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Background: Fungal meningitis can be associated with epidural anesthesia procedures. Fusariosis is a rare infection typically affecting immunocompromised patients and rarely causes meningitis. During 2022-2023, public health officials responded to a large outbreak of Fusarium solani meningitis associated with epidural anesthesia in Durango, Mexico. Methods: The public health response and epidemiological and clinical features of patients affected by this outbreak were described. Coordinated actions were addressed to identify the etiological agent, determine its drug susceptibility, develop diagnostic tests, and implement clinical and epidemiological protocols. Retrospective analyses of clinical variables and outcomes were performed to determine association with better patient survival. Results: A total of 1801 persons exposed to epidural anesthesia were identified, of whom 80 developed meningitis. Fusarium solani was found in 3 brain biopsies and showed susceptibility to voriconazole and amphotericin B. After F solani polymerase chain reaction (PCR) implementation, 57 patients with meningitis were PCR-screened, and 31 (38.8%) had a positive result. Most patients were female (95%), and cesarean section was the most common surgical procedure (76.3%). The case fatality rate was 51.3% (41 patients) and the median hospitalization duration was 39.5 days (interquartile range, 18-86 days). Seventy-one patients (88.8%) received voriconazole/amphotericin B and 64 subjects (80%) additionally received steroids. Cox regression analysis showed an increased lethality risk in patients who received antifungal treatment after 5 days (hazard ratio, 2.1 [95% confidence interval, 1.01-4.48], P < .05). Conclusions: The F solani meningitis outbreak in Durango was an unprecedented medical challenge. Timely treatment and effective healthcare management were associated with better survival outcomes.

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Pharmacovigilance (PV) activities aim to identify potential risks of medicines and vaccines after they have been authorised in the market by collecting and analysing information on suspected adverse events from different stakeholders. These can be captured and transmitted electronically in the form of Individual Case Safety Reports (ICSRs). Hence, up-to-date ICSRs management systems, like VigiFlow and signal detection and management systems as VigiLyze, have an important role in the PV system of a country. In 2019, after various attempts to establish a PV database that could fulfil the needs of the country, Mexico's National Regulatory Authority, COFEPRIS (Federal Commission for the Prevention against Sanitary Risks) decided to implement these tools. This has been a successful project that is still ongoing, it has involved national and international organisations, and has required the participation and integration of different components of the national PV system. The implementation of these tools has allowed COFEPRIS to increase its reporting trends and quality of reporting, while contributing to make more efficient interactions and processes with PV stakeholders, even during the COVID-19 pandemic. It has also allowed them to strengthen their commitment to the WHO-Programme for International Drug Monitoring, while highlighting opportunities for improvement in the national PV scenario and in the PV tools themselves. The aim of this article is to describe the implementation process, give an overview of current results regarding ICSR data and processes, and highlight the achievements, challenges, and opportunities for improvement after the three years since the beginning of the project.

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OBJECTIVE: Variants in STAT4 are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. We undertook this study to investigate how disease-associated variants affect STAT4 expression, in particular in CD4+ T cells where STAT4 plays an essential role. METHODS: We compared Th1 differentiation between naive CD4+ T cells from healthy donors homozygous for the risk (R/R) or nonrisk (NR/NR) alleles. We analyzed epigenetic marks in STAT4 and evaluated the relevance of its third intron, assessed the consequences of Stat4 overexpression in vivo in mice, and analyzed the effects of the STAT4 genotype in patients with lupus nephritis. RESULTS: Naive CD4+ T cells from NR/NR healthy donors down-regulated STAT4 in response to interleukin-12 (IL-12). In contrast, cells from R/R healthy donors maintained high levels. R/R cells exhibited a higher abundance of transcriptionally active STAT4 and increased interferon-γ production. Accordingly, R/R healthy donors exhibited a stronger induction of local active enhancer marks. Genetic editing confirmed the presence of a negative regulatory region in the STAT4 third intron, where most of the SLE-associated STAT4 single-nucleotide polymorphisms (SNPs) are located. In vivo forced expression demonstrated that increases in Stat4 levels in T cells enhanced glomerulonephritis in mice. Accordingly, the R/R genotype was associated with suboptimal response to treatment and with worse clinical outcomes in patients with proliferative lupus nephritis. CONCLUSION: The SLE-associated STAT4 haplotype correlates with an abnormal IL-12-mediated STAT4 transcriptional regulation. Carriers of the risk variant exhibit exaggerated CD4+ proinflammatory capacities that, in the context of SLE, contribute to more severe disease. R/R patients may benefit from blockade of the IL-12/STAT4 pathway.

