Dematiaceous fungal infections in solid organ transplantation: Systematic review and Bayesian meta-analysis.

BACKGROUND: Dematiaceous fungi cause a number of infectious syndromes referred to as phaeohyphomycosis among both immunocompetent and immunocompromised hosts. We performed a systematic review to characterize these infections in solid organ transplant recipients (SOTR). METHODS: We searched PubMed database (last searched 1/6/2022) for English-language reports on dematiaceous fungal infections in SOTR. Included reports needed individualized demographic, treatment, and outcome data; pediatric reports were excluded. A universally applicable bias assessment was performed on reports. Models for infection type and outcome were created using the Bayesian paradigm. RESULTS: We included 149 reports on 201 cases of dematiaceous fungal infections in SOTR. The mean age was 54 years, 72% were men, and kidney recipients accounted for 61% of cases. Skin and soft tissue infection (SSTI) was the most common infectious syndrome (73%). Death from infection occurred in 7% of cases (14/201), with disseminated (32%) cases having the highest mortality. Our model for infection type predicted the relative probability of central nervous system infection to be highest in liver recipients. Across all transplant types, higher relative probabilities of disseminated and pulmonary infections occur in the early post-transplant period, and the predicted probabilities for these infection types decreased after 100 months post-transplantation. DISCUSSION: We identified SSTI as the most common dematiaceous fungal infections in SOTR. Disseminated infections carried the worst prognosis. The evidence in this review is limited by the heterogeneity of included cases. No funding source was used, and this review's protocol was not registered.

Dropwise Additive Manufacturing of Pharmaceutical Products Using Particle Suspensions.

The principal method of drug delivery is by oral solid doses, the production of which often necessitates multiple post-crystallization unit operations to ensure content uniformity or enhance bioavailability. As an alternative to conventional dose production methods, applications of additive manufacturing technologies based on solvent- or melt-based formulations have demonstrated the potential for improvements to process efficiency, flexibility, and dosing precision. Here we explore the use of particulate suspensions in a dropwise additive manufacturing process as a method for dosing active ingredients in crystalline form, which may be difficult to achieve via powder processing due to poor flow properties. By employing a fluid-based method, powder flow issues are alleviated and adaptation of the process to new particles/crystals is facilitated by dimensional analysis. In this work, a feasibility study was conducted using 4 active ingredient powders, each with non-ideal particle properties, and 2 carrier fluids, in which the active ingredient does not dissolve, to formulate suspensions for dose manufacturing; drug products were analyzed to show reproducibility of dosing and to assess preservation of particle size through the process. Performance across particle types is affected by particle size and shape, and is related through effects on the rheological properties of the formulation.