Clinical Disease Research Articles

Psychosocial stressors of adolescents with E-cigarette, or vaping, product-use associated lung injury: A qualitative study

Background and objectivesAdolescent electronic cigarette (EC) use has reached epidemic rates and has been linked to numerous mental health and psychosocial stressors (PS). There is limited qualitative data on PS for adolescents with e-cigarette, or vaping, product-use associated lung injury (EVALI), a severe complication of EC use. MethodsAll patients hospitalized at Children’s Medical Center in Dallas, Texas from 2018 to 2022 and met CDC case definitions for EVALI were included in the analysis. PS were extracted from the electronic health record and analyzed for recurring themes using the HEADSS assessment as a framework. Results were summarized using descriptive statistics, and representative quotations were selected to highlight each theme. ResultsForty-three adolescents (mean age 16.3 years; 62.8 % male; 39.5 % Non-Hispanic White, 60.5 % Hispanic) were included in the analysis, and 40 (93 %) reported PS. The most common themes were family (51 %; “restraining order issued against 28-year-old brother”), polysubstance use (77 %; “experimenting with…ecstasy, LSD, CCC, misusing Adderall”), and mental health (63 %; “has been suicidal since he was ‘a toddler’”). Less commonly, patients reported PS related to peers (28 %; “spending the entire day at the cemetery where his best friend was buried”), school (49 %; “attending his second alternative school”), and the legal system (19 %; “placed in juvenile detention, released, and will be on probation”). ConclusionsAdolescents with EVALI had PS that were chronic, severe, and involving multiple domains. These findings emphasize the importance of psychosocial screening in adolescents and coordinating interdisciplinary care with mental health and social services.

Implementation and evaluation of a SARI surveillance system in a tertiary hospital in Scotland in 2021/2022

ObjectiveTo set up and evaluate a new surveillance system for severe acute respiratory infection (SARI) in Scotland. Study designCross-sectional study and evaluation of surveillance system. MethodsThe SARI case definition comprised patients aged 16 years or over with an acute respiratory illness presentation requiring testing for influenza and SARS-CoV-2 and hospital admission. Data were collected from SARI cases by research nurses in one tertiary teaching hospital using a bespoke data collection tool from November 2021 to May 2022. Descriptive analyses of SARI cases were carried out. The following attributes of the surveillance system were evaluated according to Centers for Disease Control and Prevention (CDC) guidelines: stability, data quality, timeliness, positive predictive value, representativeness, simplicity, acceptability and flexibility. ResultsThe final surveillance dataset comprised 1163 records, with cases peaking in ISO week 50 (week ending 19/12/2021). The system produced a stable stream of surveillance data, with the proportion of SARI records with sufficient information for effective surveillance increasing from 65.4% during the first month to 87.0% over time. Similarly, the proportion where data collection was completed promptly was low initially, but increased to 50%–65% during later periods. ConclusionSARI surveillance was successfully established in one hospital, but for a national system, additional sentinel hospital sites across Scotland, with flexibility to ensure consistently high data completeness and timeliness are needed. Data collection should be automated where possible, and demands on clinicians minimised. SARI surveillance should be embedded and resourced as part of a national respiratory surveillance strategy.

Chest X-Ray-Based Telemedicine Platform for Pediatric Tuberculosis Diagnosis in Low-Resource Settings: Development and Validation Study.

Tuberculosis (TB) remains a major cause of morbidity and death worldwide, with a significant impact on children, especially those under the age of 5 years. The complex diagnosis of pediatric TB, compounded by limited access to more accurate diagnostic tests, underscores the need for improved tools to enhance diagnosis and care in resource-limited settings. This study aims to present a telemedicine web platform, BITScreen PTB (Biomedical Image Technologies Screen for Pediatric Tuberculosis), aimed at improving the evaluation of pulmonary TB in children based on digital chest x-ray (CXR) imaging and clinical information in resource-limited settings. The platform was evaluated by 3 independent expert readers through a retrospective assessment of a data set with 218 imaging examinations of children under 3 years of age, selected from a previous study performed in Mozambique. The key aspects assessed were the usability through a standardized questionnaire, the time needed to complete the assessment through the platform, the performance of the readers to identify TB cases based on the CXR, the association between the TB features identified in the CXRs and the initial diagnostic classification, and the interreader agreement of the global assessment and the radiological findings. The platform's usability and user satisfaction were evaluated using a questionnaire, which received an average rating of 4.4 (SD 0.59) out of 5. The average examination completion time ranged from 35 to 110 seconds. In addition, the study on CXR showed low sensitivity (16.3%-28.2%) but high specificity (91.1%-98.2%) in the assessment of the consensus case definition of pediatric TB using the platform. The CXR finding having a stronger association with the initial diagnostic classification was air space opacification (χ21>20.38, P<.001). The study found varying levels of interreader agreement, with moderate/substantial agreement for air space opacification (κ=0.54-0.67) and pleural effusion (κ=0.43-0.72). Our findings support the promising role of telemedicine platforms such as BITScreen PTB in enhancing pediatric TB diagnosis access, particularly in resource-limited settings. Additionally, these platforms could facilitate the multireader and systematic assessment of CXR in pediatric TB clinical studies.

