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Alumina oxide ceramics were produced by plasma pressure compaction (P2C) sintering process. Two types of pure α-alumina (Al2O3) and a mixture of alumina and titanium diboride (TiB2) powders were used as starting materials. Microstructure and mechanical properties, namely hardness, elastic modulus, and fracture toughness, were analyzed and correlated to the type of the sintered powders and the adopted manufacturing route. The microstructural development and the chemical composition variation induced by the sintering process were assessed by using scanning electron microscopy and x-ray diffraction. Nano-indentation and Chevron notch beam techniques were adopted to estimate the mechanical properties of the sintered ceramics. The conducted analyses show the capability of P2C technique to produce sound alumina ceramics. Pure alumina bulks exhibit a good level of compaction and mechanical properties close to those achievable with conventional sintering processes, such as hot isostatic pressing or spark plasma sintering. No significant alterations in the chemical composition of the ceramics were observed. The addition of the titanium diboride in the alumina powders caused a moderate increase in the grain size lowering the hardness and Young's modulus of the sintered alumina and, at the same time, increased its fracture toughness to the occurrence of toughening mechanisms, like crack bridging and crack deflection. [ABSTRACT FROM AUTHOR]

Background: Coronary microvascular function is impaired in patients with obesity, contributing to myocardial dysfunction and heart failure. Bariatric surgery decreases cardiovascular mortality and heart failure, but the mechanisms are unclear., Objectives: The authors studied the impact of bariatric surgery on coronary microvascular function in patients with obesity and its relationship with metabolic syndrome., Methods: Fully automated quantitative perfusion cardiac magnetic resonance and metabolic markers were performed before and 6 months after bariatric surgery., Results: Compared with age- and sex-matched healthy volunteers, 38 patients living with obesity had lower stress myocardial blood flow (MBF) (P = 0.001) and lower myocardial perfusion reserve (P < 0.001). A total of 27 participants underwent paired follow-up 6 months post-surgery. Metabolic abnormalities reduced significantly at follow-up including mean body mass index by 11 ± 3 kg/m 2 (P < 0.001), glycated hemoglobin by 9 mmol/mol (Q1-Q3: 4-19 mmol/mol; P < 0.001), fasting insulin by 142 ± 131 pmol/L (P < 0.001), and hepatic fat fraction by 5.6% (Q1-Q3: 2.6%-15.0%; P < 0.001). Stress MBF increased by 0.28 mL/g/min (Q1-Q3: -0.02 to 0.75 mL/g/min; P = 0.003) and myocardial perfusion reserve by 0.13 (Q1-Q3: -0.25 to 1.10; P = 0.036). The increase in stress MBF was lower in those with preoperative type 2 diabetes mellitus (0.1 mL/g/min [Q1-Q3: -0.09 to 0.46 mL/g/min] vs 0.75 mL/g/min [Q1-Q3: 0.31-1.25 mL/g/min]; P = 0.002). Improvement in stress MBF was associated with reduction in fasting insulin (beta = -0.45 [95% CI: -0.05 to 0.90]; P = 0.03)., Conclusions: Coronary microvascular function is impaired in patients with obesity, but can be improved significantly with bariatric surgery. Improvements in microvascular function are associated with improvements in insulin resistance but are attenuated in those with preoperative type 2 diabetes mellitus., Competing Interests: Funding Support and Author Disclosures Dr Joy has been supported by a British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/21/2469). Dr McGowan was supported by project grants from Guys and St. Thomas’ Charity Grant, Janet James Fund; has undertaken advisory work for Novo Nordisk and Lilly; has performed educational work with Novo Nordisk and Biogen; has an academic grant with Novo Nordisk; and is a shareholder in Reset health. Dr Manisty has been supported by funding with the University Hospitals London NHS Trust National Institute for Health and Care Research Biomedical Research Centre. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: In Lyme-endemic areas, limited research has investigated the risk of tick-borne diseases among frontline workers in fire management. This study aimed to compare the exposure histories to ticks and tick-borne pathogens, knowledge, and prevention practices between individuals engaged in fire-related forest management and those participating in recreational activities within Santa Cruz County, CA, in an area of high risk of tick exposure. Methods: Blood samples from 55 forest workers and 58 members of the public were tested for bacterial DNA of and antibodies to Borrelia burgdorferi , Anaplasma phagocytophilum , and Rickettsia species. In addition, a questionnaire was administered to 54 workers and 84 members of the public to identify gaps in knowledge and prevention practices. Results: Although workers had a higher percentage of positive B. burgdorferi antibodies than the public (5.5% compared with 1.7%), the difference was not statistically significant. Conversely, rickettsial antibodies were more prevalent among the public (17.2% versus 3.6% for workers), but specificity to pathogenic bacteria could not be confirmed. No DNA for the three pathogens or antibodies against A. phagocytophilum were detected. Many workers and members of the public reported tick bites (67.4% of participants), with a notable 11% increase among workers in the odds of being bitten for each additional year spent working in forests. Although workers took greater precautions, significant knowledge and practice gaps were identified among both populations, such as an inability to distinguish tick species from common arthropods (mites, spiders, fleas), overestimating the size of ticks, and inappropriate tick-removal techniques. Conclusion: This study underscores the risk of tick-borne diseases faced by fire management workers in Lyme disease-endemic regions. The findings emphasize the necessity for future studies of Lyme disease within this population, and highlight the urgent need for enhanced training programs to minimize these risks.

Background: Distal trans-radial access (dTRA) for percutaneous coronary interventions (PCI) is increasingly gaining attention due to its potential to mitigate radial artery occlusion (RAO). However, a comprehensive understanding of the mechanical impact of the devices on the radial artery (RA) wall remains limited. Using a complete intravascular ultrasound (IVUS) evaluation of the RA, including also the vascular access site, we aimed to evaluate all the consequences related to the catheterization on the RA wall, starting from the vascular access, comparing conventional sheath and sheathless approaches., Methods: This is an observational, prospective, multicenter study aimed to assess the entire RA wall immediately after IVUS-guided PCI via-dTRA. IVUS assessment included quantitative measurements (minimal lumen area [MLA], minimal vessel area [MVA]) and qualitative observations (dissections, vasospasm). Study objectives included delineating RA wall structure post-PCI and comparing findings between conventional and sheathless approaches., Results: Fifty patients (21 [42%] with conventional sheath, 29 [58%] sheathless) were enrolled between March 2023 and February 2024. Female patients were more prevalent in the convention sheath group (38% vs. 7%, p < 0.001). Sheathless approach utilized 7-French guiding catheters more frequently (33% vs. 86%, p < 0.001). Post-procedural IVUS identified dissections in 12% of cases, with no significant difference between approaches. Arterial vasospasm was present in a quarter of patients, numerically higher in the conventional sheath group (29% vs. 21%, p = 0.5). MLA and MVA were comparable between groups, though MLA and MVA were lowest at the proximal segment of the RA only in the conventional sheath group (p < 0.001). No RAO was documented during the IVUS evaluation., Conclusions: The intravascular assessment of dTRA after coronary interventions, utilizing either conventional or sheathless approaches, including large-bore guiding catheters, demonstrated a relatively low incidence of access-related complications such as dissection and vasospasm, without affecting the flow and patency of the proximal RA., (© 2024 Wiley Periodicals LLC.)

