The ecto-enzyme CD38 modulates CD4 T cell immunometabolic responses and participates in HIV pathogenesis.

Despite abundant evidence correlating T cell CD38 expression and HIV infection pathogenesis, its role as a CD4 T cell immunometabolic regulator remains unclear. We find that CD38's extracellular glycohydrolase activity restricts metabolic reprogramming after TCR-engaging stimulation in Jurkat T CD4 cells, together with functional responses, while reducing intracellular NAD and NMN concentrations. Selective elimination of CD38's ectoenzyme function licenses them to decrease the OCR/ECAR ratio upon TCR signaling and to increase cycling, proliferation, survival, and CD40L induction. Pharmacological inhibition of ectoCD38 catalytic activity in memory CD4 T cells from chronic HIV-infected patients rescued TCR-triggered responses, including differentiation and effector functions, while reverting abnormally increased basal glycolysis, cycling, and spontaneous pro-inflammatory cytokine production. Additionally, ecto-CD38 blockage normalized basal and TCR-induced mitochondrial morpho-functionality, while increasing respiratory capacity in cells from HIV+ patients and healthy individuals. Ectoenzyme CD38's immunometabolic restriction of TCR-involving stimulation is relevant to CD4 T cell biology and to the deleterious effects of CD38 overexpression in HIV disease.

Global expression profiling of CD10 + /CD19 + pre-B lymphoblasts from Hispanic B-ALL patients correlates with comparative TARGET database analysis.

Mexico City has one of the highest incidences of acute lymphoblastic leukemia (ALL) globally, with patients showing low survival, and high relapse rates. To gain more insight into the molecular features of B-ALL in Mexican children, we isolated CD10 + /CD19 + precursor B lymphoblasts from four bone marrow and nine peripheral blood samples of B-ALL patients using a fluorescence-activated cell sorting protocol. The global gene expression profile (BM vs PB) revealed 136 differentially expressed genes; 62 were upregulated (45.6%) and 74 were downregulated (54.4%). Pearson's correlation coefficient was calculated to determine the similarity between pre-B lymphoblast populations. We selected 26 highly significant genes and validated 21 by RT-qPCR (CNN3, STON2, CALN1, RUNX2, GADD45A, CDC45, CDC20, PLK1, AIDA, HCK, LY86, GPR65, PIK3CG, LILRB2, IL7R, TCL1A, DOCK1, HIST1H3G, PTPN14, CD72, and NT5E). The gene set enrichment analysis of the total expression matrix and the ingenuity pathway analysis of the 136 differentially expressed genes showed that the cell cycle was altered in the bone marrow with four overexpressed genes (PLK1, CDC20, CDC45, and GADD45A) and a low expression of IL7R and PIK3CG, which are involved in B cell differentiation. A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for PIK3CG. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets.

Multi-Year Mass-Trapping With Autocidal Gravid Ovitraps has Limited Influence on Insecticide Susceptibility in Aedes aegypti (Diptera: Culicidae) From Puerto Rico.

Mass-trapping has been used to control outbreaks of Aedes aegypti (Linnaeus) (Diptera: Culicidae) in Puerto Rico since 2011. We investigated the effect of multi-year, insecticide-free mass trapping had on the insecticide susceptibility profile of Ae. aegypti. Eggs collected in southern Puerto Rico were used to generate F1 populations that were tested for susceptibility to permethrin, sumethrin, bifenthrin, deltamethrin, and malathion according to CDC bottle bioassays protocols. All populations of Ae. aegypti were resistant to the synthetic pyrethroids and mosquitoes from two locations were partially resistant to malathion. Population genetic analysis, using a double digest restriction sites associated DNA sequencing (ddRADseq) approach, indicated a large amount of migration between study sites effectively homogenizing the mosquito populations. Mass-trapping using noninsecticidal autocidal gravid ovitraps did not restore susceptibility to five active ingredients that are found in commercial insecticides. Migration between communities was high and would have brought outside alleles, including resistant alleles to the treatment communities. Further investigation suggests that household use of commercially available insecticide products may continue to select for resistance in absence of public health space spraying of insecticides.

