bluuebunny/crossref_metadata_2025 huggingface dataset:
Teratoma Development in 129.MOLF-Chr19 Mice Elicits Two Waves of Immune Cell Infiltration
Authors: Klaus Lucas , Reichardt Sybille D. , Neif Maria , Walter Lutz , Gayer Fabian A. , Reichardt Holger M.
Published: November 2024

Teratomas are a highly differentiated type of testicular germ cell tumors (TGCTs), the most common type of solid cancer in young men. Prominent inflammatory infiltrates are a hallmark of TGCTs, although their compositions and dynamics in teratomas remain elusive. Here, we reached out to characterize the infiltrating immune cells and their activation and polarization state by using high-throughput gene expression analysis of 129.MOLF-Chr19 mice that spontaneously develop testicular teratomas. We showed that inconspicuous testes without any apparent alterations in size or morphology can be clustered into three groups based on their expression of stemness and immune genes, supporting a model in which initial oncogenic transformation elicits a first wave of T-cell infiltration. Moderately and severely enlarged tumorous testes then displayed a progressive infiltration with T cells, monocytes/macrophages, and B cells. Importantly, T cells seem to adopt an inactive state caused by an overexpression of immune checkpoint molecules and the polarization of monocytes/macrophages to an anti-inflammatory phenotype. Our findings are supported by the analysis of metabolic gene expression, which unveiled alterations indicative of tumor growth and immune cell infiltration. Collectively, testicular teratomas, at least in mice, are characterized by a diverse inflammatory infiltrate containing T cells that putatively become inactivated, allowing the tumors to further grow. We believe that these findings may provide a rationale for the development of new immunomodulatory therapies for TGCTs.
Theoretical Insight into Antioxidant Mechanism of Caffeic Acid Against Hydroperoxyl Radicals in Aqueous Medium at Different pH-Thermodynamic and Kinetic Aspects
Authors: Kowalska-Baron Agnieszka
Published: November 2024

In this study, the DFT/M062X/PCM method was applied to investigate thermodynamic and kinetic aspects of reactions involved in possible mechanisms of antioxidant activity of caffeic acid against HOO● radicals in aqueous medium at different pH values. Kinetic parameters of the reactions involved in HAT (Hydrogen Atom Transfer), RAF (Radical Adduct Formation), and SET (Single Electron Transfer) mechanisms, including reaction energy barriers and bimolecular rate constants, were determined, and identification and characterization of stationary points along the reaction pathways within HAT and RAF mechanisms were performed. Inspection of geometrical parameters and spin densities of the radical products formed within HAT and RAF mechanisms revealed that they are stabilized by hydrogen bonding interactions and the odd electron originated through the reaction with the HOO● radical is spread over the entire molecule, resulting in significant radical stabilization. Thermodynamic and kinetic data collected in this study indicated that increasing pH of the medium boosts the antioxidant activity of caffeic acid by reducing the energy required to generate radicals within the RAF and/or HAT mechanism and, at extremely high pH, where the trianionic form of caffeic acid is a dominant species, by the occurrence of an additional fast, diffusion-limited electron-related channel.
Non-Susceptibility Gene Variants in Head and Neck Paragangliomas
Authors: Snezhkina Anastasiya V. , Pavlov Vladislav S. , Krasnov George S. , Kalinin Dmitry V. , Pudova Elena A. , Stolbovskaya Olga V. , Dunshina Anastasiya V. , Fedorova Maria S. , Kudryavtseva Anna V.
Published: November 2024

Head and neck paragangliomas (HNPGLs) are rare neoplasms that, along with pheochromocytomas and extra-adrenal paragangliomas, are associated with inherited mutations in at least 12 susceptibility genes in approximately 40% of cases. However, due to the rarity of HNPGLs, only a series of small-scale studies and individual cases have reported mutations in additional genes that may be involved in tumorigenesis. Consequently, numerous disease-causing mutations and genes responsible for the pathogenesis of HNPGLs remain poorly investigated. The aim of this study was to gain a deeper understanding of the genetic basis of HNPGLs by focusing on variants in genes that were not previously identified as well-known drivers. A whole-exome data analysis was conducted on a representative set of 152 HNPGLs. In 30% of the tumors examined, 53 potentially deleterious variants were identified in 36 different genes. The analysis identified pathogenic or likely pathogenic variants in the ARNT, IDH2, L2HGDH, MYH3, PIK3CA, and TERT genes. A functional network analysis of the mutated genes revealed numerous associations and a list of metabolic pathways (e.g., the TCA cycle, carbon metabolism, pyruvate metabolism, etc.) and signaling pathways (e.g., HIF1, PI3K-Akt, FoxO, AMPK, MAPK, etc.) that may play an important role in the development of HNPGLs. The identified range of genetic alterations affecting multiple genes and, potentially, influencing diverse cellular pathways provides an enhanced molecular genetic characterization of HNPGLs.
Analysis of CD1a-Positive Monocyte-Derived Cells in the Regional Lymph Nodes of Patients with Gallbladder Cancer
Authors: Maeda Sachiko , Kai Keita , Kawasaki Kanako , Tanaka Tomokazu , Ide Takao , Noshiro Hirokazu
Published: November 2024

