Antifungal Treatment Duration in Hematology Patients With Invasive Mold Infections: A Real-life Update.

Background: Limited data exist on when and how to stop antifungal treatment (AFT) in patients with invasive mold infections (IMIs) who are immunocompromised. Methods: This retrospective multicenter study included adult patients with acute myelogenous leukemia and proven/probable IMI (1 January 2010-31 December 2022) in 3 university hospitals. The primary objective was to describe AFT duration and adaptation. Secondary objectives were to investigate the reasons for AFT adjustments and prolongation. Results: In total 71 patients with 73 IMIs were identified; 51 (71.8%) had an allogeneic hematopoietic cell transplant. Most infections were invasive aspergillosis (IA; 49/71, 69%), followed by mucormycosis (12, 16.9%) and other (12, 16.9%); there were 2 mixed infections. Median treatment duration was 227 days (IQR, 115.5-348.5). There was no difference in AFT duration between patients with IA and non-IA IMI (P = .85) or by center (P = .92). Treatment was longer in patients with an allogeneic hematopoietic cell transplant vs not (P = .004). Sixteen patients (22.5%) had no therapy modifications. In 55 patients (77.5%), a median 2 changes (IQR, 1-3; range, 1-8) were observed. There were 182 reasons leading to 165 changes, associated with clinical efficacy (82/182, 44.5%), toxicity (47, 25.8%), and logistical reasons (22, 12.1%); no reason was documented in 32 changes (18.8%). AFT was continued beyond days 90 and 180 in 59 (83%) and 39 (54.9%) patients, respectively, mostly due to persistence of immunosuppression. Conclusions: AFT in patients with acute myelogenous leukemia and IMI is longer than that recommended by guidelines and is frequently associated with treatment adjustments due to variable reasons. More data and better guidance are required to optimize AFT duration and secondary prophylaxis administration according to immunosuppression.

Inducible Nitric Oxide Synthase Embedded in Alginate/Polyethyleneimine Hydrogel as a New Platform to Explore NO-Driven Modulation of Biological Function.

Nitric oxide (NO), a small free radical molecule, turned out to be pervasive in biology and was shown to have a substantial influence on a range of biological activities, including cell growth and apoptosis. This molecule is involved in signaling and affects a number of physiologic functions. In recent decades, several processes related to cancer, such as angiogenesis, programmed cell death, infiltration, cell cycle progression, and metastasis, have been linked with nitric oxide. In addition, other parallel work showed that NO also has the potential to operate as an anti-cancer agent. As a result, it has gained attention in cancer-related therapeutics. The nitric oxide synthase enzyme family (NOS) is required for the biosynthesis of nitric oxide. It is becoming increasingly popular to develop NO-releasing materials as strong tumoricidal therapies that can deliver sustained high concentrations of nitric oxide to tumor sites. In this paper, we developed NO-releasing materials based on sodium alginate hydrogel. In this regard, alginate hydrogel discs were modified by adsorbing layers of polyethyleneimine and iNOS-oxygenase. These NO-releasing hydrogel discs were prepared using the layer-by-layer film building technique. The iNOS-oxygenase is adsorbed on the positively charged polyethyleneimine (PEI) matrix layer, which was formed on a negatively charged sodium alginate hydrogel. We show that nitric oxide is produced by enzymes contained within the hydrogel material when it is exposed to a solution containing all the components necessary for the NOS reaction. The electrostatic chemical adsorption of the layer-by-layer process was confirmed by FTIR measurements as well as scanning electron microscopy. We then tested the biocompatibility of the resulting modified sodium alginate hydrogel discs. We showed that this NOS-PEI-modified hydrogel is overall compatible with cell growth. We characterized the NOS/hydrogel films and examined their functional features in terms of NO release profiles. However, during the first 24 h of activity, these films show an increase in NO release flux, followed by a gradual drop and then a period of stable NO release. These findings show the inherent potential of using this system as a platform for NO-driven modulation of biological functions, including carcinogenesis.

Assessing the intra-urban variability of nitrogen oxides and ozone across a highly heterogeneous urban area.

High-resolution air quality maps are critical towards assessing and understanding exposures to elevated air pollution in dense urban areas. However, these surfaces are rarely available in low- and middle-income countries that suffer from some of the highest air pollution levels worldwide. In this study, we make use of land use regressions (LURs) to generate annual and seasonal, high-resolution nitrogen dioxide (NO2), nitrogen oxides (NOx), and ozone (O3) exposure surfaces for the Greater Beirut Area (GBA) in Lebanon. NO2, NOx and O3 concentrations were monitored using passive samplers that were deployed at 55 pre-defined monitoring locations. The average annual concentrations of NO2, NOx, and O3 across the GBA were 36.0, 89.7, and 26.9 ppb, respectively. Overall, the performance of the generated models was appropriate, with low biases, high model robustness, and acceptable R2 values that ranged between 0.66 and 0.73 for NO2, 0.56 and 0.60 for NOx, and 0.54 and 0.65 for O3. Traffic-related emissions as well as the operation of a fossil-fuel power plant were found to be the main contributors to the measured NO2 and NOx levels in the GBA, whereas they acted as sinks for O3 concentrations. No seasonally significant differences were found for the NO2 and NOx pollution surfaces; as their seasonal and annual models were largely similar (Pearson's r > 0.85 for both pollutants). On the other hand, seasonal O3 pollution surfaces were significantly different. The model results showed that around 99% of the population of the GBA were exposed to NO2 levels that exceeded the World Health Organization defined annual standard.

Assessing the transferability of landuse regression models for ultrafine particles across two Canadian cities.

Land use regression (LUR) models have been increasingly used to predict intra-city variations in the concentrations of different air pollutants. However, limited research assessing the transferability of these models between cities has been published to date. In this study, LUR models were generated for Ultra-Fine Particles (UFP) (<0.1 um) using data collected from mobile monitoring campaigns in two Canadian cities, Montreal and Toronto. City-specific models were first generated for each city before the models were transferred to the second city with and without recalibration. The calibrated transferred models showed only a slight decrease in performance, with the coefficient of determination (R2), dropping from 0.49 to 0.36 for Toronto and from 0.41 to 0.38 for Montreal. Transferring models between cities with no calibration resulted in low R2; 0.11 in Toronto and 0.18 in Montreal. Moreover, two additional models were generated by combining data from the two cities. The first combined model (CM1) assumed a spatially invariant effect of the predictors, while the second (CM2) relaxed the assumption of spatial invariance for some of the model coefficients. The performance of both combined models (R2 ranged between 0.41 for CM1 and 0.43 for CM2; root mean squared error (RMSE) ranged between 0.34 for CM1 and 0.33 for CM2) was found to be on par with the Toronto city-specific model and outperformed the Montreal model. The results of this study highlight that the UFP LUR models appear to support transferability of model structures between cities with similar geographical characteristics, with a minor drop in model fit and predictive skill.