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Search Results (1,328)

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Keywords = treatment response criteria

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23 pages, 406 KiB  
Systematic Review
Advances in Bidirectional Therapy for Peritoneal Metastases: A Systematic Review of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Combined with Systemic Chemotherapy
by Manuela Robella, Marco Vitturini, Andrea Di Giorgio, Matteo Aulicino, Martin Hubner, Emanuele Koumantakis, Felice Borghi, Paolo Catania, Armando Cinquegrana and Paola Berchialla
Cancers 2025, 17(15), 2580; https://doi.org/10.3390/cancers17152580 - 6 Aug 2025
Abstract
Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic [...] Read more.
Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article
(This article belongs to the Section Cancer Therapy)
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28 pages, 1577 KiB  
Article
Prevalence of Anti-Anisakis simplex Antibodies in a Cohort of Patients with Inflammatory Bowel Disease in Norway
by María P. de la Hoz-Martín, Juan González-Fernández, Juan Carlos Andreu-Ballester, Marte L. Hoivik, Petr Ricanek, Torunn Bruland, Arne K. Sandvik, Carmen Cuéllar and Ignacio Catalán-Serra
Pathogens 2025, 14(8), 769; https://doi.org/10.3390/pathogens14080769 - 4 Aug 2025
Viewed by 23
Abstract
This study assessed the seroprevalence of anti-Anisakis simplex antibodies in Norwegian patients with inflammatory bowel disease (IBD), specifically ulcerative colitis (UC) and Crohn’s disease (CD), compared with healthy controls. Associations between anti-A. simplex antibody positivity and clinical or laboratory parameters in [...] Read more.
This study assessed the seroprevalence of anti-Anisakis simplex antibodies in Norwegian patients with inflammatory bowel disease (IBD), specifically ulcerative colitis (UC) and Crohn’s disease (CD), compared with healthy controls. Associations between anti-A. simplex antibody positivity and clinical or laboratory parameters in IBD were also explored. A total of 86 UC patients, 68 CD patients, and 41 healthy controls were prospectively enrolled from four Norwegian hospitals (2013–2022). Diagnosis and disease activity were established using standard clinical, endoscopic, and biomarker criteria. Serum samples were analyzed for total Ig, IgG, IgM, IgA, and IgE antibodies against A. simplex and Pseudoterranova decipiens using ELISA. Anti-A. simplex IgG seroprevalence was 4.9% in controls and 3.2% in IBD (3.5% UC, 2.9% CD). IgM seroprevalence was 0% in all groups. IgA seroprevalence was higher in IBD (16.2%) than controls (4.9%), with 14.0% in UC and 19.1% in CD. IgE seroprevalence was low across all groups. Smoking correlated with lower antibody levels and higher surgery rates. In UC, higher anti-A. simplex IgG and IgE levels were associated with milder disease and better prognosis. Anti-TNFα and azathioprine treatments were linked to higher anti-A. simplex IgA. Norwegian UC and CD patients had significantly higher anti-A. simplex total Ig and IgA seroprevalence than healthy controls, indicating increased exposure or immune response. Anti-A. simplex IgG and IgE may serve as markers of clinical activity in UC. Further research is warranted to clarify the clinical significance of these findings. Full article
(This article belongs to the Section Parasitic Pathogens)
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23 pages, 1139 KiB  
Article
A Critical Appraisal of Off-Label Use and Repurposing of Statins for Non-Cardiovascular Indications: A Systematic Mini-Update and Regulatory Analysis
by Anna Artner, Irem Diler, Balázs Hankó, Szilvia Sebők and Romána Zelkó
J. Clin. Med. 2025, 14(15), 5436; https://doi.org/10.3390/jcm14155436 - 1 Aug 2025
Viewed by 242
Abstract
Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to [...] Read more.
Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. Full article
(This article belongs to the Section Pharmacology)
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18 pages, 1404 KiB  
Article
Comparative Analysis of the Long-Term Real-World Efficacy of Interleukin-17 Inhibitors in a Cohort of Patients with Moderate-to-Severe Psoriasis Treated in Poland
by Wiktor Kruczek, Aleksandra Frątczak, Iga Litwińska-Inglot, Karina Polak, Zuzanna Pawlus, Paulina Rutecka, Beata Bergler-Czop and Bartosz Miziołek
J. Clin. Med. 2025, 14(15), 5421; https://doi.org/10.3390/jcm14155421 - 1 Aug 2025
Viewed by 142
Abstract
Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, [...] Read more.
Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article
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11 pages, 1914 KiB  
Case Report
Case Report of Nephrogenic Diabetes Insipidus with a Novel Mutation in the AQP2 Gene
by Alejandro Padilla-Guzmán, Vanessa Amparo Ochoa-Jiménez, Jessica María Forero-Delgadillo, Karen Apraez-Murillo, Harry Pachajoa and Jaime M. Restrepo
Int. J. Mol. Sci. 2025, 26(15), 7415; https://doi.org/10.3390/ijms26157415 - 1 Aug 2025
Viewed by 133
Abstract
Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the [...] Read more.
Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article
(This article belongs to the Special Issue A Molecular Perspective on the Genetics of Kidney Diseases)
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35 pages, 887 KiB  
Review
Prognostic Factors in Colorectal Liver Metastases: An Exhaustive Review of the Literature and Future Prospectives
by Maria Conticchio, Emilie Uldry, Martin Hübner, Antonia Digklia, Montserrat Fraga, Christine Sempoux, Jean Louis Raisaro and David Fuks
Cancers 2025, 17(15), 2539; https://doi.org/10.3390/cancers17152539 - 31 Jul 2025
Viewed by 168
Abstract
Background: Colorectal liver metastasis (CRLM) represents a major clinical challenge in oncology, affecting 25–50% of colorectal cancer patients and significantly impacting survival. While multimodal therapies—including surgical resection, systemic chemotherapy, and local ablative techniques—have improved outcomes, prognosis remains heterogeneous due to variations in [...] Read more.
Background: Colorectal liver metastasis (CRLM) represents a major clinical challenge in oncology, affecting 25–50% of colorectal cancer patients and significantly impacting survival. While multimodal therapies—including surgical resection, systemic chemotherapy, and local ablative techniques—have improved outcomes, prognosis remains heterogeneous due to variations in tumor biology, patient factors, and institutional practices. Methods: This review synthesizes current evidence on prognostic factors influencing CRLM management, encompassing clinical (e.g., tumor burden, anatomic distribution, timing of metastases), biological (e.g., CEA levels, inflammatory markers), and molecular (e.g., RAS/BRAF mutations, MSI status, HER2 alterations) determinants. Results: Key findings highlight the critical role of molecular profiling in guiding therapeutic decisions, with RAS/BRAF mutations predicting resistance to anti-EGFR therapies and MSI-H status indicating potential responsiveness to immunotherapy. Emerging tools like circulating tumor DNA (ctDNA) and radiomics offer promise for dynamic risk stratification and early recurrence detection, while the gut microbiome is increasingly recognized as a modulator of treatment response. Conclusions: Despite advancements, challenges persist in standardizing resectability criteria and integrating multidisciplinary approaches. Current guidelines (NCCN, ESMO, ASCO) emphasize personalized strategies but lack granularity in terms of incorporating novel biomarkers. This exhaustive review underscores the imperative for the development of a unified, biomarker-integrated framework to refine CRLM management and improve long-term outcomes. Full article
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14 pages, 619 KiB  
Article
Validation of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)-Related Pediatric Treatment Evaluation Checklist (PTEC)
by Andrey Vyshedskiy, Anna Conkey, Kelly DeWeese, Frank Benno Junghanns, James B. Adams and Richard E. Frye
Pediatr. Rep. 2025, 17(4), 81; https://doi.org/10.3390/pediatric17040081 - 28 Jul 2025
Viewed by 314
Abstract
Background/Objectives: The objective of this study was to validate a new parent-reported scale for tracking Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is a condition characterized by a sudden and severe onset of neuropsychiatric symptoms. To meet diagnostic criteria, an individual must present with [...] Read more.