Background: Spinal arteriovenous fistulas (SAVFs) are direct communication between arteries and veins without intervening abnormal vessel nidus, which often results in venous congestion and spinal cord dysfunction. Ventrally located SAVF can be challenging to treat through traditional open or endovascular approaches., Case Description: We describe a hybrid (open/endovascular) procedure in a 72-year-old male with a Takai Type IVb SAVF presenting with paraparesis and sphincter dysfunction. Imaging revealed a conus medullaris SAVF in which the main fistulous connection was located ventrally. The conventional endovascular approach was deemed risky, and open surgery failed in the first attempt. The SAVF was resolved using a hybrid approach: under direct visualization, an engorged dorsal vein was punctured with an Angiocath, and a fluoroscopy-guided microcatheter was advanced through it to reach and embolize the ventral perimedullary fistulous connection. After surgery, his progressive neurological decline stabilized, radiographic spinal cord edema improved, and follow-up angiography confirmed obliteration of the fistula. Neurological function remained at the preoperative baseline., Conclusion: This approach may be a treatment for selected cases of type IVb SAVF. Easily accessible feeding vessels are coagulated and cut; the inaccessible ones can be embolized endovascularly during the same procedure., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Multivessel coronary artery disease (CAD), defined as ≥50% stenosis in 2 or more epicardial arteries, is associated with a high burden of morbidity and mortality in acute coronary syndrome (ACS) patients. A salient challenge for managing this cohort is selecting the optimal revascularisation strategy, for which the use of coronary physiology has been increasingly recognised. Fractional flow reserve (FFR) is an invasive, pressure wire-based, physiological index measuring the functional significance of coronary lesions. Understanding this can help practitioners evaluate which lesions could induce myocardial ischaemia and, thus, decide which vessels require urgent revascularisation. Non-hyperaemic physiology-based indices, such as instantaneous wave-free ratio (iFR), provide valid alternatives to FFR. While FFR and iFR are recommended by international guidelines in stable CAD, there is ongoing discussion regarding the role of physiology in patients with ACS and multivessel disease (MVD); growing evidence supports FFR use in the latter. Compelling findings show FFR-guided complete percutaneous coronary intervention (PCI) can reduce adverse cardiovascular events, mortality, and repeat revascularisations in ACS and MVD patients compared to angiography-based PCI. However, FFR is limited in identifying non-flow-limiting vulnerable plaques, which can disadvantage high-risk patients. Here, integrating coronary physiology assessment with intracoronary imaging in decision-making can improve outcomes and quality of life. Further research into novel physiology-based tools in ACS and MVD is needed. This review aims to highlight the key evidence surrounding the role of FFR and other functional indices in guiding PCI strategy in ACS and MVD patients., Competing Interests: The authors have no conflicts of interest to declare.

Background and Objectives: The impact of prior local therapies, including radiation and surgery, on reconstruction outcomes after endonasal surgery is currently not well known. Reconstruction nuances in the preoperative setting merit further evaluation to avoid potential postoperative complications that can hinder overall tumor management and negatively impact patient outcome. We sought to determine whether prior treatments increase risk of reconstruction-related postoperative morbidity and to evaluate the effectiveness of our current treatment paradigm for skull base reconstruction., Methods: A retrospective review of all endonasal surgeries for tumor resection between March 2000 and March 2022 was performed. Patients were grouped based on treatment history. Patient demographics, operative, and postoperative reconstruction-related morbidity data were collected, including cerebrospinal fluid leak, sinonasal morbidity, and infectious complications. Variables significantly associated with postoperative complications in the univariate analysis were included in the multivariate Cox proportional hazards regression model. Complication-free survival curves were generated, and the log-rank test evaluated the relationship between complication-free survival and the different clinical, surgical, and treatment parameters. All statistical analyses were performed with SPSS 26 (IBM Corp) and Graph Pad 9.0 (GraphPad Software)., Results: A total of 418 patients were included. 