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Purpose This study describes the creation of patient-specific (PS) osteo-ligamentous finite element (FE) models of the spine, ribcage, and pelvis, simulation of up to three years of region-specific, stress-modulated growth, and validation of simulated curve progression with patient clinical angle measurements. Research Question: Does the inclusion of region-specific, stress-modulated vertebral growth, in addition to scaling based on age, weight, skeletal maturity, and spine flexibility allow for clinically accurate scoliotic curve progression prediction in patient-specific FE models of the spine, ribcage, and pelvis? Methods Frontal, lateral, and lateral bending X-Rays of five AIS patients were obtained for approximately three-year timespans. PS-FE models were generated by morphing a normative template FE model with landmark points obtained from patient X-rays at the initial X-ray timepoint. Vertebral growth behavior and response to stress, as well as model material properties were made patient-specific based on several prognostic factors. Spine curvature angles from the PS–FE models were compared to the corresponding X-ray measurements. Results Average FE model errors were 6.3 ± 4.6°, 12.2 ± 6.6°, 8.9 ± 7.7°, and 5.3 ± 3.4° for thoracic Cobb, lumbar Cobb, kyphosis, and lordosis angles, respectively. Average error in prediction of vertebral wedging at the apex and adjacent levels was 3.2 ± 2.2°. Vertebral column stress ranged from 0.11 MPa in tension to 0.79 MPa in compression. Conclusion Integration of region-specific stress-modulated growth, as well as adjustment of growth and material properties based on patient-specific data yielded clinically useful prediction accuracy while maintaining physiological stress magnitudes. This framework can be further developed for PS surgical simulation.

Funding Acknowledgements Type of funding sources: None. Introduction Historically, the prognosis of those women suffering a STelevation myocardial infarction (STEMI), has been worse compared to men. Some causal factors are presentation at later ages, atypical symptoms, lower perception of risk and less sensitivity of the health care providers. Purpose Our hypothesis is that there are still differences in the presentation of STEMI based on gender, which could be identified to guide new public campaigns in this perspective. Therefore our primary outcome is to find gender differences in symptoms and time delays in a cohort of STEMI patients, and secondary outcomes are differences in mortality and bleeding. Methods We conducted a retrospective analysis carried out in the Acute Cardiac Care Unit (ACCU) of a tertiary care hospital, where 50% of the medical staff are women. Patients hospitalized for STEMI for one year were included and a detailed caracterization of symptoms, time delays, and adverse events was recorded. Finally, the patients were classified according to gender, and differences in primary and secondary outcomes between both groups were analyzed. Results Between May/2020 and May/2021, 1056 patients were admitted to the ACCU, 33% were women. A total of 115 STEMI patients were included for the analysis, 21% were women. Basal characteristics of both groups were equivalent, except for a non significand trens towards less prevalence of peripheral arterial disease in women (0% vs. 11%; OR 0.890, IC 95% 0.828-0.957; p=0.089). Opressive chest pain was the most frequent symptom, but it was less frequent in women (75% vs. 91.4%, OR 0.284, IC 95% 0.085-0.948; p=0.033), whereas they presented more frequently with stabbing pain (13% vs. 2.4%, OR 6, IC 95% 1.073-38.35; p=0.035), and their pain was more frequently radiated towards the neck (28.6% vs. 4.9%, OR 7.7, IC 95% 1.1936-30.631; p=0.001), and associated to nausea/vomiting (45% vs. 1.3%, OR 5.809, IC 95% 1.930-17.486; p=0.001). There was a non-significant trend towards a longer time delay between pain onset and seek for help in women (185min IQR 747 vs. 60min IQR 454, p=0.098), being the other system time delays equivalent between both gender groups. Women had an increased bleeding risk, with a higher CRUSADE score (47.48 ± 22.92 vs. 28.60 ± 16.72, p=0.001) and higher incidence of bleeding events (12.55% vs. 0%, OR 11.68, IC 95% 9.82-13.29, p=0.001). There were no differences in the treatments administered or in mortality (12.5% vs. 14.3%, p=0.822). Conclusions Women suffering a STEMI more often reported stabbing chest pain, radiating to the neck, and associated to nausea/vomiting compared with men, and took longer to seek for help. These findings could help in the design of future campaigns to minimize time delays, targeting these different symptoms in female population.

