bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Organotypic Systems for Modelling and Understanding Molecular Regulation of Oral Dentogingival Tissues
Authors: Lu Emily Ming-Chieh
Published: October 2024

Three-dimensional organotypic models benefit from the ability to mimic physiological cell–cell or cell–matrix interactions and therefore offer superior models for studying pathological or physiological conditions compared to 2D cultures. Organotypic models consisting of keratinocytes supported by fibroblasts embedded in collagen matrices have been utilised for the study of oral conditions. However, the provision of a suitable model for investigating the pathogenesis of periodontitis has been more challenging. Part of the complexity relates to the different regional epithelial specificities and connective tissue phenotypes. Recently, it was confirmed, using 3D organotypic models, that distinct fibroblast populations were implicated in the provision of specific inductive and directive influences on the overlying epithelia. This paper presents the organotypic model of the dentogingival junction (DGJ) constructed to demonstrate the differential fibroblast influences on the maintenance of regionally specific epithelial phenotypes. Therefore, the review aims are (1) to provide the biological basis underlying 3D organotypic cultures and (2) to comprehensively detail the experimental protocol for the construction of the organotypic cultures and the unique setup for the DGJ model. The latter is the first organotypic culture model used for the reconstruction of the DGJ and is recommended as a useful tool for future periodontal research.
Cell Wall Invertases from Maternal Tissues Modulate Sucrose Flux in Apoplastic Pathways During Rice Anther and Seed Development
Authors: Lee Sang-Kyu , Shim Su-Hyeon , Eom Joon-Seob , Cho Jung-Il , Kwak Jae-Ung , Eom Seong-Cheol , Jeon Jong-Seong
Published: October 2024

Efficient sucrose transport and metabolism are vital for seed and pollen development in plants. Cell wall invertases (CINs) hydrolyze sucrose into glucose and fructose, maintaining a sucrose gradient in the apoplast of sink tissues. In rice, two CIN isoforms, OsCIN1 and OsCIN2, were identified as being specifically expressed in the anthers but not in pollen. Functional analyses through genetic crosses and mutant characterization showed that oscin1/2 double mutants exhibit a sporophytic male-sterile phenotype and produce shrunken seeds. This suggests that CIN activity is essential for proper pollen development and seed formation in rice. Observation of the progeny genotypes and phenotypes from various genetic crosses revealed that the phenotype of oscin1/2 seeds is determined by the genotype of the maternal tissue, indicating the critical role of CIN function in the apoplast between maternal and filial tissues for sucrose transport and metabolism. The CIN activity in the anthers and seeds of wild-type rice was found to be significantly higher—over 500-fold in the anthers and 5-fold in the seeds—than in the leaves, highlighting the importance of CIN in facilitating the efficient unloading of sucrose. These findings suggest that the fine-tuning of CIN activity in the apoplast, achieved through tissue-specific expression and CIN isoform regulation, plays a key role in determining the carbohydrate distribution across different tissues. Understanding this regulatory mechanism could provide opportunities to manipulate carbohydrate allocation to sink organs, potentially enhancing crop yields.
High Behavioral Reactivity to Novelty as a Susceptibility Factor for Memory and Anxiety Disorders in Streptozotocin-Induced Neuroinflammation as a Rat Model of Alzheimer’s Disease
Authors: Dunacka Joanna , Świątek Grzegorz , Wrona Danuta
Published: October 2024

Individual differences in responsiveness to environmental factors, including stress reactivity and anxiety levels, which differ between high (HR) and low (LR) responders to novelty, might be risk factors for development of memory and anxiety disorders in sporadic Alzheimer’s disease (sAD). In the present study, we investigated whether behavioral characteristics of the HR and LR rats, influence the progression of sAD (neuroinflammation, β-amyloid peptide, behavioral activity related to memory (Morris water maze) and anxiety (elevated plus maze, white and illuminated open field test) in streptozotocin (STZ)-induced neuroinflammation as a model of early pathophysiological alterations in sAD. Early (45 days) in disease progression, there was a more severe impairment of reference memory and higher levels of anxiety in HRs compared with LRs. Behavioral depression in HRs was associated with higher expression of β-amyloid deposits, particularly in the NAcS, and activation of microglia (CD68+ cells) in the hypothalamus, as opposed to less inflammation in the hippocampus, particularly in CA1, compared with LRs in late (90 days) sAD progression. Our findings suggest that rats with higher behavioral activity and increased responsivity to stressors show more rapid progression of disease and anxiety disorders compared with low responders to novelty in the STZ-induced sAD model.
Antibacterial Properties of Copper Oxide Nanoparticles (Review)
Authors: Gudkov Sergey V. , Burmistrov Dmitry E. , Fomina Polina A. , Validov Shamil Z. , Kozlov Valery A.
Published: October 2024