Dendritic cells (DCs) are known to be major antigen-presenting cells, and lymph nodes (LNs) play an important role in DC-mediated immune response. CD1a is known as a marker of monocyte-derived DCs. The present study focused on the infiltration of CD1a-positive DCs (CD1a-DCs) into regional LNs in 70 cases of gallbladder cancer (GBC). After univariate analyses, the results showed that LN infiltration by CD1a-DCs was associated with unfavorable clinical outcomes in patients with GBC, with all cases categorized in the CD1a-DCs high group had nodal metastasis. LN infiltration by CD1a-DCs was not an independent prognostic factor identified by multivariate analyses. After subgroup analyses of cases with LN metastasis (n = 32), no significant impacts of CD1a-DCs infiltration into metastatic LNs were observed. In contrast, CD1a-DCs infiltration into primary tumors had a significant impact on surgical outcomes. The results of strong confounding between CD1a-DCs and LN metastasis support the theory that CD1a-DCs are developed from monocytes at tumor sites. As the results of previous research focused on CD1a-DCs infiltration into regional LNs of other organs varied, the role and significance of CD1a-DCs infiltration in regional LNs may be different according to the tumor histology or its primary site. Thus, further studies are needed to clarify the role and significance of CD1a-DCs infiltration into regional LNs of solid cancers.
The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model
Authors: Song Hwa Young , Jin Sejong , Lee Sekwang , Jalin Angela Melinda Anthony , Roh Kyung-Hye , Kim Won-Ki
Published: November 2024

An ischemic cerebral stroke results from the interruption of blood flow to the brain, triggering rapid and complex cascades of excitotoxicity, oxidative stress, and inflammation. Current reperfusion therapies, including intravenous thrombolysis and mechanical thrombectomy, cause further brain injury due to reperfusion-induced cytotoxicity. To date, novel cytoprotective therapies that could address these challenges have yet to be developed, likely due to the limitations of targeting a single pathologic mechanism. To address these unmet clinical needs, we investigated a synthetic verbenone derivative, SP-8356, as a potential multi-target cytoprotective agent for acute ischemic strokes. In transient middle cerebral artery occlusion (MCAO) rats, SP-8356 significantly reduced brain infarct and edema volumes while improving acute neurological deficits in a dose-dependent manner. Furthermore, SP-8356 improved long-term outcomes, particularly by reducing mortality. These potent cytoprotective effects of SP-8356 were achieved by suppressing the excessive production of free radicals and pro-inflammatory cytokines, reducing the infiltration of inflammatory cells, and mitigating increases in blood–brain barrier permeability. Additional research is needed to determine whether co-administration of SP-8356 can extend the therapeutic time window of reperfusion therapies by mitigating ischemia/reperfusion injury.
Qualitative Transcriptional Signature for Predicting the Pathological Response of Colorectal Cancer to FOLFIRI Therapy
Authors: He Jun , Wang Mengyao , Wu Dandan , Fu Hao , Shen Xiaopei
Published: November 2024

FOLFIRI (5-FU, leucovorin, irinotecan) is the first-line chemotherapy for metastatic colorectal cancer (mCRC), but response rates are under 50%. This study aimed to develop a predictive signature for FOLFIRI response in mCRC patients. Firstly, Spearman’s rank correlation and Wilcoxon rank-sum test were used to select chemotherapy response genes and gene pairs, respectively. Then, an optimization procedure was used to determine the final signature. A predictive signature consisting of three gene pairs (3-GPS) was identified. In the training set, 3-GPS achieved an accuracy of 0.94. In a validation set of 60 samples, predicted responders had significantly better progression-free survival than the predicted non-responders (HR = 0.47, p = 0.01). A comparable result was observed in an additional validation set of 27 samples (HR = 0.06, p = 0.02). The co-expressed genes of the signature were enriched in pathways associated with the immunotherapy response, and they interacted extensively with FOLFIRI-related genes. Notably, the expression of signature genes significantly correlated with various immune cell types, including plasma cells and memory-resting CD4+ T cells. In conclusion, the REO-based signature effectively identifies mCRC patients likely to benefit from FOLFIRI. Furthermore, these signature genes may play a crucial role in the chemotherapy.
Parasitism Affects Entomofauna Dynamics in Infected and Uninfected Plants: A Case Study of Orobanche anatolica Parasitizing Salvia absconditiflora
Authors: Özenirler Çiğdem
Published: November 2024

Salvia absconditiflora and Orobanche anatolica exhibit a parasitic relationship. S. absconditiflora serves as a rich food resource for insects due to its abundant nectar. O. anatolica demonstrates host specificity towards S. absconditiflora. The objective of this study is to assess potential variations in entomofauna dynamics and nectar chemistry attributable to parasitism. The observational groups consisted of S. absconditiflora individuals infected and uninfected by O. anatolica, as well as O. anatolica individuals. Entomofauna was monitored during the flowering periods of target species. The collected data were analyzed using biodiversity indexes. The nectar of the plant groups was evaluated with LC-QTOF-MS analysis to identify possible repellents for insects. S. absconditiflora plants free from infection had significantly higher insect diversity and abundance compared to those infected by O. anatolica. Parasitism by O. anatolica appeared to modify the entomofauna dynamics of S. absconditiflora, as demonstrated by the disparities in insect diversity metrics between infected and uninfected plants. When comparing the nectars of the plant groups, it was determined that the nectar from the parasitic plant and the infected S. absconditiflora contained substances with repellent properties in higher quantities than that of uninfected S. absconditiflora, including thymol, n-benzyloleamide, azadirachtin, capsaicin, azatadine maleate, and andrachcinidine. This study concluded that parasitism could lead to differences in entomofauna associated with these species.
New Mitochondrial Genomes of Ithonidae (Neuroptera) and Higher Phylogenetic Implications
Authors: Zhang Ruyue , Jiang Yunlan , Zhong Mina , Wang Shutong , Wang Yuyu
Published: November 2024

