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Throughout history, many innovations have contributed to the development of modern cardiothoracic surgery, improving patient outcomes and expanding the range of treatment options available to patients. This article explores five key historical innovations that have shaped modern cardiothoracic surgery: cardiopulmonary bypass, surgical pacemakers, video assisted thoracic surgery, robotic surgery and mechanical circulatory support. We will review the development, impact and significance of each innovation, highlighting their contributions to the field of cardiothoracic surgery and their ongoing relevance in contemporary and perioperative practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Objective: We examine whether the rise in neurological death rates over the 21st century are solely explained by the Gompertzian hypothesis., Study Design: We examine two data-sets. First, Office of National Statistics (ONS, 2022) for nineteen mortality categories in England/Wales, including Alzheimer's, Dementias and Parkinson's Disease. Secondly, WHO (2020) Combined Neurological Mortality (CNM), from WHO Global mortality categories, Nervous Disease Deaths, and Alzheimer's & Other Dementias., Methods: Based on ONS data we investigate trends in Age-Standardised Mortality Rates (ASMR) of CNM 2000-2022. Based on WHO data we examine rates of Early Deaths (55-74) and ASMR, for CNM between 2000 and 2015 in the ten Major 'Western' economies: Australia, Canada, France, Germany, Italy, Japan, Netherlands, Spain, UK, and the USA., Results: In England & Wales death rates have increased 348% for Alzheimer's, 235% for Dementias, and 105% for Parkinson's Disease in contrast with falls in most other cause mortality. Early Adults Deaths CNM rates increased in eight countries, an average of 19%. Neurological ASMR rose in every country, averaging 43%, the highest was the UK 95%., Conclusion: We reject the Gompertzian hypothesis as an all-encompassing explanation for these marked increases in ASMR. Increases in early adult neurological deaths suggests this cannot be solely explained by an aging population. Furthermore, increases in mortality could be related to an increased prevalence of neurological conditions in this age group. Action is urgently needed to investigate factors - whether environmental, lifestyle or health systems - that could explain these findings., Competing Interests: Declaration of competing interest No author has conflicts or vested interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Throughout history, many innovations have contributed to the development of modern otolaryngological surgery, improving patient outcomes and expanding the range of treatment options available to patients. This article explores five key historical innovations that have shaped modern otolaryngological surgery: Operative Microscope, Hopkins Rigid Endoscope, Laryngeal Nerve monitoring, Cochlear implants and Laser surgery. The selection of innovations for inclusion in this article was meticulously determined through expert consensus and an extensive literature review. We will review the development, impact and significance of each innovation, highlighting their contributions to the field of otolaryngological surgery and their ongoing relevance in contemporary and perioperative practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Throughout history, many innovations have contributed to the development of modern urological surgery, improving patient outcomes and expanding the range of treatment options available to patients. This article explores five key historical innovations that have shaped modern urological surgery: External shockwave lithotripsy, transurethral resection of prostate, cystoscope, perioperative prostate-specific antigen and robotic surgery. The selection of innovations for inclusion in this article was meticulously determined through expert consensus and an extensive literature review. We will review the development, impact and significance of each innovation, highlighting their contributions to the field of urological surgery and their ongoing relevance in contemporary and perioperative practice.

A woman in her late 50s with a left frontal lobe convexity meningioma underwent an elective endovascular embolisation of the left middle meningeal artery and distal branches of the left superficial temporal artery prior to surgical resection of the tumour. On postoperative day 46, she developed scalp necrosis, leading to poor wound healing requiring wound debridement and a complex plastic surgery reconstruction with a rotational flap. Endovascular embolisation of vascular tumours prior to surgical resection does not come without risks. The lack of consistency in the literature regarding indication, technique and outcomes makes it difficult to define the exact role of preoperative meningioma embolisation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The azygos system of veins has many anatomical variations that can impact mediastinal and vascular interventions. While radiological reports on these are of great clinical value, this study is among the first to present a high-quality cadaveric dissection of a rare anatomical variant to supplement previously published radiologic studies. The azygos venous system consists of the azygos vein (AV), hemiazygos vein (HAV), and the accessory hemiazygos vein (AHAV), which develop from the last portion of the posterior cardinal veins. The normal anatomical configuration includes drainage of the posterior intercostal veins, vertebral vein, esophageal veins, HAV, and AHAV to an unpaired right-side AV at the level of the 8th/9th thoracic vertebra. The reported incidence of AHAV draining directly into the left brachiocephalic vein is 1-2%., Methods: An adult formalin-fixed 70-year-old female cadaver was dissected as part of a medical gross anatomy elective course., Results: Gross documentation of a direct connection of the HAV to the AHAV with the AHAV draining into the left brachiocephalic vein., Conclusion: It is important to note the variations of the azygos system to avoid confusion with a potential pathology such as mediastinal masses. Understanding of the rare variant reported here could be useful in the prevention of iatrogenic bleeding from the misplacement of venous catheters and help facilitate radiological diagnosis in the incidence of venous clot formation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: The U grading of Ultrasound scan (USS) is used to assess the likelihood of malignancy in a thyroid nodule and help determine those that warrant an FNAC confirmation. All those of a U3-5 warrant an FNAC for confirmation and typing. This study aims to review the follow-up practice and the likelihood of picking up a malignancy on subsequent USS and FNAC, for those determined as an indeterminate U3 nodule., Methods: We retrospective reviewed the trust database (Portal) for patients who had a U3 nodule reported on USS identified, and clinical, operative and outcomes data were analysed., Results: 258 scans were identified over a 5-year period. The average age was 59 (range 15- 95) years old at first USS with a female to the male sex ratio of 4:1. The average number of USS that each patient prior to final diagnosis had averaged at 2.8 (range 1-12). Of those with an initial Thy status, 64 (33%) were benign (Thy2) and a further 49 (25%) were non diagnostics (Thy1). Over time, only 7 nodules were upgraded to a potential malignancy. Of those who underwent surgery, a final histological diagnosis was obtained in 41 cases. Only Thy1, 2 and 3f produced benign final histology results., Conclusions: For those indeterminate (U3) nodules of Th1-3f, electing for a watch and wait management strategy is reasonable for up to 2.5 years and 4 follow-up scans at an interval of 6-12 months should be implemented. A Thy2 result on a U3 nodule should not be taken as completely reassuring, a high index of suspicion of malignancy must be maintained.

