Search

Short-term studies have shown an attenuated immune response in hemodialysis patients after COVID-19-vaccination. The present study examines how antibody response is maintained after vaccination against SARS-CoV-2 in a large population of hemodialysis patients from six outpatient dialysis centers. We retrospectively assessed serum antibody levels against SARS-CoV-2 spike protein and nucleocapsid protein (electrochemiluminescence immunoassays, Roche Diagnostics) after COVID-19-vaccination in 298 hemodialysis and 103 non-dialysis patients (controls), comparing early and late antibody response. Compared to a non-dialysis cohort hemodialysis patients showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up measurement (median 6 months after vaccination). Significantly more hemodialysis patients had anti-SARS-CoV-2-S antibody titers below 100 U/mL (p < 0.001), which increased during follow-up from 23% to 45% but remained low in the control group (3% vs. 7%). In multivariate analysis, previous COVID-19 infections (p < 0.001) and female gender (p < 0.05) were significantly associated with higher early as well as late antibody vaccine response in hemodialysis patients, while there was a significant inverse correlation between patient age and systemic immunosuppression (p < 0.001). The early and late antibody responses were significantly higher in patients receiving vaccination after a SARS-CoV-2 infection compared to uninfected patients in both groups (p < 0.05). We also note that a higher titer after complete immunization positively affected late antibody response. The observation, that hemodialysis patients showed a significantly stronger decline of SARS-CoV-2 vaccination antibody titers within 6 months, compared to controls, supports the need for booster vaccinations to foster a stronger and more persistent antibody response.

Abstract Introduction Survival of critically buried avalanche victims is directly dependent on the patency of the airway and the victims’ ability to breathe. While guidelines and avalanche research have consistently emphasized on the importance of airway patency, there is a notable lack of evidence regarding its prevalence. Objective The aim of this review is to provide insight into the prevalence of airway patency and air pocket in critically buried avalanche victims. Methods A scoping review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline extension for scoping reviews. MEDLINE and Cochrane databases, as well as additional manual searching was performed to identify literature reporting data on airway patency and the presence of an air pocket in critically buried avalanche victims. After eliminating duplicates, we screened abstracts and main texts to identify eligible studies. Results Of 4,109 studies identified 154 were eligible for further screening. Twenty-four publications and three additional data sources with a total number of 566 cases were included in this review. The proportion of short-term (

Abstract Background Suspension syndrome describes a multifactorial cardio-circulatory collapse during passive hanging on a rope or in a harness system in a vertical or near-vertical position. The pathophysiology is still debated controversially. Aims The International Commission for Mountain Emergency Medicine (ICAR MedCom) performed a scoping review to identify all articles with original epidemiological and medical data to understand the pathophysiology of suspension syndrome and develop updated recommendations for the definition, prevention, and management of suspension syndrome. Methods A literature search was performed in PubMed, Embase, Web of Science and the Cochrane library. The bibliographies of the eligible articles for this review were additionally screened. Results The online literature search yielded 210 articles, scanning of the references yielded another 30 articles. Finally, 23 articles were included into this work. Conclusions Suspension Syndrome is a rare entity. A neurocardiogenic reflex may lead to bradycardia, arterial hypotension, loss of consciousness and cardiac arrest. Concomitant causes, such as pain from being suspended, traumatic injuries and accidental hypothermia may contribute to the development of the Suspension Syndrome. Preventive factors include using a well-fitting sit harness, which does not cause discomfort while being suspended, and activating the muscle pump of the legs. Expediting help to extricate the suspended person is key. In a peri-arrest situation, the person should be positioned supine and standard advanced life support should be initiated immediately. Reversible causes of cardiac arrest caused or aggravated by suspension syndrome, e.g., hyperkalaemia, pulmonary embolism, hypoxia, and hypothermia, should be considered. In the hospital, blood and further exams should assess organ injuries caused by suspension syndrome.

