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19 pages, 684 KiB  
Article
Does the Timing of Response Impact the Outcome of Relapsed/Refractory Acute Myeloid Leukemia Treated with Venetoclax in Combination with Hypomethylating Agents? A Proof of Concept from a Monocentric Observational Study
by Ermelinda Longo, Fanny Erika Palumbo, Andrea Duminuco, Laura Longo, Daniela Cristina Vitale, Serena Brancati, Cinzia Maugeri, Marina Silvia Parisi, Giuseppe Alberto Palumbo, Giovanni Luca Romano, Filippo Drago, Francesco Di Raimondo, Lucia Gozzo and Calogero Vetro
J. Clin. Med. 2025, 14(15), 5586; https://doi.org/10.3390/jcm14155586 (registering DOI) - 7 Aug 2025
Abstract
Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing [...] Read more.
Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article
(This article belongs to the Section Hematology)
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11 pages, 365 KiB  
Review
Precision Oncology in Hodgkin’s Lymphoma: Immunotherapy and Emerging Therapeutic Frontiers
by Adit Singhal, David Mueller, Benjamin Ascherman, Pratik Shah, Wint Yan Aung, Edward Zhou and Maria J. Nieto
Lymphatics 2025, 3(3), 24; https://doi.org/10.3390/lymphatics3030024 - 6 Aug 2025
Abstract
Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined [...] Read more.
Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article
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15 pages, 357 KiB  
Article
Apalutamide Monotherapy in Metastatic Hormone-Sensitive Prostate Cancer: A Viable Alternative to First-Generation Anti-Androgen Agents to Avoid the Flare Phenomenon and an Effective Treatment for Achieving Early PSA Response
by Gaetano Facchini, Andrea D’Arienzo, Antonella Nicastro, Fabiano Flauto, Michela Izzo, Liliana Montella, Filippo Riccardo, Giovanni Maria Fusco, Francesco Trama, Giovanni Di Lauro, Giuseppe Di Costanzo, Anna Giacoma Tucci, Francesca Iasiello, Lorena Di Lorenzo, Salvatore Maddaluno, Carmela Liguori, Rita Assante di Cupillo, Paola Coppola, Angela Minissale, Maria Teresa Di Nardo, Luigi Formisano, Erika Martinelli, Giuliana Ciappina, Salvatore Pisconti, Massimiliano Berretta and Chiara Barracoadd Show full author list remove Hide full author list
Cancers 2025, 17(15), 2573; https://doi.org/10.3390/cancers17152573 - 5 Aug 2025
Viewed by 25
Abstract
Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor [...] Read more.
Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies for Prostate Cancer)
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13 pages, 2174 KiB  
Article
Characterization of QuantiFERON-TB-Plus Results in Patients with Tuberculosis Infection and Multiple Sclerosis
by Elisa Petruccioli, Luca Prosperini, Serena Ruggieri, Valentina Vanini, Andrea Salmi, Gilda Cuzzi, Simonetta Galgani, Shalom Haggiag, Carla Tortorella, Gabriella Parisi, Alfio D’Agostino, Gina Gualano, Fabrizio Palmieri, Claudio Gasperini and Delia Goletti
Neurol. Int. 2025, 17(8), 119; https://doi.org/10.3390/neurolint17080119 - 2 Aug 2025
Viewed by 68
Abstract
Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. [...] Read more.
Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article
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24 pages, 2128 KiB  
Article
Central Insulin-Like Growth Factor-1-Induced Anxiolytic and Antidepressant Effects in a Rat Model of Sporadic Alzheimer’s Disease Are Associated with the Peripheral Suppression of Inflammation
by Joanna Dunacka, Beata Grembecka and Danuta Wrona
Cells 2025, 14(15), 1189; https://doi.org/10.3390/cells14151189 - 1 Aug 2025
Viewed by 294
Abstract
(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with [...] Read more.
