Background: Low back pain (LBP) is one of the common musckloskeletal diseases and usual treated by epidural steroid injection (ESI). ESIs improve patients' quality of life, reduce lumbar radicular pain, and postpone spinal surgery. The mechanism of improvement is yet unscertain, perhaps involve type α collagen (COL2α) for bone maintenance, hence, we sought to investigate the role of injected steroids in bone healing focusing on the role of COL2α.Methods: All patients in this research were diagnosed by specialists based on their histories and clinical features and associated diseaeses or compiling therapy. Serum samples collected from LBP patients and control group for comparisons.Results: The present study found a significant (<0.0001) increase in the concentration of COL2α in patients with LBP after injection with ESI treatment compared with patients before injection and healthy individuals.Conclusion: ESI helps LBP sufferers by boosting COL2α, which repairs damaged tissues.

• MeSH
• Biomarkers analysis   MeSH
• Back Pain * drug therapy   MeSH
• Glucocorticoids administration & dosage   pharmacology   therapeutic use   MeSH
• Injections, Epidural * methods   MeSH
• Clinical Studies as Topic methods   MeSH
• Collagen Type II * administration & dosage   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Pain Management methods   MeSH
• Radiculopathy etiology   drug therapy   MeSH
• Bone Regeneration drug effects   MeSH
• Check Tag
• Humans MeSH

PURPOSE: Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep-learning strategies on histology samples to predict outcome for osteosarcoma in the neoadjuvant setting. EXPERIMENTAL DESIGN: Our study relies on a training cohort from New York University (NYU; New York, NY) and an external cohort from Charles University (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content and compared predicted overall survival (OS) using Kaplan-Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphologic features could serve as a potential marker for OS in the neoadjuvant setting. RESULTS: Excellent correlation between the trained network and pathologists was obtained for the quantification of necrosis content (R2 = 0.899; r = 0.949; P < 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). The morphology-based supervised approach predicted OS; P = 0.0028, HR = 2.43 (1.10-5.38). The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS [log-2 hazard ratio (lg2 HR); -2.366; -1.164; -1.175; 95% confidence interval, (-2.996 to -0.514)]. Viable/partially viable tumor and fat necrosis were associated with worse OS [lg2 HR; 1.287; 0.822; 0.828; 95% confidence interval, (0.38-1.974)]. CONCLUSIONS: Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphologic biomarkers specific to the necrotic and tumor regions, which could serve as predictors.

• MeSH
• Deep Learning MeSH
• Child MeSH
• Adult MeSH
• Kaplan-Meier Estimate MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Bone Neoplasms * mortality   pathology   MeSH
• Necrosis * MeSH
• Neoadjuvant Therapy * methods   MeSH
• Neural Networks, Computer * MeSH
• Osteosarcoma * mortality   pathology   therapy   MeSH
• Prognosis MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

NASA has encouraged studies on 226Ra deposition in the human brain to investigate the effects of exposure to alpha particles with high linear energy transfer, which could mimic some of the exposure astronauts face during space travel. However, this approach was criticized, noting that radium is a bone-seeker and accumulates in the skull, which means that the radiation dose from alpha particles emitted by 226Ra would be heavily concentrated in areas close to cranial bones rather than uniformly distributed throughout the brain. In the high background radiation areas of Ramsar, Iran, extremely high levels of 226Ra in soil contribute to a large proportion of the inhabitants' radiation exposure. A prospective study on Ramsar residents with a calcium-rich diet was conducted to improve the dose uniformity due to 226Ra throughout the cerebral and cerebellar parenchyma. The study found that exposure of the human brain to alpha particles did not significantly affect working memory but was significantly associated with increased reaction times. This finding is crucial because astronauts on deep space missions may face similar cognitive impairments due to exposure to high charge and energy particles. The current study was aimed to evaluate the validity of the terrestrial model using the Geant4 Monte Carlo toolkit to simulate the interactions of alpha particles and representative cosmic ray particles, acknowledging that these radiation types are only a subset of the complete space radiation environment.