Piloting wastewater-based surveillance of norovirus in England

Wastewater-based epidemiology (WBE) gained widespread use as a tool for supporting clinical disease surveillance during the COVID-19 pandemic. There is now significant interest in the continued development of WBE for other pathogens of clinical significance. In this study, approximately 3,200 samples of wastewater from across England, previously collected for quantification of SARS-CoV-2, were re-analysed for the quantification of norovirus genogroup I (GI) and II (GII). Overall, GI and GII were detected in 93% and 98% of samples respectively, and at least one of the genogroups was detected in 99% of samples. GI was found at significantly lower concentrations than GII, but the proportion of each genogroup varied over time, with GI becoming more prevalent than GII in some areas towards the end of the study period (May 2021 – March 2022). Using relative strength indices (RSI), it was possible to study the trends of each genogroup, and total norovirus over time. Increases in norovirus levels appeared to coincide with the removal of COVID-19 related lockdown restrictions within England. Local Moran's I analyses indicated several localised outbreaks of both GI and GII across England, notably the possible GI outbreak in the north of England in early 2022. Comparisons of national average norovirus concentrations in wastewater against concomitant norovirus reported case numbers showed a significant linear relationship. This highlights the potential for wastewater-based monitoring of norovirus as a valuable approach to support surveillance of norovirus in communities.

The Diagnostic Value of Serum Amyloid A and Other Laboratory and Clinical Variables in Cats with Increased Liver Enzyme Activity.

Distinguishing inflammatory from non-inflammatory liver disease in cats may impact management. The study aim was to evaluate if certain diagnostic variables, including Serum Amyloid A (SAA), differ (1) between various clinical disease categories (Primary liver disease, Extrahepatic, Trauma and Inconclusive) and (2) between cytological findings of severe hepatic lipidosis and other cytological findings in cats with increased liver enzymes. Medical records from 5042 cats, where SAA had been measured, were reviewed, and 566 cats fulfilled inclusion criteria consisting of increased liver enzymes and available biochemical panel results. SAA was higher in cats diagnosed with trauma compared to other diseases (p = 0.008). Cytology results were available in 85 cats, and cats with severe lipidosis had lower serum SAA concentration (p < 0.0001) and were younger (p < 0.0002) compared to cats with other cytological findings. The study shows that SAA was higher in cats diagnosed with trauma compared to cats with other causes of increased liver enzymes and that SAA may be useful to distinguish cats with cytologic evidence of hepatic lipidosis from cats with other liver pathologies. Serum Amyloid A may be a valuable complement to liver cytology when investigating cats with increased liver enzymes.

Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque.

Mayaro virus (MAYV), a mosquito-borne alphavirus, is considered an emerging threat to public health with epidemic potential. Phylogenetic studies show the existence of three MAYV genotypes. In this study, we provide a preliminary analysis of the pathogenesis of all three MAYV genotypes in cynomolgus macaques (Macaca facicularis, Mauritian origin). Significant MAYV-specific RNAemia and viremia were detected during acute infection in animals challenged intravenously with the three MAYV genotypes, and strong neutralizing antibody responses were observed. MAYV RNA was detected at high levels in lymphoid tissues, joint muscle and synovia over 1 month after infection, suggesting that this model could serve as a promising tool in studying MAYV-induced chronic arthralgia, which can persist for years. Significant leucopenia was observed across all MAYV genotypes, peaking with RNAemia. Notable differences in the severity of acute RNAemia and composition of cytokine responses were observed among the three MAYV genotypes. Our model showed no outward signs of clinical disease, but several major endpoints for future MAYV pathology and intervention studies are described. Disruptions to normal blood cell counts and cytokine responses were markedly distinct from those observed in macaque models of CHIKV infection, underlining the importance of developing non-human primate models specific to MAYV infection.