Funding Acknowledgements Type of funding sources: None. Background Aadverse left ventricle remodeling’s natural evolution without proper therapy leads to low left ventricle ejection fraction (LVEF) and high morbidity and mortality. LVEF evolution after discharge in patients with de novo LV dysfunction (≤40%) detected during an intensive cardiac care unit (ICCU) hospitalization is not well known. Purpose To characterize LVEF evolution after discharge in patient with de novo LV dysfunction (≤40%) detected during an Intensive Cardiac Care Unit (ICCU) admission according to etiology: ischemic etiology (IE)Vs non-ischemic etiology (NIE). Methods We retrospectively analyzed clinical, echocardiographyc, pharmacological and coronary angiography -related variables from 154 consecutive patients admitted from May 2020 to July 2022 in the ICCU of a tertiary hospital and whose LVEF at discharge was ≤40%. Patients were grouped according to LV dysfunction etiology in ischemic and non-ischemic. LVEF at follow-up was registered when available. Results This cohort had a mean age of 64.8 ±14 years and 127 (82%) were male. Mean left ventricle ejection fraction was 30 ±6.8%. Among them, 119 (77%) had ischemic etiology (IE) and 35 (23%) non-Ischemic (NIE). Inotropes during admission were required in 29 (19%) and 151 (98%) were studied with coronary angiography. 70 (46%) were also studied with MRI during hospitalization; 35 (23%) had right ventricular dysfunction (RVD) and 39 (25%) had any kind of bundle branch block at discharge’s EKG. At discharge, 121 (78%) received betablockers (BB), 69 (45%) received Angiotensin Converser Enzyme Inhibitor (ACEI), 17 (11%) received Angiotensin Receptor Blocker (ARB), 24 (16%) received sacubitril-valsartan (ARNI), 88 (57%) received Mineralcorticoid Receptor Antagonist (ARM) and 39 (25%) received Sodium-Glucos type-2 inhibitors. At discharge, LVEF in patients with IE was 31 ±6% and 27 ±8% in NIE (p=0,01). Follow-up echocardiography was available in 119 (77%) of them. Mean last available follow-up LVEF was 46% ±11 in NIE while among IE was 40% ±11 (p=0,02). LVEF increase was of 17±11% in NIE and 9±9% in IE (p=0,0004). Among all, 36 patients normalized LVEF, 14 (50%) in NIE group and 22 (25%) in IE (P=0.01). In a multiple linear regression model adjusting by age, sex, QRS duration, left bundle branch block, TRC implantation and modifying-disease drugs, NIE etiology was independently associated with a 7,6% increase in LVEF compared to IE (p=0,003). Conclusions Our findings support that LVEF improvement after admission to ICCU with de novo LV dysfunction is strongly dependent on etiology. Patients with NIE tend to have an initial worse LVEF but greater improvement at follow-up.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Saludo Carlos III (ISCIII)-FEDER PI19/00264 Ministerio de Universidades - FPU19/04925 Background Inflammation and hypoxia are key players in the pathophysiology of Out-of-Hospital Cardiac Arrest (OHCA), and may be directly associated with neurological outcomes (NO). MicroRNAs that control inflammation (inflam-miRNAs) and hypoxia (hypoxi-miRNAs) have been largely associated with cardiovascular and neurological diseases. However, the kinetics and regulatory role of inflam- and hypoxi-miRNAs on NO in OHCA have been poorly studied. Purpose To associate inflam- and hypoxi-miRNA expression kinetics with NO in OHCA survivors. Methods Consecutive OHCA patients were prospectively recruited from March 2019 to November 2020. Blood samples were taken during hospitalization at 0 and 24 hours after admission. Patients were grouped according to their cerebral performance category (CPC) at hospital discharge. In silico analysis determined miRNAs to be analysed in serum. Results A total of 40 patients (10% women, age 60 ± 10 years) were analysed. At hospital discharge, 17 patients survived with good NO (GNO; CPC 1-2) and 13 patients presented a poor NO (PNO; CPC 3-5). In silico analysis unveiled a network of 11 miRNAs related to cardiovascular and coronary artery disease as well as hypoxic encephalopathy and neuro-inflammation (Figure 1). At their hospital admission, differences between GNO and PNO patients in anti-inflammatory (AI) miR-181a-5p and pro-inflammatory (PI) miR-155-5p levels were observed (p-value = 0.0355 and 0.0310 respectively) (Figure 2A). However, there were no differences in levels of AI miR-let-7a-5p and PI miR-1-3-p at 0h and 24h between both groups (Figure 2B). When comparing changes in inflam-miRNA expression between 0 and 24 h, PNO patients showed an augmented total inflammatory response (TIR), increasing the levels of a) AI miR-181-5p (p-value = 0.0295) and miR-let-7a-5p (p-value = 0.0013); and b) PI miR-155-5p (p-value = 0.0112) and miR-1-3-p (p-value = 0.0375) (Figure 2C). Changes in inflam-miRNAs in PNO were associated to an increase in blood C-reactive protein levels during hospitalization (GNO 18.73 ± 5.4 mg/L vs. PNO 26.00 ± 10.31 mg/L, p-value = 0.0055). (Figure 2D). In this inflammatory scenario, only GNOP patients were able to increase levels of key ischemia-protective hypoxi-miRNA miR-484 during first 24h (p-value = 0.0301) (Figure 2E). Conclusions In survivors of OHCA, the kinetic of inflam- and hipoxi-miRNAs expression changes during first 24h hospital admission is correlated with inflammation and NO. GNO Patients have decreased miRNA-mediated changes in TIR and increased miRNA-mediated hypoxic protection while PNO patients have increased miRNA-mediated changes in TIR with reduced miRNA-mediated hypoxic protection. These results focus the importance to contain inflammatory response in OHCA survivors as well as to stimulate mechanisms in front of ischemia, giving relevance to novel miRNA-mediated targetable mechanisms.