Background: Acute kidney injury (AKI) after robot-assisted partial nephrectomy (RAPN) is a robust surrogate for chronic kidney disease. The objective of this study was to evaluate the association of ischemia type and duration during RAPN with postoperative AKI. Materials and methods: We reviewed all patients who underwent RAPN at our institution since 2011. The ischemia types were warm ischemia (WI), selective artery clamping (SAC), and zero ischemia (ZI). AKI was defined according to the Risk Injury Failure Loss End-Stage (RIFLE) criteria. We calculated ischemia time thresholds for WI and SAC using the Youden and Liu indices. Logistic regression and decision curve analyses were assessed to examine the association with AKI. Results: Overall, 154 patients met the inclusion criteria. Among all RAPNs, 90 (58.4%), 43 (28.0%), and 21 (13.6%) were performed with WI, SAC, and ZI, respectively. Thirty-three (21.4%) patients experienced postoperative AKI. We extrapolated ischemia time thresholds of 17 min for WI and 29 min for SAC associated with the occurrence of postoperative AKI. Multivariable logistic regression analyses revealed that WIT ≤ 17 min (odds ratio [OR] 0.1, p < 0.001), SAC ≤ 29 min (OR 0.12, p = 0.002), and ZI (OR 0.1, p = 0.035) significantly reduced the risk of postoperative AKI. Conclusions: Our results confirm the commonly accepted 20 min threshold for WI time, suggest less than 30 min ischemia time when using SAC, and support a ZI approach if safely performable to reduce the risk of postoperative AKI. Selecting an appropriate ischemia type for patients undergoing RAPN can improve short- and long-term functional kidney outcomes.

Abstract Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue, and the initial response of microglia determines the severity of neuro-inflammatory diseases. The CD83 molecule has been recently shown to modulate the activation status of dendritic cells and macrophages. Although the expression of CD83 is associated with early microglia activation in various disease settings, its functional relevance for microglial biology has been elusive. Here, we describe a thorough assessment of CD83 regulation in microglia and show that CD83 expression in murine microglia is not only associated with cellular activation but also with pro-resolving functions. Using single-cell RNA-sequencing, we reveal that conditional deletion of CD83 results in an over-activated state during neuroinflammation in the experimental autoimmune encephalomyelitis model. Subsequently, CD83-deficient microglia recruit more pathogenic immune cells to the central nervous system, deteriorating resolving mechanisms and exacerbating the disease. Thus, CD83 in murine microglia orchestrates cellular activation and, consequently, also the resolution of neuroinflammation.

Abstract Background A major challenge in the management of avalanche victims in cardiac arrest is differentiating hypothermic from non-hypothermic cardiac arrest, as management and prognosis differ. Duration of burial with a cutoff of 60 min is currently recommended by the resuscitation guidelines as a parameter to aid in this differentiation However, the fastest cooling rate under the snow reported so far is 9.4 °C per hour, suggesting that it would take 45 min to cool below 30 °C, which is the temperature threshold below which a hypothermic cardiac arrest can occur. Case presentation We describe a case with a cooling rate of 14 °C per hour, assessed on site with an oesophageal temperature probe. This is by far the most rapid cooling rate after critical avalanche burial reported in the literature and further challenges the recommended 60 min threshold for triage decisions. The patient was transported under continuous mechanical CPR to an ECLS facility and rewarmed with VA-ECMO, although his HOPE score was 3% only. After three days he developed brain death and became an organ donor. Conclusions With this case we would like to underline three important aspects: first, whenever possible, core body temperature should be used instead of burial duration to make triage decisions. Second, the HOPE score, which is not well validated for avalanche victims, had a good discriminatory ability in our case. Third, although extracorporeal rewarming was futile for the patient, he donated his organs. Thus, even if the probability of survival of a hypothermic avalanche patient is low based on the HOPE score, ECLS should not be withheld by default and the possibility of organ donation should be considered.