Background/Objectives: The objective of this study was to validate a new parent-reported scale for tracking Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is a condition characterized by a sudden and severe onset of neuropsychiatric symptoms. To meet diagnostic criteria, an individual must present with either obsessive–compulsive disorder (OCD) or severely restricted food intake, accompanied by at least two additional cognitive, behavioral, or emotional symptoms. These may include anxiety, emotional instability, depression, irritability, aggression, oppositional behaviors, developmental or behavioral regression, a decline in academic skills such as handwriting or math, sensory abnormalities, frequent urination, and enuresis. The onset of symptoms is usually triggered by an infection or an abnormal immune/inflammatory response. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a subtype of PANS specifically linked to strep infections. Methods: We developed a 101-item PANS/PANDAS and Related Inflammatory Brain Disorders Treatment Evaluation Checklist (PTEC) designed to assess changes to a patient’s symptoms over time along 10 subscales: Behavior/Mood, OCD, Anxiety, Food intake, Tics, Cognitive/Developmental, Sensory, Other, Sleep, and Health. The psychometric quality of PTEC was tested with 225 participants. Results: The internal reliability of the PTEC was excellent (Cronbach’s alpha = 0.96). PTEC exhibited adequate test–retest reliability (r = 0.6) and excellent construct validity, supported by a strong correlation with the Health subscale of the Autism Treatment Evaluation Checklist (r = 0.8). Conclusions: We hope that PTEC will assist parents and clinicians in the monitoring and treatment of PANS. The PTEC questionnaire is freely available at neuroimmune.org/PTEC. Full article
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14 pages, 690 KiB  
Article
Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15)
by Yvonne Efebera, Vera Suman, Shira Dinner, Taylor O’Donnell, Ashley Rosko, John Mckay, Peter Barth, Patrick Hagen, Saad Usmani, Paul Richardson and Jacob Laubach
Cancers 2025, 17(15), 2433; https://doi.org/10.3390/cancers17152433 - 23 Jul 2025
Viewed by 279
Abstract
Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the [...] Read more.
Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article
(This article belongs to the Special Issue Multiple Myeloma: Diagnosis and Therapy)
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34 pages, 2191 KiB  
Review
Applications of Functional Near-Infrared Spectroscopy (fNIRS) in Monitoring Treatment Response in Psychiatry: A Scoping Review
by Ciprian-Ionuț Bǎcilǎ, Gabriela Mariana Marcu, Bogdan Ioan Vintilă, Claudia Elena Anghel, Andrei Lomnasan, Monica Cornea and Andreea Maria Grama
J. Clin. Med. 2025, 14(15), 5197; https://doi.org/10.3390/jcm14155197 - 22 Jul 2025
Viewed by 300
Abstract
Background/Objective: Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique with growing relevance in psychiatry. Its ability to measure cortical hemodynamics positions it as a potential tool for monitoring neurofunctional changes related to treatment. However, the specific features and level of consistency [...] Read more.
Background/Objective: Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique with growing relevance in psychiatry. Its ability to measure cortical hemodynamics positions it as a potential tool for monitoring neurofunctional changes related to treatment. However, the specific features and level of consistency of its use in clinical psychiatric settings remain unclear. A scoping review was conducted under PRISMA-ScR guidelines to systematically map how fNIRS has been used in monitoring treatment response among individuals with psychiatric disorders. Methods: Forty-seven studies published between 2009 and 2025 were included based on predefined eligibility criteria. Data was extracted on publication trends, research design, sample characteristics, fNIRS paradigms, signal acquisition, preprocessing methods, and integration of clinical outcomes. Reported limitations and conflicts of interest were also analyzed. Results: The number of publications increased sharply after 2020, predominantly from Asia. Most studies used experimental designs, with 31.9% employing randomized controlled trials. Adults were the primary focus (93.6%), with verbal fluency tasks and DLPFC-targeted paradigms most common. Over half of the studies used high-density (>32-channel) systems. However, only 44.7% reported motion correction procedures, and 53.2% did not report activation direction. Clinical outcome linkage was explicitly stated in only 12.8% of studies. Conclusions: Despite growing clinical interest, with fNIRS showing promise as a non-invasive neuroimaging tool for monitoring psychiatric treatment response, the current evidence base is limited by methodological variability and inconsistent outcome integration. There is a rising need for the adoption of standardized protocols for both design and reporting. Future research should also include longitudinal studies and multimodal approaches to enhance validity and clinical relevance. Full article
(This article belongs to the Special Issue Neuro-Psychiatric Disorders: Updates on Diagnosis and Treatment)
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18 pages, 1243 KiB  
Article
Incidence and Clinical Features of Pseudoprogression in Brain Metastases After Immune-Checkpoint Inhibitor Therapy: A Retrospective Study
by Chris W. Govaerts, Miranda C. A. Kramer, Ingeborg Bosma, Frank A. E. Kruyt, Frederike Bensch, J. Marc C. van Dijk, Mathilde Jalving and Anouk van der Hoorn
Cancers 2025, 17(15), 2425; https://doi.org/10.3390/cancers17152425 - 22 Jul 2025
Viewed by 236
Abstract
Background: Pseudoprogression is known to occur after immune-checkpoint inhibitor (ICI) therapy in brain metastasis and can complicate clinical decision-making. Still, its incidence, timing, and clinical presentation remain unclear. A retrospective cohort study in melanoma and non-small cell lung cancer brain metastasis patients was [...] Read more.
