Von Hippel-Lindau syndrome (FHL) is a rare autosomal dominant disease that leads to the formation of multiple organ tumor syndrome. The pathology is primarily caused by the inactivation of the VHL gene, which is located on chromosome 3 (3p25/26) and encodes ubiquitin ligase, which destroys hypoxia-induced factor-1α (HIF-1α). The genetic defect leads to the accumulation of HIF-1a protein, activating key carcinogenic pathways, and activated cytokines cause abnormal proliferation of tumor cells and oncogenesis. To date, more than 500 mutations have been registered in VHL. FHL syndrome is characterized by various tumors, including hemangioblastomas of the retina and central nervous system, pheochromocytomas, clear cell renal cell carcinoma, cystic adenoma and others. In the presented clinical description, pheochromocytoma was initially diagnosed in the patient’s mother, and 2 months later in the eldest son. Subsequently, the results of a molecular genetic study made it possible to verify the diagnosis, since in the gene in exon 3 of VHL, a single nucleotide was replaced in the heterozygous state of C.500 G>A, leading to the replacement of the amino acid p.R167Q. Identification of the VHL gene mutation required genetic counseling of all family members, during which a similar mutation was identified in the younger brother. Surgical treatment is the main method of treating FHL syndrome, but advances in genetic research technologies provide new opportunities for the treatment of tumors associated with this syndrome.
Introduction. Although urolithiasis is more common in adults, kidney stones can be visualized in children. The increased incidence of urolithiasis in children is associated with changes in diet, genetic factors, and lifestyle. Extracorporeal shock wave lithotripsy (ESWL) is a minimally invasive treatment option for urolithiasis in children. Objective: to evaluate the effectiveness of extracorporeal shock wave lithotripsy in children at the City Clinical Hospital of Emergency Medical Care (hereinafter referred to as the City Clinical Hospital of Emergency Medical Care) in Stavropol. Materials and methods. A retrospective analysis of the treatment outcomes for urolithiasis in pediatric patients (n=37) using extracorporeal shock wave lithotripsy was conducted between 2015 and 2023. Treatment efficacy was assessed based on the number of procedures required for a given patient to achieve satisfactory fragmentation of the calculus, as well as the presence of complications. Results. From 2015 to 2023, extracorporeal shock wave lithotripsy was performed on 37 pediatric patients (hereinafter n) in the Stavropol City Clinical Hospital of Emergency Medical Care, including 24 (64.9 %) boys and 13 (35.1 %) girls. The average age of the patients was 12.1±3.2 years. The most common location of stones in pediatric patients was the renal pelvis (17; 45.9 %). Most patients required one fragmentation session (n=20; 54.0 %), 14 (37.8 %) patients required two sessions, and the remaining children required a third (n=2; 5.4 %) or even a fourth session (n=1; 2.7 %) to achieve satisfactory fragmentation of the stone. We did not observe any complications during the lithotripsy session itself in pediatric patients. After performing extracorporeal shock wave lithotripsy in children, we encountered the following complications: hematuria (n=9; 24.3 %), renal colic (n=5; 13.5 %), urinary tract infection (n=2; 8.3 %), which were stopped by conservative therapy methods. Conclusion. Extracorporeal shock wave lithotripsy is an effective, virtually non-invasive treatment for urolithiasis in children with stones up to 20 mm in diameter. Its high efficacy, feasibility, and minimal recovery time make it the preferred treatment method for urolithiasis in children.
Background. Prior to the introduction of new agents — immune checkpoint inhibitors — for inoperable and/or metastatic melanoma (IMM), chemotherapy outcomes were generally poor. The median (Me) overall survival (OS) in IMM was no more than 6-9 months, and the Me of progression-free survival (PFS) was about 2 months. The introduction of immune checkpoint inhibitors and targeted therapy changed the prognosis for the life of IMM patients dramatically. The development, studies, and approval of a new original PD-1 inhibitor, prolgolimab, in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess its real-world efficacy and safety. Aim To evaluate the real-world efficacy and safety of prolgolimab in patients with IMM. Materials and methods. From October 2020 to October 2022, 700 patients with IMM receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation were included in the study. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma; metastatic and/or inoperable type; use of prolgolimab outside of clinical trials; and signed informed consent. Objective response rate in the general population and the Intention-to-treat and Per Protocol populations was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 3-4 adverse events (AEs). PFS and OS rates were also assessed. Statistical analysis was performed using the SPSS 25.0 software package. Results. The objective response rate for the Per Protocol population (with radiographic assessment available) was 42% (n=235/559). Disease progression was reported in 26.7% (n=149) of patients, stabilization in 31.3% (n=175), and disease control in 73.3% of patients with IMM, regardless of the line of therapy. At the follow-up Me of 12 months (0-36), PFS for all patients regardless of the line of therapy was 8 months (95% confidence interval [Cl] 6.537-9.463), 6-month PFS was 55%, and 12-month PFS was 41%. OS Me for all included patients was 32 months, 6-month OS was 82%, and 12-month OS was 69%. Depending on the line of therapy, the OS Me was: line 1 - not reached, line 2-30 months (95% Cl 16.007-43.993), line 3 and subsequent- 22 months (95% Cl 14.264-29.736); p=0.736. According to the CTCAE 5.0 general terminology criteria for AEs, a total of 136/693 (19.6%) AEs of varying degrees were reported, in particular: grade 1-2 - 105/693 (15.2%), grade 3-4 - 25/693 (3.6%), unknown grade - 5/693 (0.7%), as well as one fatal case (0.1%) due to thromboembolism in the vascular center with an unclear (according to the investigator's assessment) relation with prolgolimab. Conclusion The results obtained at 12 months of follow-up confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with IMM in real-world practice, regardless of the line of therapy and other characteristics.