Investigation of the water environmental DNA/RNA profile for non‐invasive biomonitoring of the fish pathogen Aeromonas salmonicida subsp. salmonicida and detection of immune responses in rainbow trout (Oncorhynchus mykiss)

AbstractAquaculture industries face challenges in fish production, primarily due to disease occurrence. Clinical manifestations of these diseases often indicate a considerable advancement in the pathological process. Infected fish often experience morbidity, leading to compromised welfare and substantial economic losses for production facilities. Therefore, prophylaxis and early detection of the pathogens could allow the facility managers to intervene or treat the disease before clinical disease signs occur. For the first time, environmental DNA/RNA (collectively eNA) was used to detect the salmonid pathogen Aeromonas salmonicida subsp. salmonicida in the water hosting rainbow trout (Oncorhynchus mykiss). This took place under controlled experimental conditions, before the occurrence of clinical outcome and mortality. The concentration of bacteria in the water was determined by using a standard curve. To determine the window of possible intervention, bacterial concentration was measured from an early stage of disease and throughout when fish became moribund. Furthermore, the acute phase protein, serum amyloid A produced by rainbow trout, was detected in the water and was found to be up‐regulated 4 days post challenge. It was thereby shown that it is possible to detect strong immune responses in the fish in a non‐invasive manner. The detection of eNA from the water can be used as a tool to detect pathogens in the early phase of infection before the disease becomes severe. This will facilitate interventions to limit the disease and increase the welfare of the fish, which is becoming a requirement for a more sustainable and ethical animal production.

Hepatocyte-specific loss of DDB1 attenuates hepatic steatosis but aggravates liver inflammation and fibrosis in MASH.

MASH is a common clinical disease that can lead to advanced liver conditions, but no approved pharmacotherapies are available due to an incomplete understanding of its pathogenesis. Damaged DNA binding protein 1 (DDB1) participates in lipid metabolism. Nevertheless, the function of DDB1 in MASH is unclear. Clinical liver samples were obtained from patients with MASH and control individuals by liver biopsy. Hepatocyte-specific Ddb1-knockout mice and liver Hmgb1 knockdown mice were fed with a methionine-and choline-deficient diet to induce MASH. We found that the expression of DDB1 in the liver was significantly decreased in MASH models. Hepatocyte-specific ablation of DDB1 markedly alleviated methionine-and choline-deficient diet-induced liver steatosis but unexpectedly exacerbated inflammation and fibrosis. Mechanistically, DDB1 deficiency attenuated hepatic steatosis by downregulating the expression of lipid synthesis and uptake genes. We identified high-mobility group box 1 as a key candidate target for DDB1-mediated liver injury. DDB1 deficiency upregulated the expression and extracellular release of high-mobility group box 1, which further increased macrophage infiltration and activated HSCs, ultimately leading to the exacerbation of liver inflammation and fibrosis. These data demonstrate the independent regulation of hepatic steatosis and injury in MASH. These findings have considerable clinical implications for the development of therapeutic strategies for MASH.

Newly Recognized Spotted Fever Group Rickettsia as Cause of Severe Rocky Mountain Spotted Fever-Like Illness, Northern California, USA.

The incidence of spotted fever group (SFG) rickettsioses in the United States has tripled since 2010. Rocky Mountain spotted fever, the most severe SFG rickettsiosis, is caused by Rickettsia rickettsii. The lack of species-specific confirmatory testing obfuscates the relative contribution of R. rickettsii and other SFG Rickettsia to this increase. We report a newly recognized rickettsial pathogen, Rickettsia sp. CA6269, as the cause of severe Rocky Mountain spotted fever-like illness in 2 case-patients residing in northern California. Multilocus sequence typing supported the recognition of this pathogen as a novel Rickettsia genotype most closely related to R. rickettsii. Cross-reactivity observed for an established molecular diagnostic test indicated that Rickettsia sp. CA6269 might be misidentified as R. rickettsii. We developed a Rickettsia sp. CA6269-specific real-time PCR to help resolve this diagnostic challenge and better characterize the spectrum of clinical disease and ecologic epidemiology of this pathogen.

