RESUMEN
BACKGROUND: The demand for healthcare services during the COVID-19 pandemic was excessive for less-resourced settings, with intensive care units (ICUs) taking the heaviest toll. OBJECTIVE: The aim was to achieve adequate personal protective equipment (PPE) use in 90% of patient encounters, to reach 90% compliance with objectives of patient flow (OPF) and to provide emotional support tools to 90% of healthcare workers (HCWs). METHODS: We conducted a quasi-experimental study with an interrupted time-series design in 14 ICUs in Argentina. We randomly selected adult critically ill patients admitted from July 2020 to July 2021 and active HCWs in the same period. We implemented a quality improvement collaborative (QIC) with a baseline phase (BP) and an intervention phase (IP). The QIC included learning sessions, periods of action and improvement cycles (plan-do-study-act) virtually coached by experts via platform web-based activities. The main study outcomes encompassed the following elements: proper utilisation of PPE, compliance with nine specific OPF using daily goal sheets through direct observations and utilisation of a web-based tool for tracking emotional well-being among HCWs. RESULTS: We collected 7341 observations of PPE use (977 in BP and 6364 in IP) with an improvement in adequate use from 58.4% to 71.9% (RR 1.2, 95% CI 1.17 to 1.29, p<0.001). We observed 7428 patient encounters to evaluate compliance with 9 OPF (879 in BP and 6549 in IP) with an improvement in compliance from 53.9% to 67% (RR 1.24, 95% CI 1.17 to 1.32, p<0.001). The results showed that HCWs did not use the support tool for self-mental health evaluation as much as expected. CONCLUSION: A QIC was effective in improving healthcare processes and adequate PPE use, even in the context of a pandemic, indicating the possibility of expanding QIC networks nationwide to improve overall healthcare delivery. The limited reception of emotional support tools requires further analyses.
Asunto(s)
COVID-19 , Unidades de Cuidados Intensivos , Mejoramiento de la Calidad , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Argentina , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Femenino , Equipo de Protección Personal/estadística & datos numéricos , Persona de Mediana Edad , Pandemias/prevención & control , Atención a la Salud/normas , Adulto , Salud Pública/métodos , Personal de Salud/estadística & datos numéricos , Personal de Salud/psicología , Análisis de Series de Tiempo Interrumpido/métodosRESUMEN
OBJECTIVE: Because the role of white matter (WM) degenerating microglia (DM) in remyelination failure is unclear, we sought to define the core features of this novel population of aging human microglia. METHODS: We analyzed postmortem human brain tissue to define a population of DM in aging WM lesions. We used immunofluorescence staining and gene expression analysis to investigate molecular mechanisms related to the degeneration of DM. RESULTS: We found that DM, which accumulated myelin debris were selectively enriched in the iron-binding protein light chain ferritin, and accumulated PLIN2-labeled lipid droplets. DM displayed lipid peroxidation injury and enhanced expression for TOM20, a mitochondrial translocase, and a sensor of oxidative stress. DM also displayed enhanced expression of the DNA fragmentation marker phospho-histone H2A.X. We identified a unique set of ferroptosis-related genes involving iron-mediated lipid dysmetabolism and oxidative stress that were preferentially expressed in WM injury relative to gray matter neurodegeneration. INTERPRETATION: Ferroptosis appears to be a major mechanism of WM injury in Alzheimer's disease and vascular dementia. WM DM are a novel therapeutic target to potentially reduce the impact of WM injury and myelin loss on the progression of cognitive impairment. ANN NEUROL 2023;94:1048-1066.
