Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Study Protocol of a Randomized, Two-Arm, Phase I/II Trial Investigating the Feasibility, Safety, and Efficacy of Local Treatment with US-Guided High-Intensity Focused Ultrasound in Combination with Palliative Chemotherapy in Inoperable Pancreatic Cancer.

BACKGROUND: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients' quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients' QOL with few side effects. STUDY DESIGN: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).

Stereocontrol of Metal-Centred Chirality in Rhodium(III) and Ruthenium(II) Complexes with N2N'P Ligand.

Rh(III) and Ru(II) complexes, [RhCl2(κ4-N2N'P-L)][SbF6] (1) and [RuCl2(κ4-N2N'P-L)] (2), were synthesised using the tetradentate ligand L (L=N,N-bis[(pyridin-2-yl)methyl]-[2-(diphenylphosphino)phenyl]methanamine). In each case only one diastereomer is detected, featuring cis-disposed pyridine groups. The chloride ligand trans to pyridine can be selectively abstracted by AgSbF6, with the ruthenium complex (2) reacting more readily at room temperature compared to the rhodium complex (1) which requires elevated temperatures. Rhodium complexes avoid the second chloride abstraction, whereas ruthenium complexes can form the chiral bisacetonitrile complex [Ru(κ4-N2N'P-L)(NCMe)2][SbF6]2 (5) upon corresponding treatment with AgSbF6. The complex [RhCl2(κ4-N2N'P-L)][SbF6] (1) has also been used to synthesise polymetallic species, such as the tetrametallic complex [{RhCl2(κ4-N2N'P-L)}2(µ-Ag)2][SbF6]4 (6) which was formed with complete diastereoselectivity and chiral molecular self-recognition. In addition, a stable bimetallic mixed-valence complex [{Rh(κ4-N2N'P-L)}{Rh(COD)}(µ-Cl)2][SbF6]2 (7) (COD=cyclooctadiene) was synthesised. These results highlight the significant differences in chloride lability between Rh3+ and Ru2+ complexes and demonstrate the potential for complexes to act as catalyst precursors and ligands in further chemistry applications.

Anatomical Studies Evaluating Pediatric Regional Anesthesia: A Scoping Review.

BACKGROUND: Pediatric regional anesthesia has been driven by the gradual rise in the adoption of opioid-sparing strategies and the growing concern over the possible adverse effects of general anesthetics on neurodevelopment. Nonetheless, performing regional anesthesia studies in a pediatric population is challenging and accounts for the scarce evidence. This study aimed to review the scientific foundation of studies in cadavers to assess regional anesthesia techniques in children. METHODS: We searched the following databases MEDLINE, EMBASE, and Web of Science. We included anatomical cadaver studies assessing peripheral nerve blocks in children. The core data collected from studies were included in tables and comprised block type, block evaluation, results, and conclusion. RESULTS: The search identified 2409 studies, of which, 16 were anatomical studies on the pediatric population. The techniques evaluated were the erector spinae plane block, ilioinguinal/iliohypogastric nerve block, sciatic nerve block, maxillary nerve block, paravertebral block, femoral nerve block, radial nerve block, greater occipital nerve block, infraclavicular brachial plexus block, and infraorbital nerve block. CONCLUSION: Regional anesthesia techniques are commonly performed in children, but the lack of anatomical studies may result in reservations regarding the dispersion and absorption of local anesthetics. Further anatomical research on pediatric regional anesthesia may guide the practice.

Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

External validation of two clinical prediction models for mortality in COVID-19 patients (4C and NEWS2), in three centers in Medellín, Colombia: Assessing the impact of vaccination over time.

