Radoslav Zamborsky

Background: Developmental dysplasia of the hip (DDH) is a common orthopedic disorder characterized by abnormal development of the hip joint, which can lead to pain, instability, and early-onset osteoarthritis if left untreated. Its etiology is multifactorial, involving both genetic and environmental factors. Methods: This study investigated the association between selected single-nucleotide polymorphisms (SNPs) related to joint and bone development and the occurrence of DDH. It assessed potential copy number variations (CNVs) in key skeletal genes using MLPA. A total of 125 individuals were examined, including 43 patients with DDH and 82 healthy controls. Six SNPs were genotyped using real-time PCR with TaqMan assays: TGFB1 (rs1800470), CX3CR1 (rs3732378, rs3732379), GDF5 (rs143384), COL1A1 (rs113647555), and MMP24 (rs12479765). Allele and genotype distributions were compared between cases and controls, and CNVs in COL1A1, COL2A1, LRP5, DKK1, FZD4, and NDP genes were analyzed using Multiplex Ligation-Dependent Probe Amplification. Results: Among the examined variants, only GDF5 rs143384 showed a nominally significant association with DDH (p = 0.040), with the A allele more common in affected individuals. However, after correcting for multiple testing, this result no longer remained significant. No significant associations were detected for TGFB1, CX3CR1, COL1A1, or MMP24. Although CX3CR1 rs3732378 allele frequencies differed slightly from international reference data, no link to DDH was confirmed. Conclusions: MLPA analysis did not identify pathogenic CNVs in the analyzed loci, which indicates that the studied genes have no association with DDH in the Slovak population. Similarly, SNPs in the studied genes yielded no significant results, apart from rs143384 in GDF5, which requires further investigation to confirm our findings.

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.

Osteoarthritis (OA) belongs to chronic degenerative disorders and is often a leading cause of disability in elderly patients. Typically, OA is manifested by articular cartilage erosion, pain, stiffness, and crepitus. Currently, the treatment options are limited, relying mostly on pharmacological therapy, which is often related to numerous complications. The proper management of the disease is challenging because of the poor regenerative capacity of articular cartilage. During the last decade, cell-based approaches such as implantation of autologous chondrocytes or mesenchymal stem cells (MSCs) have shown promising results. However, the mentioned techniques face their hurdles (cell harvesting, low proliferation capacity). The invention of induced pluripotent stem cells (iPSCs) has created new opportunities to increase the efficacy of the cartilage healing process. iPSCs may represent an unlimited source of chondrocytes derived from a patient’s somatic cells, circumventing ethical and immunological issues. Aside from the regenerative potential of iPSCs, stem cell-derived cartilage tissue models could be a useful tool for studying the pathological process of OA. In our recent article, we reviewed the progress in chondrocyte differentiation techniques, disease modeling, and the current status of iPSC-based regenerative therapy of OA.

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.

Purpose: The aim of this study was to investigate the most appropriate surgical interventions for patients with knee articular cartilage defects from the level I randomized clinical trials. Methods: We searched five databases for level I randomized clinical trials. Treatments were compared if reported in more than one study using network meta‐analysis to boost the number of included studies per comparison. Results: We studied 21 articles that included 891 patients. Traumatic lesion was the most common cause in the included patients. There were significantly higher failure rates in the microfracture (MF) group compared to autologous chondrocyte implantation (ACI) group at 10‐year follow‐up. Moreover, osteochondral autograft transplantation (OAT) showed significantly more excellent or good results at > 3‐year follow‐up compared to MF, whereas MF showed significantly more poor results versus ACI and matrix‐induced autologous chondrocyte implantation (MACI). Furthermore, OAT showed significantly more poor results than MACI at 1‐year follow‐up. Similarly, patients who underwent OAT had higher return‐to‐activity rates than those with MF. It is noteworthy that the Knee injury and Osteoarthritis Outcome Score was higher in patients who underwent characterized chondrocyte implantation or MACI compared to MF. Finally, there were no significant differences among the various interventions regarding reintervention, biopsy types or adverse events. According to the P scores for interventions ranking, there was a disagreement concerning the best intervention; however, MF was always ranked as the last. Conclusions: Cartilage repair techniques, rather than MF, provide higher quality repair of tissue and have lower failure and higher return‐to‐activity rates. Moreover, OAT had significantly more excellent or good results compared to MF, whereas MF had significantly more poor results than ACI and MACI. Future studies need to have longer follow‐up periods and more representative populations to investigate the efficacy and safety of these interventions. Level of evidence: Level I: meta‐analysis of Level I studies.

A series of ring-substituted N-arylcinnamamides was prepared, characterized, and investigated for their antimicrobial efficacy in detail

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.