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15 pages, 975 KiB  
Article
Decoding the Effect of Frailty vs. Physiologic Age in Octogenarian and Nonagenarian Colectomy Outcomes for Colon Cancer
by Philip Drohat, Alexandra E. Hernandez, Ana M. Reyes, Karishma Kodia, Chelsea Caplan, Talia R. Arcieri, Shayan Khalafi, Matthew S. Meece and Vanessa W. Hui
J. Clin. Med. 2025, 14(17), 5985; https://doi.org/10.3390/jcm14175985 - 24 Aug 2025
Abstract
Background/Objectives: Colorectal surgeons continue to care for an aging cancer population with increasing comorbidities and frailty. Frailty, characterized by a systemic physiologic decline associated with aging, is an increasingly popular focus in surgical outcomes research. This retrospective study investigates how frailty impacts [...] Read more.
Background/Objectives: Colorectal surgeons continue to care for an aging cancer population with increasing comorbidities and frailty. Frailty, characterized by a systemic physiologic decline associated with aging, is an increasingly popular focus in surgical outcomes research. This retrospective study investigates how frailty impacts outcomes in the octogenarian and nonagenarian populations undergoing surgical treatment for colon cancer. Methods: Data from the National Surgical Quality Improvement Program (NSQIP) colectomy-targeted variables dataset from 2015 to 2021 were utilized for this analysis, including patients 80 years of age and older. Frailty was assessed using the five-factor modified frailty index (mFI-5). The study examined post-operative outcomes across frailty groups in this population. Results: From 2015–2021, there were 10,671 patients aged 80 years and older who underwent colectomy for colon cancer, of whom 1,259 (11.8%) were 90 years or older and 2,844 (26.7%) were severely frail. Frailty significantly impacted post-operative colectomy outcomes in this population. On univariate analysis, frail patients had higher rates of pneumonia (p = 0.015), unplanned intubation (p = 0.012), stroke (p < 0.001), myocardial infarction (p = 0.011), readmission (p < 0.001), long length of stay (p < 0.001), and mortality (p < 0.001) compared to non-frail patients. On multivariate analysis, severe frailty (mFI-5 of 2 or more) was associated with an increased odds of unplanned intubation (aOR 2.41, 95% CI 1.27–4.59), long length of stay (aOR 1.73, 95% CI 1.44–2.09), readmission (aOR 1.84, 95% CI 1.42–2.39), and mortality (aOR 1.95, 95% CI 1.20–3.15) compared to non-frail patients. Conclusions: Frailty plays a critical role in influencing the outcomes of octogenarians and nonagenarians undergoing colectomy for colon cancer within the NSQIP dataset. Future work should investigate whether addressing frailty prior to surgery in this population can improve patients’ post-operative courses. Full article
(This article belongs to the Special Issue Clinical Aspects and Outcomes in Contemporary Colorectal Surgery)
19 pages, 2536 KiB  
Systematic Review
From Subtle Signs to Severe Sequelae—A Century of Symptomatology and Comorbidities in the Diagnosis of GH-Secreting Pituitary Neuroendocrine Tumors: A Systematic Review
by María José Ayora, Lizeth Vinueza-Mera, Santiago Aynaguano, David Poma Jimenez, Felipe Loza Hernandez, Sebastian Jara Jimenez, Jose A. Rodas and Jose E. Leon-Rojas
Diagnostics 2025, 15(17), 2137; https://doi.org/10.3390/diagnostics15172137 - 24 Aug 2025
Abstract
Background/Objectives: Somatotropinomas rank as the second most prevalent functional pituitary neuroendocrine tumors (PitNETs), responsible for acromegaly in adults and gigantism in children. Early diagnosis and treatment would help prevent irreversible physical changes and other associated comorbidities. The aim of this review is [...] Read more.