• MeSH
• DNA MeSH
• Humans MeSH
• Linear Energy Transfer MeSH
• Monte Carlo Method MeSH
• Brain MeSH
• Prospective Studies MeSH
• Radium * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Sarcoma is a heterogeneous group of malignancies often resistant to conventional chemotherapy and radiation therapy. The phosphatidylinositol-3-kinase/ protein kinase B /mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway has emerged as a critical cancer target due to its central role in regulating key cellular processes such as cell growth, proliferation, survival, and metabolism. Dysregulation of this pathway has been implicated in the development and progression of bone sarcomas (BS) and soft tissue sarcomas (STS). PI3K/Akt/mTOR inhibitors have shown promising preclinical and clinical activity in various cancers. These agents can inhibit the activation of PI3K, Akt, and mTOR, thereby reducing the downstream signaling events that promote tumor growth and survival. In addition, PI3K/Akt/mTOR inhibitors have been shown to enhance the efficacy of other anticancer therapies, such as chemotherapy and radiation therapy. The different types of PI3K/Akt/mTOR inhibitors vary in their specificity, potency, and side effect profiles and may be effective depending on the specific sarcoma type and stage. The molecular targeting of PI3K/Akt/mToR pathway using drugs, phytochemicals, nanomaterials (NMs), and microbe-derived molecules as Pan-PI3K inhibitors, selective PI3K inhibitors, and dual PI3K/mTOR inhibitors have been delineated. While there are still challenges to be addressed, the preclinical and clinical evidence suggests that these inhibitors may significantly improve patient outcomes. Further research is needed to understand the potential of these inhibitors as sarcoma therapeutics and to continue developing more selective and effective agents to meet the clinical needs of sarcoma patients.

• MeSH
• Phosphatidylinositol 3-Kinases * metabolism   MeSH
• Phosphoinositide-3 Kinase Inhibitors pharmacology   therapeutic use   MeSH
• Protein Kinase Inhibitors pharmacology   chemistry   therapeutic use   MeSH
• Humans MeSH
• MTOR Inhibitors pharmacology   therapeutic use   MeSH
• Antineoplastic Agents * pharmacology   chemistry   therapeutic use   MeSH
• Proto-Oncogene Proteins c-akt * metabolism   antagonists & inhibitors   MeSH
• Sarcoma * drug therapy   metabolism   pathology   MeSH
• Signal Transduction * drug effects   MeSH
• TOR Serine-Threonine Kinases * antagonists & inhibitors   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Vertebral fragility fractures (VFFs) commonly result from low bone mass and microarchitecture deterioration of bone tissue. spinal orthoses are common non-pharmacological options for managing vertebral fracture pain. However, the effects of spinal orthoses on pain, physical functioning, and quality of life (QoL) are still debated. OBJECTIVE: This survey aimed to investigate the patients-reported outcomes of a dynamic spinal orthosis prescribed in the routine clinical practice of VFFs management. METHODS: This multi-center national-wide prospective cohort study assessed older patients (aged > 60 years) diagnosed with acute VFFs and prescribed with a dynamic spinal orthosis (Spinfast®). A survey questionnaire was realized and included sections on patient characterization, osteoporosis characterization, spinal orthosis, clinical outcomes, pain medications, and osteoporosis medications. The questionnaire was administered at baseline and after three months. A total of 68 patients completed the questionnaire at three months. Most patients had one or two VFFs and were treated with pain medications and osteoporosis medications. Compliance and tolerability of the spinal orthosis were assessed, and clinical outcomes such as pain intensity, physical functioning, and QoL were measured. RESULTS: The results showed no significant differences in outcomes between age subgroups. Italian physical medicine and rehabilitation physicians were commonly involved in the management of VFFs patients. Sixty-six patients completed the questionnaire. The results showed that pain intensity, physical functioning and QoL improved after three months of spinal orthosis wearing (p< 0.0001). CONCLUSION: The correct management of VFFs is mandatory to improve pain and reduce disability, and our findings suggested a positive role of dynamic spinal orthosis to improve the comprehensive management of VFFs patients. However, high-quality research trials are warranted to provide clear recommendations for the correct clinical management of VFF.

