OBJECTIVES To determine NKX3.1 expression in prostatic adenocarcinoma and benign prostate hyperplasia on Immunohistochemistry at a tertiary care hospital in Karachi. METHODOLOGY 74 prostatic specimens were recruited in this comparative cross-sectional study at the Department of Pathology, Pakistan Navy Station Shifa Hospital, Karachi, from January 2018 to February 2019. Of these, 37 specimens were of prostatic adenocarcinoma, and 37 were benign prostate hyperplasia. All specimens were subjected to immunohistochemical staining with NKX3.1. Statistical analysis was done by using SPSS version 23.0. The association of the extent of NKX3.1 staining between the adenocarcinoma and hyperplasia group was assessed using the Chi-square test x2. RESULTSOf the 37 cases of benign prostatic hyperplasia subjected to NKX3.1 staining, 32 showed positive staining with strong to moderate intensity. No staining was observed in 5 cases. 37 cases of adenocarcinoma prostate stained for NKX3.1 revealed positive staining in 30 cases with strong to moderate intensity. Negative staining was seen in 7 cases. The prostatic adenocarcinoma showed a statistically significant association of NKX3.1 positivity compared to benign prostatic hyperplasia cases. The p-value was found to be 0.03. CONCLUSION NKX3.1 staining was highly specific for prostate epithelium, as it was positive in most cases. This immune marker was useful for distinguishing prostatic origin in the context of metastatic lesions. Adding NKX3.1 protein staining to a panel of features may add value to the diagnosis if applied in the appropriate clinicopathologic context.

The article presents an assessment of the results of surgical treatment of bladder urothelial carcinoma using the Da Vinci Si robotic system. The experience of treating 11 patients who underwent robot-assisted cystectomy (RACE) was analysed. This study demonstrates the effectiveness of RACE due to minimal trauma, blood loss, transfusion frequency, and length of patient stay in the hospital.

BACKGROUND: Congenital knee dislocation is a very rare musculoskeletal disease, and it occurs in approximately 1 per 100,000 live births. Many researchers note that the treatment of congenital knee dislocation should begin with conservative methods, during which various complications arise.
 AIM: This study aimed to compare the clinical and radiological classifications of congenital knee dislocation and show the results of the treatment of this deformation using a Von Rosen splint and plaster corrections.
 MATERIALS AND METHODS: The study included 58 patients (34 boys and 24 girls) with congenital knee dislocation (83 knee joints). Congenital knee dislocation with arthrogryposis and other systemic pathologies were not included in the study. Before treatment, all patients were assessed for the severity of congenital knee dislocation according to the Tarek and J. Leveuf system. To evaluate the obtained results, nonparametric statistics were used. To search for differences between groups, the KruskalWallis test and the median test were used. To search for correlations, Spearman coefficients were used. Statistica v10 was used for statistical analysis.
 RESULTS: Clinical and radiological data were compared. In both groups, after conservative treatment, excellent and good results were obtained in nearly 98% and satisfactory in 2%. After conservative therapy, surgical treatment was required in 2 of 37 knee joints with the initial severity of Tarek III deformity.
 CONCLUSIONS: The severity of the deformity according to the Tarek system makes it possible to predict the effectiveness of the conservative treatment of congenital knee dislocation at a statistically significant level.

