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Omicron is the evolutionarily most distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) to date. We report that Omicron BA.1 breakthrough infection in BNT162b2-vaccinated individuals resulted in strong neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 VOCs but not against the Omicron sublineages BA.4 and BA.5. BA.1 breakthrough infection induced a robust recall response, primarily expanding memory B (BMEM) cells against epitopes shared broadly among variants, rather than inducing BA.1-specific B cells. The vaccination-imprinted BMEM cell pool had sufficient plasticity to be remodeled by heterologous SARS-CoV-2 spike glycoprotein exposure. Whereas selective amplification of BMEM cells recognizing shared epitopes allows for effective neutralization of most variants that evade previously established immunity, susceptibility to escape by variants that acquire alterations at hitherto conserved sites may be heightened.
Einleitung: Die Wiederverwendung resterilisierter PTCA Ballonkatheter wird in Herzzentren weltweit in steigendem Maße durchgeführt, obwohl die Ballonkatheter vom Hersteller nur zum Einmalgebrauch zugelassen sind. Methoden: Diese prospektive in vitro Studie untersucht die Qualität von PTCA Ballonkathetern nach dreimaliger Resterilisation. Vierzig PTCA Ballonkatheter zweier unterschiedlicher Hersteller (mit den jeweiligen Nominaldiametern von 1,5 mm und 3,0 mm) wurden ausgewählt. In enger Zusammenarbeit mit dem Kunststoffzentrum in Leipzig haben wir die mechanischen Parameter wie den Berstdruck, den Nominaldiameter, das Durchtrittsprofil (crossing profile) und die Ballonoberfläche untersucht. Ergebnisse: Das Durchtrittsprofil steigt um 22,5% bis 39,2% (± 4,69% bis ± 19%), ohne zusätzliche Schädigung der Ballonoberfläche nach wiederholter Resterilisation. Der Nominaldiameter steigt oder fallt mit einem Maximum von 47% (n=I). Bei den 1,5 mm grossen Ballonkathetern bleibt der Berstdruck oberhalb des Berstdruckwertes der Hersteller, wobei es bei den 3,0 mm grossen Ballonkathetern zu einem Absinken des Berstdrucks um 40% (n=l) bis 50% (n=l) kommt. Schlussfolgerung: Unsere Ergebnisse zeigen bei beiden untersuchten Ballonkathetern im Verlauf einen Rückgang der Qualitätsparameter bei bis zu dreimaliger Resterilisation. Trotzdem können die therapeutischen Kurz- und Langzeiterfolge des Einsatzes resterilisierter PTCA Ballonkatheter nur in einer randomisierten klinischen Studie untersucht und interpretiert werden. Durch unsere Studie wurde jedoch dafiir die mechanisch-physikalische Grundlage geliefert.
For medicine to fulfill its promise of personalized treatments based on a better understanding of disease biology, computational and statistical tools must exist to analyze the increasing amount of patient data that becomes available. A particular challenge is that several types of data are being measured to cope with the complexity of the underlying systems, enhance predictive modeling and enrich molecular understanding.
Here we review a number of recent approaches that specialize in the analysis of multimodal data in the context of predictive biomedicine. We focus on methods that combine different OMIC measurements with image or genome variation data. Our overview shows the diversity of methods that address analysis challenges and reveals new avenues for novel developments.
Aims: To investigate real-world clinical and patient-related variables associated with initiating GLP-1 receptor agonist (GLP-1RA) treatment relative to initiation of other glucose-lowering therapies in type 2 diabetes (T2D) patients of primary care in Germany.
Methods: Data for 938 T2D patients who started therapy with a GLP-1RA within 823 practices of primary care throughout Germany were retrospectively analyzed (Disease Analyser: 01/2011–03/2014). 5,197 T2D patients who initiated other non-GLP-1RA antidiabetic therapies were selected as controls. Multivariate logistic regression analyses were applied to identify factors associated with GLP-1RA initiation in primary care.
Results: Mean age (SD) of GLP-1RA users was 57.8 (11.8) years (males: 55.5%) and the average BMI was 36.1 (6.7) kg/m2. 22.8% were in diabetologist care and 12.0% had private health insurance. In multivariate regression, choice of GLP-1RA therapy instead of a different glucose-lowering drug class was associated with obesity (odds ratio: 1.68; 95% CI: 1.34–2.10), private health insurance (2.42; 1.89–3.09), younger age (0.94; 0.93–0.95 per year), male sex (0.85; 0.73–0.99), diabetologist care (2.11; 1.73–2.57), and geographic practice location (East vs. West-Germany; 1.25; 1.05–1.49). Among co-medication, angiotensin II antagonists (increased) and non-steroidal antirheumatic agents (decreased) were related to GLP-1RA prescriptions (both p<0.001).