291 patients had no prior treatments, 49 patients had previously received radiation, and 78 patients had prior surgeries. Of the 49 patients who had prior radiation, 27% underwent reconstruction with tunneled pericranial flaps vs 16% of treatment-naïve patients. On multivariate analysis, prior treatment was not significantly associated with reconstruction-related complications. Negative smoking history, no leak or small intraoperative leak, and use of vascularized flap in reconstruction were protective factors., Conclusion: In patients undergoing endonasal surgery, prior radiation and/or surgery does not appear to significantly increase the risk of immediate or delayed reconstruction complications using our current reconstructive management plan, which incorporates an upfront regional flap for high-risk cases., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: The prognostic significance of inflammatory markers on the long-term risk of major adverse cardiovascular and cerebrovascular events (MACCE) in older NSTEACS patients remains unclear., Methods: NSTEACS patients aged 75 and older were recruited to the multicentre cohort study Improve Cardiovascular Outcomes in High-Risk PatieNts with Acute Coronary Syndrome (ICON1). Inflammatory markers including interleukin-6 (IL-6), myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), fibrinogen and tumor necrosis factor-alpha (TNF-α) were collected at baseline. Primary outcome was MACCE consisting of all-cause mortality, reinfarction, stroke/transient ischaemic attack, urgent revascularization, and significant bleeding at 5-year follow-up., Results: There were 230 patients with baseline IL-6 (median age 80.9 [interquartile range (IQR):78.2-83.9] years). High IL-6 was not associated with MACCE, but it was independently associated with all-cause mortality (adjusted hazard ratio [aHR]: 2.26 [95% Confidence Interval (CI):1.34-3.82]; P = 0.002). For patients with hsCRP (n = 260, median age 80.9 [IQR:77.9-84.1] years), higher levels were significantly associated with increased risk of MACCE (aHR:1.77 [95% CI:1.26-2.49], P = 0.001). In the cohort with MPO (230 patients, median age 80.9 [IQR:78.2-83.9] years), lower MPO was independently associated with the risk of MACCE (aHR: 0.67 [95%CI:0.46-0.96]; P = 0.029). There was no prognostic significance with fibrinogen and TNF-α., Conclusion: Among older NSTEACS patients, elevated IL-6 and hsCRP were associated with increased risk of all-cause mortality and MACCE, respectively. Low MPO levels were associated with higher MACCE. Further studies are required to determine how these biomarkers should influence treatment strategy in this understudied subset., Clinical Trial Registration: NCT01933581., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The relationship between postoperative dietary intake and weight loss after bariatric surgery remains unclear. We performed a systematic review and meta-analysis of studies published between January 2000 and May 2023, reporting weight loss outcomes, and dietary intake before and after Roux-en-Y gastric bypass and sleeve gastrectomy. A total of 42 studies were included. There was no detectable difference in dietary intake between the two procedures. Roux-en-Y gastric bypass induced an average decrease in energy intake of 886 kcal/day at 12-month post-surgery; however, there was no correlation between daily energy intake and weight loss. These findings show a substantial reduction of energy intake in the first year after bariatric surgery but do not support a link between lower energy intake and greater weight loss., (© 2024. The Author(s).)

We conducted surveillance of mammals to investigate their associations with argasid ticks and tick-borne pathogens. During 2021, a total of 20 wild carnivores and 57 lagomorphs were sampled, and 39 argasid ticks belonging to two species were collected. All mammals and ticks were tested by molecular assays to detect Borrelia and Rickettsia infections. Nine ticks identified as Otobius megnini were collected from two coyotes (Canis latrans) and 30 Alveonasus cooleyi (McIvor 1941) were collected from six bobcats (Lynx rufus) and one rabbit (Sylvilagus auduboni). We detected Rickettsia spp. DNA in 21 of the 27 (77.8%) tested Av. cooleyi and none of the O. megnini. No ticks were PCR-positive for borreliae and all mammals were PCR-negative for both pathogen genera. Phylogenetic analysis based on gltA, htrA, and 16 S rRNA targets revealed that all rickettsiae from Av. cooleyi clustered with ancestral group rickettsiae, likely representing a novel species of possibly endosymbiotic Rickettsia. The significance of Av. cooleyi and the newly identified Rickettsia sp. to the health of wildlife is unknown, and further work is indicated to determine whether they may be relevant to public health or carnivore conservation., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Adverse cardiac events are common in older patients with non-ST elevation acute coronary syndrome (NSTEACS), yet prognostic predictors are still lacking. This study investigated the long-term prognostic significance of non-invasive measures including endothelial function, carotid intima-media thickness (CIMT), and vascular stiffness in older NSTEACS patients referred for invasive treatment., Methods: NSTEACS patients aged 75 years and older recruited to a multicentre