Juan Pablo Caeiro

Context: Hepatitis C virus (HCV) remains a significant public health challenge in the United States, particularly among underserved populations. Despite curative treatments, systemic barriers often delay the care cascade. Program: This quality improvement program aimed at improving the care of patients with chronic Hepatitis C within a Federally Qualified Health Center system in Southern California, known as AltaMed Health Services. The program involves AltaMed, serving more than 700 000 patients, primarily low-income people in underserved communities through an integrated delivery system for Latino and multiethnic individuals, focusing on enhancing screening and treatment processes for Hepatitis C. Methods: A multipronged clinical workflow redesign was evaluated utilizing the RE-AIM framework to assess process and clinical between 2022 and 2024. Intervention included an electronic health record (EHR) Best Practice Advisory to identify patients due for HCV screening, a standardized direct-referral workflow, and a Linkage to Care team to manage prior authorization administrative tasks and patient outreach efforts. Evaluation: Total descriptive HCV screening volumes increased from 30 212 to 47 951, with screening rates expanding from 3.4% to 7.3% in nonspecialty clinics. Treatment initiation rates shifted from 36% to 45%, and post-treatment patient outreach documentation changed from 48% to 73%. The average duration from diagnosis to treatment initiation was observed to be 55.9% lower, changing from 34 weeks in 2022 and 15 weeks in 2024. Discussion: Establishing an Linkage to Care team, combined with automated EHR tools, can track alongside meaningful improvements in the safety-net HCV care cascade. Scaling models require careful consideration of specialized staffing and localized EHR infrastructure to advance health equity and global HCV elimination goals.

Candida albicans is the primary agent of acute vulvovaginal candidiasis (VVC) and its recurrent form (RVVC). Local innate immunity contributes to both defense and pathogenesis during vaginal Candida infection, where epithelial β-defensins (BD) constitute key components of the mucosal barrier. We previously reported that epithelial BD-1 expression is dynamically modulated during murine and human vaginitis, revealing strain-dependent and stimulus-specific regulation but leaving the host pathways involved unresolved. This study functionally defines the contribution of key immune pathways to epithelial antimicrobial peptide regulation. Using a murine model of VVC and the virulent C. albicans strain SC5314, we aimed to evaluate the immune signaling pathways governing the temporal regulation of epithelial BD-1 and BD-3 expression during vaginal infection. In wild-type mice, both defensins displayed a biphasic pattern: early induction followed by attenuation as infection progressed. Genetic loss-of-function approaches revealed that NLRP3/IL-1β signaling is required for early BD-1 induction, whereas IL-17RA signaling preferentially supports sustained BD-3 expression. Together, these findings establish a causal and temporal link between host immune signaling and epithelial defensin regulation and reveal a transient subversion of mucosal defenses by C. albicans. This work advances understanding of epithelial innate immunity, defining distinct temporal programs for BD-1 and BD-3 and identifying NLRP3/IL-1β and IL-17RA signaling as key pathways shaping mucosal defensin expression.

Candida albicans is the primary agent of acute vulvovaginal candidiasis(VVC) and its recurrent form(RVVC). Local innate immunity contributes to both defense and pathogenesis during vaginal Candida infection, where epithelial β-defensins(BD) constitute key components of the mucosal barrier. We previously reported that epithelial BD-1 expression is dynamically modulated during murine and human vaginitis, revealing strain-dependent and stimulus-specific regulation but leaving the host pathways involved unresolved. This study functionally defines the contribution of key immune pathways to epithelial antimicrobial peptide regulation. Using a murine model of VVC and the virulent C. albicans strain SC5314, we analyzed the temporal expression of BD-1 and extended our study to BD-3. In wild-type mice, both defensins displayed a biphasic pattern: early induction followed by attenuation as infection progressed. Genetic loss-of-function approaches revealed that NLRP3/IL-1β signaling is required for early BD-1 induction, whereas IL-17RA signaling preferentially supports sustained BD-3 expression. Together, these findings establish a causal and temporal link between host immune signaling and epithelial defensin regulation, and reveal a transient subversion of mucosal defenses by C. albicans. This work advances understanding of epithelial innate immunity, defining distinct temporal programs for BD-1 and BD-3, and identifying NLRP3/IL-1β and IL-17RA signaling as key pathways shaping mucosal defensin expression.

Introduction: Candida spp. bloodstream infection is a frequent form of mycosis with high mortality rates. Biofilm formation is a potent virulence factor for Candida albicans and Candida parapsilosis , that confers significant resistance to antifungal agents and to the innate immune response. Echinocandins such as anidulafungin are new drugs that broaden the available therapeutic arsenal for invasive fungal infection treatment. Here we evaluated the effect of anidulafungin, human-Monocytes and combined treatment on mature biofilms of clinical isolates of Candida albicans and Candida parapsilosis with different intrinsic capacity to form biofilm, and on biofilm with low (LB) and high biomass (HB). Methods: Yeasts from blood isolates were molecularly identified. Lipase and acid aspartic protease production, adhesion capacity, and ability to form biofilm were evaluated; strains were classified as Weak, Moderate or Strong biofilm forming capacity. Mature biofilm with LB and HB were incubated with anidulafungin, THP-1 cell alone or exposed to both, for 22 h. Fungal damage induced by antifungal agents and/or monocytes was determined by XTT[2,3-bis(2-methoxy-4-nitro-5-sulfophenyl) 2H-tetrazolium-5-carboxanilide] metabolic assay. Results: Our results showed that anidulafungin alone could be effective to reduce mature biofilms with LB of most of the C. parapsilosis sensu stricto isolates, independent of intrinsic BF capacity of the strain. Anidulafungin in combination with human-Monocytes was effective in biofilm with LB of C. albicans and C. parapsilosis sensu stricto clinical isolates. Conclusions: The effectiveness of ANF treatment in biofilm with LB seems to be species specific, since the antifungal agent and monocytes exhibits synergistic activity on C. albicans and C. parapsilosis sensu stricto biofilm.