OBJECTIVES: External validation of the 4C and NEWS2 scores for the prediction of in-hospital mortality in COVID-19 patients, and evaluation of its operational performance in two time periods: before and after the start of the vaccination program in Colombia. METHODS: Retrospective cohort in three high complexity hospitals in the city of Medellín, Colombia, between June 2020 and April 2022. RESULTS: The areas under the ROC curve (AUC) for the 4C mortality risk score and the NEWS2 were 0.75 (95% CI 0.73-0.78) and 0.68 (95% CI 0.66-0.71), respectively. For the 4C score, the AUC for the first and second periods was 0.77 (95% CI 0.74-0.80) and 0.75 (95% CI 0.71-0.78); whilst for the NEWS2 score, it was 0.68 (95% CI 0.65-0.71) and 0.69 (95% CI 0.64-0.73). The calibration for both scores was adequate, albeit with reduced performance during the second period. CONCLUSIONS: The 4C mortality risk score proved to be the more adequate predictor of in-hospital mortality in COVID-19 patients in this Latin American population. The operational performance during both time periods remained similar, which shows its utility notwithstanding major changes, including vaccination, as the pandemic evolved.

Lung Function and Symptoms of Exposure to the Volcanic Eruption in the Canary Islands: First Follow-Up of the ASHES Study.

INTRODUCTION: Exposure to gases and particulate matter released during volcanic eruptions can prove harmful to population health. This paper reports the preliminary results of the ASHES study, aimed at ascertaining the respiratory health effects of the 2021 volcanic eruption in La Palma Island (Spain) on the adult population without previous respiratory disease. METHODS: Ambispective cohort study on the healthy adult population. Three exposure groups were considered: Group 1, high exposure; Group 2, moderate exposure; and Group 3, minor or no exposure. We carried out a descriptive analysis of symptoms during and after the eruption, as well as measure lung function after the eruption (through forced spirometry and diffusing capacity of carbon monoxide). RESULTS: The analysis included 474 subjects: 54 in Group 1, 335 in Group 2, and 85 in Group 3. A significant increase in most symptoms was observed for subjects in the groups exposed during the eruption. After the eruption, this increase remained for some symptoms. There seems to be a dose-response relationship, such that the higher the exposure, the higher the odds ratio. A prebronchodilator FEV1/FVC ratio<70% was observed in 13.0% of subjects in Group 1, 8.6% of subjects in Group 2, and 7.1% of subjects in Group 3. CONCLUSIONS: This study is the first to report a dose-response relationship between exposure to volcanic eruptions and the presence of symptoms in adults. Furthermore, there is a tendency toward obstructive impairment in individuals with higher exposure.

Ultrasound Changes in the Enthesis and Peri-enthesis Area of the Patellar and Achilles Tendons in Response to Physical Exercise: Comparison Between Healthy Subjects and Patients with Spondyloarthritis in Clinical Remission.

RATIONALE AND OBJECTIVES: The goal of achieving clinical remission in patients with spondyloarthritis does not necessarily include the resolution of entheseal inflammation from a histological perspective. However, enthesis not clinically inflamed, under mechanical stress, may behave differently from healthy subjects considering the physiopathology of SpA. Our goal was to determine whether ultrasound changes in entheses differ between SpA patients in clinical remission and healthy subjects. METHODS: SpA patients in clinical remission and matched healthy controls were recruited. At baseline, the following variables were measured on the dominant side by ultrasound: thickness of the distal patellar enthesis (hDP), the deep infrapatellar bursa (hDIB), the Achilles enthesis (hA), the preachilleal bursa (hPAB), effusion in the preachileal bursa (hePAB), and the presence of power Doppler signal in both enthesis. All measurements except hDP and hA were collected again after exercise (post-stress ultrasound). RESULTS: 30 patients and 30 controls were enrolled. In all subjects, hDIB, hPAB, and the preachileal bursa occupancy index increased significantly after the exercise. The increase was significantly greater in patients for all variables. At baseline, in patients, hyperemia was detected in one patellar tendon (3.3%) and in two Achilles tendons (6.7%). After exercise, the number of tendons with hyperemia increased to 11/30 (36.7%) and 12/30 (40%), respectively. Among controls, there was no detectable basal hyperemia, but after exercise, it was detected in 1/30 patellar tendons (3.3%) and 2/30 Achilles tendons (6.7%). CONCLUSION: Exercise triggers a greater effusive and hyperemic synovial response in patients in remission than in healthy controls. These findings suggest that the definition of remission should also include an assessment of the synovial response to mechanical stress.

