Proximity superconductivity in atom-by-atom crafted quantum dots.

Gapless materials in electronic contact with superconductors acquire proximity-induced superconductivity in a region near the interface1,2. Numerous proposals build on this addition of electron pairing to originally non-superconducting systems and predict intriguing phases of matter, including topological3-7, odd-frequency8, nodal-point9 or Fulde-Ferrell-Larkin-Ovchinnikov10 superconductivity. Here we investigate the most miniature example of the proximity effect on only a single spin-degenerate quantum level of a surface state confined in a quantum corral11 on a superconducting substrate, built atom by atom by a scanning tunnelling microscope. Whenever an eigenmode of the corral is pitched close to the Fermi energy by adjusting the size of the corral, a pair of particle-hole symmetric states enters the gap of the superconductor. We identify these as spin-degenerate Andreev bound states theoretically predicted 50 years ago by Machida and Shibata12, which had-so far-eluded detection by tunnel spectroscopy but were recently shown to be relevant for transmon qubit devices13,14. We further find that the observed anticrossings of the in-gap states are a measure of proximity-induced pairing in the eigenmodes of the quantum corral. Our results have direct consequences on the interpretation of impurity-induced in-gap states in superconductors, corroborate concepts to induce superconductivity into surface states and further pave the way towards superconducting artificial lattices.

Towards Clinical Development of Scandium Radioisotope Complexes for Use in Nuclear Medicine: Encouraging Prospects with the Chelator 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) and Its Analogues.

Scandium (Sc) isotopes have recently attracted significant attention in the search for new radionuclides with potential uses in personalized medicine, especially in the treatment of specific cancer patient categories. In particular, Sc-43 and Sc-44, as positron emitters with a satisfactory half-life (3.9 and 4.0 h, respectively), are ideal for cancer diagnosis via Positron Emission Tomography (PET). On the other hand, Sc-47, as an emitter of beta particles and low gamma radiation, may be used as a therapeutic radionuclide, which also allows Single-Photon Emission Computed Tomography (SPECT) imaging. As these scandium isotopes follow the same biological pathway and chemical reactivity, they appear to fit perfectly into the "theranostic pair" concept. A step-by-step description, initiating from the moment of scandium isotope production and leading up to their preclinical and clinical trial applications, is presented. Recent developments related to the nuclear reactions selected and employed to produce the radionuclides Sc-43, Sc-44, and Sc-47, the chemical processing of these isotopes and the main target recovery methods are also included. Furthermore, the radiolabeling of the leading chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and its structural analogues with scandium is also discussed and the advantages and disadvantages of scandium complexation are evaluated. Finally, a review of the preclinical studies and clinical trials involving scandium, as well as future challenges for its clinical uses and applications, are presented.

Midterm Outcomes of Endoleak Type 2 Embolization after Endovascular Aortic Aneurysm Repair Using a Neurointerventional Approach.

BACKGROUND: Type 2 endoleaks (T2ELs) have been considered a benign condition and intervention is recommended when they are associated to sac expansion. The aim of this study was to report on T2EL embolization midterm outcomes, using neurointerventional material. METHODS: A single-center retrospective analysis of consecutive patients treated with transarterial embolization, using neurointerventional material, for T2EL after standard endovascular aortic aneurysm repair (EVAR) between January 01, 2017 and July 30, 2022, was undertaken. Primary outcome was technical success and secondary outcome was T2EL recurrence during follow-up. RESULTS: Twenty six patients [92.3% males, mean age 73.9 ± 7.7 years] were included. The median time between EVAR and T2EL diagnosis was 12 months (range: 1-84 months). In 38.5% of patients, T2EL was detected at first month after EVAR. The time to embolization was 18 months (range: 1-96 months). In 42.3% of cases, a patent inferior mesenteric artery was suspected to relate to T2EL formation while in 42.3% of cases, a lumbar artery. Twelve procedures (38.4%) were performed using coils and Onyx and 13 (50%), using only Onyx. Technical success was 84.6%. The mean follow-up was 24 months (range: 1-60 months), including 20 patients. In 30% of cases, an T2EL recurrence was detected. Three patients (11.5%) underwent secondary embolization. CONCLUSIONS: Transarterial embolization for T2EL, using neurointerventional material, provided acceptable technical success and T2EL recurrence rates at 2 years of follow-up. Longer follow-up data would further estimate the durability of the technique.