Background: Pseudoprogression is known to occur after immune-checkpoint inhibitor (ICI) therapy in brain metastasis and can complicate clinical decision-making. Still, its incidence, timing, and clinical presentation remain unclear. A retrospective cohort study in melanoma and non-small cell lung cancer brain metastasis patients was conducted to address this. Materials and Methods: Brain metastasis patients showing progression on MRI according to response assessment in neuro-oncology brain metastases criteria after starting ICI therapy were included, irrespective of prior irradiation. Lesions were classified as tumour progression (TP) or pseudoprogression based on three-month radiological follow-up or histopathology. TP was assigned if progression was again shown at three months. Pseudoprogression was assigned if lesions showed stability, partial, or complete response at three months. ‘Non-classified’ lesions were those with new or changed treatment during follow-up. Results: A cohort of 98 patients with 233 lesions was included over a 13-year period; 170 lesions were considered non-classified, and 41 and 22 lesions were classified as TP and pseudoprogression respectively. This resulted in a lesion- and patient-specific incidence for pseudoprogression of 9.4% and 17.3% respectively. Due to the large number of lesions that could not be classified, as is the case in clinical practice, the reported incidence in this study is likely an underestimation and can be seen as a ‘minimum’ incidence rate. Ten pseudoprogression (45.5%) and 13 (31.7%) TP lesions were previously irradiated. Pseudoprogression occurred at a median of 2.7 months after starting ICI therapy. The only clinical feature distinguishing patients with TP from pseudoprogression was that TP patients were more likely to need dexamethasone for neurological symptoms. Conclusions: Pseudoprogression has a lesion-specific incidence rate of at least 9.4% and occurs at a median of 2.7 months after starting ICI therapy. Severe neurological symptoms requiring dexamethasone may be a clinical feature typical for TP. Full article
(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025)
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24 pages, 1654 KiB  
Review
Acute Respiratory Distress Syndrome: Pathophysiological Insights, Subphenotypes, and Clinical Implications—A Comprehensive Review
by Mairi Ziaka and Aristomenis Exadaktylos
J. Clin. Med. 2025, 14(15), 5184; https://doi.org/10.3390/jcm14155184 - 22 Jul 2025
Viewed by 850
Abstract
Increased epithelial and endothelial permeability, along with dysregulated inflammatory responses, are key aspects of acute respiratory distress syndrome (ARDS) pathophysiology, which not only impact the lungs but also contribute to detrimental organ crosstalk with distant organs, ultimately leading to multiple organ dysfunction syndrome [...] Read more.