(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with IGF-1 in a rat model of streptozotocin (STZ)-induced neuroinflammation can prevent the emergence of anhedonia and anxiety-like behavior by impacting the peripheral inflammatory responses. (2) Male Wistar rats were subjected to double ICVSTZ (total dose: 3 mg/kg) and ICVIGF-1 injections (total dose: 2 µg). We analyzed the level of anhedonia (sucrose preference), anxiety (elevated plus maze), peripheral inflammation (hematological and cytometric measurement of leukocyte populations, interleukin (IL)-6), and corticosterone concentration at 7 (very early stage, VES), 45 (early stage, ES), and 90 days after STZ injections (late stage, LS). (3) We found that ICVIGF-1 administration reduces behavioral symptoms: anhedonia (ES and LS) and anxiety (VES, ES), and peripheral inflammation: number of leukocytes, lymphocytes, T lymphocytes, monocytes, granulocytes, IL-6, and corticosterone concentration (LS) in the rat model of sAD. (4) The obtained results demonstrate beneficial effects of central IGF-1 administration on neuropsychiatric symptoms and peripheral immune system activation during disease progression in the rat model of sAD. Full article
(This article belongs to the Section Cells of the Nervous System)
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45 pages, 770 KiB  
Review
Neural Correlates of Burnout Syndrome Based on Electroencephalography (EEG)—A Mechanistic Review and Discussion of Burnout Syndrome Cognitive Bias Theory
by James Chmiel and Agnieszka Malinowska
J. Clin. Med. 2025, 14(15), 5357; https://doi.org/10.3390/jcm14155357 - 29 Jul 2025
Viewed by 364
Abstract
Introduction: Burnout syndrome, long described as an “occupational phenomenon”, now affects 15–20% of the general workforce and more than 50% of clinicians, teachers, social-care staff and first responders. Its precise nosological standing remains disputed. We conducted a mechanistic review of electroencephalography (EEG) studies [...] Read more.
Introduction: Burnout syndrome, long described as an “occupational phenomenon”, now affects 15–20% of the general workforce and more than 50% of clinicians, teachers, social-care staff and first responders. Its precise nosological standing remains disputed. We conducted a mechanistic review of electroencephalography (EEG) studies to determine whether burnout is accompanied by reproducible brain-function alterations that justify disease-level classification. Methods: Following PRISMA-adapted guidelines, two independent reviewers searched PubMed/MEDLINE, Scopus, Google Scholar, Cochrane Library and reference lists (January 1980–May 2025) using combinations of “burnout,” “EEG”, “electroencephalography” and “event-related potential.” Only English-language clinical investigations were eligible. Eighteen studies (n = 2194 participants) met the inclusion criteria. Data were synthesised across three domains: resting-state spectra/connectivity, event-related potentials (ERPs) and longitudinal change. Results: Resting EEG consistently showed (i) a 0.4–0.6 Hz slowing of individual-alpha frequency, (ii) 20–35% global alpha-power reduction and (iii) fragmentation of high-alpha (11–13 Hz) fronto-parietal coherence, with stage- and sex-dependent modulation. ERP paradigms revealed a distinctive “alarm-heavy/evaluation-poor” profile; enlarged N2 and ERN components signalled hyper-reactive conflict and error detection, whereas P3b, Pe, reward-P3 and late CNV amplitudes were attenuated by 25–50%, indicating depleted evaluative and preparatory resources. Feedback processing showed intact or heightened FRN but blunted FRP, and affective tasks demonstrated threat-biassed P3a latency shifts alongside dampened VPP/EPN to positive cues. These alterations persisted in longitudinal cohorts yet normalised after recovery, supporting trait-plus-state dynamics. The electrophysiological fingerprint differed from major depression (no frontal-alpha asymmetry, opposite connectivity pattern). Conclusions: Across paradigms, burnout exhibits a coherent neurophysiological signature comparable in magnitude to established psychiatric disorders, refuting its current classification as a non-disease. Objective EEG markers can complement symptom scales for earlier diagnosis, treatment monitoring and public-health surveillance. Recognising burnout as a clinical disorder—and funding prevention and care accordingly—is medically justified and economically imperative. Full article
(This article belongs to the Special Issue Innovations in Neurorehabilitation)
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16 pages, 1724 KiB  
Article
Apitherapy with Royal Jelly and Green Propolis EPP-AF® Improves Cardiovascular Risk Markers in Patients Undergoing Hemodialysis
by Julie Ann Kemp, Marianna Mendonça, Paloma Chrispim, Marcia Ribeiro, Isadora Britto, Karen S. Coutinho-Wolino, Marcelo Ribeiro-Alves, Lia S. Nakao, Fernanda Kussi, Eduardo B. Coelho, Andresa A. Berretta, Denise Mafra and Ludmila Cardozo
Toxins 2025, 17(8), 369; https://doi.org/10.3390/toxins17080369 - 26 Jul 2025
Viewed by 444
Abstract
Background: Reducing cardiovascular risk markers is an essential target in chronic kidney disease (CKD). Thus, this study aimed to evaluate the effect of royal jelly plus green propolis supplementation on cardiovascular disease (CVD) risk factors in patients with CKD undergoing hemodialysis (HD). Methods: [...] Read more.
