Post-intensive care syndrome and health-related quality of life in long-term survivors of cardiac arrest: a prospective cohort study.

Patients discharged from intensive care are at risk for post-intensive care syndrome (PICS), which consists of physical, psychological, and/or neurological impairments. This study aimed to analyze PICS at 24 months follow-up, to identify potential risk factors for PICS, and to assess health-related quality of life in a long-term cohort of adult cardiac arrest survivors. This prospective cohort study included adult cardiac arrest survivors admitted to the intensive care unit of a Swiss tertiary academic medical center. The primary endpoint was the prevalence of PICS at 24 months follow-up, defined as impairments in physical (measured through the European Quality of Life 5-Dimensions-3-Levels instrument [EQ-5D-3L]), neurological (defined as Cerebral Performance Category Score > 2 or Modified Rankin Score > 3), and psychological (based on the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised) domains. Among 107 cardiac arrest survivors that completed the 2-year follow-up, 46 patients (43.0%) had symptoms of PICS, with 41 patients (38.7%) experiencing symptoms in the physical domain, 16 patients (15.4%) in the psychological domain, and 3 patients (2.8%) in the neurological domain. Key predictors for PICS in multivariate analyses were female sex (adjusted odds ratio [aOR] 3.17, 95% CI 1.08 to 9.3), duration of no-flow interval during cardiac arrest (minutes) (aOR 1.17, 95% CI 1.02 to 1.33), post-discharge job-loss (aOR 31.25, 95% CI 3.63 to 268.83), need for ongoing psychological support (aOR 3.64, 95% CI 1.29 to 10.29) or psychopharmacologic treatment (aOR 9.49, 95% CI 1.9 to 47.3), and EQ-visual analogue scale (points) (aOR 0.88, 95% CI 0.84 to 0.93). More than one-third of cardiac arrest survivors experience symptoms of PICS 2 years after resuscitation, with the highest impairment observed in the physical and psychological domains. However, long-term survivors of cardiac arrest report intact health-related quality of life when compared to the general population. Future research should focus on appropriate prevention, screening, and treatment strategies for PICS in cardiac arrest patients.

The association of vaccination status with perceived discrimination in patients with COVID-19: results from a cross-sectional study.

STUDY AIMS: During the COVID-19 pandemic, there was increasing pressure to be vaccinated to prevent further spread of the virus and improve outcomes. At the same time, part of the population expressed reluctance to vaccination, for various reasons. Only a few studies have compared the perceptions of vaccinated and non-vaccinated patients being treated in hospitals for COVID-19. Our aim was to investigate the association between vaccination status and perceived healthcare-associated discrimination in patients with COVID-19 receiving hospital treatment. METHODS: Adult patients presenting to the emergency department or hospitalised for inpatient care due to or with COVID-19 from 1 June to 31 December 2021 in two Swiss hospitals were eligible. The primary endpoint was patients' perceived healthcare-associated discrimination, measured with the Discrimination in Medical Settings (DMS) scale. Secondary endpoints included different aspects of perceived quality of care and symptoms of psychological distress measured with the Hospital Anxiety and Depression Scale. RESULTS: Non-vaccinated patients (n = 113) had significantly higher DMS scores compared to vaccinated patients (n = 80) (mean: 9.54 points [SD: 4.84] vs 7.79 points [SD: 1.85]; adjusted difference: 1.18 [95% CI: 0.04-2.33 points]) and 21 of 80 vaccinated patients felt discriminated against vs 54 of 113 non-vaccinated patients (adjusted OR: 2.09 [95% CI: 1.10-3.99 ]). Non-vaccinated patients reported lower scores regarding respectful treatment by the nursing team (mean: 8.39 points [SD: 2.39] vs 9.30 points [SD: 1.09]; adjusted difference: -0.6 [95% CI: -1.18 - -0.02 points]). CONCLUSION: We found an association between vaccination status and perceived healthcare-associated discrimination. Healthcare workers should act in a professional manner regardless of a patient's vaccination status; in doing so, they might prevent the creation of negative perceptions in patients.

Alzheimer's disease-related presenilins are key to intestinal epithelial cell function and gut immune homoeostasis.