Increased epithelial and endothelial permeability, along with dysregulated inflammatory responses, are key aspects of acute respiratory distress syndrome (ARDS) pathophysiology, which not only impact the lungs but also contribute to detrimental organ crosstalk with distant organs, ultimately leading to multiple organ dysfunction syndrome (MODS)—the primary cause of morbidity and mortality in patients with lung injury (LI) and ARDS. It is predominantly manifested by hypoxemic respiratory failure and bilateral pulmonary infiltrates, which cannot be fully attributed to cardiac failure or hypervolemia, but rather to alveolo-capillary barrier dysfunction, dysregulated systemic and pulmonary inflammation, immune system abnormalities, and mechanical stimuli-related responses. However, these pathological features are not uniform among patients with ARDS, as distinct subphenotypes with unique biological, clinical, physiological, and radiographic characteristics have been increasingly recognized in recent decades. The severity of ARDS, clinical outcomes, mortality, and efficacy of applied therapeutic measures appear significant depending on the respective phenotype. Acknowledging the heterogeneity of ARDS and defining distinct subphenotypes could significantly modify therapeutic strategies, enabling more precise and targeted treatments. To address these issues, a comprehensive literature search was conducted in PubMed using predefined keywords related to ARDS pathophysiology, subphenotypes, and personalized therapeutic approaches. Optimizing the identification and characterization of discrete ARDS subphenotypes—based on clinical, biological, physiological, and radiographic criteria—will deepen our understanding of ARDS pathophysiology, promote targeted recruitment in prospective clinical studies to define patient clusters with heterogeneous therapeutic responses, and support the shift toward individualized treatment strategies. Full article
(This article belongs to the Special Issue Ventilation in Critical Care Medicine: 2nd Edition)
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15 pages, 1448 KiB  
Review
Acute Myeloid Leukemia in the Elderly: Molecular Abnormalities and Molecular Classification
by Ugo Testa, Elvira Pelosi Pelosi and Germana Castelli
Hemato 2025, 6(3), 22; https://doi.org/10.3390/hemato6030022 - 21 Jul 2025
Viewed by 295
Abstract
Acute myeloid leukemia (AML), a heterogeneous and aggressive clonal disease, is predominantly observed in older individuals, with a median age at diagnosis of 68–69 years. With the aging population, there is a significant increase in the occurrence of some genetic alterations, including detrimental [...] Read more.
Acute myeloid leukemia (AML), a heterogeneous and aggressive clonal disease, is predominantly observed in older individuals, with a median age at diagnosis of 68–69 years. With the aging population, there is a significant increase in the occurrence of some genetic alterations, including detrimental gene mutations and cytogenetic abnormalities, and a higher incidence of secondary AML (s-AML) and therapy-related AML (t-AML), compared to younger AML patients. Outcomes of AML patients and their response to therapy are associated with the molecular features of AML subtypes and with individual variables. The current criteria for risk classification predict outcomes in younger AML patients treated with intensive chemotherapy but are less predictive for older AML patients treated with lower-intensity treatments. Thus, this review analyzes and discusses the development of new risk stratification models adapted to the study of older AML patients and how these new criteria may significantly contribute to a more rational classification and treatment of older AML patients. Full article
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8 pages, 530 KiB  
Case Report
An Unusual Case of Anuric Acute Kidney Injury Secondary to the Use of Low-Dose Acetazolamide as Preventive Management for Acute Mountain Sickness
by Marco Dominguez Davalos, Raúl Valenzuela Córdova, Celia Rodríguez Tudero, Elena Jiménez Mayor, Carlos Bedia Castillo, José C. De La Flor, Roger Leon Montesinos, Cristian León Rabanal, Michael Cieza Terrones and Javier A. Neyra
Diseases 2025, 13(7), 228; https://doi.org/10.3390/diseases13070228 - 21 Jul 2025
Viewed by 334
Abstract
Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature [...] Read more.
Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature on its nephrotoxicity at prophylactic doses. Methods: A 54-year-old previously healthy male ingested 250 mg/day of oral acetazolamide for two days. He developed acute anuria and lumbar pain. Diagnostic evaluation included laboratory tests, imaging, microbiological cultures, autoimmune panels, and diuretic response. No signs of infection, urinary tract obstruction, or systemic disease were found. Results: The patient met KDIGO 2012 criteria for stage 3 AKI, with peak serum creatinine of 10.6 mg/dL and metabolic acidosis. Imaging confirmed non-obstructive nephrolithiasis. Conservative treatment failed; intermittent hemodialysis was initiated. Renal function recovered rapidly, with the normalization of serum creatinine and urinary output by day 4. Conclusions: This case represents the lowest cumulative dose of acetazolamide reported to cause stage 3 AKI. The findings support a pathophysiological mechanism involving sulfonamide-induced crystalluria and intratubular obstruction. Physicians should consider acetazolamide in the differential diagnosis of AKI, even with short-term prophylactic use. Full article
(This article belongs to the Section Respiratory Diseases)
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12 pages, 907 KiB  
Review
Effects of Probiotics as an Adjunct to Non-Surgical Periodontal Therapy (NSPT): A Narrative Review
by Leopoldo Mauriello, Alessandro Cuozzo, Vitolante Pezzella, Vincenzo Iorio-Siciliano, Gaetano Isola, Gianrico Spagnuolo, Luca Ramaglia and Andrea Blasi
J. Clin. Med. 2025, 14(14), 5114; https://doi.org/10.3390/jcm14145114 - 18 Jul 2025
Viewed by 369
Abstract
Background: Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues due to biofilm deposits and altered host immune response. Non-surgical periodontal therapy (NSPT) still represents the gold standard for treatment; however, its effectiveness in deep periodontal pockets is limited. [...] Read more.
