Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.

BACKGROUND: Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. METHODS: We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. RESULTS: Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. CONCLUSIONS: We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.

Factors that influence the provision of home-based rehabilitation services for people needing rehabilitation: a qualitative evidence synthesis.

BACKGROUND: To increase people's access to rehabilitation services, particularly in the context of the COVID-19 pandemic, we need to explore how the delivery of these services can be adapted. This includes the use of home-based rehabilitation and telerehabilitation. Home-based rehabilitation services may become frequently used options in the recovery process of patients, not only as a solution to accessibility barriers, but as a complement to the usual in-person inpatient rehabilitation provision. Telerehabilitation is also becoming more viable as the usability and availability of communication technologies improve. OBJECTIVES: To identify factors that influence the organisation and delivery of in-person home-based rehabilitation and home-based telerehabilitation for people needing rehabilitation. SEARCH METHODS: We searched PubMed, Global Health, the VHL Regional Portal, Epistemonikos, Health Systems Evidence, and EBM Reviews as well as preprints, regional repositories, and rehabilitation organisations websites for eligible studies, from database inception to search date in June 2022.  SELECTION CRITERIA: We included studies that used qualitative methods for data collection and analysis; and that explored patients, caregivers, healthcare providers and other stakeholders' experiences, perceptions and behaviours about the provision of in-person home-based rehabilitation and home-based telerehabilitation services responding to patients' needs in different phases of their health conditions.   DATA COLLECTION AND ANALYSIS: We used a purposive sampling approach and applied maximum variation sampling in a four-step sampling frame. We conducted a framework thematic analysis using the CFIR (Consolidated Framework for Implementation Research) framework as our starting point. We assessed our confidence in the findings using the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach.  MAIN RESULTS: We included 223 studies in the review and sampled 53 of these for our analysis. Forty-five studies were conducted in high-income countries, and eight in low-and middle-income countries. Twenty studies addressed in-person home-based rehabilitation, 28 studies addressed home-based telerehabilitation services, and five studies addressed both modes of delivery. The studies mainly explored the perspectives of healthcare providers, patients with a range of different health conditions, and their informal caregivers and family members.  Based on our GRADE-CERQual assessments, we had high confidence in eight of the findings, and moderate confidence in five, indicating that it is highly likely or likely respectively that these findings are a reasonable representation of the phenomenon of interest. There were two findings with low confidence. High and moderate confidence findings Home-based rehabilitation services delivered in-person or through telerehabilitation  Patients experience home-based services as convenient and less disruptive of their everyday activities. Patients and providers also suggest that these services can encourage patients' self-management and can make them feel empowered about the rehabilitation process. But patients, family members, and providers describe privacy and confidentiality issues when services are provided at home. These include the increased privacy of being able to exercise at home but also the loss of privacy when one's home life is visible to others.  Patients and providers also describe other factors that can affect the success of home-based rehabilitation services. These include support from providers and family members, good communication with providers, the requirements made of patients and their surroundings, and the transition from hospital to home-based services. Telerehabilitation specifically Patients, family members and providers see telerehabilitation as an opportunity to make services more available. But providers point to practical problems when assessing whether patients are performing their exercises correctly. Providers and patients also describe interruptions from family members.  In addition, providers complain of a lack of equipment, infrastructure and maintenance and patients refer to usability issues and frustration with digital technology. Providers have different opinions about whether telerehabilitation is cost-efficient for them. But many patients see telerehabilitation as affordable and cost-saving if the equipment and infrastructure have been provided. Patients and providers suggest that telerehabilitation can change the nature of their relationship. For instance, some patients describe how telerehabilitation leads to easier and more relaxed communication. Other patients describe feeling abandoned when receiving telerehabilitation services.  Patients, family members and providers call for easy-to-use technologies and more training and support. They also suggest that at least some in-person sessions with the provider are necessary. They feel that telerehabilitation services alone can make it difficult to make meaningful connections. They also explain that some services need the provider's hands. Providers highlight the importance of personalising the services to each person's needs and circumstances. AUTHORS' CONCLUSIONS: This synthesis identified several factors that can influence the successful implementation of in-person home-based rehabilitation and telerehabilitation services. These included factors that facilitate implementation, but also factors that can challenge this process. Healthcare providers, program planners and policymakers might benefit from considering these factors when designing and implementing programmes.

