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20 pages, 3918 KB  
Review
Allergic Contact Dermatitis: Immunopathology and Potential Therapeutic Strategies
by Anders Boutrup Funch, Carsten Geisler and Charlotte Menné Bonefeld
J. Clin. Med. 2025, 14(20), 7175; https://doi.org/10.3390/jcm14207175 - 11 Oct 2025
Viewed by 1972
Abstract
Allergic contact dermatitis (ACD) is a common inflammatory skin disease induced by exposure of the skin to contact allergens. Classically, ACD is defined as a delayed-type (type IV) hypersensitivity reaction mediated by allergen-specific T cells, with symptoms peaking 48–72 h after exposure to [...] Read more.
Allergic contact dermatitis (ACD) is a common inflammatory skin disease induced by exposure of the skin to contact allergens. Classically, ACD is defined as a delayed-type (type IV) hypersensitivity reaction mediated by allergen-specific T cells, with symptoms peaking 48–72 h after exposure to the contact allergen. This delayed response to the contact allergen is seen during patch testing, where allergen-naïve, unaffected skin of allergic individuals is exposed to the contact allergen. However, in daily life and in certain occupational settings, allergic individuals often experience rapid flare-ups/exacerbations with intensely itching erythema, oedema, and often vesicles within hours after re-exposure to the specific contact allergen. These rapid flare-ups only develop at skin sites previously exposed to the contact allergen. Thus, it is important to distinguish between the rapid-onset reaction typically experienced by the allergic individual and the delayed-type reaction typically seen after patch testing. This review summarizes current insights into the immunopathology of rapid- versus delayed-type ACD reactions and outlines potential therapeutic opportunities, as well as their current limitations, against rapid-onset ACD, including modulation of cytokine signaling, T cell survival, checkpoint pathways, and redox balance. Full article
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11 pages, 614 KB  
Article
Factors Influencing the Healing of Maxillary Sinusitis of Endodontic Origin After Non-Surgical Endodontic Treatment
by Paweł Szczurowski, Krzysztof Gronkiewicz and Barbara Czopik
J. Clin. Med. 2025, 14(19), 6778; https://doi.org/10.3390/jcm14196778 - 25 Sep 2025
Viewed by 3011
Abstract
Background/Objectives: The purpose of this study was to indicate factors influencing the healing of maxillary sinusitis of endodontic origin (MSEO) after non-surgical endodontic treatment. Methods: The study was performed retrospectively on medical records and CBCT data of 114 teeth in 114 [...] Read more.
Background/Objectives: The purpose of this study was to indicate factors influencing the healing of maxillary sinusitis of endodontic origin (MSEO) after non-surgical endodontic treatment. Methods: The study was performed retrospectively on medical records and CBCT data of 114 teeth in 114 patients, who were referred to endodontic treatment between 2016 and 2024, performed by the same operator and according to the same treatment protocol. Fifteen factors were chosen for their possible influence on the healing of MSEO. Results: The rate of the complete healing of MSEO after RCT was 76.32%. The healing of MSEO was higher when CHX was applied in the final irrigation protocol (p = 0.022) and was less likely when there was a flare-up in-between visits or after obturation of the canals (p = 0.002). MSEO was more likely to heal when a tooth was treated in two appointments than with single-visit RCT (p = 0.012). The number of endodontic interventions significantly influenced the healing of MSEO, as it was less likely to heal when there was more than one endodontic retreatment for a tooth (p = 0.01). Conclusions: Within the limitations of this retrospective study, four factors significantly influenced the healing of MSEO, and these should be taken into consideration in obtaining treatment protocols for dental-induced sinusitis and the better assessment of the possible success of this non-invasive treatment approach. Full article
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22 pages, 4010 KB  
Article
Continuous Activity Monitoring Using a Wearable Sensor in Dogs with Osteoarthritis: An Exploratory Case Series
by Carina Sacoor, Sara Leitão, Carolina Domingues, Joana Babo, Cátia M. Sá, Ricardo Cabeças and Felisbina L. Queiroga
Animals 2025, 15(18), 2639; https://doi.org/10.3390/ani15182639 - 9 Sep 2025
Viewed by 2120
Abstract
Canine osteoarthritis (OA) is a chronic, progressive disease that impacts mobility and welfare, often with subtle clinical signs that fluctuate over time. This exploratory case series evaluated the potential of a wearable sensor system (Maven Pet AI System) to detect real-time deviations in [...] Read more.
