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BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

A two-dimensional, finite-difference numerical model is developed to simulate the breach evolution of noncohesive optimally compacted earthen dams. The main feature of the model is the inclusion of a source term in the sediment mass conservation equation that explicitly describes breach widening due to mass slumping of the breach sides. Model results are compared against experimental measurements of time variation of breach width and depth, breach discharge, and reservoir water depth for embankments of different sizes, sediment median grain sizes, inflow discharges, and reservoir volumes. The numerical model successfully captures the two stages of failure, namely, prewidening and widening. Then, the model is applied to simulate the overtopping failure of an earthen dam that occurred due to Hurricane Joaquin in October 2015 in Lexington, South Carolina. A sensitivity analysis is conducted to assess the effect of the main model parameters on the prediction of breach evolution. This analysis shows that breaching is affected more by tailwater depth than the soil failure angle and inlet discharge. [ABSTRACT FROM AUTHOR]

Light-chain multiple myeloma (LCMM) is a rare subtype of plasma cell neoplasm, usually linked to kidney involvement and lytic bone lesions. However, case presents as osseus tumors are very uncommon. A 63-year-old male patient complained of persistent rib pain. Computed tomographic imaging showed an isolated bone tumor in the eighth rib. Further positron emission tomography–computed tomographic scan revealed multiple lytic bone lesions in other areas. Biopsy of the rib lesion confirmed the presence of plasma cells producing kappa light chains. The patient received 4 cycles of daratumumab, bortezomib, lenalidomide, and dexamethasone treatments, resulting in significant improvement. Reviewing literatures, osseus tumor with osteosclerotic lesions has been rarely described in LCMM, underlining the challenge in diagnosis and stressing the importance of considering LCMM in the differential diagnosis of bone tumors. [ABSTRACT FROM AUTHOR]

This paper focuses on deploying Computational Fluid Dynamics (CFD) and Fluid-Structure Interaction (FSI) to investigate key characteristics associated with Cardiovascular Diseases (CVDs), a leading cause of global mortality. CVDs encompass various heart and blood vessel disorders, including coronary artery disease, stroke and atherosclerosis, which significantly impact arteries. Risk factors such as high blood pressure and obesity contribute to atherosclerosis, which is characterized by narrowed arteries due to fatty deposits, impeding blood flow and increasing heart attack and stroke risks. To simulate blood flow behaviour and its effects on artery stenosis formation, ANSYS-based CFD and monolithic (one-way) FSI analyses are deployed in this work. Extensive visualization of blood flow patterns relevant to patient-specific conditions is included using the non-Newtonian (Carreau shear-thinning) bio-rheological model. These simulations start with creating a three-dimensional patient artery model, followed by applying CFD/FSI methodologies to solve the equations iteratively with realistic boundary conditions. Velocity, pressure, wall shear stress (WSS), Von Mises stress and strain characteristics are all computed for multiple curvature cases and different stenotic depths. Factors such as blood viscosity, density and its nonNewtonian behaviour due to red blood cells are considered. FSI analysis extends CFD by including the interaction between blood flow and deformable (elastic) arterial walls, accounting for the arterial mechanical properties and the flow-induced pressure changes. Here we do not consider the two-way case where deformation in turn affects the flow, only the one-way case where the blood flow distorts the arterial wall. This approach allows for deeper insight into the interaction between rheological blood flow and elastic arterial walls which aids in highlighting high stress zones, recirculation and hemodynamic impedance of potential use in identifying rupture or plaque formation, contributing significantly to the management and prevention of CVDs. The novelties of the present study are the simultaneous consideration of rigorous visualization of hemodynamic characteristics for a wide range of stenotic depths of direct relevance to patient-specific conditions (both diastolic and systolic phases are included), inclusion of non-Newtonian (Carreau shear-thinning) bio-rheology, multiple arterial curvatures, and also flow-structural interaction analysis. Previous studies have invariably considered only aspects of these multiple features. This article therefore generalizes and significantly extends previous studies and will be of benefit to clinicians and other researchers engaged in computational medical fluid dynamics. [ABSTRACT FROM AUTHOR]