A new hip fracture risk index derived from FEA-computed proximal femur fracture loads and energies-to-failure.

Hip fracture risk assessment is an important but challenging task. Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur. We developed a global FEA-computed fracture risk index to increase the prediction accuracy of hip fracture incidence. PURPOSE: Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur to compute the force (fracture load) and energy necessary to break the proximal femur in a particular loading condition. The fracture loads and energies-to-failure are individually associated with incident hip fracture, and provide different structural information about the proximal femur. METHODS: We used principal component analysis (PCA) to develop a global FEA-computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies-to-failure in four loading conditions of 110 hip fracture subjects and 235 age- and sex-matched control subjects from the AGES-Reykjavik study. Using a logistic regression model, we compared the prediction performance for hip fracture based on the stratified resampling. RESULTS: We referred the first principal component (PC1) of the FE parameters as the global FEA-computed fracture risk index, which was the significant predictor of hip fracture (p-value < 0.001). The area under the receiver operating characteristic curve (AUC) using PC1 (0.776) was higher than that using all FE parameters combined (0.737) in the males (p-value < 0.001). CONCLUSIONS: The global FEA-computed fracture risk index increased hip fracture risk prediction accuracy in males.

Trajectories of insomnia following bereavement.

BACKGROUND: Insomnia symptoms are common following bereavement and may exacerbate severe and protracted grief reactions, such as prolonged grief disorder (PGD). However, typical trajectories of insomnia symptoms and risk factors for having a more chronic insomnia trajectory following bereavement are yet unknown. METHOD: In the current investigation, 220 recently bereaved (≤6 months post-loss) participants, completed questionnaires assessing sociodemographic and loss-related characteristics, rumination, experiential avoidance and symptoms of (prolonged) grief and depression, on three time-points (6 months apart). We applied growth mixture models to investigate the typical trajectories of insomnia symptoms following bereavement. RESULTS: Three insomnia trajectory classes emerged, characterized by a resilient (47 %), recovering (43 %), and a chronic trajectory (10 %). Baseline depression symptoms best predicted the type of insomnia trajectory. At one-year follow-up, 9 %, 27 %, and 60 % of participants met the criteria for probable PGD within the resilient, recovering and chronic trajectory, respectively. A parallel process model showed that temporal changes in insomnia symptoms were strongly related to changes in prolonged grief symptoms. CONCLUSION: The results suggest, that targeting insomnia symptoms in the treatment of PGD, particularly with comorbid depression, may be a viable option.

Cross-Lagged Analyses of Prolonged Grief and Depression Symptoms With Insomnia Symptoms.

Prolonged grief disorder, characterized by severe, persistent and disabling grief, has recently been added to the DSM-5-TR and ICD-11. Treatment for prolonged grief symptoms shows limited effectiveness. It has been suggested that prolonged grief symptoms exacerbate insomnia symptoms, whereas insomnia symptoms, in turn, may fuel prolonged grief symptoms. To help clarify if treating sleep disturbances may be a viable treatment option for prolonged grief disorder, we examined the proposed reciprocal relationship between symptoms of prolonged grief and insomnia. On three time points across 6-month intervals, 343 bereaved adults (88% female) completed questionnaires to assess prolonged grief, depression, and insomnia symptoms. We applied random intercept cross-lagged panel models (RICLPMs) to assess reciprocal within-person effects between prolonged grief and insomnia symptoms and, as a secondary aim, between depression and insomnia symptoms. Changes in insomnia symptoms predicted changes in prolonged grief symptoms but not vice versa. Additionally, changes in depression and insomnia symptoms showed a reciprocal relationship. Our results suggest that targeting insomnia symptoms after bereavement is a viable option for improving current treatments for prolonged grief disorder.

Button Battery Ingestions cause the Majority of Severe Complications.

BACKGROUND: Foreign body ingestion in children is a clinically important reason for presentation to the emergency department. The individual outcome ranges from benign spontaneous courses to severe complications. Fatal outcomes occur rarely and complications are related to patient's age as well as type and location of the foreign body. The aim of our present study was to evaluate the outcome of children and adolescents with foreign body ingestion with a focus on complications, which mainly occurred after button battery ingestion. METHODS: We reviewed medical records of patients between 0 and 18 years of age who had presented to the paediatric emergency department of our hospital with suspected foreign body ingestion between January 2011 and March 2021 (123 months). Clinical, imaging, and endoscopic data as well as treatment modalities were analysed. RESULTS: In the ten10 year period under review, a total of 1,162 children and adolescents (6 months - 18 years) presented to our emergency room with suspected foreign body ingestion. Among those, 398 ingestions (34%) could be verified radiologically and/or endoscopically, while in the remaining 764 cases (66%) the suspicion could not be confirmed. The majority of patients with verified ingestion (n=324; 81%) presented with ingestion of a metallic foreign body. We observed 55 cases with verified ingestion of a button battery. Five of these cases had severe complications, with a near-fatal course in two patients who developed an oesophageal-tracheal fistula. CONCLUSION: In contrast to all other ingestions of foreign bodies in children, button battery ingestions lead to mucosal damage and severe complications in a significant number of children.