cohort study (NCT01933581) were assessed for baseline endothelial function using endoPAT logarithm of reactive hyperemia index (LnRHI), CIMT using B-mode ultrasound, and vascular stiffness using carotid-femoral pulse wave velocity (cfPWV). Long-term outcomes included major adverse cardiovascular events (MACE), a composite of death, reinfarction, urgent revascularization, stroke/transient ischemic attack, and significant bleeding., Results: Recruitment resulted in 214 patients assessed for LnRHI, 190 patients assessed for CIMT and 245 patients assessed for cfPWV. For LnRHI group (median follow-up 4.73 years [IQR: 1.41-5.00]), Cox regression analysis revealed a trend towards increased risk of MACE (HR: 1.24 [95% CI: 0.80-1.93]; P  = 0.328) and mortality (HR: 1.49 [95% CI: 0.86-2.59]; P  = 0.157), but no significance was reached. No difference for other components of MACE was found. For CIMT group (median follow up 4.74 years [IQR: 1.55-5.00]), no statistically significant difference in MACE was found (HR: 0.92 [95% CI: 0.53-1.59]; P  = 0.754). Similarly, for cfPWV group (median follow-up 4.96 years [IQR: 1.55-5.00]), results did not support prognostic significance (for MACE, HR: 0.95 [95% CI: 0.65-1.39]; P  = 0.794)., Conclusion: Endothelial function, CIMT and vascular stiffness were proven unsuitable as strong prognostic predictors in older patients with NSTEACS., Clinical Trial Registration: NCT01933581., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Roxadustat, recently approved, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has demonstrated favorable safety and efficacy in the treatment of renal anemia. This article reviews main features and possible effects by activation of pathway sequences HREs., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

There are no general guidelines for the treatment of acetabular fractures. Open reduction and internal fixation is advised in young and active patients, while acute total hip arthroplasty (THA) is recommended for elderly patients in order to allow immediate weight bearing. Various THA systems have been reported. We present four cases, mean age 79 years (range 67-92), of closed acetabular fractures managed with acute cementless THA, comprising a highly-porous multi-hole acetabular cup and a CLS-type femoral stem. After extensive pre-operative planning, autograft was used to fill in the acetabulum defects left by the trauma and the press-fit acetabular cup were implanted. One or more screws were used to improve primary stability and secure bone fragments. Patients were follow-up for mean 1.5 years (range 1.1-2.0). A Brooker III heterotopic ossification was the only complication occurred postoperatively. All the patients were satisfied, with a mean Harris Hip Score of 90 and Postel Merle D'Aubigné score of 16.3. There were no radiolucency lines nor osteolysis, showing that the cups were well osteointegrated and fractures united. As the bone bed after acetabular fracture might be highly compromised, whenever acute THA is indicated, a highly-porous multi-hole cup could be used to limit radiolucency lines and aseptic loosening. The series is limited by the small number of cases but is significant for the promising results., Competing Interests: MC is paid employee as clinical researcher for Permedica. Other authors declare no conflict of competing interest., (© 2024 The Authors.)

Background: Cavernous sinus cavernous malformations (CSCMs) is a vascular malformation of the cavernous sinus. Nowadays, there is an increasing preference to withhold using the terms cavernoma or cavernous hemangioma in order to stop considering these lesions as vascular neoplasms. These lesions are highly vascularized making surgical resection a challenge, mainly in endoscopic approaches. We present a case of this tumor treated in our institution with an endoscopic endonasal approach and incomplete resection. Because of the strenuous resection through this approach, we systematically reviewed the reported endoscopic cases of CSCMs to determine their intraoperative complications, results and tumor features., Methods: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, one database (PubMed) and crossed references were queried for CSCMs from 1948 to 2020. Data regarding demographic features, clinical presentation, MRI features, surgical results and overall pathology features extracted., Results: Eighteen patients were selected (including our case). The mean age was 50.4 ± 14 years. Pituitary dysfunction and cavernous sinus nerve compression were the most reported symptoms. Only five cases (27%) reported a gross total resection (GTR) through endoscopic endonasal approach. Intraoperative bleeding was the most frequent intraoperative complication., Conclusion: We present a comprehensive analysis of every reported CSCM treated through endoscopic approach. Partial or subtotal resection are the most used techniques because of the intraoperative bleeding and the adherence to surrounding structures. Radiotherapy is a very good option for patients with incomplete resections.