Background: Reducing cardiovascular risk markers is an essential target in chronic kidney disease (CKD). Thus, this study aimed to evaluate the effect of royal jelly plus green propolis supplementation on cardiovascular disease (CVD) risk factors in patients with CKD undergoing hemodialysis (HD). Methods: This randomized, double-blind, placebo-controlled trial involved HD patients allocated to receive either royal jelly plus green propolis EPP-AF® (100 mg RJ + 500 mg GP) or placebo capsules daily for 2 months. Before and after the intervention period, the biochemical parameters, inflammatory cytokines, and uremic toxins were measured. Results: A total of 38 HD patients completed the 2-month supplementation study, with 19 patients in each group. After 2 months, the treated group showed a significant reduction in plasma levels of IL-6 (0.78 to 0.63 pg/mL, p = 0.008) and total cholesterol (138.60 to 111.85 mg/dL, p = 0.03), whereas no changes were observed in the placebo group. Uremic toxins did not change after intervention. Conclusion: Apitherapy with RJ + GP EPP-AF® extract significantly reduced plasma IL-6 and total cholesterol in HD patients. This supplementation shows promise as a non-pharmacological strategy to reduce cardiovascular risk markers in this population. Full article
(This article belongs to the Special Issue The Role of Uremic Toxins in Comorbidities of Chronic Kidney Disease)
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17 pages, 440 KiB  
Review
Diagnosis and Management of Upper Tract Urothelial Carcinoma: A Review
by Domenique Escobar, Christopher Wang, Noah Suboc, Anishka D’Souza and Varsha Tulpule
Cancers 2025, 17(15), 2467; https://doi.org/10.3390/cancers17152467 - 25 Jul 2025
Viewed by 500
Abstract
Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable [...] Read more.
Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable prognosis compared to urothelial carcinoma of the bladder. Current treatment strategies for UTUC are largely derived from bladder cancer studies, underscoring the need for UTUC-directed research. This review provides a comprehensive overview of UTUC, encompassing diagnostic approaches, systemic and intraluminal therapies, surgical management, and future directions. Methods: A narrative review was conducted synthesizing evidence from guideline-based recommendations, retrospective and prospective clinical studies, and ongoing trials focused on UTUC. Results: Neoadjuvant cisplatin-based chemotherapy is increasingly preferred in UTUC due to the risk of postoperative renal impairment that may preclude adjuvant cisplatin use. Surgical management includes kidney-sparing approaches and radical nephroureterectomy (RNU), with selection guided by tumor risk and patient comorbidities. While endoscopic management (EM) preserves renal function, it carries a higher recurrence and surveillance burden; RNU remains standard for high-risk cases. Systemic therapy for advanced and metastatic UTUC mirrors that of bladder urothelial carcinoma. Enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy over chemotherapy in the EV-302 trial, with improved response rate, progression-free survival, and overall survival across subgroups, including UTUC. For patients ineligible for EV, the CheckMate-901 study supported first-line chemoimmunotherapy with gemcitabine, cisplatin, and nivolumab. Further systemic therapy strategies include maintenance avelumab post-chemotherapy (JAVELIN Bladder 100), targeted therapies such as erdafitinib (THOR trial), and trastuzumab deruxtecan (DESTINY-PanTumor02) in FGFR2/3-altered and HER2-positive disease, respectively. Conclusions: Historically, the therapeutic landscape of UTUC has been extrapolated from bladder cancer; however, ongoing research specific to UTUC is deriving more precise regimens involving the use of immune checkpoint inhibitors, antibody–drug conjugates, and biomarker-driven therapies. Full article
(This article belongs to the Special Issue Upper Tract Urothelial Carcinoma: Current Knowledge and Perspectives)
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10 pages, 212 KiB  
Article
Heart Rate Variability Frequency-Domain Analysis Across Glaucoma Subtypes
by Misaki Ukisu, Yuto Yoshida, Hinako Takei, Keigo Takagi and Masaki Tanito
Biomedicines 2025, 13(8), 1805; https://doi.org/10.3390/biomedicines13081805 - 23 Jul 2025
Viewed by 320
Abstract
Background/Objectives: Heart rate variability (HRV) is a marker of autonomic nervous system function, based on fluctuations in heartbeat intervals. Although several studies have investigated the association between frequency-domain HRV parameters and glaucoma, evidence based on large sample sizes remains limited. Therefore, the [...] Read more.
Background/Objectives: Heart rate variability (HRV) is a marker of autonomic nervous system function, based on fluctuations in heartbeat intervals. Although several studies have investigated the association between frequency-domain HRV parameters and glaucoma, evidence based on large sample sizes remains limited. Therefore, the present study aimed to examine the relationship between frequency-domain HRV parameters and glaucoma subtypes, including primary open-angle glaucoma (PG) and exfoliation glaucoma (EG), using a larger sample size. Methods: Participants with primary open-angle glaucoma (PG), exfoliation glaucoma (EG), or no ocular disease other than cataract (controls) were recruited at Shimane University between June 2023 and July 2024. Frequency-domain HRV parameters (total power [TP], very-low-frequency [VLF], low-frequency [LF], high-frequency [HF], and LF/HF) were measured using a sphygmograph (TAS9 Pulse Analyzer Plus View). Group comparisons were conducted using unpaired t-tests, Fisher’s exact tests, and Tukey’s HSD test. Multivariate analyses were performed to identify factors associated with each HRV parameter. Results: A total of 809 participants were analyzed, including 522 with PG, 191 with EG, and 96 controls. The EG group showed significantly lower values across all frequency-domain HRV parameters compared to the PG group, and significantly lower LnLF values than the control group (p = 0.012). Multivariate analyses revealed that no significant associations were found between HRV measures and the presence of glaucoma or pseudoexfoliation material (PEM) deposition. Older age was significantly associated with lower values across all HRV parameters. Conclusions: In elderly glaucoma patients, age-related alterations in frequency-domain HRV parameters have been observed. Full article
(This article belongs to the Special Issue Glaucoma: New Diagnostic and Therapeutic Approaches, 2nd Edition)
12 pages, 255 KiB  
Article
Anti-HMGCR-Antibody-Positive Statin-Induced Myositis: A Pilot Case Series on Treatment with Bempedoic Acid and Immunosuppressive Therapy
by Maurizio Benucci, Riccardo Terenzi, Francesca Li Gobbi, Emanuele Antonio Maria Cassarà, Tommaso Picchioni, Edda Russo, Barbara Lari, Mariangela Manfredi and Maria Infantino
Antibodies 2025, 14(3), 63; https://doi.org/10.3390/antib14030063 - 23 Jul 2025
Viewed by 328
Abstract
Background/Objectives: Immune-mediated necrotizing myopathy (IMNM) is a severe inflammatory myopathy marked by proximal muscle weakness, elevated creatine kinase (CK), and the presence of anti-HMGCR antibodies. Statin exposure is a recognized trigger for anti-HMGCR-positive IMNM, which may persist despite statin withdrawal. This pilot case [...] Read more.