Combined surgical and endovascular approach to treat a ventrally located perimedullary arteriovenous fistula.

Perimedullary arteriovenous fistulae (PMAVFs) (also called type IV spinal cord arteriovenous malformations) are rare lesions. They are located in the subarachnoid space or just under the pia. The shunt occurs between the anterior spinal artery (ASA) and/or posterior spinal artery (PSA) and a network of perimedullary veins. The aim of the treatment, surgical or endovascular, is to occlude the fistula. This article presents a unique treatment strategy of a demanding strictly ventral PMAVF in the lower thoracic cord. A posterior surgical approach with spinal cord rotation followed by direct puncture of a distally located arterial feeder was achieved. Precise identification of the fistula with superselective contrast injections was obtained and accurate catheterization of the venous pouch with a microcatheter was performed. Complete occlusion of the PMAVF was achieved with coils.

Inflammatory Myofibroblastic Tumor Arising in the Cul-De-Sac, Mimicking Ectopic Decidua.

Extra-ovarian neoplasms incidentally discovered during cesarean section are very rare. Here we report a case of inflammatory myofibroblastic tumor found during cesarean section of a 30-year-old, full-term woman, forming a mass in her cul-de-sac. Histology revealed an extensively decidualized spindle cell process, positive for anaplastic large cell lymphoma kinase (ALK) through immunohistochemistry and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first presentation of inflammatory myofibroblastic tumor in this location without concurrent intrauterine component, that additionally demonstrates this degree of decidualization, mimicking ectopic decidua.

Possible mechanisms of direct cardiovascular impact of GLP-1 agonists and DPP4 inhibitors.

Diabetes mellitus is a leading cause of cardiovascular morbidity and mortality worldwide. Traditional antidiabetic therapies targeting hyperglycemia reduce diabetic microvascular complications but have minor effects on macrovascular complications, including cardiovascular disease. Instead, cardiovascular complications are improved by antidiabetic medications (metformin) and other therapies (statins, antihypertensive medications) ameliorating insulin resistance and other associated metabolic abnormalities. Novel classes of antidiabetic drugs have proven efficacious in improving glycemia, while at the same time exert beneficial effects on pathophysiologic mechanisms of diabetes-related cardiovascular disease. In the present review, we will present current evidence of the cardiovascular effects of two new classes of antidiabetic medications, glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP4) inhibitors, focusing from mechanistic preclinical and clinical investigation to late-phase clinical testing.

Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures.

Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory disease in infants, but no vaccine or effective therapy is available. The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate (HS), a receptor for the RSV attachment (G) glycoprotein in immortalized cells. However, RSV infects the ciliated cells in primary well differentiated human airway epithelial (HAE) cultures via the apical surface, but HS is not detectable on this surface. Here we show that soluble HS inhibits infection of immortalized cells, but not HAE cultures, confirming that HS is not the receptor on HAE cultures. Conversely, a "non-neutralizing" monoclonal antibody against the G protein that does not block RSV infection of immortalized cells, does inhibit infection of HAE cultures. This antibody was previously shown to block the interaction between the G protein and the chemokine receptor CX3CR1 and we have mapped the binding site for this antibody to the CX3C motif and its surrounding region in the G protein. We show that CX3CR1 is present on the apical surface of ciliated cells in HAE cultures and especially on the cilia. RSV infection of HAE cultures is reduced by an antibody against CX3CR1 and by mutations in the G protein CX3C motif. Additionally, mice lacking CX3CR1 are less susceptible to RSV infection. These findings demonstrate that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlight the importance of using a physiologically relevant model to study virus entry and antibody neutralization.

Diet, life-style and cardiovascular morbidity in the rural, free living population of Elafonisos island.