OBJECTIVE: Mutations in presenilin genes are the major cause of Alzheimer's disease. However, little is known about their expression and function in the gut. In this study, we identify the presenilins Psen1 and Psen2 as key molecules that maintain intestinal homoeostasis. DESIGN: Human inflammatory bowel disease (IBD) and control samples were analysed for Psen1 expression. Newly generated intestinal epithelium-specific Psen1-deficient, Psen2-deficient and inducible Psen1/Psen2 double-deficient mice were used to dissect the functional role of presenilins in intestinal homoeostasis. RESULTS: Psen1 expression was regulated in experimental gut inflammation and in patients with IBD. Induced deletion of Psen1 and Psen2 in mice caused rapid weight loss and spontaneous development of intestinal inflammation. Mice exhibited epithelial barrier disruption with bacterial translocation and deregulation of key pathways for nutrient uptake. Wasting disease was independent of gut inflammation and dysbiosis, as depletion of microbiota rescued Psen-deficient animals from spontaneous colitis development but not from weight loss. On a molecular level, intestinal epithelial cells lacking Psen showed impaired Notch signalling and dysregulated epithelial differentiation. CONCLUSION: Overall, our study provides evidence that Psen1 and Psen2 are important guardians of intestinal homoeostasis and future targets for barrier-promoting therapeutic strategies in IBD.

Prediction of outcomes after cardiac arrest by a generative artificial intelligence model.

Aims: To investigate the prognostic accuracy of a non-medical generative artificial intelligence model (Chat Generative Pre-Trained Transformer 4 - ChatGPT-4) as a novel aspect in predicting death and poor neurological outcome at hospital discharge based on real-life data from cardiac arrest patients. Methods: This prospective cohort study investigates the prognostic performance of ChatGPT-4 to predict outcomes at hospital discharge of adult cardiac arrest patients admitted to intensive care at a large Swiss tertiary academic medical center (COMMUNICATE/PROPHETIC cohort study). We prompted ChatGPT-4 with sixteen prognostic parameters derived from established post-cardiac arrest scores for each patient. We compared the prognostic performance of ChatGPT-4 regarding the area under the curve (AUC), sensitivity, specificity, positive and negative predictive values, and likelihood ratios of three cardiac arrest scores (Out-of-Hospital Cardiac Arrest [OHCA], Cardiac Arrest Hospital Prognosis [CAHP], and PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages [PROLOGUE score]) for in-hospital mortality and poor neurological outcome. Results: Mortality at hospital discharge was 43% (n = 309/713), 54% of patients (n = 387/713) had a poor neurological outcome. ChatGPT-4 showed good discrimination regarding in-hospital mortality with an AUC of 0.85, similar to the OHCA, CAHP, and PROLOGUE (AUCs of 0.82, 0.83, and 0.84, respectively) scores. For poor neurological outcome, ChatGPT-4 showed a similar prediction to the post-cardiac arrest scores (AUC 0.83). Conclusions: ChatGPT-4 showed a similar performance in predicting mortality and poor neurological outcome compared to validated post-cardiac arrest scores. However, more research is needed regarding illogical answers for potential incorporation of an LLM in the multimodal outcome prognostication after cardiac arrest.

Misconceptions and do-not-resuscitate preferences of healthcare professionals commonly involved in cardiopulmonary resuscitations: A national survey.

Aims: To assess the DNR preferences of critical care-, anesthesia- and emergency medicine practitioners, to identify factors influencing decision-making, and to raise awareness for misconceptions concerning CPR outcomes. Methods: A nationwide multicenter survey was conducted in Switzerland confronting healthcare professionals with a case vignette of an adult patient with an out-of-hospital cardiac arrest (OHCA). The primary outcome was the rate of DNR Code Status vs. CPR Code Status when taking the perspective from a clinical case vignette of a 70-year-old patient. Secondary outcomes were participants' personal preferences for DNR and estimates of survival with good neurological outcome after in- and out-of-hospital cardiac arrest. Results: Within 1803 healthcare professionals, DNR code status was preferred in 85% (n = 1532) in the personal perspective of the case vignette and 53.2% (n = 932) when making a decision for themselves. Main predictors for a DNR Code Status regarding the case vignette included preferences for DNR Code Status for themselves (n [%] 896 [58.5] vs. 87 [32.1]; adjusted odds ratio [OR] 2.97, 95% confidence interval [CI] 2.25-3.92; p < 0.001) and lower estimated OHCA survival (mean [±SD] 12.3% [±11.8] vs. 14.7%[±12.8]; adjusted OR 0.98, 95% CI 0.97-0.99; p = 0.001). Physicians chose a DNR order more often when compared to nurses and paramedics. Conclusions: The estimation of outcomes following cardiac arrest and personal living conditions are pivotal factors influencing code status preferences in healthcare professionals. Healthcare professionals should be aware of cardiac arrest prognosis and potential implications of personal preferences when engaging in code status- and end-of-life discussions with patients and their relatives.

ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo.

OBJECTIVE: Mucosal T cells play a major role in inflammatory bowel disease (IBD). However, their immunometabolism during intestinal inflammation is poorly understood. Due to its impact on cellular metabolism and proinflammatory immune cell function, we here focus on the enzyme ATP citrate lyase (ACLY) in mucosal T cell immunometabolism and its relevance for IBD. DESIGN: ACLY expression and its immunometabolic impact on colitogenic T cell function were analysed in mucosal T cells from patients with IBD and in two experimental colitis models. RESULTS: ACLY was markedly expressed in colon tissue under steady-state conditions but was significantly downregulated in lamina propria mononuclear cells in experimental dextran sodium sulfate-induced colitis and in CD4+ and to a lesser extent in CD8+ T cells infiltrating the inflamed gut in patients with IBD. ACLY-deficient CD4+ T cells showed an impaired capacity to induce intestinal inflammation in a transfer colitis model as compared with wild-type T cells. Assessment of T cell immunometabolism revealed that ACLY deficiency dampened the production of IBD-relevant cytokines and impaired glycolytic ATP production but enriched metabolites involved in the biosynthesis of phospholipids and phosphatidylcholine. Interestingly, the short-chain fatty acid butyrate was identified as a potent suppressor of ACLY expression in T cells, while IL-36α and resolvin E1 induced ACLY levels. In a translational approach, in vivo administration of the butyrate prodrug tributyrin downregulated mucosal infiltration of ACLYhigh CD4+ T cells and ameliorated chronic colitis. CONCLUSION: ACLY controls mucosal T cell immunometabolism and experimental colitis. Therapeutic modulation of ACLY expression in T cells emerges as a novel strategy to promote the resolution of intestinal inflammation.

Myenteric Plexus Immune Cell Infiltrations and Neurotransmitter Expression in Crohn's Disease and Ulcerative Colitis.

BACKGROUND AND AIMS: Pain is a cardinal symptom in inflammatory bowel disease [IBD]. An important structure in the transduction of pain signalling is the myenteric plexus [MP]. Nevertheless, IBD-associated infiltration of the MP by immune cells lacks in-depth characterisation. Herein, we decipher intra- and periganglionic immune cell infiltrations in Crohn´s disease [CD] and ulcerative colitis [UC] and provide a comparison with murine models of colitis. METHODS: Full wall specimens of surgical colon resections served to examine immune cell populations by either conventional immuno-histochemistry or immunofluorescence followed by either bright field or confocal microscopy. Results were compared with equivalent examinations in various murine models of intestinal inflammation. RESULTS: Whereas the MP morphology was not significantly altered in IBD, we identified intraganglionic IBD-specific B cell- and monocyte-dominant cell infiltrations in CD. In contrast, UC-MPs were infiltrated by CD8+ T cells and revealed a higher extent of ganglionic cell apoptosis. With regard to the murine models of intestinal inflammation, the chronic dextran sulphate sodium [DSS]-induced colitis model reflected CD [and to a lesser extent UC] best, as it also showed increased monocytic infiltration as well as a modest B cell and CD8+ T cell infiltration. CONCLUSIONS: In CD, MPs were infiltrated by B cells and monocytes. In UC, mostly CD8+ cytotoxic T cells were found. The chronic DSS-induced colitis in the mouse model reflected best the MP-immune cell infiltrations representative for IBD.

IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling.

OBJECTIVE: We sought to investigate the role of interleukin (IL)-20 in IBD and experimental colitis. DESIGN: Experimental colitis was induced in mice deficient in components of the IL-20 and signal transducer and activator of transcription (STAT)2 signalling pathways. In vivo imaging, high-resolution mini-endoscopy and histology were used to assess intestinal inflammation. We further used RNA-sequencing (RNA-Seq), RNAScope and Gene Ontology analysis, western blot analysis and co-immunoprecipitation, confocal microscopy and intestinal epithelial cell (IEC)-derived three-dimensional organoids to investigate the underlying molecular mechanisms. Results were validated using samples from patients with IBD and non-IBD control subjects by a combination of RNA-Seq, organoids and immunostainings. RESULTS: In IBD, IL20 levels were induced during remission and were significantly higher in antitumour necrosis factor responders versus non-responders. IL-20RA and IL-20RB were present on IECs from patients with IBD and IL-20-induced STAT3 and suppressed interferon (IFN)-STAT2 signalling in these cells. In IBD, experimental dextran sulfate sodium (DSS)-induced colitis and mucosal healing, IECs were the main producers of IL-20. Compared with wildtype controls, Il20-/-, Il20ra-/- and Il20rb-/- mice were more susceptible to experimental DSS-induced colitis. IL-20 deficiency was associated with increased IFN/STAT2 activity in mice and IFN/STAT2-induced necroptotic cell death in IEC-derived organoids could be markedly blocked by IL-20. Moreover, newly generated Stat2ΔIEC mice, lacking STAT2 in IECs, were less susceptible to experimental colitis compared with wildtype controls and the administration of IL-20 suppressed colitis activity in wildtype animals. CONCLUSION: IL-20 controls colitis and mucosal healing by interfering with the IFN/STAT2 death signalling pathway in IECs. These results indicate new directions for suppressing gut inflammation by modulating IL-20-controlled STAT2 signals.

Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer.

Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology-a strategy that is based on perturbing primary tumor cells from cancer patients-could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-specific off-target effects and pathway crosstalk. Reconstruction of the kinase networks revealed that the signaling rewiring is modestly affected by mutations. We show non-genetic heterogeneity of the PDOs and upregulation of stemness and differentiation genes by kinase inhibitors. Using imaging mass-cytometry-based profiling of the primary tumors, we characterize the tumor microenvironment (TME) and determine spatial heterocellular crosstalk and tumor-immune cell interactions. Collectively, we provide a framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno-) oncology in CRC.

The peritonsillar abscess and its management - is incision and drainage only a makeshift to the tonsillectomy or a permanent solution?

Introduction: This study aims to examine the long-term management of peritonsillar abscess and compare needle aspiration, incision with drainage, and tonsillectomy in terms of comorbidities, complication rates, and recurrences in the largest study cohort published to date. Methods: We conducted a retrospective analysis of patients, both adults and children, who were treated for peritonsillar abscess between 2007 and 2019. Patient charts were analyzed to assess surgical treatment, infection and inflammation rates, risk of bleeding, recurrence rates, duration of illness, and sick certificates. Additionally, patient imaging and blood levels were compared. Postal questionnaires were sent to all patients to evaluate subjective success rates, complications, and long-term benefits of the different treatment regimens. General practitioners and ENT doctors in private practices were contacted to gather missing data on the long-term course of the disease. Results: A total of 821 patients with peritonsillar abscess were included in this study. Two patients had to be excluded due to incidental pathological findings. Of the remaining 819 patients, 180 were successfully treated with needle aspiration or incision. Among these patients, 37.7% required tonsillectomy during the same inpatient stay. Laboratory parameters such as leukocyte count or C-reactive protein levels were not indicative of the need for tonsillectomy. Furthermore, computed tomography was only necessary in cases of suspected parapharyngeal abscess, not in clear cases of peritonsillar abscess. Among the 641 patients who underwent tonsillectomy, 11.4% experienced postoperative bleeding requiring treatment. Only patients who underwent bilateral tonsillectomy reported recurrent episodes of sore throat and pharyngitis resulting in absence from work. The ipsilateral recurrence rate for peritonsillar abscess after needle aspiration or incision was 2.8%. There were no contralateral recurrences during the observation period. Conclusion: Due to the lower risk of postoperative bleeding, shorter absence from work, and shorter inpatient stay, incision and drainage are the preferable treatment for peritonsillar abscess. Additionally, patients who underwent bilateral tonsillectomy reported higher rates of work incapacity due to sore throat caused by pharyngitis. No patient met the clear indication for bilateral tonsillectomy due to recurrent acute tonsillitis. The recurrence rate after drainage without tonsillectomy was very low (2.8% ipsilaterally, no recurrence contralaterally).