Conclusions: Consistent with German guidelines, GLP-1RA is mainly prescribed preferentially in T2D patients who are obese. GLP-1RA drugs were more frequently used than other options in privately health insured patients and in patients seeing a diabetologist.
AIM: To evaluate and compare the effect of combined transarterial chemoembolization (TACE) and arterial administration of Bletilla striata (a Chinese traditional medicine against liver tumor) versus TACE alone for the treatment of hepatocellular carcinoma (HCC) in ACI rats.
METHODS: Subcapsular implantation of a solid Morris hepatoma 3 924A (2 mm3) in the liver was carried out in 30 male ACI rats. Tumor volume (V1) was measured by magnetic resonance imaging (MRI) on day 13 after implantation. The following different agents of interventional treatment were injected after retrograde catheterization via gastroduodenal artery (on day 14), namely, (A) TACE (0.1 mg mitomycin + 0.1 ml Lipiodol) + Bletilla striata (1.0 mg) (n=10); (B) TACE + Bletilla striata (1.0 mg) + ligation of hepatic artery (n=10), (C) TACE alone (control group, n=10). Tumor volume (V2) was assessed by MRI (on day 13 after treatment) and the tumor growth ratio (V2/V1) was calculated.
RESULTS: The mean tumor volume before (V1) and after (V2) treatment was 0.0355 cm3 and 0.2248 cm3 in group A, 0.0374 cm3 and 0.0573 cm3 in group B, 0.0380 cm3 and 0.3674 cm3 in group C, respectively. The mean ratio (V2/V1) was 6.2791 in group A, 1.5324 in group B and 9.1382 in group C. Compared with the control group (group C), group B showed significant inhibition of tumor growth (P<0.01), while group A did not (P>0.05). None of the animals died during implantation or in the postoperative period.
CONCLUSION: Combination of TACE and arterial administration of Bletilla striata plus ligation of hepatic artery is more effective than TACE alone in the treatment of HCC in rats.
Background: Following elective craniotomy patients routinely receive monitoring on ICU. However, the benefit of ICU monitoring in these patients is discussed controversially. Due to the current COVID-19 pandemic, there are further limitations of ICU capacities. This study aimed to compare this strategy with a standardized management of post-craniotomy patients on ICU.
Methods: Two postoperative strategies were compared in a matched-pair analysis: The first cohort included patients treated between May-August 2021 according to the “No ICU – unless” concept (NIU group), where patients were managed on the normal ward postoperatively. The second cohort contained patients routinely admitted to the ICU between February-April 2021 (control group). Outcome parameters contained complications, length of stay, duration to first postoperative mobilization, number of unplanned imaging, number/type of ICU interventions and pre- and postoperative mRS. Patient characteristics were analyzed using electronic medical records.
Results: The NIU group consisted of 96 patients, the control group of 75 patients. Complication rates were comparable in both cohorts (16% in NIU vs. 17% in control; p=0.123). Groups did not differ significantly in the number of imaging (10% in NIU vs. 13% in control; p=0.67), in the type of interventions on ICU (antihypertensive therapy 5% (NIU) vs. 6% (control); p=0.825) or in the time to first postoperative mobilization (average 1.1± 1.6 days vs. 0.9± 1.2 days; p=0.402). Length of hospital stay was shorter in the NIU group without reaching statistical significance (average 5.8 vs. 6.8 days; p=0.481). There was no significant change in the distribution of preoperative (p=0.960) and postoperative (p=0.425) mRS scores.
Conclusion: Postoperative ICU management does not reduce postoperative complications and has no effect on the surgical outcome of elective craniotomies. The majority of postoperative complications are detected after a 24-hour observation period. This approach may represent a potential strategy to prevent overutilization of ICU capacities while maintaining sufficient postoperative care for neurosurgical patients.