BACKGROUND: There are about 70 small islands in the Aegean and Ionian Sea, of less than 300 Km2 and 5000 inhabitants each, comprising a total population of more than 75,000 individuals with geographical and socioeconomic characteristics of special interest. The objective of the present study was to assess lifestyle characteristics and the state of cardiovascular risk of the population of a small Eastern Mediterranean island, Elafonisos. METHODS: PERSEAS (Prospective Evaluation of cardiovascular Risk Surrogates in Elafonisos Area Study) is an ongoing, population-based, longitudinal survey of cardiovascular risk factors, life-style characteristics and related morbidity/mortality performed in a small and relatively isolated island of the Aegean Sea, named Elafonisos. Validated, closed-ended questionnaires for demographic, socio-economic, clinical and lifestyle characteristics were distributed and analyzed. The MedDietScore, a validated Mediterranean diet score was also calculated. In addition, all participants underwent measurement of anthropometric parameters, blood pressure and a full blood panel for glucose and lipids. RESULTS: The analysis included 596 individuals who represented 74.5% of the target population. The mean age of the population was 49.5 ± 19.6 years and 48.2% were males. Fifty participants (8.4%) had a history of cardiovascular disease (CVD). The rates of reported diabetes, hypertension, and hypercholesterolemia were 7.7%, 30.9% and 30.9% respectively, with screen-detection of each condition accounting for an additional 4.0%, 12.9%, and 23.3% of cases, respectively. Four hundred and seven individuals (68.3%) were overweight or obese, 25% reported being physically inactive and 36.6% were active smokers. The median MedDietScore was 25 [interquartile range: 6, range 12-47] with higher values significantly associated with older age, better education, increased physical activity, absence of history of diabetes and known history of hypercholesterolemia. CONCLUSIONS: Obesity and traditional risk factors for CVD are highly prevalent among the inhabitants of a small Mediterranean island. Adherence to the traditional Mediterranean diet in this population is moderate, while physical activity is low. There seems to be a need for lifestyle modification programs in order to reverse the increasing cardiovascular risk trends in rural isolated areas of the Mediterranean basin.

Toll-like receptor expression and induction of type I and type III interferons in primary airway epithelial cells.

Interferons (IFNs) are a critical component of the first line of antiviral defense. The activation of Toll-like receptors (TLRs) expressed by dendritic cells triggers different signaling cascades that result in the production of large amounts of IFNs. However, the functional consequences of TLR activation and differential IFN production in specific cell populations other than antigen-presenting cells have not yet been fully elucidated. In this study, we investigated TLR expression and polarization in airway epithelial cells (AECs) and the consequences of TLR agonist stimulation for the production of type I (IFN-α/ß) and type III (IFN-λ) IFNs. Our results show that the pattern of expression and polarization of all TLRs in primary AEC cultures mirrors that of the human airways ex vivo and is receptor specific. The antiviral TLRs (TLR3, TLR7, and TLR9) are mostly expressed on the apical cell surfaces of epithelial cells in the human trachea and in primary polarized AECs. Type III IFN is the predominant IFN produced by the airway epithelium, and TLR3 is the only TLR that mediates IFN production by AECs, while all TLR agonists tested are capable of inducing AEC activation and interleukin-8 production. In response to influenza virus infection, AECs can produce IFN-λ in an IFNAR- and STAT1-independent manner. Our results emphasize the importance of using primary well-differentiated AECs to study TLR and antiviral responses and provide further insight into the regulation of IFN production during the antiviral response of the lung epithelium.

Incidental Petrous Apex Cephalocele Presenting With Transient Global Amnesia: A Case Report and Rapid Literature Review.

