributions in patients and healthy controls. Results: The association analysis of genotypes of DDH and rs143383 revealed a significant association. Also, the association of GDF5 and selected contributing factors was statistically significant in female gender (p=0.002), family history (p<0.001), count of pregnancy (p=0.009), laterality of hip involvement and initial US examination. Conclusions: 1. The results indicate an important effect of rs143383 polymorphism in the GDF5 gene on DDH development. 2. However, our results also suggest that rs143383 is not the only contributing factor in the genetic component of DDH.

Background: Developmental dysplasia of the hip (DDH) is one of the most prevalent skeletal disorders. DDH is considered a pathologic condition with polygenic background, but environmental and mechanic factors significantly contribute to its multifactorial etiology. Inheritance consistent with autosomal dominant type has also been observed. Single-nucleotide polymorphisms (SNPs) in various genes mostly related to formation of connective tissue are studied for a possible association with DDH. Methods: We genotyped three SNPs, rs1800796 located in the promoter region of the IL6 gene, rs143383 located in the 5′ untranslated region (UTR) of the GDF5 gene and rs726252 located in the fifth intron of the PAPPA2 gene. The study consisted of 45 subjects with DDH and 85 controls from all regions of Slovakia. Results: Association between DDH occurrence and studied genotypes affected by aforementioned polymorphisms was confirmed in the case of rs143383 in the GDF5 gene (p = 0.047), where the T allele was over-expressed in the study group. Meanwhile, in the matter of IL6 and PAPPA2, we found no association with DDH (p = 0.363 and p = 0.478, respectively). Conclusions: These results suggest that there is an association between DDH and GDF5 polymorphisms and that the T allele is more frequently presents in patients suffering from DDH.

In the last decade, the advances in the molecular analyses and sequencing techniques allowed researchers to study developmental dysplasia of the hip (DDH) more thoroughly. Certain chromosomes, genes, loci and polymorphisms are being associated with variable severity of this disorder. The wide range of signs and symptoms is dependent either on isolated or systemic manifestation. Phenotypes of isolated cases range from only a mild ligamental laxity, through subluxation, to a complete dislocation of the femoral head. Systemic manifestation is connected to various forms of skeletal dysplasia and other malformations characterized by significant genetic aberrations. To reveal the background of DDH heredity, multiple studies focused on large sample sizes with an emphasis on the correlation between genotype, phenotype and continuous clinical examination. Etiological risk factors that have been observed and documented in patients include genetic, environmental, and mechanical factors, which significantly contribute to the familial or nonfamilial occurrence and phenotypic variability of this disorder. Still, since the multifactorial etiology and pathogenesis of DDH is not yet sufficiently clarified, explained, or understood. Formation of connective tissue, osteogenesis, chondrogenesis, and all other affected pathways and variations in the function of their individual elements contribute to the creation of the pathology in a developing human body. This review article presents an up-to-date list of known DDH associated genes, their products, and functional characteristics.

As one of the most frequent skeletal anomalies, developmental dysplasia of the hip (DDH) is characterized by a considerable range of pathology, from minor laxity of ligaments in the hip joint to complete luxation. Multifactorial etiology, of which the candidate genes have been studied the most, poses a challenge in understanding this disorder. Candidate gene association studies (CGASs) along with genome-wide association studies (GWASs) and genome-wide linkage analyses (GWLAs) have found numerous genes and loci with susceptible DDH association. Studies put major importance on candidate genes associated with the formation of connective tissue (COL1A1), osteogenesis (PAPPA2, GDF5), chondrogenesis (UQCC1, ASPN) and cell growth, proliferation and differentiation (TGFB1). Recent studies show that epigenetic factors, such as DNA methylation affect gene expression and therefore could play an important role in DDH pathogenesis. This paper reviews all existing risk factors affecting DDH incidence, along with candidate genes associated with genetic or epigenetic etiology of DDH in various studies.

Development dysplasia of the hip (DDH) is a complex developmental disorder despite being a relatively common condition mainly caused by incompatibility of the femoral head and the abnormal joint socket. Development dysplasia of the hip describes a wide spectrum of disorders ranging from minor acetabular dysplasia to irreducible dislocation of the hip. Modern medicine still suffers from lack of information about screening and precise genetic examination. Genome wide linkage and association studies have brought significant progress to DDH diagnosis. Association studies managed to identify many candidate (susceptible) genes, such as PAPPA2, COL2A1, HOXD9, GDF-5, and TGFB1, which play a considerable role in the pathogenesis of DDH. Early detection of DDH has a big chance to help in preventing further disability and improve the psychological health and quality of life in those children. This emphasizes the importance to establish a universal screening program along with the genetic counseling.

