Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients

Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1mg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2mg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations

Technological and sustainability implications of dry, near-dry, and wet turning of Ti-6Al-4V alloy

Titanium-based alloys are commonly applied in high-performing structural components. Their machinability could be penalized by severe tool wear and poor surface quality. As a result, cutting fluids are widely used to improve the production rate without negatively affecting the machined surface integrity and the tool life. The experimental research activities presented in this paper are focusing on the effects of dry and near-dry cutting conditions on machining process performance when turning Ti-6Al-4V. Minimum Quantity Cooling/Lubrication systems have been exploited to supply low cutting fluid volumes to the cutting area in the form of a precisionmetered droplets mist. The conventional flood cooling (i.e., wet cutting) has been assumed as benchmark. Results are discussed with respect to tool wear/life, cutting forces, process power demand, surface quality, lubricoolant consumption, and human health hazards. All the main factors of influence are highlighted, and guidelines for identifying the trade-off between the minimization of environmental impact and the enhancement of process productivity are proposed

Tool life and surface integrity when turning titanium aluminides with PCD tools under conventional wet cutting and cryogenic cooling

The high-performance machining of difficult-to-cut alloys requires the development and optimization of high performance tools, able to withstand the thermo-mechanical tool load without compromising the surface quality of produced components. In this context, the machinability of titanium aluminides still represents a demanding challenge. In this paper, the performance of cubic boron nitride (CBN) and polycrystalline diamond (PCD) cutting inserts is compared to that of uncoated and coated carbide tools. Longitudinal external turning tests were performed on a Ti-43.5Al-4Nb-1Mo-0.1B (TNM) at.% cast and hot isostatically pressed (HIPed) γ-TiAl alloy, by using a conventional lubrication supply. In addition, PCD tools were also applied under cryogenic cooling with liquid nitrogen. Results proved that PCD cutting tools have the potential to improve the machining productivity of titanium aluminides, due to their high hardness and excellent thermal conductivity. A noteworthy further increase of tool life was possible by using PCD cutting inserts under cryogenic cooling condition

AlSiTiN and AlSiCrN multilayer coatings: Effects of structure and surface composition on tribological behavior under dry and lubricated conditions

Nanocomposite coatings have been widely studied over the last years because of their high potential in several applications. The increased interest for these coatings prompted the authors to study the tribological properties of two nanocomposites under dry and lubricated conditions (applying typical MQL media), in order to assess the influence of the surface and bulk properties on friction evolution. To this purpose, multilayer and nanocomposite AlSiTiN and AlSiCrN coatings were deposited onto tungsten carbide-cobalt (WC-Co) samples. Uncoated WC-Co materials were used as reference. Coatings were analyzed in terms of hardness and adhesion. The structure of the samples was assessed by X-ray diffraction (XRD), while the surface composition was studied by XPS analysis. Friction tests were carried out under both dry and lubricated conditions using an inox ball as counterpart. Both coatings showed high hardness and good adhesion to the substrate. As far as the friction properties are concerned, in dry conditions the surface properties affect the sliding contact at the early beginning, while bulk structure and tribolayer formation determine the main behavior. Only AlSiTiN coating shows a low and stable coefficient of friction (COF) under dry condition, while the use of MQL media results in a rapid stabilization of the COF for all the material

Ventriculoperitoneal shunts for treating increased intracranial pressure in cryptococcal meningitis with or without ventriculomegaly

Introduction Cryptococcosis is an opportunistic mycosis, especially in patients that are human immunodeficiency virus (HIV)-positive, and frequently involves the central nervous system. Methods We assessed the potential of ventriculoperitoneal shunting (VPS) in preventing mortality due to uncontrollable intracranial hypertension (ICH) in 15 patients with acquired immunodeficiency syndrome (AIDS)-related cryptococcal meningitis. Results After 2 weeks of antifungal therapy consisting of amphotericin B deoxycholate with or without fluconazole, patients with persistent ICH underwent VPS, despite having persistent Cryptococcus neoformans infection. In 12 patients, the uncontrollable ICH was resolved by VPS. Conclusions Patients with cryptococcal meningoencephalitis who have ICH must be considered for VPS even with positive cerebrospinal fluid cultures

Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients

Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1mg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2mg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations.Fil: Fernandez, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Marson, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; ArgentinaFil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; ArgentinaFil: Corti, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Fleitas, Ulises Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; ArgentinaFil: Lloveras, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Lista, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Priarone, Maria M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Dominguez, Cecilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Garcia-Bournissen, Facundo. Western University; Canad