The use of metal and metal oxide nanoparticles is frequently regarded as a potential solution to the issue of bacterial antibiotic resistance. Among the proposed range of nanoparticles with antibacterial properties, copper oxide nanoparticles are of particular interest. Although the antibacterial properties of copper have been known for a considerable period of time, studies on the effects of copper oxide nanomaterials with respect to biological systems have attracted considerable attention in recent years. This review presents a summary of the antibacterial properties of copper oxide nanoparticles, the mechanisms by which the antibacterial effect is realized, and the key reported methods of modifying these nanoparticles to improve their antibacterial activity. A comparative analysis of the effectiveness of these nanoparticles is presented depending on the type of microorganism, the shape of the nanoparticles, and the Gram classification of bacteria based on data from published sources. In addition, the review addresses the biological activities of copper oxide nanoparticles, including their antifungal and cytotoxic properties, as well as their “antioxidant” activity. According to the conducted analysis of the literature data, it can be concluded that copper oxide nanoparticles have a significant bacteriostatic potential with respect to a wide range of microorganisms and, in some cases, contribute to the inhibition of fungal growth. At the same time, the sensitivity of Gram-positive bacteria to the effect of copper oxide nanoparticles was often higher than that of Gram-negative bacteria.
The Therapeutic Potential of Exosomes vs. Matrix-Bound Nanovesicles from Human Umbilical Cord Mesenchymal Stromal Cells in Osteoarthritis Treatment
Authors: Klyucherev Timofey O. , Peshkova Maria A. , Revokatova Daria P. , Serejnikova Natalia B. , Fayzullina Nafisa M. , Fayzullin Alexey L. , Ershov Boris P. , Khristidis Yana I. , Vlasova Irina I. , Kosheleva Nastasia V. , Svistunov Andrey A. , Timashev Peter S.
Published: October 2024

Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, where inflammation plays a critical role in disease progression. Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) have shown potential as a therapeutic approach for OA by modulating inflammation and alleviating degenerative processes in the joint. This study evaluated the therapeutic effects for the treatment of OA of two types of EV—exosomes and matrix-bound nanovesicles (MBV)—both derived from the human umbilical cord MSC (UC-MSC) via differential ultracentrifugation. Different phenotypes of human monocyte-derived macrophages (MDM) were used to study the anti-inflammatory properties of EV in vitro, and the medial meniscectomy-induced rat model of knee osteoarthritis (MMx) was used in vivo. The study found that both EV reduced pro-inflammatory cytokines IL-6 and TNF-α in MDM. However, exosomes showed superior results, preserving the extracellular matrix (ECM) of hyaline cartilage, and reducing synovitis more effectively than MBVs. Additionally, exosomes downregulated inflammatory markers (TNF-α, iNOS) and increased Arg-1 expression in macrophages and synovial fibroblasts, indicating a stronger anti-inflammatory effect. These results suggest UC-MSC exosomes as a promising therapeutic option for OA, with the potential for modulating inflammation and promoting joint tissue regeneration.
Evaluation of Targeted Alpha Therapy Using [211At]FAPI1 in Triple-Negative Breast Cancer Xenograft Models
Authors: Abe Kaori , Watabe Tadashi , Kaneda-Nakashima Kazuko , Shirakami Yoshifumi , Kadonaga Yuichiro , Naka Sadahiro , Ooe Kazuhiro , Toyoshima Atsushi , Giesel Frederik , Usui Takeshi , Masunaga Nanae , Mishima Chieko , Tsukabe Masami , Yoshinami Tetsuhiro , Sota Yoshiaki , Miyake Tomohiro , Tanei Tomonori , Shimoda Masafumi , Shimazu Kenzo
Published: October 2024

Triple-negative breast cancer (TNBC) presents limited therapeutic options and is associated with poor prognosis. Early detection and the development of novel therapeutic agents are therefore imperative. Fibroblast activation protein (FAP) is a membrane protein expressed on cancer-associated fibroblasts (CAFs) that plays an essential role in TNBC proliferation, migration, and invasion. Consequently, it is hypothesized that the Astatine (211At)-labeled FAP inhibitor (FAPI) selectively exerts anti-tumor effects through alpha-particle emission. In this study, we aimed to assess its theranostic capabilities by integrating [18F]FAPI-74 PET imaging with targeted alpha therapy using [211At]FAPI1 in TNBC models. Mice xenografts were established by transplanting MDA-MB-231 and HT1080 cells (control). As a parallel diagnostic method, [18F]FAPI-74 was administered for PET imaging to validate FAP expression. A single dose of [211At]FAPI1 (1.04 ± 0.10 MBq) was administered to evaluate the therapeutic efficacy. [18F]FAPI-74 exhibited high accumulation in MDA-MB-231 xenografts, and FAP expression was pathologically confirmed via immunostaining. The group that received [211At]FAPI1 (n = 11) demonstrated a significantly enhanced anti-tumor effect compared with the control group (n = 7) (p = 0.002). In conclusion, [18F]FAPI-74 PET imaging was successfully used to diagnose FAP expression, and as [211At]FAPI1 showed promising therapeutic efficacy in TNBC models, it is expected to be a viable therapeutic option.
Poly-D,L-Lactic Acid Filler Attenuates Ultraviolet B-Induced Skin Pigmentation by Reducing Destruction of the Basement Membrane
Authors: Byun Kyung-A , Seo Suk Bae , Oh Seyeon , Jang Jong-Won , Son Kuk Hui , Byun Kyunghee
Published: October 2024