A Collaborative Self-supervised Domain Adaptation for Low-Quality Medical Image Enhancement.

Medical image analysis techniques have been employed in diagnosing and screening clinical diseases. However, both poor medical image quality and illumination style inconsistency increase uncertainty in clinical decision-making, potentially resulting in clinician misdiagnosis. The majority of current image enhancement methods primarily concentrate on enhancing medical image quality by leveraging high-quality reference images, which are challenging to collect in clinical applications. In this study, we address image quality enhancement within a fully self-supervised learning setting, wherein neither high-quality images nor paired images are required. To achieve this goal, we investigate the potential of self-supervised learning combined with domain adaptation to enhance the quality of medical images without the guidance of high-quality medical images. We design a Domain Adaptation Self-supervised Quality Enhancement framework, called DASQE. More specifically, we establish multiple domains at the patch level through a designed rule-based quality assessment scheme and style clustering. To achieve image quality enhancement and maintain style consistency, we formulate the image quality enhancement as a collaborative self-supervised domain adaptation task for disentangling the low-quality factors, medical image content, and illumination style characteristics by exploring intrinsic supervision in the low-quality medical images. Finally, we perform extensive experiments on six benchmark datasets of medical images, and the experimental results demonstrate that DASQE attains state-of-the-art performance. Furthermore, we explore the impact of the proposed method on various clinical tasks, such as retinal fundus vessel/lesion segmentation, nerve fiber segmentation, polyp segmentation, skin lesion segmentation, and disease classification. The results demonstrate that DASQE is advantageous for diverse downstream image analysis tasks.

Relationship of serum and dietary vitamin D with high cardiometabolic risk in Mexican systemic lupus erythematosus patients: A cross-sectional study.

Objetive: Serum and dietary vitamin D could influence clinical disease activity and cardiometabolic outcomes in systemic lupus erythematosus (SLE). This study aimed to assess the relationship of serum and dietary vitamin D with cardiometabolic risk in Mexican SLE patients and healthy subjects (HS).Methods: 224 SLE patients and 201 HS were included in this cross-sectional study. Serum calcidiol was measured using a competitive enzyme-linked immunosorbent assay (ELISA). Vitamin D dietary intake was assessed by collecting three 24h food records. Dietary patterns (DPs) were identified using principal component analysis (PCA). Cardiometabolic status was analyzed through biochemical measurements and cardiometabolic indexes.Results: Calcidiol deficiency (<20 ng/mL) was associated with 1.66-fold higher risk of excess weight by body mass index (BMI) (≥25 kg/m2) (p = .02), 2.25-fold higher risk to low high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) (p < .001), and 1.74-fold higher risk to high triglycerides (TG) ≥150 mg/dL (p = .02). Inadequate vitamin D dietary intake was associated with 1.92-fold higher risk of presenting non-healthy waist circumference (WC) (>80 cm) (p < .01), 2.05-fold higher risk of android waist to hip ratio (WHR ≥85) (p < .01), and 1.72-fold higher risk to excess weight (p = .02). Non-adherence to a DP rich in vitamin D food sources was associated with higher WC, WHR, triglycerides, and lower high-density lipoprotein-cholesterol (HDL-C); furthermore, in HS, non-adherence to the DP rich in vitamin D food sources provided 2.11-fold higher risk to calcidiol deficiency.In Cconclusion: A pattern of Calcidiol deficiency, inadequate vitamin D dietary intake, and non-adherence to a DP rich in vitamin D food sources was related to high cardiometabolic risk in SLE patients and HS.

Ethnoracial Disparities in Perinatal Outcomes Among Women Veterans.

