Activity

The recurrence of the reason was more common than other reasons after index rTKA for infection (18%), instability (8%), stiffness (7%), and loosening (5%).Interpretation – Poorest outcomes were found for rTKA for infection over 1 out of 4 infection rTKAs required another surgical intervention, mostly due to infection. Recurrence of other reasons for revision (instability, stiffness, and loosening) was also considerable. Our findings also emphasize the importance of a clear diagnosis before doing rTKA to avert second revision surgeries.This case report presents the first reported pediatric case of primary classical nodular sclerosing Hodgkin Lymphoma (HL) with pineal gland involvement, presenting without CNS symptoms, which completely resolved after 2 cycles of chemotherapy. The 12 year-old male first presented with a right inguinal mass and external iliac lymphadenopathy accompanied by B symptoms. He was diagnosed with stage IV B classical HL, and as part of the staging work-up, a full-body PET/CT scan was performed. Setanaxib purchase In addition to the right inguinal mass, the PET/CT demonstrated increased FDG uptake at the pineal gland along with level II lymph nodes. The patient was treated with ABVE-PC chemotherapy (Doxorubicin, Bleomycin, Vincristine, Etoposide, Prednisone, and Cyclophosphamide) as per standard arm of AHOD1331 COG protocol for newly diagnosed high-risk HL patients, which resolved the pineal mass after 2 cycles without requiring radiation therapy. Following 5 cycles, a full-body PET/CT showed no brain or neck activity, along with decreased size and activity of the right groin mass. To our knowledge, there are no other documented cases of primary HL with specific pineal involvement, and no cases that lack CNS symptoms altogether like this one did. Additionally, this is the third published pediatric case of primary CNS-HL, both of the previous cases were treated with radiotherapy and presented with CNS symptoms. Thus, this case demonstrates the importance of ordering a full-body PET/CT as part of the initial HL work-up and provides evidence that chemotherapy alone is a treatment option for some patients with primary intracranial HL.This study reports the synthesis of new indol(1H-3-yl) pyrimidine derivatives 4(a-e) using various substituted indole-3-carbaldehydes, urea and malononitrile in the presence of ammonium chloride. The resulting compounds were characterized using analytical and spectroscopic methods. The molecular docking study exhibits that among the synthesized compounds, 4(c-e) have great binding ability toward B-DNA. The binding efficiencies of compounds 4(c-e) with CT-DNA were evaluated via UV-visible absorption spectral and viscosity studies. The findings establish that the compounds firmly bind through an intercalative mode to CT-DNA and provide a unique pattern of DNA binding. The photo-induced cleavage indicates that the compounds have UV-visible photo nuclease properties toward plasmid DNA as revealed by agarose gel electrophoresis approach.At present, disrupting p53-MDM2 interactions through small molecule ligands is a promising approach to safe treatment and management of human cancer. Tumor cells unlike the normal cells, are rapidly evolving affecting the efficacy of many approved anti-cancer agents due to drug resistance. Therefore, identifying a potential anticancer compound is crucial. Pharmacophore based virtual screening, followed by molecular docking, ADMET evaluation, and molecular dynamics studies against MDM2 protein was investigated to identify potential ligands that may act as inhibitors. The model (AHRR_1) with survival score (4.176) was selected among the top ranked generated Pharmacophore hypothesis. Validation of the model hypothesis by an external dataset of actives and inactive compounds produced significant validation attributes including; AUC = 0.85, BEDROC = 0.56 at α = 20.0, RIE = 8.18, AUAC = 0.88, and EF of 6.2 at the top 2% of the dataset. The model was use for screening the ZINC database, and the top 1375 hits satisfying the model hypothesis were subjected to molecular docking studies to understand the molecular and structural basis of selectivity of compounds for MDM2 protein. A sub-set of 25 compounds with binding energy lower than the reference inhibitors were evaluated for pharmacokinetic properties. Four compounds (ZINC02639178, ZINC06752762, ZINC38933175, and ZINC77969611) showed the most desired pharmacokinetic profile. Lastly, investigation of the dynamic behaviour of leads-protein complexes through MD simulation showed similar RMSD, RMSF, and H-bond occupancy profile compared to a reference inhibitor, suggesting stability throughout the simulation time. However, ZINC02639178 was found to satisfy the molecular enumeration the most compared to the other three leads. It may emerge as potential treatment option after extensive experimental studies. Communicated by Ramaswamy H. Sarma.Background and purpose – Extensive research and national multidisciplinary programs have striven to introduce uniform standards of treatment and mitigate mortality and adverse events after hip fracture surgery over the past decades. A large-scale overview of temporal developments in hip fracture surgery and care is warranted.Patients and methods – We studied Danish patients aged ≥ 60 years, sustaining their first ever hip fracture between 1997 and 2017. Patients were identified from the Danish National Patient Registry (DNPR). Incidence rates of first hip fracture were calculated per 1,000 patient-years and stratified by age group and sex. Information on pre-injury living settings, comorbidities, and medications were obtained from national administrative registers. Type of fracture and treatment choice were recorded, and patients were followed for 1 year to observe mortality, readmission, and surgical complications.Results – Data from 153,058 patients was analyzed. Incidence rate decreased in both sexes, but only led to a reduction in the annual number of hip fractures in the female population. Choice of surgery shifted away from sliding hip screws and parallel implants (SHS-PI), towards intramedullary nailing and hemi-/arthroplasties for trochanteric and femoral neck fractures, respectively. Pre-injury diagnosed morbidity and 1-year readmissions increased contrary to mortality. Median age remained stable around 83 (IQR 77-88) for women and 80 (IQR 73-86) for men.Interpretation – Over the past 2 decades important aspects of hip fracture management have improved. However, sex differences were observed, and men remain more vulnerable than women in terms of morbidity, mortality, and incidence rate.