Background/Objectives: Immune-mediated necrotizing myopathy (IMNM) is a severe inflammatory myopathy marked by proximal muscle weakness, elevated creatine kinase (CK), and the presence of anti-HMGCR antibodies. Statin exposure is a recognized trigger for anti-HMGCR-positive IMNM, which may persist despite statin withdrawal. This pilot case series explores, for the first time, the use of bempedoic acid—a liver-specific lipid-lowering agent with minimal muscle toxicity—as an alternative to statins in these patients. Methods: We report 10 anti-HMGCR-antibody-positive IMNM patients (6 females, 4 males) previously on statins for primary prevention (8 on atorvastatin, 2 on simvastatin) without prior cardiovascular events. Statins were discontinued at myositis onset. All patients received prednisone and immunosuppressants (methotrexate in 7, mycophenolate in 3), plus bempedoic acid. Anti-HMGCR antibodies were measured using a chemiluminescence method. Results: Their mean anti-HMGCR antibody levels decreased significantly from 390.93 ± 275.22 to 220.89 ± 113.37 CU/L (p = 0.027) after 6 months of treatment. Their CK levels dropped from 1278.9 ± 769.39 to 315.1 ± 157.72 IU/L (p = 0.001), and aldolase dropped from 11.63 ± 2.18 to 6.61 ± 1.22 U/L (p = 0.0001). The mean LDL-C value was 96.1 ± 8.16 mg/dL. No disease recurrence was observed. Autoimmune panels were negative for other myositis-associated and/or -specific antibodies. Conclusions: Bempedoic acid appears to be a safe, effective, and cost-efficient lipid-lowering alternative in statin-intolerant IMNM patients. Larger studies are warranted to confirm its efficacy across different subgroups and to optimize dyslipidemia management in this setting. Full article
(This article belongs to the Section Antibody-Based Diagnostics)
10 pages, 615 KiB  
Article
The Impact of DDR Gene Mutations on the Efficacy of Etoposide Plus Cisplatin in Grade 3 Metastatic Gastroenteropancreatic (GEP)—Neuroendocrine Carcinoma (NEC)
by Ji Eun Shin, Minsuk Kwon, Sung Hee Lim, Jung Yong Hong and Seung Tae Kim
Cancers 2025, 17(15), 2436; https://doi.org/10.3390/cancers17152436 - 23 Jul 2025
Viewed by 218
Abstract
Purpose: Neuroendocrine carcinomas (NECs) are aggressive tumors treated with cisplatin-based chemotherapy, though responses vary. As DNA damage response (DDR) pathways influence cisplatin sensitivity, this single-center retrospective study evaluates the efficacy of first-line cisplatin in recurrent or metastatic NEC based on DDR mutation status. [...] Read more.