Elbasvir/grazoprevir in children aged 3-18 years with chronic HCV genotype 1 or 4 infection: a pharmacokinetic modeling study.

BACKGROUND: Approximately 3.5 million children and adolescents worldwide are chronically infected with HCV. This study uses pharmacokinetic modeling to identify pediatric doses of elbasvir/grazoprevir (EBR/GZR) that achieve plasma concentrations similar to those seen in adults receiving the approved fixed-dose combination regimen of EBR/GZR. PATIENTS AND METHODS: We conducted a nonrandomized, single-arm, multicenter, open-label phase 2b trial in children and adolescents aged 3 to <18 years with chronic HCV genotype 1 or 4 infection (NCT03379506). Pharmacokinetic data were used to bridge efficacy and safety data from adults to children in a stepwise (oldest to youngest) manner. A total of 57 participants were enrolled: cohort 1 (aged 12 to <18 y), n=22; cohort 2 (aged 7 to <12 y), n=17; and cohort 3 (aged 3 to <7 y), n=18. RESULTS: Steady-state plasma exposures were achieved by week 4 for EBR and GZR in all cohorts and daily dosing achieved geometric mean steady-state area under the concentration-time curve at 0-24 hours that fell within comparability bounds established for adults. All participants achieved sustained virologic response 12 weeks after completing treatment (ie, undetectable HCV RNA 12 wk following completion of treatment). Headache (n=4), fatigue (n=4), and nausea (n=2) were the most common treatment-related adverse events (all mild or moderate); no participant discontinued because of an adverse event. CONCLUSIONS: Pediatric EBR/GZR pharmacokinetic models were successfully developed based on complex adult population pharmacokinetic models. At appropriate age-related doses, EBR/GZR is safe and effective in pediatric and adolescent participants with HCV infection.

Hemodiafiltration: Technical and Medical Insights.

Despite the significant medical and technical improvements in the field of dialytic renal replacement modalities, morbidity and mortality are excessively high among patients with end-stage kidney disease, and most interventional studies yielded disappointing results. Hemodiafiltration, a dialysis method that was implemented in clinics many years ago and that combines the two main principles of hemodialysis and hemofiltration-diffusion and convection-has had a positive impact on mortality rates, especially when delivered in a high-volume mode as a surrogate for a high convective dose. The achievement of high substitution volumes during dialysis treatments does not only depend on patient characteristics but also on the dialyzer (membrane) and the adequately equipped hemodiafiltration machine. The present review article summarizes the technical aspects of online hemodiafiltration and discusses present and ongoing clinical studies with regards to hard clinical and patient-reported outcomes.

Different treatment strategies versus a common standard arm (CSA) in patients with newly diagnosed AML over the age of 60 years: a randomized German inter-group study.

A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA (n = 132) or to the study group arms (n = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60-87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45-64)) and the study group arms (53% (95%CI: 47-60) and 59% (95%CI: 58-63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7-14.0) in the CSA, 7.6% (95%CI: 4.5-12.8) in study group A and 11.1% (95%CI: 9.0-13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0-26.9), 17.0% (95%CI: 2.0-23.9), and 19.5% (95%CI: 16.7-22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA.

Impact of Hydrophilic Modification of Synthetic Dialysis Membranes on Hemocompatibility and Performance.

The dialyzer is the core element in the hemodialysis treatment of patients with end-stage kidney disease (ESKD). During hemodialysis treatment, the dialyzer replaces the function of the kidney by removing small and middle-molecular weight uremic toxins, while retaining essential proteins. Meanwhile, a dialyzer should have the best possible hemocompatibility profile as the perpetuated contact of blood with artificial surfaces triggers complement activation, coagulation and immune cell activation, and even low-level activation repeated chronically over years may lead to undesired effects. During hemodialysis, the adsorption of plasma proteins to the dialyzer membrane leads to a formation of a secondary membrane, which can compromise both the uremic toxin removal and hemocompatibility of the dialyzer. Hydrophilic modifications of novel dialysis membranes have been shown to reduce protein adsorption, leading to better hemocompatibility profile and performance stability during dialysis treatments. This review article focuses on the importance of performance and hemocompatibility of dialysis membranes for the treatment of dialysis patients and summarizes recent studies on the impact of protein adsorption and hydrophilic modifications of membranes on these two core elements of a dialyzer.