Poly-D,L-lactic acid (PDLLA) filler, which increases volume and collagen synthesis, is used for skin rejuvenation. PDLLA filler also increases M2 macrophages and IL-10. Ultraviolet (UV) radiation induces dermal hyperpigmentation by disrupting the basement membrane (BM), allowing melanin to move into the dermis. Therefore, using UV-irradiated macrophages and animal skin, we determined whether PDLLA filler decreased M1 macrophages and skin inflammation, thereby reducing BM destruction and dermal hyperpigmentation. UV radiation increased the M1 macrophage marker CD86 and TNF-α expression, which was inhibited by the treatment of macrophages with PDLLA. In fibroblasts treated with conditioned medium from UV-irradiated macrophages, NF-κB activity, NLRP3 inflammasome components (NLRP3, ASC, and pro-caspase-1), IL-18, MMP2, and MMP9 increased, but all decreased after PDLLA treatment. Similar to the in vitro study, UV-irradiated mouse skin showed increased CD86, NLRP3, ASC, pro-caspase-1, MMP2, and MMP9, which decreased after PDLLA injection. Disruption of the lamina densa of the BM and dermal pigmentation increased after UV irradiation and decreased after PDLLA injection. In conclusion, PDLLA reduced dermal pigmentation by decreasing BM destruction in UV-irradiated skin. PDLLA has the potential to reduce dermal pigmentation by regenerating the BM.
Hydroxyacid Oxidase 1, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Luminal Breast Cancer
Authors: Erkan Busra , MacIntyre Skye , Brown Charlotte , Fakroun Ali , Lashen Ayat G. , Mongan Nigel P. , Ellis Ian O. , Rakha Emad A. , Green Andrew R.
Published: October 2024

Breast cancer (BC), which remains the most prevalent malignancy among women, is characterised by significant heterogeneity across its molecular subtypes. Oestrogen receptor-positive (ER+) (luminal) BC represents approximately 75% of cases, and despite advancements in treatment there remains around a 40% recurrence rate. Cellular uptake of glutamine is conducted by solute carriers (SLCs), which are significantly associated with outcome in luminal BC. In this study, differential gene expression analysis was carried out using The Cancer Genome Atlas BC dataset. This identified hydroxyacid oxidase 1 (HAO1) as significantly overexpressed in luminal BC with a high expression of SLCs. Extended analysis in the METABRIC (n = 1980) and Breast Cancer Gene-Expression Miner (n = 4421) transcriptomic databases and the Nottingham (n = 952) BC tissue cohort showed a varied survival outcome for HAO1 expression at the genomic, transcriptomic, and proteomic levels. HAO1 copy number (CN) gain (p = 0.002) and high HAO1 protein expression (p = 0.019) were associated with poor prognosis in luminal BC, whereas high HAO1 mRNA expression correlated with better survival outcomes (p = 0.023) suggesting a complex regulatory mechanism affecting HAO1 at different biological levels. Importantly, in luminal BC patients treated with endocrine therapy, high protein expression of HAO1 predicted shorter distant-metastasis free survival (p = 0.042). The knockdown of SLC1A5 and SLC7A5 significantly reduced HAO1 expression in MCF-7 and ZR-751 BC cell lines. Protein analysis confirmed significant associations between HAO1 and SLC7A5 and SLC1A5, emphasising a potential role for the enzyme in glutamine metabolism and its potential as a therapeutic target. This study underscores the prognostic significance of HAO1 in luminal BC and its relationship with patient outcomes.
Restoring Colistin Sensitivity in Multidrug-Resistant Pathogenic E. coli Using Cinacalcet Hydrochloride
Authors: Wang Chenchen , Zhang Ziyi , Liu Di , Li Xiaodan , Zhang Zhaoran , Zeng Yan , Dong Wenqi , Tan Chen , Liu Manli
Published: October 2024

Restoring colistin’s efficacy is crucial in addressing the resistance crisis of colistin. This study utilized a high-throughput screening method to identify 43 compounds from 800 FDA-approved drugs that exhibited significant antibacterial effects when combined with colistin. Among these, cinacalcet hydrochloride (CH) was selected for its potential synergistic effect with colistin against multidrug-resistant (MDR) E. coli strains, including mcr-1-positive strains. A series of experiments revealed that the combination of CH and colistin showed strong synergy, especially in mcr-1-positive strains, restoring colistin sensitivity. The combination significantly inhibited bacterial growth and reduced CFU counts more effectively than either drug alone. Additionally, CH and colistin together significantly inhibited biofilm formation and eradicated existing biofilms, as visualized through confocal microscopy. Mechanistic studies showed that the combination increased bacterial membrane permeability and disrupted membrane integrity. The treatment also elevated extracellular ATP release and ROS production, indicating oxidative stress-induced bacterial death. Safety evaluations showed that the combination did not increase toxicity in host cells. Finally, animal models further validated the combination’s efficacy. Overall, this study showed that the combination of colistin and CH significantly restored colistin sensitivity in mcr-1-positive E. coli, revealing their synergistic antibacterial mechanism involving membrane damage and oxidative stress, with promising clinical applications.
Monitoring Cell Activation and Extracellular Vesicle Generation in Platelet Concentrates for Transfusion
Authors: Kolenc Ana , Grundner Maja , Hostnik Irma , Maličev Elvira
Published: October 2024

Platelets play a crucial role in blood transfusions, and understanding the changes that occur during their storage is important for maintaining the quality of preparations. In this study, we examined key alternating factors, with a particular focus on platelet activation and the release of extracellular vesicles. Additionally, we compared two detection methods—imaging flow cytometry (IFC) and nanoparticle tracking analysis (NTA)—for their effectiveness in detecting particles. Platelet concentrates were prepared by pooling buffy coats from five blood group-compatible donors in an additive solution. Samples were analysed after one, three, and seven days of storage for residual white blood cells (WBCs), glucose levels, platelet activation, and extracellular vesicle concentrations. Over the storage period, the total platelet concentration decreased slightly, while the residual WBC count remained stable. Glucose levels declined, whereas platelet activation and extracellular vesicle concentration increased, with a positive correlation between the two. The particle size remained relatively unchanged throughout the storage period. Ultimately, despite controlled processing and storage conditions, platelet activation, and the release of extracellular vesicles still occurred, which may have implications for transfusion recipients. Although an optimised method is still needed, IFC has proved to be specific and potentially appropriate for detecting extracellular vesicles in transfusion preparations.
Electrification or Hydrogen? The Challenge of Decarbonizing Industrial (High-Temperature) Process Heat
Authors: Leicher Jörg , Giese Anne , Wieland Christoph
Published: October 2024