Ithonidae (moth lacewings) are an enigmatic, small family of the insect order Neuroptera (lacewings). Its phylogenetic position within Neuroptera and internal subfamily relationships remain unresolved. In this study, the complete mitochondrial genome (mitogenome) of Ithone fulva Tillyard, 1916 representing the first mitogenome of Ithoninae, as well as the complete mitogenome of Rapisma gaoligongensis Liu, Li and Yang, 2018, were newly reported. Molecular phylogenetic trees recovered Ithonidae as the sister group to Chrysopidae + Hemerobiidae. Ithoninae was demonstrated to be the sister group to Polystoechotinae + Rapismatinae across all topologies. Divergence time estimation revealed that Ithonidae originated during the Mid-Triassic. Ithoninae diverged from Polystoechotinae and Rapismatinae in the Late Triassic, while Polystoechotinae diverged from Rapismatinae in the Middle Jurassic. Moreover, more comprehensive samplings, as well as whole genome data, are needed to reconstruct a comprehensive framework of the phylogeny of Ithonidae, as well as Neuropteida.
Impact of Baseline Hypoalbuminemia on Long-Term Survival Following Acute Myocardial Infarction According to Body Mass Index
Authors: Shechter Alon , Dahan Shani , Shiyovich Arthur , Gilutz Harel , Plakht Ygal
Published: November 2024

Serum albumin and body mass index (BMI, kg/m2) have been associated with outcomes following acute myocardial infarction (AMI). Aiming to assess whether the mortality risk inflicted by hypoalbuminemia (<3.5 g/dL) in this context is influenced by BMI, we conducted a retrospective analysis of AMI survivors hospitalized during 2004–2017. Stratified by admission-time albumin level and BMI, eligible cases were evaluated for all-cause mortality up to 10 years after discharge. A total of 6283 individuals (74.1% males, mean age 64.1 ± 13.1 years, 44.3% with ST-elevation MI) were included. Of them, 22.7% had hypoalbuminemia and 1.2%, 41.0%, and 28.6% were underweight (BMI < 18.5), overweight (BMI 25–30), and obese (BMI ≥ 30), respectively. Over a median of 7.9 (IQR, 4.8–10.0) years of follow-up, 42.5% of patients died. Hypoalbuminemia was independently associated with a heightened mortality risk overall (AdjHR = 1.54, 95%CI 1.42–1.67, p < 0.001), accounted for by the normal weight (AdjHR = 1.73, 95%CI 1.50–1.99, p < 0.001), overweight (AdjHR = 1.55, 95%CI 1.35–1.79, p < 0.001), and class 1 obesity (BMI 30–35) (AdjHR = 1.37, 95%CI 1.12–1.68, p = 0.002) subgroups. Upon interaction analysis, the mortality risk imposed by hypoalbuminemia was most pronounced among individuals with normal BMI. In conclusion, hypoalbuminemia constituted a negative prognostic marker for long-term survival in AMI patients with normal or mildly elevated but not reduced or severely increased BMI. Pending further research, addressing hypoalbuminemia based on BMI range may prove beneficial.
Prognostic Value of Baseline Serum Pro-Inflammatory Cytokines in Severe Multisystem Inflammatory Syndrome in Children
Authors: Bartha-Tatár Anita , Sinkovits György , Schnur János , Maráczi Veronika , Dávid Máté , Zsigmond Borbála , Rimanóczy Éva , Szalay Balázs , Biró Edina , Bekő Gabriella , Varga Petra , Szabó Tamás , Fagyas Miklós , Fejes Zsolt , Kappelmayer János , Nagy Jr. Béla
Published: November 2024

Background: Severe clinical manifestations of multisystem inflammatory syndrome in children (MIS-C) are associated with the dysregulation of immune response following SARS-CoV-2 infection. Therefore, we analyzed the levels of 10 selected cytokines at admission to estimate disease severity and to predict the length of hospitalization. In remission samples, these mediators were followed after intravenous immunoglobulin (IVIG) treatment before discharge. Methods: Thirty-five MIS-C patients at the age of 8.4 ± 4.1 years and 11 clinical controls were included. Acute MIS-C patients were divided into two severity subgroups based on their clinical score determined by the WHO criteria. Serum concentrations of IFN-γ, IL-1α, IL-1RA, IL-8, IL-10, IL-17A, IL-18, IP-10, MCP-1, and TNF-α were measured by MILLIPLEX® Human Cytokine/Chemokine panel, while ACE2 activity was determined by a fluorescent kinetic assay. These results were correlated with routinely determined laboratory parameters and clinical characteristics. Results: MIS-C patients demonstrated significantly elevated baseline levels of most of these cytokines compared to controls. Even higher concentrations of IL-18, TNF-α and ferritin with reduced lymphocyte count were found in severe subjects with elevated clinical scores of 4–5 compared to moderate cases with a clinical score of 1–3. Furthermore, the development of cardiovascular dysfunction and prolonged hospitalization (≥8 days) were related to augmented ACE2 and IL-6 levels. IL-18, IL-1RA, IL-10 and TNF-α were diminished in response to IVIG treatment in remission samples. Finally, pre-treatment IL-18 (≥516.8 pg/mL) and TNF-α (≥74.2 pg/mL) effectively differentiated disease severity in MIS-C with AUC values of 0.770 and 0.750, respectively. Conclusions: IL-18 and TNF-α have a prognostic value in disease severity at admission and are capable of monitoring the efficacy of IVIG treatment in MIS-C.
Antifungal Prophylaxis Utilization and the Associated Clinical Outcomes Among Pediatric Patients with Hematological Malignancies or Undergoing Hematopoietic Stem Cell Transplantation
Authors: Al Siyabi Bushra , Al-Maqbali Juhaina Salim , Unnikrishnan Meenakshi Dhanalekshmi , Wali Yasir , Al Yazidi Laila
Published: November 2024