Transient global amnesia (TGA) constitutes a rare clinical entity that manifests with temporary memory without any other neurological manifestation. Several pathogenetic mechanisms have been implicated, including temporal hypoperfusion, venous congestion, and cortical spreading potentials. Accordingly, the only relevant imaging findings are hippocampal CA1 areas of restricted diffusion on diffusion-weighted images. In the current case report, we present the rare case of a patient with TGA associated with bilateral petrous apex cephalocele (PAC). A 63-year-old female presented with a single episode of transient memory. The brain MRI showed a bilateral PAC and an empty sella. The patient was neurologically intact upon examination and was conservatively managed. There was no symptom recurrence during the six months of follow-up. We hypothesize that the presence of the meningocele could be associated with the pathogenesis of TGA. To the best of our knowledge, this is the first case of a petrous apex meningocele presenting with TGA. Most previously reported patients were females in their fourth decade of life, usually presenting with headaches or incidentally. Almost half of the cases were bilateral, with an empty sella. Surgical treatment was reserved for symptomatic patients with cerebrospinal fluid leaks and excruciating trigeminal neuralgia. Patients with TGA may be associated with temporal lesions, including PAC. Likewise, PAC is an extremely rare clinical entity that could occasionally present with TGA.

Cardiac risk stratification and adverse outcomes in surgically managed patients with isolated traumatic spine injuries.

INTRODUCTION: As the incidence of traumatic spine injuries has been steadily increasing, especially in the elderly, the ability to categorize patients based on their underlying risk for the adverse outcomes could be of great value in clinical decision making. This study aimed to investigate the association between the Revised Cardiac Risk Index (RCRI) and adverse outcomes in patients who have undergone surgery for traumatic spine injuries. METHODS: All adult patients (18 years or older) in the 2013-2019 TQIP database with isolated spine injuries resulting from blunt force trauma, who underwent spinal surgery, were eligible for inclusion in the study. The association between the RCRI and in-hospital mortality, cardiopulmonary complications, and failure-to-rescue (FTR) was determined using Poisson regression models with robust standard errors to adjust for potential confounding. RESULTS: A total of 39,391 patients were included for further analysis. In the regression model, an RCRI ≥ 3 was associated with a threefold risk of in-hospital mortality [adjusted IRR (95% CI): 3.19 (2.30-4.43), p < 0.001] and cardiopulmonary complications [adjusted IRR (95% CI): 3.27 (2.46-4.34), p < 0.001], as well as a fourfold risk of FTR [adjusted IRR (95% CI): 4.27 (2.59-7.02), p < 0.001], compared to RCRI 0. The risk of all adverse outcomes increased stepwise along with each RCRI score. CONCLUSION: The RCRI may be a useful tool for identifying patients with traumatic spine injuries who are at an increased risk of in-hospital mortality, cardiopulmonary complications, and failure-to-rescue after surgery.

Prioritizing patients for hip fracture surgery: the role of frailty and cardiac risk.

Introduction: The number of patients with hip fractures continues to rise as the average age of the population increases. Optimizing outcomes in this cohort is predicated on timely operative repair. The aim of this study was to determine if patients with hip fractures who are frail or have a higher cardiac risk suffer from an increased risk of in-hospital mortality when surgery is postponed >24 h. Methods: All patients registered in the 2013-2021 TQIP dataset who were ≥65 years old and underwent surgical fixation of an isolated hip fracture caused by a ground-level fall were included. Adjustment for confounding was performed using inverse probability weighting (IPW) while stratifying for frailty with the Orthopedic Frailty Score (OFS) and cardiac risk using the Revised Cardiac Risk Index (RCRI). The outcome was presented as the absolute risk difference in in-hospital mortality. Results: A total of 254,400 patients were included. After IPW, all confounders were balanced. A delay in surgery was associated with an increased risk of in-hospital mortality across all strata, and, as the degree of frailty and cardiac risk increased, so too did the risk of mortality. In patients with OFS ≥4, delaying surgery >24 h was associated with a 2.33 percentage point increase in the absolute mortality rate (95% CI: 0.57-4.09, p = 0.010), resulting in a number needed to harm (NNH) of 43. Furthermore, the absolute risk of mortality increased by 4.65 percentage points in patients with RCRI ≥4 who had their surgery delayed >24 h (95% CI: 0.90-8.40, p = 0.015), resulting in a NNH of 22. For patients with OFS 0 and RCRI 0, the corresponding NNHs when delaying surgery >24 h were 345 and 333, respectively. Conclusion: Delaying surgery beyond 24 h from admission increases the risk of mortality for all geriatric hip fracture patients. The magnitude of the negative impact increases with the patient's level of cardiac risk and frailty. Operative intervention should not be delayed based on frailty or cardiac risk.