Peripheral intravenous catheter failure, nurse staffing levels and care complexity individual factors: A retrospective multicentre cohort study.

INTRODUCTION: Short peripheral intravenous catheter (PIVC) failure is a common complication that is generally underdiagnosed. Some studies have evaluated the factors associated with these complications, but the impact of care complexity individual factors and nurse staffing levels on PIVC failure is still to be assessed. The aim of this study was to determine the incidence and risk factors of PIVC failure in the public hospital system of the Southern Barcelona Metropolitan Area. METHODS: A retrospective multicentre observational cohort study of hospitalised adult patients was conducted in two public hospitals in Barcelona from 1st January 2016 to 31st December 2017. All adult patients admitted to the hospitalisation ward were included until the day of discharge. Patients were classified according to presence or absence of PIVC failure. The main outcomes were nurse staffing coverage (ATIC patient classification system) and 27-care complexity individual factors. Data were obtained from electronic health records in 2022. RESULTS: Of the 44,661 patients with a PIVC, catheter failure was recorded in 2,624 (5.9%) patients (2,577 [5.8%] phlebitis and 55 [0.1%] extravasation). PIVC failure was more frequent in female patients (42%), admitted to medical wards, unscheduled admissions, longer catheter dwell time (median 7.3 vs 2.2 days) and those with lower levels of nurse staffing coverage (mean 60.2 vs 71.5). Multivariate logistic regression analysis revealed that the female gender, medical ward admission, catheter dwell time, haemodynamic instability, uncontrolled pain, communication disorders, a high risk of haemorrhage, mental impairments, and a lack of caregiver support were independent factors associated with PIVC failure. Moreover, higher nurse staffing were a protective factor against PIVC failure (AUC, 0.73; 95% confidence interval [CI]: 0.72-0.74). CONCLUSION: About 6% of patients presented PIVC failure during hospitalisation. Several complexity factors were associated with PIVC failure and lower nurse staffing levels were identified in patients with PIVC failure. Institutions should consider that prior identification of care complexity individual factors and nurse staffing coverage could be associated with a reduced risk of PIVC failure.

Cannabinoid products for pain management: recommendations from the São Paulo State Society of Anesthesiology.

There is growing interest in using cannabinoids across various clinical scenarios, including pain medicine, leading to the disregard of regulatory protocols in some countries. Legislation has been implemented in Brazil, specifically in the state of São Paulo, permitting the distribution of cannabinoid products by health authorities for clinical purposes, free of charge for patients, upon professional prescription. Thus, it is imperative to assess the existing evidence regarding the efficacy and safety of these products in pain management. In light of this, the São Paulo State Society of Anesthesiology (SAESP) established a task force to conduct a narrative review on the topic using the Delphi method, requiring a minimum agreement of 60% among panelists. The study concluded that cannabinoid products could potentially serve as adjuncts in pain management but stressed the importance of judicious prescription. Nevertheless, this review advises against their use for acute pain and cancer-related pain. In other clinical scenarios, established treatments should take precedence, particularly when clinical protocols are available, such as in neuropathic pain. Only patients exhibiting poor therapeutic responses to established protocols or demonstrating intolerance to recommended management may be considered as potential candidates for cannabinoids, which should be prescribed by physicians experienced in handling these substances. Special attention should be given to individual patient characteristics and the likelihood of drug interactions.

Green synthesis of chitosan- and fluoride-functionalized silver nanoparticles using Camellia sinensis: Characterization and dental applications.

