Postoperative Prophylactic Antibiotic Use in Breast Reduction Mammoplasty: A Single Centre Retrospective Cohort Study.

Introduction: Breast reduction mammoplasty (BRM) is a common procedure performed by plastic surgeons treating patients with hypermastia. It is customary to give preoperative prophylactic intravenous antibiotics for BRM, followed by several days of postoperative prophylactic oral antibiotics, despite the lack of evidence of their effectiveness in preventing surgical site infections (SSIs). The purpose of this study is to determine if the addition of prophylactic postoperative antibiotics is more effective in preventing SSIs in comparison to a single dose of preoperative prophylactic antibiotics in BRM. Methods: A retrospective analysis of 124 elective BRM cases by a single senior plastic surgeon was completed. Two study groups were formed based on the location of surgery and each group was assigned a different antibiotic regimen. The first antibiotic regimen consisted of a single preoperative intravenous dose of antibiotics (group 1), while the second regimen consisted of a preoperative intravenous dose followed by a 5-day course of oral antibiotics (group 2). Results: Overall SSI rate was 5.6%. Infection rate in group 1 was 8.1% in comparison to 3.2% for group 2 (P value .44). Overall, the incidence of complications was 29.0%; 38.7% in group 1 and 19.4% in group 2 (P value .03). Complications consisted of 35 cases of delayed wound healing, 7 SSIs and 2 hematomas requiring evacuation. Conclusion: Study results demonstrated that the use of postoperative prophylactic antibiotics for BRM had no significant effect on the rate of SSIs.

Introduction: La mammoplastie de réduction mammaire (MRM) est une procédure couramment pratiquée par les chirurgiens plastiques traitant des patientes ayant une hypertrophie mammaire. Il est habituel d'administrer une prophylaxie intraveineuse préopératoire pour la MRM puis plusieurs jours d'antibiothérapie prophylactique postopératoire par voie orale en dépit de l'absence de données probantes de leur efficacité à prévenir les infections du site chirurgical. L'objectif de cette étude était de déterminer si l'ajout d'antibiotiques postopératoires à visée prophylactique est plus efficace pour la prévention des infections de la cicatrice opératoire que la seule administration préopératoire d'une dose unique d'antibiotiques à visée prophylactique dans la MRM. Méthodes: Une analyse rétrospective a été réalisée par un seul chirurgien plastique expérimenté de 124 cas de MRM planifiés. Deux groupes d'étude ont été constitués en fonction du lieu de la chirurgie parmi deux centres chirurgicaux et chaque groupe ayant reçu l'un des deux protocoles d'antibiothérapie suivants : le premier schéma thérapeutique était constitué d'une seule dose préopératoire administrée par voie intraveineuse (groupe 1) et le deuxième consistait en l'administration de la dose préopératoire par voie intraveineuse suivie de 5 jours d'antibiotiques par voie orale (groupe 2). Résultats: Le taux global d'infections de la cicatrice opératoire était de 5,6%. Le taux d'infections dans le groupe 1 a été de 8,1%, comparativement à 3,2% dans le groupe 2 (P = 0,44). L'incidence globale des complications a été de 29,0%; 38,7% dans le groupe 1 et 19,4% dans le groupe 2 (P = 0,03). Les complications ont été 35 cas de retard de cicatrisation, 7 cas d'infection du site chirurgical et 2 hématomes nécessitant leur évacuation. Conclusion: Les résultats de l'étude ont montré que l'utilisation postopératoire d'antibiotiques à visée prophylactique pour la mammoplastie de réduction mammaire n'avait pas d'effet significatif sur le taux d'infections du site chirurgical.

Diagnosis of Waldenstrom Macroglobulinemia Using Postoperative Histopathology During Routine Total Knee Arthroplasty: A Case Report.