Background/Objectives: Invasive fungal infections (IFIs) are a prevalent complication of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) in the pediatric population and are associated with high morbidity and mortality. We aimed to identify the utilization of antifungal prophylaxis prescriptions and the associated clinical outcomes. Methods: A retrospective study included children (≤18 years old) diagnosed with hematological malignancies or undergoing HSCT who are at high risk for developing IFI and received systemic antifungal therapy between January 2018 and April 2024 at Sultan Qaboos University Hospital (SQUH), Oman. Results: A powered sample of 222 patients was included, and 208 (93.69%) received antifungal prophylaxis. Among those who received prophylaxis, 148 (66.67%) received appropriate prophylaxis, 86.06% (n = 179) received appropriate dosage. The patients who did not receive antifungal prophylaxis had higher rates of inpatient IFI requiring treatment (85.71% versus 12.02%, p < 0.01), a longer median length of hospital stay (LOS) (67.5 days versus 10 days, p = 0.015), and more incidence of 90-day all-cause mortality (21.43% versus 2.88%, p < 0.01) than those who received antifungal prophylaxis. Survival analysis demonstrated that these patients had a 12% higher risk for earlier death. Also, being on antifungal prophylaxis reduces the odds of inpatient IFI requiring treatment, with an adjusted odds ratio (aOR) of 0.13 [95% CI: 0.019–0.801]. Conclusions: Antifungal prophylaxis utilization was high, and it markedly decreases the occurrence and enhances the prognosis of IFI. Nonetheless, inconsistencies in practice and a lack of pediatric-specific data underscore the necessity for uniform guidelines and additional research to strengthen preventative methods in this population, and proper TDM utilization could provide more robust insights.
Simultaneous Carotid Artery Stenting and Coronary Artery Bypass Grafting in Urgent Patients: A Single Center Experience
Authors: Fiorentino Mariafrancesca , Mikus Elisa , Nerla Roberto , Sangiorgi Diego , Ruggiero Andrea , Tripodi Alberto , Castriota Fausto , Savini Carlo
Published: November 2024

Background: Coexisting coronary artery disease and critical carotid stenosis present challenges in revascularization, particularly in urgent cases requiring surgery. Combining carotid artery stenting (CAS) with coronary artery bypass grafting (CABG) has gained popularity. Methods: This study analyzed 36 patients who underwent simultaneous CAS and CABG from 2014 to 2024. CAS was performed first, with the patient awake for real-time neurocognitive assessment. A clopidogrel loading dose was administered three hours post-surgery. From postoperative day 1, dual antiplatelet therapy was initiated. Results: The median age was 72 years (64–77) and 22.2% were females. The median EuroSCORE II was 2.80 (2.06–3.58). Nine patients (25%) underwent associated procedures. The median cardiopulmonary bypass and cross-clamp times were 66 (54–89) and 51 (41–72) minutes. We observed no in-hospital mortality and no postoperative stroke. The median postoperative bleeding in 24 h was 500 mL and only one (2.8%) patient needed resternotomy for bleeding. The median ventilation time was 9 h (6–12). The median intensive care unit and postoperative length of stay were 2 (2–4) days and 8 (7–11) days, respectively. The median follow-up time was 6 years. Survival at 1, 5, and 10 years was 93.7%, 81.5%, and 60.2%, respectively, while freedom from PTCA/PCI at 1, 5, and 10 years was 100%, 96.7%, and 87.5%, respectively. Conclusions: Simultaneous CAS and CABG is a safe and effective procedure with low in-hospital mortality and morbidity. Our protocol carries a low risk of perioperative stroke. Antiplatelet therapy administration on the day of surgery does not increase the risk of postoperative bleeding.
Multimorbidity and COVID-19 Outcomes in the Emergency Department: Is the Association Mediated by the Severity of the Condition at Admission?
Authors: Catalano Alberto , Sacerdote Carlotta , Alvich Marco , Macciotta Alessandra , Milani Lorenzo , Destefanis Cinzia , Gebru Kibrom Teklay , Sodano Barbara , Padroni Lisa , Giraudo Maria Teresa , Ciccone Giovannino , Pagano Eva , Boccuzzi Adriana , Caramello Valeria , Ricceri Fulvio
Published: November 2024