The decarbonization of industrial process heat is one of the bigger challenges of the global energy transition. Process heating accounts for about 20% of final energy demand in Germany, and the situation is similar in other industrialized nations around the globe. Process heating is indispensable in the manufacturing processes of products and materials encountered every day, ranging from food, beverages, paper and textiles, to metals, ceramics, glass and cement. At the same time, process heating is also responsible for significant greenhouse gas emissions, as it is heavily dependent on fossil fuels such as natural gas and coal. Thus, process heating needs to be decarbonized. This review article explores the challenges of decarbonizing industrial process heat and then discusses two of the most promising options, the use of electric heating technologies and the substitution of fossil fuels with low-carbon hydrogen, in more detail. Both energy carriers have their specific benefits and drawbacks that have to be considered in the context of industrial decarbonization, but also in terms of necessary energy infrastructures. The focus is on high-temperature process heat (>400 °C) in energy-intensive basic materials industries, with examples from the metal and glass industries. Given the heterogeneity of industrial process heating, both electricity and hydrogen will likely be the most prominent energy carriers for decarbonized high-temperature process heat, each with their respective advantages and disadvantages.
Dystocia, Delivery, and Artificial Intelligence in Labor Management: Perspectives and Future Directions
Authors: Malvasi Antonio , Malgieri Lorenzo E. , Stark Michael , Tinelli Andrea
Published: October 2024

Labor management remains a critical issue in obstetrics, with dystocic labor presenting significant challenges in both management and outcomes. Recent advancements in intrapartum ultrasound have facilitated substantial progress in monitoring labor progression. This paper explores the integration of artificial intelligence (AI) into obstetric care, focusing on the Artificial Intelligence Dystocia Algorithm (AIDA) for assessing spatial dystocia during labor. The AIDA utilizes intrapartum ultrasonography to measure four geometric parameters: the angle of progression, the degree of asynclitism, the head–symphysis distance, and the midline angle. These measurements are analyzed using machine learning techniques to predict delivery outcomes and stratify risk. The AIDA classification system categorizes labor events into five classes, providing a nuanced assessment of labor progression. This approach offers several potential advantages, including objective assessment of fetal position, earlier detection of malpositions, and improved risk stratification, placing labor events within a broader context of labor dystocia and obstetric care and discussing their potential impact on clinical practice. This paper serves as a more comprehensive overview and discussion of the AIDA approach, its implications, perspectives, and future directions. However, challenges such as the technological requirements, training needs, and integration with clinical workflows are also addressed. This study emphasizes the necessity for additional validation across diverse populations and careful consideration of its ethical implications. The AIDA represents a significant advancement in applying AI to intrapartum care, potentially enhancing clinical decision-making and improving outcomes in cases of suspected dystocia. This paper explicates the key methodological approaches underpinning the AIDA, illustrating the integration of artificial intelligence and clinical expertise. The innovative framework presented offers a paradigm for similar endeavors in other medical specialties, potentially catalyzing advancements in AI-assisted healthcare beyond obstetrics.
Rates of Textbook Outcome Achieved in Patients Undergoing Liver and Pancreatic Surgery
Authors: Villodre Celia , Alcázar-López Candido F. , Carbonell-Morote Silvia , Melgar Paola , Franco-Campello Mariano , Rubio-García Juan Jesus , Ramia José M.
Published: October 2024

Backgorund: Textbook outcome (TO) is a composite measure that reflects the most desirable surgical results as a single indicator. The aim of this study was to assess the achievement of TO at a hepatopancreatobiliary (HPB) surgery unit in a Spanish tertiary hospital. Methods: We performed a retrospective observational study of all consecutive patients who underwent HPB surgery over a 4-year period. Morbidity according to the Clavien-Dindo classification at 30 days, hospital stay, risk of morbidity and mortality according to the POSSUM, and mortality and readmissions at 90 days were recorded. TO was considered when a patient presented no major complications (≥IIIA), no mortality, no readmission, and no prolonged length of stay (≤75th). Results: 283 patients were included. Morbidity >IIIA was reported in 21.6%, and 5.7% died; the median postoperative stay was 4 days. TO was achieved in 56.2% of patients. Comparing patients who presented TO with those who did not, significant differences were recorded for the type of procedure and the expected risk of morbidity and mortality calculated according to the POSSUM scale. There were significant differences between patients with major resections (TO rates: major hepatectomy (46.3%) and major pancreatectomy (52.5%)) and those with minor resections (TO rates minor hepatectomy (67.7%) and minor pancreatectomy (40.4%)). Conclusions: TO is a useful management tool for assessing postoperative results.
Effect of Statins and Renin–Angiotensin–Aldosterone System Inhibitors on IL-6 Levels in COVID-19 Patients
Authors: Pereckaite Laura , Vaguliene Neringa , Vitkauskaite Agne , Vitkauskiene Astra , Urboniene Daiva
Published: October 2024

