bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor Effects of Intravenous Natural Killer Cell Infusion in an Orthotopic Glioblastoma Xenograft Murine Model and Gene Expression Profile Analysis
Authors: Morimoto Takayuki , Nakazawa Tsutomu , Matsuda Ryosuke , Maeoka Ryosuke , Nishimura Fumihiko , Nakamura Mitsutoshi , Yamada Shuichi , Park Young-Soo , Tsujimura Takahiro , Nakagawa Ichiro
Published: February 2024

Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors’ ligands, inhibitory receptors’ ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM.
Identification of Novel Non-Nucleoside Inhibitors of Zika Virus NS5 Protein Targeting MTase Activity
Authors: Fiorucci Diego , Meaccini Micaela , Poli Giulio , Stincarelli Maria Alfreda , Vagaggini Chiara , Giannecchini Simone , Sutto-Ortiz Priscila , Canard Bruno , Decroly Etienne , Dreassi Elena , Brai Annalaura , Botta Maurizio
Published: February 2024

Zika virus (ZIKV) is a positive-sense single-stranded virus member of the Flaviviridae family. Among other arboviruses, ZIKV can cause neurological disorders such as Guillain Barré syndrome, and it can have congenital neurological manifestations and affect fertility. ZIKV nonstructural protein 5 (NS5) is essential for viral replication and limiting host immune detection. Herein, we performed virtual screening to identify novel small-molecule inhibitors of the ZIKV NS5 methyltransferase (MTase) domain. Compounds were tested against the MTases of both ZIKV and DENV, demonstrating good inhibitory activities against ZIKV MTase. Extensive molecular dynamic studies conducted on the series led us to identify other derivatives with improved activity against the MTase and limiting ZIKV infection with an increased selectivity index. Preliminary pharmacokinetic parameters have been determined, revealing excellent stability over time. Preliminary in vivo toxicity studies demonstrated that the hit compound 17 is well tolerated after acute administration. Our results provide the basis for further optimization studies on novel non-nucleoside MTase inhibitors.
Screening for Rare Mitochondrial Genome Variants Reveals a Potentially Novel Association between MT-CO1 and MT-TL2 Genes and Diabetes Phenotype
Authors: Płoszaj Tomasz , Skoczylas Sebastian , Gadzalska Karolina , Jakiel Paulina , Juścińska Ewa , Gorządek Monika , Robaszkiewicz Agnieszka , Borowiec Maciej , Zmysłowska Agnieszka
Published: February 2024

Variations in several nuclear genes predisposing humans to the development of MODY diabetes have been very well characterized by modern genetic diagnostics. However, recent reports indicate that variants in the mtDNA genome may also be associated with the diabetic phenotype. As relatively little research has addressed the entire mitochondrial genome in this regard, the aim of the present study is to evaluate the genetic variations present in mtDNA among individuals susceptible to MODY diabetes. In total, 193 patients with a MODY phenotype were tested with a custom panel with mtDNA enrichment. Heteroplasmic variants were selected for further analysis via further sequencing based on long-range PCR to evaluate the potential contribution of frequent NUMTs (acronym for nuclear mitochondrial DNA) insertions. Twelve extremely rare variants with a potential damaging character were selected, three of which were likely to be the result of NUMTs from the nuclear genome. The variant m.3243A>G in MT-TL1 was responsible for 3.5% of MODY cases in our study group. In addition, a novel, rare, and possibly pathogenic leucine variant m.12278T>C was found in MT-TL2. Our findings also found the MT-CO1 gene to be over-represented in the study group, with a clear phenotype–genotype correlation observed in one family. Our data suggest that heteroplasmic variants in MT-COI and MT-TL2 genes may play a role in the pathophysiology of glucose metabolism in humans.
K2CO3-Modified Smectites as Basic Catalysts for Glycerol Transcarbonation to Glycerol Carbonate
Authors: Snoussi Yosra , Gonzalez-Miranda David , Pedregal Tomás , Besbes Néji , Bouaid Abderrahim , Ladero Miguel
Published: February 2024

A novel and cost-effective heterogeneous catalyst for glycerol carbonate production through transesterification was developed by impregnating smectite clay with K2CO3. Comprehensive structural and chemical analyses, including X-ray diffraction Analysis (XRD), Scanning Electron Microscopy (SEM)-Electron Dispersion Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) surface area analysis measurements, were employed to characterize the catalysts. Among the various catalysts prepared, the one impregnated with 40 wt% K2CO3 on smectite and calcined at 550 °C exhibited the highest catalytic activity, primarily due to its superior basicity. To enhance the efficiency of the transesterification process, several reaction parameters were optimized, including the molar ratio between propylene carbonate and glycerol reactor loading of the catalyst and reaction temperature. The highest glycerol carbonate conversion rate, approximately 77.13% ± 1.2%, was achieved using the best catalyst under the following optimal conditions: 2 wt% reactor loading, 110 °C reaction temperature, 2:1 propylene carbonate to glycerol molar ratio, and 6h reaction duration. Furthermore, both the raw clay and the best calcined K2CO3-impregnated catalysts demonstrated remarkable stability, maintaining their high activity for up to four consecutive reaction cycles. Finally, a kinetic analysis was performed using kinetic data from several runs employing raw clay and the most active K2CO3-modified clay at different temperatures, observing that a simple reversible second-order potential kinetic model of the quasi-homogeneous type fits perfectly to such data in diverse temperature ranges.
Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer—An Exploratory Analysis of Clinical and Tumor Biological Significance
Authors: Vukovic Marko , Chamlati Jorge M. , Hennenlotter Jörg , Todenhöfer Tilman , Lütfrenk Thomas , Jersinovic Sebastian , Tsaur Igor , Stenzl Arnulf , Rausch Steffen
Published: February 2024