Plasticity and virus specificity of the airway epithelial cell immune response during respiratory virus infection.

Airway epithelial cells (AECs) provide the first line of defense in the respiratory tract and are the main target of respiratory viruses. Here, using oligonucleotide and protein arrays, we analyze the infection of primary polarized human AEC cultures with influenza virus and respiratory syncytial virus (RSV), and we show that the immune response of AECs is quantitatively and qualitatively virus specific. Differentially expressed genes (DEGs) specifically induced by influenza virus and not by RSV included those encoding interferon B1 (IFN-B1), type III interferons (interleukin 28A [IL-28A], IL-28B, and IL-29), interleukins (IL-6, IL-1A, IL-1B, IL-23A, IL-17C, and IL-32), and chemokines (CCL2, CCL8, and CXCL5). Lack of type I interferon or STAT1 signaling decreased the expression and secretion of cytokines and chemokines by the airway epithelium. We also observed strong basolateral polarization of the secretion of cytokines and chemokines by human and murine AECs during infection. Importantly, the antiviral response of human AECs to influenza virus or to RSV correlated with the infection signature obtained from peripheral blood mononuclear cells (PBMCs) isolated from patients with acute influenza or RSV bronchiolitis, respectively. IFI27 (also known as ISG12) was identified as a biomarker of respiratory virus infection in both AECs and PBMCs. In addition, the extent of the transcriptional perturbation in PBMCs correlated with the clinical disease severity. Our results demonstrate that the human airway epithelium mounts virus-specific immune responses that are likely to determine the subsequent systemic immune responses and suggest that the absence of epithelial immune mediators after RSV infection may contribute to explaining the inadequacy of systemic immunity to the virus.

Actinide Ion (Americium-241 and Uranium-232) Interaction with Hybrid Silica-Hyperbranched Poly(ethylene imine) Nanoparticles and Xerogels.

The binding of actinide ions (Am(III) and U(VI)) in aqueous solutions by hybrid silica-hyperbranched poly(ethylene imine) nanoparticles (NPs) and xerogels (XGs) has been studied by means of batch experiments at different pH values (4, 7, and 9) under ambient atmospheric conditions. Both materials present relatively high removal efficiency at pH 4 and pH 7 (>70%) for Am(III) and U(VI). The lower removal efficiency for the nanoparticles is basically associated with the compact structure of the nanoparticles and the lower permeability and access to active amine groups compared to xerogels, and the negative charge of the radionuclide species is formed under alkaline conditions (e.g., UO2(CO3)34- and Am(CO3)2-). Generally, the adsorption process is relatively slow due to the very low radionuclide concentrations used in the study and is basically governed by the actinide diffusion from the aqueous phase to the solid surface. On the other hand, adsorption is favored with increasing temperature, assuming that the reaction is endothermic and entropy-driven, which is associated with increasing randomness at the solid-liquid interphase upon actinide adsorption. To the best of our knowledge, this is the first study on hybrid silica-hyperbranched poly(ethylene imine) nanoparticle and xerogel materials used as adsorbents for americium and uranium at ultra-trace levels. Compared to other adsorbent materials used for binding americium and uranium ions, both materials show far higher binding efficiency. Xerogels could remove both actinides even from seawater by almost 90%, whereas nanoparticles could remove uranium by 80% and americium by 70%. The above, along with their simple derivatization to increase the selectivity towards a specific radionuclide and their easy processing to be included in separation technologies, could make these materials attractive candidates for the treatment of radionuclide/actinide-contaminated water.

Radioactivity/Radionuclide (U-232 and Am-241) Removal from Waters by Polyurea-Crosslinked Alginate Aerogels in the Sub-Picomolar Concentration Range.