Zetomipzomib (KZR-616) is a selective inhibitor of the immunoproteasome currently undergoing clinical investigation in autoimmune disorders. Here, we characterized KZR-616 in vitro and in vivo using multiplexed cytokine analysis, lymphocyte activation and differentiation, and differential gene expression analysis. KZR-616 blocked production of >30 pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs), polarization of T helper (Th) cells, and formation of plasmablasts. In the NZB/W F1 mouse model of lupus nephritis (LN), KZR-616 treatment resulted in complete resolution of proteinuria that was maintained at least 8 weeks after the cessation of dosing and was mediated in part by alterations in T and B cell activation, including reduced numbers of short and long-lived plasma cells. Gene expression analysis of human PBMCs and tissues from diseased mice revealed a consistent and broad response focused on inhibition of T, B, and plasma cell function and the Type I interferon pathway and promotion of hematopoietic cell lineages and tissue remodeling. In healthy volunteers, KZR-616 administration resulted in selective inhibition of the immunoproteasome and blockade of cytokine production following ex vivo stimulation. These data support the ongoing development of KZR-616 in autoimmune disorders such as systemic lupus erythematosus (SLE)/LN.

Dendroprovenancing provides critical information regarding the origin of wood, allowing further insights into economic exploitation strategies and source regions of timber products. Traditionally, dendroprovenancing relies on pattern-matching of tree rings, but its spatial resolution is limited by the geographical coverage of species-specific chronologies available for crossdating and, in the case of short-distance trades, by scarce environmental variability. Here, we present an approach to provenance timber with high spatial resolution from forested areas that have been exploited intensively throughout history, with the aim to understand the sustainability of the various woodland management practices used to supply timber products. To this end, we combined tree-ring width (TRW), wood anatomical and geochemical analyses in addition to multivariate statistical validation procedures to trace the origin of living oak trees (Quercus robur) sampled in four stands located within a 30-km radius around the city of Limoges (Haute-Vienne, France). We demonstrate that TRW and wood anatomical variables (and in particular cell density) robustly discriminate the eastern from the western site, while failing to trace the origin of trees from the northern and southern sites. Here, strontium isotopic ratios (87Sr/86Sr) and Ca concentrations identify clusters of trees which could not be identified with TRW or wood anatomy. Ultimately, our study demonstrates that the coupling of wood anatomy with geochemical signatures allows to correctly pinpoint the origin of trees. Given the small geographic scale of our study and the limited differences in elevation and climate between study sites, our results are particularly promising for future dendroprovenancing studies. We thus conclude that the combination of multiple approaches will not only increase the accuracy of dendroprovenancing studies at local scales, but could also be implemented at much larger scales to identify trends in historic timber supply throughout Europe.

Background Reperfusion networks have permitted improvements in reperfusion delays in primary percutaneous coronary intervention (PPCI)-treated ST elevation myocardial infarction (STEMI). However, the impact on myocardial salvage (MS) of direct transfer to the catheterization laboratory (cath-lab) to minimize system delay remains unknown. Objective We sought to quantify the myocardial salvage index (MSI) acutely and to assess adverse remodeling at 6 months in PPCI-treated STEMI according to the mode of patient presentation. Methods Between 2005 and 2021 we included 493 patients in a single center registry of first PPCI-treated STEMI who were studied with Late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) in the acute phase. Among them, 414 (84.0%) underwent a second LGE-CMR at 6 months. Subjects were classified depending on the mode of presentation: those diagnosed out-of-hospital and directly transferred to the cath-lab by the Emergency Medical Services (EMS group, 29.82%); subjects with first medical contact in a PCI-capable hospital (PCI-H group, 41.75%); and patients presenting to a non-PCI-capable center and transferred for PCI (non-PCI-H group, 28.43%). We computed the angiographic area at risk by BARI score, and combined it with the LGE-CMR derived infarct size to compute a validated MSI, expressed as percentage of area at risk. The change in ejection fraction (EF) and indexed left ventricle end-diastolic volume (iLVEDV) from baseline to 6 months was also computed. Results The mean age was 58.9±11.9 years, 84.5% were male and 51.4% had anterior STEMI. Total median ischaemic time was (median (interquartile range)) 126 (105–161) min in the EMS group, 201 (145–321) min in the PCI-H group and 300 (173–592) min in the non-PCI-H group (p Conclusions Patients with out-of-hospital diagnostis of STEMI by the EMS who were directly transferred to the cath-lab showed shorter total ischaemic times, resulting in increased myocardial salvage and a trend towards improved indexes of left ventricular function at 6 months. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Grant from La Maratό de TV3 and grant from Fundaciό La Caixa