Behavioural and functional evidence revealing the role of RBFOX1 variation in multiple psychiatric disorders and traits.

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.

Occurrence of Thromboembolism in Paediatric Patients With Inflammatory Bowel Disease: Data From the CEDATA-GPGE Registry.

Objective: Among patients with inflammatory bowel disease (IBD), the risk of thromboembolism (TE) is increased, representing a relevant cause of morbidity and mortality. In contrast to other extraintestinal IBD manifestations, TE receives much less attention because of its low incidence, estimated at merely 0.4-0.9% in hospitalised children with IBD. Methods: Cases with TE, as documented in the German-Austrian Paediatric IBD registry gesellschaft für pädiatrische gastroenterologie und ernährung - large paediatric patient registry (CEDATA-GPGE), were analyzed retrospectively. For all patients with signs of TE, a questionnaire was filled in by the treating paediatric gastroenterologist. Results: Over 10 years, 4,153 paediatric patients with IBD (0-18 years) were registered in the registry, and 12 of them identified with TE. Eight patients were diagnosed with ulcerative colitis (UC), three with Crohn's disease (CD), and one with IBD-unclassified. The median age at IBD diagnosis was 10 years and at the manifestation of TE 13 years, respectively, with a median latency to TE of 2 years. Prevalence of TE was 0.3%, with a significantly higher risk for patients with UC than CD (OR 5.9, CI 1.56-22.33, p = 0.008). More girls than boys were affected (f:m = 7:5) without reaching significance. Approximately 90% of patients experienced TE during active disease, with relevant cerebral and limb involvement in 6/12 patients. Various risk factors, e.g., hospitalisation, coagulopathy, or anaemia were identified. TE management included intensive care and surgery. Among the 12 patients, 11 recovered fully, in which one patient has focal epilepsy as a sequela. Conclusion: Paediatric patients with IBD have a substantially increased risk for TE. Risk factors, such as those identified should be considered when managing paediatric IBD and preventive measures for those hospitalised taken routinely. Initiating pharmacological thromboprophylaxis is challenging for the lack of published trials on efficacy and safety in paediatric IBD but should be considered carefully in each case.

Thromboprophylaxis with argatroban in critically ill patients with sepsis: a review.

During sepsis, an initial prothrombotic shift takes place, in which coagulatory acute-phase proteins are increased, while anticoagulatory factors and platelet count decrease. Further on, the fibrinolytic system becomes impaired, which contributes to disease severity. At a later stage in sepsis, coagulation factors may become depleted, and sepsis patients may shift into a hypo-coagulable state with an increased bleeding risk. During the pro-coagulatory shift, critically ill patients have an increased thrombosis risk that ranges from developing micro-thromboses that impair organ function to life-threatening thromboembolic events. Here, thrombin plays a key role in coagulation as well as in inflammation. For thromboprophylaxis, low molecular weight heparins (LMWH) and unfractionated heparins (UFHs) are recommended. Nevertheless, there are conditions such as heparin resistance or heparin-induced thrombocytopenia (HIT), wherein heparin becomes ineffective or even puts the patient at an increased prothrombotic risk. In these cases, argatroban, a direct thrombin inhibitor (DTI), might be a potential alternative anticoagulatory strategy. Yet, caution is advised with regard to dosing of argatroban especially in sepsis. Therefore, the starting dose of argatroban is recommended to be low and should be titrated to the targeted anticoagulation level and be closely monitored in the further course of treatment. The authors of this review recommend using DTIs such as argatroban as an alternative anticoagulant in critically ill patients suffering from sepsis or COVID-19 with suspected or confirmed HIT, HIT-like conditions, impaired fibrinolysis, in patients on extracorporeal circuits and patients with heparin resistance, when closely monitored.

Randomized comparison of three high-flux dialyzers during high-volume online hemodiafiltration-the comPERFORM study.