Abstract Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we identify the enzyme cis‐aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever. Infection of mice with C. burnetii induced expression of several anti‐microbial candidate genes, including Acod1. In macrophages, Acod1 was essential for restricting C. burnetii replication, while other antimicrobial pathways were dispensable. Intratracheal or intraperitoneal infection of Acod1−/− mice caused increased C. burnetii burden, weight loss and stronger inflammatory gene expression. Exogenously added itaconate restored pathogen control in Acod1−/− mouse macrophages and blocked replication in human macrophages. In axenic cultures, itaconate directly inhibited growth of C. burnetii. Finally, treatment of infected Acod1−/− mice with itaconate efficiently reduced the tissue pathogen load. Thus, ACOD1‐derived itaconate is a key factor in the macrophage‐mediated defense against C. burnetii and may be exploited for novel therapeutic approaches in chronic Q fever.

Knabl and Lee et al. use RNA sequencing to assess the impact of vaccination with BNT162b2 on the peripheral innate immune response of a small cohort of COVID-19 patients infected with the SARS-CoV-2 Beta variant. They show an increased JAK-STAT-mediated immune response in vaccinated patients as compared to unvaccinated ones.

Abstract Objective We aimed to investigate the medical characteristics of helicopter hoist operations (HHO) in HEMS missions. Methods We designed a retrospective study evaluating all HHO and other human external cargo (HEC) missions performed by Swiss Air-Rescue (Rega) between January 1, 2010, and December 31, 2019. Results During the study period, 9,963 (88.7 %) HEMS missions with HHO and HEC were conducted during the day, and 1,265 (11.3 %) at night. Of the victims with time-critical injuries (NACA ≥ 4), 21.1 % (n = 400) reached the hospital within 60 min during the day, and 9.1 % (n = 18) at night. Nighttime missions, a trauma diagnosis, intubation on-site, and NACA Score ≥ 4 were independently and highly significantly associated with longer mission times (p

Uncontrolled activation of fibroblasts contributes to tissue fibrosis and organ dysfunction. Here the authors demonstrate that the epigenetic control of autophagy is disturbed by a TGFβ-dependent downregulation of MYST1 in systemic sclerosis patients. Restoration of the epigenetic control of autophagy reduces fibroblast activation and ameliorates fibrotic tissue remodeling.

Abstract Background Hypotension is associated with worse outcome in patients with traumatic brain injury (TBI) and maintaining a systolic blood pressure (SBP) ≥110 mmHg is recommended. The aim of this study was to assess the incidence of TBI in patients suffering multiple trauma in mountain areas; to describe associated factors, treatment and outcome compared to non-hypotensive patients with TBI and patients without TBI; and to evaluate pre-hospital variables to predict admission hypotension. Methods Data from the prospective International Alpine Trauma Registry including mountain multiple trauma patients (ISS ≥ 16) collected between 2010 and 2019 were analysed. Patients were divided into three groups: 1) TBI with hypotension, 2) TBI without hypotension and 3) no TBI. TBI was defined as Abbreviated Injury Scale (AIS) of the head/neck ≥3 and hypotension as SBP

Abstract Background Over the past years, several emergency medical service providers have introduced mechanical chest compression devices (MCDs) in their protocols for cardiopulmonary resuscitation (CPR). Especially in helicopter emergency medical systems (HEMS), which have limitations regarding loading weight and space and typically operate in rural and remote areas, whether MCDs have benefits for patients is still unknown. The aim of this study was to evaluate the use of MCDs in a large Swiss HEMS system. Materials and methods We conducted a retrospective observational study of all HEMS missions of Swiss Air rescue Rega between January 2014 and June 2016 with the use of an MCD (Autopulse®). Details of MCD use and patient outcome are reported from the medical operation journals and the hospitals’ discharge letters. Results MCDs were used in 626 HEMS missions, and 590 patients (94%) could be included. 478 (81%) were primary missions and 112 (19%) were interhospital transfers. Forty-nine of the patients in primary missions were loaded under ongoing CPR with MCDs. Of the patients loaded after return of spontaneous circulation (ROSC), 20 (7%) experienced a second CA during the flight. In interhospital transfers, 102 (91%) only needed standby use of the MCD. Five (5%) patients were loaded into the helicopter with ongoing CPR. Five (5%) patients went into CA during flight and the MCD had to be activated. A shockable cardiac arrhythmia was the only factor significantly associated with better survival in resuscitation missions using MCD (OR 0.176, 95% confidence interval 0.084 to 0.372, p