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Introduction: The United States is home to 10.5 million undocumented immigrants, of which 5 out of 10 are Mexican or Central American. Their immigration status is an obstacle to secure employment that provides labor benefits such as sick leave and health insurance. Living through the global pandemic in the U.S. had a negative impact on this vulnerable population's mental and physical health. They avoided seeking primary or hospital care fearful that they were undocumented and uninsured. The services provided by the Ventanillas de Salud (VDS) "Health Windows" mitigated this pandemic's negative impact and have become an important source to support and increase access to health services among the immigrant community. Methods: De-identified data from a database system called the Continuous Information System and Health Reports of Mexicans in the United States (SICRESAL-MX) to perform this secondary analysis. The descriptive analysis describes socio-demographic, epidemiological, and situational characteristics of COVID-19. Results: Between January 2020 and July 2021, the VDS and UMS provided 11.5 million individual services to just over 4.3 million people. The main health conditions are overweight and obesity, high blood pressure and elevated cholesterol and glucose levels. Between March 2020 to July 2021 a total of 2,481,834 specific services related to COVID-19 were offered. Discussion: The Mexican migrant community in the United States is in a vulnerable situation, largely due to its immigration status which limits their access to health and human services, including primary health care services. Many of them have suffered from chronic diseases since before the pandemic, generating difficulties in monitoring the ailments and exacerbating their conditions.

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Background: Rheumatoid arthritis (RA) is a disease characterized by a chronic inflammatory state. High pro-inflammatory cytokine levels are associated with disease activity. Exercise and the Mediterranean diet (MD) exert anti-inflammatory effects; however, their impacts on inflammation in RA patients remains unknown. This study aimed to compare the effects of six-months of dynamic exercise program (DEP) vs. MD on pro- and anti-inflammatory cytokine serum concentrations. Methods: Secondary analysis of a randomized clinical trial in which 90 women with RA were randomly assigned to the DEP (n = 30), MD (n = 30), or control group (n = 30). All patients received pharmacological treatment. Serum concentrations of pro-inflammatory (TNF-α, TNF-ß, IL-1ß, IL-6 pg/mL) and anti-inflammatory (IL-10, IL-Ra pg/mL) cytokines were measured at baseline and after 6 months using the Luminex technique. Results: After 6 months of follow-up, we found an improvement of the median percentages changes concentrations of TNF-α (DEP, -12.3; MD, -13.3; control, 73.2; p = 0.01), TNF-ß (DEP, -67.4; MD, -54.9; control, 0; p = 0.04), and IL-6 (DEP, -19.9; MD, -37.7; control, 45.5; p = 0.04) in the DEP and MED groups in comparison with control group. IL-1Ra concentrations increased only in the MD group (13.8) compared to levels in the control group (-31.7), p = 0.04. There were no statistically significant differences between DEP and MD groups. Only n = 27 participants in the DEP group, n = 26 in the MD group, and n = 21 in the control group completed the follow-up. Conclusion: The DEP and the MD have potential effects in the concentrations of pro-inflammatory cytokines compared with those in a control group. Only the MD elevated the concentration of IL-Ra. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02900898].

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BACKGROUND: In patients with rheumatoid arthritis (RA) exercise improves muscle strength and decreases fat mass, whereas the consumption of a Mediterranean diet (MD) also has been associated with higher grip strength. Therefore, it is important to explore the combined effects of these interventions on hand grip strength and weight in RA. OBJECTIVE: To determine the combined effect of an MD and a dynamic exercise program (DEP) on hand grip strength in women with RA. METHOD: In a randomized clinical trial, 106 women with RA were included and assigned to the DEP-MD, DEP and MD groups. Weight, body circumferences, Disease Activity Score-28, Health Assessment Questionnaire Disability Index [HAQ-DI], and hand grip strength were measured at baseline and 24 weeks after the interventions. RESULTS: After 24 weeks, hand grip strength showed a significant increase in the DEP group (median 2 kg) compared with DEP-MD (median 0.5 kg) and MD (median -0.5 kg) groups (p = 0.03). In the MD group weight and waist circumference showed a significant decrease (-2.2 kg and -4.3 cm) compared with DEP-MD (0.85 kg and 1.9 cm) and DEP (0.35 kg and 0.5 cm) groups (p < 0.01). Finally, a significant decrease was observed in the HAQ-DI after treatment in the DEP-MD group of -0.5 and the DEP group of -0.25 compared with the MD group with no change (p = 0.03). CONCLUSION: In women with RA, in addition to pharmacological treatment, DEP increases hand grip strength and an MD decreases weight and waist circumferences, while the combination of DEP and MD improves disability.