CASE: We present a 63-year-old patient diagnosed with Waldenstrom macroglobulinemia (WM) through histopathology of bone tissue after total knee arthroplasty for routine osteoarthritis. The patient, surgical team, and the pathologist were unaware of this diagnosis before the surgery. CONCLUSION: The cost-effectiveness of routine histopathologic examination of bone cuts and synovial samples after total joint arthroplasty continues to be a source of debate. Our case highlights an example of the utility of histopathology because it led to the early detection of WM, resulting in prompt treatment to improve quality of life.

Diagnosis of medial meniscal lesions in the canine stifle using multidetector computed tomographic positive-contrast arthrography.

OBJECTIVE: To assess diagnostic value and clinical utility of multidetector computed tomographic positive contrast arthrography (CTA) for meniscal lesions in dogs. STUDY DESIGN: Prospective case series. STUDY POPULATION: Client-owned dogs (n = 55) with cranial cruciate ligament injuries. METHODS: Sedated dogs underwent CTA using a 16-slice scanner, and subsequently received mini-medial arthrotomy for meniscal assessment. Scans were anonymized, randomized, and reviewed twice for meniscal lesions by three independent observers with varying experience. Results were compared with surgical findings. Reproducibility and repeatability were assessed with kappa statistics, intraobserver changes in diagnosis by McNemar's test, and interobserver differences using Cochran's Q test. Test performance was calculated using sensitivity, specificity, proportion correctly identified, and positive and negative predictive values and likelihood ratios. RESULTS: Analysis was based on 52 scans from 44 dogs. Sensitivity for identifying meniscal lesions was 0.62-1.00 and specificity was 0.70-0.96. Intraobserver agreement was 0.50-0.78, and interobserver agreement was 0.47-0.83. There was a significant change between readings one and two for the least experienced observers (p < .05). The sum of sensitivity and specificity exceeded 1.5 for both readings and all observers. CONCLUSION: Diagnostic performance was suitable for identifying meniscal lesions. An effect of experience and learning was seen in this study.

Myenteric Plexus Immune Cell Infiltrations and Neurotransmitter Expression in Crohn's Disease and Ulcerative Colitis.

BACKGROUND AND AIMS: Pain is a cardinal symptom in inflammatory bowel disease [IBD]. An important structure in the transduction of pain signalling is the myenteric plexus [MP]. Nevertheless, IBD-associated infiltration of the MP by immune cells lacks in-depth characterisation. Herein, we decipher intra- and periganglionic immune cell infiltrations in Crohn´s disease [CD] and ulcerative colitis [UC] and provide a comparison with murine models of colitis. METHODS: Full wall specimens of surgical colon resections served to examine immune cell populations by either conventional immuno-histochemistry or immunofluorescence followed by either bright field or confocal microscopy. Results were compared with equivalent examinations in various murine models of intestinal inflammation. RESULTS: Whereas the MP morphology was not significantly altered in IBD, we identified intraganglionic IBD-specific B cell- and monocyte-dominant cell infiltrations in CD. In contrast, UC-MPs were infiltrated by CD8+ T cells and revealed a higher extent of ganglionic cell apoptosis. With regard to the murine models of intestinal inflammation, the chronic dextran sulphate sodium [DSS]-induced colitis model reflected CD [and to a lesser extent UC] best, as it also showed increased monocytic infiltration as well as a modest B cell and CD8+ T cell infiltration. CONCLUSIONS: In CD, MPs were infiltrated by B cells and monocytes. In UC, mostly CD8+ cytotoxic T cells were found. The chronic DSS-induced colitis in the mouse model reflected best the MP-immune cell infiltrations representative for IBD.

Evidence for positive long- and short-term effects of vaccinations against COVID-19 in wearable sensor metrics.