The development of new biocompatible and eco-friendly materials is essential for the future of dental practice, especially for the management of dental caries. In this study, a novel and simple method was applied for the green synthesis of silver nanoparticles (AgNPs) from the aqueous extract of Camellia sinensis (WT) and functionalized with chitosan (CHS) and NaF. The effects of WT_AgNPs application on demineralized dentin were evaluated for potential dental applications. The WT_AgNPs showed molecular groups related to organic compounds, potentially acting as reducing and capping agents. All AgNPs presented spherical shapes with crystal sizes of approximately 20 nm. Forty human molars were assigned to control: sound (SD) and demineralised dentine (DD), and experimental groups: WT_AgNPs, WT_AgNPs_NaF, and WT_AgNPs_CHS. Then, the NPs were applied to DD to evaluate the chemical, crystallographic, and microstructural characteristics of treated-dentine. In addition, a three-point bending test was employed to assess mechanical response. The application of WT_AgNPs indicated a higher mineralisation degree and crystallites sizes of hydroxyapatite than the DD group. SEM images showed that WT_AgNPs presented different degrees of aggregation and distribution patterns. The dentine flexural strength was significantly increased in all WT_AgNPs. The application of WT_AgNPs demonstrated remineralising and strengthening potential on demineralised dentine.

Appropriate Duration of Antimicrobial Treatment for Prosthetic Joint Infections: A Narrative Review.

Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.

Performance of a vaginal self-collection device versus clinician collected cervical samples for the detection of high-risk human papillomavirus.

Objective: Screening for cervical cancer requires the participation of target women. Human papillomavirus (HPV) testing can be performed on vaginal self-samples and self-sampling can improve this participation. This study aims to validate the performance of the vaginal self-sampling device (Vitroveil®) to detect high risk human papillomavirus (hrHPV) in comparison to clinician collected samples and evaluate the degree of acceptability of the Vitroveil® device. Methods: A cross-sectional observational study was carried out in a cohort of 385 participating women (median age of 44 ± 10.47 years) attending primary care centers and cervical pathology services of Granada, Spain. Two paired samples (vaginal self-sample and clinician collected cervical sample) where collected from each participant to compare the detection of HPV with the Vitro HPV Screening assay (Vitro, Granada, Spain). A questionnaire was also provided to the participants to analyze the degree of satisfaction with the device and the preference for sampling method. Results: Overall concordance for hrHPV detection was substantial (ĸ 0.804). The prevalence of any hrHPV infection was higher in self-collected samples (30.6%) than in clinician-collected samples (24.3%). The participants found the self-sampling device easy to use and preferred self-collection as the collection method. Conclusion: The Vitroveil® self-sampling device enables safe and accruable hrHPV testing, obtaining equivalent results to those of the clinician collected samples. High acceptability of the device has been demonstrated among women in the study. Nevertheless, additional studies are necessary to verify the efficacy and reliability of the device's performance.

El papel de la RMN en el diagnóstico de la patología audiovestibular / The role of MRI in the diagnosis of audio-vestibular pathology

Introducción y objetivo: El schwanoma vestibular es un tumor benigno, de lento crecimiento que aparece en la vaina de mielina que rodea al nervio vestibular. Estos tumores representan el 6% de todos los tumores intracraneales y el 85% de los tumores del ángulo pontocerebeloso. El síntoma de aparición más frecuente es la hipoacusia unilateral, seguida del acúfeno unilateral, inestabilidad, vértigo, cefalea e incluso, en determinados casos, parestesias faciales o parálisis facial. Todo ello depende del tamaño del tumor y su localización. Actualmente, el diagnóstico de estos tumores se realiza mediante la realización de una historia clínica completa, pruebas complementarias audiológicas y vestibulares y, como prueba de imagen, una RMN. Según el American College of Radiology (ACR) la RMN de base de cráneo y conductos auditivos internos es la prueba de elección para el diagnóstico del schwanoma vestibular. Ésta puede ser con y sin contraste (generalmente Gadolinio) y permite detectar tumores de muy pequeño tamaño. Nuestro objetivo con este trabajo es aportar evidencia científica que permita al profesional seguir un protocolo diagnóstico de los schwanomas vestibulares y, consecuentemente, optimizar los recursos hospitalarios. Método: De una muestra total de 685 se revisaron todas las historias clínicas de los pacientes a los que se les había solicitado una RMN por síntomas audiovestibulares (hipoacusia, acúfeno, vértigo, parálisis facial y otros). Se llevó a cabo un estudio descriptivo y observacional en el cual se mostraban los síntomas que había padecido cada paciente, el motivo de petición de la prueba de imagen, el diagnóstico final y el tipo de resonancia magnética empleada. Con toda esta información se creó una base de datos y se analizaron los resultados estadísticamente. Resultados: ... (AU)