Background Delay in primary percutaneous coronary intervention (PPCI) in ST elevation myocardial infartion (STEMI) is associated with worse prognosis. In our regional STEMI network, the first medical contact (FMC) facility type defines 4 different assistance pathways (i.e. emergency medical services'diagnosis on the field and direct transfer to the catheterization laboratory (cath. lab) of a PCI hospital (EMS group); direct admission to a PCI hospital (PCI-H group); admission to community hospital and transfer to the cath lab of the PCI-H (CH group); diagnosis in a primary care centre and transfer to the cath lab of the PCI-H (PCC group). Each different FMC has been associated with different degrees in reperfusion delay. Objective To determine the influence of FMC facility type on 1-year mortality in patients with STEMI in our regional STEMI network. Methods This is a retrospective study based on the STEMI network registry, a mandatory registry conducted since its implantation and supervised by the regional health authorities. We included STEMI patients treated with PPCI from January 2010 to December 2020. We analyzed differences in clinical variables, reprefusion times and 1-year all-cause mortality regarding the FMC facility type. Results We included 18332 patients (EMS 34.25%, PCI-H 12.28%, CH 33.47%, PCC 20.01%). Initial Killip classes III–IV: EMS 8.43%, PCI-H 7.51%, CH 5.54%, PCC 3.76%; p Conclusions First medical contact with EMS and direct transfer to the cath lab was associated with lower adjusted 1-year mortality compared to first medical contact with a PCI hospital or a community hospital. Funding Acknowledgement Type of funding sources: None.

The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens. We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection. A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4+ TILs were evident in 76.9% of cases, CD8+ in 92.3%, CD45RO+ in 92.3%, and FOXP3+ in 46.2%, as well as CD68+ TAMs in 100% and CD163+ in 100%. For the 15 BM cases, CD4+ TILs were evident in 60.0% of cases, CD8+ in 93.3%, CD45RO+ in 73.3%, and FOXP3+ in 35.7%, as well as CD68+ TAMs in 86.7% and CD163+ in 100%. An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.

Growth modulation is an emerging method for treatment of angular skeletal deformities such as adolescent idiopathic scoliosis (AIS). The Hueter-Volkmann law, by which growth is stimulated in tension and inhibited in compression, is widely understood, and applied in current growth-modulating interventions such as anterior vertebral body tethering (AVBT) for AIS. However, without quantification of the growth rate effects of tension or compression, the possibility of under- or over- correction exists. A definitive mechanical growth modulation relationship relating to treatment of such skeletal deformities is yet to exist, and the mechanisms by which growth rate is regulated and altered are not fully defined. Review of current literature demonstrates that longitudinal (i.e., lengthwise) growth rate in multiple animal models depend on load magnitude, anatomical location, and species. Additionally, alterations in growth plate morphology and viability vary by loading parameters such as magnitude, frequency, and whether the load was applied persistently or intermittently. The aggregate findings of the reviewed studies will assist in work towards increasingly precise and clinically successful growth modulation methods. Part 1 of this review focuses on the effects of mechanical loading, species, age, and anatomical location on the macro-scale alterations in longitudinal bone growth, as well as factors that affect growth plate material properties. Part 2 considers the effects on micro-scale alterations in growth plate morphology such as zone heights and proportions, chondrocyte viability, and related gene and protein expression.

Asylum seekers report exposure to human rights violations associated with a range of psychological and medical sequelae. Clinical evaluators can provide forensic evaluations that document evidence associated with their reports of persecution. The aim of this study was to characterize the forms of abuse experienced by asylum seekers, the psychological consequences of abuse, and the frequency with which clinician-evaluators found evidence that corroborated asylum seekers’ reports. We completed a retrospective chart review of 121 asylum seekers who received pro bono medical-legal evaluations through a human rights program and analyzed data using the constant comparative method. Eighty-eight percent of the clients reported experiencing multiple human rights abuses. Ninety-one percent of the clients who received psychological evaluations presented with symptoms associated with depression, anxiety, or trauma and stressor-related disorders. Clinician-evaluators found physical or psychological evidence consistent with the clients’ reports in 97% of cases. Forms, perpetrators, and psychological consequences of abuse varied significantly by gender and geographic region. Asylum seekers report diverse forms of persecution in their countries of origin that differ by gender and geographic region. Clinician-evaluators overwhelmingly found physical and psychological evidence consistent with the asylum seekers’ accounts of persecution.