Researching, co-creating and testing innovations in paper-based health information systems (PHISICC) to support health workers' decision-making: protocol of a multi-country, transdisciplinary, mixed-methods research programme in three sub-Saharan countries.

BACKGROUND: Health information systems are crucial to provide data for decision-making and demand for data is constantly growing. However, the link between data and decisions is not always rational or linear and the management of data ends up overloading frontline health workers, which may compromise quality of healthcare delivery. Despite limited evidence, there is an increasing push for the digitalization of health information systems, which poses enormous challenges, particularly in remote, rural settings in low- and middle-income countries. Paper-based tools will continue to be used in combination with digital solutions and this calls for efforts to make them more responsive to local needs. Paper-based Health Information Systems in Comprehensive Care (PHISICC) is a transdisciplinary, multi-country research initiative to create and test innovative paper-based health information systems in three sub-Saharan African countries. METHODS/DESIGN: The PHISICC initiative is being carried out in remote, rural settings in Côte d'Ivoire, Mozambique and Nigeria through partnership with ministries of health and research institutions. We began with research syntheses to acquire the most up-to-date knowledge on health information systems. These were coupled with fieldwork in the three countries to understand the current design, patterns and contexts of use, and healthcare worker perspectives. Frontline health workers, with designers and researchers, used co-creation methods to produce the new PHISICC tools. This suite of tools is being tested in the three countries in three cluster-randomized controlled trials. Throughout the project, we have engaged with a wide range of stakeholders and have maintained the highest scientific standards to ensure that results are relevant to the realities in the three countries. DISCUSSION: We have deployed a comprehensive research approach to ensure the robustness and future policy uptake of findings. Besides the innovative PHISICC paper-based tools, our process is in itself innovative. Rather than emphasizing the technical dimensions of data management, we focused instead on frontline health workers' data use and decision-making. By tackling the whole scope of primary healthcare areas rather than a subset of them, we have developed an entirely new design and visual language for a suite of tools across healthcare areas. The initiative is being tested in remote, rural areas where the most vulnerable live.

High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection.

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206-6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36-12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

Persistent high levels of immune activation and their correlation with the HIV-1 proviral DNA and 2-LTR circles loads, in a cohort of Mexican individuals following long-term and fully suppressive treatment.

OBJECTIVES: The aim of this study was to investigate the correlation between the HIV-1 reservoir and the levels of immune activation in chronic patients under fully suppressive cART. METHODS: We quantified the HIV proviral DNA and 2-LTR circles loads from PBMCs, the levels of CD38+ and Ki-67+ T-cells, and the levels of IL-7 in a cohort of patients with more than 5 years of ART at enrollment and after 1 year. RESULTS: In 29 participants with a median of 8 years (IQR, 6.9-9.4) under suppressive cART we found higher levels of CD8+ CD38+ T-cells after 1-year (P = .000). There was a non-statistically significant poor correlation between the levels of immune activation and the proviral DNA of CD4+ and CD8+ T-cells. Ki-67+ T-cells declined without significant differences, and there was no significant correlation with the proportion of CD38+. IL-7 decreased at the follow-up observation (P = .094), but there was no correlation with the levels of CD38+ and Ki-67+ T-cells. CONCLUSIONS: We found a weak but non-statistically significant correlation of the levels of T-cell activation with the proviral DNA and 2-LTR circles. This suggests the likely occurrence of further mechanisms driving chronic versus early immune activation other than viral replication by itself in chronic patients.

Protein phosphatase 2A B55ß limits CD8+ T cell lifespan following cytokine withdrawal.

How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55ß, a regulatory subunit of protein phosphatase 2A, represents a molecular link between cytokine concentration and apoptosis in activated CD8+ T cells. Through the modulation of AKT, B55ß induced the expression of the proapoptotic molecule Hrk in response to cytokine withdrawal. Accordingly, B55ß and Hrk were both required for in vivo and in vitro contraction of activated CD8+ lymphocytes. We show that this process plays a role during clonal contraction, establishment of immune memory, and preservation of peripheral tolerance. This regulatory pathway may represent an unexplored opportunity to end unwanted immune responses or to promote immune memory.