Purpose: Neuroendocrine carcinomas (NECs) are aggressive tumors treated with cisplatin-based chemotherapy, though responses vary. As DNA damage response (DDR) pathways influence cisplatin sensitivity, this single-center retrospective study evaluates the efficacy of first-line cisplatin in recurrent or metastatic NEC based on DDR mutation status. Materials and Methods: This study analyzed patients with grade 3 recurrent or metastatic NEC treated with first-line etoposide plus cisplatin at Samsung Medical Center between January 2019 and September 2023. All patients underwent next-generation sequencing to determine DDR mutation status, defined by pathogenic alterations in major DNA repair pathways. Clinical outcomes were assessed per RECIST v1.1. Survival analyses were conducted using Kaplan–Meier methods and Cox regression models, with significance set at p ≤ 0.05. Results: A total of 40 patients with NEC were included in this study. There were 16 patients with DDR wild-type (WT) and 24 patients with DDR mutant type (MT). The most common primary tumor sites were the pancreas (25.0%), stomach (20.0%), and gallbladder/duct (12.5%). Among 40 patients, those with DDR mutations (n = 24) showed significantly higher objective response (58.3% vs. 12.5%) and disease control rates (91.7% vs. 50.0%) compared to patients with DDR WT (n = 16). The median progression-free survival (PFS) showed the favorable trend in the DDR mutant group (8.0 vs. 4.3 months; p = 0.15), with similar trends observed across homologous recombination repair (HRR), Fanconi anemia (FA), and mismatch repair (MMR) subgroups. Conclusions: This study revealed that patients with DDR mutations had significantly higher response to first-line etoposide–cisplatin, suggesting DDR mutation status as a potential predictive marker to guide treatment and improve outcomes in recurrent or metastatic NEC. Full article
(This article belongs to the Section Cancer Metastasis)
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11 pages, 402 KiB  
Article
Antibiotic Effect on Clinical Response and Remission in Pediatric Inflammatory Bowel Disease
by Caeley Dye, Caroline M. Sierra, Khaled Bahjri, Mallory Cohen and Gautam Nagendra
Pediatr. Rep. 2025, 17(4), 77; https://doi.org/10.3390/pediatric17040077 - 21 Jul 2025
Viewed by 281
Abstract
Objective: Gut dysbiosis has been implicated in the pathology of inflammatory bowel disease (IBD). There is some evidence to suggest that the use of antibiotic treatment can incite an early clinical response or remission when used in conjunction with standard-of-care (SOC) therapy [...] Read more.
Objective: Gut dysbiosis has been implicated in the pathology of inflammatory bowel disease (IBD). There is some evidence to suggest that the use of antibiotic treatment can incite an early clinical response or remission when used in conjunction with standard-of-care (SOC) therapy to treat IBD-related flares. Furthermore, antibiotics have been historically investigated for use as a bridge when initiating biologic therapy while waiting for peak biologic treatment effect to occur. This study investigated and compared the time to clinical response when treated with combination antibiotics, metronidazole monotherapy, or SOC therapy in pediatric patients with an active IBD flare. Methods: This study was a retrospective, Institution Review Board-approved, single-centered cohort study which included patients who were less than 18 years of age with a confirmed diagnosis of IBD who received conventional treatment alone or with either combination antibiotic therapy or metronidazole monotherapy to treat an active IBD flare between March 2013 and January 2024. Patients were excluded if they received antibiotic therapy to treat an active infection, had positive stool cultures or enteric pathogen polymerase chain reaction panel, or had colonic disease limited to the rectum. Results: Fifty-nine patients were included and divided into metronidazole monotherapy (n = 18), SOC therapy (n = 20), and combination antibiotics (n = 21). The primary outcome of days to clinical response was not significantly different across all groups; however, patients who received combination antibiotics achieved the fastest time to clinical response (median (IRQ))—4 days (1, 65), compared to 7.5 days (1, 119) for the SOC group and 9 days (2, 217) for the metronidazole group. Secondary outcomes of achievement of clinical response, remission, or failure were determined to be non-significant between all groups. Conclusions: There is no significant difference in time to clinical response, attaining clinical response or remission, or treatment failure rate for patients treated with combination antibiotics, metronidazole monotherapy, or SOC. However, results of this study suggest that the use of combination antibiotics plus SOC may lead to a faster time to clinical response and remission compared to SOC therapy alone. Further studies are warranted to elucidate the role of antimicrobial therapy in management of pediatric IBD. Full article
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13 pages, 266 KiB  
Article
Influence of Virginia Market-Type Cultivar and Fungicide Regime on Leaf Spot Disease and Peanut Yield in North Carolina
by Ethan Foote, David Jordan, LeAnn Lux, Jeffrey Dunne and Adrienne Gorny
Agronomy 2025, 15(7), 1731; https://doi.org/10.3390/agronomy15071731 - 18 Jul 2025
Viewed by 285
Abstract
Determining the effectiveness of fungicide programs based on cultivar resistance to pathogens, especially late leaf spot (caused by Nothopassalora personata (Berk. & M.A. Curtis) [U. Braun, C. Nakash., Videira & Crous]) is important in establishing recommendations to peanut (Arachis hypogaea L.) farmers. [...] Read more.