Posterior spinal artery syndrome has a variable presentation and often poses a clinical challenge. We describe an acute posterior spinal artery syndrome in a man in his 60s with vascular risk factors, who presented with altered sensation in the left arm and left side of his torso but with normal tone, strength and deep tendon reflexes. MR imaging showed a left paracentral T2 hyperintense area affecting the posterior spinal cord at the level of C1. Diffusion-weighted MRI (DWI) showed high signal intensity in the same location. He was medically managed as having ischaemic stroke and made a good recovery. Three-month MRI follow-up showed a persisting T2 lesion but the DWI changes had resolved, consistent with the time course for infarction. Posterior spinal artery stroke has a variable presentation and is probably under-recognised clinically, requiring careful attention to MR imaging for its diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: End-stage kidney disease is associated with a 10- to 100-fold increase in cardiovascular mortality compared with age-, sex-, and race-matched population. Cardiopulmonary resuscitation (CPR) in this cohort has poor outcomes and leads to increased functional morbidity., Objective: The aim of this study is to assess patients' preferences toward CPR and advance care planning (ACP)., Design: cross-sectional study design., Setting: Two outpatient dialysis units., Patients: Adults undergoing dialysis for more than 3 months were included. Exclusion criteria were severe cognitive impairment or non-English-speaking patients., Measurements: A structured interview with the use of Willingness to Accept Life-Sustaining Treatment (WALT) tool., Methods: Demographic data were collected, and baseline Montreal Cognitive Assessment, Patient Health Questionnaire-9, Duke Activity Status Index, Charlson comorbidity index, and WALT instruments were used. Descriptive analysis, chi-square, and t test were performed along with probability plot for testing hypotheses., Results: Seventy participants were included in this analysis representing a 62.5% response rate. There was a clear association between treatment burden, anticipated clinical outcome, and the likelihood of that outcome with patient preferences. Low-burden treatment with expected return to baseline was associated with 98.5% willingness to accept treatment, whereas high-burden treatment with expected return to baseline was associated with 94.2% willingness. When the outcome was severe functional or cognitive impairment, then 45.7% and 28.5% would accept low-burden treatment, respectively. The response changed based on the likelihood of the outcome. In terms of resuscitation, more than 75% of the participants would be in favor of receiving CPR and mechanical ventilation at their current health state. Over 94% of patients stated they had never discussed ACP, whereas 59.4% expressed their wish to discuss this with their primary nephrologist., Limitations: Limited generalizability due to lack of diversity. Unclear decision stability due to changes in health status and patients' priorities., Conclusions: ACP should be incorporated in managing chronic kidney disease (CKD) to improve communication and encourage patient involvement., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Endovascular repair of the descending thoracic aorta has gained widespread acceptance as a primary treatment modality for thoracic aortic disease due to its minimally invasive approach and improved survival rates. GORE ® TAG ® Conformable Thoracic Stent Graft was designed for descending thoracic aortic aneurysms, penetrating ulcers, aortic transections and type B aortic dissections, which are accepted indications for endovascular therapy. The aim of this review is to summarize the clinical literature, focusing mainly on the publications that came from manufacturer's pre-market and post-market studies. Including the Global Registry for Endovascular Aortic Treatment (GREAT), sponsored by WL Gore & Associates (Flagstaff, AZ, USA), which is a large database of endovascular repair of various thoracic, abdominal and thoraco-abdominal aortic pathologies to identify and evaluate only those with isolated thoracic aortic pathology (arch and descending thoracic).

