Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32+ nanoprotrusions deposit distinct plasma membrane patches onto target T cells. Transferred receptors confer cell migration and adhesion properties, and macrophage-derived membrane patches render resting CD4 T cells susceptible to infection by serving as hotspots for HIV-1 binding. Antibodies that recognize T cell epitopes enhance CD32-mediated trogocytosis. Such autoreactive anti-HIV-1 envelope antibodies can be found in the blood of HIV-1 patients and, consistently, the percentage of CD32+ CD4 T cells is increased in their blood. This CD32-mediated, antigen-independent cell communication mode transiently expands the receptor repertoire and functionality of immune cells. HIV-1 hijacks this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical to its persistence.

BACKGROUND:EsoCap is a thin mucoadhesive film designed to target the oesophageal mucosa. The device loaded with mometasone furoate (ESO-101) is under investigation for the treatment of eosinophilic oesophagitis (EoE). AIMS:To evaluate the efficacy, safety and tolerability of ESO-101 in patients with active EoE. METHODS:We conducted a randomised, placebo-controlled, phase 2, proof-of-concept trial at 14 European sites in adults with EoE. Participants received placebo, uncoated EsoCap (n = 15), or EsoCap loaded with 800 μg of mometasone furoate (n = 28) once daily during 28 days. The primary outcome was the absolute change in the peak eosinophil count; secondary outcomes were histologic, clinical and endoscopic measures. RESULTS:Treatment with ESO-101 resulted in reduction (mean ± SD) of 49.1 ± 88.4 eosinophils/high-power field from baseline, compared with 6.6 ± 65.1 with placebo (p = 0.03). With ESO-101, 48% and 44% of patients achieved < 15 and < 6 eosinophils/high-power field, respectively; these were 0% with placebo. EoE Endoscopic Reference Score reduced significantly in patients treated with ESO-101. In contrast, dysphagia and odynophagia severity decreased similarly in both groups. There were no serious treatment-emergent adverse events. Mean serum cortisol did not change significantly throughout the trial. Notably, no oropharyngeal or oesophageal candidiasis was documented. The device was well tolerated. CONCLUSIONS:ESO-101 was superior to placebo in reducing oesophageal eosinophilia. The device was safe and well tolerated in adults with EoE, supporting the continued development of ESO-101 for the treatment of EoE (Trials.gov No.: NCT04849390; Eu-CT No.: 2020-000082-16).

Abstract BackgroundThe universal availability of smartphones has created new opportunities for innovative telemedicine applications in health care. The COVID-19 pandemic has heightened the demand for contactless health care services, making SARS-CoV-2 polymerase chain reaction (PCR) testing a crucial component of pandemic containment. ObjectiveThis feasibility study aimed to examine a comprehensive telemedicine approach for SARS-CoV-2 testing, focusing on the practicality, user satisfaction, and economic implications of self-sampling guided by a telemedicine platform. MethodsThe study process involved shipping self-sampling kits, providing instructions for at-home sample collection, processing biomaterials (swabs and capillary blood), communicating test results, and providing interoperable data for clinical routine and research through a medical mobile app. A total of 100 individuals were randomly assigned to either the conventional health care professional (HCP)–performed SARS-CoV-2 testing group (conventional testing group, CG) or the telemedicine-guided SARS-CoV-2 self-sampling approach (telemedicine group, TG). Feasibility of the TG approach, user satisfaction, user-centered outcomes, and economic aspects were assessed and compared between the groups. ResultsIn the TG group, 47 out of 49 (95%) individuals received a self-sampling kit via mail (76%) individuals successfully returned at least one sample for diagnostics. SARS-CoV-2 PCR tests were conducted in 95% () of TG cases compared with 88% () in the CG. Users in the TG reported high satisfaction levels with ease of use (5.2/7), interface satisfaction (5.2/7), and usefulness (4.3/7). A microcosting model indicated a slightly higher cost for the TG approach than the CG approach. The TG demonstrated the potential to facilitate interoperable data transmission by providing anonymized, standardized datasets for extraction using Health Level 7-Fast Healthcare Interoperability Resources. This supports the national COVID-19 Data Exchange Platform and facilitates epidemiological evaluation based on the German COVID Consensus dataset. ConclusionThese preliminary findings suggest that a telemedicine-based approach to SARS-CoV-2 testing is feasible and could be integrated into existing hospital data infrastructures. This model has the potential for broader application in medical care, offering a scalable solution that could improve user satisfaction and treatment quality in the future.