Prospective Multicenter Diagnostic Performance of Technologist-Performed Screening Breast Ultrasound After Tomosynthesis in Women With Dense Breasts (the DBTUST).

PURPOSE: To assess diagnostic performance of digital breast tomosynthesis (DBT) alone or combined with technologist-performed handheld screening ultrasound (US) in women with dense breasts. METHODS: In an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant multicenter protocol in western Pennsylvania, 6,179 women consented to three rounds of annual screening, interpreted by two radiologist observers, and had appropriate follow-up. Primary analysis was based on first observer results. RESULTS: Mean participant age was 54.8 years (range, 40-75 years). Across 17,552 screens, there were 126 cancer events in 125 women (7.2/1,000; 95% CI, 5.9 to 8.4). In year 1, DBT-alone cancer yield was 5.0/1,000, and of DBT+US, 6.3/1,000, difference 1.3/1,000 (95% CI, 0.3 to 2.1; P = .005). In years 2 + 3, DBT cancer yield was 4.9/1,000, and of DBT+US, 5.9/1,000, difference 1.0/1,000 (95% CI, 0.4 to 1.5; P < .001). False-positive rate increased from 7.0% for DBT in year 1 to 11.5% for DBT+US and from 5.9% for DBT in year 2 + 3 to 9.7% for DBT+US (P < .001 for both). Nine cancers were seen only by double reading DBT and one by double reading US. Ten interval cancers (0.6/1,000 [95% CI, 0.2 to 0.9]) were identified. Despite reduction in specificity, addition of US improved receiver operating characteristic curves, with area under receiver operating characteristic curve increasing from 0.83 for DBT alone to 0.92 for DBT+US in year 1 (P = .01), with smaller improvements in subsequent years. Of 6,179 women, across all 3 years, 172/6,179 (2.8%) unique women had a false-positive biopsy because of DBT as did another 230/6,179 (3.7%) women because of US (P < .001). CONCLUSION: Overall added cancer detection rate of US screening after DBT was modest at 19/17,552 (1.1/1,000; CI, 0.5- to 1.6) screens but potentially overcomes substantial increases in false-positive recalls and benign biopsies.

Factor structure, measurement invariance and psychometric properties of the Quality of Life Scale WHOQOL-BREF in the Ecuadorian context.

BACKGROUND: The short version of the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) is a popular instrument used to assess quality of life. The objective of this study was to evaluate the following psychometric properties: structural validity, convergent validity, internal consistency, and measurement invariance across sex of the WHOQOL-BREF in a sample of Ecuadorian adults. METHODS: We used a sample of undergraduates (n = 987) to assess the WHOQOL-BREF original four-factor structure, a model with correlated factors, a hierarchical model, and two models resulting from the exploratory factor analysis and exploratory graph analysis. All the models were evaluated using confirmatory factor analysis. RESULTS: The results of the exploratory factor analysis and exploratory graph analysis suggest that the items are organized into four factors, although differently from the original version and the orthogonality assumption is not maintained. The confirmatory factor analysis shows that the original WHOQOL-BREF structure with correlated factors presents adequate psychometric properties. However, we propose a four-factor structure that has the best psychometric properties and adequate internal consistency. The results of the measurement invariance show that strict and strong invariance is achieved between men and women. Convergent validity analysis reveals moderate correlations with self-esteem, resilience, and social support. CONCLUSIONS: Despite the original version of the WHOQOL-BREF with correlated factors has acceptable psychometric properties in the Ecuadorian context, we propose a version with a different organization of its items, which is consistent with the findings of other investigations.

Non-pharmaceutical interventions for containment, mitigation and suppression of COVID-19 infection.

BACKGROUND: The best scientific evidence is required to design effective Non-pharmaceutical interventions to help policymakers to contain COVID-19. AIM: To describe which Non-pharmaceutical interventions used different countries and a when they use them. It also explores how Non-pharmaceutical interventions impact the number of cases, the mortality, and the capacity of health systems. METHODS: We consulted eight web pages of transnational organizations, 17 of international media, 99 of government institutions in the 19 countries included, and besides, we included nine studies (out of 34 identified) that met inclusion criteria. RESULT: Some countries are focused on establishing travel restrictions, isolation of identified cases, and high-risk people. Others have a combination of mandatory quarantine and other drastic social distancing measures. The timing to implement the interventions varied from the first fifteen days after detecting the first case to more than 30 days. The effectiveness of isolated non-pharmaceutical interventions may be limited, but combined interventions have shown to be effective in reducing the transmissibility of the disease, the collapse of health care services, and mortality. When the number of new cases has been controlled, it is necessary to maintain social distancing measures, self-isolation, and contact tracing for several months. The policy decision-making in this time should be aimed to optimize the opportunities of saving lives, reducing the collapse of health services, and minimizing the economic and social impact over the general population, but principally over the most vulnerable. The timing of implementing and lifting interventions could have a substantial effect on those objectives.