Background/Objectives: Severe clinical course and mortality from COVID-19 are mostly associated with increased concentrations of IL-6 and IL-10. Findings from clinical trials suggest that both statins and renin–angiotensin–aldosterone system inhibitors (RAASI) might have the potential to reduce unfavorable outcomes in patients with COVID-19. The aim of this study was to evaluate the effect of statins and RAASI on the cytokine concentrations in COVID-19 patients. Methods: SARS-CoV-2 infected patients were enrolled in this study, and demographic, clinical, and routine laboratory data were evaluated. Plasma cytokine levels were measured by multiplex assay. Results: COVID-19 patients with chronic cardiovascular diseases (CVD) had significantly lower median plasma IL-6 levels than COVID-19 patients with no co-morbidities (26 vs. 53 pg/mL, p = 0.021). COVID-19 patients with CVD who were taking statins had significantly lower median concentrations of IL-6 (21 vs. 44 pg/mL, p = 0.027), TNFα (21 vs. 39.5 pg/mL, p = 0.036), and IL-10 (19 vs. 25.5 pg/mL, p = 0.025) compared to COVID-19 patients with no CVD. In a binary logistic regression model, IL-6 was a significant variable, with an odds ratio value of 0.961 (95% CI 0.929–0.995). Regarding RAASI, only plasma IL-6 (22 vs. 44 pg/mL, p = 0.012) levels were found to be significantly lower in COVID-19 patients with CVD consuming these medications compared to patients who did not have any CVD. Conclusions: COVID-19 patients who had chronic cardiovascular co-morbidities and who were administered statins or RAASI had significantly lower concentrations of IL-6 than COVID-19 patients who did not have any co-morbidities. These findings suggest that the use of statins or RAASI may be of value in COVID-19 patients.
Psychiatric Disorders in Patients with Chronic Obstructive Pulmonary Disease: Clinical Significance and Treatment Strategies
Authors: Moretta Pasquale , Cavallo Nicola Davide , Candia Claudio , Lanzillo Anna , Marcuccio Giuseppina , Santangelo Gabriella , Marcuccio Laura , Ambrosino Pasquale , Maniscalco Mauro
Published: October 2024

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease characterized by chronic airflow limitation and persistent respiratory symptoms. It is a major cause of morbidity and mortality worldwide, significantly impacting healthcare systems with considerable socioeconomic consequences. The main risk factors include exposure to tobacco smoke, environmental pollutants, occupational dust, and genetic factors such as alpha-1 antitrypsin deficiency. COPD is often associated with extrapulmonary comorbidities, particularly psychiatric disorders like depression and anxiety, which worsen patients’ quality of life and prognosis. The prevalence of these disorders in patients with COPD varies significantly but is always higher than in healthy controls. Psychiatric disorders can negatively influence COPD management and vice versa, creating a complex bidirectional interaction. Depression and anxiety are the most common psychiatric comorbidities in patients with COPD, influenced by factors such as social isolation, physical limitations, and fear of exacerbations. Diagnosis of these psychiatric disorders is complicated by the overlap of symptoms with those of COPD. However, some screening tools can facilitate early detection. The treatment of psychiatric disorders in patients with COPD in a rehabilitation setting requires a multidisciplinary approach involving pulmonologists, neurologists and psychologists. Pharmacological therapy with antidepressants shows mixed results in terms of efficacy and safety, with some studies reporting benefits on quality of life and others suggesting an increased risk of exacerbations and pneumonia. An integrated approach that includes the assessment and intervention of mental disorders is essential to improve the overall management of COPD and the quality of life of patients. This narrative review provides an overview of the main psychiatric comorbidities in COPD patients, aiming to fill gaps in the literature and suggest areas for future research.
Liver Fibrosis Index-4 Does Not Correlate to Liver Elastography in Patients with Inflammatory Bowel Disease
Authors: Ferraz-Amaro Iván , Hernández-Camba Alejandro , Carrillo-Palau Marta , Hernández Álvarez-Buylla Noemi , de Vera-González Antonia , González-Delgado Alejandra , Heras-Recuero Elena , González-Gay Miguel Á.
Published: October 2024

Background: Inflammatory bowel disease (IBD) is associated with an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). The Fibrosis-4 (FIB-4) index is a non-invasive tool for assessing liver fibrosis that has been validated in various liver diseases. The main objective of this study was to study whether the FIB-4 index is a reliable predictor of liver fibrosis, as assessed through elastography, in patients with IBD. We additionally aimed to analyze if FIB-4 associates with IBD characteristics such as lipid profile, subclinical carotid atherosclerosis, and insulin resistance indices. Methods: A cross-sectional study was conducted, enrolling 197 patients with IBD. Subjects underwent comprehensive clinical and laboratory evaluations. Hepatic fibrosis was assessed non-invasively using the FIB-4 index and transient elastography, while abdominal ultrasonography was performed to grade hepatic steatosis based on the degree of fat infiltration. To investigate the associations between disease characteristics and FIB-4 score and the correlation of this index to elastography, a multivariable linear regression analysis was conducted. Results: The presence of diabetes, hypertension, and metabolic syndrome was associated with significantly higher FIB-4 levels. However, FIB-4 did not show a relationship with disease characteristics such as phenotype or activity indices. Furthermore, FIB-4 did not demonstrate a correlation with liver stiffness values measured by elastography. Conclusions: Our findings suggest that the FIB-4 index may not be a reliable tool for assessing hepatic fibrosis in patients with IBD. This observation is particularly significant given the high prevalence of MASLD in the IBD population.
Ultrasound-Guided Intranodal Lipiodol Lymphangiography for the Assessment and Treatment of Chylous Leaks: A Retrospective Case Series from a Single Center in Switzerland and a Systematic Review of the Literature
Authors: Schulz Stephanie Nicole , Miftaroski Almir , Rouiller Benoit , Egger Bernard , Lutz Jon A. , Widmer Lucien
Published: October 2024