Regulation of Cas9 by viral proteins Tat and Rev for HIV-1 inactivation.

While combined antiretroviral therapy (cART) has had a great impact on the treatment of HIV-1 infection, the persistence of long-lived cells with an intact provirus precludes virus eradication and sterilizing cure. CRISPR/Cas9 genome editing has become an efficient tool to eradicate HIV-1 genome or prevent replication. Furthermore, regulation of Cas9 gene expression by HIV can induce mutations that could inactivate the proviral genome, making a gene therapy safe by preventing the induction of non-specific mutations, which could compromise the integrity of healthy cells. In this study, isolated HIV-1 LTR, INS and RRE sequences were used to regulate Cas9 expression in HEK293 cells, and guide RNAs (gRNAs) were designed to target mutations in HIV-1 conserved regions such as tat and rev regulatory genes. We demonstrate that Cas9 expression in our system is controlled by the HIV-1 Tat and Rev proteins, leading to self-regulation of gene edition, and showing a strong antiviral effect by inactivating HIV-1 replication. Sequencing analysis confirmed that viral genome was partially excised by multiplex editing (90% efficiency), and viral capsid protein (CA-p24) was undetectable. In conclusion, the self-regulated CRISPR/Cas9 system may be a reliable and accurate strategy for eliminating HIV-1 infection whose effect will be restricted to infected cells.

Impacts of Hurricanes Irma and Maria on Aedes aegypti Populations, Aquatic Habitats, and Mosquito Infections with Dengue, Chikungunya, and Zika Viruses in Puerto Rico.

Puerto Rico was severely impacted by Hurricanes Irma and Maria in September 2017. The island has been endemic for dengue viruses (DENV) and recently suffered epidemics of chikungunya (CHIKV 2014) and Zika (ZIKV 2016) viruses. Although severe storms tend to increase the number of vector and nuisance mosquitoes, we do not know how they influence Aedes aegypti populations and arboviral transmission. We compared the abundance of female Ae. aegypti in autocidal gravid ovitraps (AGO traps), container habitats, and presence of RNA of DENV, CHIKV, and ZIKV in this vector before and after the hurricanes in Caguas city and in four communities in southern Puerto Rico. Two of these communities were under vector control using mass AGO trapping and the other two nearby communities were not. We also investigated mosquito species composition and relative abundance (females/trap) using Biogents traps (BG-2 traps) in 59 sites in metropolitan San Juan city after the hurricanes. Mosquitoes sharply increased 5 weeks after Hurricane Maria. Ensuing abundance of Ae. aegypti was higher in Caguas and in one of the southern communities without vector control. Aedes aegypti did not significantly change in the two areas with vector control. The most abundant mosquitoes among the 26 species identified in San Juan were Culex (Melanoconion) spp., Culex quinquefasciatus, Culex nigripalpus, and Ae. aegypti. No arboviruses were detected in Ae. aegypti following the hurricanes, in contrast with observations from the previous year, so that the potential for Aedes-borne arboviral outbreaks following the storms in 2017 was low.

Citywide Control of Aedes aegypti (Diptera: Culicidae) during the 2016 Zika Epidemic by Integrating Community Awareness, Education, Source Reduction, Larvicides, and Mass Mosquito Trapping.

This investigation was initiated to control Aedes aegypti and Zika virus transmission in Caguas City, Puerto Rico, during the 2016 epidemic using Integrated Vector Management (IVM), which included community awareness and education, source reduction, larviciding, and mass-trapping with autocidal gravid ovitraps (AGO). The epidemic peaked in August to October 2016 and waned after April 2017. There was a preintervention period in October/November 2016 and IVM lasted until August 2017. The area under treatment (23.1 km2) had 61,511 inhabitants and 25,363 buildings. The city was divided into eight even clusters and treated following a cluster randomized stepped-wedge design. We analyzed pools of female Ae. aegypti adults for RNA detection of dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) viruses using 360 surveillance AGO traps every week. Rainfall, temperature, and relative humidity were monitored in each cluster. Mosquito density significantly changed (generalized linear mixed model; F8, 14,588 = 296; P < 0.001) from 8.0 ± 0.1 females per trap per week before the intervention to 2.1 ± 0.04 after the percentage of buildings treated with traps was 60% and to 1.4 ± 0.04 when coverage was above 80%. Out of a total 12,081 mosquito pools, there were 1 DENV-, 7 CHIKV-, and 49 ZIKV-positive pools from October 2016 to March 2017. Afterward, we found only one positive pool of DENV in July 2017. This investigation demonstrated that it was possible to scale up effective Ae. aegypti control to a medium-size city through IVM that included mass trapping of gravid Ae. aegypti females.