Background/Objectives: Somatotropinomas rank as the second most prevalent functional pituitary neuroendocrine tumors (PitNETs), responsible for acromegaly in adults and gigantism in children. Early diagnosis and treatment would help prevent irreversible physical changes and other associated comorbidities. The aim of this review is to characterize the symptomatic presentation of growth hormone (GH)-secreting PitNET at the time of diagnosis. Methods: A search was conducted in PubMed, Scopus, Cochrane, and the Virtual Health Library (VHL). Primary descriptive and analytical studies were selected if they were written in Spanish or English and addressed the symptoms of acromegaly and/or gigantism due to somatotropinomas. Results: Out of 8470 articles, 93 fulfilled the inclusion criteria, covering 1745 patients (55.4% women). The most frequent diagnostic signs/symptoms were enlarged extremities (12.4%) and facial changes (13.1%). Endocrine–metabolic (42.82%) and cardiovascular (31.45%) were the most prevalent comorbidities. The average diagnostic delay was 6.7 years, with the number of reports of the disease significantly increasing in recent decades, most likely due to ongoing advances in imaging and standardized hormonal tests. Conclusions: Timely recognition of a somatotropinoma’s symptoms and comorbidities is crucial for early diagnosis and referral to specialized care and the prevention of permanent physical and/or physiological changes. Full article
(This article belongs to the Special Issue Diagnosis and Management of Neuroendocrine Tumors)
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24 pages, 1045 KiB  
Review
Anti-B Cell Strategy in Nephrotic Syndrome: Beyond Rituximab
by Yanyan Jin, Yi Xie, Haidong Fu, Fei Liu and Jianhua Mao
Biomedicines 2025, 13(9), 2063; https://doi.org/10.3390/biomedicines13092063 - 24 Aug 2025
Abstract
Nephrotic syndrome (NS) is a complex kidney disorder characterized by profound proteinuria, hypoalbuminemia, hyperlipidemia, and edema, significantly impacting patients’ quality of life. While corticosteroids and calcineurin inhibitors (CNIs) have traditionally been the primary treatments, B cell-targeted therapies, especially the anti-CD20 monoclonal antibody rituximab, [...] Read more.
Nephrotic syndrome (NS) is a complex kidney disorder characterized by profound proteinuria, hypoalbuminemia, hyperlipidemia, and edema, significantly impacting patients’ quality of life. While corticosteroids and calcineurin inhibitors (CNIs) have traditionally been the primary treatments, B cell-targeted therapies, especially the anti-CD20 monoclonal antibody rituximab, have transformed the management of steroid-dependent and multidrug-resistant NS (MRNS). Rituximab has demonstrated efficacy in reducing relapse rates and steroid dependence by depleting CD20+ B cells, which play a pivotal role in autoantibody production and immune dysregulation. However, limitations such as incomplete B cell depletion, immunogenicity leading to anti-rituximab antibodies, and variable efficacy in refractory cases have led to the development of next-generation therapies. This review critically examines recent advances in B cell-targeted therapies for NS, with a particular focus on overcoming the limitations of conventional rituximab treatment. This review systematically analyzes next-generation anti-CD20 monoclonal antibodies, CD38-targeted therapies, and emerging CAR-T cell approaches, evaluating their distinct mechanisms of action and clinical trial outcomes. The analysis extends to innovative combination strategies and biomarker-guided treatment algorithms for refractory cases. By synthesizing preclinical data with clinical evidence, this work provides a framework for optimizing therapeutic decision-making in NS, while identifying key knowledge gaps that warrant future investigation. Collaborative research and translational studies are essential for advancing precision medicine in NS, ensuring that new therapies provide lasting clinical benefits for patients. The evolving field of anti-B cell therapies marks a new era in managing refractory NS, offering hope for better long-term prognoses. Full article
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18 pages, 806 KiB  
Article
History of Pulmonary Tuberculosis Accelerates Early Onset and Severity of COPD: Evidence from a Multicenter Study in Romania
by Ramona Cioboata, Silviu Gabriel Vlasceanu, Denisa Maria Mitroi, Ovidiu Mircea Zlatian, Mara Amalia Balteanu, Gabriela Marina Andrei, Viorel Biciusca and Mihai Olteanu
J. Clin. Med. 2025, 14(17), 5980; https://doi.org/10.3390/jcm14175980 - 24 Aug 2025
Abstract
Background: Pulmonary tuberculosis (TB) is increasingly recognized as a risk factor for chronic obstructive pulmonary disease (COPD), but its impact on COPD onset and severity remains poorly characterized, particularly in low- and middle-income countries. This multicenter study aimed to assess the impact of [...] Read more.