Determining the effectiveness of fungicide programs based on cultivar resistance to pathogens, especially late leaf spot (caused by Nothopassalora personata (Berk. & M.A. Curtis) [U. Braun, C. Nakash., Videira & Crous]) is important in establishing recommendations to peanut (Arachis hypogaea L.) farmers. Research was conducted in North Carolina during 2021 and 2022 at three locations to compare the incidence of late leaf spot (e.g., visual estimates of percent of peanut leaflets with lesions), percentage of the peanut canopy defoliated caused by this disease, and yield of the peanut cultivars Bailey II, Emery, and Sullivan when exposed to five fungicide regimens including a non-treated control. Peanut yield was not affected by the interaction of cultivar × fungicide regimens. While differences in leaf spot incidence and canopy defoliation were noted for cultivars, these differences did not translate into differences in peanut yield. All fungicides regimens protected peanut yield from leaf spot disease regardless of the number of sprays during the cropping cycle (e.g., three, four, or five sprays). Peanut yield in the absence of fungicides was 4410 kg/ha compared with a range of 5000 to 5390 kg/ha when fungicides were applied. Peanut yield was greater when fungicides were applied four or five times compared with only three sprays or non-treated peanut. The regimen with five consecutive sprays of chlorothalonil alone for the first and final spray in the regimen and when this fungicide was applied with tebuconazole for the second, third, and fourth sprays was as effective as fungicide regimens including combinations of pydiflumetofen plus azoxystrobin plus benzovindiflupyr, mefentrifluconazole plus pyraclostrobin plus fluxapyroxad, bixafen plus flutriafol, and prothioconazole plus tebuconazole. Full article
(This article belongs to the Special Issue Environmentally Friendly Ways to Control Plant Disease)
11 pages, 263 KiB  
Article
Prevalence and Diagnostic Comparison of Helicobacter pylori and Non-Helicobacter pylori Helicobacter Infections in Patients Undergoing Upper Gastrointestinal Endoscopy with Gastric Biopsy in Algarve, Portugal
by Francisco Cortez Nunes, Teresa Letra Mateus, Catarina Aguieiras, Ricardo Louro, Bruno Peixe, Mauro Calhindro, Patrícia Queirós and Pedro Castelo-Branco
Microorganisms 2025, 13(7), 1684; https://doi.org/10.3390/microorganisms13071684 - 17 Jul 2025
Viewed by 1094
Abstract
H. pylori infects over half of the global population and is associated with various gastric and extra-gastric diseases. Other species, such as zoonotic non-Helicobacter pylori Helicobacters (NHPHs), have shown similar associations with gastritis and MALT lymphoma and H. pylori-negative cases with [...] Read more.