Vaccines are among the most powerful tools to combat the COVID-19 pandemic. They are highly effective against infection and substantially reduce the risk of severe disease, hospitalization, ICU admission, and death. However, their potential for attenuating long-term changes in personal health and health-related wellbeing after a SARS-CoV-2 infection remains a subject of debate. Such effects can be effectively monitored at the individual level by analyzing physiological data collected by consumer-grade wearable sensors. Here, we investigate changes in resting heart rate, daily physical activity, and sleep duration around a SARS-CoV-2 infection stratified by vaccination status. Data were collected over a period of 2 years in the context of the German Corona Data Donation Project with around 190,000 monthly active participants. Compared to their unvaccinated counterparts, we find that vaccinated individuals, on average, experience smaller changes in their vital data that also return to normal levels more quickly. Likewise, extreme changes in vitals during the acute phase of the disease occur less frequently in vaccinated individuals. Our results solidify evidence that vaccines can mitigate long-term detrimental effects of SARS-CoV-2 infections both in terms of duration and magnitude. Furthermore, they demonstrate the value of large-scale, high-resolution wearable sensor data in public health research.

A Novel Positioning Technique for Olecranon Fracture Fixation.

Various positioning techniques have been described for the osteosynthesis of olecranon fractures, each with their own pros and cons. The supine position is time-efficient and better suited in a polytrauma setting but frequently requires an assistant to maintain optimal limb positioning. Also, adequate fluoroscopic imaging is not possible without moving the operative extremity outside the sterile field. We describe a simple and reproducible method addressing these limitations while providing excellent surgical access and intraoperative imaging.

Vegetation structure from LiDAR explains the local richness of birds across Denmark.

Classic ecological research into the determinants of biodiversity patterns emphasised the important role of three-dimensional (3D) vegetation heterogeneity. Yet, measuring vegetation structure across large areas has historically been difficult. A growing focus on large-scale research questions has caused local vegetation heterogeneity to be overlooked compared with more readily accessible habitat metrics from, for example, land cover maps. Using newly available 3D vegetation data, we investigated the relative importance of habitat and vegetation heterogeneity for explaining patterns of bird species richness and composition across Denmark (42,394 km2 ). We used standardised, repeated point counts of birds conducted by volunteers across Denmark alongside metrics of habitat availability from land-cover maps and vegetation structure from rasterised LiDAR data (10 m resolution). We used random forest models to relate species richness to environmental features and considered trait-specific responses by grouping species by nesting behaviour, habitat preference and primary lifestyle. Finally, we evaluated the role of habitat and vegetation heterogeneity metrics in explaining local bird assemblage composition. Overall, vegetation structure was equally as important as habitat availability for explaining bird richness patterns. However, we did not find a consistent positive relationship between species richness and habitat or vegetation heterogeneity; instead, functional groups displayed individual responses to habitat features. Meanwhile, habitat availability had the strongest correlation with the patterns of bird assemblage composition. Our results show how LiDAR and land cover data complement one another to provide insights into different facets of biodiversity patterns and demonstrate the potential of combining remote sensing and structured citizen science programmes for biodiversity research. With the growing coverage of LiDAR surveys, we are witnessing a revolution of highly detailed 3D data that will allow us to integrate vegetation heterogeneity into studies at large spatial extents and advance our understanding of species' physical niches.

Efficacy and safety of molnupiravir for the treatment of SARS-CoV-2 infection: a systematic review and meta-analysis.

BACKGROUND: The role of molnupiravir for coronavirus disease 2019 (COVID-19) treatment is unclear. METHODS: We conducted a systematic review until 1 November 2022 searching for randomized controlled trials (RCTs) involving COVID-19 patients comparing molnupiravir [±standard of care (SoC)] versus SoC and/or placebo. Data were pooled in random-effects meta-analyses. Certainty of evidence was assessed according to the Grading of Recommendations, Assessment, Development and Evaluations approach. RESULTS: Nine RCTs were identified, eight investigated outpatients (29 254 participants) and one inpatients (304 participants). Compared with placebo/SoC, molnupiravir does not reduce mortality [risk ratio (RR) 0.27, 95% CI 0.07-1.02, high-certainty evidence] and probably does not reduce the risk for 'hospitalization or death' (RR 0.81, 95% CI 0.55-1.20, moderate-certainty evidence) by Day 28 in COVID-19 outpatients. We are uncertain whether molnupiravir increases symptom resolution by Day 14 (RR 1.20, 95% CI 1.02-1.41, very-low-certainty evidence) but it may make no difference by Day 28 (RR 1.05, 95% CI 0.92-1.19, low-certainty evidence). In inpatients, molnupiravir may increase mortality by Day 28 compared with placebo (RR 3.78, 95% CI 0.50-28.82, low-certainty evidence). There is little to no difference in serious adverse and adverse events during the study period in COVID-19 inpatients/outpatients treated with molnupiravir compared with placebo/SoC (moderate- to high-certainty evidence). CONCLUSIONS: In a predominantly immunized population of COVID-19 outpatients, molnupiravir has no effect on mortality, probably none on 'hospitalization or death' and effects on symptom resolution are uncertain. Molnupiravir was safe during the study period in outpatients although a potential increase in inpatient mortality requires careful monitoring in ongoing clinical research. Our analysis does not support routine use of molnupiravir for COVID-19 treatment in immunocompetent individuals.