Asunto(s)
Ferroptosis , Sustancia Blanca , Humanos , Microglía/metabolismo , Sustancia Blanca/patología , Envejecimiento/patología , Encéfalo/patologíaRESUMEN
A major limitation of mechanistic studies in aging brains is the lack of routine methods to robustly visualize and discriminate the cellular distribution of tissue antigens using fluorescent immunohistochemical multi-labeling techniques. Although such approaches are routine in non-aging brains, they are not consistently feasible in the aging brain due to the progressive accumulation of autofluorescent pigments, particularly lipofuscin, which strongly excite and emit over a broad spectral range. Consequently, aging research has relied upon colorimetric antibody techniques, where discrimination of tissue antigens is often challenging. We report the application of a simple, reproducible, and affordable protocol using multispectral light-emitting diodes (mLEDs) exposure for the reduction/elimination of lipofuscin autofluorescence (LAF) in aging brain tissue from humans, non-human primates, and mice. The mLEDs lamp has a broad spectral range that spans from the UV to infrared range and includes spectra in the violet/blue and orange/red. After photo quenching, the LAF level was markedly reduced when the tissue background fluorescence before and after mLEDs exposure was compared (p < 0.0001) across the spectral range. LAF elimination was estimated at 95 ± 1%. This approach permitted robust specific fluorescent immunohistochemical co-visualization of commonly studied antigens in aging brains. We also successfully applied this method to specifically visualize CD44 variant expression in aging human cerebral white matter using RNAscope fluorescent in-situ hybridization. Photo quenching provides an attractive means to accelerate progress in aging research by increasing the number of molecules that can be topologically discriminated by fluorescence detection in brain tissue from normative or pathological aging.
Asunto(s)
Envejecimiento , Encéfalo , Receptores de Hialuranos , Primates , Envejecimiento/genética , Envejecimiento/metabolismo , Animales , Encéfalo/metabolismo , Variación Genética , Humanos , Receptores de Hialuranos/genética , Inmunohistoquímica , Hibridación in Situ , Lipofuscina/química , Ratones , Primates/genéticaRESUMEN
Bartonella henselae es el agente etiológico de la enfermedad por arañazo de gato. Típicamente, se presenta como una linfadenopatía regional autolimitada y, con menor frecuencia, con compromiso sistémico y manifestaciones extraganglionares: hígado, bazo, hueso y ojo, entre otros. Se presenta un caso de enfermedad por arañazo de gato atípica en un paciente pediátrico inmunocompetente, en la que se evidenció compromiso meníngeo y ocular, este último como neurorretinitis. Se destaca la importancia de la búsqueda activa de complicaciones oculares en pacientes con compromiso sistémico por Bartonella henselae, que implica un cambio en el tratamiento y pronóstico de la enfermedad
Bartonella henselae is the etiologic agent of cat scratch disease. It typically presents as a self-limited regional lymphadenopathy and less frequently with systemic involvement and extranodal manifestations: liver, spleen, bone, eye, among others. A case of atypical cat scratch disease is presented in an immunocompetent pediatric patient, in which meningeal and ocular involvement was evidenced, the latter manifested as neuroretinitis. The importance of the active search for ocular complications in patients with systemic involvement by Bartonella henselae is highlighted, implying a change in the treatment and prognosis of the disease
Asunto(s)
Humanos , Masculino , Adolescente , Retinitis/complicaciones , Enfermedad por Rasguño de Gato/complicaciones , Enfermedad por Rasguño de Gato/diagnóstico , Bartonella henselaeRESUMEN
Bartonella henselae is the etiologic agent of cat scratch disease. It typically presents as a self-limited regional lymphadenopathy and less frequently with systemic involvement and extranodal manifestations: liver, spleen, bone, eye, among others. A case of atypical cat scratch disease is presented in an immunocompetent pediatric patient, in which meningeal and ocular involvement was evidenced, the latter manifested as neuroretinitis. The importance of the active search for ocular complications in patients with systemic involvement by Bartonella henselae is highlighted, implying a change in the treatment and prognosis of the disease.
Bartonella henselae es el agente etiológico de la enfermedad por arañazo de gato. Típicamente, se presenta como una linfadenopatía regional autolimitada y, con menor frecuencia, con compromiso sistémico y manifestaciones extraganglionares: hígado, bazo, hueso y ojo, entre otros. Se presenta un caso de enfermedad por arañazo de gato atípica en un paciente pediátrico inmunocompetente, en la que se evidenció compromiso meníngeo y ocular, este último como neurorretinitis. Se destaca la importancia de la búsqueda activa de complicaciones oculares en pacientes con compromiso sistémico por Bartonella henselae, que implica un cambio en el tratamiento y pronóstico de la enfermedad.
