CLINICAL FEATURES OF CONNECTIVE TISSUE DYSPLASIA, OSGOOD-SCHLATTER DISEASE AND MULTIPLE CORTICAL DISORDERS IN A CHILD.

OBJECTIVE: The aim: To analyze scientific data on the problems of disorders of bone morphogenesis in children, in particular, non-ossifying fibroma. To analyze modern methods of diagnosis and treatment of this disease in the context of the latest scientific achievements. PATIENTS AND METHODS: Materials and methods: The latest data of scientists from the world's leading clinics describing various forms of fibrous skeletal lesions in children of differ¬ent ages were analyzed. We examined a boy with fibrous lesions of the cortical layer of the knee joint bones and a girl with a large fibrous focus of the distal femoral metaphysis, which resulted in a closed pathological bone fracture. Surgical treatment, osteosynthesis, marginal resection of the tumor, bone grafting and histological examination were conducted. CONCLUSION: Conclusions: Despite numerous studies of this disease, the etiopathogenesis of this disease has not been studied. There are no early symptoms of fibrous bone lesions in children. Diagnosis is possible only when a pathological fracture of the affected bone occurs due to extensive growth of fibrous tissue and a significant decrease in the mechanical strength of the bone. Most cases of recognition of such a disease occur accidentally when performing X-ray examinations for other reasons - bruises, sprains, arthralgias, osteochondropathy, infectious diseases, etc. It is known that boys are more mobile and require more frequent X-ray examinations for limb injuries than girls, so the likelihood of accidental detection of such changes increases significantly. Thus, long-term observations of children with fibrous bone lesions have shown that after 40 years, patients rarely developed malignant tumors - osteogenic sarcoma, fibrosarcoma, malignant fibroma of tubular bones, pelvic bones. There are no early symptoms of fibrous bone lesions in children. Recognition of such a disease occurs by chance when X-ray examinations are performed for other reasons.

Newborn screening for severe combined immunodeficiency: The results of the first pilot TREC and KREC study in Ukraine with involving of 10,350 neonates.

Severe combined immunodeficiency (SCID) is a group of inborn errors of immunity (IEI) characterized by severe T- and/or B-lymphopenia. At birth, there are usually no clinical signs of the disease, but in the first year of life, often in the first months the disease manifests with severe infections. Timely diagnosis and treatment play a crucial role in patient survival. In Ukraine, the expansion of hemostatic stem cell transplantation and the development of a registry of bone marrow donors in the last few years have created opportunities for early correction of IEI and improving the quality and life expectancy of children with SCID. For the first time in Ukraine, we initiated a pilot study on newborn screening for severe combined immunodeficiency and T-cell lymphopenia by determining T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). The analysis of TREC and KREC was performed by real-time polymerase chain reaction (RT-PCR) followed by analysis of melting curves in neonatal dry blood spots (DBS). The DBS samples were collected between May 2020 and January 2022. In total, 10,350 newborns were screened. Sixty-five blood DNA samples were used for control: 25 from patients with ataxia-telangiectasia, 37 - from patients with Nijmegen breakage syndrome, 1 - with X-linked agammaglobulinemia, 2 - with SCID (JAK3 deficiency and DCLRE1C deficiency). Retest from the first DBS was provided in 5.8% of patients. New sample test was needed in 73 (0.7%) of newborns. Referral to confirm or rule out the diagnosis was used in 3 cases, including one urgent abnormal value. CID (TlowB+NK+) was confirmed in a patient with the urgent abnormal value. The results of a pilot study in Ukraine are compared to other studies (the referral rate 1: 3,450). Approbation of the method on DNA samples of children with ataxia-telangiectasia and Nijmegen syndrome showed a high sensitivity of TRECs (a total of 95.2% with cut-off 2000 copies per 106 cells) for the detection of these diseases. Thus, the tested method has shown its effectiveness for the detection of T- and B-lymphopenia and can be used for implementation of newborn screening for SCID in Ukraine.

Newborn screening for severe combined immunodeficiency: clinical and cost-effectiveness approaches.

