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Tumoral heterogeneity has been associated with treatment resistance and failure in patients with cancer. Tumoral heterogeneity can be either intertumoral (static variation of cancer cells) or intratumoral (spatial and temporal variation of cancer cells). Nonsmall-cell lung cancer (NSCLC) is considered a model disease for the study of tumoral heterogeneity, given the emerging evidence about the clinical implications of genetic variations among NSCLC subtypes. This review provides an overview of the etiology, detection, and management methods of intratumoral heterogeneity in NSCLC and discusses their clinical implications.

Andreas Koulouris,1 Christos Tsagkaris,2 Vasiliki Spyrou,3 Eleni Pappa,4 Aikaterini Troullinou,2 Michail Nikolaou5 1Resident of Medical Oncology, University General Hospital of Heraklion, University of Crete, Crete, Greece; 2Medical School, University of Crete, Crete, Greece; 3Hygeia Hospital, Athens, Greece; 4Medical School, National and Kapodistrian University of Athens, Athens, Greece; 5 1st Oncology Department, “Saint Savas” Anticancer - Oncology Hospital, Athens, GreeceCorrespondence: Michail Nikolaou 1st Oncology Department, “Saint Savas” Anticancer - Oncology Hospital, Athens, GreeceEmail nikolaoumike@hotmail.comAbstract: The last three years have seen remarkable progress in comprehending predisposing factors and upgrading our treatment arsenal concerning hepatocellular carcinoma (HCC). Until recently, there were no means to withstand the progression of viral hepatitis-associated liver cirrhosis to HCC. A deeper understanding of the molecular mechanism of the disease, the use of biomarkers, and the follow-up, allowed us to realize that conventional chemotherapy failing to increase survival in patients with advanced HCC tends to be exiled from clinical practice. Multi-kinase inhibitors (TKIs) such as sorafenib, lenvatinib targeting mainly the vascular endothelial growth factor receptors 1– 3 VEGFRs 1– 3 provided until recently the standard of care for these patients, as first- or second-line treatment. Since May 2020, the atezolizumab plus bevacizumab combination (immunotherapy plus anti-VEGF) has become the new reference standard in first-line HCC treatment. Additionally, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy can be used as a second-line treatment following first-line treatment’s failure. Phase III clinical trials have recently suggested the efficacy of novel anti-angiogenic factors such as cabozantinib and ramucirumab as a second-line treatment option. With considerations about toxicity arising, clinical trials are investigating combinations of the aforementioned targeted therapies with immunotherapy as first-line treatment. This paper aims to perform a systematic review describing the evolving treatment options for HCC over the last decades, ranging from neoadjuvant treatment to systemic therapy of advanced-stage HCC. With the landscape of HCC treatment shifting towards novel agents the forming of a new therapeutic algorithm for HCC seems to be imperative.Keywords: hepatocellular carcinoma, immunotherapy, targeted therapy, tyrosine kinase inhibitors, biomarkers

Tumoral heterogeneity has been associated with treatment resistance and failure in patients with cancer. Tumoral heterogeneity can be either intertumoral (static variation of cancer cells) or intratumoral (spatial and temporal variation of cancer cells). Nonsmall-cell lung cancer (NSCLC) is considered a model disease for the study of tumoral heterogeneity, given the emerging evidence about the clinical implications of genetic variations among NSCLC subtypes. This review provides an overview of the etiology, detection, and management methods of intratumoral heterogeneity in NSCLC and discusses their clinical implications. The authors searched biomedical databases (Medline, Scopus, Embase) for studies reporting on intratumoral heterogeneity in NSCLC. Intratumoral heterogeneity occurs in single tumors, multiple tumors in the same organs, primary tumors and metastases, and among distinct metastases. Genetic (selective pressure, clonal evolution, genomic instability) and nongenetic pathways (tumor metabolism, hypoxia) precipitate heterogeneity across the spatial and temporal progression of the disease. Proposed classifications are based either on cancer subtypes or mutations detected and metastasis sites. Liquid biopsies (cell-free DNA, circulating tumor cells) combined with imaging (computed tomographies (CTs), positron emission tomography/computed tomographies (PET/CTs)) have a major potential for the continuous minimally invasive monitoring of intratumoral heterogeneity in comparison to conventional biopsies. Targeted therapies have a higher likelihood to induce heterogeneity and resistance, while PD-L1 immunotherapy represents a promising therapeutic strategy. Spatial and temporal intratumoral heterogeneity within a single patient sets additional challenges to personalized precision medicine, calling for continuous cellular and molecular-level surveillance and adequate adjustment of the treatment plan. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is considered the most common sustained arrhythmia. Major cardiovascular risk factors that have been identified to initiate and perpetuate AF include age, sex, arterial hypertension, heart failure, valvular heart disease and diabetes mellitus. In the literature, several studies aimed to formulate easily – applied and accurate risk stratification scores, based on antecedent cardiovascular events, comorbidities and biomarkers for the prediction of new-onset AF. The present narrative review addresses the most universally accepted and efficient clinical scores, with an extended applicability in different populations and ages, particularly scores derived from the Framingham Heart Study, the Atherosclerosis Risk in Communities, the Malmo Diet and Cancer Study, as well as the CHARGE-AF, the CHADS2, CHA2DS2-VASc, HATCH and CH2EST scores. Identification of incident AF can be challenging, thus dictating for utilization of validated clinical instruments in everyday clinical practice.