Vaccination with human papillomavirus-18 E1 protein plus α-galactosyl-ceramide induces CD8+ cytotoxic response and impairs the growth of E1-expressing tumors.

CD8+ T cell-mediated immune response plays a major role in the clearance of virus-infected cells, including human papillomavirus (HPV). The effective treatment of women with normal cytology but persistent high risk-HPV infection or with low-grade intraepithelial lesions could take advantage of novel strategies based on vaccination with viral immunological targets with a wide spectrum of cross-protection. The helicase E1, expressed early during viral replication in HPV infection, is among the most conserved papillomavirus proteins, which makes it a good vaccine candidate. In the present study, we examined E1-specific CD8+ T cell and NK immune responses in a mouse model with α-galactosylceramide (α-GalCer) as an adjuvant. We found that mice immunized with E1 combined with α-GalCer elicited an E1-specific CD8+ T and NK cell cytotoxic responses, which correlated with growth inhibition of grafted melanoma B16-F0 cells expressing E1, both in prophylactic and therapeutic protocols.

Using a service design model to develop the "Passport to Safer Birth" in Nigeria and Uganda.

OBJECTIVE: To demonstrate how a human-centered service design approach can generate practical tools for good-quality childbirth care in low-resource settings. METHODS: As part of the WHO "Better Outcomes in Labour Difficulty" (BOLD) project, a service design approach was used in eight Ugandan and Nigerian health facilities and communities to develop the "Passport to Safer Birth." There are three phases: Research for Design, Concept Design, and Detail Design. These generated design principles, design archetype personas, and Passport prototypes. Data collection methods included desk research, interviews, group discussions, and journey mapping to identify touchpoints where the woman interacts with the health system. RESULTS: A total of 90 interviews, 12 observation hours, and 15 group discussions were undertaken. The resulting design principles were: a shared and deeper understanding of pregnancy and childbirth among family and community; family readiness for decision-making and action; and the woman's sense of being in control and being cared for. Four archetype personas of women emerged: Vulnerable; Passive; Empowered; Accepter. Subsequent development of the Passport to Safer Birth tools addressed three domains: Care Mediator; Expectation Manager; and Pregnancy Assistant. CONCLUSION: The service design approach can create innovative, human-centered service solutions to improve maternity care experiences and outcomes in low-resource settings.

A service concept and tools to improve maternal and newborn health in Nigeria and Uganda.

OBJECTIVE: The "Better Outcomes in Labor Difficulty" (BOLD) project used a service design process to design a set of tools to improve quality of care during childbirth by strengthening linkages between communities and health facilities in Nigeria and Uganda. This paper describes the Passport to Safer Birth concept and the tools developed as a result. METHODS: Service design methods were used to identify facilitators and barriers to quality care, and to develop human-centered solutions. The service design process had three phases: Research for Design, Concept Design, and Detail Design, undertaken in eight hospitals and catchment communities. RESULTS: The service concept "Better Beginnings" comprises three tools. The "Pregnancy Purse" provides educational information to women throughout pregnancy. The "Birth Board" is a visual communication tool that presents the labor and childbirth process. The "Family Pass" is a set of wearable passes for the woman and her supporter to facilitate communication of care preferences. CONCLUSION: The Better Beginnings service concept and tools form the basis for the promotion of access to information and knowledge acquisition, and could improve communication between the healthcare provider, the woman, and her family during childbirth.

CD38 Expression in a Subset of Memory T Cells Is Independent of Cell Cycling as a Correlate of HIV Disease Progression.