Objective: Non-Hispanic Black women have increased rates of preterm birth and low infant birth weight. However, we do not know if these disparities replicate in women veterans, a population that may be at further risk for poor perinatal outcomes. This study sought to examine ethnoracial differences in preterm birth and low infant birth weight in veterans. Methods: A national sample of randomly chosen women veterans (i.e., oversampled for residency in high crime neighborhoods) reported information about all pregnancies they have had in their life, demographic characteristics, and history of childhood trauma exposures. The analytic sample was limited to individuals who identified as Hispanic/Latinx, Black, or White (n = 972). Mixed-effects regression models were used to examine ethnoracial differences in gestational age at delivery and infant birth weight, controlling for age at pregnancy, childhood trauma exposure, pregnancy during military service, income, and education. Results: Both Black and Hispanic/Latinx veterans were significantly more likely to have an infant born at lower gestational age (B = -1.04 and B = -1.11, respectively) and lower infant birth weight (B = -195.83 and B = -144.27, respectively) as compared with White veterans in covariate-adjusted models. Black (odds ratio = 3.24, confidence interval = 1.16, 9.09) veterans were more likely to meet the clinical definition of preterm birth as compared with White veterans. Conclusions: Results align with what is seen in the general population regarding ethnoracial disparities in gestational age at delivery and infant birth weight. Findings highlight the critical need for more research on mechanisms and prevention efforts for ethnoracial disparities in perinatal outcomes.

Research Progress of Chinese Medicine Regulating Intestinal Flora to Prevent Chronic Atrophic Gastritis

Chronic atrophic gastritis is a kind of common digestive disease in clinic, because of its insidious symptoms and easy to recur, and accompanied by a certain risk of cancer, in recent years in the clinic more and more attention to the incidence of this disease in the world is rising. This disease has the characteristics of complex pathogenesis, high therapeutic difficulty and prolonged recovery, etc. Western medicine treatment of chronic atrophic gastritis has side effects and the role is not significant, the motherland medicine in the treatment of this disease has a unique advantage, and the advantages of high safety, small side effects, significant efficacy, etc. The author will be from the intestinal flora of the relationship between the traditional Chinese medicine to elaborate the progress of the research on the regulation of intestinal flora of traditional Chinese medicine. In this paper, we reviewed the relevant literature from China Knowledge, Wanfang, Wipro, PubMed and other databases, and screened out 36 pieces of target literature. We will review the relationship between intestinal flora and CAG, and at the same time, we will discuss the feasibility of CAG treatment by TCM based on the regulation of intestinal flora, and we will look forward to the important role of the intestinal microenvironment in the future research on CAG flora. We will also review the relationship between intestinal flora and CAG.

Invasive methods for detection of Helicobacter pylori infection in gastric disorders patients undergoing endoscopy from Mosul city, Iraq

Objectives. The identification of H. pylori in Iraq lacks a standardized technique and there is limited information on the efficacy of different diagnostic methods. This research aims to determine the prevalence of H. pylori and evaluate the effectiveness of invasive techniques, namely the Rapid Urease Test (RUT), histopathological examination, and ure A gene by PCR, for detecting H. pylori. Method. Gastric biopsies specimens were collected from 50 patients with gastric disorders who underwent endoscopy after meeting the inclusion criteria. Patients were classified into H. pylori-positive cases and negative cases by testing positive with at least two of the three testing methods, according to the case definition used in the study. Outcomes. Of the 50 gastric biopsies, 58% were H. pylori-positive cases, 26% were H. pylori -negative cases, and the last 16% were indeterminate case according to cases definition. The ure A gene PCR was the most sensitive method, followed by histopathological examination and RUT testing, with sensitivities of 96.6%, 86.2% and 79.3% respectively. Histopathology examination was the most specific with a specificity of 95.2%, followed by ure A gene PCR with 85.7%, while RUT was the least specific with a specificity of 81%. Conclusion. The current study revealed a moderate prevalence of H. pylori infection compared with previous studies. The sensitivity and specificity of the three invasive methods varied, and a combination of two methods may be necessary for a definitive diagnosis of H. pylori infection.

Progress of Chinese and Western Medicine Research on Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common clinical disease of reproductive endocrine hormone abnormalities and metabolic disorders, with a variety of clinical symptoms and complex etiology. Recent studies have shown that genetics, reproductive endocrine hormones, inflammatory factors, intestinal flora, microRNAs, signal transduction pathways and insulin resistance are closely related to the development of PCOS. Regarding the treatment modalities of PCOS, Western medicine mostly focuses on symptomatic treatment for elevated androgens, ovulation abnormalities, menstrual irregularities and insulin resistance. Chinese medicine focuses on conditioning, and adopts Chinese medicine, acupuncture and needle-medicine combination for different identification and typing through the idea of holistic view. The combination of Chinese and Western medicine gives full play to the advantages between modern medicine and traditional medicine, and combines Western medicine with Chinese medicine for symptomatic treatment, which is a holistic approach and has significant therapeutic effects. Therefore, this paper provides an overview of the research on the etiology and pathogenesis of PCOS in recent years, as well as an overview of the treatment of PCOS by Western medicine, Chinese medicine and the combination of Chinese and Western medicine.