Background/Objectives: Charlson Comorbidity Index (CCI) is one of the most reliable indicators to assess the impact of multimorbidity on COVID-19-related outcomes. Moreover, the patient’s clinical conditions are associated with SARS-CoV-2 outcomes. This study aimed to analyze the association between multimorbidity and COVID-19-related outcomes, evaluating whether the National Early Warning Score 2 (NEWS2) mediated these associations. Methods: Data were obtained through the platform “EPICLIN”. We analyzed all patients who tested positive for COVID-19 after accessing the emergency department (ED) of San Luigi Gonzaga (Orbassano) and Molinette (Turin) hospitals from 1 March to 30 June 2020. Different outcomes were assessed: non-discharge from the ED, 30-day mortality, ICU admission/death among hospitalized patients, and length of hospitalization among surviving patients. Two subgroups of patients (<65 and 65+ years old) were analyzed using logistic regressions, Cox models, and mediation analyses. Results: There was a greater risk of not being discharged or dying among those who were younger and with CCI ≥ 2. Moreover, the higher the CCI, the longer the length of hospitalization. Considering older subjects, a greater CCI was associated with a higher risk of death. Regarding the mediation analyses, multimorbidity significantly impacted the hospitalization length and not being discharged in the younger population. Instead, in the older population, the NEWS2 played a mediation role. Conclusions: This research showed that multimorbidity is a risk factor for a worse prognosis of COVID-19. Moreover, there was a strong direct effect of CCI on not being discharged, and the NEWS2 was found to act as mediator in the association between multimorbidity and COVID-19-related outcomes.
Longitudinal Changes in Factors Associated with Walking Independence at Hospital Discharge in Patients with Stroke: A Retrospective Study
Authors: Yamamoto Ryosuke , Murata Shin , Sawai Shun , Fujikawa Shoya , Shizuka Yusuke , Maru Takayuki , Nakagawa Kotaro , Nakano Hideki
Published: November 2024

Background/Objectives: Patients with stroke usually have long-term residual gait disability. However, temporal changes in factors associated with gait independence in these patients at the time of hospital discharge have not been clarified. This study aimed to determine changes over time in factors associated with gait independence in patients with stroke at the time of hospital discharge. This would predict that factors associated with the level of walking independence in patients with stroke at discharge from the hospital would show different results depending on the changes over time post-stroke onset. Methods: This retrospective observational study used data from the medical records of patients with stroke with unilateral supratentorial lesions who were admitted and rehabilitated at Tesseikai Neurosurgical Hospital between October 2020 and July 2024. The Functional Ambulation Category (FAC), Stroke Impairment Assessment Set-lower extremity motor items, Trunk Control Test, Mini-Balance Evaluation Systems Test (Mini-BESTest), and Functional Independence Measure cognitive items were assessed monthly for 3 months post-stroke onset. Participants were classified into independent and non-independent walking groups using the FAC. Logistic regression analysis was performed with walking independence at discharge and other assessment indicators as the dependent and independent variables, respectively, to identify factors influencing walking independence at discharge. Independent variables were entered by month from 1 to 3 months. Results: Logistic regression analysis revealed that Mini-BESTest scores at 2 and 3 months post-stroke onset were significantly associated with walking independence at discharge (p < 0.05). Conclusions: This study suggests the importance of assessing the Mini-BESTest scores over time, starting at 2 months post-stroke onset, when determining walking independence in patients with stroke. Providing balance training to patients with low Mini-BESTest scores between 1 and 3 months post-stroke onset may contribute to improved walking independence at discharge.
Real-Life Use of Filgotinib in Rheumatoid Arthritis: A Retrospective Cohort Study
Authors: Raimondo Vincenzo , Caminiti Maurizio , Olivo Domenico , Gigliotti Pietro , L’Andolina Massimo , Muto Pietro , Pellegrini Roberta , Varcasia Giuseppe , Bruno Caterina , Massaro Laura , Pagano Mariano Giuseppa , Luppino Jessica Maria Elisa , Cirillo Mariateresa , Caira Virginia , Calabria Marilena , Ciaffi Jacopo , Ferri Clodoveo , Ursini Francesco
Published: November 2024

Background: Janus kinase inhibitors (JAKis) are a novel class of drugs interfering with intracellular signaling of type I and type II cytokines, which play a crucial role in immune dysregulation associated with several chronic inflammatory diseases. Filgotinib (FIL), in particular, is the newest member of the JAKi class and exerts its therapeutic effects by selectively targeting and inhibiting the kinase activity of JAK1. While the efficacy of FIL in rheumatoid arthritis (RA) has been confirmed in clinical trials, real-world evidence may provide better insights into its effectiveness and safety in routine clinical practice. Methods: We performed a multicenter, retrospective cohort study investigating the real-life effectiveness and safety of FIL in adult patients with RA. Demographic information, disease characteristics, prior treatment history, and comorbid conditions were retrieved from clinical records at baseline (M0) and after 3 (M3) and 6 months (M6) of treatment. Results: A total of 82 patients (63 women) agreed to participate in the study, of whom 39 (47.6%) were older than 65 years. The average RA duration was 13 ± 9 years; 19 patients (23.1%) were current or former smokers, and 4 patients (4.9%) had a history of cardiovascular events. Most patients had previously received at least one biologic disease-modifying antirheumatic drug (range: 1–6+); in addition, 11 patients (13.4%) had been already exposed to another JAKi. During the follow-up, 7 patients discontinued treatment due to primary failure (n = 3) or adverse events (n = 4). Significant reductions in pain and number of tender and swollen joints were observed at M3 and M6. A relevant proportion of patients achieved DAS28-CRP remission at M3 and M6 (46.3% and 66.2%, respectively). Conclusions: Our data provide additional insight into the effectiveness of filgotinib in a real-world setting, even among patients with difficult-to-treat RA and a high prevalence of cardiovascular risk factors.
Association Between Transient Hemodialysis and Risk of Bleeding During Peritoneal Dialysis Catheterization
Authors: Kim A Young , Cho Kyu Hyang , Park Jong Won , Do Jun Young , Kang Seok Hui
Published: November 2024