Brain metastases from lung adenocarcinoma (BM-LUAD) frequently cause patient mortality. To identify genomic alterations that promote brain metastases, we performed whole-exome sequencing of 73 BM-LUAD cases. Using case-control analyses, we discovered candidate drivers of brain metastasis by identifying genes with more frequent copy-number aberrations in BM-LUAD compared to 503 primary LUADs. We identified three regions with significantly higher amplification frequencies in BM-LUAD, including MYC (12 versus 6%), YAP1 (7 versus 0.8%) and MMP13 (10 versus 0.6%), and significantly more frequent deletions in CDKN2A/B (27 versus 13%). We confirmed that the amplification frequencies of MYC, YAP1 and MMP13 were elevated in an independent cohort of 105 patients with BM-LUAD. Functional assessment in patient-derived xenograft mouse models validated the notion that MYC, YAP1 or MMP13 overexpression increased the incidence of brain metastasis. These results demonstrate that somatic alterations contribute to brain metastases and that genomic sequencing of a sufficient number of metastatic tumors can reveal previously unknown metastatic drivers.

This study describes the creation of patient-specific (PS) osteo-ligamentous finite element (FE) models of the spine, ribcage, and pelvis, simulation of up to three years of region-specific, stress-modulated growth, and validation of simulated curve progression with patient clinical angle measurements.Does the inclusion of region-specific, stress-modulated vertebral growth, in addition to scaling based on age, weight, skeletal maturity, and spine flexibility allow for clinically accurate scoliotic curve progression prediction in patient-specific FE models of the spine, ribcage, and pelvis?Frontal, lateral, and lateral bending X-Rays of five AIS patients were obtained for approximately three-year timespans. PS-FE models were generated by morphing a normative template FE model with landmark points obtained from patient X-rays at the initial X-ray timepoint. Vertebral growth behavior and response to stress, as well as model material properties were made patient-specific based on several prognostic factors. Spine curvature angles from the PS-FE models were compared to the corresponding X-ray measurements.Average FE model errors were 6.3 ± 4.6°, 12.2 ± 6.6°, 8.9 ± 7.7°, and 5.3 ± 3.4° for thoracic Cobb, lumbar Cobb, kyphosis, and lordosis angles, respectively. Average error in prediction of vertebral wedging at the apex and adjacent levels was 3.2 ± 2.2°. Vertebral column stress ranged from 0.11 MPa in tension to 0.79 MPa in compression.Integration of region-specific stress-modulated growth, as well as adjustment of growth and material properties based on patient-specific data yielded clinically useful prediction accuracy while maintaining physiological stress magnitudes. This framework can be further developed for PS surgical simulation.

Funding Acknowledgements Type of funding sources: None. Background Recovered out-of-hospital cardiac arrest (OHCA) is associated with high morbidity and mortality. Having prognostic tools within the first hours of admission to hospital is critical. The pH is a widespread arterial blood gas marker, but the influence of its respiratory/metabolic components has not yet been established. Purpose The objective of the study is to analyze the utility of first bicarbonate measure as a predictor of in-hospital mortality after OHCA. Methods This is a prospective observational study carried out on survivors to the initial phase of an OHCA, who were admitted to the Acute Cardiovascular Care Unit of our single terciary center. Clinical characteristics and initial blood gas data were analyzed. The primary objective was in-hospital mortality. Results A total of 50 patients were included (2019-2021), of which 40% died during the course of the hospitalization. First pH determination showed significant differences between survivors and dead. Of its two components, the bicarbonate was lower in the patients who died (13.93 ± 3.01 vs. 18.48 ± 4.15, p Conclusions Bicarbonate was the best initial predictor of mortality after an OHCA, above pH, which, although being a good predictor, is potentially altered by PCO2 (which was not a good predictor).

Funding Acknowledgements Type of funding sources: None. Background Mortality in cardiogenic shock (CS) remains very high, although the CS aetiology could influence in the acute-phase and long term prognosis. Purpose The aim is to investigate in-hospital mortality and 6 months prognosis (all-cause mortality and cardiovascular readmission) in CS patients depending on the CS aetiology in a Mediterranean cohort. Method Shock CAT study was a multicentre, prospective, observational study conducted between December 2018 and December 2019 in eight public University hospitals in Catalonia (Spain), including CS patients due to acute coronary syndrome (ACS) and other aetiologies. Data on clinical presentation, biomarkers, management, including mechanical assistance support were analyzed comparing ACS and non-ACS patients. In-hospital and 90-days mortality and 6-months prognosis (mortality and cardiovascular readmission) were available and have been compared between groups. Results A total of 382 CS patients were included, mean age was 65.3 (SD 13.9) years and 75.1% were men. Patient were classified in ACS (n=232, 60.7%) and non-ACS (n=150, 39.3%). In ACS group, 77.6% were STEMI, reperfusion in 84.7% of cases, all with primary angioplasty, 9% developed mechanical complications and 19.4% primary ventricular fibrillation. Main non-ACS aetiologies were severe heart failure (36.2%), malignant arrhythmias (22.1%), valve disease (8.0%) and myocarditis (7.4%). ACS group had less prevalence of women (17.7% vs 36%, p=0.001) and previous myocardial infarction (13.9% vs 24.8%, p=0.007). Mechanical assistance device was implanted more frequently in ACS patients (43.1% vs 16.7%, p Conclusions One-third of cardiogenic shock patients died during hospital admission. Patients with CS due to ACS had 28% higher in-hospital mortality than non-ACS, although this difference decreased at 90 days and 6 months. Cardiovascular 6-months readmission was 8.7%, without differences between groups.