Background: Pulmonary tuberculosis (TB) is increasingly recognized as a risk factor for chronic obstructive pulmonary disease (COPD), but its impact on COPD onset and severity remains poorly characterized, particularly in low- and middle-income countries. This multicenter study aimed to assess the impact of prior pulmonary TB on COPD onset, severity, the timing of the first severe exacerbation, and progression among Romanian patients with and without a history of pulmonary TB. Methods: This retrospective multicenter study included adults hospitalized for their first severe COPD exacerbation at two tertiary care centers in Romania between April 2020 and April 2025. Patients were grouped based on smoking status and prior TB history. Propensity score matching was used to control for confounding factors. Clinical characteristics, spirometry, and radiological TB patterns were analyzed comparatively between patients with prior TB and TB-naïve patients. Results: Among 403 COPD patients, those with prior TB had significantly earlier COPD onset (mean age 48.67 ± 6.42 vs. 65.61 ± 5.14 years in smokers, p < 0.001) and shorter intervals to their first severe COPD exacerbation compared to patients without prior TB (6.35 ± 4.71 vs. 15.14 ± 6.93 years in smokers, p < 0.001). COPD prevalence was higher among TB survivors compared to those without TB history, especially in smokers (OR = 5.73; 95% CI, 3.30–9.94, p < 0.001), versus non-smokers (OR =2.23; 95% CI, 1.37–3.64, p = 0.001). Radiological severity of TB lesions significantly influenced COPD prevalence among smokers (OR = 10.79, p < 0.001). Conclusions: Prior pulmonary TB substantially accelerates COPD onset, exacerbation timing, and disease severity, particularly in smokers. This multicenter comparative study demonstrates that prior pulmonary TB significantly accelerates COPD onset, exacerbation timing, and disease severity, especially among smokers. Recognizing TB history as a significant COPD risk factor underscores the importance of targeted COPD screening and tailored management in populations with high TB prevalence. Full article
25 pages, 1944 KiB  
Article
Cachexia Phenotyping Through Morphofunctional Assessment and Mitocondrial Biomarkers (GDF-15 and PGC-1α) in Idiopathic Pulmonary Fibrosis
by Alicia Sanmartín-Sánchez, Rocío Fernández-Jiménez, Josefina Olivares-Alcolea, Eva Cabrera-César, Francisco Espíldora-Hernández, Isabel Vegas-Aguilar, María del Mar Amaya-Campos, Víctor José Simón-Frapolli, María Villaplana-García, Isabel Cornejo-Pareja, Ana Sánchez-García, Mora Murri, Patricia Guirado-Peláez, Álvaro Vidal-Suárez, Lourdes Garrido-Sánchez, Francisco J. Tinahones, Jose Luis Velasco-Garrido and Jose Manuel García-Almeida
Nutrients 2025, 17(17), 2739; https://doi.org/10.3390/nu17172739 - 24 Aug 2025
Abstract
Background/Objetives: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Nutritional disorders, particularly cachexia, significantly impact morbidity and mortality in IPF but remain under-investigated. This study aimed to characterize cachexia phenotypes in IPF through morphofunctional assessment (MFA) and [...] Read more.
Background/Objetives: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Nutritional disorders, particularly cachexia, significantly impact morbidity and mortality in IPF but remain under-investigated. This study aimed to characterize cachexia phenotypes in IPF through morphofunctional assessment (MFA) and to evaluate their prognostic relevance, including the role of mitochondrial biomarkers. Methods: In this prospective bicenter study, 85 IPF patients underwent MFA including bioelectrical impedance vector analysis (BIVA), nutritional ultrasound (NU), and T12-level computed tomography (T12-CT) for body composition. Functional and strength assessments included timed up and go test (TUG) and handgrip strength (HGS), respectively. Cachexia was defined by Evans’ criteria, Martin’s CT-based criteria, and our IPF-specific proposed definition. Serum GDF-15 and PGC-1α levels were also measured. Results: Cachexia prevalence varied by definition: 24.71% (Evans), 29.5% (Martin) and 42.4% (IPF Cachexia Syndrome). Cachectic patients showed significantly lower muscle mass, function, and quality (measured by reduced muscle attenuation at T12-CT), along with higher GDF-15 and lower PGC-1α levels. The presence of IPF Cachexia syndrome (HR 2.56; 95% CI, 1.08–6.07; p = 0.033), GDF-15 > 4412.0 pg/mL (HR 3.21; 95% CI, 1.04–9.90; p = 0.042) and impaired TUG (>8 s) (HR 3.77; 95% CI, 1.63–8.71; 0.002) were all independently associated with increased 24-month mortality. Conclusions: Cachexia is prevalent in IPF and showed strong concordance between the three diagnostic criteria. The IPF Cachexia syndrome, based on comprehensive morphofunctional phenotyping, demonstrated superior discriminatory capacity. The addition of mitochondrial biomarkers may improve early detection and support personalized interventions to improve patient outcomes. Full article
(This article belongs to the Section Clinical Nutrition)
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16 pages, 1635 KiB  
Article
Expression Analysis of let-7a-5p and miR-21-3p in Extracellular Vesicles Derived from Serum of NSCLC Patients
by Dian Jamel Salih, Katrin S. Reiners, Domenico Loizzi, Nicoletta Pia Ardò, Teresa Antonia Santantonio, Francesco Sollitto and Gunther Hartmann
Biomedicines 2025, 13(9), 2060; https://doi.org/10.3390/biomedicines13092060 - 24 Aug 2025
Abstract
Background/Objectives: Despite the significant advancements made in the diagnosis of lung cancer, the traditional diagnostic methods remain limited because they are often invasive, expensive, and not suitable for regular screening, creating a need for more accessible and non-invasive alternatives. In this context, [...] Read more.