Postoperative drainage management and wound complications following resection of lower limb soft tissue tumors: a retrospective cohort study.

PURPOSE: Postoperative wound complications are common in patients undergoing resection of lower extremity soft tissue tumors. Postoperative drainage therapy ensures adequate wound healing but may delay or complicate it. The aim of this study is to evaluate the incidence of postoperative wound complications and delayed or prolonged drainage treatment and to propose a standardized definition and severity grading of complex postoperative courses. METHODS: A monocentric retrospective analysis of 80 patients who had undergone primary resection of lower extremity soft tissue tumors was performed. A new classification was developed, which takes into account postoperative drainage characteristics and wound complications. Based on this classification, risk factors and the prognostic value of daily drainage volumes were evaluated. RESULTS: According to this new definition, regular postoperative course grade 0 (no wound complication and timely drainage removal) occurred in 26 patients (32.5%), grade A (minor wound complications or delayed drainage removal) in 12 (15.0%), grade B (major wound complication or prolonged drainage therapy) in 31 (38.8%), and grade C (reoperation) in 11 (13.7%) patients. Tumor-specific characteristics, such as tumor size (p = 0.0004), proximal tumor location (p = 0.0484), and tumor depth (p = 0.0138) were identified as risk factors for complex postoperative courses (grades B and C). Drainage volume on postoperative day 4 was a suitable predictor for complex courses (cutoff of 70 ml/d). CONCLUSION: The proposed definition incorporates wound complications and drainage management while also being clinically relevant and easy to apply. It may serve as a standardized endpoint for assessing the postoperative course after resection of lower extremity soft tissue tumors.

Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing.

The paracaspase MALT1 is a crucial regulator of immune responses in various cellular contexts. Recently, there is increasing evidence suggesting that MALT1 might represent a novel key player in mucosal inflammation. However, the molecular mechanisms underlying this process and the targeted cell population remain unclear. In this study, we investigate the role of MALT1 proteolytic activity in the context of mucosal inflammation. We demonstrate a significant enrichment of MALT1 gene and protein expression in colonic epithelial cells of UC patients, as well as in the context of experimental colitis. Mechanistically we demonstrate that MALT1 protease function inhibits ferroptosis, a form of iron-dependent cell death, upstream of NF-κB signaling, which can promote inflammation and tissue damage in IBD. We further show that MALT1 activity contributes to STAT3 signaling, which is essential for the regeneration of the intestinal epithelium after injury. In summary, our data strongly suggests that the protease function of MALT1 plays a critical role in the regulation of immune and inflammatory responses, as well as mucosal healing. Understanding the mechanisms by which MALT1 protease function regulates these processes may offer novel therapeutic targets for the treatment of IBD and other inflammatory diseases.

Immune response to mRNA-based COVID-19 booster vaccination in people living with HIV.