Funding Acknowledgements Type of funding sources: None. Background Mortality in cardiogenic shock (CS) remains very high. Several risk scores have been purposed to early stratification. The aetiology of CS could influence in the usefulness of different risk scores. Purpose The aim is to investigate in-hospital prognosis and mortality risk in CS patients comparing the prognostic accuracy of CardShock and IABP scores in a Mediterranean cohort depending on the CS aetiology. Method Shock CAT study was a multicentre, prospective, observational study conducted between December 2018 and December 2019 in eight public University hospitals in Catalonia (Spain), including CS patients due to acute coronary syndrome (ACS) and other aetiologies. Data on clinical presentation, biomarkers, management, including mechanical assistance support were analyzed. Cardshock and IABP score have been compared to assess 90-days mortality risk in a Mediterranean cohort. Results A total of 382 CS patients were included, mean age was 65.3 (SD 13.9) years and 75.1% were men. The most common cause of CS was ACS (61%, n=233); of them, 77.6% were STEMI, 9% developed mechanical complications and 19.4% primary ventricular fibrillation. STEMI patients were reperfused in 84.7% of cases, all with primary angioplasty. Main non-ACS aetiologies were severe acute heart failure, malignant arrhythmias and myocarditis. Mechanical assistance device was implanted in one third of patients (n=119), mainly intraaortic balloon pump (26.1%), ECMO in 7.8% and Impella CP in 4.5%. Average Cardshock score was 4.3 (SD 1.74) and mean IABP score was 2.2 (SD 1.61). In-hospital mortality was 33% (126 patients) and 90-days mortality was 37.3% (141 patients). Receiver-operating characteristic (ROC) curves demonstrated that IABP shock score had superior prognostic power for predicting 90-days mortality when compared with Cardshock score (area under the curve 0.72 vs 0.66) respectively, p=0.042; Figure 1. Although this superiority only was reached in ACS patients (area under the curve -AUC- 0.74 vs 0.66) respectively, p=0.047; because both scores were similar in non-ACS (AUC 0.64 vs 0.62, p=0.693), Figure 2. Conclusions Even though invasive management with STEMI reperfusion and mechanical assistance devices, cardiogenic shock in-hospital mortality remains 33% in a contemporary Mediterranean cohort. In this population, IABP shock score provided better 90-days mortality risk prediction than CardShock score, mainly in CS sue to ACS.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

The Knosp criteria have been the historical standard for predicting cavernous sinus invasion, and therefore extent of surgical resection, of pituitary macroadenomas. Few studies have sought to reappraise the utility of this tool after recent advances in visualization and modeling of tumors in complex endoscopic surgery.To evaluate our proposed alternative method, using 3-dimensional (3D) volumetric imaging, and whether it can better predict extent of resection in nonfunctional pituitary adenomas.Patients who underwent endoscopic transsphenoidal resection of pituitary macroadenomas at our institution were reviewed. Information was collected on neurological, endocrine, and visual function. Volumetric segmentation was performed using 3D Slicer software. Relationship of tumor volume, clinical features, and Knosp grade on extent of resection was examined.One hundred forty patients were identified who had transsphenoidal resection of nonfunctional pituitary adenomas. Macroadenomas had a median volume of 6 cm 3 (IQR 3.4-8.7), and 17% had a unilateral Knosp grade of at least 3B. On multiple logistic regression, only smaller log-transformed preoperative tumor volume was independently associated with increased odds of gross total resection (GTR; odds ratio: 0.27, 95% CI: 0.07-0.89, P.05) when controlling for tumor proliferative status, age, and sex (area under the curve 0.67). The Knosp criteria did not independently predict GTR in this cohort ( P.05, area under the curve 0.46).Increasing use of volumetric 3D imaging may better anticipate extent of resection compared with the Knosp grade metric and may have a greater positive predictive value for GTR. More research is needed to validate these findings and implement them using automated methods.