Previous data indicate a role of IL-1 and IL-1RA imbalance in bladder carcinoma (BC); the inhibition of IL-1 signaling might be considered a treatment option. Objective: To assess expression patterns and the prognostic role of IL-1β and IL-1RA in invasive BC and to evaluate their interaction with AKT signaling and proliferation. The study included two independent cohorts of n = 92 and n = 102 patients who underwent a radical cystectomy for BC. Specimen from BC and benign urothelium (n = 22 and n = 39) were processed to a tissue microarray and immunohistochemically stained for IL-1β, IL-1RA, AKT, and Ki-67. Expression scores were correlated to clinical variables and Ki-67 and AKT expression. An association with outcome was assessed using Wilcoxon Kruskal–Wallis tests, Chi-square tests or linear regression, dependent on the variable’s category. Kaplan–Meier and Cox proportional hazard analyses were used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Both IL-1β and IL-1RA were significantly overexpressed in invasive BC compared to benign urothelium in both cohorts (p < 0.005). IL-1β was associated with vascular invasion (210 vs. 183, p < 0.02), lymphatic invasion (210 vs. 180, <0.05) and G3 cancer (192 vs. 188, <0.04). The survival analysis revealed favorable RFS, CSS, and OS in the case of high IL-1β expression (p < 0.02, <0.03, and <0.006, respectively). Multivariate analyses revealed an independent impact of (low) IL1β expression on RFS, CSS, and OS. The IL-1β and IL-1β/IL-1RA ratios were positively correlated to the AKT expression (p < 0.05 and <0.01, respectively). Additionally, the high expression of Ki-67 (>15%) correlated with higher levels of IL-1β (p = 0.01). The overexpression of IL-1β and IL-1RA is frequently found in BC, with a prognostic significance observed for the IL-1β protein expression. The observed link between the IL-1β/IL-1RA axis and AKT signaling may indicate possible autophagy activation processes besides the known tumor-promoting effects of AKT.
Nonsteroidal Anti-Inflammatory Drug Injections versus Steroid Injections in the Management of Upper and Lower Extremity Orthopedic Conditions: A Systematic Review with Meta-Analysis
Authors: Rhim Hye Chang , Ruiz Joseph , Taseh Atta , Afunugo Wilma , Crockett Zack , Schon Jason , Pan Xiaoyu , Shin Jaehyung , Schowalter Sean , Jang Ki-Mo , Robinson David M
Published: February 2024

Background: Although corticosteroid injections are an effective treatment for musculoskeletal pathologies, they may not be suitable for all patients. The purpose of this systematic review was to compare clinical outcomes between patients who received NSAID and corticosteroid injections for various orthopedic conditions. Methods: Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched, and meta-analyses were performed using a random-effects model for outcomes presented in three or more studies. Other studies were qualitatively analyzed. Results: A total of 28 articles with 2113 patients were included. A meta-analysis of five studies in patients with shoulder impingement syndrome demonstrated that there was no significant difference in the pain visual analogue scale (VAS) between subacromial NSAID injections and corticosteroid injections at 1 month [weighted mean difference (WMD) −0.244; 95% CI, −1.232 to 0.745; I2, 94.5%]. For patients with knee osteoarthritis, a meta-analysis of three studies demonstrated that there was no significant difference between intraarticular NSAID injections and corticosteroid injections in pain VAS at 1 month (WMD 0.754; 95% CI, −0.413 to 1.921; I2, 90.2%) and 3 months (WMD−0.089; 95% CI, −0.345 to 0.166; I2, 0%). A review of the studies assessing pain outcomes for hip osteoarthritis, adhesive capsulitis, and plantar fasciitis showed no significant differences between the NSAID and corticosteroid groups. Conclusion: NSAID injections may be safe and effective alternatives to steroid injections, especially in shoulder impingement syndrome and knee osteoarthritis.
Prognostic Factors for Severe-to-Fatal Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Multicenter Prospective Cohort Study
Authors: Matsumoto Kazuya , Noma Hisashi , Fujita Koichi , Tomoda Takeshi , Onoyama Takumi , Hanada Keiji , Okazaki Akihito , Hirao Ken , Goto Daisuke , Moriyama Ichiro , Kushiyama Yoshinori , Takenaka Mamoru , Maruo Toru , Matsumoto Hisakazu , Asada Masanori , Nebiki Hiroko , Katayama Toshihiro , Kawamura Takashi , Kurita Akira , Ueki Toshiharu , Tsujimae Masahiro , Matsubara Tokuhiro , Yamada Satoshi , Tamura Takashi , Marui Saiko , Mitoro Akira , Isomoto Hajime , Yazumi Shujiro , Kawamoto Hirofumi
Published: February 2024