For every 2 h without electricity, in-patient mortality increases by 43%, affecting primarily patients in intensive care units and operating theaters.[2] Although electricity generators may be available in hospitals, home-dwelling patients rarely have such a back-up plan. The 15th November 2022 marked the heaviest missile attack since the beginning of the Russia-Ukraine war. [Extracted from the article]

Space Medicine has grown in parallel to Space Exploration since the second half of the 20th century. Surgery and anesthesia procedures with a special focus on acute surgical conditions management have been investigated and/or performed on animal models and astronauts/cosmonauts. Although total anesthesia has been successfully performed on animal models it is considered of high risk for humans and regional anesthesia techniques have been the method of choice so far. The history of surgery and anesthesia in Space has expanded the limits of these fields and is expected to skyrocket their conjugation with modern technology such as 3D printing. [ABSTRACT FROM AUTHOR]

Background Context: Pedicle screw instrumentation is widely used in spine surgery. Axial screw misplacement is a common complication. In addition to the recognized neurovascular risks associated with screw misplacement, the biomechanical stability of misplaced screws remains a subject of debate., Purpose: The present study investigates whether screw misplacement in the lumbar spine reduces mechanical screw hold., Study Design/setting: Cadaveric biomechanical study., Methods: Pedicle screw (mis)placement was planned for 12 fresh frozen cadaveric spines between the T12 and the L5 levels. The screws were then implanted into the vertebrae with the help of 3D-printed template guides. Pre- and postinstrumentation computed tomography (CT) scans were acquired for instrumentation planning and quantification of the misplacement. The instrumented vertebrae were potted into CT transparent boxes using Polymethyl methacrylate and mounted on a standardized biomechanical setup for pull-out (PO) testing with uniaxial tensile load., Results: The bone density of all the specimens as per HU was comparable. The predicted pull-out force (POF) for screws medially misplaced by 2 , 4, and 6 mm was respectively 985 N (SD 474), 968 N (SD 476) and 822 N (SD 478). For screws laterally misplaced by 2 , 4, and 6 mm the POF was respectively 605 N (SD 473), 411 N (SD 475), and 334 N (SD 477). Screws that did not perforate the pedicle (control) resisted pull-out forces of 837 N (SD 471)., Conclusions: Medial misplacement is associated with increased axial screw hold against static loads compared to correctly placed screws and laterally placed screws., Clinical Significance: In clinical settings, the reinsertion of medially misplaced screws should primarily aim to prevent neurological complications while the reinsertion of lateral misplaced screws should aim to prevent screw loosening., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024. Published by Elsevier Inc.)

Mpox, also known as Monkeypox, is an infectious disease known to spread via direct contact and fomites, which poses a significant contagion risk in surgical settings and may increase the challenges already posed by COVID-19. Within the three years following the outbreak of Mpox, we conducted a review of the impact of Mpox on surgical practice. We searched Pubmed/Medline and Scopus, focusing on original studies and case reports in English or German. Our search terms included "Mpox", "Monkeypox", and "Surgery". Out of 60 clinical or epidemiological studies, as well as expert opinions, brief reports, and pertinent literature reviews, eight were included after full-text assessment. We also incorporated two pertinent literature reviews, including a total of 10 papers, in this analysis. The main topics addressed by the literature are 1. manifestations of Mpox for surgical consideration or urgent management, for which it is important to consider whether a surgical approach is needed to address long-term Mpox-related lesions and 2. infection control in surgical settings, especially considering its impact on elective surgery and the well-being of healthcare workers. Mpox could affect surgical services and access to operating theaters. Unlike COVID-19, Mpox, compared to initial concerns, has not substantially compromised surgical delivery. However, limited reports exist on the surgical impact of Mpox. It is crucial to involve surgeons in Mpox diagnosis, educate surgical practitioners on its mimicry of common surgical conditions, enhance infection control during surgery, and ensure access to corrective surgery as a means of tackling the stigmatization associated with Mpox and sexually transmitted diseases in general.

