Search

Abstract Background Osteoporosis is characterized by a deterioration of bone structure and quantity that leads to an increased risk of fractures. The primary diagnostic tool for the assessment of the bone quality is currently the dual-energy X-ray absorptiometry (DXA), which however only measures bone quantity. High-resolution multidetector computed tomography (HR-MDCT) offers an alternative approach to assess bone structure, but still lacks evidence for its validity in vivo. The objective of this study was to assess the validity of HR-MDCT for the evaluation of bone architecture in the lumbar spine. Methods We conducted a prospective cross-sectional study to compare the results of preoperative lumbar HR-MDCT scans with those from microcomputed tomography (μCT) analysis of transpedicular vertebral body biopsies. For this purpose, we included patients undergoing spinal surgery in our orthopedic department. Each patient underwent preoperative HR-MDCT scanning (L1-L4). Intraoperatively, transpedicular biopsies were obtained from intact vertebrae. Micro-CT analysis of these biopsies was used as a reference method to assess the actual bone architecture. HR-MDCT results were statistically analyzed regarding the correlation with results from μCT. Results Thirty-four patients with a mean age of 69.09 years (± 10.07) were included in the study. There was no significant correlation for any of the parameters (bone volume/total volume, trabecular separation, trabecular thickness) between μCT and HR-MDCT (bone volume/total volume: r = − 0.026 and p = 0.872; trabecular thickness: r = 0.074 and r = 6.42; and trabecular separation: r = − 0.18 and p = 0.254). Conclusion To our knowledge, this is the first study comparing in vivo HR-MDCT with μCT analysis of vertebral biopsies in human patients. Our findings suggest that lumbar HR-MDCT is not valid for the in vivo evaluation of bone architecture in the lumbar spine. New diagnostic tools for the evaluation of osteoporosis and preoperative orthopedic planning are urgently needed.

Abstract The COVID-19 pandemic affected the diagnostics and treatment of breast cancer. Numerous studies reported an early decline in breast cancer (BC) incidence during the COVID-19 pandemic. Less evidence is available on changes in medical care. Reports from individual patients have provided anecdotal evidence for a shift from breast-conserving surgery to mastectomy to reduce the number of visits to radiation units during the pandemic. This study aimed to explore changes in BC incidence and surgical treatment in the south of Germany. Using data from the Baden-Württemberg Cancer Registry, the age-standardized incidence of BC (ICD-10 C50 and D05) (women) in 2018–2021 was investigated overall and by age and stage using standardized incidence ratios. Among pre-operative stage I/IIA BC patients, differences in the time to surgery and type of surgery were investigated using negative binomial and logistic regression models. The incidence of invasive BC decreased significantly from 170.9 per 100,000 women in 2018/2019 to 159.7 in 2020 and increased to 169.2 in 2021. This decrease resulted from a lower incidence around April 2020 and was also observed for non-invasive BC. In 2021, incidence of invasive BC was still decreased by 8% in women aged 80 + years. Surgical treatment was analyzed in 22,708 BC patients with a pre-operative stage ≤ IIA. The median time to surgery was 33 days in 2018/2019, 32 days in 2020 and 36 days in 2021. The proportion of mastectomies increased from 16.1% in 2018/2019 to 17.1% in 2020 and 17.3% in 2021 (adjusted odds ratio and 95% confidence interval (2021 vs. 2018/2019): 1.13 (1.03–1.24)). The adjusted increase was strongest for patients aged 50–59 years (1.34 (1.09–1.64)) and those with high-grade tumors (1.27 (1.07–1.51)). While the early return to pre-pandemic age-standardized BC incidence rates is promising, missed cases have not been caught up until 2021. Furthermore, the decreased incidence in elderly women in 2021 warrants further attention. In early-stage BC, a slightly greater rate of mastectomies was observed, although such a change was not recommended. This result underlines the importance of good communication of adapted treatment guidelines in such exceptional circumstances.

BackgroundSecondary use of clinical data for biomedical research purposes holds great potential for various types of noninterventional, data-driven studies. Patients’ willingness to support research with their clinical data is a crucial prerequisite for research progress. ObjectiveThe aim of the study was to learn about patients’ attitudes and expectations regarding secondary use of their clinical data. In a next step, our results can inform the development of an appropriate governance framework for secondary use of clinical data for research purposes. MethodsA questionnaire was developed to assess the willingness of patients with cancer to provide their clinical data for biomedical research purposes, considering different conditions of data sharing and consent models. The Cancer Registry of the German federal state of Baden-Württemberg recruited a proportionally stratified random sample of patients with cancer and survivors of cancer based on a full census. ResultsIn total, 838 participants completed the survey. Approximately all participants (810/838, 96.7%) showed general willingness to make clinical data available for biomedical research purposes; however, they expected certain requirements to be met, such as comparable data protection standards for data use abroad and the possibility to renew consent at regular time intervals. Most participants (620/838, 73.9%) supported data use also by researchers in commercial companies. More than half of the participants (503/838, 60%) were willing to give up control over clinical data in favor of research benefits. Most participants expressed acceptance of the broad consent model (494/838, 58.9%), followed by data use by default (with the option to opt out at any time; 419/838, 50%); specific consent for every study showed the lowest acceptance rate (327/838, 39%). Patients expected physicians to share their data (763/838, 91.1%) and their fellow patients to support secondary use with their clinical data (679/838, 81%). ConclusionsAlthough patients’ general willingness to make their clinical data available for biomedical research purposes is very high, the willingness of a substantial proportion of patients depends on additional requirements. Taking these perspectives into account is essential for designing trustworthy governance of clinical data reuse and sharing. The willingness to accept the loss of control over clinical data to enhance the benefits of research should be given special consideration.