OBJECTIVES: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)-based COVID-19 booster vaccination (third dose). METHODS: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT-162b2 or mRNA-1273 between October 2021 and January 2022. We assessed anti-spike receptor-binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID100 ), and T-cell response (using interferon-gamma-release-assay [IGRA]) at baseline and quarterly follow-up visits. Patients with reported COVID-19 during follow-up were excluded. Predictors of serological immune response were analyzed using multivariate regression models. RESULTS: Of 84 people living with HIV who received an mRNA-based booster vaccination, 76 were eligible for analysis. Participants were on effective antiretroviral therapy (ART) and had a median of 670 CD4+ cells/µL (interquartile range [IQR] 540-850). Following booster vaccination, median anti-spike RBD IgG increased by 705.2 binding antibody units per millilitre (BAU/mL) and median VNA titres increased by 1000 ID100 at the follow-up assessment (median 13 weeks later). Multivariate regression revealed that time since second vaccination was a predictor of stronger serological responses (p < 0.0001). No association was found for other factors, including CD4+ status, choice of mRNA vaccine, or concomitant influenza vaccination. In total, 45 patients (59%) had a reactive baseline IGRA, of whom two lost reactivity during follow-up. Of 31 patients (41%) with non-reactive baseline IGRA, 17 (55%) converted to reactive and seven (23%) remained unchanged following booster vaccination. CONCLUSIONS: People living with HIV with ≥500 CD4+ cells/µL showed favourable immune responses to mRNA-based COVID-19 booster vaccination. A longer time (up to 29 weeks) since second vaccination was associated with higher serological responses, whereas choice of mRNA vaccine or concomitant influenza vaccination had no impact.

Association Between Prosthetic Knee Effusions and Phosphodiesterase Type-5 Enzyme Inhibitor Use After Total Knee Arthroplasty: A Case Report.

CASE: Phosphodiesterase type-5 enzyme (PDE5) inhibitors are well tolerated and used to treat erectile dysfunction. We report a case of prosthetic knee effusions associated with PDE5 inhibitor use in a 65-year-old man after total knee arthroplasty (TKA). PDE5 inhibitor treatment was stopped, and the patient had no further episodes of painful effusions. CONCLUSION: This report describes a previously unknown adverse effect of PDE5 inhibitor use in a prosthetic joint after TKA. We hope to encourage physicians managing patients after joint replacement to be aware of the association between PDE5 inhibitor use and recurrent joint effusions to improve postoperative outcomes.

Longitudinal fluctuations of common antimicrobial resistance genes in the gut microbiomes of healthy Dutch individuals.

The human gut microbiome is an important reservoir of antimicrobial resistance genes (ARGs), collectively termed the 'resistome'. To date, few studies have examined the dynamics of the human gut resistome in healthy individuals. Previously, the authors observed high rates of ARG acquisition and significant abundance shifts during international travel. In order to provide insight into commonly occurring dynamics, this study investigated longitudinal fluctuations in prevalent ARGs (cfxA, tetM and ermB) in the resistomes of non-travelling healthy volunteers. In addition, this study assessed the prevalence of acquirable ARGs (blaCTX-M, qnrB, qnrS, vanA and vanB) over time. Faecal samples from 23 participants were collected at baseline and after 2 and 4 weeks. DNA was isolated, and ARG quantification was performed by quantitative polymerase chain reaction adjusting for the total amount of bacterial 16S rDNA. vanA and qnrS were not detected in any of the samples, while the prevalence rates of vanB of non-enterococcal origin and qnrB were 73.9% and 5.7%, respectively. The ß-lactamase encoding blaCTX-M was detected in 17.4% of healthy participants. The results were compared with previous data from 122 travellers. ARG acquisitions observed in travellers were rare in non-travelling individuals during 4 weeks of follow-up, supporting the hypothesis of ARG acquisition during international travel. However, median -1.04- to 1.04-fold abundance changes were observed for 100% of cfxA, tetM and ermB, which did not differ from those found in travellers. Thus, common abundance shifts in prevalent ARGs of the gut resistome were found to occur independent of travel behaviour.

Prevalence of Positive COVID-19 Test Results Collected by Digital Self-report in the US and Germany.

This cohort study examines traditional surveillance and self-reported COVID-19 test result data collected from independent smartphone app­based studies in the US and Germany.