The prognostic factors associated with severe-to-fatal post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remain unclear despite the extensive number of studies on PEP. In total, 3739 ERCP patients with biliary disease with an intact papilla and indicated for ERCP were prospectively enrolled at 36 centers from April 2017 to March 2018. Those with acute pancreatitis diagnosed before ERCP, altered gastrointestinal anatomy, and an American Society of Anesthesiologists (ASA) physical status > 4 were excluded. Univariate and multivariate logistic regression analyses were performed on patient-related factors, operator-related factors, procedure-related factors, and preventive measures to identify potential prognostic factors for severe-to-fatal PEP. Multivariate analyses revealed pancreatic guidewire-assisted biliary cannulation (OR 13.59, 95% CI 4.21–43.83, p < 0.001), post-ERCP non-steroidal anti-inflammatory drug (NSAID) administration (OR 11.54, 95% CI 3.83–34.81, p < 0.001), and previous pancreatitis (OR 6.94, 95% CI 1.45–33.33, p = 0.015) as significant risk factors for severe-to-fatal PEP. Preventive measures included endoscopic biliary sphincterotomy (EST; OR 0.29, 95% CI, 0.11–0.79, p = 0.015) and prophylactic pancreatic stents (PPSs; OR 0.11, 95% CI, 0.01–0.87, p = 0.036). In biliary ERCP, pancreatic guidewire-assisted biliary cannulation, NSAID administration after ERCP, and previous pancreatitis were risk factors for severe-to-fatal PEP, whereas EST and PPS were significant preventive measures for severe-to-fatal PEP.
Transient Neonatal Myasthenia Gravis as a Common Complication of a Rare Disease: A Systematic Review
Authors: Lindroos Jenny Linnea Victoria , Bjørk Marte-Helene , Gilhus Nils Erik
Published: February 2024

Myasthenia gravis (MG) is a rare autoimmune disease. Transient neonatal myasthenia gravis (TNMG) is caused by pathogenic maternal autoantibodies that cross the placenta and disrupt signaling at the neuromuscular junction. This is a systematic review of this transient immunoglobulin G (IgG)-mediated disease. TNMG affects 10–20% of children born to mothers with MG. The severity of symptoms ranges from minor feeding difficulties to life-threatening respiratory weakness. Minor symptoms might go unnoticed but can still interfere with breastfeeding. Acetylcholine-esterase inhibitors and antibody-clearing therapies such as immunoglobulins can be used to treat TNMG, but most children do well with observation only. TNMG is self-limiting within weeks as circulating antibodies are naturally cleared from the blood. In rare cases, TNMG is associated with permanent skeletal malformations or permanent myopathy. The mother’s antibodies can also lead to spontaneous abortions. All healthcare professionals meeting pregnant or birthing women with MG or their neonates should be aware of TNMG. TNMG is hard to predict. Reoccurrence is common among siblings. Pre-pregnancy thymectomy and intravenous immunoglobulins during pregnancy reduce the risk. Neonatal fragment crystallizable receptor (FcRn) blocking drugs for MG might reduce TNMG risk.
Long-Term Intraocular Pressure Fluctuation and Epiretinal Membrane in Patients with Glaucoma or Glaucoma Suspect
Authors: Jung Kyoung In , Lee Jiyun , Shin Da Young , Park Chan Kee
Published: February 2024

Background: A relationship between glaucoma and epiretinal membrane (ERM) has been suggested previously. We investigated the association between intraocular pressure (IOP) fluctuation and idiopathic ERM in patients with glaucoma or glaucoma suspect. Methods: Among patients with glaucoma or glaucoma suspect, data from 43 patients with ERM and 41 patients without ERM were reviewed and analyzed in this retrospective study. The long-term fluctuation of IOP was defined based on the standard deviation of IOP across all visits. Results: Patients with ERM were older and had a higher SD of IOP and a higher proportion of having a history of cataract surgery and greater macular thickness (p = 0.018, 0.049, 0.013, and <0.001, respectively). In multiple logistic regression analysis, the high-IOP-fluctuation group was associated with the presence of ERM (p = 0.047). Among patients with ERM, eyes with stage-3 or -4 ERM had worse visual field defects based on mean deviation than those with stage-1 or -2 ERM (p = 0.025). Conclusions: Long-term IOP fluctuation was associated with idiopathic ERM in patients with glaucoma or glaucoma suspect. Idiopathic ERM could serve as a biomarker for long-term IOP fluctuation in glaucoma patients, particularly in clinics where measuring long-term IOP fluctuation during the first visit is not feasible due to its time-consuming nature.
Down Syndrome—Basque Alzheimer Initiative (DS-BAI): Clinic-Biological Cohort
Authors: Altuna Miren , Estanga Ainara , Garrido Adolfo , Saldias Jon , Cañada Marta , Echeverria Maitane , Larrea José Ángel , Ayo Patricia , Fiz Ainhoa , Muñoz María , Santa-Inés José , García-Landarte Valeria , García-Sebastián Maite
Published: February 2024