Impact of a Multidisciplinary Head and Neck Tumor Board on Treatment and Survival in Laryngeal Carcinoma.

BACKGROUND: Pretherapeutic discussion in the head and neck tumor board (HNT) has been mandatory at the University Medical Center Freiburg since 01/2015, and it is intended to contribute to a survival benefit through interdisciplinary decision making. Prior to 2015, an optional HNT existed in which mainly advanced tumor stages were discussed. The aim of this study was to determine the effect of a pretherapeutic HNT on treatment and survival in laryngeal cancer. METHODS: A retrospective data analysis of 412 laryngeal carcinoma patients treated at the Head and Neck Cancer Center of the University Medical Center Freiburg between 01/2010 and 12/2020 was conducted. Differences regarding TNM status, UICC classification, tumor localization, gender and age at initial diagnosis, recurrence, secondary tumors, therapy, 5-year survival, and 5-year recurrence-free survival (5YSR/5Y-RFS) were assessed for therapy initiation with or without a pretherapeutic HNT. RESULTS: In total, 314 patients underwent a pretherapeutic HNT, and 98 received therapy initiation without an HNT. The HNT group showed significantly more advanced T stages and UICC classifications (p < 0.001; p = 0.003) and more frequent primary chemo/radiotherapy (p < 0.001). There was no significant difference regarding 5YSR (43 vs. 47 months, p = 0.96) or 5Y-RFS (48 vs. 52 months, p = 0.16). The time between initial diagnosis and therapy initiation was significantly longer when an HNT was performed (38 vs. 20 days, p = 0.008). CONCLUSIONS: The HNT group showed significantly more advanced tumor stages, suggesting that even before it became mandatory, it was frequently used for interdisciplinary case discussion in more complex cases. Due to the small number of T3/4 patients in the non-HNT group, a survival advantage of an HNT cannot be validly demonstrated in our study. However, the HNT led to broader patient counselling regarding their therapy options. At the same time, a significant delay in therapy initiation could be seen, suggesting that workflows between diagnosis, HNT presentation, and therapy initiation should be optimized.

STAT2 Controls Colorectal Tumorigenesis and Resistance to Anti-Cancer Drugs.

Colorectal cancer (CRC) is a significant socioeconomic burden in modern society and is accountable for millions of premature deaths each year. The role of signal transducer and activator of transcription 2 (STAT2)-dependent signaling in this context is not yet fully understood, and no therapies targeting this pathway are currently being pursued. We investigated the role of STAT2 in CRC using experimental mouse models coupled with RNA-sequencing (RNA-Seq) data and functional assays with anti-cancer agents in three-dimensional tumoroids. Stat2-/- mice showed greater resistance to the development of CRC in both inflammation-driven and inflammation-independent experimental CRC models. In ex vivo studies, tumoroids derived from Stat2-/- mice with the multiple intestinal neoplasia (Min) mutant allele of the adenomatous polyposis coli (Apc) locus exhibited delayed growth, were overall smaller and more differentiated as compared with tumoroids from ApcMin/+ wildtype (WT) mice. Notably, tumoroids from ApcMin/+ Stat2-/- mice were more susceptible to anti-cancer agents inducing cell death by different mechanisms. Our findings clearly indicated that STAT2 promotes CRC and suggested that interventions targeting STAT2-dependent signals might become an attractive therapeutic option for patients with CRC.

[Antibody-drug conjugates directed against NECTIN-4 as a new treatment option for patients with metastatic urothelial carcinoma]. / Gegen Nectin-4 gerichtete Antikörper-Wirkstoff-Konjugate als neue Behandlungsoption für Patienten mit metastasiertem Urothelkarzinom.