Background/Objectives: Despite the significant advancements made in the diagnosis of lung cancer, the traditional diagnostic methods remain limited because they are often invasive, expensive, and not suitable for regular screening, creating a need for more accessible and non-invasive alternatives. In this context, the analysis of miRNAs in EVs and free circulating microRNA may be used as liquid biopsies in lung cancer to identify individuals at risk. This study aimed to compare miRNA profiles in the serum and EVs derived from lung cancer patients by focusing on Let-7a-5p and miR-21-3p. Materials and Methods: Serum and EVs were isolated from lung cancer patients and healthy controls. EVs were characterized using nanoparticle tracking analysis, electron microscopy, and Western blotting for surface markers (CD63, CD81, TSG101). Total miRNA levels were quantified in the serum and EVs, and specific miRNAs (hsa-let-7a-5p and hsa-miR-21-3p) were analyzed using RT-qPCR. Statistical analysis evaluated miRNA expression across clinicopathological features, including age, gender, smoking status, tumor stage, cancer type, and EGFR mutation status. Results: Total miRNA levels were significantly enriched in EVs compared to the serum. Let-7a-5p was downregulated in EVs from patients with advanced-stage lung cancer (Stage III–IV) compared to those with early-stage cancer and controls (p < 0.05), while no differences were observed in the serum. Conversely, miR-21-3p was significantly upregulated in EVs and serum from advanced-stage patients (p < 0.01) and in adenocarcinoma compared to squamous cell carcinoma (p < 0.05). No significant differences were observed for age, gender, or smoking status. Conclusions: Our findings highlight the differential expression of miRNAs in EVs and the serum, emphasizing the diagnostic potential of EV-associated Let-7a-5p and miR-21-3p in lung cancer. These results suggest that EVs are a more robust source for miRNA biomarkers compared to the serum. Full article
(This article belongs to the Special Issue Extracellular Vesicles and Exosomes as Therapeutic Agents)
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23 pages, 5200 KiB  
Article
Genomic Insights into Tumorigenesis in Newly Diagnosed Multiple Myeloma
by Marina Kyriakou and Costas Papaloukas
Diagnostics 2025, 15(17), 2130; https://doi.org/10.3390/diagnostics15172130 - 23 Aug 2025
Abstract
Background: Multiple Myeloma (MM) is a malignant plasma cell dyscrasia that progresses through the consecutive asymptomatic, often undiagnosed, precancerous stages of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Asymptomatic Multiple Myeloma (SMM). MM is characterized by low survival rates, severe complications and [...] Read more.
Background: Multiple Myeloma (MM) is a malignant plasma cell dyscrasia that progresses through the consecutive asymptomatic, often undiagnosed, precancerous stages of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Asymptomatic Multiple Myeloma (SMM). MM is characterized by low survival rates, severe complications and drug resistance; therefore, understanding the molecular mechanisms of progression is crucial. This study aims to detect genetic mutations, both germline and somatic, that contribute to disease progression and drive tumorigenesis at the final stage of MM, using samples from patients presenting MGUS or SMM, and newly diagnosed MM patients. Methods: Mutations were identified through a fully computational pipeline, implemented in a Linux and RStudio environment, applied to each patient sequence, obtained through single-cell RNA-sequencing (scRNA-seq), separately. Structural and functional mutation types were identified by stage, along with the affected genes. The analysis included quality control, removal of the Unique Molecular Identifiers (UMIs), trimming, genome mapping and result visualization. Results: The findings revealed frequent germline and somatic mutations, with distinct structural and functional patterns across disease stages. Mutations in key genes were identified, pointing to molecules that may play a central role in carcinogenesis and disease progression. Notable examples include the HLA-A, HLA-B and HLA-C genes, as well as the KIF, EP400 and KDM gene families, with the first four already confirmed. Comparative analysis between the stages highlighted molecular transition events from one stage to another. Emphasis was given to novel genes discovered in newly diagnosed MM patients, that might contribute to the tumorigenesis that takes place. Conclusions: This study contributes to the understanding of the genetic basis of plasma cell dyscrasias and the transition events between the stages, offering insights that could aid in early detection and diagnosis, guide the development of personalized therapeutic strategies, and improve the understanding of mechanisms responsible for resistance to existing therapies. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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28 pages, 1193 KiB  
Article
Profiling of Volatile Metabolites of Escherichia coli Using Gas Chromatography–Mass Spectrometry
by Karolina Żuchowska, Alicja Tracewska, Dagmara Depka-Radzikowska, Tomasz Bogiel, Robert Włodarski, Barbara Bojko and Wojciech Filipiak
Int. J. Mol. Sci. 2025, 26(17), 8191; https://doi.org/10.3390/ijms26178191 - 23 Aug 2025
Abstract
Current diagnostic methods for bacterial infections in critically ill patients, including ventilator-associated pneumonia (VAP), are time-consuming, while empirical antibiotic therapy contributes to rising resistance. Bacteria-derived volatile organic compounds (VOCs) are being explored as specific biomarkers for pathogen identification and treatment monitoring. This study [...] Read more.
