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Assessing the potential seasonality of COVID-19 dynamic in Africa: a mathematical modeling study
No full textPulmonary stereotactic body radiation therapy of oligometastatic head-and-neck squamous cell carcinoma: a multicenter retrospective study
No full textPurposeThe value of stereotactic body radiation therapy (SBRT) in patients with oligometastatic head-and-neck squamous cell carcinoma (HNSCC) remains unclear, as existing evidence is primarily derived from retrospective single-center analyses with small patient cohorts. This study aimed to evaluate the outcomes of pulmonary SBRT in patients with oligometastatic HNSCC and to identify factors associated with survival.Methods and MaterialsThis trinational multicenter cohort study, including 16 centers from Germany, Austria, and Switzerland, retrospectively analyzed patients with oligometastatic HNSCC undergoing SBRT for pulmonary metastases between 2010 and 2023. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival and incidence of local failures.ResultsA total of 178 patients with 284 irradiated lung metastases were analyzed. The most common primary HNSCC subsites were oropharyngeal (n = 71), laryngeal (n = 37), and hypopharyngeal (n = 31). Lung metastases were treated with a median biologically effective dose (BEDα/β=10 Gy) of 105 Gy (IQR, 84-113) at the planning target volume periphery. After a median follow-up of 40 months (95% CI, 34-46), the median OS and progression-free survival were 33 months (95% CI, 26-40) and 9 months (95% CI, 7-11), respectively. The 1-year cumulative incidence of local failures was 5.5% (95% CI, 3.2-8.8). One patient (0.6%) developed acute grade 3 dysphagia, and among 146 patients assessed for chronic toxicities, 2 (1.4%) experienced grade 3 events, with no grade 4-5 toxicities. On multivariable analysis, older (>65 years) patients (hazard ratio [HR], 1.59; 95% CI, 1.02-2.49; P = .040) and females (HR, 1.76; 95% CI, 1.04-2.99; P = .035) exhibited worse OS, whereas longer time between HNSCC diagnosis and first SBRT was associated with longer OS (HR, 0.99; 95% CI, 0.99-1.00; P = .045).ConclusionSBRT for pulmonary metastases achieves excellent local control with minimal toxicity in patients with oligometastatic HNSCC. Prospective trials are needed to determine the optimal timing for integrating SBRT with systemic treatment
Modeling abscission of cacti branches
No full textDuring evolution, various functional principles have evolved that allow plants to create predetermined breaking points for the spatially defined abscission of organs. In the plant family of cacti, some species, such as Cylindropuntia bigelovii, have fragile branch–branch junctions that serve vegetative reproduction, while in other species, such as Opuntia ficus-indica, they are very stable. The fracture behavior of these junctions has been thoroughly characterized anatomically and mechanically, the data being the prerequisite for the performance of cactus- inspired phase field simulations. We have found that models composed of homogeneous materials or material systems with low elastic modulus contrast (analogous to Cylindropuntia bigelovii) exhibit a fracture mode where cracks initiation occurs at the epidermis of the junction notch. In comparison, heterogeneous material systems with high elastic modulus contrast (similar to Opuntia ficus-indica) show fracture nucleation along the inner vascular bundles, with an increase in the maximum fracture energy by a factor of 2.2. In the high contrast heterogeneous models, the V-notch and stiffening of the dermal tissue (‘‘periderm’’) have a negligible effect on their fracture behavior. In addition, the fracture morphologies of these models resemble the rough junction fracture sites found experimentally. The knowledge gained about the geometric influences and the importance of the contrasts in the mechanical properties of the individual materials in the overall system can be transferred as functional principles to bioinspired engineering composites in order to program their fracture behavior
Prospective REALITI-A study : 2-year real-world benefits of mepolizumab in severe asthma