Background: Lymphatic leaks are well-known complications of major thoracic or abdominal surgeries, which significantly heighten morbidity and mortality rates. While the existing literature provides insights into managing these post-operative leaks, with a step-up approach from conservative measures (CMs) to surgical intervention, there are no standardized treatment guidelines. The purpose of this paper is to offer a management algorithm of post-operative lymphatic leaks based on a systematic literature review (SLR) of the therapeutic effect of Lipiodol lymphangiography (LL), completed by a case series of five patients who underwent LL in our department. Methods: In this IRB-approved study, we conducted an SLR following the PRISMA guidelines, using a PICOS. A quality assessment was performed for each study. The case series consisted of consecutive patients who underwent LL for diagnostic and therapeutic purposes at our institution between September 2018 and December 2020. Results: A total of 39 observational studies were included in the SLR comprising 11 retrospective case reviews (Group 1), and 3 case series as well as 25 case reports (Group 2). In total, these studies report cases of 557 patients (51.52% presenting oncological diagnoses; 43.98% having benefited from lymphadenectomy). Lymphatic or chylous fistulas were the most encountered complication, followed by chylothorax. The median volume of Lipiodol injected during lymphography was 11.7 mL (range: 9.8–75 mL). Overall, LL was technically successful in 77.7% (366/471) of patients. The clinical success of all technically successful LLs was 80.6% (295/366). Time-to-leak resolution after lymphography varied between 1 and 31 days. The factors associated with treatment failure were a high leak output (>500 mL/day) and Lipiodol extravasation on post-LL imaging. Our case series consisted of five patients (mean age: 62 ± 9.24 years; 20% female; 100% oncological diagnoses; 60% having beneficiated from lymphadenectomy). Technical and clinical successes were 80% (4/5) and 75% (3/4), respectively. Time-to-leak resolution varied between 1 and 4 days. The volume and technique of LL was not different from that identified in the SLR. Conclusions: LL is a safe procedure with high technical and clinical success rates that could be proposed as both a diagnostic and therapeutic solution for patients with post-operative central lymphatic lesions.
Assessing the Influence of Hyaluronan Dressing on Wound Healing on Split-Thickness Skin Graft Donor Sites Using a Three-Dimensional Scanner
Authors: Bock Anna , Peters Florian , Heitzer Marius , Winnand Philipp , Kniha Kristian , Katz Marie Sophie , Hölzle Frank , Modabber Ali
Published: October 2024

Objectives: The topical application of hyaluronic acid after injury may accelerate the wound healing process. We aimed to retrospectively investigate whether the topical application of hyaluronic acid on standardized wounds after split-thickness skin graft removal on the thigh would accelerate wound healing and improve scarring outcomes. Additionally, we aimed to evaluate the usefulness of three-dimensional (3D) scanning to assess scars. Methods: The wound healing process of a hyaluronan group (n = 20) and a control (n = 21) were analyzed and evaluated using 3D scans at 7 and 14 days and 1, 3, and 6 months post-operatively. Scar evaluations by the patients were conducted 6 months post-operatively using the patient and observer scar assessment scale and the Manchester scar scale. Experts evaluated the scars after 6 months using a modified version of both scales. Results: On days 7 and 14, significantly larger areas of the wound surface were closed in the hyaluronan group compared to the control group (p < 0.05). After 1 month, significantly more crusted areas remained in the control group than in the hyaluronan group (p < 0.05). At the 6-month self-assessments, the hyaluronan group evaluated their scars as being significantly better compared to the control group. Conclusions: The topical application of hyaluronic acid in combination with polyurethane foam as a wound dressing after split skin removal accelerated the wound healing rate and positively influenced scar appearance after 6 months. Three-dimensional scanning is useful for evaluating and documenting the wound healing process.
The Prognostic Value of a Naples Score in Determining in-Hospital Mortality in Patients with Acute Ischemic Stroke Undergoing Endovascular Treatment
Authors: Uysal Onur Kadir , Ozdogru Derya , Yildirim Abdullah , Ozturk Ilker , Tras Guluzar , Arlier Zulfikar
Published: October 2024

Background/Objectives: The Naples prognostic score (NPS), reflecting inflammation and nutritional status, has prognostic value, especially in cancer. This study evaluated its ability to predict in-hospital mortality in acute ischemic stroke (AIS) patients undergoing endovascular treatment (EVT). Methods: We retrospectively studied 244 patients with AIS who were admitted between April 2020 and December 2023. Patients were included if they presented within 6 h of symptom onset with evidence of intracranial proximal arterial occlusion. The EVT was performed using aspiration catheters, stent retrievers, or both. The NPS was calculated based on the neutrophil–lymphocyte ratio, lymphocyte–monocyte ratio, and albumin and total cholesterol levels. Results: We found a significant association between higher NPS scores and in-hospital mortality. Patients with a high NPS (3 or 4) had a mortality rate of 41.6% compared to 21.0% in the low-NPS group (0, 1, or 2). The full model incorporating NPS showed superior predictive ability for in-hospital mortality compared with the baseline model (areas under the curve 0.881 vs. 0.808). A receiver-operating characteristic analysis at a cutoff of >2.5 for the NPS showed a sensitivity of 86.6% and specificity of 41.9%. This study demonstrated that incorporating the NPS into the predictive model improved the accuracy and calibration for predicting in-hospital mortality. A decision curve analysis showed the net benefit of using the full model incorporating NPS over the baseline model, emphasizing its potential clinical application in prognostication. Conclusions: NPS is a reliable predictor of in-hospital mortality in AIS patients undergoing EVT. Incorporating NPS into clinical practice could help to identify high-risk patients and improve outcomes through tailored interventions.
Muscle Mass and Muscle Strength in Non-Dialysis-Dependent Chronic Kidney Disease Patients
Authors: Romejko Katarzyna , Szamotulska Katarzyna , Rymarz Aleksandra , Niemczyk Stanisław
Published: October 2024