Experiences of Patients and Therapists Testing a Virtual Reality Exposure App for Symptoms of Claustrophobia: Mixed Methods Study.

BACKGROUND: The effectiveness of virtual reality exposure (VRE) in the treatment of anxiety disorders is well established. Several psychological mechanisms of VRE have been identified, whereby both emotional processing and the sense of presence play a key role. However, there are only few studies that contribute to our knowledge of examples of implementation in the case of VRE for claustrophobia based on patients' experiences and the perspective of therapists. OBJECTIVE: This study asks for key elements of a VRE app that are necessary for effective exposure for people with claustrophobic symptoms. METHODS: A mixed methods design was applied in which patients (n=15) and therapeutic experts (n=15) tested a VRE intervention of an elevator ride at 5 intensity levels. Intensity was varied by elevator size, duration of the elevator ride, and presence of virtual humans. Quantitative measures examined self-reported presence with the Igroup Presence Questionnaire (IPQ) ranging from 0 to 6 and 15 Likert-scaled evaluation items that had been developed for the purpose of this study, ranging from 1 to 5. In both measures, higher scores indicate higher levels of presence or agreement. Think-aloud protocols of the patients and semistructured interviews posttreatment of all participants were conducted to gain in-depth perspectives on emotional processes. RESULTS: The intervention induced a feeling of presence in patients and experts, posttreatment scores showed a high IPQ presence score (mean 3.84, SD 0.88), with its subscores IPQ spatial presence (mean 4.53, SD 1.06), IPQ involvement (mean 3.83, SD 1.22), and IPQ experienced realism (mean 2.75, SD 1.02). Patients preferred a setting in the presence of a therapist (mean 4.13, SD 0.83) more than the experts did (mean 3.33, SD 1.54). Think-aloud protocols of the patients revealed that presence and anxiety both were achieved. Qualitative interviews of patients and experts uncovered 8 topics: feelings and emotions, personal story, telepresence, potential therapeutic effects, barriers, conditions and requirements, future prospects, and realization. The intensity levels were felt to appropriately increase in challenge, with ambivalent results regarding the final level. Virtual humans contributed to feelings of fear. CONCLUSIONS: Key elements of a VRE app for claustrophobic symptoms should include variation of intensity by adding challenging cues in order to evoke presence and anxiety. Virtual humans are a suitable possibility to make the intervention realistic and to provide a sense of closeness; however, some of the fears might then be related to symptoms of social phobia or agoraphobia. Patients may need the physical presence of a therapist, though not all of them share this view. A higher degree of sophistication in the intensity levels is needed to deliver targeted help for specific symptoms of anxiety.

Cross-scale regulation of seasonal microclimate by vegetation and snow in the Arctic tundra.

Climate warming is inducing widespread vegetation changes in Arctic tundra ecosystems, with the potential to alter carbon and nutrient dynamics between vegetation and soils. Yet, we lack a detailed understanding of how variation in vegetation and topography influences fine-scale temperatures ("microclimate") that mediate these dynamics, and at what resolution vegetation needs to be sampled to capture these effects. We monitored microclimate at 90 plots across a tundra landscape in western Greenland. Our stratified random study design covered gradients of topography and vegetation, while nested plots (0.8-100 m2 ) enabled comparison across different sampling resolutions. We used Bayesian mixed-effect models to quantify the direct influence of plot-level topography, moisture and vegetation on soil, near-surface and canopy-level temperatures (-6, 2, and 15 cm). During the growing season, colder soils were predicted by shrub cover (-0.24°C per 10% increase), bryophyte cover (-0.35°C per 10% increase), and vegetation height (-0.17°C per 1 cm increase). The same three factors also predicted the magnitude of differences between soil and above-ground temperatures, indicating warmer soils at low cover/height, but colder soils under closed/taller canopies. These findings were consistent across plot sizes, suggesting that spatial predictions of microclimate may be possible at the operational scales of satellite products. During winter, snow cover (+0.75°C per 10 snow-covered days) was the key predictor of soil microclimate. Topography and moisture explained little variation in the measured temperatures. Our results not only underline the close connection of vegetation and snow with microclimate in the Arctic tundra but also point to the need for more studies disentangling their complex interplay across tundra environments and seasons. Future shifts in vegetation cover and height will likely mediate the impact of atmospheric warming on the tundra soil environment, with potential implications for below-ground organisms and ecosystem functioning.