Background For disease monitoring in patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), accurate biomarkers are a prerequisite for individual disease characterization and personalized therapy. This study introduces metabolic profiling in serum samples of patients with PSC as a promising approach for biomarker determination. The study aimed to characterize metabolomic and lipidomic profiles in serum samples of patients with PSC, IBD, and other extraintestinal manifestations (EIM), as well as healthy controls (HC).

Lipedema is a chronic condition characterized by disproportionate and symmetrical enlargement of adipose tissue, predominantly affecting the lower limbs of women. This study investigated the use of metabolomics in lipedema research, with the objective of identifying complex metabolic disturbances and potential biomarkers for early detection, prognosis, and treatment strategies. The study group (n = 25) comprised women diagnosed with lipedema. The controls were 25 lean women and 25 obese females, both matched for age. In the patients with lipedema, there were notable changes in the metabolite parameters. Specifically, lower levels of histidine and phenylalanine were observed, whereas pyruvic acid was elevated compared with the weight controls. The receiver operating characteristic (ROC) curves for the diagnostic accuracy of histidine, phenylalanine, and pyruvic acid concentrations in distinguishing between patients with lipedema and those with obesity but without lipedema revealed good diagnostic ability for all parameters, with pyruvic acid being the most promising (area under the curve (AUC): 0.9992). Subgroup analysis within matched body mass index (BMI) ranges (30.0 to 39.9 kg/m2) further revealed that differences in pyruvic acid, phenylalanine, and histidine levels are likely linked to lipedema pathology rather than BMI variations. Changes in low-density lipoprotein (LDL)-6 TG levels and significant reductions in various LDL-2-carried lipids of patients with lipedema, compared with the lean controls, were observed. However, these lipids were similar between the lipedema patients and the obese controls, suggesting that these alterations are related to adiposity. Metabolomics is a valuable tool for investigating lipedema, offering a comprehensive view of metabolic changes and insights into lipedema’s underlying mechanisms.

Background At the beginning of the COVID-19 pandemic, when mortality was high, social distance was the only option to prevent transmission of SARS-CoV-2 and prohibit uncontrolled spreading. As the impact of social distancing on sexual behavior was unclear, we aimed to assess the influence of sexual risk behavior on SARS-CoV-2 seroconversion in HIV pre-exposition prophylaxis (PrEP) users after declaration of the pandemic. Methods Prospective study on SARS-CoV-2 IgG-antibody seroconversion rate over time in men having sex with men (MSM) using PrEP at a single tertiary university hospital in Munich, Germany, during quarterly (Q) routine HIV-PrEP visits over 1 year per participant (May 2020 - September 2021). Seroconversion was defined as at least one positive anti-nucleocapsid (anti-N) SARS-CoV-2 IgG antibody test as surrogate for past infection. In addition, sexually transmitted infections (STIs), personal estimated risk behavior and sexual contacts were assessed. Results Seroconversion rate during the full observation period was 7.3% (9/124 subjects) by September 2021. Percentage of subjects with symptomatic STIs (T. pallidum, N. gonorrhoeae, C. trachomatis and M. genitalium) was 18.7% in Q3-20, 8.1% in Q4-20, 11.1% in Q1-21, 11.6% in Q2-21 and 9.5% in Q3-21. Perception of subjective threat of SARS-CoV-2 infection and adequacy of preventive measures decreased during the observation period. However, self-reported sex behavior remained stable during the observation period. Conclusions Our cohort showed low proportion of PrEP-users with anti-N IgG by September 2021, comparable to the local incidence. Sexual behavior in this cohort did not change, despite local recommendations for social distancing.

The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers.