Antecedentes: Se requiere la mejor evidencia científica para diseñar intervenciones no farmacológicas efectivas para ayudar a los formuladores de políticas a contener COVID-19. OBJETIVO: Describir qué intervenciones no farmacológicas utilizaron diferentes países y cuándo las implementaron. También explora cómo las intervenciones no farmacológicas afectan el número de casos, la mortalidad y la capacidad de los sistemas de salud. MÉTODOS: Consultamos ocho páginas web de organizaciones transnacionales, 17 de medios internacionales, 99 de instituciones gubernamentales en los 19 países incluidos, y además, incluimos nueve estudios (de 34 identificados) que cumplían con los criterios de inclusión. RESULTADOS: Algunos países implementaron restricciones de viaje, aislamiento de casos identificados y personas de alto riesgo. Otros combinaron varias medidas más drásticas de distanciamiento social. El tiempo para implementar las intervenciones varió desde los primeros quince días después de detectar el primer caso hasta más de 30 días. La efectividad de las intervenciones no farmacológicas combinadas ha demostrado ser efectivas para reducir la transmisibilidad de la enfermedad, el colapso de los servicios de salud y la mortalidad. Cuando se controle el número de casos nuevos, es necesario mantener medidas de distanciamiento social, autoaislamiento y rastreo de contactos durante varios meses. La toma de decisiones políticas en este momento debe tener como objetivo optimizar las oportunidades de salvar vidas, reducir el colapso de los servicios de salud y minimizar el impacto económico y social sobre la población en general, pero principalmente sobre los más vulnerables.

Understanding the Role of Values in Health Policy Decision-Making From the Perspective of Policy-Makers and Stakeholders: A Multiple-Case Embedded Study in Chile and Colombia.

BACKGROUND: Chile and Colombia are examples of Latin American countries with health systems shaped by similar values. Recently, both countries have crafted policies to regulate the participation of private for-profit insurance companies in their health systems, but through very different mechanisms. This study asks: what values are important in the decision-making processes that crafted these policies? And how and why are they used? METHODS: An embedded multiple-case study design was carried out for 2 specific decisions in each country: (1) in Chile, the development of the Universal Plan of Explicit Entitlements -AUGE/GES - and mandating universal coverage of treatments for high-cost diseases; and (2) in Colombia, the declaration of health as a fundamental right and a mechanism to explicitly exclude technologies that cannot be publicly funded. We interviewed key informants involved in one or more of the decisions and/or in the policy analysis and development process that contributed to the eventual decision. The data analysis involved a constant comparative approach and thematic analysis for each case study. RESULTS: From the 40 individuals who were invited, 28 key informants participated. A tension between 2 important values was identified for each decision (eg, solidarity vs. individualism for the AUGE/GES plan in Chile; human dignity vs. sustainability for the declaration of the right to health in Colombia). Policy-makers used values in the decisionmaking process to frame problems in meaningful ways, to guide policy development, as a pragmatic instrument to make decisions, and as a way to legitimize decisions. In Chile, values such as individualism and free choice were incorporated in decision-making because attaining private health insurance was seen as an indicator of improved personal economic status. In Colombia, human dignity was incorporated as the core value because the Constitutional Court asserted its importance in its use of judicial activism as a check on the power of the executive and legislative branches. CONCLUSION: There is an opportunity to open further exploration of the role of values in different health decisions, political sectors besides health, and even other jurisdictions.