Current diagnostic methods for bacterial infections in critically ill patients, including ventilator-associated pneumonia (VAP), are time-consuming, while empirical antibiotic therapy contributes to rising resistance. Bacteria-derived volatile organic compounds (VOCs) are being explored as specific biomarkers for pathogen identification and treatment monitoring. This study expands knowledge of Escherichia coli metabolism by identifying VOCs produced by both multidrug-resistant and susceptible strains, characterizing their temporal profiles during growth, and assessing VOC profile changes after imipenem exposure. Reference strains and 21 clinical isolates (derived from BAL samples of VAP patients) were cultured under controlled conditions. Headspace VOCs were preconcentrated using multibed sorption tubes and analyzed by gas chromatography–mass spectrometry (GC-MS), with compound identities confirmed using external standards. Sampling at seven time points over 24 h cultures revealed three VOC emission patterns: continuous release, temporary maximum, and compound uptake. In total, 57 VOCs were identified from the susceptible strain and 41 from the resistant one, with dimethyl disulfide, 2-butenal, ethyl acetate, and furan elevated in the resistant strain. Imipenem addition altered VOC production in the susceptible strain, with levels of six compounds elevated and seven reduced, while resistant profiles remained stable. Clinical isolates produced 71 VOCs, showing greater metabolic diversity and highlighting the relevance of isolate-derived VOCs in future studies. Full article
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11 pages, 2222 KiB  
Case Report
Adenoma-like Adenocarcinoma of the Colon: Case Report and Diagnostic Pitfalls of an Underrecognized Entity with Favorable Prognosis
by Alfonso Agüera-Sánchez, Emilio Peña-Ros, Irene Martínez-Martínez and Francisco García-Molina
Onco 2025, 5(3), 39; https://doi.org/10.3390/onco5030039 - 23 Aug 2025
Abstract
Adenoma-like adenocarcinoma (ALAC) of the colon is a recently recognized histological subtype of colorectal adenocarcinoma, characterized by a villous architecture, low-grade cytologic atypia, and deceptive bland morphology despite its invasive potential, which can mimic non-invasive adenomas, leading to underdiagnosis in limited biopsy samples. [...] Read more.
Adenoma-like adenocarcinoma (ALAC) of the colon is a recently recognized histological subtype of colorectal adenocarcinoma, characterized by a villous architecture, low-grade cytologic atypia, and deceptive bland morphology despite its invasive potential, which can mimic non-invasive adenomas, leading to underdiagnosis in limited biopsy samples. Herein, we report the case of an 81-year-old male presenting with right-upper-quadrant pain that was found to have a hepatic abscess and a 4 cm villous lesion in the ascending colon. Histopathological examination of the right hemicolectomy specimen revealed a villous adenocarcinoma with invasion of the muscularis propria, consistent with adenoma-like adenocarcinoma. Isolated loss of PMS2 indicated a mismatch repair deficiency. However, adjuvant therapy was not indicated. The patient remained recurrence-free for three years, until he died from unrelated causes in the context of progressive frailty and comorbidities, with no evidence of cancer progression. This case highlights the diagnostic challenges posed by ALAC and underscores the importance of recognizing its distinct morphological features. Awareness of this entity is essential to avoid misclassification and ensure adequate treatment, especially given its typically favorable prognosis with low metastatic potential. Full article
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17 pages, 1537 KiB  
Article
Genome-Wide Association Study of Osteoporosis Risk in Korean Pre-Menopausal Women: The Korean Genome and Epidemiology Study
by Su Kang Kim, Seoung-Jin Hong, Gyutae Kim, Ju Yeon Ban and Sang Wook Kang
Int. J. Mol. Sci. 2025, 26(17), 8177; https://doi.org/10.3390/ijms26178177 - 22 Aug 2025
Abstract
Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this [...] Read more.
Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this study was to identify genetic variants associated with the development of osteoporosis in Korean premenopausal women. Subjects were recruited from the Anseong and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). Clinical and epidemiological characteristics were assessed, and participants were classified based on BMD values measured at the distal radius and mid-shaft tibia. Individuals with confounding risk factors such as low body weight, smoking, high alcohol consumption, steroid/hormone therapy, or relevant medical history were excluded. A total of 247 healthy controls and 57 osteoporosis patients were included. Genotyping was performed using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. Data were analyzed using the SNP and Variation Suite and PLINK, with quality control thresholds set at MAF ≥ 0.05 and HWE p ≥ 0.01. Functional annotation and protein structure predictions were performed using PolyPhen-2, SIFT, and PROVEAN. Genome-wide association analyses identified 113 single-nucleotide polymorphisms (SNPs) in 69 genes significantly associated with osteoporosis (p < 0.05) in both platforms, with 18 SNPs showing high cross-platform consistency (p < 0.01). Several of these genes were implicated in bone metabolism (e.g., ESRRG, PECAM1, COL6A5), vitamin D metabolism (e.g., NADSYN1, EFTUD1), skeletal muscle function (e.g., PACSIN2, ESRRG), and reproductive processes (e.g., CPEB1, EFCAB6, ASXL3). Notably, the CPEB1 rs783540 SNP exhibited the strongest association (p < 0.001) in both analyses. Our findings suggest that genetic polymorphisms in pathways related to bone metabolism, vitamin D signaling, muscle–bone interaction, and reproductive hormone regulation may contribute to the development of osteoporosis in Korean premenopausal women. These results provide a genetic basis for early identification of at-risk individuals and warrant further functional studies to elucidate the underlying mechanisms. Full article
(This article belongs to the Special Issue Molecular Biology of Osteoporosis)
14 pages, 2680 KiB  
Article
Molecular Epidemiology of tet(A)-v1-Positive Carbapenem-Resistant Klebsiella pneumoniae in Pediatric Patients in a Chinese Hospital
by Chen Xu, Chunli Li, Yuanyuan Li, Xiangkun Zeng, Yi Yang, Mi Zhou, Jiani Jiang, Yunbing Li, Guangfen Zhang, Xiaofan Li, Jiayi You, Yi Liu, Lili Huang, Sheng Chen and Ning Dong
Antibiotics 2025, 14(9), 852; https://doi.org/10.3390/antibiotics14090852 - 22 Aug 2025
Abstract
Background: The emergence and spread of the tigecycline resistance gene tet(A)-v1 in carbapenem-resistant Klebsiella pneumoniae (CRKP) poses significant public health challenges. However, the prevalence of tet(A)-v1-positive CRKP, especially in pediatric patients, remains poorly understood. This study aims to address the gap [...] Read more.
Background: The emergence and spread of the tigecycline resistance gene tet(A)-v1 in carbapenem-resistant Klebsiella pneumoniae (CRKP) poses significant public health challenges. However, the prevalence of tet(A)-v1-positive CRKP, especially in pediatric patients, remains poorly understood. This study aims to address the gap by performing an in-depth analysis of isolates collected from a children’s hospital in China. Methods: A 4-year retrospective study was conducted in the children’s hospital in Suzhou, China. Non-duplicated specimens were obtained from pediatric patients, and antimicrobial susceptibility profiles were assessed. Whole-genome sequencing and bioinformatics analyses were conducted to characterize the genetic background, antimicrobial resistance determinants, hypervirulence-associated genes, diversity of tet(A)-v1-carrying plasmids, the genetic environment of tet(A)-v1, and the potential for clonal transmission. Conjugative transferability of tet(A)-v1-carrying plasmids was also evaluated via conjugation assays. Results: Of the 73 tet(A)-v1-positive CRKP isolates from pediatric patients, 10.96% were non-susceptible to tigecycline. These isolates exhibited high genetic diversity, spanning across 13 STs (sequence types), with ST17 being predominant. Three carbapenemases were identified, with IMP being the most common. Isolates from diverse backgrounds, such as ST17, ST20, ST323, ST792, and ST3157, demonstrated evidence of clonal transmission. The tet(A)-v1 gene was located on 14 distinct plasmids across seven replicon types, with IncFIA/IncHI1 and IncFII being most commonly detected. All tet(A)-v1-carrying plasmids were multidrug-resistant, and 68.49% were conjugatively transferable, indicating a high potential for horizontal transfer. Four genetic contexts bordering tet(A)-v1 were identified, which points to active clonal dissemination. Conclusions: Although limited to a single hospital, this study represents one of the first in-depth investigations of tet(A)-v1-positive CRKP in pediatric patients, providing valuable insights into the prevalence and spread of tet(A)-v1 in this vulnerable group. These findings emphasize the urgent need for enhanced surveillance and infection control measures to curb the spread of tet(A)-v1-positive CRKP in pediatric healthcare environments, offering critical insights to mitigate its public health impact. Full article
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13 pages, 488 KiB  
Systematic Review
Carbon Ion and Proton Therapy in Sacral Chordoma: A Systematic Review
by Andrea Santoro, Riccardo Totti, Alessandro El Motassime, Cesare Meschini, Doriana Di Costa, Elena Gabrielli, Giulio Maccauro and Raffaele Vitiello
J. Clin. Med. 2025, 14(17), 5947; https://doi.org/10.3390/jcm14175947 - 22 Aug 2025
Abstract
Background: chordomas are characterized as locally aggressive yet infrequently metastasizing malignant neoplasms of bone, primarily arising in the axial skeleton, with a notable prevalence in the sacral region. En bloc resection is recognized as the standard treatment for sacral chordoma; however, its [...] Read more.