Asunto(s)
Bartonella henselae , Enfermedad por Rasguño de Gato , Retinitis , Enfermedad por Rasguño de Gato/complicaciones , Enfermedad por Rasguño de Gato/diagnóstico , Humanos , Retinitis/complicacionesRESUMEN
La enfermedad granulomatosa crónica es una inmunodeficiencia primaria infrecuente, debida a un defecto en la actividad microbicida de los fagocitos, originada por mutaciones en los genes que codifican alguna de las subunidades del complejo enzimático nicotinamida adenina dinucleótido fosfato oxidasa. La incidencia estimada es 1 en 250 000 recién nacidos vivos. Puede presentarse desde la infancia hasta la adultez, por lo general, en menores de 2 años. Las infecciones bacterianas y fúngicas, en conjunto con las lesiones granulomatosas, son las manifestaciones más habituales de la enfermedad. Los microorganismos aislados más frecuentemente son Aspergillus spp., Staphylococcus aureus, Serratia marcescens, Nocardia spp. Se reporta el caso clínico de un varón de 1 año de vida en el que se diagnosticó enfermedad granulomatosa crónica a partir de infecciones múltiples que ocurrieron simultáneamente: aspergilosis pulmonar invasiva, osteomielitis por Serratia marcescens y granuloma cervical por Enterobacter cloacae.
Chronic granulomatous disease is an uncommon primary immunodeficiency due to a defect of the killing activity of phagocytes, caused by mutations in any of the genes encoding subunits of the superoxide-generating phagocyte NADPH oxidase system. The incidence is 1 in 250 000 live births. It can occur from infancy to adulthood, usually in children under 2 years. Bacterial and fungal infections in association with granuloma lesions are the most common manifestations of the disease. Aspergillus species, Staphylococcus aureus, Serratia marcescens, Nocardia species are the most common microorganisms isolated. We describe here a case of a 1-year-old boy with chronic granulomatous disease and invasive pulmonary aspergillosis, Serratia marcescens osteomyelitis and Enterobacter cloacae cervical granuloma.
Asunto(s)
Humanos , Masculino , Lactante , Infecciones por Serratia/diagnóstico , Infecciones por Enterobacteriaceae/diagnóstico , Aspergilosis Pulmonar/diagnóstico , Enfermedad Granulomatosa Crónica/diagnóstico , Osteomielitis/diagnóstico , Osteomielitis/metabolismo , Serratia marcescens/aislamiento & purificación , Infecciones por Serratia/microbiología , Enterobacter cloacae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Enfermedad Granulomatosa Crónica/microbiologíaRESUMEN
Chronic granulomatous disease is an uncommon primary immunodeficiency due to a defect of the killing activity of phagocytes, caused by mutations in any of the genes encoding subunits of the superoxide-generating phagocyte NADPH oxidase system. The incidence is 1 in 250 000 live births. It can occur from infancy to adulthood, usually in children under 2 years. Bacterial and fungal infections in association with granuloma lesions are the most common manifestations of the disease. Aspergillus species, Staphylococcus aureus, Serratia marcescens, Nocardia species are the most common microorganisms isolated. We describe here a case of a 1-year-old boy with chronic granulomatous disease and invasive pulmonary aspergillosis, Serratia marcescens osteomyelitis and Enterobacter cloacae cervical granuloma.
La enfermedad granulomatosa crónica es una inmunodeficiencia primaria infrecuente, debida a un defecto en la actividad microbicida de los fagocitos, originada por mutaciones en los genes que codifican alguna de las subunidades del complejo enzimático nicotinamida adenina dinucleótido fosfato oxidasa. La incidencia estimada es 1 en 250 000 recién nacidos vivos. Puede presentarse desde la infancia hasta la adultez, por lo general, en menores de 2 años. Las infecciones bacterianas y fúngicas, en conjunto con las lesiones granulomatosas, son las manifestaciones más habituales de la enfermedad. Los microorganismos aislados más frecuentemente son Aspergillus spp., Staphylococcus aureus, Serratia marcescens, Nocardia spp. Se reporta el caso clínico de un varón de 1 año de vida en el que se diagnosticó enfermedad granulomatosa crónica a partir de infecciones múltiples que ocurrieron simultáneamente: aspergilosis pulmonar invasiva, osteomielitis por Serratia marcescens y granuloma cervical por Enterobacter cloacae.