Non-pharmaceutical interventions for containment, mitigation and suppression of COVID-19 infection / Intervenciones no farmacéuticas para la contención, mitigación y supresión del COVID-19

Abstract Background: The best scientific evidence is required to design effective Non-pharmaceutical interventions to help policymakers to contain COVID-19. Aim: To describe which Non-pharmaceutical interventions used different countries and a when they use them. It also explores how Non-pharmaceutical interventions impact the number of cases, the mortality, and the capacity of health systems. Methods: We consulted eight web pages of transnational organizations, 17 of international media, 99 of government institutions in the 19 countries included, and besides, we included nine studies (out of 34 identified) that met inclusion criteria. Result: Some countries are focused on establishing travel restrictions, isolation of identified cases, and high-risk people. Others have a combination of mandatory quarantine and other drastic social distancing measures. The timing to implement the interventions varied from the first fifteen days after detecting the first case to more than 30 days. The effectiveness of isolated non-pharmaceutical interventions may be limited, but combined interventions have shown to be effective in reducing the transmissibility of the disease, the collapse of health care services, and mortality. When the number of new cases has been controlled, it is necessary to maintain social distancing measures, self-isolation, and contact tracing for several months. The policy decision-making in this time should be aimed to optimize the opportunities of saving lives, reducing the collapse of health services, and minimizing the economic and social impact over the general population, but principally over the most vulnerable. The timing of implementing and lifting interventions could have a substantial effect on those objectives.

Resumen Antecedentes: Se requiere la mejor evidencia científica para diseñar intervenciones no farmacológicas efectivas para ayudar a los formuladores de políticas a contener COVID-19. Objetivo: Describir qué intervenciones no farmacológicas utilizaron diferentes países y cuándo las implementaron. También explora cómo las intervenciones no farmacológicas afectan el número de casos, la mortalidad y la capacidad de los sistemas de salud. Métodos: Consultamos ocho páginas web de organizaciones transnacionales, 17 de medios internacionales, 99 de instituciones gubernamentales en los 19 países incluidos, y además, incluimos nueve estudios (de 34 identificados) que cumplían con los criterios de inclusión. Resultados: Algunos países implementaron restricciones de viaje, aislamiento de casos identificados y personas de alto riesgo. Otros combinaron varias medidas más drásticas de distanciamiento social. El tiempo para implementar las intervenciones varió desde los primeros quince días después de detectar el primer caso hasta más de 30 días. La efectividad de las intervenciones no farmacológicas combinadas ha demostrado ser efectivas para reducir la transmisibilidad de la enfermedad, el colapso de los servicios de salud y la mortalidad. Cuando se controle el número de casos nuevos, es necesario mantener medidas de distanciamiento social, autoaislamiento y rastreo de contactos durante varios meses. La toma de decisiones políticas en este momento debe tener como objetivo optimizar las oportunidades de salvar vidas, reducir el colapso de los servicios de salud y minimizar el impacto económico y social sobre la población en general, pero principalmente sobre los más vulnerables.

Intervenciones para la salud mental de estudiantes universitarios durante la pandemia por COVID-19. Síntesis rápida. / Mental health interventions for college students during the COVID-19 pandemic. Rapid Synthesis

En esta síntesis se consideran las siguientes cuatro acciones concretas: 1. Lineamientos generales en salud mental de universitarios. 2. Promoción y prevención en salud mental. 3. Atención de síntomas mentales. 4. Adaptaciones pedagógicas con énfasis en salud mental. En general, se encontró que la sugerencia más frecuente es el diseño de un programa estructurado específico para el tema de salud mental en las universidades. En este programa se integran todas las demás acciones por lo que los desarrolladores de estas propuestas sugieren que sea diseñado por un grupo multidisciplinario de profesionales en salud mental, pedagogos y personal administrativo. Además, debe ser incluyente en el sentido de que incorpore siempre la visión de los mismos estudiantes (36). Debe ser dinámico de manera que se ajuste y actualice según se vaya monitoreando las necesidades y barreras emergentes; y, finalmente, este programa ser sensible a la cultura, pues las estrategias de afrontamiento pueden ser distintas (20) de ahí que cada universidad debe diseñarlo pensando en sus particularidades.