No full textBackgroundMepolizumab, a monoclonal antibody targeting IL-5, is of proven clinical benefit in severe asthma; however, prospective, long-term, real-world data in severe asthma are required.Research QuestionWhat is the real-world benefit of 2 years of mepolizumab treatment in severe asthma?Study Design and MethodsREALITI-A was a 2-year, international, prospective study enrolling adults with asthma on newly initiated mepolizumab 100 mg subcutaneously (physician decision). Outcomes in the 1-year premepolizumab vs 2-year follow-up periods included rates of clinically significant asthma exacerbations (CSEs) (deterioration requiring systemic corticosteroids and/or emergency department [ED] visit/hospitalization), exacerbations requiring ED visit/hospitalization, exacerbations requiring hospitalization, proportion of patients with no exacerbations, median daily maintenance oral corticosteroids (mOCSs) dose, proportion of patients discontinuing mOCSs completely, Asthma Control Questionnaire-5 score, FEV1, and adverse events (AEs).ResultsAfter 2 years’ follow-up, 73% of patients (599 of 822) had no record of mepolizumab discontinuation. During the 2-year follow-up vs premepolizumab period (N = 822), rates of CSEs, exacerbations requiring ED visit/hospitalization, or hospitalization only were reduced by 74%, 79%, and 73%, respectively (odds ratio for no CSEs, 10.0; 95% CI, 7.55- 13.25). Median daily mOCS dose decreased from 10.0 (quartile 1, 5.0; quartile 3, 14.7) mg at week 0 (n = 297) to 0.0 (quartile 1, 0.0; quartile 3, 5.0) mg at weeks 101 to 104 (n = 168), and the proportion of patients discontinuing mOCSs increased progressively to 43% at 1 year and 57% at 2 years. There was a 1.53-point reduction in Asthma Control Questionnaire-5 scores from baseline at 2 years. At months 21 to 24, least square mean FEV1 improved by 142 mL from baseline. Ninety (11%) and 7 (InterpretationIn patients with severe asthma, real-world mepolizumab treatment for 2 years was well tolerated and was associated with sustained reductions in exacerbations and progressive reductions in mOCS use
Prioritization of research questions in health crises—presentation of a concept developed during the COVID-19 pandemic
No full textIn akuten Krisen wie der COVID-19-Pandemie müssen wissenschaftliche Fragestellungen schnell bearbeitet werden, um die Gesundheit der Bevölkerung zu schützen und die Funktion des Gesundheitssystems aufrechtzuerhalten. Die vorherrschende Dringlichkeit und die Vielzahl zu bearbeitender Fragestellungen bei gleichzeitiger Limitation von zeitlichen, personellen oder monetären Ressourcen machen eine Priorisierung unabdingbar. Im Projekt COVID-19-Evidenz-Oekosystem (CEOsys) des Netzwerks Universitätsmedizin (NUM) wurde ein Verfahren zur schnellen Priorisierung von Forschungsfragen speziell für Evidenzsynthesen und klinische Leitlinienempfehlungen initiiert, das im Folgeprojekt PREparedness and Pandemic Response in Deutschland (PREPARED) weiterentwickelt wurde.Entstanden ist das „Konzeptpapier Forschungspriorisierung“, das eine generischere Ausrichtung hat. Die Inhalte des Konzepts werden in diesem Beitrag dargestellt. Kernthemen sind einerseits grundsätzliche Prinzipien einer gelingenden Priorisierung sowie ein konkreter 7‑schrittiger Prozess mit Angaben zu organisatorischen Rahmenbedingungen und zum Ablauf. Das Konzept bietet Adaptionsmöglichkeiten, da Forschungspriorisierung stark kontextabhängig ist.Die Anwendung eines solchen systematischen, transparenten Priorisierungsprozesses trägt dazu bei, nachvollziehbare und informierte Entscheidungen darüber zu treffen, welche wissenschaftlichen Fragen Relevanz und Dringlichkeit aufweisen, in welcher Bearbeitungsreihenfolge sie stehen sollten und welche Fragestellungen nicht oder zu einem späteren Zeitpunkt bearbeitet werden müssen.In acute crises such as the COVID-19 pandemic, scientific questions need to be addressed quickly in order to protect the health of the population and to maintain the function of the healthcare system. The prevailing urgency and the large number of issues to be addressed, combined with the limitation of time, personnel, or monetary resources make prioritization indispensable. In the COVID-19 Evidence Ecosystem (CEOsys) project initiated by the University Medicine Network (NUM), a procedure for the rapid prioritization of questions was used specifically for evidence syntheses and clinical guideline recommendations, which was further developed in the follow-up project PREparedness and Pandemic Response in Germany (PREPARED).The result is a