In order to determine if the expression of the activation marker CD38 can correlate with HIV disease progression independently of cycling, we performed a cluster-based multivariate correlation analysis of total circulating CD4(+) T cell counts and viral loads with frequencies of CD38 and Ki67 expression on CD4(+) lymphocytes from patients with untreated HIV infection, stratified in maturation subpopulations, and subpopulation subsets defined by the expression of CXCR5, CXCR3, and CCR4. The frequencies of the activated phenotypes %CD38(+) Ki67(-) and %CD38(+) Ki67(+) of the CXCR5(-) CXCR3(-) CCR4(+) ("pre-Th2") central memory (T(CM)) cell subset clustered together, comprising a significant negative correlate of total circulating CD4(+) T cell counts and a positive correlate of viral load in multivariate analysis. Frequency of cycling-uncoupled CD38 expression in "pre-Th2" T(CM) cells was a negative correlate of total circulating CD4(+) T cell counts in univariate analysis, which was not the case of their %CD38(+) Ki67(+). CXCR5(+) CXCR3(-) CCR4(-) T(CM) cells were underrepresented in patients, and their absolute counts correlated negatively with their %CD38(+) Ki67(-) but not with their % CD38(+) Ki67(+). Our results may imply that CD38 expression either reflects or participates in pathogenic mechanisms of HIV disease independently of cell cycling.

Transient expansion of activated CD8(+) T cells characterizes tuberculosis-associated immune reconstitution inflammatory syndrome in patients with HIV: a case control study.

BACKGROUND: CD4(+) T cell activation indicators have been reported to be a common phenomenon underlying diverse manifestations of immune reconstitution inflammatory syndrome (IRIS). However, we have found that a high frequency of circulating CD8(+) T cells is a specific risk factor for mycobacterial IRIS. Therefore, we investigated whether CD8(+) T cells from patients who develop TB IRIS were specifically activated. METHODS: We obtained PBMCs from HIV+ patients prior to and 4, 8, 12, 24, 52 and 104 weeks after initiating antiretroviral therapy. CD38 and HLADR expression on naive, central memory and effector memory CD8(+) and CD4(+) T cells were determined by flow cytometry. Absolute counts and frequencies of CD8(+) T cell subsets were compared between patients who developed TB IRIS, who developed other IRIS forms and who remained IRIS-free. RESULTS: TB IRIS patients showed significantly higher counts of naive CD8(+) T cells than the other groups at most time points, with a contraction of the effector memory subpopulation occurring later in the follow-up period. Activated (CD38(+) HLADR(+)) CD8(+) T cells from all groups decreased with treatment but transiently peaked in TB IRIS patients. This increase was due to an increase in activated naive CD8(+) T cell counts during IRIS. Additionally, the CD8(+) T cell subpopulations of TB IRIS patients expressed HLADR without CD38 more frequently and expressed CD38 without HLADR less frequently than cells from other groups. CONCLUSIONS: CD8(+) T cell activation is specifically relevant to TB IRIS. Different IRIS forms may involve different alterations in T cell subsets, suggesting different underlying inflammatory processes.

A (H1N1) pdm09 HA D222 variants associated with severity and mortality in patients during a second wave in Mexico.

