Interdisciplinary perspectives on computed tomography in sepsis: survey among medical doctors at a large university medical center.

OBJECTIVES: This study aims to describe physicians' perspectives on the use of computed tomography (CT) in patients with sepsis. METHODS: In January 2022, physicians of a large European university medical center were surveyed using a web-based questionnaire asking about their views on the role of CT in sepsis. A total of 371 questionnaires met the inclusion criteria and were analyzed using work experience, workplace, and medical specialty of physicians as variables. Chi-square tests were performed. RESULTS: Physicians considered the ability to detect an unknown focus as the greatest benefit of CT scans in sepsis (70.9%, n = 263/371). Two clinical criteria - "signs of decreased vigilance" (89.2%, n = 331/371) and "increased catecholamine demand" (84.7%, n = 314/371) - were considered highly relevant for a CT request. Elevated procalcitonin (82.7%, n = 307/371) and lactate levels (83.6%, n = 310/371) were consistently found to be critical laboratory values to request a CT. As long as there is evidence of infection in one organ region, most physicians (42.6%, n = 158/371) would order a CT scan based on clinical assessment. Combined examination of the chest, abdomen, and pelvis was favored (34.8%, n = 129/371) in cases without clinical clues of an infection source. A time window of ≥ 1-6 h was preferred for both CT examinations (53.9%, n = 200/371) and CT-guided interventions (59.3%, n = 220/371) in patients with sepsis. CONCLUSION: Despite much consensus, there are significant differences in attitudes towards the use of CT in septic patients among physicians from different workplaces and medical specialties. Knowledge of these perspectives may improve patient management and interprofessional communication. KEY POINTS: Despite interdisciplinary consensus on the use of CT in sepsis, statistically significant differences in the responses are apparent among physicians from different workplaces and medical specialties. The detection of a previously unknown source of infection and the ability to plan interventions and/or surgery based on CT findings are considered key advantages of CT in septic patients. Timing of CT reflects the requirements of specific disciplines.

Tight junctions: from molecules to gastrointestinal diseases.

Intestinal epithelium functions as a tissue barrier to prevent interaction between the internal compartment and the external milieu. Intestinal barrier function also determines epithelial polarity for the absorption of nutrients and the secretion of waste products. These vital functions require strong integrity of tight junction proteins. In fact, intestinal tight junctions that seal the paracellular space can restrict mucosal-to-serosal transport of hostile luminal contents. Tight junctions can form both an absolute barrier and a paracellular ion channel. Although defective tight junctions potentially lead to compromised intestinal barrier and the development and progression of gastrointestinal (GI) diseases, no FDA-approved therapies that recover the epithelial tight junction barrier are currently available in clinical practice. Here, we discuss the impacts and regulatory mechanisms of tight junction disruption in the gut and related diseases. We also provide an overview of potential therapeutic targets to restore the epithelial tight junction barrier in the GI tract.

Final-year medical students' perspective: a survey on the use of computed tomography in sepsis.

OBJECTIVES: To determine the perspective of final-year medical students on the use of computed tomography (CT) in patients with sepsis. METHODS: A total of 207 questionnaires were distributed to final-year medical students at a large university medical center, and 113 returned questionnaires met the criteria for inclusion in the analysis. Questions referred to sepsis guidelines, CT indications, and the use of contrast agents. Control variables included a level of practical experience as a final-year student (trimester of student's practical year) and previous radiological experience. Statistical hypothesis tests such as the Mann-Whitney U test and chi-square test were performed. RESULTS: The majority of participating students, 85% (n = 91/107), considered a Systemic Organ Failure Assessment (SOFA) score ≥ 2 as a diagnostic criterion for sepsis. The presence of ≥ 2 positive systemic inflammatory response syndrome (SIRS) criteria was considered relevant for diagnosing sepsis by 34% (n = 34/100). Ninety-nine percent (n = 64/65) of the participants who fully agreed with a SOFA score ≥ 2 being relevant for diagnosing sepsis would also use it as an indication for a CT scan. Seventy-six percent (n = 78/103) of the students rated a known severe allergic reaction to contrast agents as an absolute contraindication for its administration. Ninety-five percent (n = 78/82) considered radiation exposure as problematic in CT examinations, especially in repeat CTs. CONCLUSION: Most final-year medical students were familiar with the sepsis criteria. Still, some referred to outdated diagnostic criteria. Participants saw the ability to plan further patient management based on CT as a major benefit. Most participants were aware of radiation as a risk of CT. CRITICAL RELEVANCE STATEMENT: More detailed knowledge of CT in septic patients should be implemented in the medical curriculum. Retraining of medical students could help increase student confidence potentially improving patient care. KEY POINTS: 1. Whereas the majority of final-year medical students were familiar with sepsis criteria, some referred to outdated diagnostic criteria. 2. Participants saw the ability to plan further patient management based on CT as a major benefit. 3. Most participants were aware of radiation as a risk of CT.

Establishment of Intestinal Epithelial Cell Monolayers and Their Use in Calcium Switch Assay for Assessment of Intestinal Tight Junction Assembly.