Background: Dialyzers should be designed to efficiently eliminate uraemic toxins during dialysis treatment, given that the accumulation of small and middle molecular weight uraemic solutes is associated with increased mortality risk of patients with end-stage renal disease. In the present study we investigated the novel FX CorAL dialyzer with a modified membrane surface for performance during online hemodiafiltration (HDF) in a clinical setting. Methods: comPERFORM was a prospective, open, controlled, multicentric, interventional, crossover study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online HDF to FX CorAL 600 (Fresenius Medical Care Deutschland), xevonta Hi 15 (B. Braun) and ELISIO 150H (Nipro) each for 1 week. The primary outcome was ß2-m removal rate (ß2-m RR) during online HDF. Secondary endpoints were RR and/or clearance of ß2-m and other molecules. Albumin removal over time was an exploratory endpoint. Non-inferiority and superiority of FX CorAL 600 versus comparators were tested. Results: Fifty-two patients were included and analysed. FX CorAL 600 showed the highest ß2-m RR (75.47%), followed by xevonta Hi 15 (74.01%) and ELISIO 150H (72.70%). Superiority to its comparators was statistically significant (P = 0.0216 and P < 0.0001, respectively). Secondary endpoints related to middle molecules affirmed these results. FX CorAL 600 demonstrated the lowest albumin removal up to 60 minutes and its sieving properties changed less over time than with comparators. Conclusions: FX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in ß2-m RR. Albumin sieving kinetics point to reduced formation of a secondary membrane.

Spine Volumetric BMD and Strength in Premenopausal Idiopathic Osteoporosis: Effect of Teriparatide Followed by Denosumab.

CONTEXT: Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in bone density, microstructure, and strength. OBJECTIVE: To define effects of treatment with teriparatide followed by denosumab on lumbar spine (LS) volumetric bone mineral density (vBMD) and stiffness by finite element analysis assessed on central quantitative computed tomography (cQCT) scans. DESIGN, SETTINGS, AND PARTICIPANTS: Ancillary analysis of baseline, post-teriparatide, and post-denosumab cQCT scans from a randomized trial of 41 women allocated to teriparatide (20 mcg daily; n = 28) or placebo (n = 11). After 6 months, those on teriparatide continued for 18 months, and those on placebo switched to teriparatide for 24 months. After completing teriparatide, 33 enrolled in a Phase 2B extension with denosumab (60 mg every 6 months) for 12 months. MAIN OUTCOME MEASURES: Primary outcomes were percentage change from baseline in LS trabecular vBMD and stiffness after teriparatide and between end of teriparatide and completing denosumab. Percentage change from baseline in LS trabecular vBMD and stiffness after sequential teriparatide and denosumab were secondary outcomes. FINDINGS: There were large increases (all Ps < 0.001) in trabecular vBMD (25%), other vBMD parameters, and stiffness (21%) after teriparatide. Statistically significant increases in trabecular vBMD (10%; P < 0.001) and other vBMD parameters (P = 0.03-0.001) were seen after denosumab, while stiffness increased by 7% (P = 0.068). Sequential teriparatide and denosumab led to highly significant (all Ps < 0.001) increases LS trabecular vBMD (43%), other vBMD parameters (15-31%), and stiffness (21%). CONCLUSIONS: The large and statistically significant increases in volumetric density and stiffness after sequential treatment with teriparatide followed by denosumab are encouraging and support use of this regimen in PreMenIOP.

Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis.

Time-resolving characterization of molecular weight retention changes among three synthetic high-flux dialyzers.

BACKGROUND: Toxin removal capacity (i.e., performance) of a dialyzer is not constant but diminishes during treatment, as the adsorption of proteins to the membrane provides an additional barrier to uremic solutes. We investigated time-resolving molecular weight retention changes among synthetic high-flux dialyzers and compared the results with recent data from a randomized controlled trial. METHODS: In plasma recirculation experiments over 240 min, sieving coefficients (SC) for ß2-microglobulin, myoglobin, and albumin were determined for the FX CorAL (Fresenius Medical Care), ELISIO (Nipro), and xevonta (B. Braun). Molecular weight retention (MWR) curves were generated and the shifts over 120 min were characterized. Effective pore radius was determined, and the predicted albumin loss was compared with clinical data. RESULTS: SC decreased over time for all dialyzers (mean relative decrease across all dialyzers: ß2-microglobulin: 8.0% (120 min); myoglobin: 56.6% (240 min); albumin: 94.1% (240 min)). FX CorAL (7.3%, 52.6% and 91.1%) and ELISIO (7.7%, 51.0%, and 93.8%) showed a lower decrease than xevonta (9.0%, 66.2%, and 97.4%). For all dialyzers, MWR curves shifted toward lower molecular weight, with the lowest shift for FX CorAL (by 0.23 nm at SC50%, 120 min) and highest for xevonta (0.50 nm). FX CorAL had the highest slope over time and the smallest decrease in the effective pore radius (2 min: 2.31 nm, 120 min: 2.08 nm). Predicted albumin loss over 4 h was highest for xevonta (609.3 mg) and comparable between ELISIO (283.6 mg) and FX CorAL (313.3 mg). CONCLUSIONS: Substantial differences in the temporal performance profile of dialyzers exist. The present approach allows the characterization of dialyzer permeability changes over time using standard, clinically relevant protein markers.

Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults.

Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8 years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean ± standard deviation (SD) participant age was 81.7 ± 4.3 years, mean BMAT unsaturation was 3.5% ± 1.0%, and mean saturation was 46.3% ± 7.2% in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: -23.6% (spine) and -13.0% (total hip) (all p < 0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine) and +11.5% (total hip) (all p < 0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent (odds ratio [OR] 1.46; 95% confidence interval [CI], 1.11-1.92) and incident (OR 1.55; 95% CI, 1.03-2.34) vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture (OR 0.58; 95% CI, 0.38-0.89). In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes, whereas unsaturated lipids were associated with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. © 2022 American Society for Bone and Mineral Research (ASBMR).

Restoration-oriented stressors of bereavement.

BACKGROUND AND OBJECTIVES: The Dual Process Model of Coping with Bereavement holds that bereaved people who respond flexibly to loss-oriented stressors (i.e., relating to the loss; to the deceased person) and restoration-oriented stressors (i.e., secondary to loss; daily-life changes, taking on new roles) adapt better to bereavement. Despite growing interest in the Dual Process Model, systematic analyses of the prevalence, characteristics, and correlates of restoration-oriented stressors are lacking. Therefore, we aimed to chart restoration-oriented stressors and their relationship with post-loss adaptation. DESIGN AND METHODS: A community sample of 181 bereaved adults (63% women) completed the 20-item expert-construed Restoration-Oriented Stressors Inventory (ROSI) and questionnaires assessing background characteristics, worry, and prolonged grief and depression symptoms. RESULTS: Main findings were that younger people, and those who lost a parent, partner, or child (vs. other relationship) experienced more restoration-oriented stressors and appraised these as more stressful. Stressors' perceived stressfulness, but not their quantity, related positively to worry. Perceived stressfulness predicted prolonged grief and depression symptoms beyond background characteristics, worry, and the number of stressors. CONCLUSION: Restoration-oriented stressors and their appraisal vary and relate to coping and post-loss mental health. Future research should clarify temporal interrelations between stressors, coping mechanisms, and outcomes.

Early protein C activation is reflective of burn injury severity and plays a critical role in inflammatory burden and patient outcomes.

BACKGROUND: Navigating the complexities of a severe burn injury is a challenging endeavour where the natural course of some patients can be difficult to predict. Straddling both the coagulation and inflammatory cascades that feature strongly in the burns systemic pathophysiology, we propose the pleiotropic protein C (PC) system may produce a viable biomarker to assist traditional evaluation methods for diagnostic and prognostic purposes. METHODS: We enrolled 86 patients in a prospective observational cohort study. Over three weeks, serial blood samples were taken and measured for PC, activated (A)PC, their receptor endothelial protein C receptor (EPCR), and a panel of inflammatory cytokines including C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-17. Their temporal trends were analysed alongside clinical factors including burn size, burn depth, presence of inhalational injury, and a composite outcome of requiring increased support. RESULTS: (i) APC increased from a nadir on Day 3 (2.3±2.1ng/mL vs 4.1±2.5ng/mL by Day 18, p<0.0005), only becoming appropriately correlated to PC from Day 6 onwards (r=0.412-0.721, p<0.05 for all Days 6-21). (ii) This early disturbance in the PC system was amplified in the more severe burns (≥30% total body surface area, predominantly full thickness, or with inhalational injury), which were characterised by a marked fall in PC activation (approximated by APC/PC ratio) and APC levels during Days 0-3 with low unchanged PC levels. Critically low levels of this cytoprotective agent was associated with greater inflammatory burden, as reflected by significantly elevated CRP, IL-6, and IL-8 levels in the more severe compared to less severe burns, and by negative correlations between both PC and APC with most inflammatory cytokines. (iii) Alongside clinical markers of severity at admission (burn size, burn depth, and presence of inhalational injury), only Day 0 APC/PC ratio (OR 1.048 (1.014-1.083), p=0.006), APC (OR 1.364 (1.032-1.803), p=0.029), PC (OR 0.899 (0.849-0.953), p<0.0005), and not any inflammatory cytokines were predictive markers of requiring increased support. Uniquely, decreased Day 0 PC was further individually associated with each increased total length of stay, ICU length of stay, intravenous fluid resuscitation, and total surgeries, as well as possibly mortality. CONCLUSION: An early functional depletion of the cytoprotective PC system provides a physiological link between severe burns and the cytokine storm, likely contributing to worse outcomes. Our findings on the changes in APC, PC and PC activation during this pathological state support APC and PC as early diagnostic and prognostic biomarkers, and provides a basis for their therapeutic potential in severe burn injuries.