Background: Sarcopenia is a state with a progressive and generalized loss of skeletal muscle mass and strength. However, muscle strength and muscle mass are different features, which are usually not studied separately. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in chronic kidney disease (CKD). Methods: The study sample consisted of 84 patients with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2. Muscle strength was estimated by measuring hand grip strength (HGS). Muscle quantity was measured with bioimpedance spectroscopy (BIS). Serum creatinine, urea, uric acid (UA), and albumin were measured as well. Results: Appendicular skeletal muscle mass (ASM) significantly and positively correlated with body mass, NH weight (normally hydrated weight), height, body mass index (BMI), lean tissue mass (LTM), lean tissue index (LTI), fat mass (FM), and fat tissue index (FTI), and was negatively associated with hydration status. HGS significantly and positively correlated with body mass, NH weight, height, LTM, LTI, and ASM, and was negatively associated with UA and urea. After adjustment for age, sex, and height, HGS remained significantly and negatively related with UA and hydration status. Conclusions: In CKD patients, ASM is determined by anthropometric parameters, but HGS is determined by both anthropometric and clinical variables specific for CKD. In order to study the determinants of HGS in CKD, relationships with HGS should be adjusted for anthropometric variables.
Adaptive Hyperactivity and Biomarker Exploration: Insights from Elders in the Blue Zone of Sardinia
Authors: Scano Alessandra , Orrù Germano , Kalcev Goce , Tusconi Massimo , Spada Maura , Atzori Laura , Ferreli Caterina , Cabitza Flavio , Primavera Diego , Sancassiani Federica
Published: October 2024

Background/Objectives: Adaptive hyperactivity characterized by increased activity levels and novelty-seeking traits without mood disorders is prevalent among older adults in Sardinia’s “blue zone,” an area with high longevity. This study aims to evaluate the adaptive nature of hyperactivity concerning quality of life, social rhythms, and mood symptoms in individuals from this region, particularly among elderly adults over 80. Methods: This observational cross-sectional study included adults and older adults over 80 from Sardinia’s blue zone. This study included a sample of patients followed at the Center for Consultation Psychiatry and Psychosomatics for Bipolar Disorder of the University Hospital of Cagliari and a homogeneous comparison sample of patients without psychiatric pathologies, referred to the Dermatology Clinic of the same hospital, for a period of 6 months, from February to August 2024. The general sample, divided into two parts—cases, represented by patients with psychiatric pathology, and controls, patients without psychiatric pathology—was divided in turn into three sub-groups: “adults” (18–64 years), young elders (65–79), and old elders (over 80 years). The participants underwent psychiatric interviews and completed the Mood Disorder Questionnaire (MDQ), Patient Health Questionnaire (PHQ-9), SF-12, and Brief Social Rhythm Scale (BSRS). Data were compared with national and regional normative data. Results: Older adults in the blue zone demonstrated higher MDQ positivity (22.58%) compared to the national averages (0.87%), without corresponding increases in dysregulated rhythms, depressive symptoms, or reduced quality of life. Younger old persons (65–79 years) showed increased rhythm dysregulation (BSRS score: 20.64 ± 7.02) compared to adults (17.40 ± 6.09, p = 0.040), but this trend was not observed in the oldest group (80+ years). No significant differences were found in the CH3SH and (CH3)2S levels between groups. Conclusions: The hyperactivity observed in older adults from Sardinia’s blue zone appears adaptive and not linked to social rhythm dysregulation, depressive symptoms, or a diminished quality of life, suggesting resilience factors which may contribute to longevity. These findings support the potential classification of such hyperactivity as beneficial rather than pathological, warranting further research into biomarkers and psychoeducational interventions to prevent the onset of bipolar disorders in predisposed individuals.
The Efficacy and Outcomes of Renal Replacement Therapy in Pediatric Metabolic Disorders
Authors: Önal Hülya Gözde , Nalçacıoğlu Hülya , Özer Işıl , Karalı Demet Tekcan
Published: October 2024