Using the author’s method for determining the multidimensional relationships of ionized calcium in personal observations in 82 patients based on the analysis of the panel of ratios of indicators of water and electrolyte metabolism, it was found that hypercalcemia in the structure of these ratios can include indicators of bone tissue metabolism, while differing in their characteristics. In the discussion, the authors cite modern literary sources that substantiate the established differences in the structure of complexes of multidimensional bonds. Also, the obtained results indicate the possibility of manifestation of signs of changes in the balance of B-cross Laps and TP1N with a high strength in combination with the influence of calcium, while maintaining the absolute values of the latter within the reference values of the norm. The authors believe that in these cases there are signs of a high functional stress of the mechanisms that contribute to maintaining analyte values within the normal range. Summarizing the results of the analysis of the selected observations, the authors believe that the mechanisms involved in the regulation of bone metabolism can be divided into two levels: local and intersystem (in particular, with the participation of leukocyte subpopulations). If the first level (primarily remodeling) weakly correlated with the influence of leukocyte subpopulations on this process, then the second, which was distinguished by significant shifts in the balance of osteosynthesis and osteolysis, included signs of activation of individual leukocyte subpopulations. In conclusion, the authors come to the conclusion that the use of the proposed method of visualizing multidimensional relationships makes it possible to determine the pathogenetic features of the formation of hypercalcemia in individual cases. At the same time, in the presence of a large database on electronic media, the technique for visualizing multidimensional relationships can be proposed as, at least, as an ‘express’ method for ‘recognizing’ different ‘images’ in the structure of the electrolyte ratio panel without actually determining osteomarkers and other complex and expensive methods for the determination of analytes that reflect osteoexchange.

Introduction. Given the possibility of preserving molecular remission in 40–60 % of patients with chronic myeloid leukemia (CML) with a stable deep molecular response (MR) after discontinuation of tyrosine kinase inhibitors (TKI), it is important to determine the number of candidates for observation in a treatment-free remission (TFR) and terms of treatment cancellation.Aim — to evaluate the probability of stable deep MR and the rate of patients who meet the criteria for TFR observation in the Russian part of the international multicenter prospective population study EUTOS PBS (European Treatment and Outcome Study — Population-Based Study).Materials and methods. Registration of all CML cases in the EUTOS PBS was conducted in 6 regions of Russia from September 2009 to December 2012. The main inclusion criterion was the diagnosis of CML confirmed by cytogenetic or molecular study in patients aged over 18 years. In total, 197 CML patients were included: 181 (92 %) with chronic phase (CP) CML, 14 (7 %) with accelerated phase (AP) and 2 (1 %) with blast crisis (BC) at diagnosis. Data on therapy and results was updated annually.Results. Deep MR (at least MR4 or BCR::ABL1 level less than 0.01 % IS) was achieved in 104 (54 %) of 192 patients receiving TKI therapy, with a median observation period of 7 years (range from 3 months to 10 years). The probability of a deep MR after 5 years of treatment was 48 % (95 % confidence interval (95% CI): 40–55 %) in patients with CP. The cumulative incidence of a stable deep MR with duration of more than 2 years in CML CP patients was 16 % (95% CI: 11–22 %) after 5 years of therapy, 29 % (95% CI: 22–37 %) after 7 years of therapy and 50 % (95% CI: 38–60 %) after 9 years of therapy. The cumulative incidence of a stable deep MR was significantly higher in those patients who had achieved a deep MR at 36 months of therapy compared to patients with only MMR: 40 % (95% CI: 28–53 %) vs. 3 % (95% CI: 0–13 %) at 5 year of therapy; 66 % (95% CI: 52–77 %) vs. 15 % (95% CI: 5–30 %) at 7 year and 89 % (95% CI: 64–97 %) vs. 48 % (95% CI: 25–67 %) at 9 year (p < 0.0001) in patients without MMR by 36 months. No patients without MMR at 36 months of therapy subsequently gained a stable deep MR. Fifty four patients met the TKI discontinuation criteria for transition into TFR phase: CP CML with a typical BCR::ABL1 p210 transcript, TKI therapy for more than 3 years and a stable deep MR for over 2 years. The rate of possible candidates for cancellation of therapy was 28 % of all 192 patients who received TKI in the study or 31 % in terms of patients with CP CML. Predominantly, patients with low-risk by Sokal or ELTS score were among the potential TFR candidates 26 (48 %) and 33 (61 %), respectively. No patients with long-term resistance to therapy were the TFR candidates.Conclusion. In the Russian portion of the prospective observational multicenter study EUTOS PBS, it was found that with a median duration of TKI therapy of 7 years, about a third of patients with CP CML may be candidates for the controlled therapy discontinuation. If half of these patients remain in molecular remission, up to 15 % of the initial number of patients will be able to continue observation in the TFR. Achievement of MMR and deep MR at 36 months of therapy is associated with a significantly greater likelihood of meeting the criteria for follow-up in the TFR phase in the future.