BACKGROUND: Pandemic type A (H1N1) influenza arose in early 2009, probably in Mexico and the United States, and reappeared in North America in September for seven more months. An amino acid substitution in the hemagglutinin (HA), D222G, has been reported in a significant proportion of patients with a severe and fatal outcome. We studied the prevalence of HA222 substitutions in patients in Mexico during the second wave and its association with clinical outcome and pathogenicity in a mouse model. METHODS: The nucleotide sequences of hemagglutinin (HA) from viruses collected from 77 patients were determined including 50 severe and fatal cases and 27 ambulatory cases. Deep sequencing was done on 5 samples from severe or fatal cases in order to determine the quasispecies proportion. Weight loss and mortality due to infection with cultured influenza viruses were analyzed in a mouse model. RESULTS: Viruses from 14 out of 50 hospitalized patients (28%) had a non aspartic acid residue at the HA 222 position (nD222), while all 27 ambulatory patients had D222 (p=0.0014). G222 was detected as sole species or in coexistence with N222 and D222 in 12 patients with severe disease including 8 who died. N222 in coexistence with D222 was detected in 1 patient who died and co-occurrence of A222 and V222, together with D222, was detected in another patient who died. The patients with a nD222 residue had higher mortality (71.4%), compared to the group with only D222 (22.2%, p=0.0008). Four of the 14 viruses from hospitalized patients were cultured and intranasally infected into mice. Two viruses with G222 were lethal while a third virus, with G222, caused only mild illness in mice similar to the fourth virus that contained D222. CONCLUSIONS: We confirm the elevated incidence of HA222 (H1N1)pdm09 variants in severe disease and mortality. Both clinical and mouse infection data support the idea that nD222 mutations contribute to increased severity of disease but additional determinants in disease outcome may be present.

Severe 2009 pandemic influenza A (H1N1) infection and increased mortality in patients with late and advanced HIV disease.

OBJECTIVE: To describe the clinical course of infection by 2009 (H1N1) influenza virus in different stages of HIV disease. DESIGN: Prospective, observational study. METHODS: During the pandemic period, HIV-infected patients presenting respiratory symptoms at a third level referral hospital in Mexico City were tested for 2009 influenza A (H1N1) viral RNA. Clinical files were prospectively analyzed. RESULTS: Infection by H1N1 was confirmed in 30 (23.8%) of the total 126 HIV-infected patients studied. In the group of patients with 2009 H1N1 virus infection, 16 (53.3%) were hospitalized, 12 (40%) had active opportunistic infections and six (20%) died. In the group of 96 patients not infected with 2009 H1N1 virus, 54 (56.25%) were hospitalized with opportunistic infections and 12 (12.5%) died. For all hospitalized patients, being on HAART and having undetectable HIV viral loads at hospitalization was associated with higher survival (P = 0.019). Patients with 2009 H1N1 virus infection had a higher mortality rate, even after adjusting for HAART (P = 0.043). Coinfection by HIV and H1N1 2009 virus was more severe in patients with opportunistic infections, as shown by longer hospital stays (P = 0.0013), higher rates of hospitalization (P < 0.0001), use of mechanical ventilation (P = 0.0086) and death (P = 0.026). Delayed administration of oseltamivir in hospitalized patients was significantly associated with mortality (P = 0.0022). CONCLUSION: Our data suggest that infection by 2009 H1N1 is more severe in HIV-infected patients with late and advanced HIV disease than in well controlled patients under HAART.

Plasmaféresis en el tratamiento de la Miastenia Gravis: presentación de caso / Plasmapheresis in the treatment of the Miastenia Gravis: a case presentation

Se presentó una paciente de19 años de edad, raza blanca, femenina, con antecedentes de padecer de miastenia gravis desde hace aproximadamente 2 años, que acudió al cuerpo de guardia en plena crisis de su enfermedad de base; este cuadro progresó tomando los músculos respiratorios por lo que necesitó de ventilación mecánica artificial, cuadro clínico que llevó a realizar tres sesiones de plasmaféresis como tratamiento de la crisis aguda de la miastenia gravis con toma de la musculatura respiratoria, se efectuaron en días consecutivos con un promedio de cuatro horas y media, la albúmina humana como solución de reemplazo del plasma separado de la sangre de la paciente para eliminar los mediadores que llevaron a este cuadro a la paciente, acto seguido a la última sesión se separó del respirador artificial.

A nineteen years patient, white race, female with antecedents of suffering miastenia gravis since two years approximately, arrived to the emergency department in full crisis of her basic disease, guardhouse, this profile progressed taking respiratory muscles, reason why she needed artificial mechanical ventilation, this clinical profile carried out three sessions of plasmapheresis as acute crisis treatment of miastenia gravis with taking of respiratory muscle, they took place in consecutive days with an average of four hours and a half, human albumin as replaced solution plasma separated from the patient blood to eliminate the mediators that carried out this patient to this clinical profile, immediately after wards to the last session she was apart from the artificial respirator.