This compact review article highlights the background and importance of nectins in cancer therapy, focusing specifically on the antibody-drug conjugate enfortumab vedotin (EV) as a targeted treatment option for metastatic urothelial carcinoma. The evolving understanding of nectin-4 expression and its impact on EV therapy underscores the need for personalized approaches to ensure optimal patient outcomes. Further investigation into biomarker-guided therapies and prospective clinical trials are critical to refining patient selection and treatment strategies.

Red blood cell distribution width for the prediction of outcomes after cardiac arrest.

The red blood cell distribution width (RDW) is a routinely available blood marker that measures the variation of the size/volume of red blood cells. The aim of our study was to investigate the prognostic value of RDW in cardiac arrest patients and to assess whether RDW improves the prognostic value of three cardiac arrest-specific risk scores. Consecutive adult cardiac arrest patients admitted to the ICU of a Swiss university hospital were included. The primary outcome was poor neurological outcome at hospital discharge assessed by Cerebral Performance Category. Of 702 patients admitted to the ICU after cardiac arrest, 400 patients (57.0%) survived, of which 323 (80.8%) had a good neurological outcome. Higher mean RDW values showed an independent association with poor neurological outcomes at hospital discharge (adjusted OR 1.27, 95% CI 1.14 to 1.41; p < 0.001). Adding the maximum RDW value to the OHCA- CAHP- and PROLOGUE cardiac arrest scores improved prognostic performance. Within this cohort of cardiac arrest patients, RDW was an independent outcome predictor and slightly improved three cardiac arrest-specific risk scores. RDW may therefore support clinical decision-making.

Occurrence of sensitive topics during ward round: an ancillary analysis of the BEDSIDE-OUTSIDE trial.

OBJECTIVE: Discussing sensitive topics (eg, medical uncertainty, social issues, non-adherence) during ward rounds is challenging and may negatively impact patient satisfaction with the healthcare they are receiving. In the previous multicentre randomised BEDSIDE-OUTSIDE trial focusing on communication during ward rounds, we investigated the interplay between sensitive topics and low reported satisfaction with care. DESIGN: Pre-planned secondary analysis of a randomised controlled trial. For this analysis data of the original trial was pooled across intervention groups. SETTING: Three Swiss teaching hospitals. PARTICIPANTS: Adult patients hospitalised for medical care. INTERVENTIONS: We analysed predefined sensitive health topics and specific elements of communication from audiotapes recorded during ward rounds, for both patients dealing with and without sensitive topics. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was overall patient satisfaction with care; measured on a Visual Analogue Scale from 0 to 100. Secondary endpoints included duration of ward rounds and further satisfaction outcomes. RESULTS: Of the 919 included patients, 474 had at least one sensitive topic including medical uncertainty (n=251), psychiatric comorbidities (n=161), tumour diagnosis (n=137) and social issues (n=125). Compared with patients without sensitive topics, patients with sensitive topics reported lower satisfaction with care (mean (SD), 87.7 (±14.6) vs 90.2 (±12.1), adjusted difference -2.5 (95% CI -4.28 to -0.72), p=0.006. Among patients with sensitive topics, risk factors for low satisfaction included several parameters concerning patient-physician interaction such as disagreements during ward rounds (mean (SD), 14/212 (6.6%) vs 41/254 (16.1%), adjusted OR 2.78 (95% CI 1.47 to 5.27), p=0.002). CONCLUSIONS: A large proportion of medical inpatients must deal with sensitive health topics. This is associated with lower satisfaction with care, particularly if the patient perceives the interaction with doctors during ward rounds as unsatisfactory. Educating physicians on specific communication techniques may help improve care for these patients. TRIAL REGISTRATION NUMBER: NCT03210987.

Guardians of the gut: influence of the enteric nervous system on the intestinal epithelial barrier.