Background: Down syndrome (DS) is the most common genetically determined intellectual disability. In recent decades, it has experienced an exponential increase in life expectancy, leading to a rise in age-related diseases, including Alzheimer’s disease (AD). Specific health plans for the comprehensive care of the DS community are an unmet need, which is crucial for the early and accurate diagnosis of main medical comorbidities. We present the protocol of a newly created clinical and research cohort and its feasibility in real life. Methods: The Down Syndrome—Basque Alzheimer Initiative (DS-BAI) is a population-based, inclusive, multidisciplinary initiative for the clinical-assistance and clinical-biological research approach to aging in DS led by the CITA-Alzheimer Foundation (Donostia, Basque Country). It aims to achieve the following: (1) provide comprehensive care for adults with DS, (2) optimize access to rigorous and quality training for socio-family and healthcare references, and (3) create a valuable multimodal clinical-biological research platform. Results: During the first year, 114 adults with DS joined the initiative, with 36% of them showing symptoms indicative of AD. Furthermore, adherence to training programs for healthcare professionals and families has been high, and the willingness to collaborate in basic and translational research has been encouraging. Conclusion: Specific health plans for DS and conducting clinical and translational research on the challenges of aging, including AD, are necessary and feasible.
Medial or Lateral, That Is the Question: A Retrospective Study to Compare Two Injection Techniques in the Treatment of Knee Osteoarthritis Pain with Hyaluronic Acid
Authors: Farì Giacomo , Mancini Rachele , Dell’Anna Laura , Ricci Vincenzo , Della Tommasa Simone , Bianchi Francesco Paolo , Ladisa Ilaria , De Serio Carlo , Fiore Silvia , Donati Danilo , Ranieri Maurizio , Bernetti Andrea , Megna Marisa
Published: February 2024

Background: Mild-to-moderate knee osteoarthritis (KOA) can be successfully treated using intra-articular hyaluronic acid (IA-HA). The medial infrapatellar (MIP) approach and lateral infrapatellar (LIP) approach are two of the most used techniques for performing IA-HA, but it is still not clear which one is preferable. Objectives: The study aims to find the best knee injection technique between MIP and LIP approaches. Methods: In total, 161 patients were enrolled, divided into two groups (MIP or LIP). Each technique was performed once a week for three weeks. Patients were evaluated using the Numeric Rating Scale (NRS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Roles and Maudsley Score (RMS) at T0 (before the first injection), T1 (one week after the third injection) and T2 (six months after). Results: NRS, KOOS and RMS showed a statistically significant improvement in both groups at all the detection times, without significant differences. No differences were detected between the groups in terms of systemic effect effusions, while the MIP group presented a mildly higher number of bruises in comparison with the LIP group (p = 0.034). Conclusions: Both the IA-HA techniques are equally effective in measured outcomes. The MIP approach seems to produce some local and transient side effects. So, the choice of the LIP or MIP approach depends on the operator’s skill and experience.
Stage 5 Chronic Kidney Disease: Epidemiological Analysis in a NorthEastern District of Italy Focusing on Access to Nephrological Care
Authors: Martino Francesca K. , Fanton Giulia , Zanetti Fiammetta , Carta Mariarosa , Nalesso Federico , Novara Giacomo
Published: February 2024

Background: We conducted a retrospective epidemiological study about the prevalence of stage 5 chronic kidney disease (CKD) in a high-income district, comparing some demographic characteristics and outcomes of those patients who had nephrological consultations and those who had not. Results: In a district of 400,000 adult subjects in 2020, 925 patients had an estimated glomerular filtration rate (eGFR) under 15 mL/min and CKD. In the same period, 747 (80.4%) patients were assessed by nephrologists, while 178 (19.6%) were not. Age (88 vs. 75, p < 0.0001), female gender (66.3% vs. 47%, p < 0.001), and eGFR (12 vs. 9 mL/min, p < 0.001) were significantly different in the patients assessed by a nephrologist as compared those who did not have nephrological care. Furthermore, unfollowed CKD patients had a significantly higher death rate, 83.1% versus 14.3% (p < 0.0001). Conclusions: About 20% of ESKD patients did not receive a nephrologist consultation. Older people and women were more likely not to be referred to nephrology clinics. Unfollowed patients with stage 5 CKD had a significantly higher death rate.
Clinical, Radiologic, and Functional Outcomes following Bone Grafting for Metacarpal Non-Unions: A Systematic Review
Authors: El Sewify Omar , Abi-Rafeh Jad , Legler Jack , Karimi Shayan , Baradaran Aslan , Efanov Johnny I.
Published: February 2024

Objectives: Metacarpal non-unions are complex hand defects that can lead to severe hand impairment. Treatment may require the use of artificial or autologous bone grafts. This systematic review aims to describe the outcomes of bone grafting following metacarpal non-union in an attempt to establish an optimal therapeutic protocol for this complication. Methods: A systematic review was conducted in adherence with PRISMA guidelines. Data collection and analysis were performed in duplicate and confirmed by a third investigator. Our primary outcomes focused on radiological time to bone fusion and rates of non-union. Additionally, functional outcomes and complications were analyzed as means of central tendency. Results: Eighteen studies were included in the systematic review, accounting for a total of 47 patients. The average follow-up time was 12.4 months. Fourteen studies analyzed radiological outcomes, with atrophic non-union representing the most common type. The time to bone fusion, assessed radiologically, following bone graft was an average of 6.9 months (n = 14), with a 100% rate of union in 42 patients. Regarding patient-reported pain improvement, 76% of patients experienced pain relief. Moreover, all patients reported a complete subjective return to baseline hand function. Adverse events, limited to hematoma and seroma, were seen in three patients, representing a complication rate of 11.8% in the examined population. Conclusions: Metacarpal non-union can be treated successfully via vascularized and non-vascularized bone grafting. Based on the available evidence, bone grafts demonstrate favorable union rates, post-operative pain reduction, hand function recovery, earlier bone fusion times, and minimal complications in the context of metacarpal non-union management.
A Comparative Analysis of Liver Injury Markers in Post-COVID Syndrome among Elderly Patients: A Prospective Study
Authors: Bota Adrian Vasile , Bratosin Felix , Bandi Satya Sai Sri , Bogdan Iulia , Razvan David Vladut , Toma Ana-Olivia , Indries Mirela Florica , Csep Andrei Nicolae , Cotoraci Coralia , Prodan Mihaela , Marc Felicia , Ignuta Flavia , Marincu Iosif
Published: February 2024