Asunto(s)
Infecciones por Enterobacteriaceae/diagnóstico , Enfermedad Granulomatosa Crónica/diagnóstico , Aspergilosis Pulmonar/diagnóstico , Infecciones por Serratia/diagnóstico , Enterobacter cloacae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Enfermedad Granulomatosa Crónica/microbiología , Humanos , Lactante , Masculino , Osteomielitis/diagnóstico , Osteomielitis/metabolismo , Infecciones por Serratia/microbiología , Serratia marcescens/aislamiento & purificaciónRESUMEN
PURPOSE: To compare diagnostic capabilities and agreement between Oculus-Spark perimetry and 3 procedures of glaucoma morphologic analysis. METHODS: A total of 102 normal eyes and 104 consecutive eyes with suspected or confirmed glaucoma (1 eye per subject) were analyzed in a prospective observational case-control study, using Spark strategy (Oculus Easyfield Perimeter), Heidelberg retinal tomograph (HRT), Zeiss laser polarimetry (GDx), and Cirrus optical coherence tomography (OCT). RESULTS: Spark first phase lasted 37 seconds and all 4 phases 2:34 minutes. Specificities and sensitivities were as follows: Spark mean deviation (MD) first phase (95.1%, 85.6%), MD second and final phases (95.1%, 86.5%), GDx-nerve fiber indicator (95.1%, 57.4%), HRT-Reinhard Burk discriminant function (95.1%, 52.9%), HRT glaucoma probability score (95.1%, 71.2%), Cirrus OCT vertical cup/disc ratio (96.1%, 85.6%), and Cirrus OCT retinal nerve fiber layer thickness (95.1%, 68.0%). Diagnostic agreement between second and final Spark MD phases was kappa=0.92; between phase 1 Spark/MD and Cirrus OCT/vertical C/D ratio was kappa=0.78. Agreements between the 2 Cirrus OCT indices was kappa=0.69 and between the 2 HRT indices was kappa=0.559. The correlation coefficient between second and final MD and PSD was 0.99, and 0.98 between the number of scotomatous points. There was high concordance in scotoma position in both phases (kappa=0.86). The linear correlation coefficients between the morphologic indices were 0.48-0.78, and between morphologic and functional indices 0.51-0.76. Correlation coefficients comparing morphologic and functional indices were similar in the first and the last phase (p>0.05 in all cases). CONCLUSIONS: Spark perimetry appears to show useful sensitivity and specificity, even in the first phase, and good agreement with the morphology.
Asunto(s)
Técnicas de Diagnóstico Oftalmológico/instrumentación , Glaucoma/diagnóstico , Fibras Nerviosas/patología , Disco Óptico/patología , Enfermedades del Nervio Óptico/diagnóstico , Células Ganglionares de la Retina/patología , Estudios de Casos y Controles , Humanos , Presión Intraocular , Estudios Prospectivos , Curva ROC , Polarimetría de Barrido por Laser , Sensibilidad y Especificidad , Tomografía , Tomografía de Coherencia Óptica , Pruebas del Campo VisualRESUMEN
BACKGROUND: The aim of this study was to describe the frequency of minority populations of viruses carrying mutations K103N and M184V in drug-naive HIV type-1 (HIV-1)-infected children, and to further evaluate their effect on the selection of drug-resistant viruses within highly active antiretroviral therapy (HAART). METHODS: Newly diagnosed vertically HIV-1-infected children were evaluated. The HIV-1 pol gene was sequenced for subtyping and antiretroviral drug resistance analysis. Standard genotypic sequencing and sequence-selective real-time PCR (SPCR) to quantify minority viral populations were used. RESULTS: From December 2004 to July 2006, we included 35 children who were studied at baseline and during their first HAART regimen (follow-up median time 29.4 months). Of them, 82.9% were infected with intersubtype B/F recombinant variants. At baseline, all children had a drug-susceptible viral population that was studied by bulk sequencing. SPCR showed that 4 children had between 2-10% of M184V, 11 had <0.7%, 18 had no detectable mutation and 2 could not be amplified. No K103N minority populations were found. Once under HAART, children who had 2-10% of M184V at baseline further selected it in percentages >20% in less time than those with -0.1-0.6% or without minority populations (P=0.01). CONCLUSIONS: It was shown that having 2-10% of M184V at baseline enhanced its selection in high percentages in a short time after HAART initiation. Further research regarding the presence of minority quasispecies before initiation of HAART in large paediatric populations should be undertaken to evaluate their clinical effect during HAART.