In dieser Studie haben wir den minimalinvasiven Ersatz bzw. Rekonstuktion der Mitralklappe unter Einsatz des HEARTPORTÒ Port AccessTM - Systems über eine rechtsanterolaterale Thorakotomie und femorale Kanülierung untersucht und 20 minimalinvasiv mit 20 konventionell operierten Patienten verglichen. Ein Nachteil dieser Studie ist, dass die beiden Gruppen mit jeweils 20 Patienten sehr klein sind, um eine zuverlässige statistische Aussage treffen zu können. Außerdem war zu Beginn der Studie die operative Erfahrung mit diesem neuen System noch sehr ausgeprägt, so dass einige technische Probleme auch eventuell einer Lernkurve zugeschrieben werden können. Die hier vorliegenden Daten zeigen, dass die neuere minimalinvasive Methode durchaus mit der etablierten konventionellen Operationstechnik vergleichbar ist. Die Qualität der ersetzten und rekontruierten Mitralklappen ist sehr gut und obwohl es sich hier um das initiale Patietenkollektiv eines neu eingeführten Operationsverfahrens handelt, findet sich nur eine minimal verlängerte Operationsdauer. Intubationsdauer und postoperativer Klinikaufenthalt sind zwar nicht signifikant, aber dennoch tendenziell kürzer als die des konventionellen Kollektivs. Der postoperative Blutverlust ist identisch. Obwohl die postoperativen Ergebnisse gut waren gilt doch hervorzuheben, dass es zu einigen intraoperativen prozedurbezogenen Problemen gekommen ist. Aus diesem Grunde der komplizierten Handhabung des Systems und aus Kostengründen ist in unserer Klinik auf ein ähnliches minimalinvasives Operationsverfahren, das durch Chitwood und Kollegen beschrieben wurde, umgestiegen worden. Bei der Betrachtung der laborchemischen Marker ergeben sich insbesondere für die Kreatinkinase (CK) und Myoglobin signifikant höhere Werte in der minimalinvasiven Patientengruppe. Diese deutliche Erhöhung der Marker der muskulären Schädigung CK und Myoglobin liegt ursächlich in der kanülierungsbedingten Extremitätenischämie und der rechtsanterolateralen Thorakotomie begründet. Für die kardialen Parameter Troponin T und Troponin I, sowie für die neuronalen Marker S-100b und NSE konnte keine Signifikanz ermittelt werden. Die durchgeführten neuropsychologischen Tests zeigten ebenfalls keinen signifikanten Unterschied auf. Insgesamt läßt sich aus den hier vorliegenden initialen Ergebnissen kaum ein Nachteil bei der Verwendung der minimalinvasiven Technik ermitteln. Hinzu kommt noch der offensichtliche Vorteil des kosmetisch besseren Ergebnisses. Allerdings beschränkt sich der Einsatz dieses Verfahrens auf ein sorgfältig ausgewähltes Patientengut, da aufgrund des Risikoprofils vieler Patienten der Einsatz dieser Methode als kontraindiziert gilt. Es handelt sich bei dieser Operationsmethode somit nicht um ein Verfahren, welches die herkömmliche konventionelle Operationsmethode ersetzen könnte. Inwieweit aus dem minimalisierten thorakalen Zugang eine Erhöhung der Thoraxstabilität resultiert und inwieweit sich diese positiv auf Rehabilitationsmaßnahmen auswirkt müssen Folgestudien ergeben.
Background: Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement ‘hotspot’ loci. However, microdeletion burden not overlapping these regions or within different epilepsy subtypes has not been ascertained.
Objective: To decipher the role of microdeletions outside hotspots loci and risk assessment by epilepsy subtype.
Methods: We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1366 patients with genetic generalised epilepsy (GGE) in addition to two sets of additional unpublished genome-wide microdeletions found in 281 patients with rolandic epilepsy (RE) and 807 patients with adult focal epilepsy (AFE), totalling 2454 cases. Microdeletions were assessed in a combined and subtype-specific approaches against 6746 controls.
Results: When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted p=1.06×10−6,OR 1.89, 95% CI 1.51 to 2.35). Epilepsy subtype-specific analyses showed that hotspot microdeletions in the GGE subgroup contribute most of the overall signal (adjusted p=9.79×10−12, OR 7.45, 95% CI 4.20–13.5). Outside hotspots , microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted p=9.13×10−3,OR 2.85, 95% CI 1.62–4.94). No additional signal was observed for RE and AFE. Still, gene-content analysis identified known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes across epilepsy subtypes that were not deleted in controls.
Conclusions: Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor contribution in the aetiology of RE and AFE.
Background Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement “hotspot” loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted.
Methods We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genome-wide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls.
Results When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00×10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Sub-type specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22×10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78×10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls.
Conclusions Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.
Background: Meta-analysis of observational studies concluded that soft drinks may increase the risk of depression, while high consumption of coffee and tea may reduce the risk. Objectives were to explore the associations between the consumption of soft drinks, coffee or tea and: (1) a history of major depressive disorder (MDD) and (2) the severity of depressive symptoms clusters (mood, cognitive and somatic/vegetative symptoms). Methods: Cross-sectional and longitudinal analysis based on baseline and 12-month-follow-up data collected from four countries participating in the European MooDFOOD prevention trial. In total, 941 overweight adults with subsyndromal depressive symptoms aged 18 to 75 years were analyzed. History of MDD, depressive symptoms and beverages intake were assessed. Results: Sugar-sweetened soft drinks were positively related to MDD history rates whereas soft drinks with non-nutritive sweeteners were inversely related for the high vs. low categories of intake. Longitudinal analysis showed no significant associations between beverages and mood, cognitive and somatic/vegetative clusters. Conclusion: Our findings point toward a relationship between soft drinks and past MDD diagnoses depending on how they are sweetened while we found no association with coffee and tea. No significant effects were found between any studied beverages and the depressive symptoms clusters in a sample of overweight adults.