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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.

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OBJECTIVES: To analyse the potential contribution of low-density granulocytes (LDGs) and NETosis, as well as the differential protein cargo of neutrophil extracellular traps (NETs), as physiopathogenic mechanisms of adult-onset Still's disease (AOSD). METHODS: We recruited 30 patients with AOSD according to the Yamaguchi diagnostic criteria. LDGs were addressed by multiparametric flow cytometry as those CD14-, CD15+, CD10+ cells in the peripheral blood mononuclear cells fraction. NETs were quantified by ELISA, immunofluorescence and fluorescence spectrometry. The expression of LL-37 and high mobility group box 1 (HMGB-1) in NETs was measured by immunofluorescence and confocal microscopy. Additionally, normal density neutrophils from healthy controls were stimulated with serum from patients with AOSD and NET induction was assessed by immunofluorescence. RESULTS: Patients with active disease as well as those with arthritis, cutaneous manifestations and fever had a higher amount of NETs and LDGs. Serum NETs from AOSD patients correlated with the number of swollen joints (r=0.41, p=0.032), absolute number of monocytes (r=0.529, p=0.005). The spontaneous NETs from patients with cutaneous manifestations and fever had higher cargo of HMGB-1 compared with patients in remission. CONCLUSIONS: LDGs and NETs are increased in patients with active AOSD and correlate with particular clinical features. Patients with cutaneous lesions and fever present a higher cargo of HMGB1 in their spontaneous NETs.

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The primary aim of this study was to assess demographic, clinical, and serological factors associated with remission in systemic lupus erythematosus (SLE). A retrospective cohort study was performed. We examined relevant features in patients with SLE with a follow-up of at least 8 years from active disease (SLE Disease Activity Index-2000 [SLEDAI-2K] ≥6). The primary outcome was to assess various remission states in SLE according to disease activity and treatment. Differences between groups were assessed by Student's t test and chi-square test for continuous and categorical variables, respectively. Multivariate Cox proportional hazard analysis was used to assess association between variables, and we performed a Kaplan-Meier analysis with log rank test to evaluate time to remission. One hundred twenty-four patients fulfilled our inclusion criteria: 116 (93.54%) were women with a mean age of 30.23 ± 8.52 years. Twenty-four patients (19.35%), 25 patients (20.16%), and 16 patients (12.9%) achieved complete remission, clinical remission on corticosteroids, and clinical remission off corticosteroids, respectively. SLEDAI-2K at 3rd month of follow-up (HR = 0.85, 95% CI = 0.73-0.98, p = 0.029) and total number of disease flares (HR = 0.73, 95% CI = 0.56-0.95, p = 0.024) were associated with complete remission, and total number of disease flares (HR = 0.80, 95% CI = 0.67-0.95, p = 0.011) was associated with clinical remission on corticosteroids. Our findings are clinically relevant to encourage an intensive immunosuppressive treatment and close monitoring early after active disease.

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BACKGROUND: Rheumatoid arthritis (RA) is a complex inflammatory disease that modifies body composition. Although body mass index (BMI) is one of the clinical nutrition tools widely used to assess indirectly nutritional status, it is not able to identify these body alterations. Bioelectrical Vector Analysis (BIVA) is an alternative method to assess hydration and body cell mass of patients with wasting conditions. OBJECTIVE: To investigate the differences in nutrition status according to BMI groups (normal, overweight and obesity) and BIVA classification (cachectic and non-cachectic) in women with RA. METHODS: Women with confirmed diagnosis of RA were included from January 2015 to June 2016. Whole-body bioelectrical impedance was measured using a tetrapolar and mono-frequency equipment. Patients were classified according to BMI as: low body weight (n = 6, 2.7%), normal (n = 59, 26.3%), overweight (n = 88, 39.3%) and obese (n = 71, 31.7%), and each group was divided into BIVA groups (cachectic 51.8% and non-cachectic 48.2%). RESULTS: A total of 224 RA patients were included, with mean age 52.7 years and median disease duration of 12 years. Significant differences were found in weight, arm circumference, waist, hip, resistance/height, reactance/height and erythrocyte sedimentation rate among all BMI groups. However, serum albumin levels were significantly different between cachectic and non-cachectic patients independently of BMI. In all BMI categories, cachectic groups had lower reactance and phase angle than non-cachectic subjects. CONCLUSION: RA patients with normal or even high BMI have a significantly lower muscle component. Evaluation of body composition with BIVA in RA patients could be an option for cachexia detection.

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