Immune cell phenotyping frequently detects lineage-unrelated receptors. Here we report that a broad range of surface receptors is transferred in primary cell co-cultures from macrophages to CD4 T cells and identify the Fcg receptor CD32 as driver and cargo of this trogocytotic transfer. Imaging unveiled long filamentous nanoprotrusions that deposit distinct plasma membrane patches from CD32+ donor to target T cells. Transferred receptors conferred cell migration and adhesion properties to recipient cells and macrophage-derived membrane patches rendered resting CD4 T cells susceptible to infection by serving as hotspots for binding and fusion of HIV-1 particles. Importantly, antibodies that recognize epitopes on the surface of T cells markedly enhanced CD32-mediated trogocytosis. Such autoreactive anti-HIV-1 envelope antibodies were found in the blood of HIV-1 patients and consistently, the percentage of CD32+ CD4 T cells was increased in their peripheral blood. This Fcg receptor-mediated, antigen-independent cell communication mode transiently expands the functional plasticity of immune cells. HIV-1 hijacks this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical to its persistence.

Sexually transmitted infections (STIs) are increasing among men who have sex with men (MSM). Screening can improve the detection and outcome of asymptomatic STIs in high-risk populations. Self-sampling may be a resource-optimized strategy; however, its diagnostic reliability compared to testing by healthcare professionals (HCPs) requires further investigation. In this prospective, multicenter cohort study in a high-income country, asymptomatic MSM with a sexual risk profile for STIs were included. Sequential swabs for STI nucleic acid-based diagnosis of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were performed after randomization, either through self-sampling or HCP-performed sampling. Baseline demographic information, sexual risk behavior, and acceptance and feedback on self-sampling were recorded using an electronic questionnaire. Out of 236 asymptomatic MSM, 47 individuals (19.9%) tested positive for CT and/or NG through self- or HCP-performed sampling. For CT, the sensitivity was 93.3% for both sampling methods, while for NG, it was 90.0% for self-sampling and 95.0% for HCP-performed sampling. Our study demonstrates that self-sampling for asymptomatic STIs has a comparable diagnostic outcome to HCP-performed sampling, with high acceptance in high-risk MSM.

BACKGROUND:Large-scale, polymerase chain reaction (PCR)-based SARS-CoV-2 testing is expensive, resource intensive, and time consuming. A self-collection approach is a probable alternative; however, its feasibility, cost, and ability to prevent infections need to be evaluated.OBJECTIVE:This study aims to compare an innovative self-collection approach with a regular SARS-CoV-2 testing strategy in a large European industrial manufacturing site.METHODS:The feasibility of a telemedicine-guided PCR-based self-collection approach was assessed for 150 employees (intervention group) and compared with a regular SARS-CoV-2 testing approach used for 143 employees (control group). Acceptance, ergonomics, and efficacy were evaluated using a software application. A simulation model was implemented to evaluate the effectiveness. An interactive R shiny app was created to enable customized simulations.RESULTS:The test results were successfully communicated to and interpreted without uncertainty by 76% (114/150) and 76.9% (110/143) of the participants in the intervention and control groups, respectively (P=.96). The ratings for acceptability, ergonomics, and efficacy among intervention group participants were noninferior when compared to those among control group participants (acceptability: 71.6% vs 37.6%; ergonomics: 88.1% vs 74.5%; efficacy: 86.4% vs 77.5%). The self-collection approach was found to be less time consuming (23 min vs 38 min; P<.001). The simulation model indicated that both testing approaches reduce the risk of infection, and the self-collection approach tends to be slightly less effective owing to its lower sensitivity.CONCLUSIONS:The self-collection approach for SARS-CoV-2 diagnosis was found to be technically feasible and well rated in terms of acceptance, ergonomics, and efficacy. The simulation model facilitates the evaluation of test effectiveness; nonetheless, considering context specificity, appropriate adaptation by companies is required.