H. pylori infects over half of the global population and is associated with various gastric and extra-gastric diseases. Other species, such as zoonotic non-Helicobacter pylori Helicobacters (NHPHs), have shown similar associations with gastritis and MALT lymphoma and H. pylori-negative cases with gastric disease have been identified, including gastric MALT lymphoma, chronic gastritis, and gastroduodenal ulcers. Accurate identification of these species is of great relevance but remains challenging using conventional diagnostic methods. This cross-sectional study aimed to determine the prevalence of H. pylori and NHPH infections, comparing standard histological protocols with molecular techniques. Between December 2024 and February 2025, 54 adult patients undergoing upper gastrointestinal endoscopy (UGE) with gastric biopsy in three hospitals in Algarve, Portugal were recruited. Endoscopic assessment was performed, and gastric biopsies were collected for histological and molecular analysis. DNA was extracted from antral biopsies and analyzed by conventional PCR to detect H. pylori and NHPH. H. pylori diagnostic techniques were compared, descriptive plus statistical analysis was performed, and p-values < 0.05 were considered to be statistically significant. Fifty-four patients were included in the study, with 51.9% of them presenting symptoms. Endoscopic gastritis was observed in 66.7% of patients, while histological gastritis was present in 88.9%, with statistically significant differences between the two diagnostic techniques (p = 0.004). Helicobacter spp. were identified in 44.4% (24/54) of the patients. H. pylori was detected in 42.6% of the patients by Modified Giemsa stain and in 33.3% by PCR. H. bizzozeronii was found in 35.9% of the patients, with 22.2% showing mixed infections. This study reveals a significant prevalence of Helicobacter spp. in patients from the Algarve region, with both H. pylori and zoonotic H. bizzozeronii detected. This is the first report of H. bizzozeronii DNA detection in gastric biopsies via PCR from patients undergoing UGE in Portugal, highlighting the need to consider NHPH in clinical diagnosis. It is important to include molecular methods in routine diagnostics and the need for broader studies to assess regional and national trends in Helicobacter infections besides H. pylori. Full article
(This article belongs to the Section Public Health Microbiology)
9 pages, 290 KiB  
Article
Primary and Secondary Prophylaxis of Gastrointestinal Bleeding in Children with Portal Hypertension: A Multicenter National Study by SIGENP
by Naire Sansotta, Paola De Angelis, Daniele Alberti, Fabiola Di Dato, Serena Arrigo, Matteo Bramuzzo, Benedetta Calcaterra, Mara Cananzi, Maurizio Cheli, Andrea Chiaro, Francesco Cirillo, Mara Colusso, Grazia Di Leo, Simona Faraci, Paola Gaio, Giuseppe Indolfi, Silvia Iuliano, Daniela Liccardo, Antonio Marseglia, Matteo Motta, Federica Nuti, Filippo Parolini, Sara Renzo, Francesca Sbravati, Marco Sciveres, Claudia Mandato and Angelo Di Giorgioadd Show full author list remove Hide full author list
Children 2025, 12(7), 940; https://doi.org/10.3390/children12070940 - 17 Jul 2025
Viewed by 280
Abstract
Background/Objectives: Portal hypertension (PH) is a common complication in children with chronic liver diseases. Primary and secondary prophylaxis of variceal bleeding in these patients remains controversial. Our study aims to evaluate the management of gastrointestinal (GI) varices in children with PH in [...] Read more.
Background/Objectives: Portal hypertension (PH) is a common complication in children with chronic liver diseases. Primary and secondary prophylaxis of variceal bleeding in these patients remains controversial. Our study aims to evaluate the management of gastrointestinal (GI) varices in children with PH in Italy. Methods: A questionnaire was sent to 21 major pediatric hepatology centers. It included 34 questions referring to the medical, endoscopic, radiological, and surgical management of GI varices. Results: Out of 21 centers, 16 returned a completed questionnaire (survey response rate 76%) with a high level of completeness. A total of 1206 children with PH were under follow-up. Splenomegaly associated with hypersplenism was the main indication for endoscopic surveillance in all centers (100%). Primary prophylaxis was performed with endoscopy plus non-selective beta-blockers (NSBBs) in 50%, endoscopy alone in 38%, and NSBBs alone in 12%. All centers managed acute variceal bleeding with endoscopy within 24 h, acid suppression, and octreotide infusion. Secondary prophylaxis of variceal bleeding was conducted using endoscopy (100%) and NSBBs (87%). Transjugular intrahepatic portosystemic shunt (TIPS) was considered a good option when endoscopic treatment failed in 94% of centers. Conclusions: In Italy, there is broad consensus among centers regarding the management of gastrointestinal varices in children with portal hypertension. All participating centers endorsed the use of endoscopic screening for children presenting with clinical signs of portal hypertension. Nonetheless, further research is essential to establish evidence-based guidelines and to improve overall quality of care. Full article
(This article belongs to the Section Pediatric Gastroenterology and Nutrition)
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