Finite element (FE) modeling of the spine has increasingly been applied in orthopedic precision-medicine approaches. Previously published FE models of the pediatric spine growth have made simplifications in the geometry of anatomical structures, material properties, and representation of vertebral growth. To address those limitations, a comprehensive FE model of a pediatric (10-year-old) osteo-ligamentous thoracic and lumbar spine (T1-L5 with intervertebral discs (IVDs) and ligaments), ribcage, and pelvis with age- and level-specific ligament properties and orthotropic region-specific vertebral growth was developed and validated. Range of motion (ROM) measures, namely, lateral bending, flexion–extension, and axial rotation, of the current 10 YO FE model were generally within reported ranges of scaled in vitro adult ROM data. Changes in T1-L5 spine height, as well as kyphosis (T2-T12) and lordosis (L1-L5), angles in the current FE model for two years of growth (from ages 10 to 12 years) were within ranges reported from corresponding pediatric clinical data. The use of such comprehensive pediatric FE models can provide clinically relevant insights into normative and pathological biomechanical responses of the spine, and also contribute to the development and optimization of clinical interventions for spine deformities.

The proteasome is responsible for mediating intracellular protein degradation and regulating cellular function with impact on tumor and immune effector cell biology. The proteasome is found predominantly in two forms, the constitutive proteasome and the immunoproteasome. It has been validated as a therapeutic drug target through regulatory approval with 2 distinct chemical classes of small molecular inhibitors (boronic acid derivatives and peptide epoxyketones), including 3 compounds, bortezomib (VELCADE), carfilzomib (KYPROLIS), and ixazomib (NINLARO), for use in the treatment of the plasma cell neoplasm, multiple myeloma. Additionally, a selective inhibitor of immunoproteasome (KZR-616) is being developed for the treatment of autoimmune diseases. Here, we compare and contrast the pharmacokinetics (PK), pharmacodynamics (PD), and metabolism of these 2 classes of compounds in preclinical models and clinical studies. The distinct metabolism of peptide epoxyketones, which is primarily mediated by microsomal epoxide hydrolase, is highlighted and postulated as a favorable property for the development of this class of compound in chronic conditions.

Objective This article aims to characterize 14 patients who underwent purely endoscopic surgical debridement of acute invasive skull base fungal rhinosinusitis, and to evaluate postoperative outcomes and risk for recurrence.Design Retrospective cohort study.Setting Tertiary single-institution neurosurgery department.Participants We performed a retrospective analysis of all patients with skull base fungal infections treated with a purely endoscopic surgical approach at Mount Sinai Hospital from 1998 to 2018.Main Outcome Measures Clinical presentation, number of recurrences, and mortality rate.Results The most common underlying medical comorbidities were hematologic malignancy in 8 (57.1%) patients and poorly controlled diabetes mellitus in 7 (50%) patients. Presenting symptoms included headache (50%), eye pain (35.7%), facial pain (28.6%), visual changes (21.4%), and nasal congestion (14.3%). The fungal organisms identified on culture were Aspergillus (42.9%), Mucorales (28.6%), Fusarium (14.3%), Penicillium (7.1%), and unspecified (7.1%). Eight (57.1%) patients developed recurrence and required multiple surgical debridements. Patients who had only a hematologic malignancy were more likely to require multiple surgical debridements compared with those who did not have a hematologic malignancy or those who had both hematologic malignancy and underlying diabetes mellitus (p = 0.03). The mortality rate from surgery was 42.9%.Conclusion Surgical endoscopic intervention is an option for definitive management of acute invasive skull base fungal rhinosinusitis; however, postoperative mortality and risk of recurrence requiring additional surgical interventions remains high. Patients with hematologic malignancy may be more susceptible to recurrent infection requiring multiple surgical debridements. We recommend early aggressive multimodal treatment. Multiple debridements may be warranted in most cases; close clinical surveillance is needed during neurosurgical intervention.

El documento analiza la importancia de la inclusión financiera y la relación que genera con el desarrollo económico de la mujer a través del emprendimiento productivo. El objetivo es mostrar la importancia que produce el trabajo mancomunado entre los sectores que promuevan el acceso a servicios financieros y la creación de emprendimientos para buscar la igualdad de género, para esto se señala la rentabilidad que provocan las mujeres, la evolución de la creación de empresas y sus fuentes de financiamiento, las barreras que se enfrentan al momento de iniciar los emprendimientos y los beneficios que conlleva la inclusión financiera. Por último, los autores resaltan las buenas prácticas y políticas públicas que fomentan los objetivos de igualdad y crecimiento económico de las mujeres.