Background: In the wake of the global COVID-19 pandemic, understanding its prolonged impact on vulnerable populations has become a critical area of investigation. This study aimed to elucidate the distinctive post-acute sequelae of SARS-CoV-2 infection (PASC) and liver injury in Romania’s elderly population, hypothesizing unique demographic, clinical, and healthcare factors influencing the manifestation. Methods: A longitudinal design was employed, enrolling COVID-19 patients from the Victor Babes Hospital for Infectious Diseases and Pulmonology in Timisoara, Romania. Participants were stratified into three groups based on age and Long COVID status. The study focused on a variety of demographic, clinical, and biological parameters, including liver function tests, to assess the trajectory and severity of liver injury over six months post discharge. Results: Involving 238 participants, the study revealed a significant increase in the duration of hospitalization for those over 65 (15.8 ± 8.2 days) compared to younger groups (p < 0.001). Notably, elderly Long COVID patients exhibited a marked elevation in liver enzymes post discharge, with median ΔALT and ΔAST of 24.1 U/L and 30.2 U/L, respectively, suggesting ongoing liver injury (p < 0.001). Significant metabolic disruptions were observed, with the ΔFasting glucose showing a substantial median decrease of 21.1 mmol/L in the elderly group (p < 0.001). A pronounced reduction in ΔGGT (16.7 U/L) and ΔLDH (48.7 U/L) was noted, indicating a recovery in liver function and reduced tissue damage (p < 0.001). Coagulation profiles and liver fibrosis risk scores, particularly ΔFIB-4 and ΔAPRI, also significantly improved post discharge, indicating a reduced risk of ongoing liver complications. Conclusion: This study confirms the hypothesis of more severe PASC and liver injury among the elderly Romanian population. Significant improvements post discharge suggest a degree of recovery, yet the persistent alterations in liver enzymes, glucose metabolism, and fibrosis risk scores call for continued monitoring and tailored management strategies.
Exploring the Impact of Hand Dominance on Laparoscopic Surgical Skills Development Using Network Models
Authors: Malisetty Saiteja , Rastegari Elham , Siu Ka-Chun , Ali Hesham H.
Published: February 2024

Background: Laparoscopic surgery demands high precision and skill, necessitating effective training protocols that account for factors such as hand dominance. This study investigates the impact of hand dominance on the acquisition and proficiency of laparoscopic surgical skills, utilizing a novel assessment method that combines Network Models and electromyography (EMG) data. Methods: Eighteen participants, comprising both medical and non-medical students, engaged in laparoscopic simulation tasks, including peg transfer and wire loop tasks. Performance was assessed using Network Models to analyze EMG data, capturing muscle activity and learning progression. The NASA Task Load Index (TLX) was employed to evaluate subjective task demands and workload perceptions. Results: Our analysis revealed significant differences in learning progression and skill proficiency between dominant and non-dominant hands, suggesting the need for tailored training approaches. Network Models effectively identified patterns of skill acquisition, while NASA-TLX scores correlated with participants’ performance and learning progression, highlighting the importance of considering both objective and subjective measures in surgical training. Conclusions: The study underscores the importance of hand dominance in laparoscopic surgical training and suggests that personalized training protocols could enhance surgical precision, efficiency, and patient outcomes. By leveraging advanced analytical techniques, including Network Models and EMG data analysis, this research contributes to optimizing clinical training methodologies, potentially revolutionizing surgical education and improving patient care.
Impact of Implant Size and Position on Subsidence Degree after Anterior Cervical Discectomy and Fusion: Radiological and Clinical Analysis
Authors: Bębenek Adam , Dominiak Maciej , Karpiński Grzegorz , Pawełczyk Tomasz , Godlewski Bartosz
Published: February 2024