Background: chordomas are characterized as locally aggressive yet infrequently metastasizing malignant neoplasms of bone, primarily arising in the axial skeleton, with a notable prevalence in the sacral region. En bloc resection is recognized as the standard treatment for sacral chordoma; however, its feasibility is not universally guaranteed. Therefore, definitive proton, carbon ion, or photon therapy is often utilized as an alternative to surgical intervention or as a (neo-)adjuvant measure in conjunction with surgery, owing to their role in enhancing local control. Methods: a search of PubMed yielded 127 articles, with 18 that were ultimately included in the review. This review aims to systematically evaluate clinical outcomes and complications associated with hadron therapy in cases of sacral chordomas. The review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, including publication dates up to January 2025. Results: data extraction showed promising outcomes for patients treated with hadron therapy alone or when hadron therapy was used as an adjuvant for surgery, even if complications are described. The 5-year overall survival estimated from evaluating 10 of 18 articles was 82.4%, although some articles reported different results in shorter follow-up periods. Skin ulceration and pain were described in 323 (29%) and 186 (16%) patients, respectively. Chronic complications reported were sacral fractures, metastasis, rectal disorders, urinary disorders, and peripheral motor and sensory neuropathy. Conclusions: hadron therapy represents a highly effective and promising treatment for sacral chordomas. In cases of inoperable tumors, it has demonstrated outcomes comparable to surgery while significantly reducing treatment-related morbidity. Hadron therapy is also viable as adjuvant therapy and provides superior outcomes for patients who undergo surgery with positive margins compared to those treated with surgery alone, improving local control and overall prognosis. Full article
(This article belongs to the Section Oncology)
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18 pages, 1671 KiB  
Article
Real-World Comparison of FFR and QFR: New Perspectives on the Functional Assessment of Coronary Stenoses
by Róbert Gál, Bettina Csanádi, Tamás Ferenci, Noémi Bora and Zsolt Piróth
J. Clin. Med. 2025, 14(17), 5946; https://doi.org/10.3390/jcm14175946 - 22 Aug 2025
Abstract
Background/Objectives: The diagnostic value of Quantitative Flow Ratio (QFR) with respect to Fractional Flow Reserve (FFR) in real-world settings is not well described, and neither are the factors influencing the bias of QFR versus FFR well understood. The learning curve associated with QFR [...] Read more.
Background/Objectives: The diagnostic value of Quantitative Flow Ratio (QFR) with respect to Fractional Flow Reserve (FFR) in real-world settings is not well described, and neither are the factors influencing the bias of QFR versus FFR well understood. The learning curve associated with QFR calculation has not been thoroughly investigated. Hence, we sought to evaluate the association between the QFR and FFR, to investigate the influence of clinical parameters on both values and their difference, and to analyze the learning curve associated with QFR measurement in a real-world setting. Methods: All patients who underwent FFR and QFR measurements in 2023 at our tertiary-care center were included. The bias was characterized using a Bland–Altman plot and multivariable regression was used to uncover its potential predictors. Results: QFR calculation was successful in 73% of 595 patients with 778 vessels with FFR measurement results. Median bias of QFR was 0.011, but in 7% of the cases, the difference between the two exceeded 0.10. A good correlation was found between the two indices. Receiver operating characteristic curve analysis showed that the area under the curve of QFR for predicting FFR ≤ 0.80 was 0.912. FFR and QFR values were lower in the left anterior descending artery; acute coronary syndrome indication was associated with higher QFR values. Right coronary artery localization was associated with a greater bias of QFR, whereas female gender and aortic stenosis were associated with a lower bias of QFR. Both measurement time and bias decreased in a non-linear fashion with increasing experience. Conclusions: Clinical and angiographic factors affect the bias of QFR versus FFR. QFR has a short learning curve with growing experience leading to shorter measurement time and less bias. Full article
(This article belongs to the Section Cardiology)
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19 pages, 3775 KiB  
Article
Enhanced M2 Polarization of Retinal Microglia in Streptozotocin-Induced Diabetic Mice upon Autoimmune Stimulation
by Yoshiaki Nishio, Hideaki Someya, Kozo Harimoto, Tomohito Sato, Masataka Ito and Masaru Takeuchi
Biomedicines 2025, 13(9), 2049; https://doi.org/10.3390/biomedicines13092049 - 22 Aug 2025
Abstract
Background: This study aimed to investigate the impact of the diabetic environment on the development of experimental autoimmune uveoretinitis (EAU) and the activation status of microglia in the eye. Methods: EAU was induced in wild-type (WT) and streptozotocin (STZ)-induced diabetic mice (STZ-EAU mice). [...] Read more.