The intestinal mucosal surface forms one of the largest areas of the body, which is in direct contact with the environment. Co-ordinated sensory functions of immune, epithelial, and neuronal cells ensure the timely detection of noxious queues and potential pathogens and elicit proportional responses to mitigate the threats and maintain homeostasis. Such tuning and maintenance of the epithelial barrier is constantly ongoing during homeostasis and its derangement can become a gateway for systemic consequences. Although efforts in understanding the gatekeeping functions of immune cells have led the way, increasing number of studies point to a crucial role of the enteric nervous system in fine-tuning and maintaining this delicate homeostasis. The identification of immune regulatory functions of enteric neuropeptides and glial-derived factors is still in its infancy, but has already yielded several intriguing insights into their important contribution to the tight control of the mucosal barrier. In this review, we will first introduce the reader to the current understanding of the architecture of the enteric nervous system and the epithelial barrier. Next, we discuss the key discoveries and cellular pathways and mediators that have emerged as links between the enteric nervous, immune, and epithelial systems and how their coordinated actions defend against intestinal infectious and inflammatory diseases. Through this review, the readers will gain a sound understanding of the current neuro-immune-epithelial mechanisms ensuring intestinal barrier integrity and maintenance of intestinal homeostasis.

Analysis of the interferon-γ-induced secretome of intestinal endothelial cells: putative impact on epithelial barrier dysfunction in IBD.

The development of inflammatory bowel diseases (IBD) involves the breakdown of two barriers: the epithelial barrier and the gut-vascular barrier (GVB). The destabilization of each barrier can promote initiation and progression of the disease. Interestingly, first evidence is available that both barriers are communicating through secreted factors that may accordingly serve as targets for therapeutic modulation of barrier functions. Interferon (IFN)-γ is among the major pathogenesis factors in IBD and can severely impair both barriers. In order to identify factors transmitting signals from the GVB to the epithelial cell barrier, we analyzed the secretome of IFN-γ-treated human intestinal endothelial cells (HIEC). To this goal, HIEC were isolated in high purity from normal colon tissues. HIEC were either untreated or stimulated with IFN-γ (10 U/mL). After 48 h, conditioned media (CM) were harvested and subjected to comparative hyper reaction monitoring mass spectrometry (HRM™ MS). In total, 1,084 human proteins were detected in the HIEC-CM. Among these, 43 proteins were present in significantly different concentrations between the CM of IFN-γ- and control-stimulated HIEC. Several of these proteins were also differentially expressed in various murine colitis models as compared to healthy animals supporting the relevance of these proteins secreted by inflammatory activated HIEC in the inter-barrier communication in IBD. The angiocrine pathogenic impact of these differentially secreted HIEC proteins on the epithelial cell barrier and their perspectives as targets to treat IBD by modulation of trans-barrier communication is discussed in detail.

The Disclosure of Bad News Over the Phone vs. in Person and its Association with Psychological Distress: a Systematic Review and Meta-Analysis.

BACKGROUND: Communicating bad news such as a new cancer diagnosis to patients may have a major impact on their well-being. We investigated differences in patients' psychological distress due to the disclosure of bad news by telephone compared to in person in a systematic review and meta-analysis. METHODS: We included all studies that investigated anxiety, depressive or post-traumatic stress disorder (PTSD) symptoms in adult patients in whom bad news by telephone compared to in person were disclosed. We systematically searched PubMed, Embase, PsycINFO and CINAHL from the inception of each database to October 18, 2022. We included randomized and non-randomized trials. RESULTS: We screened 5944 studies and included 11 studies in the qualitative analysis and 9 in the meta-analyses, including four randomized controlled trials. Overall, the quality of studies was moderate to good. There was no difference regarding psychological distress when bad news was disclosed by telephone compared to in person with similar symptom levels of anxiety (3 studies, 285 participants; standardized mean difference [SMD] 0.10 [95% CI -0.15 to 0.35]), depression (3 studies, 284 participants; SMD 0.10 [95% CI -0.30 to 0.49]), and PTSD (2 studies, 171 participants; SMD -0.01 [95% CI -0.48 to 0.36]). Results were similar for satisfaction with care. DISCUSSION: This meta-analysis found no difference regarding psychological distress regardless if bad news were disclosed by telephone or in person, but there were overall only few and heterogeneous studies with a small number of eligible patients. The findings suggest that the modality of disclosure might play a secondary role and the way in which the bad news are communicated might be more important.