Background: Although the risk of serious bleeding following peritoneal dialysis catheter insertion is low, pericannular bleeding can increase the risk of catheter-related infections and reduce catheter survival. We aimed to analyze the risk factors for bleeding complications during peritoneal dialysis catheter insertion and assess whether temporary preemptive hemodialysis before catheterization can reduce bleeding and improve catheter survival. Methods: We retrospectively analyzed bleeding complications and catheter survival in patients who underwent temporary hemodialysis prior to peritoneal dialysis catheter insertion. Cox regression analysis was performed to determine the risk factors for bleeding complications and catheter survival. Results: Among 336 patients, 216 and 120 comprised the non-hemodialysis and hemodialysis groups, respectively. No significant association was found between temporary hemodialysis and bleeding (hazard ratio: 1.6, 95% confidence interval: 0.87–2.95, p < 0.134). Multivariate analysis revealed an inverse association of platelet count (hazard ratio: 0.99, 95% confidence interval: 0.99–0.99, p < 0.048) and hemoglobin level (hazard ratio: 0.78, 95% confidence interval: 0.61–0.99, p < 0.04) with bleeding. A positive association was observed between international normalized ratio (hazard ratio: 2.24, 95% confidence interval: 1.19–4.19, p < 0.012) and bleeding. Conversely, temporary hemodialysis was not associated with catheter survival (hazard ratio: 1.64, 95% confidence interval: 0.63–4.25, p < 0.308). Conclusions: Temporary hemodialysis before peritoneal dialysis catheter insertion did not significantly affect bleeding risk in patients with a high risk of uremic bleeding.
Managing Asymmetry in Breast Reconstruction After Mastectomy—A Systematic Review and Highlight of Clinical Pearls
Authors: Lipman Kelsey , Nguyen Dung
Published: November 2024

Background/Objectives: As breast reconstruction techniques continue to progress, patient satisfaction with aesthetic outcomes has become an increasingly important marker of success. Obtaining optimal symmetry often requires secondary procedures whether reconstruction is unilateral or bilateral, implant-based or autologous, immediate or delayed. Consequently, determining the ideal method to achieve symmetry, particularly in challenging scenarios, such as the radiated breast, is nuanced and requires experienced decision-making. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, including the PubMed, Cochrane Library, and Embase bibliographic databases, to identify original articles addressing asymmetry in both implant-based and autologous breast reconstruction. Studies based on benign breast disease or oncoplastic reconstruction for partial mastectomy/lumpectomy defects were excluded. Results: The search initially yielded a total of six hundred and fifty unique articles. After complete assessment of inclusion and exclusion criteria, a total of forty-one articles were included in total. Conclusions: This article provides a systematic review of the current literature available to guide surgeons on managing asymmetry in breast reconstruction and highlights case examples of frequently encountered clinical challenges. A novel treatment algorithm was then generated to serve as a comprehensive decision-making guide for both patients and surgeons.
Overcoming Resistance in Anderson–Fabry Disease: Current Therapeutic Challenges and Future Perspectives
Authors: Carella Maria Cristina , Forleo Cinzia , Caretto Pierpaolo , Naccarati Maria Ludovica , Dentamaro Ilaria , Dicorato Marco Maria , Basile Paolo , Carulli Eugenio , Latorre Michele Davide , Baggiano Andrea , Pontone Gianluca , Ciccone Marco Matteo , Guaricci Andrea Igoren
Published: November 2024

Anderson–Fabry disease (AFD) remains a therapeutic challenge despite advances in early diagnosis and the availability of enzyme replacement therapies (ERTs). While early initiation of therapy can mitigate disease progression, resistance mechanisms—such as the development of anti-drug antibodies—limit the efficacy of current treatments, particularly in patients with severe genetic variants. Chaperone therapy provides a targeted option for a subset of patients, yet significant gaps remain in treating those with complete enzyme deficiency. This perspective article explores the existing therapeutic landscape and reflects on emerging treatments, such as mRNA and gene therapies, which hold promise for overcoming the resistance mechanisms. By addressing the limitations of current pharmacological options and considering future innovations, this article aims to outline the path forward for more effective and personalized treatment strategies in Anderson–Fabry disease.
Multimorbidity in Patients with Chronic Liver Disease: A Population-Based Study in the EpiChron Cohort, Spain
Authors: Moreno-Juste Aída , Poblador-Plou Beatriz , Laguna-Berna Clara , Cruces-Mateo Belén , Lenotti Elisa , Santos-Mejías Alejandro , Gimeno-Feliú Luis A. , Gimeno-Miguel Antonio
Published: November 2024

Background/Objectives: Chronic liver disease (CLD) is highly relevant in clinical practice due to its increasing incidence and associated mortality. We aimed to exhaustively characterize the multimorbidity of patients with CLD. Methods: This is a retrospective observational study of patients aged 18 years and older with a diagnosis of CLD in 2015 in the EpiChron Cohort (Spain). We analyzed the prevalence of comorbidities according to sex and age, conducted a logistic regression analysis with CLD as the independent variable and each of the comorbidities as dependent variables to obtain odds ratios (OR) adjusted for age and sex, and performed an exploratory factor analysis to identify the presence of multimorbidity patterns. Results: A total of 6836 adults had a diagnosis of CLD (mean age 61.6 years; 62.5% women), with an average of 13 co-existing chronic conditions. Arterial hypertension, lipid metabolism disorders, diabetes, obesity, and musculoskeletal diseases were the most frequent diseases. From the list of 110 chronic conditions analyzed, 75 were systematically associated with CLD, including (OR, 95% confidence interval) chronic pancreatitis (41.2, 33.5–50.6) and inherited metabolic disorders (14.9, 11.8–18.8). Three multimorbidity patterns were identified in both men and women, including cardiovascular, metabolic-geriatric, and mental-substance use, with some differences by sex. Conclusions: Multimorbidity is the norm in patients with CLD. Our results reveal that a comprehensive and integral approach based on person-centered care, which should take into account their entire spectrum of multimorbidity, is necessary during the care of this type of patient in clinical practice.
Effects of Forearm Resistance Exercises on Breast Cancer-Related Lymphedema Using Segmental Bioelectrical Impedance Analysis: A Pilot Randomized Controlled Trial
Authors: Son Woo Chul , Kim Sang Ah , Kim Ah Hyun , Cheon Hawyeong , Jeon Jae Yong
Published: November 2024