Coronary physiological assessment has garnered extensive application in managing patients with coronary artery disease, encompassing both acute and chronic scenarios. Beyond the historical purpose as tool to define the hemodynamic significance of a given artery lesion, coronary artery physiology allows for a complete investigation of epicardial and microvascular circulation. The longitudinal assessment of the distribution pattern of coronary disease based on pressure wire technology provides crucial information to define the best management and procedural planning. Moreover, post-percutaneous coronary intervention physiology reassessment showed a strong association with clinical outcomes and, more importantly, it can spot residual pressure gradients potentially amenable to further intervention and optimization. Growing evidence about the non-invasive angiography-based indices helps to overcome the limitations of the use of intracoronary physiology. This review aims to provide an overview of different utilizations of coronary physiology offering a historical perspective with a particular focus on current challenges and future potential applications.

Background: Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS)., Methods: This study recruited older patients aged ≥ 75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints., Results: Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) ≤ 4 mm 2 demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00-5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA > 4 mm 2 . Patients with combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% showed high risk of MI (HR 5.23, 95% CI 1.05-25.9, p = 0.043). Lesions with MLA ≤ 4 mm 2 had 6-fold risk of TVF (HR 6.16, 95% CI 1.24-30.5, p = 0.026)., Conclusions: Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% was associated with high risk of MI., Clinical Trial Registration: NCT01933581., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

The role of systemic therapy in primary or advanced and metastatic chordoma has been traditionally limited because of the inherent resistance to cytotoxic therapies and lack of specific or effective therapeutic targets. Despite resection and adjuvant radiation therapy, local recurrence rates in clival chordoma remain high and the risk of systemic metastases is not trivial, leading to significant morbidity and mortality. Recently, molecular targeted therapies (MTTs) and immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic avenues in chordoma. In recent years, preclinical studies have identified potential targets based on intrinsic genetic dependencies, epigenetic modulators, or newly identified tumor-associated cell populations driving treatment resistance and recurrence. Nonetheless, the role of systemic therapies in the neoadjuvant or adjuvant setting for primary, locally progressive, and distant metastatic chordomas is still being investigated. Herein, an overview of current and emerging systemic treatment strategies in advanced clival chordoma is provided. Furthermore, several molecular biomarkers have been recently uncovered as potential predictors of the response to specific molecular therapeutics. The authors describe the recently discovered role of 1p36 and 9p21 deletions as biomarkers capable of guiding drug selection. Then they discuss completed and ongoing clinical trials of MTTs, including several tyrosine kinase inhibitors used as monotherapy or in combination, such as imatinib, sorafenib, dasatinib, and lapatinib, among others, as well as mammalian target of rapamycin inhibitors such as everolimus and rapamycin. They present their experience and other recent studies demonstrating vast benefits in advanced chordoma from ICIs. Additionally, they provide a brief overview of novel systemic strategies such as adoptive cell transfer (CAR-T and NK cells), oncolytic viruses, epigenetic targeting (KDM6, HDAC, and EZH2 inhibitors), and several promising preclinical studies with high translational potential. Finally, the authors present their institutional multidisciplinary protocol for the incorporation of systemic therapy for both newly diagnosed and recurrent chordomas based on molecular studies including upfront enrollment in MTT trials in patients with epidermal growth factor receptor upregulation or INI-1 deficiency or enrollment in ICI clinical trials for patients with high tumor mutational burden or high PD-L1 expression on tumor cells or in the tumor microenvironment.

