Malignant features of minipig melanomas prior to spontaneous regression.

In MeLiM minipigs, melanomas develop around birth, can metastasize, and have histopathologic characteristics similar to humans. Interestingly, MeLiM melanomas eventually regress. This favorable outcome raises the question of their malignancy, which we investigated. We clinically followed tens of tumors from onset to first signs of regression. Transcriptome analysis revealed an enrichment of all cancer hallmarks in melanomas, although no activating or suppressing somatic mutation were found in common driver genes. Analysis of tumor cell genomes revealed high mutation rates without UV signature. Canonical proliferative, survival and angiogenic pathways were detected in MeLiM tumor cells all along progression stages. Functionally, we show that MeLiM melanoma cells are capable to grow in immunocompromised mice, with serial passages and for a longer time than in MeLiM pigs. Pigs set in place an immune response during progression with dense infiltration by myeloid cells while melanoma cells are deficient in B2M expression. To conclude, our data on MeLiM melanomas reveal several malignancy characteristics. The combination of these features with the successful spontaneous regression of these tumors make it an outstanding model to study an efficient anti-tumor immune response.

Pulmonary Metastasising Aneurysmal Fibrous Histiocytoma: A Case Report, Literature Review and Proposal of Standardised Diagnostic Criteria.

An aneurysmal fibrous histiocytoma is a rare cutaneous soft-tissue tumour which accounts for approximately 0.06% of all dermatopathologies. Metastasis is exceedingly uncommon, to the point that there have only been eight reported cases in the scientific literature. We present the case of a 25-year-old male with a primary aneurysmal fibrous histiocytoma located in the nuchal region which exhibited rapid growth and abrupt ulceration over a short time span and showed signs of locoregional aggressive infiltration. A subsequent histopathological analysis confirmed the presence of diffuse solid and cystic pulmonary metastases. Further genetic sequencing verified LAMTOR1-PRKCD fusion. This case report seeks to review the existing literature on aneurysmal fibrous histiocytoma, discuss the challenges of differential diagnosis and propose standardised diagnostic criteria.

The impact of passive alveolar molding vs. nasoalveolar molding on cleft width and other parameters of maxillary growth in unilateral cleft lip palate.

OBJECTIVE: Passive alveolar molding (PAM) and nasoalveolar molding (NAM) are established presurgical infant orthodontic (PSIO) therapies for cleft lip palate (CLP) patients. PAM guides maxillary growth with a modified Hotz appliance, while NAM also uses extraoral taping and includes nasal stents. The effects of these techniques on alveolar arch growth have rarely been compared. MATERIAL AND METHODS: We retrospectively compared 3D-scanned maxillary models obtained before and after PSIO from infants with unilateral, non-syndromic CLP treated with PAM (n = 16) versus NAM (n = 13). Nine anatomical points were set digitally by four raters and transversal/sagittal distances and rotations of the maxilla were measured. RESULTS: Both appliances reduced the anterior cleft, but NAM percentage wise more. NAM decreased the anterior and medial transversal width compared to PAM, which led to no change. With both appliances, the posterior width increased. The alveolar arch length of the great and small segments and the sagittal length of the maxilla increased with PAM but only partially with NAM. However, NAM induced a significant greater medial rotation of the larger and smaller segment compared to PAM with respect to the lateral angle. CONCLUSIONS: NAM and PAM presented some significant differences regarding maxillary growth. While NAM reduced the anterior cleft and effectively rotated the segments medially, PAM allowed more transversal and sagittal growth. CLINICAL RELEVANCE: The results of this study should be taken into consideration when to decide whether to use PAM or NAM, since they show a different outcome within the first few months. Further studies are necessary regarding long-term differences.

Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1)-A Prospective Multicentric Cohort Study.

(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.

Detailed chemical analysis of honey bee (Apis mellifera) worker brood volatile profile from egg to emergence.

Chemical communication is a widely used mode of communication for social insects and has been demonstrated to be involved in many behaviours and physiological processes such as reproduction, nutrition or the fight against parasites and pathogens. In the honey bee, Apis mellifera, the release of chemical compounds by the brood plays a role in worker behaviour, physiology, and foraging activities and colony health as a whole. Several compounds have already been described as brood pheromones, such as components of the brood ester pheromone and (E)-ß-ocimene. Several other compounds originating from diseased or varroa-infested brood cells have been described as triggering the hygienic behaviour of workers. So far, studies of brood emissions have focused on specific stages of development and little is known about the emission of volatile organic compounds by the brood. In this study, we investigate the semiochemical profile of worker honey bee brood during its whole developmental cycle, from egg to emergence, with a specific focus on volatile organic compounds. We describe variation in emissions of thirty-two volatile organic compounds between brood stages. We highlight candidate compounds that are particularly abundant in specific stages and discuss their potential biological significance.