Background: Breast cancer-related lymphedema (BCRL) reduces the quality of life of patients and limits their activities of daily living. Even though resistance exercises seemed to be safe in BCRL patients, it was still controversial that resistance exercises improve lymphedema. Therefore, we sought to evaluate the effects of forearm-targeted resistance exercises on BCRL using segmental bioelectrical impedance analysis (BIA). Methods: This study was a pilot-controlled randomized trial, with patients divided into the intervention and the control group. Both groups received 30 min of complete decongestive therapy (CDT) for 2 weeks. In addition, the intervention group received forearm strengthening training including warm-up and cool-down for an extra 20 min, and the control group received stretching exercises. 5 kHz impedance ratios were assessed by segmental BIA before and after treatments. Results: Among the eighteen patients enrolled, ten were assigned to the intervention group, and eight were in the control group. Only the 5 kHz impedance ratio in the forearm segment of the intervention group showed a statistically significant difference. The effect sizes of the groups were 0.71 for the intervention group and 0.93 in the between-group comparison. Conclusions: Forearm resistance exercises in patients with BCRL showed a significant decrease in extracellular fluid in the proximal forearm segment when using segmental BIA. Therefore, we suggest that resistance exercises targeting the forearm might be effective in treating lymphedema.
Retinal Ganglion Cell Replacement in Glaucoma Therapy: A Narrative Review
Authors: Kosior-Jarecka Ewa , Grzybowski Andrzej
Published: November 2024

Glaucoma is a leading cause of irreversible blindness worldwide. It leads to the progressive degeneration of retinal ganglion cells (RGCs), the axons of which form the optic nerve. Enormous RGC apoptosis causes a lack of transfer of visual information to the brain. The RGC loss typical of the central nervous system is irreversible, and when glaucoma progresses, the total amount of RGCs in the retina enormously diminishes. The successful treatment in glaucoma patients is a direct neuroprotection by decreasing the intraocular pressure, which enables RGC protection but does not revive the lost ones. The intriguing new therapy for advanced glaucoma is the possibility of RGC replacement with new healthy cells. In this review article, the strategies regarding RGC replacement therapy are presented with the latest advances in the technique and the obstacles that it meets.
History of Breast Cancer in Patients with Oral Lichen Planus: A Case–Control Study
Authors: García-Pola María , Rodríguez-Fonseca Lucía , Llorente-Álvarez Claudia , Llorente-Pendás Santiago
Published: November 2024

Objectives: The purpose of this study was to determine the association between oral lichen planus (OLP) and the history of cancer outside of oral cavity and the predominance of its location. Methods: This case–control study included 600 OLP patients and 600 control subjects evaluated in the same section, matched for age and sex to the OLP patients. OLP patients were diagnosed clinically and histologically. Initially, the prevalence of the most frequent types of cancers was described. A Pearson chi-squared test model was used to determine the association of cancer history and OLP. It was considered statistically significant whether p value was ≤0.05. The final multivariate regression model was built after applying a backward selection method to the complete multivariate model considering the odds ratio (OR) with a 95% confidence interval (CI). Results: The history of cancer was significantly associated with OLP regardless of age, sex, tobacco and or alcohol use in both univariate [OR = 2.26 (95%CI: 1.26–4.24); p = 0.008] and multivariate analyses [OR = 2.21 (95%CI: 1.21–4.19); p = 0.012]. According to the location of cancer, there was an association between OLP and history of breast cancer [OR = 3.71 (95%CI = 1.03–13.38); p = 0.032]. Conclusions: This case–control study suggests a higher frequency of cancer, particularly breast cancer, among patients with OLP compared to the control group. Due to the study’s design and sample limitations, these findings should be interpreted cautiously. Future longitudinal, multi-institutional studies with rigorous control for cancer history and other confounding factors are essential to further explore the association between OLP and cancer, particularly breast cancer.
Amyloids and the Heart: An Update
Authors: Triposkiadis Filippos , Briasoulis Alexandros , Xanthopoulos Andrew
Published: November 2024

Amyloids consist of fibrils that can be formed by a large variety of different precursor proteins. In localized amyloidosis, amyloids accumulate at the production site with a single organ being affected, whereas in systemic amyloidosis several organs are affected, with the heart being the most common, followed by the kidneys, liver, and the nervous system. The two most frequent systemic amyloidosis types affecting the heart in the vast majority (>95%) of cases are immunoglobulin light chain (AL) amyloidosis and transthyretin (TTR) amyloidosis (ATTR amyloidosis). Patients with amyloid cardiopathy (CA) often present with non-specific heart failure symptoms as well as other clinical manifestations depending on the organ or systems involved. However, there are some findings associated with amyloidosis called “red flags” (clinical, echocardiographic, magnetic resonance imaging), which may assist in guiding the physician to the correct diagnosis. The present state-of-the-art review summarizes the features of the various cardiac phenotypic expressions of amyloidosis, proposes a simplified pathway for its diagnosis, and highlights the rapidly evolving therapeutic landscape.
Soluble ST2 as a Biomarker for Predicting Right Ventricular Dysfunction in Acute Pulmonary Embolism
Authors: Uyanik Muhammet , Cinar Ahmet , Gedikli Omer , Tuna Tibel , Avci Bahattin
Published: November 2024