Introduction and objective: Vestibular schwannoma is a benign, slow-growing tumor that appears in the myelin sheath surrounding the vestibular nerve. These tumors represent 6% of all intracranial tumors and 85% of tumors in the cerebellopontine angle. The most common initial symptom is unilateral hearing loss, followed by unilateral tinnitus, instability, vertigo, headache, and, in certain cases, facial paresthesia or facial paralysis. All of these symptoms depend on the size and location of the tumor. Currently, the diagnosis of these tumors is made through a complete medical history, complementary audiological and vestibular tests, and, as an imaging test, an MRI. According to the American College of Radiology (ACR), the MRI of the skull base and internal auditory canals is the gold standard for diagnosing vestibular schwannoma. This can be performed with and without contrast (usually Gadolinium) and allows the detection of very small tumors. Our objective with this article is to provide scientific evidence that enables professionals to diagnose vestibular schwannomas and optimize hospital resources. Method: From a total sample of 685 patients, all medical records of them who had been requested an MRI for audiovestibular symptoms (hearing loss, tinnitus, vertigo, facial paralysis, and others) were reviewed. A descriptive and observational study was carried out, showing the symptoms experienced by each patient, the reason for requesting the imaging test, the final diagnosis, and the type of MRI used. With all this information, a database was created, and the results were analyzed statistically. Results: ... (AU)

ADJUBIL: phase II study of adjuvant immunotherapy with STRIDE regimen with/without capecitabine in biliary tract cancers.

Biliary tract cancer is a highly heterogeneous group of gastrointestinal cancers, and the only curative treatment is surgery, which is only applicable at early stages of the malignancy. ADJUBIL, a phase II trial (NCT05239169), aims to evaluate immunotherapy with durvalumab and tremelimumab with or without capecitabine in adjuvant situations for biliary tract cancers. A total of 40 prospective patients will be randomly assigned following surgery, consisting of a two-arm feasibility pilot part with a pick-the-winner design with durvalumab and tremelimumab in combination with or without capecitabine.

This article describes the design of a phase II clinical trial called ADJUBIL, which evaluates the use of immunotherapy (durvalumab and tremelimumab) with or without classic chemotherapy (capecitabine) in biliary tract cancer patients who have undergone curative surgery. This type of treatment is also called adjuvant therapy, meaning it is used after the primary treatment. Biliary tract cancer is a rare type of liver cancer, often diagnosed late. Following surgery, patients may experience an early return of the disease, called tumor relapse. To avoid or delay tumor relapse, patients need extra treatment. Pure chemotherapy (capecitabine) is the standard after curative surgery. For patients with no option for cure, chemotherapy together with new powerful immunotherapy has become standard. This study will recruit 40 adult patients with tumor removal, who will be randomly divided into two groups. Half of them will be treated with immunotherapy only (durvalumab and tremelimumab). The other half will be treated with capecitabine together with immunotherapy. This study will continue for 12 months, but the treatment can be stopped if, for example, the tumor reoccurs or any possible side effect of the therapy is detected. The most effective treatment type will be selected. This type of selection is called pick-the winner.

Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis.

BACKGROUND: The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. METHODS: Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients' sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. RESULTS: Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2-deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p<0.001), alanine transaminase (r=0.4704, p<0.0001), and gamma-glutamyl transpeptidase activities (r=0.6629, p<0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, ß and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC. CONCLUSIONS: The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.