Ambient Particulate Matter Induces In Vitro Toxicity to Intestinal Epithelial Cells without Exacerbating Acute Colitis Induced by Dextran Sodium Sulfate or 2,4,6-Trinitrobenzenesulfonic Acid.

Inflammatory bowel disease (IBD) is an immunologically complex disorder involving genetic, microbial, and environmental risk factors. Its global burden has continued to rise since industrialization, with epidemiological studies suggesting that ambient particulate matter (PM) in air pollution could be a contributing factor. Prior animal studies have shown that oral PM10 exposure promotes intestinal inflammation in a genetic IBD model and that PM2.5 inhalation exposure can increase intestinal levels of pro-inflammatory cytokines. PM10 and PM2.5 include ultrafine particles (UFP), which have an aerodynamic diameter of <0.10 μm and biophysical and biochemical properties that promote toxicity. UFP inhalation, however, has not been previously studied in the context of murine models of IBD. Here, we demonstrated that ambient PM is toxic to cultured Caco-2 intestinal epithelial cells and examined whether UFP inhalation affected acute colitis induced by dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid. C57BL/6J mice were exposed to filtered air (FA) or various types of ambient PM reaerosolized in the ultrafine size range at ~300 μg/m3, 6 h/day, 3-5 days/week, starting 7-10 days before disease induction. No differences in weight change, clinical disease activity, or histology were observed between the PM and FA-exposed groups. In conclusion, UFP inhalation exposure did not exacerbate intestinal inflammation in acute, chemically-induced colitis models.

Assessment of Antimicrobial Therapy in Eradicating Chlamydia muridarum in Research Mice: Immune Status and its Impact on Outcomes.

Chlamydia muridarum (Cm) is a moderately prevalent, gram-negative, intracellular bacterium that affects laboratory mice, causing subclinical to severe disease, depending on the host's immune status. The effectiveness of various antibiotic regimens aimed at eradicating Cm in both immunodeficient and immunocompetent laboratory mice was evaluated. NSG mice were cohoused with Cm-shedding BALB/cJ mice for 14 days to simulate natural exposure. Four groups of 8 infected NSG mice were treated for 7 days with either 0.08% sulfamethoxazole and 0.016% trimethoprim (TMS) in water, 0.0625% doxycycline in feed, 0.124%/0.025% TMS in feed, or 0.12% amoxicillin in feed. A control group was provided standard water and feed. The impact of treatment on gastrointestinal microbiota (GM) was performed through shotgun sequencing on the last day of treatment. TMS and Amoxicillin had negligible effects on GM, while doxycycline had the largest effect. All antibiotic treated NSG mice exhibited clinical disease, including dehydration, hunched posture, >20% weight loss, and dyspnea, leading to euthanasia 21-40 days post-treatment (32.6 ± 4.2 days; mean ± SD). Untreated controls were euthanized 14-33 days post-exposure (23.75 ± 5.9 days). All mice were fecal PCR positive for Cm at euthanasia. Histological evaluation revealed multifocal histiocytic and neutrophilic bronchointerstitial pneumonia and/or bronchiolitis featuring prominent intralesional chlamydial inclusion bodies in all mice. Subsequently, groups of 8 C57BL/6J, BALB/cJ, NOD.SCID, and NSG mice infected with Cm were treated with 0.124%/0.025% TMS in feed for 7 (BALB/cJ and C57BL/6J) or 21 days (NSG and NOD.SCID). All immunocompetent and NOD.SCID mice were negative for Cm by PCR 14 days post-treatment, remained clinically normal and had no evidence of Cm infection at necropsy, all NSG mice remained Cm positive and were euthanized. While these findings highlight the difficulties in eradicating Cm from highly immunodeficient mice, eradication of Cm from immunocompetent or moderately immunocompromised mice with antibiotics is feasible.