The removal of radionuclide/radioactivity from laboratory and environmental water samples under ambient conditions was investigated via batch-type experiments using polyurea-crosslinked calcium alginate (X-alginate) aerogels. Water samples were contaminated with traces of U-232 and Am-241. The removal efficiency of the material depends strongly on the solution pH; it is above 80% for both radionuclides in acidic solutions (pH 4), while it decreases at about 40% for Am-241 and 25% for U-232 in alkaline solutions (pH 9). This is directly associated with the presence of the radionuclide species in each case; the cationic species UO22+ and Am3+ prevail at pH 4, and the anionic species UO2(CO3)34- and Am(CO3)2- prevail at pH 9. Adsorption on X-alginate aerogels is realized by coordination of cationic species on carboxylate groups (replacing Ca2+) or other functional groups, i.e., -NH and/or -OH. In environmental water samples, i.e., ground water, wastewater and seawater, which are alkaline (pH around 8), the removal efficiency for Am-241 is significantly higher (45-60%) compared to that for U-232 (25-30%). The distribution coefficients (Kd) obtained for the sorption of Am-241 and U-232 by X-alginate aerogels are around 105 L/kg, even in environmental water samples, indicating a strong sorption affinity of the aerogel material for the radionuclides. The latter, along with their stability in aqueous environments, make X-alginate aerogels attractive candidates for the treatment of radioactive contaminated waters. To the best of our knowledge, this is the first study on the removal of americium from waters using aerogels and the first investigation of adsorption efficiency of an aerogel material at the sub-picomolar concentration range.

Comparing Different Grasping Visualizations for Object Manipulation in VR using Controllers.

Virtual grasping is one of the most common and important interactions performed in a Virtual Environment (VE). Even though there has been substantial research using hand tracking methods exploring different ways of visualizing grasping, there are only a few studies that focus on handheld controllers. This gap in research is particularly crucial, since controllers remain the most used input modality in commercial Virtual Reality (VR). Extending existing research, we designed an experiment comparing three different grasping visualizations when users are interacting with virtual objects in immersive VR using controllers. We examine the following visualizations: the Auto-Pose (AP), where the hand is automatically adjusted to the object upon grasping; the Simple-Pose (SP), where the hand closes fully when selecting the object; and the Disappearing-Hand (DH), where the hand becomes invisible after selecting an object, and turns visible again after positioning it on the target. We recruited 38 participants in order to measure if and how their performance, sense of embodiment, and preference are affected. Our results show that while in terms of performance there is almost no significant difference in any of the visualizations, the perceived sense of embodiment is stronger with the AP, and is generally preferred by the users. Thus, this study incentivizes the inclusion of similar visualizations in relevant future research and VR experiences.

Radionuclide Removal from Aqueous Solutions Using Oxidized Carbon Fabrics.

The adsorption of actinide ions (Am(III) and U(VI)) from aqueous solutions using pristine and oxidized carbon fabrics was investigated by means of batch experiments at different pH values (pH 4, 7 and 9) and temperatures (25, 35 and 45 °C) under ambient atmospheric conditions. The experimental results indicated that both the pH and the fabric texture affected the adsorption rate and the relative removal efficiency, which was 70% and 100% for Am(III) and U(VI), respectively. The Kd (L/kg) values for U(VI) were generally found to be higher (2 < log10(Kd)< 3) than the corresponding values for Am(III) adsorption (1.5 < log10(Kd) < 2). The data obtained from the experiments regarding the temperature effect implied that the relative adsorption for both actinides increases with temperature and that adsorption is an endothermic and entropy-driven reaction. The application of the fabrics to remove the two actinides from contaminated seawater samples showed that both the relative removal efficiency and the Kd values decreased significantly due to the presence of competitive cations (e.g., Ca2+ and Fe3+) and complexing anions (CO32-) in the respective waters. Nevertheless, the removal efficiency was still remarkable (50% and 90% for Am(III) and U(VI), respectively), demonstrating that these materials could be attractive candidates for the treatment of radionuclide/actinide-contaminated waters.