Intestinal barrier function relies primarily on the assembly and integrity of tight junctions, which forms a size-selective barrier. This barrier restricts paracellular movement of solutes in various types of epithelia. Of note, extracellular Ca2+ concentration affects tight junction assembly. Therefore, the removal and re-addition of Ca2+ into cell culture medium of cultured intestinal epithelial cells causes destabilization and reassembly of tight junction to membrane periphery near apical surface, respectively. Based on this principle, the Ca2+-switch assay was established to investigate tight junction assembly in fully differentiated intestinal epithelial cells. This chapter provides a stepwise protocol for culture of intestinal epithelial cell monolayers using T84 cell line as an in vitro model and the Ca2+-switch assay for evaluating tight junction assembly.

Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice.

The tight junction protein claudin-2 is upregulated in disease. Although many studies have linked intestinal barrier loss to local and systemic disease, these have relied on macromolecular probes. In vitro analyses show, however, that these probes cannot be accommodated by size- and charge-selective claudin-2 channels. We sought to define the impact of claudin-2 channels on disease. Transgenic claudin-2 overexpression or IL-13-induced claudin-2 upregulation increased intestinal small cation permeability in vivo. IL-13 did not, however, affect permeability in claudin-2-knockout mice. Claudin-2 is therefore necessary and sufficient to effect size- and charge-selective permeability increases in vivo. In chronic disease, T cell transfer colitis severity was augmented or diminished in claudin-2-transgenic or -knockout mice, respectively. We translated the in vitro observation that casein kinase-2 (CK2) inhibition blocks claudin-2 channel function to prevent acute, IL-13-induced, claudin-2-mediated permeability increases in vivo. In chronic immune-mediated colitis, CK2 inhibition attenuated progression in claudin-2-sufficient, but not claudin-2-knockout, mice, i.e., the effect was claudin-2 dependent. Paracellular flux mediated by claudin-2 channels can therefore promote immune-mediated colitis progression. Although the mechanisms by which claudin-2 channels intensify disease remain to be defined, these data suggest that claudin-2 may be an accessible target in immune-mediated disorders, including inflammatory bowel disease.

Effectiveness and Safety of Vedolizumab in Anti-TNF-Naïve Patients With Inflammatory Bowel Disease-A Multicenter Retrospective European Study.

Background: Vedolizumab (VDZ) is effective for treatment of ulcerative colitis (UC) and Crohn's disease (CD). In GEMINI trials, anti-tumor necrosis factor (anti-TNF)-naïve patients had a superior response compared with anti-TNF-exposed patients. In real-world experience (RWE), the number of included anti-TNF-naïve patients was low. We aimed to evaluate the effectiveness and safety of VDZ in anti-TNF-naïve patients in an RWE setting. Methods: This retrospective multicenter European pooled cohort study included consecutive active anti-TNF-naïve IBD patients treated with VDZ. The primary end point was clinical response at week 14. Patients with follow-up beyond week 14 and those discontinuing VDZ at any time were included for maintenance outcomes analysis. Results: Since January 2015, 184 anti-TNF-naïve patients from 23 centers initiated VDZ treatment (Crohn's disease [CD], 50; ulcerative colitis [UC], 134). In CD, 42/50 (82%) patients responded by week 14 and 32 (64%) were in clinical remission; 26/50 (52%) achieved corticosteroid-free remission (CSFR). At last follow-up (44 weeks; interquartile range [IQR], 30-52 weeks), 27/35 (77.1%) patients with available data responded to treatment; 24/35 (68.6%) were in clinical remission, 21/35 (60%) were in CSFR. For UC, 116/134 (79.1%) responded to treatment by week 14, including 53 (39.5%) in clinical remission; 49/134 (36.6%) achieved CSFR. At last follow-up (42.5 weeks; IQR, 30-52 weeks), 79/103 (76.7%) patients responded to treatment, 69/103 (67.0%) were in remission, and 61/103 (59.2%) were in CSFR. Adverse effects were reported in 20 (11%) of the patients, leading to treatment discontinuation in 6 (3.3%). Conclusions: VDZ is similarly effective in ant-TNF-naïve CD and UC patients. The efficacy is higher than reported in anti-TNF-experienced patients and is comparable to that of anti-TNF biologics in this population.

The involvement of retroperitoneal lymph nodes in primary serous-papillary peritoneal carcinoma. a systematic review of the literature.

BACKGROUND: Primary serous-papillary peritoneal carcinoma is able to spread to the retroperitoneal lymph nodes, but there is no evidence of the pattern of lymphatic metastasis. Because of the fact that this tumor entity is indistinguishable histologically from primary serous-papillary ovarian carcinoma, its taxonomic position has thus far remained unclear. MATERIALS AND METHODS: The Medline database was used to identify studies about lymphatic spread pattern and to compare those studies. RESULTS: Four out of the fifteen studies were selected. Each based their analysis on a different classification of the pelvic and para-aortal lymph nodes; 63.9% of the women with primary serous-papillary peritoneal carcinoma had retroperitoneal lymph node involvement. CONCLUSION: Metastasis of primary serous-papillary peritoneal carcinoma to retroperitoneal lymph nodes is not an infrequent occurrence, but there is no evidence of a distinct pattern of spread.