Impact of dental restorations and removable prostheses on potentially malignant oral mucosal disorders in the general population.

STATEMENT OF PROBLEM: Dental restorations and removable dental prostheses have been considered as risk factors for potentially malignant disorders of the oral mucosa. It remains unclear whether amalgam, composite resins, and prosthesis materials can induce potentially malignant disorders. PURPOSE: The purpose of this clinical study was to determine the relationship between the presence of amalgam and composite resin restorations, crowns and fixed partial dentures, and removable prostheses in potentially malignant disorders. MATERIAL AND METHODS: The data of 6041 participants in the population-based Studies of Health in Pomerania (SHIP) were accessed. Potentially malignant disorders had been clinically diagnosed by calibrated dentists and documented with photographs. Dental treatment was subdivided into restored and replaced teeth. Dental restorations were subclassified as buccal composite resin or amalgam restorations. Prosthetic treatment was subclassified into removable partial or complete prostheses and definitive restorations with crowns and fixed partial dentures. RESULTS: In the maxilla, participants with removable prostheses had a higher incidence of potentially malignant disorders than participants not undergoing treatment with removable prostheses (OR 2.12; 95% CI: 1.08-4.18), but not in the mandible (OR 1.30; 95% CI: 0.67-2.53). The surfaces with composite resin restorations were associated with a slightly higher risk of mucosal lesions than those without the restorations (OR 1.04; 95% CI: 1.01-1.07). No significant association was found between amalgam restorations and mucosal lesions. CONCLUSIONS: Participants with removable prostheses have a higher risk of potentially malignant disorders. Composite resin restorations are associated with a higher risk of mucosal lesions, whereas no significant association was found between amalgam restorations and mucosal lesions.

Pedicled buccal flaps as a backup procedure for intraoral reconstruction.

BACKGROUND: Intraoral soft tissue deficiency and impaired wound beds are common problems after cleft and tumour surgery or after dental trauma. Frequently, limited defects are overtreated with extensive microvascular reconstruction procedures, but pedicled flaps remain useful, as they are simple to harvest, and they provide a reliable outcome. The buccal flap, first described in the 1970s, has been used for palatine lengthening in cleft patients over decades. In the following, we present an expanded indication in cases of palatal fistula, complex vestibulum, exposed bone in orthognathic surgery, and osteoradionecrosis. METHODS: We conducted a retrospective chart review and report on all buccal flaps harvested in our department within the last 3 years with a follow-up period of at least half a year after flap surgery. Patients of all age groups and treatment indications in which a buccal flap was used were implicated in the evaluation. RESULTS: Sixteen buccal flaps were performed in 10 patients. The median age at the time of surgery was 42 years, reaching from 12 up to 66 years. Fourteen buccal flaps were used for upper jaw or palatal coverage; two buccal flaps were used in the mandible. In terms of complications (four flaps; 25%), there were two partial flap failures, one wound dehiscence and one wound dehiscence. There were no failures of the remaining mucosal flap islands after pedicle dissection. CONCLUSION: The buccal flap is a reliable and straightforward approach to challenging intraoral wound beds with soft tissue deficiency. We thoroughly discuss the additional indications for buccal flap surgery, describe the harvest technique, and provide strategies to prevent intra- and postoperative complications.

Accounting for overlapping annotations in genomic prediction models of complex traits.

BACKGROUND: It is now widespread in livestock and plant breeding to use genotyping data to predict phenotypes with genomic prediction models. In parallel, genomic annotations related to a variety of traits are increasing in number and granularity, providing valuable insight into potentially important positions in the genome. The BayesRC model integrates this prior biological information by factorizing the genome according to disjoint annotation categories, in some cases enabling improved prediction of heritable traits. However, BayesRC is not adapted to cases where markers may have multiple annotations. RESULTS: We propose two novel Bayesian approaches to account for multi-annotated markers through a cumulative (BayesRC+) or preferential (BayesRC[Formula: see text]) model of the contribution of multiple annotation categories. We illustrate their performance on simulated data with various genetic architectures and types of annotations. We also explore their use on data from a backcross population of growing pigs in conjunction with annotations constructed using the PigQTLdb. In both simulated and real data, we observed a modest improvement in prediction quality with our models when used with informative annotations. In addition, our results show that BayesRC+ successfully prioritizes multi-annotated markers according to their posterior variance, while BayesRC[Formula: see text] provides a useful interpretation of informative annotations for multi-annotated markers. Finally, we explore several strategies for constructing annotations from a public database, highlighting the importance of careful consideration of this step. CONCLUSION: When used with annotations that are relevant to the trait under study, BayesRC[Formula: see text] and BayesRC+ allow for improved prediction and prioritization of multi-annotated markers, and can provide useful biological insight into the genetic architecture of traits.

A Prospective Comparative Analysis Regarding the Assessment of Oral Mucosal Disease Using a Validated Questionnaire to Improve the Teaching of Dental Students.

Structured examination and treatment are essential in medicine. For dental students, a structured approach to the assessment of oral mucosal lesions is missing thus far. To validate an approach, a structured questionnaire was compared with the habitually used free description of oral lesions (white lesions, ulcers, hyperplasia). Thirty-three dental students were divided into two groups (Group 1 (n = 17) used the free description; Group 2 (n = 16) used a guided questionnaire) to characterize mucosal lesions in patients and make a tentative diagnosis. Although no difference was found between the groups regarding the suspected diagnosis or the histopathological findings, there was a significant advantage of the structured questionnaire in all aspects of the description compared to the free description (p = 0.000018). Thus, a structured description is an important aspect in the evaluation of oral mucosal changes, and a guided questionnaire should be implemented in the study of dentistry.

Comparative analysis of the caecal tonsil transcriptome in two chicken lines experimentally infected with Salmonella Enteritidis.

Managing Salmonella enterica Enteritidis (SE) carriage in chicken is necessary to ensure human food safety and enhance the economic, social and environmental sustainability of chicken breeding. Salmonella can contaminate poultry products, causing human foodborne disease and economic losses for farmers. Both genetic selection for a decreased carriage and gut microbiota modulation strategies could reduce Salmonella propagation in farms. Two-hundred and twenty animals from the White Leghorn inbred lines N and 61 were raised together on floor, infected by SE at 7 days of age, transferred into isolators to prevent oro-fecal recontamination and euthanized at 12 days post-infection. Caecal content DNA was used to measure individual Salmonella counts (ISC) by droplet digital PCR. A RNA sequencing approach was used to measure gene expression levels in caecal tonsils after infection of 48 chicks with low or high ISC. The analysis between lines identified 7516 differentially expressed genes (DEGs) corresponding to 62 enriched Gene Ontology (GO) Biological Processes (BP) terms. A comparison between low and high carriers allowed us to identify 97 DEGs and 23 enriched GO BP terms within line 61, and 1034 DEGs and 288 enriched GO BP terms within line N. Among these genes, we identified several candidate genes based on their putative functions, including FUT2 or MUC4, which could be involved in the control of SE infection, maybe through interactions with commensal bacteria. Altogether, we were able to identify several genes and pathways associated with differences in SE carriage level. These results are discussed in relation to individual caecal microbiota compositions, obtained for the same animals in a previous study, which may interact with host gene expression levels for the control of the caecal SE load.

COVID-19 pandemic and its impact on dental education: digitalization - progress or regress? Example of an online hands-on course.

BACKGROUND: Due to the SARS-CoV-2 pandemic and the accompanying contact restrictions, a new challenge arose for dental education. Despite the limited overall situation, it must be ensured that, in addition to theoretical content, practical skills in particular continue to be taught. Therefore, the aim of this study was to develop and implement an online hands-on course for dental students that ensures practical training, even during the pandemic. METHODS: The newly developed course was held from April 2020 to March 2021. A total of six groups (each consisting of approximately 40-50 students) took part in the course. The participating students were in their 3rd, 4th or 5th year of study. The course taught theoretical basics (via an online platform) and promoted the learning of practical/surgical techniques on models such as bananas, pork bellies, or chicken thighs with live demonstrations (via ZOOM) and interactive post-preparation by students at home (and in a rotating small group of 3-7 students on site). Student self-evaluation (at the beginning and end of the course) and course evaluation were performed using questionnaires. The learning success was analyzed (through self-evaluations) using Wilcoxon signed-rank tests (significance level alpha = 0.05). RESULTS: Concerning students´ self-evaluations, the theoretical knowledge, general surgical skills (such as surgical instrument handling), and specific surgical skills (such as performing a kite flap) improved during the course, with significant results (p < 0.001 for each). About 60% of the students rated the course overall as excellent (grades 9 or 10 on a Likert scale of 1 to 10). The technical implementation of the course was rated with a median of 9 (= very good, on a Likert scale of 1 to 10). 38.5% described the applicability of the skills learned for their later professional life as extremely good. CONCLUSIONS: The results of this work suggest that, within the limitations of this study, the introduced concept of an online hands-on course could be an appropriate form of teaching practical dental skills, even during a pandemic. Further research is needed in the field of digital education for dental students.

Integrated sRNA-seq and RNA-seq Analyses Reveal a microRNA Regulation Network Involved in Cold Response in Pisum sativum L.

(1) Background: Cold stress affects growth and development in plants and is a major environmental factor that decreases productivity. Over the past two decades, the advent of next generation sequencing (NGS) technologies has opened new opportunities to understand the molecular bases of stress resistance by enabling the detection of weakly expressed transcripts and the identification of regulatory RNAs of gene expression, including microRNAs (miRNAs). (2) Methods: In this study, we performed time series sRNA and mRNA sequencing experiments on two pea (Pisum sativum L., Ps) lines, Champagne frost-tolerant and Térèse frost-sensitive, during a low temperature treatment versus a control condition. (3) Results: An integrative analysis led to the identification of 136 miRNAs and a regulation network composed of 39 miRNA/mRNA target pairs with discordant expression patterns. (4) Conclusions: Our findings indicate that the cold response in pea involves 11 miRNA families as well as their target genes related to antioxidative and multi-stress defense mechanisms and cell wall biosynthesis.

Potential genetic robustness of Prnp and Sprn double knockout mouse embryos towards ShRNA-lentiviral inoculation.

The Shadoo and PrP prion protein family members are thought to be functionally related, but previous knockdown/knockout experiments in early mouse embryogenesis have provided seemingly contradictory results. In particular, Shadoo was found to be indispensable in the absence of PrP in knockdown analyses, but a double-knockout of the two had little phenotypic impact. We investigated this apparent discrepancy by comparing transcriptomes of WT, Prnp0/0 and Prnp0/0Sprn0/0 E6.5 mouse embryos following inoculation by Sprn- or Prnp-ShRNA lentiviral vectors. Our results suggest the possibility of genetic adaptation in Prnp0/0Sprn0/0 mice, thus providing a potential explanation for their previously observed resilience.

Differences in caecal microbiota composition and Salmonella carriage between experimentally infected inbred lines of chickens.

BACKGROUND: Salmonella Enteritidis (SE) is one of the major causes of human foodborne intoxication resulting from consumption of contaminated poultry products. Genetic selection of animals that are more resistant to Salmonella carriage and modulation of the gut microbiota are two promising ways to decrease individual Salmonella carriage. The aims of this study were to identify the main genetic and microbial factors that control the level of Salmonella carriage in chickens (Gallus gallus) under controlled experimental conditions. Two-hundred and forty animals from the White Leghorn inbred lines N and 61 were infected by SE at 7 days of age. After infection, animals were kept in isolators to reduce recontamination of birds by Salmonella. Caecal contents were sampled at 12 days post-infection and used for DNA extraction. Microbiota DNA was used to measure individual counts of SE by digital PCR and to determine the bacterial taxonomic composition, using a 16S rRNA gene high-throughput sequencing approach. RESULTS: Our results confirmed that the N line is more resistant to Salmonella carriage than the 61 line, and that intra-line variability is higher for the 61 line. Furthermore, the 16S analysis showed strong significant differences in microbiota taxonomic composition between the two lines. Among the 617 operational taxonomic units (OTU) observed, more than 390 were differentially abundant between the two lines. Furthermore, within the 61 line, we found a difference in the microbiota taxonomic composition between the high and low Salmonella carriers, with 39 differentially abundant OTU. Using metagenome functional prediction based on 16S data, several metabolic pathways that are potentially associated to microbiota taxonomic differences (e.g. short chain fatty acids pathways) were identified between high and low carriers. CONCLUSIONS: Overall, our findings demonstrate that the caecal microbiota composition differs between genetic lines of chickens. This could be one of the reasons why the investigated lines differed in Salmonella carriage levels under experimental infection conditions.

Prevalence of SARS-CoV-2 IgG antibodies among dental teams in Germany.

OBJECTIVES: During the corona pandemic, dental practices temporarily closed their doors to patients except for emergency treatments. Due to the daily occupational exposure, the risk of SARS-CoV-2 transmission among dentists and their team is presumed to be higher than that in the general population. This study examined this issue among dental teams across Germany. MATERIALS AND METHODS: In total, 2784 participants provided usable questionnaires and dry blood samples. Dry blood samples were used to detect IgG antibodies against SARS-CoV-2. The questionnaires were analyzed to investigate demographic data and working conditions during the pandemic. Multivariable logistic mixed-effects models were applied. RESULTS: We observed 146 participants with positive SARS-CoV-2 IgG antibodies (5.2%) and 30 subjects with a borderline finding (1.1%). Seventy-four out of the 146 participants with SARS-CoV-2 IgG antibodies did not report a positive SARS-CoV-2 PCR test (50.7%), while 27 participants without SARS-CoV-2 IgG antibodies reported a positive SARS-CoV-2 PCR test (1.1%). Combining the laboratory and self-reported information, the number of participants with a SARS-CoV-2 infection was 179 (6.5%). Though after adjustment for region, mixed-effects models indicated associations of use of rubber dams (OR 1.65; 95% CI: 1.01-2.72) and the number of protective measures (OR 1.16; 95% CI: 1.01-1.34) with increased risk for positive SARS-CoV-2 status, none of those variables was significantly associated with a SARS-CoV-2 status in fully adjusted models. CONCLUSIONS: The risk of SARS-CoV-2 transmission was not higher among the dental team compared to the general population. CLINICAL RELEVANCE: Following hygienic regulations and infection control measures ensures the safety of the dental team and their patients.

Individualized multi-omic pathway deviation scores using multiple factor analysis.

Malignant progression of normal tissue is typically driven by complex networks of somatic changes, including genetic mutations, copy number aberrations, epigenetic changes, and transcriptional reprogramming. To delineate aberrant multi-omic tumor features that correlate with clinical outcomes, we present a novel pathway-centric tool based on the multiple factor analysis framework called padma. Using a multi-omic consensus representation, padma quantifies and characterizes individualized pathway-specific multi-omic deviations and their underlying drivers, with respect to the sampled population. We demonstrate the utility of padma to correlate patient outcomes with complex genetic, epigenetic, and transcriptomic perturbations in clinically actionable pathways in breast and lung cancer.

A Retrospective Analysis of Postoperative Abscess Formation Following Wisdom Tooth Removal and Their Clinical Condition and Localization.

AIM: As a common procedure in oral surgery, the removal of wisdom teeth (3M) is associated with a variety of postoperative complications. This study reports of deep tissue abscesses after the removal of 3M in correlation to several factors. MATERIALS AND METHODS: Patients between 2012 and 2017 with removed 3M were retrospectively evaluated in terms of clinical condition and localization and thus assigned tog A (removal of asymptomatic 3M) or group B (removal of symptomatic 3M). Moreover, they were analyzed in terms of abscesses after the removal and correlation with various parameters: localization of the abscess, general diseases, perioperative antibiotic treatment, number of days from removal of the tooth to abscess formation, and postoperative complications after primary abscess incision. RESULTS: About 82 patients (male n = 44, female n = 38) were included, with 88 wisdom teeth removed and postoperative abscesses. Postoperative abscesses occurred more frequently in group B (n = 53) with n = 29 in IIB localization, without a significant correlation. Patients in this group were older, and there were more surgical abscess incisions needed, despite a longer treatment with oral and intravenous antibiosis that correlated with neurologic diseases and age. Younger patients reported significantly more pain. CONCLUSIONS: Detection of potential 3M pathologies at an early and asymptomatic stage is essential to avoid postoperative complications following 3M removal. Additional prospective studies are necessary to develop corresponding guidelines. CLINICAL SIGNIFICANCE: Wisdom tooth extraction is the most common operation in oral surgery, and therefore, adequate risk evaluation is still required.

An evaluation of the predictive performance and mapping power of the BayesR model for genomic prediction.

Technological advances and decreasing costs have led to the rise of increasingly dense genotyping data, making feasible the identification of potential causal markers. Custom genotyping chips, which combine medium-density genotypes with a custom genotype panel, can capitalize on these candidates to potentially yield improved accuracy and interpretability in genomic prediction. A particularly promising model to this end is BayesR, which divides markers into four effect size classes. BayesR has been shown to yield accurate predictions and promise for quantitative trait loci (QTL) mapping in real data applications, but an extensive benchmarking in simulated data is currently lacking. Based on a set of real genotypes, we generated simulated data under a variety of genetic architectures and phenotype heritabilities, and we evaluated the impact of excluding or including causal markers among the genotypes. We define several statistical criteria for QTL mapping, including several based on sliding windows to account for linkage disequilibrium (LD). We compare and contrast these statistics and their ability to accurately prioritize known causal markers. Overall, we confirm the strong predictive performance for BayesR in moderately to highly heritable traits, particularly for 50k custom data. In cases of low heritability or weak LD with the causal marker in 50k genotypes, QTL mapping is a challenge, regardless of the criterion used. BayesR is a promising approach to simultaneously obtain accurate predictions and interpretable classifications of SNPs into effect size classes. We illustrated the performance of BayesR in a variety of simulation scenarios, and compared the advantages and limitations of each.

A prospective comparative study to assess the risk of postoperative bleeding after dental surgery while on medication with direct oral anticoagulants, antiplatelet agents, or vitamin K antagonists.

BACKGROUND: The aim of this prospective study was to investigate the occurrence and severity of postoperative bleeding following dentoalveolar surgery in patients with uninterrupted anticoagulation therapy (AT). METHODS: Patients receiving AT (vitamin k antagonist (VK), direct oral anticoagulants (DOAC) or antiplatelet therapy (APT) and in need of surgical intervention classified as A, B or C (single or serial tooth extraction, osteotomy, or implant placement) were studied between 2019 and 2021. A healthy, non-anticoagulated cohort (CG) served as a control group. The main outcomes measured were the frequency of postoperative bleeding, the classification of the severity of postoperative bleeding (1a, 1b, 1c, 2, 3), and the correlation with the AT surgical intervention classification. RESULTS: In total, 195 patients were included in the study, with 95 patients in the AT group and 100 in the CG. Postoperative bleeding was significant in the AT group vs. the CG (p = 0.000), with a significant correlation with surgical intervention class C (p = 0.013) and the severity class of bleeding 1a (p = 0.044). There was no significant correlation with procedures of type A, B or C for the other postoperative bleeding gradations (1b, 1c, 2 and 3). There was a statistically significant difference in the occurrence of postoperative bleeding events between the DOAC/APT group and the VK group (p = 0.036), but there were no significant differences regarding the other AT agents. CONCLUSION: The continuation of anticoagulation therapy for surgical interventions also seems reasonable for high-risk interventions. Although significantly more postoperative bleeding occurs, the severity of bleeding is low. The perioperative management of anticoagulated patients requires well-coordinated interdisciplinary teamwork and detailed instruction of patients. Clinical trial registration The study is registered (29.03.2021) at the German clinical trial registry (DRKS00024889).

Hypervirulent Klebsiella pneumoniae Sequence Type 420 with a Chromosomally Inserted Virulence Plasmid.

BACKGROUND: Klebsiella pneumoniae causes severe diseases including sepsis, pneumonia and wound infections and is differentiated into hypervirulent (hvKp) and classic (cKp) pathotypes. hvKp isolates are characterized clinically by invasive and multiple site infection and phenotypically in particular through hypermucoviscosity and increased siderophore production, enabled by the presence of the respective virulence genes, which are partly carried on plasmids. METHODS: Here, we analyzed two K. pneumoniae isolates of a human patient that caused severe multiple site infection. By applying both genomic and phenotypic experiments and combining basic science with clinical approaches, we aimed at characterizing the clinical background as well as the two isolates in-depth. This also included bioinformatics analysis of a chromosomal virulence plasmid integration event. RESULTS: Our genomic analysis revealed that the two isolates were clonal and belonged to sequence type 420, which is not only the first description of this K. pneumoniae subtype in Germany but also suggests belonging to the hvKp pathotype. The latter was supported by the clinical appearance and our phenotypic findings revealing increased siderophore production and hypermucoviscosity similar to an archetypical, hypervirulent K. pneumoniae strain. In addition, our in-depth bioinformatics analysis suggested the insertion of a hypervirulence plasmid in the bacterial chromosome, mediated by a new IS5 family sub-group IS903 insertion sequence designated ISKpn74. CONCLUSION: Our study contributes not only to the understanding of hvKp and the association between hypervirulence and clinical outcomes but reveals the chromosomal integration of a virulence plasmid, which might lead to tremendous public health implications.