Medidas y adaptaciones para la reapertura segura de escuelas y colegios durante la pandemia por COVID-19. Síntesis rápida / Measures and adaptations for the safe reopening of schools during the COVID-19 pandemic. Rapid Synthesis

En esta síntesis se consideran cuatro elementos que se abordaran de manera independiente: 1. La transmisibilidad y gravedad de la infección por SARS-CoV-2 en los niños, niñas y adolescentes. 2. Medidas y adaptaciones para un retorno seguro a las aulas durante la pandemia. 3. Comunicación efectiva con el entorno académico, las familias y la comunidad. 4. Consideraciones de equidad para tener en cuenta en los niños, niñas, adolescentes, padres, profesores e instituciones durante el regreso a la educación presencial. Aunque los gobiernos instauraron la medida de cierre de escuelas para disminuir la transmisión de la enfermedad, y reducir la presión sobre los servicios asistenciales y/o proteger a las poblaciones en riesgo, la evidencia es controvertida sobre el papel de los niños en la transmisión de la infección.

Vacunas para la COVID-19: evidencia sobre seguridad, inmunogenicidad y eficacia. Síntesis rápida / Vaccines for COVID-19: security, immunogenicity, and efficacy evidence. Rapid living synthesis

El fuerte impacto de la enfermedad COVID-19 en la salud, las relaciones sociales y la economía del orbe, presiona el desarrollo de una vacuna efectiva y segura. Sin embargo, la urgencia y premura en el desarrollo de los ensayos clínicos, la reducción ostensible del tiempo de estudio de las vacunas candidatas, el cual ha pasado de casi 10 años a 12-18 meses, hace emerger cuestionamientos sobre la eficacia y seguridad de la(s) vacuna(s) que salgan al mercado. La evidencia que se presenta proviene de los reportes de 15 ensayos clínicos fases I, II o combinada (I/II) y 17 recursos web que han hecho seguimiento al desarrollo de vacunas. Los recursos web son fundamentalmente documentos o páginas de monitoreo y reporte de los ensayos clínicos de las vacunas, y noticias importantes asociadas a estas. La evidencia disponible sobre el desarrollo de las vacunas para COVID-19 es aún limitada dado que los resultados de los estudios fase III provienen de comunicados de prensa preliminares. Doce vacunas se encuentran en fase III de desarrollo. Dos vacunas están basadas en ARN (Moderna/NIAID y Pfizer/BioNTech), cuatro usan vectores no replicativos tipo adenovirus (AstraZeneca/Oxford, Cansino, Gamaleya, Johnson & Johnson), cuatro utilizan el virus inactivado (Sinovac, Sinopharm- Wuhan, Sinopharm-Beijing, Bharat Biotech), una utiliza una unidad proteica recombinante asociada a una matriz adyuvante (Novavax), y una última es la vacuna BCG estudiada para valorar su efectividad sobre la infección COVID-19 en dos ensayos clínicos.

Vacunas para la COVID-19: capacidad de producción y distribución e implicaciones económicas y políticas. Síntesis rápida. / Vaccines for COVID-19: production, distribution capacity, and economic and political implications. Rapid living synthesis

A pesar de los 58.5 millones de casos notificados hasta ahora en el mundo, la mayor parte de la población sigue siendo susceptible a la infección, con un importante número de estudios de seroprevalencia reportando un bajo porcentaje de anticuerpos contra el SARSCoV-2, en un rango entre 1.0% y 10.8% (12­15). Como conclusión, se espera en 2021 una gran demanda de vacunas para la COVID-19. Todo este panorama se esta desarrollando en un contexto complejo, pues la pandemia por la COVID-19 ha hecho evidentes las grandes inequidades a nivel mundial, tanto dentro de los países, como entre ellos, y ha sembrado controversias y preocupaciones asociadas a la capacidad y estrategias de distribución de las vacunas, la priorización de grupos poblacionales y países con mayor riesgo en el contexto de la equidad, y el temor de una monopolización de la vacuna por los países de mayores ingresos, con las implicaciones políticas y económicas que todo esto puede desencadenar (8­11,16­18). Esta síntesis de evidencia aborda las consideraciones sobre la producción y distribución de estas vacunas para COVID-19 y sus implicaciones políticas y económicas.

Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient.

PURPOSE: CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C. cassiicola. We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C. cassiicola and we searched for mutations in CARD9. METHODS: We reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting. RESULTS: The patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C. cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient. CONCLUSION: We describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C. cassiicola in a Colombian child.

Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rß1 Deficiency.

PURPOSE: Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. METHODS: We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rß1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. CONCLUSIONS: To our knowledge, this is the third patient with MSMD due to IL-12Rß1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.