Invasive candidiasis encompassing Candida bloodstream infections and deep-seated candidiasis can become a persistent health problem. These infections are caused by Candida species and have high morbidity and mortality rates. Species distribution, access to diagnosis, treatment and mortality are different around the world. The mortality rate is high in South America (30–70%), and Candida albicans is the most prevalent species in this region. However, a global epidemiological shift to non-albicans species has been observed. In this group, C. parapsilosis is the species most frequently detected, followed by C. tropicalis, and at a slower rate, C. glabrata, which has also increased, in addition to the emerging C. auris, resistance to several drugs. This article summarizes relevant aspects of candidemia pathogenesis, such as the mechanisms of fungal invasion, immune response, and the impact of genetic defects that increase host susceptibility to developing the infection. We also discuss relevant aspects of treatment and future challenges in South America.

Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are two forms of a disease caused by Candida spp. β-defensin (BD) is one of the most important families of antimicrobial peptides in the female genital tract and includes molecules that exert essential local functions as antimicrobial and PMN chemoattractant peptides. However, the information on their role during murine and human VVC and RVVC is limited. Thus, we analyzed the behavior and contribution of BD1 to the local response in a VVC mice model and the local cytokine profile and human BD1 and BD3 expression in cervicovaginal lavage from patients with VVC and RVVC. We demonstrated that, in patients with RVVC BD1, mRNA and protein expression were severely diminished and that the aspartate proteinase and lipase secreted by C. albicans are involved in that decrease. This study provides novel information about the pathogenesis of VVC and describes a highly efficient C. albicans escape strategy for perpetuating the infection; these results may contribute to the development of new or combined treatment approaches.

Introducción: La enfermedad COVID-19 muestra una marcada heterogeneidad en su curso clínico, habiéndose descripto algunos factores que se asocian un peor pronóstico. El conocimiento del comportamiento de la enfermedad en el escenario local es de gran relevancia para permitir un mejor abordaje. Métodos: Estudio retrospectivo en dos hospitales de la ciudad de Córdoba, Argentina, de pacientes de 18 años o más hospitalizados por infección activa por SARS-CoV-2, desde marzo a octubre del año 2020. Resultados: Se incluyeron 448 pacientes, de los cuales el 95.75% correspondieron a neumonía COVID-19. La mayoría de los episodios ocurrieron en hombres (63.6%), la mediana de edad fue 63 años (RIC:53-75), y las comorbilidades más frecuentes fueron hipertensión arterial (55.1%), obesidad (31.7%) y diabetes mellitus (28.1%). Requirieron ingreso a unidad de cuidados intensivos 162 pacientes (36.2%) y 66 (14.7%), asistencia respiratoria mecánica. Fallecieron 67 pacientes (15%) dentro de los primeros 30 días de seguimiento. En el análisis multivariado la única variable independiente predictora de mortalidad a los 30 días fue la edad (Odds ratio ajustado [ORa]=1.08, IC95%=1.04-1.11, p<0.001). Los scores pronósticos 4C-Score y CALL-Score presentaron muy buena discriminación (Área bajo la curva [ABC]=0.766, IC95%=0.72-0.80 y ABC=0.785, IC95%=0.70-0.85, respectivamente) y los porcentajes predichos de mortalidad se aproximaron bastante a lo observado en el presente estudio. Conclusiones: La mayoría de los pacientes hospitalizados por infección por SARS-CoV-2 presentaban comorbilidades y se presentaron como neumonía, asociada a una elevada mortalidad. Los scores pronósticos con mejor rendimiento para predecir complicaciones fueron el 4C-Score y el CALL score.

Introducción: La enfermedad COVID-19 es una neumonía viral aguda causada por el SARS-CoV-2. Su principal medio de transmisión es de persona a persona a través de gotas respiratorias. Se presenta como un cuadro febril con síntomas respiratorios con una alta tasa de transmisibilidad. No existe vacuna, por lo que la sospecha y aislamiento inmediato del enfermo son primordiales. Objetivo: El propósito de este trabajo es informar el primer caso de enfermedad COVID-19 confirmado en Córdoba (Argentina), destacando a la telemedicina como una novedosa forma de manejo ambulatorio. Metodología: Se describe el primer caso confirmado de enfermedad COVID-19 en Córdoba (Argentina), en un paciente sin comorbilidades, con buen estado clínico, manejándose el mismo mediante telemedicina. Resultados: El manejo ambulatorio mediante telemedicina resultó ser óptimo, evitando la utilización de camas y la transmisión del virus intrahospitalaria mediante el manejo en su domicilio. Conclusión: El manejo ambulatorio de pacientes seleccionados evita la transmisión del virus dentro del hospital y la saturación de camas. La telemedicina es una estrategia efectiva y novedosa para esta situación.