[Integrative medicine: what's new in 2023]. / Médecine intégrative : ce qui a changé en 2023.

To illustrate the news of 2023 in integrative medicine, the authors summarized four particularly relevant studies. The first highlights one of the foundational principles of integrative medicine, describing the importance of respecting patient preference in the choice of a therapeutic approach, promoting their «empowerment¼. The second article proposes methodological recommendations to improve the scientific value of studies assessing the efficacy and mechanisms of non-pharmacological approaches. Finally, the last two articles are randomized studies designed to either demonstrate the feasibility and effect of hypnosis in geriatrics, or evaluate the efficacy of a several combined complementary approaches for cancer-related fatigue.

Dans cette nouvelle édition consacrée aux nouveautés en médecine intégrative, les auteurs ont choisi de résumer quatre études particulièrement pertinentes parmi les articles publiés en 2023. La première souligne l'un des principes fondateurs de la médecine intégrative en décrivant l'importance du respect de la préférence du patient dans le choix d'une approche thérapeutique, favorisant leur « empowerment ¼. La deuxième propose des recommandations méthodologiques afin d'améliorer la valeur scientifique des études de l'efficacité et des mécanismes d'approches non pharmacologiques. Enfin, les deux dernières sont des études randomisées visant à démontrer, d'une part, la faisablité et l'effet de l'hypnose en gériatrie et, d'autre part, l'efficacité d'une combinaison d'approches complémentaires pour lutter contre la fatigue liée au cancer.

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.

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.

Improved broad-spectrum antibiotics against Gram-negative pathogens via darobactin biosynthetic pathway engineering.

The development of new antibiotics is imperative to fight increasing mortality rates connected to infections caused by multidrug-resistant (MDR) bacteria. In this context, Gram-negative pathogens listed in the WHO priority list are particularly problematic. Darobactin is a ribosomally produced and post-translationally modified bicyclic heptapeptide antibiotic selectively killing Gram-negative bacteria by targeting the outer membrane protein BamA. The native darobactin A producer Photorhabdus khanii HGB1456 shows very limited production under laboratory cultivation conditions. Herein, we present the design and heterologous expression of a synthetically engineered darobactin biosynthetic gene cluster (BGC) in Escherichia coli to reach an average darobactin A production titre of 13.4 mg L-1. Rational design of darA variants, encoding the darobactin precursor peptide with altered core sequences, resulted in the production of 13 new 'non-natural' darobactin derivatives and 4 previously hypothetical natural darobactins. One of the non-natural compounds, darobactin 9, was more potent than darobactin A, and showed significantly improved activity especially against Pseudomonas aeruginosa (0.125 µg mL-1) and Acinetobacter baumannii (1-2 µg mL-1). Importantly, it also displayed superior activity against MDR clinical isolates of E. coli (1-2 µg mL-1) and Klebsiella pneumoniae (1-4 µg mL-1). Independent deletions of genes from the darobactin BGC showed that only darA and darE, encoding a radical forming S-adenosyl-l-methionine-dependent enzyme, are required for darobactin formation. Co-expression of two additional genes associated with the BGCs in hypothetical producer strains identified a proteolytic detoxification mechanism as a potential self-resistance strategy in native producers. Taken together, we describe a versatile heterologous darobactin platform allowing the production of unprecedented active derivatives in good yields, and we provide first experimental evidence for darobactin biosynthesis processes.

In vivo and in vitro reconstitution of unique key steps in cystobactamid antibiotic biosynthesis.

Cystobactamids are myxobacteria-derived topoisomerase inhibitors with potent anti-Gram-negative activity. They are formed by a non-ribosomal peptide synthetase (NRPS) and consist of tailored para-aminobenzoic acids, connected by a unique α-methoxy-L-isoasparagine or a ß-methoxy-L-asparagine linker moiety. We describe the heterologous expression of the cystobactamid biosynthetic gene cluster (BGC) in Myxococcus xanthus. Targeted gene deletions produce several unnatural cystobactamids. Using in vitro experiments, we reconstitute the key biosynthetic steps of linker formation and shuttling via CysB to the NRPS. The biosynthetic logic involves a previously uncharacterized bifunctional domain found in the stand-alone NRPS module CysH, albicidin biosynthesis and numerous BGCs of unknown natural products. This domain performs either an aminomutase (AM) or an amide dehydratase (DH) type of reaction, depending on the activity of CysJ which hydroxylates CysH-bound L-asparagine. Furthermore, CysQ O-methylates hydroxyl-L-(iso)asparagine only in the presence of the AMDH domain. Taken together, these findings provide direct evidence for unique steps in cystobactamid biosynthesis.

Germline genetics of the p53 pathway affect longevity in a gender specific manner.