Both adolescents and children suffer from osteosarcoma, localized in the metaphysis of the long bones. This is the most common primary high-grade bone tumor in this patient group. Early tumor detection is the key to ensuring effective treatment. Improved osteosarcoma outcomes in clinical trials have been contingent on biomarker discovery and an evolving understanding of molecules and their complex interactions. In this review, we present a short overview of biomarkers for osteosarcoma, and highlight advances in osteosarcoma-related biomarker research. Many studies show that several biomarkers undergo critical changes with osteosarcoma progression. Growing knowledge about osteosarcoma-related markers is expected to positively impact the development of therapeutics for osteosarcoma, and ultimately of clinical care. It has also become important to develop new biomarkers, which can identify vulnerable patients who should be treated with more intensive and aggressive therapy after diagnosis.

Základným princípom pri operačnej liečbe skolióz je stabilizácia krivky a zastavenie jej progresie so snahou o čo najlepšiu a najbezpečnejšiu korekciu. Hoci pracujeme s najlepšími anatomickými znalosťami, používame najvhodnejšie inštrumentárium za použitia neuromonitoringu, občas sa stretávame s neurologickými komplikáciami. Peroperačné využitie neuromonitoringu hrá v súčasnej dobe kľúčovú úlohu v redukcii iatrogénneho neurologického poškodenia počas korekčných výkonov pri idiopatických skoliózach u detí. Medzi symptómy pooperačného neurologického poškodenia najčastejšie patrí čiastočná alebo úplná monoparéza, paraparéza, a rôzne druhy parestézií. Mnohokrát sú neurologické komplikácie výsledkom komplikácií cievneho zásobenia alebo majú mechanickú príčinu. Kľúčové slová: chrbtica, skolióza, parestéza, paréza, neuromonitoring Summary The main principle at surgical treatment of scoliotic deformities is stabilisation of the curve and stopping it's progression reaching the best and the safest correction of spine. Although we are using all the best anatomical knowledge, instrumentation and also neuromonitoring, we sometimes see some neurological complications. Intraoperative neuromonitoring (IONM) plays an important role in reducing iatrogenic neurologic deficits during surgical procedures for scoliosis. Symptoms of neurological damage after surgery are most often partial or total mono-paresis, paraparesis, and all kinds of paresthesia. Many times neurological deficits can result from vascular or mechanical complications of spinal surgery. Key words: spine, scoliosis, paresthesia, paresis, neuromonitoring

Coccygodynia is painful condition around the gluteal muscles and the end of a spine, which can have various reasons. The most frequented reasons are trauma, childbirth, but they can also be presented from unknown reasons (idiopathic coccygodynia). The predispositions for coccygodynia are female sex, depression, hysteria, lesions of rectum and lumbar spine. Right after physical examination is the most moderate method X-ray examination of sacral spine and pelvis when we can measure the inclination of coccyx and determine the diagnosis. Therapeutic methods are non-operative and operative. The non-operative therapy consists of physical therapy, nonsteroidal anti-inflammatory drugs and local injections of corticoids or combination with analgesics. The operative therapy means coccygectomy and is mentioned as definitive therapy.

Osteochondroma is characterized as cartilage-covered benign bone tumor, usually seen in the second decade of life. The most common locations for these type of lesions are distal femur and proximal tibia. Scapula is an unusual sight to occur with an overall incidence of 3-4.6 % worldwide. Ventral side of scapula is more often affected which is causing scapular asymmetry and should be ruled out as part of a differential diagnosis to a "winged" scapula. Dorsal scapular side is usually asymptomatic. Authors present three cases of osteochondromas which all resulted in painful dislocation of scapula, with need of surgical treatment.

Background: Aim of the study was to analyze effectivity of conservative versus surgical treatment (arthroereisis with bioresorbable screw) of flexible painful flatfoot in children. Patients and methods: In 2007-2014, were operated 47 children (83 feet) with this method at Orthopaedic department, Children university hospital in Bratislava. Indication for surgery was pain limiting daily activities, footprint with grade III. flatfoot in Godunov scale, heel valgus ≥ 5°, foot X-raylateral with Meary angle ≥ 10° and calcaneal pitch ≤ 15°. Arthroereses were combined with other soft tissue procedures in all cases. The mean age of the pacients during surgery was 8-13 years. Results of arthroereises were compared with 50 patients (100 feet) treated conservatively using AOFAS midfoot scale test. The mean follow up in group passed arthroereisis was 3.5 years. Results: The mean AOFAS midfoot scale test improved from 52 points preoperatively to 89 points after surgery. Preoperative and postoperative radiological comparison of Meary's angle and calcaneal pitch in 27 feet treated surgically point out excellent results in this group. In the group of patients treated conservatively, no subjective, clinical and radiological improvement were registered. Conclusion: We consider arthroereisis in combination with soft tissue procedures as effective method in the treatment of flexible flatfoot in children, with minimal rate of complications.