The DUALIS study demonstrated efficacy and safety of switching to dolutegravir plus ritonavir-boosted darunavir (DRV/r) (2DR) as compared to standard-of-care-therapy with two nucleoside reverse transcriptase inhibitors + DRV/r (3DR) in pretreated people living with HIV (PLWH), 48 weeks after switching. This DUALIS sub-study investigates health-related-quality-of-life (HrQoL) in this study-population. The Hospital Anxiety and Depression Scale (HADS) and the Medical Outcome Survey-HIV (MOS-HIV) were used assessing anxiety and depression symptoms, respectively HrQoL. Data were collected at baseline, 4, 24, and 48 weeks after randomization. Outcome scores were dichotomized and used as criteria in longitudinal models identifying differential developments. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed as main measures of effects. ORs<1 indicate better results for HADS, and worse for MOS-HIV scores in the 2DR compared to 3DR group. In total, 263 subjects were randomized and treated (2DR n=131, 3DR n=132; median age 48 years). Significant different progressions could only be found for HADS-Depression scores (OR=.87, 95% CI: .78, .98, p=.02). While HADS-Depression scores decreased in the 2DR group, they increased in 3DR group. This sub-study showed no disadvantages regarding HrQoL in PLWH after switching to DTG+DRV/r. Considering lifelong requirements for antiretroviral medication, close attention to HrQL is required.

Ein breites Spektrum gutartiger Erkrankungen der Speiseröhre stellt den Hausarzt vor große differenzialdiagnostische Herausforderungen. Hinzu kommt, dass die Beschwerden der Patienten oft unspezifisch sind und durch verschiedene Krankheiten verursacht sein können. In diesem Beitrag werden die häufigsten dieser benignen Krankheitsbilder zusammengefasst und ein pragmatisches diagnostisches sowie therapeutisches Vorgehen vorgestellt.

Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet–leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls ( p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.

Additional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection.

Background Symptoms of primary HIV infection, including fever, rash, and headache, are nonspecific and are often described as flu-like. COVID-19 vaccination side effects, such as fever, which occur in up to 10% of people following COVID-19 vaccination, can make the diagnosis of acute HIV infection even more challenging. Case presentation A 26-year-old man presented with fever and headache following COVID-19 vaccination. The symptoms were initially thought to be vaccine side effects. A diagnostic workup was conducted due to persisting fever and headache > 72 h following vaccination, and he was diagnosed with Fiebig stage II acute HIV infection, 3 weeks after having unprotected anal intercourse with another man. Conclusion Thorough anamnesis is key to estimating the individual risk of primary HIV infection, in patients presenting with flu-like symptoms. Early diagnosis and initiation of antiretroviral therapy is associated with better prognosis and limits transmission of the disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a coagulopathy characterized by platelet activation and a hypercoagulable state with an increased incidence of cardiovascular events. The viral spike protein S has been reported to enhance thrombosis formation, stimulate platelets to release procoagulant factors, and promote the formation of platelet-leukocyte aggregates even in absence of the virus. Although SARS-CoV-2 vaccines induce spike protein overexpression to trigger SARS-CoV-2-specific immune protection, thrombocyte activity has not been investigated in this context. Here, we provide the first phenotypic platelet characterization of healthy human subjects undergoing BNT162b2 vaccination. Using mass cytometry, we analyzed the expression of constitutive transmembrane receptors, adhesion proteins, and platelet activation markers in 12 healthy donors before and at five different time points within 4 weeks after the first BNT162b2 administration. We measured platelet reactivity by stimulating thrombocyte activation with thrombin receptor-activating peptide. Activation marker expression (P-selectin, LAMP-3, LAMP-1, CD40L, and PAC-1) did not change after vaccination. All investigated constitutive transmembrane proteins showed similar expressions over time. Platelet reactivity was not altered after BNT162b2 administration. Activation marker expression was significantly lower compared with an independent cohort of mild symptomatic COVID-19 patients analyzed with the same platform. This study reveals that BNT162b2 administration does not alter platelet protein expression and reactivity.