Severe combined immunodeficiency (SCID) is a group of lifethreatening diseases, for which early diagnostics, before the development of infectious complications, is extremely important. Newborn screening for SCID with T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) assay for the identification of T- and B-lymphopenia has been implemented in a number of highly developed countries of the world. A number of studies proved the clinical and cost-effectiveness of screening for SCID by using TREC assay. However, both clinical benefits and economic costs for screening may vary depending on country and continent, requiring pilot projects to establish reference values of TREC and KREC levels for the diagnosis of SCID and other diseases associated with T- and B-lymphopenia, as well as determination of cost-effectiveness/costbenefit ratio and expediency of their further implementation. Other challenges, outlined in the article, need to be solved. The development of hematopoietic stem cell transplantation in Ukraine opens up full opportunities for the implementation of newborn screening for SCID. The expediency of conducting a pilot study to determine the most effective method (TREC or TREC/KREC) and the algorithm for SCID detection has been shown.

Clinico-pathogenic aspects of osteodeficiency in osteoarthritis in combination with chronic pancreatitis.

OBJECTIVE: Introduction: Pathology of the musculoskeletal system creates a number of important and complex medical problems affecting the economic situation of society, health and quality of life of individuals and their families. One of these problems and the most common disease of the joints which is diagnosed in 20% of the population of the planet is osteoarthritis (OA). The aim: The article deals with modern views on the problem of comorbidity of osteoarthritis, chronic pancreatitis and osteodefiсiency. Dual energy X-ray densitometry data were analyzed, as well as indicators of activation of lipid peroxidation (malonic aldehyde), antioxidant protection system (superoxide dismutase and SH-group, ceruloplasmin, сatalase) and tissue destruction (oxyproline). PATIENTS AND METHODS: Materials and Methods:The complex examination of 72 patients was made. Patients were divided into two groups: 30 patients with OA and 42 - with OA in combination with CP. The control group included 20 apparently healthy individuals. Evaluation of CT scan was performed using Dual Energy X-Ray Absorptiometry - DXA by Lunar corp. (Madison, WI) - Lunar DPX-A No. 2589 in the lumbar region of the vertebral column. The evaluation of the indicators was carried out in accordance with WHO recommendations (WHO, Geneva, 1994) [1]. The study of LPO was carried out on the level of malonic aldehyde (MA). To assess AOP, we determined SOD, ceruloplasmin (CPN); SH-groups; catalase. The endogenous intoxication and the level of degradation of the connective tissue in the body was estimated by levels of free oxyproline. The influence of CP on the state of LPO-AOP was established by the following clinical characteristics of CP: age of the patients, structural condition of the pancreas with the help of the method of ultrasound, expressed in points. Excretory function of the pancreas was investigated on the level of fecal α-elastase ( by ELISA test using the kits BIOSERV ELASTASE 1-ELISA). RESULTS: Results: During the examination of the mineral bone density by the dual energy X-ray densitometry it was discovered that the presence of CP in patients with OA led to a significant reduction of BMD and deterioration of the bone tissue (BT): the proportion of patients with normal bone decreased from 67% to 16%, the number of patients with osteopenia increased from 10% to 67%; patients with OP appeared - 17%.Besides, the increased degradation of bone tissue in OA with CP was accompanied by strengthening of oxidative changes (by MA-level), weakening of the antioxidant defense (SOD and SH-groups), the increase in the severity of inflammation and endotoxemia (levels of catalase and ceruloplasmin), as well as increased degradation of connective and bone tissue in the joints and progression of fibrosis in tissue (the level of oxyproline). CONCLUSION: Conclusions: It was found out that the presence of CP in patients with OA led to a significant reduction of BMD and the deterioration of the bone tissue. It was discovered that during the combined course of OA and CP with osteopenia there occurs the weakening of the AOP (by SOD and SH-groups) and a relatively high level of LPO activation (by MAlevel) as well as the increased deterioration in connective and bone tissue and aggravation of osteopenia which is indicated by the increased levels of oxyproline.