Background: Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues due to biofilm deposits and altered host immune response. Non-surgical periodontal therapy (NSPT) still represents the gold standard for treatment; however, its effectiveness in deep periodontal pockets is limited. Probiotics seem to modulate both oral microbiota and inflammatory response and have been proposed as an adjunctive therapy to NSPT. Methods: An electronic search was conducted on PubMed, Scopus, Medline, and Google Scholar to identify English randomized controlled trials (RCTs) evaluating probiotics as adjunctive treatments to NSPT. Studies were selected based on inclusion and exclusion criteria, and clinical outcomes such as probing depth (PD) and clinical attachment level (CAL) were extracted and analyzed. Results: Seven RCTs met the inclusion criteria. These studies showed significant improvements in PD and CAL when probiotics were used, specifically with Lactobacillus and Bifidobacterium species. However, outcomes ranged depending on the strain, dosage, and delivery method. Conclusions: Probiotics may be used as an adjunct treatment to NSPT; however, further studies are needed to define valid clinical guidelines. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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12 pages, 481 KiB  
Review
Potential miRNAs as Diagnostic Biomarkers for Differentiating Disease States in Ulcerative Colitis: A Systematic Review
by Atta Ullah Khan, Pilar Chacon-Millan and Paola Stiuso
Int. J. Mol. Sci. 2025, 26(14), 6822; https://doi.org/10.3390/ijms26146822 - 16 Jul 2025
Viewed by 294
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, triggering persistent inflammation and ulceration, resulting in a severe impact on patients’ quality of life. Currently, the standard diagnostic methods for UC include invasive procedures such as colonoscopy and the use [...] Read more.
Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, triggering persistent inflammation and ulceration, resulting in a severe impact on patients’ quality of life. Currently, the standard diagnostic methods for UC include invasive procedures such as colonoscopy and the use of non-specific inflammatory markers like C-reactive protein, which can be inconvenient or painful and lack specificity. This underscores the need for non-invasive and highly specific biomarkers for UC. MicroRNAs (miRNAs) are small non-coding RNAs, typically 22 nucleotides in length, which are well described as gene expression regulators. Several studies have reported their differential expression in various pathological conditions, including UC. Due to their role in gene regulation and stability in biological fluids, miRNAs present a promising opportunity as biomarkers. This systematic review explores the potential use of miRNAs as diagnostic biomarkers to distinguish between active and inactive ulcerative colitis. Following PRISMA guidelines and based on inclusion and exclusion criteria, seven studies, encompassing a total of 514 participants (181 with active UC and 116 with inactive UC), were included. Multiple miRNAs exhibiting differential expression between active and inactive UC were identified. Most notably, miR-21, miR-126, miR-146b-5p, and miR-223 exhibited consistent upregulation in active UC, suggesting their potential as diagnostic biomarkers. Supporting these findings is the fact that these miRNAs are involved in inflammatory pathways, further highlighting their relevance to the pathogenesis of UC. This review emphasizes the need for further validation studies with larger cohorts to confirm the utility of miRNAs as diagnostic tools for UC disease activity differentiation, which could enhance non-invasive disease monitoring and inform therapeutic decision-making. Future research should also evaluate the prognostic potential of these miRNAs for predicting treatment responses and long-term disease outcomes. Full article
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