Deep impact? Is mercury in dab (Limanda limanda) a marker for dumped munition? Results from munition dump site Kolberger Heide (Baltic Sea).

Dumped munitions contain various harmful substances which can affect marine biota like fish. One of them is mercury (Hg), included in the common explosive primer Hg fulminate. There is still a lack of knowledge whether dumped munitions impact the Hg concentrations in the Baltic Sea environment. This study aims to answer the question if dab caught at the dump site Kolberger Heide show higher Hg concentrations released from munition sources and whether Hg in fish is a usable marker for munition exposure. Therefore, a total of 251 individual dab (Limanda limanda) were analysed including 99 fish from the dump site. In fish from the Kolberger Heide, no elevated Hg concentrations were found compared to reference sites when age-dependent bioaccumulation of mercury was considered. Therefore we conclude that Hg in fish is no suitable indicator for exposure to munition dumping, e.g. in the frame of possible future monitoring studies as Hg exposure originating from dumped munition is only a small contributor to overall Hg exposure of fish.

Intraoperative completion studies in carotid endarterectomy: systematic review and meta-analysis of techniques and outcomes.

BACKGROUND: Declining perioperative stroke and death rates over the past 3 decades have been paralleled by an increasing use of intraoperative completion studies (ICS) following carotid endarterectomy (CEA). Techniques applied include angiography, intraoperative duplex ultrasound (IDUS), flowmetry, and angioscopy. This systematic review and meta-analysis is aiming on providing an overview of techniques and corresponding outcomes. METHODS: A PubMed based systematic literature review comprising the years 1980 through 2020 was performed using predefined keywords to identify articles on different ICS techniques. Pooled analyses and meta-analyses estimating risk ratios (RR) and 95% confidence intervals (CI) were performed to compare outcomes of different ICS modes to nonapplication of any ICS. I2 values were assessed to quantify study heterogeneities. RESULTS: Identification of 34 studies including patients undergoing CEA with angiography (n=53,218), IDUS (n=20,030), flowmetry (n=16,812), and angioscopy (n=2,291). Corresponding rates of perioperative stroke were 1.5%, 1.8%, 3.6%, and 1.5%, perioperative stroke or death occurred in 1.7%, 1.9%, 2.2%, and 2.0%. Intraoperative surgical revision rates were 6.2%, 5.9%, and 7.9% after CEA with angiography, IDUS, and angioscopy, respectively. Compared to nonapplication of any ICS, the pooled analysis revealed angiography to be significantly associated with lower rates of stroke (RR 0.47; 95% CI, 0.36-0.62; P<0.0001) and stroke or death (RR 0.76; 95% CI, 0.70-0.83; P<0.0001). IDUS was significantly associated with lower rates of stroke (RR 0.56; 95% CI, 0.43-0.73; P<0.0001) and stroke or death (RR 0.83; 95% CI, 0.74-0.93; P=0.0018), whereas angioscopy showed a significant association with a lower stroke rate (RR 0.48; 95% CI, 0.033-0.68; P=0.0001), but no effect on the combined stroke or death rate. Angioscopy was associated with a higher intraoperative revision rate compared to angiography (RR 1.29; 95% CI, 1.07-1.54; P=0.006). The meta-analyses confirmed lower perioperative stroke or death rates for angiography (RR 0.83; 95% CI, 0.76-0.91) and IDUS (RR 0.86; 95% CI, 0.76-0.98) compared to non-application of any ICS, whereas flowmetry showed no significant association. CONCLUSIONS: This study represents the first systematic literature review and meta-analysis on usage of ICSs in CEA. Data strongly indicate a significant beneficial effect of angiography, IDUS, and angioscopy on perioperative CEA outcomes. Any carotid surgeon should consider implementation of ICSs in his routine armamentarium.