Background: Evidence-based Infection Prevention and Control (IPC) measures are critical in protecting medical doctors from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Concerns surrounding access to personal protective equipment (PPE), compliance with IPC measures and the quality of available PPE have been raised as possible causes for high rates of SARS-CoV-2 infection in medical doctors in high transmission settings. This study aimed to determine the prevalence of SARS-CoV-2 infection and the risk factors for occupational infection in doctors in the hospitals in Nelson Mandela Bay (NMB). Methods: We conducted a cross-sectional study wherein we electronically surveyed medical doctors in public-sector NMB hospitals from 01 March 2020 to 31 December 2020. We collected demographic, health, occupational and SARS-CoV-2 infection and exposure data. Categorical data were described as proportions and a multiple variable logistic regression model was used to identify risk factors for SARS-CoV-2 infection. Results: The survey was distributed amongst 498 doctors, 141 (28%) of whom replied. Forty-three (31%) participants reported that they had tested positive for SARS-CoV-2 during the study period. Eighty-nine participants (64%) reported inadequate access to PPE whilst only 68 (49%) participants adhered to PPE recommendations when interacting with patients with confirmed or suspected SARS-CoV-2 infection. We were unable to identify any significant predictors of SARS-CoV-2 infection. Conclusion: This study demonstrates a high prevalence of SARS-CoV-2 infection in public hospital doctors in NMB. Most participants reported inadequate access to PPE and poor compliance with IPC protocols. These findings suggest an urgent need for the improved implementation of IPC measures to protect doctors from SARS-CoV-2 infection.

Acute kidney injury (AKI) is a severe complication of rhabdomyolysis. The pathophysiology of rhabdomyolysis-associated AKI is complex, but myoglobin related damage plays a major role. Extracorporeal removal of myoglobin is therefore an appealing target to prevent AKI, however, attempts to remove myoglobin with standard dialysis membranes have so far been disappointing. Here we report the case of a 12-year-old boy with severe trauma-related rhabdomyolysis where we successfully utilized continuous renal replacement therapy in combination with Cytosorb® to eliminate myoglobin and prevent AKI. The early use of extracorporeal myoglobin removal with Cytosorb® after severe rhabdomyolysis might be an option and should be further investigated as a tool to prevent the development of AKI.

Objective: Interferon regulatory factor (IRF) 5 is a transcription factor known for promoting M1 type macrophage polarization in vitro. Given the central role of inflammatory macrophages in promoting atherosclerotic plaque progression, we hypothesize that myeloid cell-specific deletion of IRF5 is protective against atherosclerosis. Methods: Female Apoe–/– LysmCre/+ Irf5fl/fl and Apoe −/− Irf5fl/fl mice were fed a high-cholesterol diet for three months. Atherosclerotic plaque size and compositions as well as inflammatory gene expression were analyzed. Mechanistically, IRF5-dependent bone marrow-derived macrophage cytokine profiles were tested under M1 and M2 polarizing conditions. Mixed bone marrow chimeras were generated to determine intrinsic IRF5-dependent effects on macrophage accumulation in atherosclerotic plaques. Results: Myeloid cell-specific Irf5 deficiency blunted LPS/IFNγ-induced inflammatory gene expression in vitro and in the atherosclerotic aorta in vivo. While atherosclerotic lesion size was not reduced in myeloid cell-specific Irf5-deficient Apoe–/– mice, plaque composition was favorably altered, resembling a stable plaque phenotype with reduced macrophage and lipid contents, reduced inflammatory gene expression and increased collagen deposition alongside elevated Mertk and Tgfβ expression. Irf5-deficient macrophages, when directly competing with wild type macrophages in the same mouse, were less prone to accumulate in atherosclerotic lesion, independent of monocyte recruitment. Irf5-deficient monocytes, when exposed to oxidized low density lipoprotein, were less likely to differentiate into macrophage foam cells, and Irf5-deficient macrophages proliferated less in the plaque. Conclusion: Our study provides genetic evidence that selectively altering macrophage polarization induces a stable plaque phenotype in mice.