• MeSH
• Back Pain rehabilitation   therapy   MeSH
• Spinal Fractures * rehabilitation   MeSH
• Patient Reported Outcome Measures MeSH
• Quality of Life * MeSH
• Middle Aged MeSH
• Humans MeSH
• Pain Measurement MeSH
• Osteoporotic Fractures * rehabilitation   MeSH
• Prospective Studies MeSH
• Orthotic Devices * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Self Report MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.

• MeSH
• Progression-Free Survival MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   administration & dosage   MeSH
• Carcinoma, Transitional Cell therapy   pathology   mortality   drug therapy   MeSH
• Combined Modality Therapy MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Bladder Neoplasms therapy   pathology   mortality   drug therapy   MeSH
• Antineoplastic Agents, Immunological therapeutic use   MeSH
• Radiosurgery methods   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Urologic Neoplasms pathology   mortality   therapy   drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment. Building on previous findings that identified the loss of IL-7 receptor expression as a possible cause of the immunodeficiency and increased sensitivity to radiation-induced damage, we have employed spectral cytometry and multiplex RNA-sequencing to assess the phenotype and function of T cells ex-vivo and to study changes induced by in-vitro UV irradiation and reaction of cells to the presence of IL-7. Our findings highlight the mature phenotype of T cells with proinflammatory Th1 skew and signs of exhaustion and lack of response to IL-7. UV light irradiation caused a severe increase in the apoptosis of T cells, however the expression of the genes related to immune response and regulation remained surprisingly similar to healthy cells. Due to the disease's rarity, more studies will be necessary for complete understanding of this unique immunodeficiency.

• MeSH
• Apoptosis genetics   MeSH
• Arteriosclerosis genetics   etiology   immunology   MeSH
• Child MeSH
• DNA Helicases genetics   MeSH
• Humans MeSH
• Bone Diseases, Metabolic etiology   genetics   MeSH
• Nephrotic Syndrome etiology   genetics   MeSH
• DNA Repair * genetics   MeSH
• Osteochondrodysplasias * genetics   immunology   MeSH
• Pulmonary Embolism genetics   etiology   MeSH
• Growth Disorders genetics   etiology   MeSH
• Primary Immunodeficiency Diseases * genetics   diagnosis   immunology   MeSH
• Immunologic Deficiency Syndromes genetics   immunology   MeSH
• T-Lymphocytes immunology   MeSH
• Ultraviolet Rays adverse effects   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes. METHODS: We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration's RoB tool. Random-effects models were used for the meta-analysis. RESULTS: A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes. CONCLUSIONS: The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.

• Publication type
• Journal Article MeSH
• Review MeSH

Effects of pre/postnatal 2.45 GHz continuous wave (CW), Wireless-Fidelity (Wi-Fi) Microwave (MW) irradiation on bone have yet to be well defined. The present study used biochemical and histological methods to investigate effects on bone formation and resorption in the serum and the tibia bone tissues of growing rats exposed to MW irradiation during the pre/postnatal period. Six groups were created: one control group and five experimental groups subjected to low-level different electromagnetic fields (EMF) of growing male rats born from pregnant rats. During the experiment, the bodies of all five groups were exposed to 2.45 GHz CW-MW for one hour/day. EMF exposure started after fertilization in the experimental group. When the growing male rats were 45 days old in the postnatal period, the control and five experimental groups' growing male and maternal rats were sacrificed, and their tibia tissues were removed. Maternal rats were not included in the study. No differences were observed between the control and five experimental groups in Receptor Activator Nuclear factor-kB (RANK) biochemical results. In contrast, there was a statistically significant increase in soluble Receptor Activator of Nuclear factor-kB Ligand (sRANKL) and Osteoprotegerin (OPG) for 10 V/m and 15 V/m EMF values. Histologically, changes in the same groups supported biochemical results. These results indicate that pre/postnatal exposure to 2.45 GHz EMF at 10 and 15 V/m potentially affects bone development.