Effect of biologic agents and inflammation on lipid levels and cardiovascular risk in rheumatoid arthritis patients

BackgroundCardiovascular disease (CVD) is the main cause of mortality in Rheumatoid Arthritis (RA). ObjectiveTo investigate the effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) on lipids and CVD risk and evaluate associations with changes in systemic inflammation. MethodsPatients with RA initiating a bDMARD were evaluated at baseline, 3 and 6 months later. Longitudinal mixed effects models examined the association of individual biologics with changes in lipid levelsm Reynolds Risk Score (RRS) and Framingham risk score. Mediation by CRP, clinical disease activity index (CDAI) or swollen joint count on lipid changes were modeled using structural equation models. The correlation between CRP changes and LDL changes was estimated. Changes of LDL-C at 6 months among patients with low baseline LDL-C (<90 mg/dl) vs higher baseline LDL-C(90–130, and >130 mg/dl) were compared. The association between LDL-C changes across baseline LDL-C groups and disease activity improvement was evaluated. Results1698 bDMARD initiations were analyzed. Patients initiating tocilizumab had a significant increase in lipid levels but RRS at 3 and 6 months was similar across all biologics. Framingham risk score increased for patients treated with tocilizumab. Mediator analyses were statistically significant for the effects of CRP on lipid levels. Increases in LDL-C from baseline were independent of clinical response. An association of changes from baseline CRP and LDL-C were observed across all of the bDMARDs studied. ConclusionModerate increases in lipid levels on bDMARD treatment were not associated with an increased CVD risk by RRS regardless of the bDMARD initiated. Changes in CRP were significantly associated with changes in lipids in a mediator analysis.

Hypertrophic Pachymeningitis, Associated with Eosinophilic Granulomatosis with Polyangiitis, and ANCA-Negative Serology.

Hypertrophic pachymeningitis (HP) is a disease with diverse aetiologies, including the autoimmune one, either associated with antineutrophil cytoplasmic antibodies or immunoglobulin G4. A 65-year-old woman with a history of systemic arterial hypertension, presented with intense progressive headaches. HP and hemispheric vasogenic oedema were observed by nuclear magnetic resonance (NMR) study. During the six months before the headache, she had developed progressive hearing loss which she attributed to age. A biopsy of dura mater showed necrotising vasculitis with peripheral inflammatory infiltrate, made up of accumulations of epithelioid cells and multinucleated giant cells, and abundant eosinophils. A final diagnosis of HP with eosinophilic granulomatosis with polyangiitis (EGPA) was made. The patient had eosinophilic granulomatosis with polyangiitis (EGPA) histology, ANCA-negative serology and HP. This case is important because it shows that EGPA seems to have a spectrum of clinical diseases, including HP with negative serology, and bilateral sensorineural hearing loss. We are facing a wide spectrum of EGPA, breaking the paradigm of only systemic involvement. Hypertrophic pachymeningitis (HP) has several aetiologies; if the systemic investigation is not contributory to a diagnosis, a meningeal biopsy is necessary.This is the first case report of HP, associated with eosinophilic granulomatosis with polyangiitis (EGPA), and ANCA-negative serology.EGPA is probably a spectrum of diseases with predominant systemic involvement, but there may be cases where there is histological evidence, without the systemic context or positive serology.

Sustained Alleviation of Autoimmunity by Activating α2B-adrenergic Receptors.

Catecholamines binding to α- and β-adrenergic receptors on immune cells have recently been shown to play an important role in regulating immune responses. Although α2-adrenergic receptors are known to modulate the immune response in different ways, the therapeutic exploration of their utility has been limited by the lack of agonists selective for the three α2-adrenergic subtypes. We report in this study the identification of the agonist AGN-762, which activates α2B- and α2C-adrenergic subtypes, but not the α2A subtype. We show that AGN-762 reduced clinical disease in an experimental autoimmune encephalitis model of autoimmune disease via direct or indirect effects on T regulatory cells. The activity of AGN-762 was abrogated by depletion of T regulatory cells, which express the α2B-adrenergic receptor. Furthermore, a drug-induced shift to an anti-inflammatory phenotype was demonstrated in immune cells in the spleen of drug-treated experimental autoimmune encephalitis mice. AGN-762 does not display sedative and cardiovascular side effects associated with α2A subtype agonists. Immune modulation by selective α2-adrenergic agonists represents a novel, to our knowledge, approach for treating autoimmune disease.