concept paper on the prioritization of research questions and topics with a more generic orientation. The content of the concept is presented in this article. The core subjects are basic principles of successful prioritization as well as an explicit seven-step process with information on organizational framework conditions and the procedure. The concept offers possibilities for adaptation, as research prioritization is highly context-dependent.The application of such a systematic, transparent prioritization process contributes to comprehensible and informed decisions about which research questions are relevant and urgent, in which order they should be processed, and which issues are not critically urgent or have to be postponed
The "good is up" metaphoric effects on recognition: true for source guessing but false for item memory
No full textThe “good is up” metaphor, which links valence and verticality was found to influence affective judgement and to direct attention, but its effects on memory remain unclear with contradictory research findings. To provide a more accurate assessment of memory components involved in recognition, such as item memory and source-guessing biases, a standard source monitoring paradigm was applied in this research. A series of three experiments provided a conceptual replication and extension of Experiment 2 by Crawford et al., (2014) and yielded a consistent result pattern suggesting that the “good is up” metaphor biases participants’ guessing of source location. That is, when source memory failed, participants were more inclined to guess the “up” location versus “down” location for positive items (and vice versa for negative items). It did, however, not affect source memory or item memory for valenced stimuli learned from metaphor-congruent versus incongruent locations (i.e., no metaphor-(in)congruent effects in memory). We suggest that the “good is up” metaphor may affect cognitive processes in a more subtle way than originally suggested
Cervicothoracic volumetric bone mineral density assessed by opportunistic QCT may be a reliable marker for osteoporosis in adults
No full textSummaryThis study aimed to validate the correlation between volumetric bone mineral density in the cervicothoracic and lumbar spine using measurements from opportunistic CT scans. The bone density assessment proved feasible, allowing us to propose optimal cut-off values for diagnosing osteoporosis and predicting vertebral fractures in the cervical and thoracic spine.ObjectivesTo investigate the performance of cervicothoracic volumetric bone mineral density (vBMD), obtained through opportunistic quantitative computed tomography (QCT), in discriminating patients with/without osteoporosis and with/without vertebral fractures (VFs), using lumbar vBMD as the reference.MethodsThree hundred twenty-five patients (65.3 ± 19.2 years, 140 women) with routine non-contrast or contrast-enhanced multi-detector CT (MDCT) scans were included. Trabecular vBMD was automatically extracted from each vertebra using a convolutional neural network (CNN)–based framework (SpineQ software v1.0) with asynchronous calibration and contrast phase correction. The correlations of vBMD between each vertebra spanning C2–T12 and the averaged lumbar spine (L1–L3, or L4 and L5) vBMD values were analyzed, considering fracture status and degeneration. Vertebra-specific linear regression equations were used to approximate lumbar vBMD at the cervicothoracic spine.ResultsCervicothoracic vBMD correlated well with lumbar vBMD (r = 0.79), with significant improvement after excluding degenerated vertebrae (p ConclusionCervicothoracic vBMD may allow for determination of osteoporosis and prediction of VFs
HBV shows different levels of adaptation to HLA class I-associated selection pressure correlating with markers of replication
No full textBackground & AimsImmune responses by CD8 T cells are essential for control of HBV replication. Although selection of escape mutations in CD8 T-cell epitopes has previously been described in HBV infection, its overall influence on HBV sequence diversity and correlation with markers of HBV replication remain unclear.MethodsWhole-genome sequencing was applied to HBV isolates from 532 patients with chronic HBV infection and high-resolution HLA class I genotyping. Using a Bayesian model (HAMdetector) for identification of HLA-associated mutational states (HAMs), the frequency and location of residues under CD8 T-cell selection pressure were determined and the levels of adaptation of individual isolates were quantified.ResultsUsing previously published thresholds for the identification of HAMs, a total of 295 residues showed evidence of CD8 T-cell escape, the majority of which were located in previously unidentified epitopes. Interestingly, HAMs were highly enriched in the HBV core protein compared to all other proteins. When individual HBV isolates were compared, different levels of adaptation to HLA class I immune pressure were noted. The level of adaptation increased with patient age and correlated with markers of replication, with low levels of adaptation in HBeAg-positive infection. Furthermore, the levels of adaptation negatively correlated with HBV viral load and HBsAg levels, consistent with high levels of HLA class I-associated selection pressure in patients with low replication levels.ConclusionsHBV sequence diversity is shaped by HLA class I-associated selection pressure with the HBV core protein being a predominant target of selection. Importantly, different levels of adaptation to immune pressure were observed between HBV infection stages, which need to be considered in the context of T-cell-based therapies.Impact and implicationsThe immune response mediated by CD8 T cells plays a critical role in controlling HBV infection and shows promise for therapeutic strategies aimed at achieving a functional cure. This study demonstrates that mutational escape within CD8 T-cell epitopes is common in HBV and represents a key factor in the failure of immune control. Notably, the HBV core protein emerges as the primary target of CD8 T-cell selection pressure. Additionally, the observed correlation between HBV adaptation levels and viral replication markers indicates that CD8 T-cell immunity may influence transitions between phases of chronic HBV infection
The Freiburg Index of Post-TIPS Survival (FIPS) identifies patients at risk for further decompensation and ACLF after TIPS
No full textBackground & AimsThe Freiburg index of post-TIPS survival (FIPS) defines a high-risk group of patients with significantly reduced survival following transjugular intrahepatic portosystemic shunt (TIPS) implantation. However, the clinical hallmarks responsible for these patients’ unfavorable outcome remain to be identified. Therefore, the present study aimed to characterize the clinical course after TIPS implantation according to the FIPS.MethodsA total of 1,359 patients with cirrhosis allocated to TIPS implantation for treatment of recurrent or refractory ascites or secondary prophylaxis of variceal bleeding from eight tertiary centers were retrospectively included. The patients’ clinical course following TIPS placement was analyzed, stratified according to the FIPS. The primary study outcome was further decompensation within 90 days after TIPS; secondary outcomes were acute-on-chronic liver failure (ACLF) within 90 days and 1-year transplant-free survival.ResultsFurther decompensation after TIPS implantation was significantly more frequent in FIPS high-risk patients compared to low-risk patients (cumulative incidence function 0.58 vs. 0.38, p ConclusionsThe present study reveals that the FIPS predicts development of further decompensation and ACLF after TIPS implantation. These events are responsible for impaired transplant-free survival in FIPS high-risk patients. These results pave the way for the development of tailored clinical management strategies.Impact and implicationsPrognostication after transjugular intrahepatic portosystemic shunt (TIPS) implantation is challenging. Several clinical scores have been proposed in this context, such as the Freiburg index of post-TIPS survival (FIPS). The FIPS can identify a high-risk group of patients with significantly reduced survival after TIPS. However, to understand the reasons for these patients’ unfavorable outcome, their clinical course after TIPS needs to be characterized. This study reveals that the FIPS predicts development of further decompensation and acute-on-chronic liver failure after TIPS implantation, which are responsible for the poor prognosis of FIPS high-risk patients. Therefore, the present results may be useful for tailored decision making in patients allocated to TIPS implantation