BACKGROUND:Mycobacterium fortuitum complex is a group of rapidly growing nontuberculous mycobacteria (NTM) associated with skin and soft-tissue infections after surgery or trauma. Treatment of NTM is challenging, due to resistance to multiple antimycobacterial agents. Bedaquiline is a diarylquinoline that inhibits mycobacterial ATP-synthase. The drug has recently been approved for the treatment of multidrug-resistant tuberculosis and evidence of its in vitro efficacy against NTM, including Mycobacterium fortuitum complex, has been published.CASE PRESENTATION:A 20-year-old Caucasian woman with chronic skin and soft tissue infection in the lower leg following a traffic accident in Vietnam underwent a tedious journey of healthcare visits, hospital admissions, empiric antimicrobial treatments, surgical debridement and plastic reconstruction before definite diagnosis of Mycobacterium fortuitum complex-infection was established by culture from a tissue biopsy and targeted antimycobacterial therapy was administered. Histopathological examination revealed granulomatous purulent inflammation, which strongly supported the diagnosis. Genotypic identification was performed and broth microdilution for susceptibility testing showed macrolide resistance. Five weeks of induction treatment with intravenous amikacin, imipenem / cilastin, and oral levofloxacin was administered, followed by all-oral treatment with bedaquiline combined with levofloxacin for four months, which was well-tolerated and led to persistent healing with scars but without signs of residual infection.CONCLUSIONS:Bedaquiline is a promising novel agent for NTM treatment, although clinical data are limited and trials evaluating efficacy, safety, and resistance of bedaquiline are required. To our knowledge, this is the first reported case of successful in vivo use of bedaquiline for a skin and soft tissue infection caused by Mycobacterium fortuitum complex.

BACKGROUND:Data on ocular syphilis (OS) and its clinical presentation are currently insufficient. This study aimed to investigate the characteristics of a cohort with a high OS incidence at a university hospital in Germany, focusing on the clinical presentation of OS.METHODS:This single-center cohort study retrospectively analyzed data on 90 patients with 109 episodes of syphilis between 2008 and 2018. Cases of OS were identified and additionally reevaluated through a study-specific secondary assessment by an ophthalmologist specializing in uveitis.RESULTS:Twenty-three patients (26%) were diagnosed with OS, 16 (70%) of whom were with binocular involvement. Uveitis, especially that of the posterior segment, showed a high prevalence. Lumbar puncture was performed in 20 OS patients (87%), of whom 17 (85% of those with lumbar puncture/74% in total) met the 2018 Centers for Disease Control and Prevention criteria for likely neurosyphilis. Five (22%) of 23 patients had HIV infection, of whom 2 did not receive antiretroviral therapy. The preferred syphilis treatment regimens were benzylpenicillin and ceftriaxone, which yielded favorable serological, clinical, and ophthalmological outcomes.CONCLUSIONS:A high incidence of OS was identified, and physicians should be aware of uveitis as a manifestation of syphilis. Most patients presented with uveitis and syphilis in an early or late latent stage and showed central nervous system involvement.

Background:For eosinophilic esophagitis (EoE) recently an association with immunoglobulin (Ig)G4 rather than IgE has been reported. Gastroesophageal reflux disease (GERD) is the most important differential diagnosis of EoE. We compared esophageal IgG4 plasma cell infiltration and serum IgG4 levels of EoE patients (before and after budesonide therapy) with GERD patients.Methods:Prospectively collected serum samples of 17 EoE patients before and after 8 weeks of therapy with budesonide (1mg BID) were analyzed for total and antigen-specific IgG4 and IgE levels. Also, immunohistochemical analysis of total and IgG4-positive plasma cells was performed on esophageal biopsies of these patients. In total, 14 GERD patients without histologic proof of eosinophilic infiltration were taken as a control group.Results:Total IgG4 serum levels in EoE patients were significantly higher than in GERD patients (121.0 vs. 71.2mg/dL; P=0.038) and decreased under budesonide therapy (121.0 vs. 104.2mg/dL; P=0.019). IgE levels did not differ significantly between all groups. In EoE patients also a high number of esophageal IgG4-positive plasma cells was detected and significantly reduced under therapy (29.1 vs. 0.1 IgG4-positive cells; P<0.001). In GERD patients no relevant esophageal plasma cell infiltration could be seen.Conclusions:In EoE patients elevated systemic IgG4 serum levels compared with GERD patients can be seen and decrease under topical steroid therapy. Also, local IgG4 plasma cells expression is high in EoE, but not in GERD patients and normalize under therapy. These findings are further proof for a possible association of EoE with IgG4.