Background: Implant subsidence is recognized as a complication of interbody stabilization, although its relevance remains ambiguous, particularly in terms of relating the effect of the position and depth of subsidence on the clinical outcome of the procedure. This study aimed to evaluate how implant positioning and size influence the incidence and degree of subsidence and to examine their implications for clinical outcomes. Methods: An observational study of 94 patients (157 levels) who underwent ACDF was conducted. Radiological parameters (implant position, implant height, vertebral body height, segmental height and intervertebral height) were assessed. Clinical outcomes were evaluated using the Visual Analogue Scale (VAS) and Neck Disability Index (NDI). Subsidence was evaluated in groups according to its degree, and statistical analyses were performed. Results: The findings revealed that implant-to-endplate ratio and implant height were significant risk factors associated with the incidence and degree of subsidence. The incidence of subsidence varied as follows: 34 cases (41.5%) exhibited displacement of the implant into the adjacent endplate by 2–3 mm, 32 cases (39%) by 3–4 mm, 16 cases (19.5%) by ≥4 mm and 75 (47.8%) cases exhibited no subsidence. Conclusions: The findings underscore that oversized or undersized implants relative to the disc space or endplate length elevate the risk and severity of subsidence.
Perspectives for the Use of Umbilical Cord Blood in Transplantation and Beyond: Initiatives for an Advanced and Sustainable Public Banking Program in Greece
Authors: Pateraki Patra , Latsoudis Helen , Papadopoulou Anastasia , Gontika Ioanna , Fragiadaki Irene , Mavroudi Irene , Bizymi Nikoleta , Batsali Aristea , Klontzas Michail , Xagorari Angeliki , Michalopoulos Efstathios , Sotiropoulos Damianos , Yannaki Evangelia , Stavropoulos-Giokas Catherine , Papadaki Helen
Published: February 2024

The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system.
Utilization of Tenting Pole Abutments for the Reconstruction of Severely Resorbed Alveolar Bone: Technical Considerations and Case Series Reports
Authors: Sohn Dong-Seok , Lui Albert , Choi Hyunsuk
Published: February 2024

Introduction: Although various surgical techniques have been utilized in the reconstruction of severely resorbed alveolar bone, its regeneration is still regarded as a major challenge. Most of the surgical techniques used in advanced ridge augmentation have the disadvantages of prolonging the patient’s edentulous healing and increasing the need for surgical revisits because simultaneous implant placement is not allowed. This report presents a new and simplified method for advanced ridge augmentation, which utilizes a vertical tenting device. Case Presentation: The first case presented the reconstruction of the mandibular posterior region with severely resorbed alveolar bone due to peri-implantitis using tenting pole abutment for ridge augmentation. The second and third cases presented three-dimensional ridge augmentations in severely resorbed ridges due to periodontitis. The last case presented horizontal ridge augmentation using a vertical tenting device. All cases were performed under local anesthesia. Implants were simultaneously placed in the bone defect area. A vertical tensioning device was then connected to the implant platform to minimize the collapse of the bone graft during the bone regeneration period due to the contraction of the soft tissue matrix. A sticky bone graft was transplanted onto the exposed surface of the implant and on top of the vertical tensioning device. After covering with an absorbable barrier membrane, the soft tissues were sutured without tension. Conclusions: In all cases, prosthetic restorations were provided to patients after a bone grafting period of 5–6 months, leading to a rapid restoration of masticatory function. Results tracked for up to 6 years revealed observed stable reconstruction of the alveolar bone. The use of a vertical tenting device can prevent the collapse of biomaterials in the augmented ridge during the healing period, leading to predictable outcomes when achieving three-dimensional ridge augmentation.
New Designs of Spectacle Lenses for the Control of Myopia Progression: A Scoping Review
Authors: Lupon Marta , Nolla Carme , Cardona Genis
Published: February 2024

Myopia control with new designs of spectacle lenses is a flourishing area of research. The present work reviews the effectiveness of new designs (DIMSs, defocus-incorporated multiple segments; CARE, cylindrical annular refractive element; HALs/SALs, highly/slightly aspherical lenslets; DOT, diffusion optics technology) aiming at slowing myopia progression. A search through the PubMed database was conducted for articles published between 1 January 2003 and 28 February 2023. Publications were included if they documented baseline central refraction (SER) and/or axial length (AL) data, and the change in these parameters, in myopic children wearing new designs of spectacle lenses (treatment group) compared to myopic children using single-vision lenses, SVLs (control group). The selection process revealed nine suitable articles. Comparing the mean and standard error values of the treatment and control groups, the highest differences in the change in the SER and AL were −0.80 (1.23) D [95% CI: −1.053 to −0.547; p < 0.001] and 0.35 (0.05) mm [95% CI: 0.252 to 0.448; p < 0.001], respectively; the effect of treatment provided by a HAL design, compared to SVLs, led to a deceleration of 54.8% in the SER and 50.7% in the AL. However, the heterogeneity of the results prevents reaching strong conclusions about the effectiveness of these new designs.
Prevalence of Steatotic Liver Disease Based on a New Nomenclature in the Japanese Population: A Health Checkup-Based Cross-Sectional Study
Authors: Miwa Takao , Tajirika Satoko , Imamura Nanako , Adachi Miho , Horita Ryo , Hanai Tatsunori , Fukao Taku , Shimizu Masahito , Yamamoto Mayumi
Published: February 2024