Understanding the implications of decreased femoral torsion on gait and running in children and adolescents might help orthopedic surgeons optimize treatment decisions. To date, there is limited evidence regarding the kinematic gait deviations between children with decreased femoral torsion and typically developing children, as well as the implications of the same on the adaptation of walking to running. A three-dimensional gait analysis study was undertaken to compare gait deviations during running and walking among patients with decreased femoral torsion ( n = 15) and typically developing children ( n = 11). Linear mixed models were utilized to establish comparisons within and between the two groups and investigate the relationship between clinical examination, spatial parameters, and the difference in hip rotation between running and walking. Patients exhibited increased external hip rotation during walking in comparison to controls, accompanied by higher peaks for the same as well as for knee valgus and external foot progression angle. A similar kinematic gait pattern was observed during running, with significant differences noted in peak knee valgus. In terms of variations from running to walking, patients internally rotated their initially externally rotated hip by 4°, whereas controls maintained the same internal hip rotation. Patients and controls displayed comparable kinematic gait deviations during running compared to walking. The passive hip range of motion, torsions, and velocity did not notably influence the variation in mean hip rotation from running to walking. This study underlines the potential of 3D gait kinematics to elucidate the functional implications of decreased FT and, hence, may contribute to clinical decision making.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females. PCOS is associated with various metabolic and cardiovascular complications, including insulin resistance, dyslipidemia, and an increased risk of type 2 diabetes mellitus and cardiovascular disease. The role of serum prolactin (PRL) in the development of these complications in PCOS is not well understood., Aim: This study aims to investigate the correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS., Methods: The study utilized secondary outcomes from a prospectively collected patient database at the Third Department of Obstetrics and Gynecology, Medical School of the University of Athens. Data were collected from patients who visited the Gynecological Endocrinology - Pediatric and Adolescence Endocrinology Outpatient Clinic between January 2007 and December 2015. Measurements of various parameters, including PRL levels, BMI, waist circumference, hormone levels, lipid profiles, and insulin sensitivity, were obtained. Statistical analyses, including Mann-Whitney tests, chi-square tests, Spearman correlations, and multiple linear regression analyses, were conducted using SPSS software (IBM Corp., Armonk, NY, USA)., Results: The study included 247 women with PCOS, with a mean age of 24.7 years. Participants were divided into two groups based on the median PRL level. Women with higher PRL levels (>14.9) had lower BMI and waist circumference, higher levels of certain hormones and insulin sensitivity, and lower levels of fasting insulin, total cholesterol, and total lipids. Factors associated with lower PRL levels included being overweight/obese and smoking more than 10 cigarettes per day. Higher age, BMI, waist circumference, and certain hormone levels were associated with lower PRL levels., Conclusion: The findings suggest a correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. Further research is needed to elucidate the role of PRL in the pathophysiology of PCOS and to explore its potential as a diagnostic and therapeutic target., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kastrinakis et al.)

Young health advocates have the legitimate aspiration to be masters of their future and are increasingly contributing to public health research and practice worldwide, yet their potential to contribute to the documentation and communication of outputs from public health conferences has not been fully realised. This short communication highlights the Youth Committee of the 2023 European Conference on Tobacco or Health as an example of youth involvement in a major public health conference focused on tobacco control. The authors explore the benefits, practicalities and challenges of incorporating young professionals into conference workflow, including creativity, networking and engagement with broader public health challenges within their communities. This article emphasises the active participation of Youth Committees in public health fora as a model for future conferences and underscores a commitment to achieving a tobacco-free generation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Surgery is one of the most energy-intensive branches of healthcare. Although the COVID-19 pandemic has reduced surgical volumes, infection control protocols have increased the ecological footprint of surgery owing to the extensive use of personal protective equipment, sanitation, testing and isolation resources. The burden of environmental diseases requiring surgical care, the international commitment towards environmental sustainability and the global efforts to return to the pre-pandemic surgical workflow call for action towards climate-friendly surgery. The authors have searched the peer-reviewed and gray literature for clinical studies, reports and guidelines related to the ecological footprint of surgical care and the available solutions and frameworks to reduce it. Numerous studies concede that surgery is associated with a high rate of energy utilization and waste generation that is comparable to major non-medical sources of pollution. Recommendations and research questions outlining environmentally sustainable models of surgical practices span from sanitation and air quality improvement systems to the allocation of non-recyclable consumables and energy-efficient surgical planning. The latter are particularly relevant to infection control protocols for COVID-19. Paving the way towards climate-friendly surgery is a worthy endeavor with a major potential to improve surgical practice and outcomes in the long term.