Obesity is a significant public health problem. Prevalence is rising in children and young people, with lifelong health impacts and implications for paediatric clinical practice. Obesity stigma is increasingly acknowledged as a problem within health services. Health professionals can inadvertently contribute to this stigma, which is harmful and in itself can promote weight gain. A complex web of factors contributes to obesity, and a simplistic approach exclusively focused on personal responsibility, diet and exercise is unhelpful. A more nuanced, sensitive and informed approach is needed, with careful use of language and non-judgemental partnership working., Competing Interests: Competing interests: FR reports receiving investigator-initiated research grants from Ethicon (Johnson & Johnson), Novo Nordisk and Medtronic; receiving consulting fees from GI Dynamics; receiving speaking honoraria from Medtronic, Ethicon and Novo Nordisk; and serving (unpaid) as a member of the scientific advisory board for Keyron and member of DSMB for GI Metabolic Solution., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The rumen represents a dynamic microbial ecosystem where fermentation metabolites and microbial concentrations change over time in response to dietary changes. The integration of microbial genomic knowledge and dynamic modelling can enhance our system-level understanding of rumen ecosystem's function. However, such an integration between dynamic models and rumen microbiota data is lacking. The objective of this work was to integrate rumen microbiota time series determined by 16S rRNA gene amplicon sequencing into a dynamic modelling framework to link microbial data to the dynamics of the volatile fatty acids (VFA) production during fermentation. For that, we used the theory of state observers to develop a model that estimates the dynamics of VFA from the data of microbial functional proxies associated with the specific production of each VFA. We determined the microbial proxies using CowPi to infer the functional potential of the rumen microbiota and extrapolate their functional modules from KEGG (Kyoto Encyclopedia of Genes and Genomes). The approach was challenged using data from an in vitro RUSITEC experiment and from an in vivo experiment with four cows. The model performance was evaluated by the coefficient of variation of the root mean square error (CRMSE). For the in vitro case study, the mean CVRMSE were 9.8% for acetate, 14% for butyrate and 14.5% for propionate. For the in vivo case study, the mean CVRMSE were 16.4% for acetate, 15.8% for butyrate and 19.8% for propionate. The mean CVRMSE for the VFA molar fractions were 3.1% for acetate, 3.8% for butyrate and 8.9% for propionate. Ours results show the promising application of state observers integrated with microbiota time series data for predicting rumen microbial metabolism., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Davoudkhani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Evidence on patellar height changes following unicompartmental knee arthroplasty (UKA) is lacking. Therefore, this study compared the patella height in patients who underwent medial versus lateral UKA. Moreover, a subgroup analysis was conducted to investigate whether sex, age, and BMI of the patients exert an influence on the postoperative patellar height., Methods: Radiographs and hospital records of patients undergoing UKA were prospectively collected. Surgeries were performed by one author with long experience in UKA in a highly standardised fashion. The implants were fixed-bearing medial PPK (Zimmer Biomet, Warsaw, Indiana, USA) and fixed-bearing lateral ZUK (Lima Corporate, Udine, Italy). The patellar height was measured using the Insall-Salvati and Caton-Deschamps indices., Results: A total of 203 patients were included: 119 patients were included in the medial and 84 in the lateral UKA. The mean age of the patients was 68.9 ± 6.7 years, and the mean BMI was 28.1 ± 4.1 kg/m 2 . 54% (110 of 203 patients) were women. On admission, between-group comparability was found in age, BMI, sex, and length of the follow-up. No between-group and within-group difference was detected pre- and post-operatively in the Insall-Salvati and Caton-Deschamps indices in patients who have undergone medial versus lateral UKA. Concerning the subgroup analyses, no between-group and within-group difference was detected pre- and post-operatively in all comparisons according to sex, age, and BMI., Conclusion: No difference was found in patella height in patients who have undergone medial compared to lateral UKA. Furthermore, there was no evidence of an association between patient characteristics (sex, age, BMI) and patella height between medial and lateral UKA., (© 2023. The Author(s).)