This cross-sectional study examined the prevalence and characteristics of steatotic liver disease (SLD) based on a recently introduced nomenclature in the Japanese health checkup population. SLD was evaluated using liver ultrasonography, and participants were categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol associated steatotic liver disease (MetALD), alcohol-associated/related liver disease (ALD), and cryptogenic SLD groups. The prevalence and characteristics of the SLD subclasses were assessed, and subgroup analyses were conducted for the non-obese (body mass index [BMI] ≤ 25 kg/m2) and lean (BMI ≤ 23 kg/m2) populations. Among the 694 participants, with a median age of 47 years and comprising 54% males, the prevalence of MASLD, MetALD, ALD, and cryptogenic SLD was 26%, 2%, 1%, and 2%, respectively. A remarkable difference was observed in the prevalence of SLD subclasses according to age, sex, and BMI. Subgroup analyses revealed heterogeneous demographic, clinical, and biochemical parameters between the SLD categories. Individuals with MetALD had higher gamma-glutamyl transferase levels, lower platelet counts, and higher fibrosis-4 index than did those with MASLD. Furthermore, the prevalence of non-obese and lean MASLD was 13% and 6%, respectively. This study provides preliminary information on the prevalence of SLD based on a new nomenclature in the Japanese population.
Diagnostic Value of Ileal Lesions Found during Colonoscopy with Reference to Endoscopic Indications and Findings
Authors: Kim Dae Sung , Ryu Ji Eun , Shin Jieun , Koo Hoon Sup , Lee Sanghyuk , Cho Hwanhyi , Na Jongheon , Huh Kyu Chan
Published: February 2024

The diagnostic value of ileoscopy is not well established, and its routine practice is controversial. We aimed to investigate the diagnostic value of biopsy for macroscopically abnormal lesions in the terminal ileum and to identify the association between endoscopic indications and findings and the presence of significant disease. This retrospective study included 551 patients who underwent biopsy of abnormal lesions in the terminal ileum (TI) during colonoscopy between February 2000 and June 2019. Biopsy results were analyzed in relation to the endoscopic indications and gross findings. Significant disease was defined as a case in which a specific disease was suspected or confirmed by the biopsy results, requiring additional examination or treatment. Among the 551 biopsies from macroscopically abnormal lesions in the TI, 44 (8.0%) had significant diseases. The frequency of significant disease was high in patients with clinically suspected inflammatory bowel disease (IBD) (50.0%), anemia (31.6%), right lower quadrant (RLQ) pain (28.6%), and radiological abnormalities in the TI (27.5%). The frequency of Crohn’s disease (CD) was high in patients with clinically suspected IBD. A concurrent abnormality in the ileocecal valve (ICV) (14.3%) and the presence of an ulcer (14.2%), mass, or polyp (25.4%) correlated with a high incidence of significant disease, particularly CD. In cases of suspected IBD, anemia, RLQ pain, and radiologic abnormalities in the TI, there is a high possibility of significant disease. Ulcers, masses, polyps, and concurrent abnormalities in the ICV were also associated with significant disease.
Long-Term Functional Limitations on Cardiopulmonary Exercise Testing in Emotion-Triggered Takotsubo Syndrome
Authors: Jabbour Jean Pierre , Arcari Luca , Cacciotti Luca , Magrì Damiano , Recchioni Tommaso , Valeri Livia , Maggio Enrico , Vizza Carmine Dario , Badagliacca Roberto , Papa Silvia
Published: February 2024

Background: In patients with prior Takotsubo syndrome (TTS), long-lasting functional cardiac limitations were described as compared with normal subjects. Emotion-triggered Takotsubo syndrome (E-TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable factors. The aim of the present study was to assess long-term cardiac functional limitations in a cohort of asymptomatic E-TTS patients. Methods: We enrolled n = 40 asymptomatic patients with a diagnosis of E-TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 (12–40) months median follow-up from the acute event. A cohort of n = 40 individuals matched for age, sex, body mass index and comorbidities served as control. Results: Despite recovery of left ventricular ejection fraction, patients with prior E-TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs. 22.1 ± 6.5; p < 0.001 and 75.2 ± 14.1% vs. 100.6 ± 17.1%, p < 0.001), VO2 at anaerobic threshold (AT) (11.5 [10.1–12.9] vs. 14.4 [12.5–18.7]; p < 0.001), peak O2 pulse (9.8 ± 2.5 vs. 12.9 ± 3.5; p < 0.001) and higher VE/VCO2 slope (30.5 ± 3.7 vs. 27.3 ± 3.5; p < 0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Conclusions: Despite its favorable outcome, patients with E-TTS in our population were found to have subclinical long-term functional cardiac limitations as compared with a control cohort.
Suitable Patient Selection and Optimal Timing of Treatment for Persistent Air Leak after Lung Resection
Authors: Yamauchi Yoshikane , Adachi Hiroyuki , Takahashi Nobumasa , Morohoshi Takao , Yamamoto Taketsugu , Endo Makoto , Ueno Tsuyoshi , Woo Tekkan , Saito Yuichi , Sawabata Noriyoshi
Published: February 2024