Overdrinking and non-osmotic arginine vasopressin release are the main risk factors for exercise-associated hyponatremia (EAH) in ultra-marathon events. However, particularly during ultra-marathon running in mountainous regions, eccentric exercise and hypoxia, which have been shown to modulate inflammation, hormones regulating fluid homeostasis (hypoxia), and oxidative stress, could contribute to serum sodium changes in a dose-dependent manner. To the best of our knowledge, the contribution of these factors, the extent of which depends on the duration and geographical location of the race, has not been well studied. Twelve male participants (11 finishers) of the short (69km, 4,260m elevation-gain) and 15 male participants (seven finishers) of the long (121km, 7,554m elevation-gain) single-stage Südtirol Ultra Sky-Race took part in this observational field study. Venous blood was drawn immediately before and after the race. Analyses included serum sodium concentration, copeptin (a stable marker for vasopressin), markers of inflammation, muscle damage and oxidative stress. Heart rate was measured during the race and race time was obtained from the race office. During the short and the long competition two and one finishers, respectively showed serum sodium concentrations >145mmol/L. During the long competition, one athlete showed serum sodium concentrations

Collinear laser spectroscopy in the 1s2s3S1→1s2p3P0,2 transitions of helium-like 11B3+ was performed using the HITRAP beamline at the GSI Helmholtz Centre. The ions were produced in an electron beam ion source, extracted, and accelerated to a beam energy of 4 keV/q. Results agree with previous measurements within uncertainty. Thus, it was demonstrated that the metastable state in He-like ions is sufficiently populated to carry out collinear laser spectroscopy. The measurement is a pilot experiment for a series of measurements that will be performed at a dedicated collinear laser spectroscopy setup at TU Darmstadt with light helium-like ions.

Highly charged heavy ions at rest offer a wide spectrum of precision measurements. The GSI Helmholtzzentrum für Schwerionenforschung GmbH is able to deliver ions up to U92+. As the production of these heavy, highly charged ions requires high kinetic energies, it is necessary to decelerate these ions for ultimate precision. The broad energy distribution, which results from the deceleration in the HITRAP linear decelerator, needs to be reduced to allow for further transportation and experiments. The HITRAP cooling trap is designed to cool, i.e., reduce, this energy spread by utilizing electron cooling. The commissioning of this trap is done with Ar16+-ions from a local EBIT ion source. By analyzing the signal of stored ions after ejection, properties such as ion lifetime, charge exchange, and ion motions can be observed. Here, we provide an overview of the recent results of the commissioning process and discuss future experiments.

Abstract Background Human external cargo (HEC) extrication during helicopter rescue missions is commonly used in mountain emergency medical services. Furthermore, longline or winch operations offer the opportunity to deliver professional medical care onsite. As the safety and quality of emergency medical care depends on training and experience, we aimed to investigate characteristics of mountain rescue missions with HEC. Methods We retrospectively reviewed all rescue missions conducted by Air Zermatt (a commercial rescue service in the high-alpine region of Switzerland) from January 2010 to September 2016. Results Out of 11,078 rescue missions 1137 (10%) required a HEC rescue. In 3% (n = 29) rapid sequence induction and endotracheal intubation, in 2% (n = 14) cardiopulmonary resuscitation, and in 0.4% (n = 3) a chest tube insertion had to be performed onsite prior to HEC extraction. The most common medical intervention onsite is analgesia or analgosedation, in 17% (n = 142) fentanyl or ketamine was used in doses of ≥ 0.2 mg or ≥ 50 mg, respectively. Conclusions As these interventions have to be performed in challenging terrain, with reduced personnel resources, and limited monitoring, our results point out the need for physicians onsite who are clinically experienced in these procedures and specially and intensively trained for the specific characteristics and challenges of HEC rescue missions.