A nationwide analysis on the interaction between frailty and beta-blocker therapy in hip fracture patients.

INTRODUCTION: Hip fracture patients, who are often frail, continue to be a challenge for healthcare systems with a high postoperative mortality rate. While beta-blocker therapy (BBt) has shown a strong association with reduced postoperative mortality, its effect in frail patients has yet to be determined. This study's aim is to investigate how frailty, measured using the Orthopedic Hip Frailty Score (OFS), modifies the effect of preadmission beta-blocker therapy on mortality in hip fracture patients. METHODS: This retrospective register-based study included all adult patients in Sweden who suffered a traumatic hip fracture and subsequently underwent surgery between 2008 and 2017. Treatment effect was evaluated using the absolute risk reduction (ARR) in 30-day postoperative mortality when comparing patients with (BBt+) and without (BBt-) ongoing BBt. Inverse probability of treatment weighting (IPTW) was used to reduce potential confounding when examining the treatment effect. Patients were stratified based on their OFS (0, 1, 2, 3, 4 and 5) and the treatment effect was also assessed within each stratum. RESULTS: A total of 127,305 patients were included, of whom 39% had BBt. When IPTW was performed, there were no residual differences in observed baseline characteristics between the BBt+ and BBt- groups, across all strata. This analysis found that there was a stepwise increase in the ARRs for each additional point on the OFS. Non-frail BBt+ patients (OFS 0) exhibited an ARR of 2.2% [95% confidence interval (CI) 2.0-2.4%, p < 0.001], while the most frail BBt+ patients (OFS 5) had an ARR of 24% [95% CI 18-30%, p < 0.001], compared to BBt- patients within the same stratum. CONCLUSION: Beta-blocker therapy is associated with a reduced risk of 30-day postoperative mortality in frail hip fracture patients, with a greater effect being observed with higher Orthopedic Hip Frailty Scores.

The mortality burden of frailty in hip fracture patients: a nationwide retrospective study of cause-specific mortality.

PURPOSE: Frailty is a condition characterized by a reduced ability to adapt to external stressors because of a reduced physiologic reserve, which contributes to the high risk of postoperative mortality in hip fracture patients. This study aims to investigate how frailty is associated with the specific causes of mortality in hip fracture patients. METHODS: All adult patients in Sweden who suffered a traumatic hip fracture and underwent surgery between 2008 and 2017 were eligible for inclusion. The Orthopedic Hip Frailty Score (OFS) was used to classify patients as non-frail (OFS 0), pre-frail (OFS 1), and frail (OFS ≥ 2). The association between the degree of frailty and both all-cause and cause-specific mortality was determined using Poisson regression models with robust standard errors and presented using incidence rate ratios (IRRs) with corresponding 95% confidence intervals (CIs), adjusted for potential sources of confounding. RESULTS: After applying the inclusion and exclusion criteria, 127,305 patients remained for further analysis. 23.9% of patients were non-frail, 27.7% were pre-frail, and 48.3% were frail. Frail patients exhibited a 4 times as high risk of all-cause mortality 30 days [adj. IRR (95% CI): 3.80 (3.36-4.30), p < 0.001] and 90 days postoperatively [adj. IRR (95% CI): 3.88 (3.56-4.23), p < 0.001] as non-frail patients. Of the primary causes of 30-day mortality, frailty was associated with a tripling in the risk of cardiovascular [adj. IRR (95% CI): 3.24 (2.64-3.99), p < 0.001] and respiratory mortality [adj. IRR (95% CI): 2.60 (1.96-3.45), p < 0.001] as well as a five-fold increase in the risk of multiorgan failure [adj. IRR (95% CI): 4.99 (3.95-6.32), p < 0.001]. CONCLUSION: Frailty is associated with a significantly increased risk of all-cause and cause-specific mortality at 30 and 90 days postoperatively. Across both timepoints, cardiovascular and respiratory events along with multiorgan failure were the most prevalent causes of mortality.