Introduction: Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 (IL-1) superfamily, is recognized as an important biomarker in inflammatory responses and cardiovascular diseases. Elevated serum levels of sST2 have prognostic value, particularly in cases of cardiac stress such as heart failure and acute pulmonary embolism (APE). We aimed to assess ST2 levels as a potential biomarker for right heart dysfunction in APE patients, particularly in the context of its limited predictive value for mortality and risk stratification. Methods: Patients diagnosed with APE confirmed via computed tomography pulmonary angiography (CTPA) were enrolled in this study. To ensure the specificity of sST2 elevation to APE, patients with other conditions known to cause elevated sST2 levels were excluded. Results: After pre-clinical evaluation, 66 patients diagnosed with APE who met the study criteria, and 62 healthy subjects in the control group, were included in this study. sST2 levels were positively correlated with APE. Conclusions: In patients diagnosed with APE, sST2 levels had high sensitivity. sST2 levels are elevated in APE and are associated with right ventricular dysfunction, but do not independently predict mortality or risk stratification based on Pulmonary Embolism Severity Index (PESI) scores.
No Effect of Cigarette Smoking in the Outcome of Arthroscopic Management for Femoroacetabular Impingement: A Systematic Review
Authors: Lucenti Ludovico , Maffulli Nicola , Bardazzi Tommaso , Pipino Gennaro , Pappalardo Gaetano , Migliorini Filippo
Published: November 2024

Background: The impact of smoking in arthroscopic surgery for femoroacetabolar impingement (FAI) is controversial. This systematic review updates and discusses current evidence on the influence of cigarette smoking on the outcome of arthroscopic management of FAI. The outcomes of interest were to compare patient-reported outcome measures (PROMs) and complications. Methods: The present systematic review followed the PRISMA guidelines. Embase, Web of Science, and PubMed were accessed in June 2024 without additional filters or temporal constraints. All the clinical investigations comparing smokers versus nonsmokers in patients who underwent arthroscopic management for FAI were considered. The risk of bias in nonrandomised controlled trials was assessed using the Risk of Bias in Nonrandomised Studies of Interventions (ROBINS-I). Results: Data from 368 patients were retrieved. The mean length of follow-up was 34.1 ± 7.1 months. The mean age was 40.4 ± 4.0 years and the mean BMI was 27.1 ± 1.6 kg/m2. No significant difference was evidenced in the visual analogue scale, Harris hip score, Hip Outcome Score—Sport subscale, and Non-Arthritic Hip Score. No difference was observed in the complication rate: reoperation (p = 0.6) and progression to THA (p = 0.4). Conclusions: Tobacco smoking does not appear to influence the outcomes of arthroscopic management for FAI. At approximately 34 months of follow-up, no difference was found in pain, PROMs, reoperation rate, and progression to THA.
Fractures of the Pelvis and Acetabulum: Novel Insights into Diagnostics and Treatment
Authors: Baumann Florian , Herrmann-Johns Anne , Alt Volker , Freigang Viola
Published: November 2024

Over the past decade, the number of fractures of the pelvis and acetabulum has increased dramatically, by up to 58% [...]
Sleep-Disordered Breathing in Patients with Chronic Heart Failure and Its Implications on Real-Time Hemodynamic Regulation, Baroreceptor Reflex Sensitivity, and Survival
Authors: Lang-Stöberl Anna S. , Fabikan Hannah , Ruis Maria , Asadi Sherwin , Krainer Julie , Illini Oliver , Valipour Arschang
Published: November 2024

Background: Impairment in autonomic activity is a prognostic marker in patients with heart failure (HF), and its involvement has been suggested in cardiovascular complications of obstructive sleep apnea syndrome (OSAS) and Cheyne–Stokes respiration (CSR). This prospective observational study aims to investigate the implications of sleep-disordered breathing (SDB) on hemodynamic regulation and autonomic activity in chronic HF patients. Methods: Chronic HF patients, providing confirmation of reduced ejection fraction (≤35%), underwent polysomnography, real-time hemodynamic, heart rate variability (HRV), and baroreceptor reflex sensitivity (BRS) assessments using the Task Force Monitor. BRS was assessed using the sequencing method during resting conditions and stress testing. Results: Our study population (n = 58) was predominantly male (41 vs. 17), with a median age of 61 (±11) yrs and a median BMI of 30 (±5) kg/m2. Patients diagnosed with CSR were 13.8% (8/58) and 50.0% (29/58) with OSAS. No differences in the real-time assessment of hemodynamic regulation, heart rate variability, or baroreceptor reflex function were found between patients with OSAS, CSR, and patients without SDB. A subgroup analysis of BRS and HRV in patients with severe SDB (AHI > 30/h) and without SDB (AHI < 5) revealed numerically reduced BRS and increased LF/HF-RRI values under resting conditions, as well as during mental testing in patients with severe SDB. Patients with moderate-to-severe SDB had a shorter overall survival, which was, however, dependent upon age. Conclusions: Chronic HF patients with severe SDB may exhibit lower baroreceptor function and impaired cardiovascular autonomic function in comparison with HF patients without SDB.