Rocky Mountain spotted fever (RMSF) is an international and quintessential One Health problem. This paper synthesizes recent knowledge in One Health, binational RMSF concerns, and veterinary and human medical perspectives to this fatal, reemerging problem. RMSF, a life-threatening tick-borne disease caused by the bacterium Rickettsia rickettsii, emerged during the first decade of the 21st century in impoverished communities in the southwestern US and northern Mexico. Lack of an index of suspicion, delay in diagnosis, and delayed initiation of antibiotic treatment contribute to fatality. Campaigns targeting dog neutering, restraint to residents' properties, and on-dog and on-premises treatment with acaricides temporarily reduce prevalence but are often untenable economically. Contemporary Mexican RMSF is hyperendemic in small communities and cities, whereas epidemics occur in the western US primarily in small tribal communities. In in both locations, the epidemics are fueled by free-roaming dogs and massive brown dog tick populations. In the US, RMSF has a case fatality rate of 5% to 7%; among thousands of annual cases in Mexico, case fatality often exceeds 30%.1,2 Numerous case patients in US border states have recent travel histories to northern Mexico. Veterinarians and physicians should alert the public to RMSF risk, methods of prevention, and the importance of urgent treatment with doxycycline if symptomatic. One Health professionals contribute ideas to manage ticks and rickettsial disease and provide broad education for the public and medical professionals. Novel management approaches include vaccine development and deployment, acaricide resistance monitoring, and modeling to guide targeted dog population management and other interventions.

Objective: This study aimed to explore the prognostic impact of cognitive impairment on the long-term risk of major adverse cardiovascular events (MACEs) in older patients with non-ST-elevation acute coronary syndrome (NSTEACS) undergoing invasive treatment., Methods: Patients aged ≥75 years with NSTEACS undergoing an invasive strategy were included in the multicentre prospective study (NCT01933581). Montreal Cognitive Assessment was used to evaluate cognitive status at baseline (scores ≥26 classified as normal, <26 as cognitive impairment). Long-term follow-up data were obtained from electronic patient care records. The primary endpoint was MACE as a composite of all-cause deaths, reinfarction, stroke/transient ischaemic attack, urgent revascularisation and significant bleeding., Results: 239 patients with baseline cognitive assessment completed long-term follow-up. Median age was 80.9 years (IQR 78.2-83.9 years) and 62.3% were male. On 5-year follow-up, there was no significant difference in the occurrence of MACE between the cognitively impaired group and the normal cognition group (p=0.155). Cognition status was not associated with MACE (HR 1.37 (95% CI 0.96 to 1.95); p=0.082). However, there was significantly more deaths (p=0.005) in those with cognitive impairment. Kaplan-Meier survival analysis (log-rank p=0.003) and Cox regression analysis (aHR 1.85 (95% CI 1.11 to 3.08); p=0.018) revealed increased risk of all-cause mortality, even after adjusting for frailty and GRACE (Global Registry of Acute Coronary Events) score., Conclusion: Cognitive impairment in older patients with NSTEACS undergoing an invasive strategy was associated with long-term all-cause mortality. Routine cognitive screening may aid risk stratification and further studies are needed to identify how this should influence management strategies and individual decision-making in this patient group., Trial Registration Number: NCT01933581., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Coronary physiology assessment, including epicardial and microvascular investigations, is a fundamental tool in the contemporary management of patients with coronary artery disease. Coronary revascularisation guided by functional evaluation has demonstrated superiority over angiography-only-guided treatment. In patients with chronic coronary syndrome, revascularisation did not demonstrate prognostic advantage in terms of mortality over optimal medical therapy (OMT). However, revascularisation of coronary stenosis, which induces myocardial ischaemia, has demonstrated better outcome than OMT alone. Pressure wire (PW) or angiography-based longitudinal coronary physiology provides a point-by-point analysis of the vessel to detect the atherosclerotic pattern of coronary disease. A careful evaluation of this disease pattern allows clinicians to choose the appropriate management strategy.Patients with diffuse disease showed a twofold risk of residual angina after percutaneous coronary intervention (PCI) than those with focal disease. Therefore, OMT alone or coronary artery bypass graft might be considered over PCI. In addition, the post-PCI physiological assessment aims to optimise the result revealing residual myocardial ischaemia. Improvement in post-PCI PW or angiography-based functional indices has been associated with better quality of life and reduced risk of cardiac events and residual angina. Therefore, the information obtained from coronary physiology allows for an optimised treatment strategy, which ultimately leads to improve patient's prognosis and quality of life. This review provides an overview of the latest available evidence in the literature regarding the use of functional assessment of epicardial coronary stenosis in different settings in the contemporary patient-tailored management of coronary disease., Competing Interests: Competing interests: VK is an associate editor for Heart., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)