Objective structured clinical examination to teach competency in planetary health care and management - a prospective observational study.

BACKGROUND: Health professionals are increasingly called upon and willing to engage in planetary health care and management. However, so far, this topic is rarely covered in medical curricula. As the need for professional communication is particularly high in this subject area, this study aimed to evaluate whether the objective structured clinical examination (OSCE) could be used as an accompanying teaching tool. METHODS: During the winter semester 2022/2023, 20 third- and fifth-year medical students voluntarily participated in a self-directed online course, three workshops, and a formal eight-station OSCE on planetary health care and management. Each examinee was also charged alternatingly as a shadower with the role of providing feedback. Experienced examiners rated students' performance using a scoring system supported by tablet computers. Examiners and shadowers provided timely feedback on candidates` performance in the OSCE. Immediately after the OSCE, students were asked about their experience using a nine-point Likert-scale survey and a videotaped group interview. Quantitative analysis included the presentation of the proportional distribution of student responses to the survey and of box plots showing percentages of maximum scores for the OSCE performance. The student group interview was analyzed qualitatively. RESULTS: Depending on the sub-theme, 60% -100% of students rated the subject of planetary health as likely to be useful in their professional lives. Similar proportions (57%-100%) were in favour of integrating planetary health into required courses. Students perceived learning success from OSCE experience and feedback as higher compared to that from online courses and workshops. Even shadowers learned from observation and feedback discussions. Examiners assessed students' OSCE performance at a median of 80% (interquartile range: 83%-77%) of the maximum score. CONCLUSIONS: OSCE can be used as an accompanying teaching tool for advanced students on the topic of planetary health care and management. It supports learning outcomes, particularly in terms of communication skills to sensitise and empower dialogue partners, and to initiate adaptation steps at the level of individual patients and local communities.

Immunomodulator comedication promotes the reversal of anti-drug antibody-mediated loss of response to anti-TNF therapy in inflammatory bowel disease.

PURPOSE: Loss of therapeutic response (LOR) due to anti-drug antibodies (ADA) against tumor necrosis factor (TNF) inhibitors is common in patients with inflammatory bowel disease (IBD). We aimed to investigate whether immunomodulator comedication can reverse the immunogenic LOR to TNF inhibitors in IBD. METHODS: In this real-world retrospective cohort study, 123 IBD patients with neutralizing ADA to infliximab or adalimumab and concomitant subtherapeutic trough levels were screened for clinical LOR. Subsequent ADA and trough level measurements and clinical outcomes were analyzed for patients who received either immunomodulator comedication or dose intensification of infliximab or adalimumab to overcome LOR. RESULTS: Following immunogenic LOR, the initial anti-TNF regimen was optimized in 33 patients. In univariable and multivariable logistic regression analyses, immunomodulator comedication was identified as the crucial factor for regaining clinical remission and ADA clearance. Detectable trough levels (≥ 0.98 or ≥ 1.00 mg/L, respectively) had optimal predictive performance for both endpoints in receiver operating characteristics curves [area under the curve 0.86 (95% confidence interval 0.68-1.00) for regaining clinical remission, 0.87 (0.71-1.00) for ADA clearance]. Furthermore, 11/20 patients (55%) on a comedication with azathioprine or methotrexate and 2/13 patients (15%) receiving anti-TNF dose intensification exclusively (P = 0.032) exhibited ADA elimination, regain of therapeutic trough levels, and clinical remission. Regain of clinical remission alone was achieved in 17/20 (85%) patients receiving comedication and 2/13 (15%) patients receiving anti-TNF dose intensification (P = 1.6 × 10-4). CONCLUSION: Immunogenic LOR to infliximab or adalimumab in IBD can be successfully reversed using immunomodulator comedication.

Effects of Antibiotics on Gut Microbiota.

The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease. Common features of post-antibiotic dysbiosis include a loss of taxonomic and functional diversity combined with reduced colonization resistance against invading pathogens, which harbors the danger of antimicrobial resistance. This review summarizes the antibiotic-related changes of the gut microbiota and potential consequences in health and disease.

[Drug treatment of chronic inflammatory bowel diseases-What must the surgeon know and perioperatively pay attention to?] / Medikamentöse Therapie chronisch entzündlicher Darmerkrankungen ­ Was muss der Chirurg wissen und perioperativ beachten?

Mesalamine and topical or systemic corticosteroids form the basis of medicinal treatment of patients with chronic inflammatory bowel diseases (IBD), whereas immunosuppressants, biologicals and JAK inhibitors, so-called small molecules, are administered within so-called step-up treatment algorithms. Even though the frequency of operations has decreased during the last decades, surgical interventions still represent a relevant part of the overall concept in IBD treatment. Therefore, the effects of drug pretreatment on surgical approaches have to be put into specific perspectives and contexts. Treatment with corticosteroids unquestionably increases the rate of perioperative complications but there is no such correlation for the use of biologicals or immunosuppressants. Data from older studies pointed towards slightly increased rates of postoperative complications in patients treated with TNF-alpha antibodies; however, more recent studies have not confirmed this risk. The occurrence of postoperative complications is due to the multifactorial origin and is more dependent on the activity of the underlying disease, the comorbidities and the preoperative nutritional status. Preoperative use of the integrin inhibitor vedolizumab is comparable to TNF-alpha antibodies with respect to the postoperative complication rate. This also seems to apply to the interleukin 12/23 antagonist ustekinumab, although the data are still unreliable. The risks after treatment with the Janus kinase inhibitor tofacitinib cannot currently reliably be estimated. For the postoperative care an endoscopic follow-up should be performed within 6 months and prophylactic treatment with immunosuppressors or biologicals can be considered after taking the individual risk factors into account.

Development of an advanced diagnostic concept for intestinal inflammation: molecular visualisation of nitric oxide in macrophages by functional poly(lactic-co-glycolic acid) microspheres.

We here describe a new approach to visualise nitric oxide (NO) in living macrophages by fluorescent NO-sensitive microspheres based on poly(lactic-co-glycolic acid) (PLGA). PLGA microspheres loaded with NO550 dye were prepared through a modified solvent-evaporation method. Microparticles were characterized by a mean hydrodynamic diameter of 3000 nm, zeta potential of -26.000 ± 0.351 mV and a PDI of 0.828 ± 0.298. Under abiotic conditions, NO release was triggered through UV radiation (254 nm) of 10 mM sodium nitroprusside dehydrate (SNP). After incubation, AZO550 microspheres exhibited an about 8-fold increased emission at 550 nm compared to NO550 particles. For biotic NO release, RAW 264.7 murine macrophages were activated with lipopolysaccharide (LPS) of Salmonella typhimurium. After treatment with NO550 microparticles, only activated cells caused a green particle fluorescence and could be detected by laser scanning microscopy. NO release was confirmed indirectly with Griess reaction. Our functional NO550 particles enable a simple and early evaluation of inflammatory and immunological processes. Furthermore, our results on particle-based NO sensing and previous studies in targeting intestinal inflammation via (PLGA)-based microspheres demonstrate that an advanced concept for visualizing intestinal inflammation is tangible.

The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels.

PURPOSE: The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. METHODS: BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 µg Fe/cm(2)) or mitomycin C (up to 1.5 µg/cm(2), 24 hours) in the presence or absence of hyperthermia (43°C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. RESULTS: When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. DISCUSSION: The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our results could be used to develop new treatment strategies by repressing mechanisms that actively export drugs from the target cell, thereby improving the therapeutic outcome in oncology.