Vancomycin is a drug of choice for the infections caused by methicillin-resistant strains of staphylococci. Its use requires individualised dosing and renal function monitoring.The aim of the study was to evaluate, using therapeutic drug monitoring (TDM), the frequency of reaching target trough serum concentrations (TSCs) and the frequency of renal function impairment in orthopaedic infection patients receiving vancomycin therapy.Materials and methods: the authors carried out a retrospective analysis of vancomycin TSC test results of 457 patients admitted to a purulent osteology department in 2019–2021. The results were grouped according to the number of TSC determination performed as part of TDM (tests 1, 2, and 3). Each of the 3 groups was further divided into 4 subgroups according to the TSCs of vancomycin: ≤9.9 µg/ml (extremely low), 10–14.9 µg/ml (recommended for mild infections), 15–19.9 µg/ml (recommended for bone and joint infections), ≥20 µg/ml (potentially toxic). The results obtained in each group were analysed separately.Results: according to the 1st TDM test, only 9.6% of patients achieved the TSCs of vancomycin recommended for bone and joint infections. Extremely low TSCs, insufficient for treatment of the infections, were found in 64.8% of patients. According to the 2nd and 3rd TSC determinations, dose corrections decreased the percentage of patients with extremely low TSCs to 49.9% and 41.2%, respectively. Potentially toxic TSCs of vancomycin were detected in 48 (10.5%) patients, but renal dysfunction was observed only in 8 (1.75%) of them. The authors exemplify the use of TDM to control the efficacy and safety of vancomycin in patients with pronounced signs of renal function impairment by two clinical cases.Conclusion: with a standard dose of vancomycin, the concentrations recommended for bone and joint infections were reached only in every tenth patient. There was a large percentage of patients with extremely low serum concentrations of the medicinal product (64.8%), but it decreased after dose adjustments. Monitoring of vancomycin concentrations allows for individualised dosing, efficacy control and significant reduction of the risk of adverse kidney reactions.

BackgroundThe Interleukin-1 (IL-1) mediated systemic autoinflammatory diseases (SAIDs), including the cryopyrin-associated periodic syndromes (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), and deficiency of the IL-1 receptor antagonist (DIRA) belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, recently-approved treatments targeting the pro-inflammatory cytokine IL-1 have been life-changing and have significantly improved patient outcomes.ObjectivesWe aimed to establish evidence-based recommendations on diagnosis, treatment, and monitoring to standardize the management of these patients.MethodsA multinational, multidisciplinary task force consisting of physician experts including rheumatologists, patients or caregivers, and allied health care professionals was established. Evidence synthesis including systematic literature review and expert consensus (Delphi) via surveys were conducted. Consensus methodology was utilized to formulate and vote on statements to guide optimal patient care.ResultsThe task force devised five overarching principles, 14 statements related to diagnosis, 10 on therapy, and 9 focused on long-term monitoring that were evidence and/or consensus-based for patients with IL-1 mediated diseases. An outline was developed for disease-specific monitoring of inflammation-induced organ damage progression and reported therapies of CAPS, TRAPS, MKD, and DIRA.ConclusionThe 2021 EULAR/ACR points to consider provide state-of-the-art knowledge based on published data and expert opinion to guide diagnostic evaluation, treatment, and monitoring of patients with CAPS, TRAPS, MKD and DIRA, and inform the various stakeholders about optimized patient care to improve disease outcomes.