Background/Objectives: This study aims to evaluate the efficacy and outcomes of renal replacement therapy (RRT) in pediatric patients with metabolic diseases, specifically focusing on the impact of hemodialysis (HD) and peritoneal dialysis (PD) on clinical parameters, toxin reduction, and long-term survival. Methods: This retrospective study included 10 pediatric patients (eight females and two males) treated at a pediatric nephrology department between 2020 and 2023. Patients diagnosed with metabolic disorders, including maple syrup urine disease (MSUD), methylmalonic acidemia (MMA), and glycogen storage disease (GSD), underwent RRT. Clinical data, demographic information, and biochemical parameters were collected and analyzed. Results: Among the patients, 50% were diagnosed with MSUD, 30% with MMA, and 20% with GSD. RRT, including HD and PD, was administered to manage acute metabolic crises. HD was particularly effective in rapidly reducing toxic metabolite levels. Patients treated with HD showed significant reductions in leucine and ammonium levels, with median reductions of 94.5% and 86%, respectively. Overall, 60% of the patients demonstrated long-term survival, highlighting the critical role of RRT in managing metabolic crises. In conclusion, RRT, including HD and PD, is crucial in managing pediatric metabolic disorders by effectively reducing toxic metabolite levels and improving clinical outcomes. Conclusions: The results of this study are consistent with previous research, highlighting the critical role of RRT in the acute management of metabolic crises and supporting its adoption as a standard treatment method.
Evaluating Biomarkers of Bone Health After an 8-Week Walking Program in Non-Ambulatory Stroke Survivors: A Pilot Study
Authors: Alajam Ramzi A. , Alqahtani Abdulfattah S. , Moon Sanghee , Sarmento Caio V. M. , Smirnova Irina V. , Pang Marco Y. C. , Liu Wen
Published: October 2024

Background/Objectives: Stroke survivors have a significantly increased likelihood of developing osteoporosis, a condition characterized by weak and brittle bones as well as an elevated risk of bone fractures. However, previous studies on exercise intervention have mostly been on stroke survivors who are able to walk. The objective of this study was to examine the effect of walking exercise on bone health in non-ambulatory stroke survivors. Methods: This pre- and post-test study enrolled a group of chronic non-ambulatory stroke survivors. They were instructed to complete an 8-week aerobic walking exercise program, three sessions per week. Serum concentrations of osteocalcin (OC) and carboxy-terminal telopeptides of type I collagen (ICTP) were evaluated at baseline and after completing the walking exercise program. In addition, we assessed the ambulation capacity and balance control using the functional ambulation category (FAC) and Berg Balance Scale (BBS), respectively. Results: A total of 9 out of 10 non-ambulatory stroke survivors who were recruited completed the intervention. The serum concentration of OC significantly increased from 8.51 ± 2.28 ng/mL to 9.39 ± 2.97 ng/mL (p < 0.10). The serum concentration of ICTP significantly increased from 4.45 ± 2.58 ng/mL to 5.31 ± 2.92 ng/mL (p < 0.10). Both FAC and BBS scores significantly improved from 1.0 ± 0 to 1.33 ± 0.5 (p < 0.1) and from 7.22 ± 10.02 to 15.78 ± 14.81 (p < 0.01), respectively. Conclusions: The findings of this pilot study suggest that walking exercise may improve bone health by initiating a bone remodeling process in chronic non-ambulatory stroke survivors.
Sexual Dysfunctions and Gynecomastia in Male Rheumatological Patients Treated with Methotrexate: A Systematic Review
Authors: Napolitano Luigi , Abate Marco , Di Bello Francesco , Morra Simone , Cirillo Luigi , Fusco Giovanni Maria , Califano Gianluigi , Collà Ruvolo Claudia , Creta Massimiliano , La Rocca Roberto , Crocetto Felice , Barone Biagio , Pantano Ilenia , Russo Pierluigi , Arcaniolo Davide , Manfredi Celeste
Published: October 2024

Objectives: The aim of the current review was to elucidate the clinical context and presentation of sexual dysfunction (SD) and gynecomastia in rheumatological patients undergoing methotrexate treatment. Moreover, we aimed also to make physicians aware of the occurrence of these side effects, to adequately inform the patient before starting treatment. Methods: Systematic review (PROSPERO id: CRD42022358275) was performed according to preferred reporting items for systematic reviews and meta-analyses. Studies (1 January 1995 to 31 May 2022) were identified by highly sensitive searches of electronic databases (Medline, Embase, Cochrane Library databases). Key terms included: ((“sexual dysfunction” OR “erectile dysfunction” OR “impotence”) AND (“methotrexate” OR “MTX”)) and ((“gynecomastia” OR “male breast”) AND (“methotrexate” OR “MTX”)). Results: A total of seven papers (seven case reports), involving a total of eleven patients (min one, max three), were included in the final analysis. The age of the patients ranged from 19 to 68 years (median: 50.9 years). Rheumatoid arthritis (RA) was the most frequent rheumatic disease reported (n = 8, 72.7%). No patients reported erectile dysfunction (ED) and/or gynecomastia before using MTX. Time to onset of SD and gynecomastia after MTX ranged from 2 to 104 weeks (median: 22.7 weeks). ED (n = 5, 45.4%) and gynecomastia (n = 3, 27.2%) were the most common forms of presentation. Conclusions: Future prospective controlled studies with a large sample size and long follow-up as well as randomized controlled trials are needed to confirm this association, investigate its pathophysiological basis, assess the safest dosages, evaluate the most appropriate management, and provide clear recommendations.
Tonsillectomy May Not Be the Answer in All OSA Cases
Authors: Bargagna Belén , O’Connor-Reina Carlos , Rodriguez-Alcala Laura , Navarro Andrés , Bosco Gabriela , Pérez-Martín Nuria , Baptista Peter M. , Carrasco-Llatas Marina , Plaza Guillermo
Published: October 2024

Tonsillectomy is considered the standard of care in patients with obstructive sleep apnea (OSA) and large tonsils; however, there are selected cases where this procedure should not be considered. We present two patients with tonsil grade 4 and severe OSA where tonsillectomy was not the solution for their problem and could be a superfluous procedure. In our experience, a preoperatory drug-induced sleep endoscopy (DISE) and proper patient phenotyping will prevent this type of surgical failure.