Background Optimal management of patients with cancer during COVID-19 pandemic is still pending.Methods Our patients were advised to maintain their scheduled appointments, and planned cancer treatment was continued without unnecessary delays in an outpatient setting. Additional strict preventive infection measures were rapidly implemented at our outpatient department. When COVID-19 test became widely available, universal testing of healthcare workers and vigorous screening of all patients coming to our facility for COVID-19 infection were performed by SARS-CoV-2 real-time reverse transcription PCR on rhinopharyngeal swab.Results As of the data cut-off on 9 April 2020, a total of 156 oncology patients with a median age of 67 (range 26–86) years and 63 haematology patients (median age 69 years, range 23–89) were screened for COVID-19 during active cancer treatment. Prevalence (1.8%; 4/219) of COVID-19 in patients with cancer was significantly higher compared with a respective control group of asymptomatic counterparts (p=0.018). Outcomes of COVID-19 positive patients were good, with only one observed death due to progression of advanced metastatic disease.Conclusion Our data indicate that continuation of anticancer treatment in epidemic areas during the COVID-19 pandemic seems to be safe and feasible, if adequate and strict preventive measures are vigorously and successfully carried out.

Abstract Background Lightning strikes are rare but potentially lethal. The risk for suffering a lightning strike in a mountain environment is unknown. The aim of this nationwide study was to analyse all lightning accidents in the Austrian Alps from 2005 to 2015, to assess the circumstances of the accident, the injury pattern as well as the outcome. Methods From 2005 to 2015, data from the national Austrian Alpine Police database as well as the Clinical Information System of Innsbruck Medical University Hospital were searched for the keywords lightning injury, lightning strike, lightning as well as ICD-10 Code T75.0. Additionally, the archive data of Innsbruck Medical University Hospital was searched manually. Results The Austrian Alpine Police database, containing 109.168 patients for the years 2005–2015, was screened for lightning accidents. Sixty-four patients had been hit by lightning in the Austrian Alps, 54 were male. Four persons died on scene; survival rate was 93.8%. Two deceased persons were hunters, who were killed by the same lightning strike. Sixty-three patients suffered a lightning strike while doing a recreational activity, mostly hiking (n = 55), a few hunting and only one doing occupational timberwork. Sixty-three patients suffered a lightning strike between June and August with nearly half (46.9%) of the accidents happening on a Saturday or Sunday, and mainly (95.3%) between 12:00 and 22:00 h. Discussion Persons who perform recreational outdoor and occupational activities in an alpine environment during summer and after noon incur a higher risk of sustaining a lightning strike. The primary risk group includes young male mountaineers and hunters. The mortality rate was low. Trial registration The study was approved by the Ethics Committee of the Medical University of Innsbruck (AN4757 315/4.4) and retrospectively registered with Clinical Trials NCT03405467, January 19, 2018.

Abstract In this prospective, observational study we describe the incidence and characteristics of out of hospital cardiac arrest (OHCA) cases who received mechanical CPR, after the implementation of a mechanical CPR device (LUCAS 2; Physio Control, Redmond, WA, USA) in a physician staffed helicopter emergency medical service (HEMS) in South Tyrol, Italy. During the study period (06/2013–04/2016), 525 OHCA cases were registered by the dispatch centre, 271 (51.6%) were assisted by HEMS. LUCAS 2 was applied in 18 (6.6%) of all HEMS-assisted OHCA patients; ten were treated with LUCAS 2 at the scene only, and eight were transported to hospital with ongoing CPR. Two (11.1%) of the 18 patients survived long term with full neurologic recovery. In seven of eight patients transferred to hospital with ongoing CPR, CPR was ceased in the emergency room without further intervention. Retrospectively, all HEMS-assisted OHCA cases were screened for proposed indication criteria for prolonged CPR. Thirteen patients fulfilled these criteria, but only two of them were transported to hospital. Based on these results, we propose a standard operating procedure for HEMS-assisted patients with refractory OHCA in a region without hospitals with ECLS capacity.