• MeSH
• Electromagnetic Fields * adverse effects   MeSH
• Rats MeSH
• Microwaves * adverse effects   MeSH
• Rats, Sprague-Dawley MeSH
• Pregnancy MeSH
• Bone Development MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

PURPOSE OF THE STUDY: Temporary hemiepiphyseodesis using figure-eight plates is currently one of the main surgical techniques to correct axial deformities of lower limbs in paediatric patients. Comprehensive analysis, correct indication and monitoring of treatment are the basic prerequisites for successful therapy. The aim of the study was to analyse parameters that could become an alternative to standard parameters used nowadays, namely the inserted screw angle (SA), and a new parameter - condylar ratio (CR). MATERIAL AND METHODS: The study included 47 patients treated at the Department of Paediatric Surgery, Orthopaedics and Traumatology at the University Hospital in Brno between 2014 and 2021 and diagnosed with idiopathic bilateral axis deviation of lower limbs, namely genu valgum. After having met the inclusion criteria, the patients underwent a clinical check-up, and long leg radiographs were also obtained. Anthropometric parameters (age, sex, BMI, intermalleolar distance (IMD)), duration of treatment as well as radiographic parameters - mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), SA and CR, and their derived parameters expressing the change per unit time and defined as a rate of correction (r-mLDFA, r-mMPTA, r-SA, r-CR) were recorded. The obtained values were subsequently statistically analysed, namely by comparing the pretreatment and posttreatment values and through correlation analysis. RESULTS: The mean age of the population was 11.4 years, BMI 26.9 and IMD 14.1. The mean duration of treatment in the study population was 13.9 months. A significant difference was established between the pretreatment and posttreatment values of all measured radiographic parameters (p<.05). A significant correlation was identified between r-mLDFA and r-SA (p=.002), while no significant correlation was found between r-mLDFA and r-CA or between r-CA and r-SA (p=.650; p=.884). DISCUSSION: Comprehensive evaluation of the treatment of axial deformities of lower limbs and its optimization are crucial for successful therapy. In addition to the standard mechanical or even anatomical parameters assessing the axis deviation of lower limbs, the authors seek to evaluate also other parameters that may provide a new insight into the deformity or offer additional benefits such as reduced radiation exposure. Such a parameter is for instance the angle of inserted screws in the eight-figure plate system, although there is a difference in opinion among the authors. In our study, we concluded that it is the change in the screw angle that significantly correlates with the mechanical axis of the femur, and thus, under certain circumstances, can become a monitoring parameter. Contrarily, the condylar ratio is a newly introduced quantity which in our study did not show any significant correlation with the mechanical axis of the femur, although a significant change before and after therapy was observed. CONCLUSIONS: A significant correlation was established between the rate of change in screw angle and r-mLDFA, which may, under certain circumstances, serve as a parameter for treatment evaluation, with the advantage of reduced radiation exposure since the assessment requires one scan of the knee joints under loading only. On the other hand, though, no significant correlation was established between the CR as the newly defined parameter and r-mLDFA, which is why it can only be considered as a complementary parameter rather than a decisive one. KEY WORDS: temporary hemiepiphysiodesis, growth plate, genua valga, screw angle, correlation.

• MeSH
• Child MeSH
• Femur surgery   abnormalities   diagnostic imaging   MeSH
• Genu Valgum * surgery   MeSH
• Bone Plates * MeSH
• Bone Screws * MeSH
• Humans MeSH
• Adolescent MeSH
• Radiography methods   MeSH
• Tibia surgery   abnormalities   diagnostic imaging   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH