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OBJECTIVES This study sought to evaluate the long-term differences in survival between multiple arterial grafts (MAG) and single arterial grafts (SAG) in patients who underwent coronary artery bypass grafting (CABG) in the SYNTAX study. METHODS The present analysis included the randomized and registry-treated CABG patients (n = 1509) from the SYNTAX Extended Survival study (SYNTAXES). Patients with only venous (n = 42) or synthetic grafts (n = 1) were excluded. The primary end point was all-cause death at the longest follow-up. Multivariable Cox regression was used to adjust for differences in baseline characteristics. Sensitivity analysis using propensity matching with inverse probability for treatment weights was performed. RESULTS Of the 1466 included patients, 465 (31.7%) received MAG and 1001 (68.3%) SAG. Patients receiving MAG were younger and at lower risk. At the longest follow-up of 12.6 years, all-cause death occurred in 23.6% of MAG and 40.0% of SAG patients [adjusted hazard ratio (HR) 0.74, 95% confidence interval (CI) (0.55–0.98); P = 0.038], which was confirmed by sensitivity analysis. MAG in patients with the three-vessel disease was associated with significant lower unadjusted and adjusted all-cause death at 12.6 years [adjusted HR 0.65, 95% CI (0.44–0.97); P = 0.033]. In contrast, no significance was observed after risk adjustment in patients with the left main disease, with and without diabetes, or among SYNTAX score tertiles. CONCLUSIONS In the present post hoc analysis of all-comers patients from the SYNTAX trial, MAG resulted in markedly lower all-cause death at 12.6-year follow-up compared to a SAG strategy. Hence, this striking long-term survival benefit of MAG over SAG encourages more extensive use of multiple arterial grafting in selected patients with reasonable life expectancy. Trial registration SYNTAXES ClinicalTrials.gov reference: NCT03417050; SYNTAX ClinicalTrials.gov reference: NCT00114972.

Background Vascular and bleeding complications are common after transcatheter aortic valve implantation (TAVI) and are associated with worse outcomes. The plug-based Manta (M) vascular closure device (VCD) is a novel option to achieve haemostasis for large-bore arterial access sites. Objective We aimed to compare vascular and bleeding complications between the M-VCD and the established suture-based Perclose ProGlide (P)-VCD. Methods From February to September 2019 a total of 578 patients underwent transfemoral TAVI at a single high-volume centre. Access site closure was performed using M-VCD in 195 patients (33.7%) and P-VCD in 383 patients (66.3%). We assessed vascular and access site-related complications as well as bleeding events according to the Valve Academic Research Consortium-2 definition. Results Overall vascular complications occurred less frequently in the M-VCD group (10.7% vs. 19.0%, p = 0.011) driven by a significantly lower rate of major vascular events (2.0% vs. 6.5%, p = 0.025). Access site-related complications were significantly less frequent in the M-VCD cohort (10.7% vs. 16.6%, p = 0.048). The M-VCD was associated with significantly lower rates of major (0.5% vs. 4.4%, p = 0.009) and life-threatening bleeding (0% vs. 2.3%, p = 0.032). In multivariable analysis, the use of M-VCD was the only independent predictor of vascular complications (odds ratio 0.54, 95% confidence interval 0.32–0.91, p = 0.022). Conclusions The M-VCD was associated with a reduction of vascular and access-site complications as well as severe bleeding after transfemoral TAVI compared to the P-VCD in this observational study.

Objectives To analyze the ability of machine-learning (ML)-based computed tomography (CT)-derived fractional flow reserve (CT-FFR) to further improve the diagnostic performance of coronary...

Background: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. Methods: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site– or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site– or access-related bleeding, VCD failure, and time to hemostasis. Results: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07–2.44], P =0.029). Access site– or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91–2.73], P =0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40–1.82], P =0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32–180] versus 240 [174–316] seconds, P Conclusions: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site– or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04459208.

Zusammenfassung. Hintergrund: Eine Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Kindesalter stellt einen Risikofaktor für Substanzmissbrauch und Störungen durch Substanzgebrauch (Substance Use Disorder, SUD) in der Pubertät und dem (frühen) Erwachsenenalter dar. ADHS und SUD treten auch häufig bei therapiesuchenden Jugendlichen auf, was die Diagnosestellung und Therapie erschwert sowie mit schlechten Behandlungsergebnissen verbunden ist. Forschungsergebnisse über die Wirkung der Behandlung von ADHS im Kindesalter auf die Prävention von SUD im Jugendalter sind nicht eindeutig und Studien über die Diagnose und Behandlung von Jugendlichen mit ADHS und SUD sind selten. Daher reicht die verfügbare Evidenz allgemein nicht aus, um starke Behandlungsempfehlungen zu rechtfertigen. Fragestellung: Ziel dieser Arbeit war es, eine Konsenserklärung auf der Grundlage von wissenschaftlichen Daten und klinischen Erfahrungen zu erhalten. Methodik: Es wurde eine modifizierte Delphi-Studie durchgeführt, um basierend auf der Kombination von wissenschaftlichen Daten und klinischer Erfahrung mit einer multidisziplinären Gruppe von 55 Expert_innen aus 17 Ländern einen Konsens zu erzielen. Die Expert_innen wurden gebeten, eine Reihe von Aussagen über die Wirkung der Behandlung von ADHS im Kindesalter auf die SUD bei Jugendlichen sowie über das Screening, die Diagnostik und die Behandlung von Jugendlichen mit komorbidem ADHS und SUD zu bewerten. Ergebnisse: Nach drei iterativen Bewertungsrunden und der Anpassung von 37 Aussagen wurde ein Konsens über 36 dieser Aussagen erzielt, die sechs Bereiche repräsentieren: allgemein ( n = 4), Risiko der Entwicklung einer SUD ( n = 3), Screening und Diagnostik ( n = 7), psychosoziale Behandlung ( n = 5), pharmakologische Behandlung ( n = 11) und komplementäre Behandlungen ( n = 7). Der Einsatz von Routinescreenings auf ADHS wird bei adoleszenten Patient_innen in einer Suchtbehandlung ebenso wie Routinescreenings auf SUD bei jugendlichen Patient_innen mit ADHS in allgemeinpsychiatrischen Therapiesettings empfohlen. Langwirksame Stimulanzien werden als Behandlung der ersten Wahl von ADHS bei Jugendlichen mit gleichzeitiger ADHS und SUD empfohlen. Die Pharmakotherapie sollte vorzugsweise in psychosoziale Behandlung eingebettet werden. Die einzige nichtkonsentierte Aussage betraf die Notwendigkeit von Abstinenz vor Beginn einer pharmakologischen Behandlung bei Jugendlichen mit ADHS und gleichzeitigem SUD. Im Gegensatz zur Mehrheit verlangten einige Expert_innen eine vollständige Abstinenz vor Beginn einer pharmakologischen Behandlung, einige waren gegen die Verwendung von Stimulanzien bei der Behandlung dieser Patient_innen (unabhängig von Abstinenz), während einige sich gegen die alternative Anwendung von Bupropion aussprachen. Schlussfolgerungen: Diese internationale Konsenserklärung kann von Kliniker_innen und Patient_innen zusammen in einem gemeinsamen Entscheidungsprozess genutzt werden, um die besten Interventionen auszuwählen und die bestmöglichen Ergebnisse bei adoleszenten Patient_innen mit gleichzeitiger ADHS und SUD zu erzielen.

Aim The aim of this study was to compare long-term all-cause mortality between patients receiving percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) using multiple (MAG) or single arterial grafting (SAG). Methods and results The current study is a post hoc analysis of the SYNTAX Extended Survival Study, which compared PCI with CABG in patients with three-vessel (3VD) and/or left main coronary artery disease (LMCAD) and evaluated survival with ≥10 years of follow-up. The primary endpoint was all-cause mortality at maximum follow-up (median 11.9 years) assessed in the as-treated population. Of the 1743 patients, 901 (51.7%) underwent PCI, 532 (30.5%) received SAG, and 310 (17.8%) had MAG. At maximum follow-up, all-cause death occurred in 305 (33.9%), 175 (32.9%), and 70 (22.6%) patients in the PCI, SAG, and MAG groups, respectively (P Conclusion Our findings suggest that MAG might be the more desirable configuration for CABG to achieve lower long-term all-cause mortality than PCI in patients with 3VD and/or LMCAD. Trial registration Registered on clinicaltrial.gov. SYNTAXES: NCT03417050 (https://clinicaltrials.gov/ct2/show/NCT03417050); SYNTAX: NCT00114972 (https://www.clinicaltrials.gov/ct2/show/NCT00114972).

Halting transmission The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein binds to host cells and initiates membrane fusion and cell infection. This stage in the virus life history is currently a target for drug inhibition. De Vries et al. designed highly stable lipoprotein fusion inhibitors complementary to a conserved repeat in the C terminus of S that integrate into host cell membranes and inhibit conformational changes in S necessary for membrane fusion. The authors tested the performance of the lipoproteins as a preexposure prophylactic in a ferret-to-ferret transmission study. Intranasal administration of the peptide 2 days before cohousing with an infected ferret for 24 hours completely protected animals in contact from infection and showed efficacy against mutant viruses. Because ferrets do not get sick from SARS-CoV-2, disease prevention could not be tested in this model. Science, this issue p. 1379, A dimeric form of a SARS-CoV-2–derived lipopeptide is a potent inhibitor of fusion and infection in vitro and transmission in vivo., Containment of the COVID-19 pandemic requires reducing viral transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by membrane fusion between the viral and host cell membranes, which is mediated by the viral spike protein. We have designed lipopeptide fusion inhibitors that block this critical first step of infection and, on the basis of in vitro efficacy and in vivo biodistribution, selected a dimeric form for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour cohousing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and thus may readily translate into safe and effective intranasal prophylaxis to reduce transmission of SARS-CoV-2.

Due to their immunomodulatory and regenerative capacity, human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising in the treatment of patients suffering from polytrauma. However, few studies look at the effects of sera from polytraumatized patients on hBMSCs. The aim of this study was to explore changes in hBMSC properties in response to serum from polytrauma patients taken at different time points after the trauma incident. For this, sera from 84 patients with polytrauma (collected between 2010 and 2020 in our department) were used. In order to test the differential influence on hBMSC, sera from the 1st (D1), 5th (D5), and 10th day (D10) after polytrauma were pooled, respectively. As a control, sera from three healthy donors (HS), matched with respect to age and gender to the polytrauma group, were collected. Furthermore, hBMSCs from four healthy donors were used in the experiments. The pooled sera of HS, D1, D5, and D10 were analyzed by multicytokine array for pro-/anti-inflammatory cytokines. Furthermore, the influence of the different sera on hBMSCs with respect to cell proliferation, colony forming unit-fibroblast (CFU-F) assay, cell viability, cytotoxicity, cell migration, and osteogenic and chondrogenic differentiation was analyzed. The results showed that D5 serum significantly reduced hBMSC cell proliferation capacity compared with HS and increased the proportion of dead cells compared with D1. However, the frequency of CFU-F was not reduced in polytrauma groups compared with HS, as well as the other parameters. The serological effect of polytrauma on hBMSCs was related to the time after trauma. It is disadvantageous to use BMSCs in polytraumatized patients at least until the fifth day after polytrauma as obvious cytological changes could be found at that time point. However, it is promising to use hBMSCs to treat polytrauma after five days, combined with the concept of “Damage Control Orthopedics” (DCO).

Zusammenfassung Fragestellung (Teil-)stationäre Psychotherapie ist in Deutschland gut implementiert. Um Wirksamkeitsfaktoren und Effekte besser zu verstehen, sind Effektivitätsstudien notwendig. Diese naturalistische Studie untersucht die Effektivität stationärer und teilstationärer Psychotherapie sowie patientenzentrierte und störungsbezogene Einflussfaktoren auf individuelle Symptomverbesserungen. Methoden Analysiert werden Patient*innen einer psychosomatisch-psychotherapeutischen Universitätsklinik, die in den Jahren 2015 bis 2019 behandelt wurden und das BSI-18 entweder bei Aufnahme und Entlassung (N=1366) oder bei Aufnahme und Dreimonatskatamnese (N=497) ausfüllten. Ergebnisse Die Verbesserungen in der globalen Symptomschwere zeigen moderate Effektstärken. Deskriptiv sind diese größer bei teilstationärer als bei stationärer Behandlung–besonders im Follow-up-Vergleich (direkt nach Entlassung: dstationär=0.401, dteilstationär=0,482; drei Monate nach Entlassung: dstationär=0,403, dteilstationär=0,807). Die teilstationären unterscheiden sich signifikant von den stationären Patient*innen – gering in Alter, Beschäftigungsstatus, Arbeitsfähigkeit und initialen Symptombelastungen, moderat in der Anzahl psychischer Komorbiditäten und stark in ihren Hauptdiagnosen. Soziodemographische Faktoren zeigen keinen, die initiale Symptomschwere einen moderaten positiven und die Anzahl psychischer Komorbiditäten einen komplexen Einfluss auf die Symptomverbesserungen. Diskussion Allgemein bestätigt diese Studie die Wirksamkeit (teil-)stationärer psychosomatischer Therapie. Die Relevanz teilstationärer Angebote wird vor dem Hintergrund von Kosteneffizienz und guter Integration in den Alltag betont, unter Beachtung individueller Behandlungsindikationen.

Objectives To investigate plaque inhibition of 0.1% octenidine mouthwash (OCT) vs. placebo over 5 days in the absence of mechanical plaque control. Materials and methods For this randomized, placebo-controlled, double-blind, parallel group, multi-center phase 3 study, 201 healthy adults were recruited. After baseline recording of plaque index (PI) and gingival index (GI), collection of salivary samples, and dental prophylaxis, subjects were randomly assigned to OCT or placebo mouthwash in a 3:1 ratio. Rinsing was performed twice daily for 30 s. Colony forming units in saliva were determined before and after the first rinse. At day 5, PI, GI, and tooth discoloration index (DI) were assessed. Non-parametric van Elteren tests were applied with a significance level of p Results Treatment with OCT inhibited plaque formation more than treatment with placebo (PI: 0.36 vs. 1.29; p p = 0.003) and salivary bacterial counts (2.73 vs. placebo 0.24 lgCFU/ml; p p = 0.0011). Mild tongue staining and dysgeusia occurred. Conclusions OCT 0.1% mouthwash inhibits plaque formation over 5 days. It therefore can be recommended when regular oral hygiene is temporarily compromised. Clinical relevance When individual plaque control is compromised, rinsing with octenidine mouthwash is recommended to maintain healthy oral conditions while side effects are limited.

Background: The significant interaction between major infection and 5-year mortality after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for complex coronary artery disease (CAD) was observed previously. However, the very long-term outcomes beyond 5 years remains unclear. Methods and results: This is a subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the randomized SYNTAX trial comparing PCI versus CABG in patients with three-vessel disease (3VD) or left-main CAD (LMCAD). Out of 1517 patients enrolled in the SYNTAX trial with available survival status from 5 to 10 years, 140 patients had experienced major infections and survived at 5 years (major infection group). From 5 to 10 years, the mortality of major infection group was 19.8% whereas the mortality of no major infection group was 15.1% (p = 0.157). After the adjustment of other clinical factors, the risk of mortality from 5 to 10 years did not significantly differ between major infection and no major infection groups (HR: 1.10; 95% CI: 0.62–1.96; p = 0.740). When stratified by the presence or absence of periprocedural major infections, defined as a major infection within 60 days after index procedure, there was also no significant difference in 10-year mortality between two groups (30.8% vs. 24.5%; p = 0.057). Conclusions: Despite the initial association between major infections and 5 years mortality, postprocedural major infection was not evident in the 10 years follow-up, suggesting that the impact of major infection on mortality subsided over time beyond 5 years. Trial registration: SYNTAXES ClinicalTrials.gov reference: NCT03417050 SYNTAX ClinicalTrials.gov reference: NCT00114972

Objectives The aim of this study was to evaluate clinical characteristics, mechanisms of failure, and outcomes of transcatheter aortic valve replacement (TAVR) explantation. Background Surgical explantation following TAVR may be required for structural valve degeneration, paravalvular leak, infection, or other reasons. However, in-depth data on indications and outcomes are lacking. Methods Data from a multicenter, international registry (EXPLANT-TAVR) of patients who underwent TAVR explantation were reviewed retrospectively. Explantations performed during the same admission as initial TAVR were excluded. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 6.7 months (interquartile range [IQR]: 1.0-18.8 months) after TAVR explantation and was 97.7% complete at 30 days and 86.1% complete at 1 year. Results From November 2009 to September 2020, 269 patients across 42 centers with a mean age of 72.7 ± 10.4 years underwent TAVR explantation. About one quarter (25.9%) were deemed low surgical risk at index TAVR, and median Society of Thoracic Surgeons risk at TAVR explantation was 5.6% (IQR: 3.2%-9.6%). The median time to explantation was 11.5 months (IQR: 4.0-32.4 months). Balloon-expandable and self-expanding or mechanically expandable valves accounted for 50.9% and 49.1%, respectively. Indications for explantation included endocarditis (43.1%), structural valve degeneration (20.1%), paravalvular leak (18.2%), and prosthesis-patient mismatch (10.8%). Redo TAVR was not feasible because of unfavorable anatomy in 26.8% of patients. Urgent or emergency cases were performed in 53.1% of patients, aortic root replacement in 13.4%, and 54.6% had concomitant cardiac procedures. Overall survival at last follow-up was 76.1%. In-hospital, 30-day, and 1-year mortality rates were 11.9%, 13.1%, and 28.5%, respectively, and stroke rates were 5.9%, 8.6%, and 18.7%, respectively. Conclusions The EXPLANT-TAVR registry reveals that surgical risks associated with TAVR explantation are not negligible and should be taken into consideration in the lifetime management of aortic stenosis.

Objectives The aim of this study was to determine clinical and echocardiographic characteristics, mechanisms of failure, and outcomes of mitral valve (MV) surgery after transcatheter edge-to-edge repair (TEER). Background Although >100,000 mitral TEER procedures have been performed worldwide, longitudinal data on MV surgery after TEER are lacking. Methods Data from the multicenter, international CUTTING-EDGE registry were retrospectively analyzed. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 9.0 months (interquartile range [IQR]: 1.2-25.7 months) after MV surgery, and follow-up was 96.1% complete at 30 days and 81.1% complete at 1 year. Results From July 2009 to July 2020, 332 patients across 34 centers underwent MV surgery after TEER. The mean age was 73.8 ± 10.1 years, median Society of Thoracic Surgeons risk for MV repair at initial TEER was 4.0 (IQR: 2.3-7.3), and primary/mixed and secondary mitral regurgitation were present in 59.0% and 38.5%, respectively. The median interval from TEER to surgery was 3.5 months (IQR: 0.5-11.9 months), with overall median Society of Thoracic Surgeons risk of 4.8% for MV replacement (IQR: 2.8%-8.4%). The primary indication for surgery was recurrent mitral regurgitation (33.5%), and MV replacement and concomitant tricuspid surgery were performed in 92.5% and 42.2% of patients, respectively. The 30-day and 1-year mortality rates were 16.6% and 31.3%, respectively. On Kaplan-Meier analysis, the actuarial estimates of mortality were 24.1% at 1 year and 31.7% at 3 years after MV surgery. Conclusions In this first report of the CUTTING-EDGE registry, the mortality and morbidity risks of MV surgery after TEER were not negligible, and only

SARS-CoV-2 infection—which involves both cell attachment and membrane fusion—relies on the angiotensin-converting enzyme 2 (ACE2) receptor, which is paradoxically found at low levels in the respiratory tract1–3, suggesting that there may be additional mechanisms facilitating infection. Here we show that C-type lectin receptors, DC-SIGN, L-SIGN and the sialic acid–binding immunoglobulin-like lectin 1 (SIGLEC1) function as attachment receptors by enhancing ACE2-mediated infection and modulating the neutralizing activity of different classes of spike-specific antibodies. Antibodies to the amino-terminal domain or to the conserved site at the base of the receptor-binding domain, while poorly neutralizing infection of ACE2-overexpressing cells, effectively block lectin-facilitated infection. Conversely, antibodies to the receptor binding motif, while potently neutralizing infection of ACE2-overexpressing cells, poorly neutralize infection of cells expressing DC-SIGN or L-SIGN and trigger fusogenic rearrangement of the spike, promoting cell-to-cell fusion. Collectively, these findings identify a lectin-dependent pathway that enhances ACE2-dependent infection by SARS-CoV-2 and reveal distinct mechanisms of neutralization by different classes of spike-specific antibodies. C-type lectins and SIGLEC1 function as attachment receptors for SARS-CoV-2 and enhance ACE2-mediated infection.

Exposure is a highly effective treatment for pathological fear and anxiety, but rarely used in routine care. Issues of practicability and lack of therapists in rural areas are main barriers for the dissemination of exposure. Smartglass devices may enable therapists to guide exposure from their own office via real-time feedback and may thereby increase practicability. The present study explored the technological usability and clinical feasibility of Smartglass-guided exposure in a behavioral approach test in spider-fearful individuals (N = 40). Fearful individuals were asked to start the Smartglass themselves and established a connection to a therapist, who guided the exposure test from afar. Clinical severity of spider fear was assessed via questionnaire. Technological usability was assessed with established measures of usability, user experience, and user acceptance. Exploratory, individual characteristics of exposure were collected (e.g., within-session fear reduction, duration, safety behavior). Overall, fearful individuals (94.9%) and therapists (100%) were able to establish a connection. Usability of Smartglass-guided exposure was evaluated as positive. Within-session fear reduction was large (d = 1.91). Adverse events were minimal. There were, however, some associations between exposure characteristics and usability evaluation (e.g., lower user-friendliness and exposure duration). Two case examples further highlight chances and risks of Smartglass-guided exposure. These findings provide first evidence that Smartglass-guided exposure could be useful in exposure therapy. Smartglass-guided exposure may ultimately help to increase practicability of exposure and increase dissemination, also in rural areas. These findings are promising for future research on the long-term outcome of evidence-based exposure in treatment seeking patients.

Objectives To systematically review the prevalence of bacteraemia, triggered by dental intervention and home oral hygiene practices, in children. The network meta-analysis (NMA) quantitatively compared the risk of bacteraemia triggered by dental extractions and home and professional cleaning procedures. Materials and methods Clinical trials with the outcome 'bacteraemia in children' were searched. The NMA was performed using the frequentist weighted least-squares approach comparing the odds ratios (OR) of different interventions. Results Among 11 of 13 studies, dental treatment was performed under general anaesthesia. In 2,381 patients, bacteraemia occurred in 38.7-56% patients following single-tooth extractions, in 22-46% after manual toothbrushing (MTB), and in 26-78% after power toothbrushing (PTB). When MTB was set as the reference (OR 1), rubber cup polishing showed a slightly higher risk (OR 1.26) of bacteraemia. PTB presented a higher risk (OR 1.79-2.27) than with single-tooth extractions (OR 1.55) but lower than that with multiple extractions (OR 2.55). Conclusion Daily use of MTB and routine professional cleaning were associated with the lowest risk of developing bacteraemia in children with gingivitis, almost as much as with a single-tooth extractions. Improved plaque control with PTB increased the risk of bacteraemia. There is limited evidence on gingivitis-free and systemically-diseased children.

Numerous studies have demonstrated a paradoxical association between higher baseline body mass index (BMI) and lower long-term mortality risk after coronary revascularization, known as the “obesity paradox”, possibly relying on the single use of BMI. The current study is a post-hoc analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the SYNTAX trial comparing percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in patients with left-main coronary artery disease (LMCAD) or three-vessel disease (3VD). Patients were stratified according to baseline BMI and/or waist circumference (WC). Out of 1,800 patients, 1,799 (99.9%) and 1,587 (88.2%) had available baseline BMI and WC data, respectively. Of those, 1,327 (73.8%) patients had High BMI (≥25 kg/m2), whereas 705 (44.4%) patients had High WC (>102 cm for men or >88 cm for women). When stratified by both BMI and WC, 10-year mortality risk was significantly higher in patients with Low BMI/Low WC (adjusted hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 1.09 to 2.51), Low BMI/ High WC (adjusted HR: 2.74; 95% CI: 1.12 to 6.69), or High BMI/High WC (adjusted HR: 1.59; 95% CI: 1.11 to 2.27) compared to those with High BMI/Low WC. In conclusion, the “obesity paradox” following coronary revascularization would be driven by low long-term mortality risk of the High BMI/Low WC group. Body composition should be assessed by the combination of BMI and WC in the appropriate evaluation of the long-term risk of obesity in patients with LMCAD or 3VD.

Background: The benefit of optimal medical therapy (OMT) on 5-year outcomes in patients with 3-vessel disease and/or left main disease after percutaneous coronary intervention or coronary artery bypass grafting (CABG) was demonstrated in the randomized SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. Objectives: The objective of this analysis is to assess the impact of the status of OMT at 5 years on 10-year mortality after percutaneous coronary intervention or CABG. Methods: This is a subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which evaluated for up to 10 years the vital status of patients who were originally enrolled in the SYNTAX trial. OMT was defined as the combination of 4 types of medications: at least 1 antiplatelet drug, statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. After stratifying participants by the number of individual OMT agents at 5 years and randomized treatment, a landmark analysis was conducted to assess the association between treatment response and 10-year mortality. Results: In 1,472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; 95% CI: 0.292-0.757; P = 0.002) but had a mortality similar to those on 3 types of medications. Furthermore, patients undergoing CABG with the individual OMT agents, antiplatelet drug and statin, at 5 years had lower 10-year mortality than those without. Conclusions: In patients with 3-vessel and/or left main disease undergoing percutaneous coronary intervention or CABG, medication status at 5 years had a significant impact on 10-year mortality. Patients on OMT with guideline-recommended pharmacologic therapy at 5 years had a survival benefit. (Synergy Between PCI With Taxus and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Zusammenfassung Hintergrund Im Rettungsdienst können, im Gegensatz zum stationären Setting, adäquate Dolmetscher häufig nicht ohne Weiteres hinzugezogen werden. Gleichzeitig erfordern Notfallsituationen aber eine rasche Anamnese und ein Assessment als Basis für jedes therapeutische Handeln. Material und Methoden Eine Smartphone-App, die auf 18 Sprachen eine basale Kommunikation mittels 600 fest eingesprochener unterschiedlicher Phrasen auf 20 Sprachen ermöglicht, wurde über 6 Monate in vier Rettungswachen pilotiert. Abschließend wurde die Nutzbarkeit der App durch das gesamte Rettungsdienstpersonal in einer Fragebogenstudie unter Verwendung des System Usability Scores und des AttrakDiff-Fragebogens bewertet. Ergebnisse Die Rücklaufquote betrug 48,5 % und n = 48 Fragebögen wurden ausgewertet. Das Durchschnittsalter der Befragten betrug 36 Jahre und fast zwei Drittel waren männlichen Geschlechts. Der System Usability Score zeigte im Median 67,5 Punkte, was eine grenzwertig gute Nutzbarkeit zeigte. Im AttrakDiff-Fragebogen zeigte sich die pragmatische Qualität mit durchschnittlich 0,69 (SD 0,86), die hedonische Qualität mit 0,59 (SD 0,58) und die Attraktivität (ATT) mit 0,64 Punkten (SD 0,83). Die Durchschnittswerte zeigen zufriedenstellende Werte jeweils oberhalb der neutral markierenden Grenze von 0. Auffällig zeigte sich, dass in wesentlichen Bewertungskriterien diejenigen Rettungsdienstkräfte, die angaben, die App bereits aktiv im Einsatz mit Patienten genutzt zu haben, die App signifikant besser einschätzten. Diskussion Vor dem Hintergrund, dass es sich bei der untersuchten App um ein komplexes Arbeitswerkzeug handelt, werden die Nutzbarkeit und Attraktivität als insgesamt gut eingeschätzt, wobei in der Nutzung erfahrene Rettungskräfte diese noch positiver einschätzten. Dies könnte auf eine Art Schwellenangst hindeuten, einer bereits durch Sprach- und kulturelle Barrieren geprägten Rettungssituation mit einer ebenfalls recht komplexen Intervention zu begegnen.

Effective clinical intervention strategies for coronavirus disease 2019 (COVID-19) are urgently needed. Although several clinical trials have evaluated use of convalescent plasma containing virus-neutralizing antibodies, levels of neutralizing antibodies are usually not assessed and the effectiveness has not been proven. We show that hamsters treated prophylactically with a 1:2560 titer of human convalescent plasma or a 1:5260 titer of monoclonal antibody were protected against weight loss, had a significant reduction of virus replication in the lungs, and showed reduced pneumonia. Interestingly, this protective effect was lost with a titer of 1:320 of convalescent plasma. These data highlight the importance of screening plasma donors for high levels of neutralizing antibodies. Our data show that prophylactic administration of high levels of neutralizing antibody, either monoclonal or from convalescent plasma, prevent severe SARS-CoV-2 pneumonia in a hamster model, and could be used as an alternative or complementary to other antiviral treatments for COVID-19.

Background: The optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear. Objectives: The goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD). Methods: In the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models. Results: Among 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; pinteraction = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; pinteraction = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: −0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients. Conclusions: Elderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050) (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Objectives A new oral care nursing plan format for improved communication among dentists, nursing staff, and caregivers has been developed in Germany. We aimed to (1) describe this plan, (2) investigate the prevalence of oral health problems among elderly patients with care needs documented by the plan, and outline the recommendations in the plans, and (3) investigate whether the accommodation costs or care needs of patients influenced oral care quality or the need for oral hygiene support documented within the plan. Methods In this cross-sectional trial, oral care nursing plans were collected from outpatient and inpatient care clinics. Items on the oral care nursing plan were divided into three areas (oral health, oral hygiene needs, coordination needs and dental therapy), and were correlated with care level and accommodation costs. Results Oral care nursing plans were collected from seven dentists (N = 747; 94.5% from inpatient, 5.5% from outpatient care). The plans enabled documentation of well-known oral health and hygiene problems among elderly patients. In their current form, the plans provided recommendations for obvious oral hygiene tasks such as toothbrushing or fluoridating, rather than specialized tasks such as nutritional advice or dry mouth asymptomatic therapeutic approaches. While accommodation costs were associated with the need for oral hygiene support (not with oral care condition), the care level influenced both measures. Conclusions The oral care nursing plan can facilitate documentation of oral health and hygiene among elderly individuals with care needs. Further clarification of the plan would help promote careful documentation by dentists.

Background Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient’s conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. Methods Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient’s comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. Discussion The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD. Trial registration ClinicalTrials.gov Identifier: NCT04831073.

Underlying pathomechanisms of osteoporosis are still not fully elucidated. Cell-based therapy approaches pose new possibilities to treat osteoporosis and its complications. The aim of this study was to quantify differences in human bone marrow-derived mesenchymal stem cells (hBMSCs) between healthy donors and those suffering from clinically manifest osteoporosis. Cell samples of seven donors for each group were selected retrospectively from the hBMSC cell bank of the Trauma Department of Hannover Medical School. Cells were evaluated for their adipogenic, osteogenic and chondrogenic differentiation potential, for their proliferation potential and expression of surface antigens. Furthermore, a RT2 Osteoporosis Profiler PCR array, as well as quantitative real-time PCR were carried out to evaluate changes in gene expression. Cultivated hBMSCs from osteoporotic donors showed significantly lower cell surface expression of CD274 (4.98 % ± 2.38 %) than those from the control group (26.03 % ± 13.39 %; p = 0.007), as assessed by flow cytometry. In osteoporotic patients, genes involved in inhibition of the anabolic WNT signalling pathway and those associated with stimulation of bone resorption were significantly upregulated. Apart from these changes, no significant differences were found for the other cell surface antigens, adipogenic, osteogenic and chondrogenic differentiation ability as well as proliferation potential. These findings supported the theory of an influence of CD274 on the regulation of bone metabolism. CD274 might be a promising target for further investigations of the pathogenesis of osteoporosis and of cell-based therapies involving MSCs.

Recent advances in artificial intelligence, particularly in the field of deep learning, have enabled researchers to create compelling algorithms for medical image analysis. Histological slides of basal cell carcinomas (BCCs), the most frequent skin tumor, are accessed by pathologists on a daily basis and are therefore well suited for automated prescreening by neural networks for the identification of cancerous regions and swift tumor classification. In this proof-of-concept study, we implemented an accurate and intuitively interpretable artificial neural network (ANN) for the detection of BCCs in histological whole-slide images (WSIs). Furthermore, we identified and compared differences in the diagnostic histological features and recognition patterns relevant for machine learning algorithms vs. expert pathologists. An attention-ANN was trained with WSIs of BCCs to identify tumor regions (n = 820). The diagnosis-relevant regions used by the ANN were compared to regions of interest for pathologists, detected by eye-tracking techniques. This ANN accurately identified BCC tumor regions on images of histologic slides (area under the ROC curve: 0.993, 95% CI: 0.990–0.995; sensitivity: 0.965, 95% CI: 0.951–0.979; specificity: 0.910, 95% CI: 0.859–0.960). The ANN implicitly calculated a weight matrix, indicating the regions of a histological image that are important for the prediction of the network. Interestingly, compared to pathologists’ eye-tracking results, machine learning algorithms rely on significantly different recognition patterns for tumor identification (p