Abstract Background Providing sufficient oxygenation and ventilation is of paramount importance for the survival of emergency patients. Therefore, advanced airway management is one of the core tasks for every rescue team. Endotracheal intubation is the gold standard to secure the airway in the prehospital setting. This review aims to highlight special considerations for advanced airway management preceding human external cargo (HEC) evacuations. Methods We systematically searched MEDLINE, EMBASE, and PubMed in August 2017 for articles on airway management and ventilation in patients before hoist or longline operation in HEMS. Relevant reference lists were hand-searched. Results Three articles with regard to advanced airway management and five articles concerning the epidemiology of advanced airway management in hoist or longline rescue missions were included. We found one case report regarding ventilation during hoist operations. The exact incidence of advanced airway management before evacuation of a patient by HEC is unknown but seems to be very low (

Microenvironment and activation signals likely imprint heterogeneity in the lymphatic endothelial cell (LEC) population. Particularly LECs of secondary lymphoid organs are exposed to different cell types and immune stimuli. However, our understanding of the nature of LEC activation signals and their cell source within the secondary lymphoid organ in the steady state remains incomplete. Here we show that integrin alpha 2b (ITGA2b), known to be carried by platelets, megakaryocytes and hematopoietic progenitors, is expressed by a lymph node subset of LECs, residing in medullary, cortical and subcapsular sinuses. In the subcapsular sinus, the floor but not the ceiling layer expresses the integrin, being excluded from ACKR4+ LECs but overlapping with MAdCAM-1 expression. ITGA2b expression increases in response to immunization, raising the possibility that heterogeneous ITGA2b levels reflect variation in exposure to activation signals. We show that alterations of the level of receptor activator of NF-κB ligand (RANKL), by overexpression, neutralization or deletion from stromal marginal reticular cells, affected the proportion of ITGA2b+ LECs. Lymph node LECs but not peripheral LECs express RANK. In addition, we found that lymphotoxin-β receptor signaling likewise regulated the proportion of ITGA2b+ LECs. These findings demonstrate that stromal reticular cells activate LECs via RANKL and support the action of hematopoietic cell-derived lymphotoxin.

Background: Abiraterone acetate (AA), a selective inhibitor of the CYP17 enzyme, demonstrated a significant improvement in the treatment of patients with metastatic castration-resistant prostate cancer. The risk of endocrine side effects, mainly an increased adrenal mineralocorticoid production, could limit its use in patients with atrial fibrillation. Methods: We retrospectively reviewed the clinical records of 85 metastatic castration-resistant prostate cancer patients treated with AA at our institutions and identified six patients suffering from concomitant atrial fibrillation. Results: In these six patients, the median duration of AA treatment was 11.5 months (range 4–22 months) with a biochemical response in three patients. No significant cardiac events were observed during the treatment. Conclusion: Our data suggest that AA may be safely administered in patients with atrial fibrillation.

On a closed 4-dimensional Riemannian manifold, we give a lower bound for the square of the first eigenvalue of the Yamabe operator in terms of the total Branson's $Q$-curvature. As a consequence, if the manifold is spin, we relate the first eigenvalue of the Dirac operator to the total Branson's $Q$-curvature. On a closed $n$-dimensional manifold, $n ge 5$, we compare the three basic conformally covariant operators: the Branson-Paneitz, the Yamabe and the Dirac operator (if the manifold is spin) through their first eigenvalues. Equality cases are also characterized.