Asunto(s)
Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral/genética , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/efectos de los fármacos , Mutación , Adolescente , Terapia Antirretroviral Altamente Activa , Argentina/epidemiología , Niño , Preescolar , Esquema de Medicación , Femenino , Genes pol , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Lactante , Estimación de Kaplan-Meier , Lamivudine/farmacología , Masculino , Nevirapina/farmacología , Reacción en Cadena de la Polimerasa , Inhibidores de la Transcriptasa Inversa/farmacología , Selección Genética , Análisis de Secuencia de ADNRESUMEN
El objetivo de este estudio fue analizar prospectivamente los niveles de resistencia a las drogas antirretrovirales y el progreso de la carga viral plasmática (CV) en niños infectados verticalmente por HIV-1 antes y durante el tratamiento antirretroviral (TARV).
The aim of this study was to prospectively analyze antiretroviral drug resistance and plasma viral load in HIV-1 vertically-infected children beforme and during antiretroviral therapy (ART).
Asunto(s)
Humanos , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Anamnesis/estadística & datos numéricos , Carga Viral/estadística & datos numéricos , VIH , Estimación de Kaplan-Meier , Mutación , Resistencia a Medicamentos , Terapia Antirretroviral Altamente Activa/efectos adversosRESUMEN
El objetivo de este estudio fue analizar prospectivamente los niveles de resistencia a las drogas antirretrovirales y el progreso de la carga viral plasmática (CV) en niños infectados verticalmente por HIV-1 antes y durante el tratamiento antirretroviral (TARV).(AU)
The aim of this study was to prospectively analyze antiretroviral drug resistance and plasma viral load in HIV-1 vertically-infected children beforme and during antiretroviral therapy (ART).(AU)
Asunto(s)
Humanos , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , VIH/inmunología , Terapia Antirretroviral Altamente Activa/efectos adversos , Resistencia a Medicamentos/efectos de los fármacos , Carga Viral/estadística & datos numéricos , Mutación/efectos de los fármacos , Estimación de Kaplan-Meier , Anamnesis/estadística & datos numéricosRESUMEN
INTRODUCTION: The aim of our study was to analyse the frequency of primary mutations associated with HIV drug resistance in a population of children born to HIV-infected mothers. DESIGN: A prospective study included newly HIV-diagnosed children treated at two public paediatric hospitals. PATIENTS AND METHODS: Clinical and antiretroviral therapy (ART) data were collected in mother-child pairs. HIV-1 subtyping and ART resistance mutations were assayed in children by sequencing a region of HIV pol gene. RESULTS: A total of 67 children were enrolled: 22 less than 12 months of age, 20 between 1 and 5 years and 25 between 6 and 14 years. Six (9.0%) children had viral strains with at least one primary mutation associated with resistance to reverse transcriptase and protease inhibitors. A significantly (P = 0.019) higher frequency of resistance (22.7%, n = 5/22) was found among children aged < 12 months. Fourteen children (20.9%) had a subtype B HIV-1 strain and 53 (79.1%) had an inter-subtype B/F recombinant variant. DISCUSSION: A high percentage of recently diagnosed infants were found to carry primary ART resistance mutations. Limited options for ART of HIV-infected children might lead to increased HIV-associated morbidity and mortality. Thus, consideration should be given to mandatory screening for primary ART resistance before initiating therapy for infants aged < 12 months in countries where HIV mother-to-child transmission is still present, such as in Argentina. This will allow for the rationalized and individualized use of drugs and will contribute to the increased cost-effectiveness of local health systems.
Asunto(s)
Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral/genética , Infecciones por VIH/virología , VIH/genética , Mutación , Adolescente , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , Estudios ProspectivosRESUMEN
Palabras preliminares, Dra. Lidia Pinola. Marco general. Bioseguridad. Pacientes discapacitados físico mentales. Pacientes inmuno comprometidos. Pacientes sistémicos. Pacientes con malformaciones cráneo máxilo faciales y fisurados. Unidad de Internación. Traumatología
Asunto(s)
Recién Nacido , Lactante , Preescolar , Niño , Atención Odontológica , Niño , Factores de RiesgoRESUMEN
Palabras preliminares, Dra. Lidia Pinola. Marco general. Bioseguridad. Pacientes discapacitados físico mentales. Pacientes inmuno comprometidos. Pacientes sistémicos. Pacientes con malformaciones cráneo máxilo faciales y fisurados. Unidad de Internación. Traumatología