Deep-learning analysis of micropattern-based organoids enables high-throughput drug screening of Huntington's disease models.

Organoids are carrying the promise of modeling complex disease phenotypes and serving as a powerful basis for unbiased drug screens, potentially offering a more efficient drug-discovery route. However, unsolved technical bottlenecks of reproducibility and scalability have prevented the use of current organoids for high-throughput screening. Here, we present a method that overcomes these limitations by using deep-learning-driven analysis for phenotypic drug screens based on highly standardized micropattern-based neural organoids. This allows us to distinguish between disease and wild-type phenotypes in complex tissues with extremely high accuracy as well as quantify two predictors of drug success: efficacy and adverse effects. We applied our approach to Huntington's disease (HD) and discovered that bromodomain inhibitors revert complex phenotypes induced by the HD mutation. This work demonstrates the power of combining machine learning with phenotypic drug screening and its successful application to reveal a potentially new druggable target for HD.

Current trends and outcomes of non-elective neurosurgical care in Central Europe during the second year of the COVID-19 pandemic.

Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th-April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017-2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017-2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

Improving ecological insights from dendroecological studies of Arctic shrub dynamics: Research gaps and potential solutions.

Rapid climate change has been driving changes in Arctic vegetation in recent decades, with increased shrub dominance in many tundra ecosystems. Dendroecological observations of tundra shrubs can provide insight into current and past growth and recruitment patterns, both key components for understanding and predicting ongoing and future Arctic shrub dynamics. However, generalizing these dynamics is challenging as they are highly scale-dependent and vary among sites, species, and individuals. Here, we provide a perspective on how some of these challenges can be overcome. Based on a targeted literature search of dendrochronological studies from 2005 to 2022, we highlight five research gaps that currently limit dendro-based studies from revealing cross-scale ecological insight into shrub dynamics across the Arctic biome. We further discuss the related research priorities, suggesting that future studies could consider: 1) increasing focus on intra- and interspecific variation, 2) including demographic responses other than radial growth, 3) incorporating drivers, in addition to warming, at different spatial and temporal scales, 4) implementing systematic and unbiased sampling approaches, and 5) investigating the cellular mechanisms behind the observed responses. Focusing on these aspects in dendroecological studies could improve the value of the field for addressing cross-scale and plant community-framed ecological questions. We outline how this could be facilitated through the integration of community-based dendroecology and dendroanatomy with remote sensing approaches. Integrating new technologies and a more multidisciplinary approach in dendroecological research could provide key opportunities to close important knowledge gaps in our understanding of scale-dependencies, as well as intra- and inter-specific variation, in vegetation community dynamics across the Arctic tundra.

Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS-CoV-2 mRNA vaccination.

Durable cell-mediated immune responses require efficient innate immune signaling and the release of pro-inflammatory cytokines. How precisely mRNA vaccines trigger innate immune cells for shaping antigen specific adaptive immunity remains unknown. Here, we show that SARS-CoV-2 mRNA vaccination primes human monocyte-derived macrophages for activation of the NLRP3 inflammasome. Spike protein exposed macrophages undergo NLRP3-driven pyroptotic cell death and subsequently secrete mature interleukin-1ß. These effects depend on activation of spleen tyrosine kinase (SYK) coupled to C-type lectin receptors. Using autologous cocultures, we show that SYK and NLRP3 orchestrate macrophage-driven activation of effector memory T cells. Furthermore, vaccination-induced macrophage priming can be enhanced with repetitive antigen exposure providing a rationale for prime-boost concepts to augment innate immune signaling in SARS-CoV-2 vaccination. Collectively, these findings identify SYK as a regulatory node capable of differentiating between primed and unprimed macrophages, which modulate spike protein-specific T cell responses.