In Brassicaceae, tissue damage triggers the mustard oil bomb i.e., activates the degradation of glucosinolates by myrosinases leading to a rapid accumulation of isothiocyanates at the site of damage. Isothiocyanates are reactive electrophilic species (RES) known to covalently bind to thiols in proteins and glutathione, a process that is not only toxic to herbivores and microbes but can also cause cell death of healthy plant tissues. Previously, it has been shown that subtoxic isothiocyanate concentrations can induce transcriptional reprogramming in intact plant cells. Glutathione depletion by RES leading to breakdown of the redox potential has been proposed as a central and common RES signal transduction mechanism. Using transcriptome analyses, we show that after exposure of Arabidopsis seedlings (grown in liquid culture) to subtoxic concentrations of sulforaphane hundreds of genes were regulated without depletion of the cellular glutathione pool. Heat shock genes were among the most highly up-regulated genes and this response was found to be dependent on the canonical heat shock factors A1 (HSFA1). HSFA1-deficient plants were more sensitive to isothiocyanates than wild type plants. Moreover, pretreatment of Arabidopsis seedlings with subtoxic concentrations of isothiocyanates increased resistance against exposure to toxic levels of isothiocyanates and, hence, may reduce the autotoxicity of the mustard oil bomb by inducing cell protection mechanisms.

Interaction of plants with the environment affects lipid metabolism. Changes in the pattern of phospholipids have been reported in response to abiotic stress, particularly accumulation of triacylglycerols, but less is known about the alteration of lipid metabolism in response to biotic stress and leaves have been more intensively studied than roots. This work investigates the levels of lipids in roots as well as leaves of Arabidopsis thaliana in response to pathogens and elicitor molecules by UPLC-TOF-MS. Triacylglycerol levels increased in roots and systemically in leaves upon treatment of roots with the fungus Verticillium longisporum. Upon spray infection of leaves with the bacterial pathogen Pseudomonas syringae, triacylglycerols accumulated locally in leaves but not in roots. Treatment of roots with a bacterial lipopolysaccharide elicitor induced a strong triacylglycerol accumulation in roots and leaves. Induction of the expression of the bacterial effector AVRRPM1 resulted in a dramatic increase of triacylglycerol levels in leaves, indicating that elicitor molecules are sufficient to induce accumulation of triacylglycerols. These results give insight into local and systemic changes to lipid metabolism in roots and leaves in response to biotic stresses.

Background and study aims Clip-assisted endoscopic full-thickness resection has great potential for treatment of difficult-to-resect colorectal neoplasia. Here, we report on endoscopic full-thickness resection at the appendiceal orifice with the appendix in situ requiring emergency surgery due to acute appendicitis. Final histopathology showed appendicitis and residual serrated adenoma within the appendiceal stump, but unexpectedly, also a displaced adenoma fragment at the serosal surface of the cecum. Given the transmural placement of the clip prior to snare resection, translocation of neoplastic tissue to the extra luminal site in cases of incomplete adenoma/carcinoma resection could be a concern.

Reactive electrophile species (RES), including prostaglandins, phytoprostanes and 12-oxo phytodienoic acid (OPDA), activate detoxification responses in plants and animals. However, the pathways leading to the activation of defense reactions related to abiotic or biotic stress as a function of RES formation, accumulation or treatment are poorly understood in plants. Here, the thiol-modification of proteins, including the RES-activated basic region/leucine zipper transcription factor TGA2, was studied. TGA2 contains a single cysteine residue (Cys186) that was covalently modified by reactive cyclopentenones but not required for induction of detoxification genes in response to OPDA or prostaglandin A1. Activation of the glutathione-S-transferase 6 (GST6) promoter was responsive to cyclopentenones but not to unreactive cyclopentanones, including jasmonic acid suggesting that thiol reactivity of RES is important to activate the TGA2-dependent signaling pathway resulting in GST6 activation We show that RES modify thiols in numerous proteins in vivo, however, thiol reactivity alone appears not to be sufficient for biological activity as demonstrated by the failure of several membrane permeable thiol reactive reagents to activate the GST6 promoter.

Cell-wall and glucopeptide components of yeast have been reported to exhibit elicitor activity. The mode of action of defense activation by yeast is not known so far. In this study, we used the model plant Arabidopsis to investigate the activation of defense responses by yeast, the effect on resistance against different pathogens, and the mode of action. Treatment of Arabidopsis plants with an autoclaved yeast suspension induced the expression of systemic acquired resistance-related genes and accumulation of the phytoalexin camalexin. Symptom development and bacterial growth after infection with a virulent strain of the pathogen Pseudomonas syringae was reduced in yeast-pretreated plants. No protection was detectable in mutants affected in the salicylate pathway, while mutants in the jasmonate or camalexin pathway were protected by yeast, indicating that the salicylate pathway is necessary for the yeast-induced resistance against P. syringae. Yeast also reduced symptom development after challenge with Botrytis cinerea. This protection was detectable in all mutants tested, indicating that it is independent of the salicylate, jasmonate, and camalexin pathway.