Aging is thought to occur through the accumulation of molecular and cellular damage. A key regulator of the cell's stress response is p53. In mice, the activity of p53 associates with lifespan. We were therefore interested whether SNPs in members of the p53-pathway are associated with longevity in humans. We genotyped the following SNPs: p53 - rs1042522 (Arg72Pro), MDM2 - rs2279744 (SNP309), MDM4 - rs4245739 (SNP34091), rs1563828 (SNP31826), PPP2R2B (rs319217) in 155 long-lived individuals (LLIs) who died at the age of 91 and over and in 171 ethnically-matched control subjects. Kaplan-Meier survival curves and log-Rank-test were used to determine the mean and median survival times. In female LLIs, the Pro-allele of rs1042522 (Arg72Pro) and the G-allele of rs2279744 (SNP309) were significantly associated with an increased survival time (P=0.026, P<0.001, respectively, log-Rank-test). In contrast, there was no difference regarding the survival time in male LLIs (rs1042522: P=0.58, rs2279744: P=0.503, log-Rank-test). There was no difference regarding the average age of death for the genotypes of the respective SNPs in the MDM4 gene (rs1563828: P=0.99; rs4245739: P=0.179, respectively). Here we show for the first time that the G-allele of rs2279744 (SNP309) is associated with increased lifespan. Importantly, this effect is gender-specific. Our data support the hypothesis that genetic variants that are associated with lower activity of p53--and therefore increased tumor risk--are associated with prolonged lifespan in a gender-specific manner.

Computer-based classification of small colorectal polyps by using narrow-band imaging with optical magnification.

BACKGROUND: Recent studies have shown that narrow-band imaging (NBI) is a powerful diagnostic tool for the differentiation between neoplastic and non-neoplastic colorectal polyps. OBJECTIVE: To develop a computer-based method for classification of colorectal polyps. DESIGN: A prospective study. SETTING: University hospital. PATIENTS: A total of 214 patients with colorectal polyps who underwent a zoom NBI colonoscopy. INTERVENTIONS: A total of 434 detected polyps 10 mm or smaller were imaged and subsequently removed for histological analysis. MAIN OUTCOME MEASUREMENTS: Diagnostic performance in polyp classification by 2 experts, 2 nonexperts, and a computer-based algorithm. RESULTS: The expert group and the computer-based algorithm achieved a comparable diagnostic performance (expert group: 93.4% sensitivity, 91.8% specificity, and 92.7% accuracy; computer-based algorithm: 95.0% sensitivity, 90.3% specificity, and 93.1% accuracy) and were both significantly superior to the nonexpert group (86.0% sensitivity, 87.8% specificity, and 86.8% accuracy) in terms of sensitivity, negative predictive value, and accuracy. Subgroup analysis of 255 polyps 5 mm or smaller revealed comparable results without significant differences in the overall analysis of all polyps. LIMITATIONS: No fully automatic classification system. CONCLUSIONS: The study demonstrates that computer-based classification of colon polyps can be achieved with high diagnostic performance.

Gap detection in endoscopic video sequences using graphs.

In minimal invasive surgery (MIS) a complete and seamless inspection of organs, e.g. the urinary bladder, using video endoscopes is often required for diagnostics. Since the endoscope is usually guided by free-hand, it is difficult to ensure a sequence of seamless frame transitions. Also 2-D panoramic images showing an extended field of view (FOV) do not provide always reliable results, since their interpretations are limited by potentially strong geometric distortions. To overcome these limitations and provide a direct verification method, we develop a gap detection algorithm using graphs. Exploiting the motion information of the applied zig-zag scan, we construct a graph representation of the video sequence. Without any explicit global image visualization our graph search algorithm identifies reliably frame discontinuities, which would lead to holes and slit artifacts in a panoramic view. The algorithm shows high detection rates and provides a fast method to verify frame discontinuities in the whole video sequence. Missed regions are highlighted by local image compositions which can be displayed during the intervention for assistance and inspection control.

Inertial navigation system for bladder endoscopy.

The usage of video endoscopes in cystoscopic interventions of the urinary bladder impedes an intuitive navigation. Although image-based solutions such as panorama images can provide extended views of the surgical field, a real-time 3-D navigation is not supported. Furthermore, the integration of common tracking systems in ambulant clinics is often hindered due to low usability and high costs. Thus, we discuss in this paper a first low-cost inertial navigation system. Our evaluation results show that in spite of lower sensor accuracies, mean errors between < 1° and 4° are achieved for solid angles. Using endoscopes with different view angles we apply an extended endoscope model for an adaptive displacement correction. Furthermore, we implement a first guided navigation tool for tumor re-identification in real-time.

Local and global panoramic imaging for fluorescence bladder endoscopy.

Endoscopic treatment of bladder cancer is more and more often based on photodynamic diagnostics (PDD), a specialized endoscopic technique where a narrow-band bluish illumination causes tumors to fluoresce reddish. Contrast between tumors and healthy bladder tissue is thus noticeably increased compared to white light endoscopy. A downside of PDD is the low illumination power, which requires that the distance between endoscope and bladder wall be kept low, thus resulting in a small field of view (FOV). We therefore describe an approach to combine several successive frames into a local PDD panorama, which provides a larger and sufficiently bright FOV for treatment. Furthermore, the endoscopic cancer treatment generally starts with a complete scan of the bladder to detect the tumors. For diagnosis, navigation and reporting, a global overview image of the bladder wall is often desired. While construction of such a global panorama can be based on the same algorithm as the local panorama, direct planar visualization of the sphere-shaped bladder may cause severe distortions. Apart from the global panorama computation itself, we therefore analyze these distortions, and provide an alternative visualization which is based on bladder depictions used in standard reporting forms and anatomy textbooks.