BACKGROUND: Ciliopathies include the large group of hereditary diseases caused by mutations in the genes encoding primary cilia components. The largest type of skeletal ciliopathies is short-rib thoracic dysplasia.
 AIM: This study describes the clinical and genetic characteristics of Russian patients with STRD with or without polydactyly caused by mutations in the genes DYNC2H1, DYNC2I2, IFT80, and IFT140.
 MATERIALS AND METHODS: A comprehensive examination of 10 unrelated children aged from 9 days to 9 years, with phenotypic signs of short-rib thoracic dysplasia with or without polydactyly, was conducted. The diagnosis was confirmed using genealogical analysis, clinical examination, neurological examination, radiography, and targeted sequencing of a panel consisting of 166 genes responsible for the development of inherited skeletal pathology.
 RESULTS: As a result of the molecular genetic analysis, four short-rib thoracic dysplasia genetic variants were identified. Seven patients were diagnosed with short-rib thoracic dysplasia type 3, and three unique patients were diagnosed with types 11, 2, and 9 due to mutations in the DYNC2H1 and DYNC2I2, IFT80, and IFT140 genes, respectively. From the 14 detected variants, six were identified for the first time. As in the previously described patient samples, in the analyzed sample, more than half of the cases were due to a mutation in the DYNC2H1 gene, which is responsible for the SRTD type 3. The differences in the severity of clinical manifestations and the disease course in patients with mutations in certain regions of the gene, which have a different effect on its protein product function, have been shown.
 CONCLUSIONS: The results of this molecular genetic study broaden the spectrum of mutations in the DYNC2H1, DYNC212, and IFT140 genes causing short-rib thoracic dysplasia and confirm the usefulness of the whole-exome sequencing as the most informative method for identifying mutations of the genetically heterogeneous short-rib thoracic dysplasia group.

PLX3397 is an orally administrable CSF1 receptor inhibitor that is expected to be a therapeutic agent for cell tumors such as tendon synovial giant cell tumors. Administration of high doses of PLX3397 is known to eliminate microglia selectively and may affect neuronal functions via the loss of microglia. The elimination of microglia has been known to affect exploratory tasks involving aversive stimuli. However, the effect of the microglial elimination on the ability of reward-based reinforcement learning has been unknown. In this study, C57BL6 mice were administrated with PLX3397 for three weeks and were tested with a 5-armed bandit task (5-ABT). 5-ABT is an exploratory operant conditioning task in which each of the five choices has a different reward probability. The task contains three subtasks: one in which all choices had a reward probability of 30% (ALL), a subtask in which only one choice had a reward probability of 50% and the rest had a reward probability of 0% (BIT), and a subtask in which the correct choice in BIT was reversed and four options had a reward probability of 30% (REV). As a result, there was no significant difference in the entropy of choice (exploration pattern) in the subtask ALL between the PLX3397-treated group and the control group. There was no significant difference between the groups in the number of steps required for the BIT and REV subtasks to exceed 50% correct. We also estimated the learning rates of the mice by fitting the behavioral sequences to a Q-learning model and found no significant differences between the groups. These results suggest that microglial elimination has no significant impact on reinforcement learning ability.

BACKGROUND: Jaw bone benign tumors and dysplasia in childhood often have an aggressive growth pattern, which requires early radical operations. Uneven growth and changing morphological characteristics of the childs dentofacial apparatus imply stage-by-stage bone and plastic surgery in the maxillofacial region.
 CLINICAL CASE: The paper presents a clinical observation of the medical rehabilitation of a patient from 5 to 24 years old with lower jaw osteoblastoclastoma following our proposed algorithm.
 DISCUSSION: The presented clinical observation demonstrates all the main stages of medical rehabilitation of a child with a benign lower jaw neoplasm. Along with timely and fully operative neoplasm removal, rational dental prosthetics, and dispensary observation with X-ray diagnostics play an important role in the childs growth period. All these measures were important to prevent a possible neoplasm recurrence, partially maintain the masticatory function for the growth period, and avoid secondary postoperative dental apparatus deformities. The age of repeated surgery to replace the titanium structure with autosteal tissue depends on the individual characteristics of patients. The operation can be performed, in some cases, starting from age 1617 years.
 CONCLUSIONS: Successful treatment of children with benign neoplasms of the lower jaw after post-resection defects is a complex multi-stage process of medical rehabilitation, of which the completion, most often, passes into the adult period.