Hypothyroidism is a clinical syndrome caused by hypofunction of the thyroid gland and characterized by a decrease in the content of thyroid hormones in the blood serum.Clinical manifestations of hypothyroidism can be diverse and depend on its etiology, the age of the patient, as well as the rate of development of thyroid hormone deficiency.The disease may have a pronounced clinical picture or, conversely, have no clinical manifestations and be detected randomly.Moreover, the signs of hypothyroidism very often mimic (mask) another pathology.Therefore, the diagnosis of hypothyroidism in some cases is difficult.In this work, a systematic analysis of the literature and clinical studies was carried out, and the negative effect of hypothyroidism in a patient on the liver, biliary system and pancreas was established.When analyzing the effect of hypothyroidism on the liver, no changes were observed in the organ itself.However, serum enzymes increased, such as aspartate aminotransferase, lactate dehydrogenase, and creatine phosphokinase.Violation of lipid metabolism in the liver with hypothyroidism can lead to obesity, which is never significant.Hypothyroidism revealed a violation of the biliary system and the development of cholelithiasis.There is a scientific study on the relationship between hypothyroidism and the formation of stones in the common bile duct.
e18788 Background: Maintaining relative dose intensity (RDI) of chemotherapy is important to ensure optimal patient outcomes in a variety of solid cancers. RDI < 85% significantly decrease therapy efficiency (including overall survival) in almost solid tumors (ST). Chemotherapy-induced neutropenia (CIN) is the most common adverse event (AE) leading to low RDI. Proper administration of primary G-CSF prophylaxis (PP) allows to achieve optimal therapy efficiency. There are several trials and meta-analyses have shown a superior efficiency prolonged G-CSF vs short G-CSF. This multicenter prospective observational post-registration study of prolonged G-CSF empegfilgrastim (Extimia) was designed to evaluate the RDI of the cytotoxic therapy course under PP by empegfilgrastim in patients (pts) with ST receiving myelosuppressive therapy in the routine clinical practice. Methods: 2000 pts with ST receiving cytotoxic therapy (4-8 cycles per course are allowed) under PP with empegfilgrastim by investigator choice in the routine clinical practice. RDI of therapy course was primary endpoint and presented here for pts who completed the planned regimen. For each agent, both the planned and actual dose intensity were calculated by dividing the total cumulative dose by treatment duration in days. RDI was calculated for each single agent in chemotherapy-based (CTb) regimen and for CTb regimen in total. These descriptive analyses and RDI calculations were performed for the whole CT based regimen (chemotherapeutic agents, molecular target agents, monoclonal antibodies). Funded by JSC Biocad; Defendor ClinicalTrials.gov No NCT04811443. Results: At the data cut-off 1074 pts from 31 Russian sites underwent ≥ one cycle of CTb regimens combined with empegfilgrastim. Distribution of all-cancer types was in line with epidemiology data in Russia. 526 pts completed the planned CT course. 352 (66,9%) of them have at least onе of FN risk factor. RDI≥85% were achieved in 492 (93,5%) pts. RDI by key nosology is presented in Tab.1. 118 (22,4%) cases of interval prolongation and/or dose reduction was registered. The main reasons of RDI decrease were personal pts’s issues 69 (13,1%), COVID-19 pandemic 26 (4,9%), holidays 9 (1,7%) and others. Neutropenia was in 6 (1,1%) cases as a reason of RDI decrease. Treatment-related AEs of grade 1-2 occurred 12 (2,3%) pts (back pain, ossalgia, myalgia). Conclusions: Thus, PP with prolonged G-CSF empefilgrastim allows effectively maintain RDI in different nosology and treatment groups in pts with ST in the routine clinical practice.[Table: see text]