A 44-year-old man was admitted after being found suspended by his ankles from a bridge for 5 days. The events leading to it was not clearly known initially. On examination, the patient was hypotensive and hypothermic, airway was oedematous and both lower limbs were mottled with dusky feet. Both foot pulses were impalpable, with prolonged capillary refill time and sensation barely present. Doppler signals were not heard in the feet, but groin pulses and popliteal signals were present. On CT, the patient had bilateral pneumothoraxes, extensive subcutaneous emphysema throughout the body from the subcutaneous tissue of the scalp to both lower limbs and pneumomediastinum and pneumoperitoneum. CT angiogram showed opacification up to proximal crural vessels and absence beyond. After multispeciality input and optimisation of his physiology, he underwent bilateral below knee amputations as they were non-salvageable., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Interruption of the programmed death 1 (PD-1) / programmed death ligand 1 (PD-L1) pathway is an established and effective therapeutic strategy in human oncology and holds promise for veterinary oncology. We report the generation and characterization of monoclonal antibodies specific for canine PD-1 and PD-L1. Antibodies were initially assessed for their capacity to block the binding of recombinant canine PD-1 to recombinant canine PD-L1 and then ranked based on efficiency of binding as judged by flow cytometry. Selected antibodies were capable of detecting PD-1 and PD-L1 on canine tissues by flow cytometry and Western blot. Anti-PD-L1 worked for immunocytochemistry and anti-PD-1 worked for immunohistochemistry on formalin-fixed paraffin embedded canine tissues, suggesting the usage of this antibody with archived tissues. Additionally, anti-PD-L1 (JC071) revealed significantly increased PD-L1 expression on canine monocytes after stimulation with peptidoglycan or lipopolysaccharide. Together, these antibodies display specificity for the natural canine ligand using a variety of potential diagnostic applications. Importantly, multiple PD-L1-specific antibodies amplified IFN-γ production in a canine peripheral blood mononuclear cells (PBMC) concanavlin A (Con A) stimulation assay, demonstrating functional activity., Competing Interests: The authors have declared that no competing interests exist.

To explore the utility of the azinomycin B chromophore as a platform for the development of major-groove binding small molecules, we have prepared a series of 3-methoxy-5-methylnaphthalene derivatives containing diamine, triamine, and carbohydrate linker moieties. All bis- and tris-azinomycin derivatives are intercalators that display submicromolar binding affinities for calf-thymus DNA, as revealed by viscometry measurements and fluorescent intercalator displacement (FID) assays, respectively. Although the tightest binding ligand 1d (K a = 2.42 × 10 7 M -1 ) has similar affinities for sequence diverse polynucleotides, competition binding studies with methylated phage DNA and known major and minor groove binding small molecules suggest that the tether moiety linking the naphthalene chromophores may occupy the major groove of DNA.

A current goal in nanotechnology focuses on the assembly of different nanoparticle types into 3D organized structures. In this paper we report the use of a liquid crystal host phase in a new process for the generation of micron-scale vesicle-like nanoparticle shells stabilized by ligand-ligand interactions. The constructs formed consist of a robust, thin spherical layer, composed of closely packed quantum dots (QDs) and stabilized by local crystallization of the mesogenic ligands. Ligand structure can be tuned to vary QD packing within the shell and made UV cross-linkable to allow for intact shell extraction into toluene. The assembly method we describe could be extended to other nanoparticle types (metallic, magnetic etc.), where hollow shell formation is controlled by thermally sorting mesogen-functionalized nanoparticles in a liquid crystalline host material at the isotropic to nematic transition. This process represents a versatile method for making non-planar 3D nano-assemblies.

The convergent total synthesis of polycarcin V, a gilvocarcin-type natural product that shows significant cytotoxicity with selectivity for nonsmall-cell lung cancer, breast cancer, and melanoma cells, has been achieved in 13 steps from 7, 8, and 22; the sequence features a stereoselective α-C-glycosylation reaction for the union of protected carbohydrate 7 and naphthol 8. The association constant for the binding of polycarcin V to duplex DNA is similar to that previously reported for gilvocarcin V.

The 3,3'-di-O-methyl derivative (15) of the bis-C-aryl glycoside natural product ardimerin (1) has been synthesized in 11 steps from 2,3,4,6-tetrabenzylglucose (2) and 1,2,3-trimethoxybenzene (3). Key steps in the synthesis involve a Lewis acid mediated Friedel-Crafts type glycosylation and a Yamaguchi lactonization under Yonemitsu conditions. 3,3'-Di-O-methyl ardimerin aggregates in aqueous solutions at concentrations greater than 1 μM, and both UV and fluorescence binding studies indicate that 15 has a low affinity for duplex DNA.