Breast cancer (BC) is the most prevalent neoplasm among women. Genetic and environmental factors lead to BC development and on this basis, several preventive - screening and therapeutic interventions have been developed. Hormones, both in the form of endogenous hormonal signaling or hormonal contraceptives, play an important role in BC pathogenesis and progression. On top of these, breast microbiota includes both species with an immunomodulatory activity enhancing the host's response against cancer cells and species producing proinflammatory cytokines associated with BC development. Identification of novel multitargeted therapeutic agents with poly-pharmacological potential is a dire need to combat advanced and metastatic BC. A growing body of research has emphasized the potential of natural compounds derived from medicinal plants and microbial species as complementary BC treatment regimens, including dietary supplements and probiotics. In particular, extracts from plants such as Artemisia monosperma Delile , Origanum dayi Post , Urtica membranacea Poir. ex Savigny , Krameria lappacea (Dombey) Burdet & B.B. Simpson and metabolites extracted from microbes such as Deinococcus radiodurans and Streptomycetes strains as well as probiotics like Bacillus coagulans and Lactobacillus brevis MK05 have exhibited antitumor effects in the form of antiproliferative and cytotoxic activity, increase in tumors' chemosensitivity, antioxidant activity and modulation of BC - associated molecular pathways. Further, bioactive compounds like 3,3'-diindolylmethane, epigallocatechin gallate, genistein, rutin, resveratrol, lycopene, sulforaphane, silibinin, rosmarinic acid, and shikonin are of special interest for the researchers and clinicians because these natural agents have multimodal action and act via multiple ways in managing the BC and most of these agents are regularly available in our food and fruit diets. Evidence from clinical trials suggests that such products had major potential in enhancing the effectiveness of conventional antitumor agents and decreasing their side effects. We here provide a comprehensive review of the therapeutic effects and mechanistic underpinnings of medicinal plants and microbial metabolites in BC management. The future perspectives on the translation of these findings to the personalized treatment of BC are provided and discussed.

Aims: Atrial fibrillation (AF) and cancer often co-exist. Each has been associated with an increased risk of morbidity and mortality. The aim of this meta-analysis was to synthesize available data regarding the incidence of arterial thromboembolism (TE), bleeding, and all-cause mortality in patients with AF with or without cancer., Methods: Literature search was conducted in PubMed, Ovid MEDLINE, WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases to identify studies that included patients with AF and accounted for cancer status with the incidence of TE (ischemic stroke, transient ischemic attack, or arterial thrombosis), major or clinically relevant non-major bleeding, and all-cause mortality. A random-effects meta-analysis was used., Results: Overall, 17 studies were included (3,149,547 patients). The risk of TE was similar in patients with AF with comorbid cancer compared with that in AF alone (pooled odds ratio [pOR] 0.97, 95% Confidence Interval [CI] 0.85-1.11, I 2  = 87%). Major or clinically relevant non-major bleeding (pOR 1.65, 95% CI 1.35-2.02, I 2  = 98%) and all-cause death (pOR 2.17, 95% CI 1.83-2.56, I 2  = 98%) were significantly higher in patients with AF with cancer than in patients with AF only. The history of TE and hypertension and mean age were significant moderators of TE risk., Conclusion: In patients with AF, the presence of cancer is associated with a similar risk of TE as well as an increased risk of bleeding and all-cause death compared with the absence of cancer., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Spinal fusion is the most common surgical treatment for the management of degenerative spinal disease. However, complications such as screw loosening lead to painful pseudoarthrosis, and are a common reason for revision. Optimization of screw trajectories to increase implant resistance to mechanical loading is essential. A recent optimization method has shown potential for determining optimal screw position and size based on areas of high bone elastic modulus (E-modulus). Aim: The aim of this biomechanical study was to verify the optimization algorithm for pedicle screw placement in a cadaveric study and to quantify the effect of optimization. The pull-out strength of pedicle screws with an optimized trajectory was compared to that of a traditional trajectory. Methods: Twenty-five lumbar vertebrae were instrumented with pedicle screws (on one side, the pedicle screws were inserted in the traditional way, on the other side, the screws were inserted using an optimized trajectory). Results: An improvement in pull-out strength and pull-out strain energy of the optimized screw trajectory compared to the traditional screw trajectory was only observed for E-modulus values greater than 3500 MPa cm 3 . For values of 3500 MPa cm 3 or less, optimization showed no clear benefit. The median screw length of the optimized pedicle screws was significantly smaller than the median screw length of the traditionally inserted pedicle screws, p < 0.001. Discussion: Optimization of the pedicle screw trajectory is feasible, but seems to apply only to vertebrae with very high E-modulus values. This is likely because screw trajectory optimization resulted in a reduction in screw length and therefore a reduction in the implant-bone interface. Future efforts to predict the optimal pedicle screw trajectory should include screw length as a critical component of potential stability., Competing Interests: MF reports being a Consultant for Incremed (Balgrist University Startup), Zimmer Biomet, Medacta, and 25 Segments (Balgrist Startup). All the other authors report no conflicts of interest., (Copyright © 2023 Tsagkaris, Calek, Fasser, Spirig, Caprara, Farshad and Widmer.)