Background: This study aimed to investigate the impact of the diabetic environment on the development of experimental autoimmune uveoretinitis (EAU) and the activation status of microglia in the eye. Methods: EAU was induced in wild-type (WT) and streptozotocin (STZ)-induced diabetic mice (STZ-EAU mice). Disease severity was assessed using funduscopy, optical coherence tomography (OCT), and histopathological analysis. The proportions of Th1, Th17, and regulatory T cells in the spleen were analyzed by flow cytometry. Retinal microglia were quantified using immunohistochemistry. To further characterize retinal cell populations and gene expression profiles, single-cell RNA sequencing (scRNA-seq) was performed. Results: STZ-EAU mice exhibited significant reductions in both the incidence and severity of EAU compared with WT-EAU mice. These were accompanied by a decreased proportion of Th1 cells, which are crucial for EAU pathogenesis, in the spleens of STZ-EAU mice. Retinal microglial accumulation was markedly reduced in STZ-EAU mice compared with WT-EAU mice. scRNA-seq analysis revealed a significant change in the microglial phenotype in STZ-EAU mice, characterized by decreased expression of MHC class I/II and the suppression of antigen presentation signaling pathways. Activated microglia in STZ-EAU mice showed reduced gene expression of M1 markers (CD68, CD74, and IL1B) and increased gene expression of M2 markers (MSR1, CD163, and MRC1), suggesting a shift toward an anti-inflammatory M2 phenotype. Conclusions: EAU is suppressed in STZ-induced diabetic mice, likely due to alterations in microglial polarization toward an M2 phenotype. These results suggest a decrease in T cell responses to pathogens in a diabetic environment, which could be one of the underlying factors for the increased susceptibility to infection in diabetic patients. Inhibiting the M2 polarization of microglia may reduce the susceptibility to infection in patients with diabetes. Full article
(This article belongs to the Special Issue State-of-the-Art Eye Disease Research and Treatment in Japan)
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12 pages, 366 KiB  
Article
Exceptionally High Cystic Fibrosis-Related Morbidity and Mortality in Infants and Young Children in India: The Need for Newborn Screening and CF-Specific Capacity Building
by Priyanka Medhi, Grace R. Paul, Madhan Kumar, Grace Rebekah, Philip M. Farrell, Jolly Chandran, Rekha Aaron, Aaron Chapla and Sneha D. Varkki
Int. J. Neonatal Screen. 2025, 11(3), 67; https://doi.org/10.3390/ijns11030067 - 22 Aug 2025
Abstract
Early diagnosis of cystic fibrosis (CF) through newborn screening (NBS) improves clinical outcomes, but in countries like India, delayed diagnosis increases morbidity, mortality, and likely underestimates infant deaths from CF. We performed a retrospective study at a single center in south India from [...] Read more.
Early diagnosis of cystic fibrosis (CF) through newborn screening (NBS) improves clinical outcomes, but in countries like India, delayed diagnosis increases morbidity, mortality, and likely underestimates infant deaths from CF. We performed a retrospective study at a single center in south India from 2017 to 2025 reviewing children diagnosed with CF before one year of age. Patient demographic, clinical, and genetic data were analyzed to characterize early clinical features and identify factors linked to mortality. Of 56 infants diagnosed with CF, 59% survived (median current age 55 months) while 41% died (median age of death 5 months). Key clinical indicators included sibling death with CF-like symptoms, rapid weight loss, and persistent respiratory or nutritional complications. Mortality risk under one year was significantly linked to hypoalbuminemia (OR 9.7), severe malnutrition (OR 4.4), severe anemia (hemoglobin < 7 g/dL) requiring blood transfusions (OR 3.0), and peripheral edema (OR 4.2). A triad of anemia, hypoalbuminemia, and edema was found to strongly predict death (OR 4.2). Integrating clinical checklists of these manifestations into primary healthcare may improve prompt referrals for earlier diagnosis and treatment. Continued education and advocacy for NBS are essential to reduce potentially preventable CF-related deaths in young children. Full article
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