Introduction: Condylomas or genital warts (GW) are the most frequently diagnosed sexually transmitted infection (STI) in STI centers in Chile, but there are no population statistics available. Objectives: To describe the prevalence of GW in patients from 18-60 years of age who attend outpatient dermatology, gynecology and urology practice; the demographic characteristics of the patients and the diagnostic and treatment tools. Methods: A sample of Chilean specialists stratified by region, population and gender of patients was provided with a logbook and answered a questionnaire. Results: The GW prevalence was 2.44% for the whole group; 3.76% for the 18-34 age group and 1.29% for the 35-60 years group (p = 0.0000). The average age of patients with GW was 29.4 years in women and 32.7 years in men (p = 0.019). The distribution by age was different according to gender and health system. Visual inspection was the most frequent diagnostic method used and imiquimod cream the most common treatment, however, there were differences in the use of diagnostic and therapeutic tools according to the patient’s gender, specialty of the doctor and health system. Conclusions: The high prevalence of GW confirmed the need and importance of public health interventions to address this problem.

Resumen Las neoplasias en glándulas salivales son infrecuentes, representando menos del 3% de los tumores de cabeza y cuello. El carcinoma mucoepidermoide es el tumor maligno más común en glándulas salivales, siendo su principal ubicación la parótida. Clínicamente se asemeja a otras lesiones de mucosa oral, por lo cual, es importante realizar un correcto diagnóstico diferencial. Su comportamiento biológico se relaciona con el grado histológico tumoral, factor relevante en el pronóstico y tratamiento de esta neoplasia. Presentamos el caso de un paciente hombre de 75 años afectado con un tumor en paladar con diagnóstico de carcinoma mucoepidermoide de bajo grado. Como tratamiento se realizó una maxilectomía parcial y una placa obturadora en base a una prótesis removible y posterior reconstrucción con un colgajo libre microvascularizado. Actualmente el paciente se encuentra en controles periódicos, libre de enfermedad. Los tumores de glándulas salivales son un desafío diagnóstico, requieren de exámenes imagenológicos y del estudio histopatológico. Cuando existen dudas en el diagnóstico, se debe considerar repetir la toma de la muestra o la obtención de biopsias de más de una zona representativa que permita el diagnóstico de la lesión.

Funding Acknowledgements Type of funding sources: None. Background Venous to arterial CO2 gap (CO2gap) is calculated by subtracting partial pressure of arterial CO2 to central venous partial pressure of CO2 (ScvCO2). This marker has been studied in septic shock and indicates hypoperfusion when exceeds 6mmHg. Its kinetics and applicability in cardiogenic shock (CS) are unclear, being mixed/central venous saturation and lactate more commonly used. Purpose The objective of the study is to describe CO2gap kinetics in patients with CS. Secondary objective is to analyze if CO2gap is as marker of prognosis in CS. Methods Prospective observational study that included patients admitted for CS in the Acute Cardiovascular Care Unit of a tertiary hospital. Gasometric samples were obtained at admission, 6, 12, 24 and 48 hours from the onset of shock. In-hospital mortality was registered. Results We included 40 patients with CS during 1 year. Most patients were male (80%), average age was 68 years. There was a high incidence of cardiac arrest (58%), most frequent cause of CS was STEMI (45%), in-hospital mortality was 45%, most cases from non-cardiovascular causes (61%). Refractory shock was frequent (28%). Average lactate peak was 6.02 mmol / L. CO2gap kinetics consisted in a peak at admission (8.8mmHg), a valley 6h (7.7mmHg), new peak at 12h (8.5mmHg) and progressive decrease at at 24 (6.8mmHg) and 48h (5.7 mmHg). Significantly, higher CO2gap values at admission (10.97mmHg vs 8.16mmHg, p = 0.007) was predictor of cardiovascular mortality. Lactate values at 6, 12 and 48 hours were also predictors of cardiovascular mortality, as well as ScvO2 at admission. Conclusions Patients with CS present with high CO2gap values during first hours of admission. The kinetics of this marker consists in two peaks at admission and 12 hours from CS onset, a valley at 6 hours and a progressive decrease at 24 and 48 hours. Its determination at admission is associated with cardiovascular mortality. We suggest the potential benefit of combining this marker, along with lactate and ScvO2 values, to guide management of patients with CS. Abstract Figure. CO2 gap and cardiovascular mortality

Supplemental material, sj-pdf-1-epb-10.1177_2399808320987567 for Geo-tagged environmental noise measurement with smartphones: Accuracy and perspectives of crowdsourced mapping by Andrea P��d��r and Szilard Szab�� in EPB: Urban Analytics and City Science

Die Entdeckung einer fast lebensgrossen Bronzehand und eines Dolches im Oktober 2017 bei Pr��les (Plateau de Diesse) im Berner Jura ��berraschte die Fachwelt und l��ste ein grosses Medienecho aus. Die Nachgrabung vor Ort und die Untersuchungen an der Bronzehand durch den Arch��ologischen Dienst des Kantons Bern f��hrten zu weiteren Erkenntnissen. Die Publikation versammelt die Beitr��ge des Kolloquiums vom 30. Oktober 2019 und erg��nzt sie mit weiteren Texten zum Kontext dieses bedeutenden Fundes.