Objectives: The choice of therapeutic intervention for postoperative air leak varies between institutions. We aimed to identify the optimal timing and patient criteria for therapeutic intervention in cases of postoperative air leaks after lung resection. Methods: This study utilized data from a prospective multicenter observational study conducted in 2019. Among the 2187 cases in the database, 420 cases with air leaks on postoperative day 1 were identified. The intervention group underwent therapeutic interventions, such as pleurodesis or surgery, while the observation group was monitored without intervention. A comparison between the intervention group and the observation group were analyzed using the cumulative distribution and hazard functions. Results: Forty-six patients (11.0%) were included in the intervention group. The multivariate analysis revealed that low body mass index (p = 0.019), partial resection (p = 0.010), intraoperative use of fibrin glue (p = 0.008), severe air leak on postoperative day 1 (p < 0.001), and high forced expiratory volume in 1 s (p = 0.021) were significant predictors of the requirement for intervention. The proportion of patients with persistent air leak in the observation group was 20% on postoperative day 5 and 94% on postoperative day 7. The hazard of air leak cessation peaked from postoperative day 3 to postoperative day 7. Conclusions: This research contributes valuable insights into predicting therapeutic interventions for postoperative air leaks and identifies scenarios where spontaneous cessation is probable. A validation through prospective studies is warranted to affirm these findings.
Complications and Outcomes in 39,864 Patients Receiving Standard Care Plus Mechanical Circulatory Support or Standard Care Alone for Infarct-Associated Cardiogenic Shock
Authors: Padberg Jan-Sören , Feld Jannik , Padberg Leonie , Köppe Jeanette , Makowski Lena , Gerß Joachim , Dröge Patrik , Ruhnke Thomas , Günster Christian , Lange Stefan Andreas , Reinecke Holger
Published: February 2024

Background: Temporary mechanical circulatory support devices (tMCS) are increasingly being used in patients with infarct-associated cardiogenic shock (AMICS). Evidence on patient selection, complications and long-term outcomes is lacking. We aim to investigate differences in clinical characteristics, complications and outcomes between patients receiving no tMCS or either intra-aortic balloon pump (IABP), veno-arterial extracorporeal membrane oxygenation (V-A ECMO) or Impella® for AMICS, with a particular focus on long-term outcomes. Methods: Using health claim data from AOK—Die Gesundheitskasse (local health care funds), we retrospectively analysed complications and outcomes of all insured patients with AMICS between 1 January 2010 and 31 December 2017. Results: A total of 39,864 patients were included (IABP 5451; Impella 776; V-A ECMO 833; no tMCS 32,804). In-hospital complications, including renal failure requiring dialysis (50.3% V-A ECMO vs. 30.5% Impella vs. 29.2 IABP vs. 12.1% no tMCS), major bleeding (38.1% vs. 20.9% vs. 18.0% vs. 9.3%) and sepsis (22.5% vs. 15.9% vs. 13.9% vs. 9.3%) were more common in V-A ECMO patients. In a multivariate analysis, the use of both V-A ECMO (HR 1.57, p < 0.001) and Impella (HR 1.25, p < 0.001) were independently associated with long-term mortality, whereas use of IABP was not (HR 0.89, p < 0.001). Kaplan–Meier estimates showed better survival for patients on IABP compared with Impella, V-A ECMO and no-tMCS. Short- and long-term mortality was high across all groups. Conclusions: Our data show noticeably more in-hospital complications in patients on tMCS and higher mortality with V-A ECMO and Impella. The use of both devices is an independent risk factor for mortality, whereas the use of IABP is associated with a survival benefit.
Expression of Tissue Inhibitors of Metalloproteinases (TIMP-1, TIMP-2, TIMP-3, TIMP-4) in Blood Serum of Patients with Keratoconus
Authors: Nowak-Wąs Marta , Wąs Paweł , Czuba Zenon , Wojnicz Romuald , Wyględowska-Promieńska Dorota
Published: February 2024

Background: The etiology of keratoconus is unclear. Current evidence suggests that inflammatory and systemic mechanisms might play a role in its pathophysiology. The proper interaction of proteolytic enzymes—matrix metalloproteinases—and their specific tissue inhibitors (TIMPs) within the cornea is essential in maintaining its structure, transparency and healing processes. The aim of the study was to determine the concentration of the TIMPs TIMP-1, TIMP-2, TIMP-3, and TIMP-4 in the blood serum samples of patients with keratoconus compared to the control group. Methods: The study encompassed 132 patients, of which 83 people constituted the study group and 49 the control group. The concentration of selected TIMPs was determined using the Human Magnetic Luminex® Performance Assay method. Results: In the study group, the concentrations of TIMP-1 and TIMP-3 were statistically significantly reduced, and TIMP-2 and TIMP-4 increased compared to the control group. The analysis of individual TIMPs in terms of their usefulness as potential predictors of keratoconus showed high results of diagnostic sensitivity and specificity for all TIMPs, in particular for TIMP-1 and TIMP-2. Conclusion: The above results may indicate systemic disturbances in the TIMPs regulation among keratoconus patients. High diagnostic sensitivity and specificity of all TIMPs, in particular TIMP-1 and TIMP-2, may confirm their participation in the etiopathogenesis of this disease.
Reply to Ronsivalle, S.; Di Luca, M. Exploring the Choice of Graft Materials in Tympanoplasty: A Perspective on the Use of Temporalis Fascia and Cartilage Grafts. Comment on “Ferlito et al. Type 1 Tympanoplasty Outcomes between Cartilage and Temporal Fascia Grafts: A Long-Term Retrospective. J. Clin. Med. 2022, 11, 7000”
Authors: Maniaci Antonino , Lechien Jerome R. , Mayo-Yanez Miguel , Lentini Mario , Merlino Federico
Published: February 2024

We sincerely appreciate the valuable insights Ronsivalle et al [...]