Canine osteoarthritis (OA) is a chronic, progressive disease that impacts mobility and welfare, often with subtle clinical signs that fluctuate over time. This exploratory case series evaluated the potential of a wearable sensor system (Maven Pet AI System) to detect real-time deviations in activity and rest patterns in dogs with OA under home-based conditions. Five client-owned dogs were monitored over periods ranging from 56 to 126 days, generating longitudinal data on activity and rest patterns. Nine clinically relevant events were identified: seven OA-related flare-ups and two non-orthopedic health issues. In eight of these events, deviations in activity profiles were temporally aligned with symptom onset, therapeutic response, or recovery. Statistically significant changes were observed in six out of nine events, particularly in the Active and Excited categories, while visual trend analysis revealed clinically relevant deviations even in the absence of statistical significance. In one case, decreased activity preceded owner recognition, suggesting potential for early detection. Sensor data also contextualized episodes of overexertion and non-orthopedic conditions, such as pruritus and gastroenteritis. Owner and clinician feedback indicated high usability and perceived clinical value. Despite the small sample, these findings suggest that continuous sensor-based monitoring may complement conventional evaluations and support earlier, more individualized OA management in real-world settings. Further studies are needed to validate and expand these preliminary observations. Full article
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22 pages, 1987 KB  
Article
Predictive Microbial Markers Distinguish Responders and Non-Responders to Adalimumab: A Step Toward Precision Medicine in Ulcerative Colitis
by Shaghayegh Baradaran Ghavami, Arfa Moshiri, Carola Bonaretti, Maryam Farmani, Margherita Squillario, Eddi Di Marco, Shabnam Shahrokh, Hedieh Balaii, Maria Valeria Corrias, Mirco Ponzoni, Amir Sadeghi and Roberto Biassoni
Microorganisms 2025, 13(8), 1941; https://doi.org/10.3390/microorganisms13081941 - 20 Aug 2025
Viewed by 1029
Abstract
Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon, often associated with gut microbial dysbiosis. Although anti-TNF-α agents, such as Adalimumab (Cinnora®), are used to treat moderate-to-severe UC, the treatment response is highly variable. Identifying early microbial biomarkers [...] Read more.
Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon, often associated with gut microbial dysbiosis. Although anti-TNF-α agents, such as Adalimumab (Cinnora®), are used to treat moderate-to-severe UC, the treatment response is highly variable. Identifying early microbial biomarkers of response could help support personalized therapeutic strategies and prevent unnecessary exposure to ineffective treatments. However, the long-term effects of anti-TNF therapy on both stool and mucosal microbiota remain poorly understood. This prospective longitudinal study included 23 corticosteroid-refractory or -dependent UC patients who started Adalimumab after endoscopy-confirmed flare-ups. Stool samples and inflamed colonic biopsies were collected at baseline, and 3 and 6 months. Microbiota profiling was performed using 16S rRNA sequencing. Microbial changes were analyzed over time and compared between responders (Mayo score 0–1) and non-responders (Mayo score ≥ 2). Sixty percent of patients achieved clinical remission. In responders, stool microbiota showed increased Bacteroidetes and decreased Proteobacteria abundances, along with an enrichment of beneficial taxa including Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila. Mucosal microbiota exhibited persistent dysbiosis, characterized by an increase in Proteobacteria and a reduced Firmicutes/Proteobacteria ratio. Notably, responders showed distinct compartment-specific microbial changes, with a decrease in Gammaproteobacteria in stool and an increase in Corynebacterium in tissue. Adalimumab induces divergent microbial changes in stool and mucosa. While stool microbiota trends toward eubiosis in responders, persistent mucosal dysbiosis may reflect asymptomatic inflammation. These findings underscore the importance of niche-specific microbiome profiling in UC and support its integration into personalized treatment monitoring. Full article
(This article belongs to the Section Microbiomes)
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13 pages, 1083 KB  
Article
Beyond the Plate: Patient Perspectives on Diet and Daily Life with Crohn’s Disease—A National Survey
by Sarah Bencardino, Ferdinando D’Amico, Ambra Ciliberto and Silvio Danese
J. Clin. Med. 2025, 14(16), 5648; https://doi.org/10.3390/jcm14165648 - 9 Aug 2025
Viewed by 930
Abstract
Background: Crohn’s disease (CD) is a chronic inflammatory bowel disease that significantly affects patients’ quality of life. Nutrition is increasingly recognized as a modifiable factor influencing disease activity and symptom management. Despite growing interest, structured dietary guidelines for CD are lacking, and patients [...] Read more.
Background: Crohn’s disease (CD) is a chronic inflammatory bowel disease that significantly affects patients’ quality of life. Nutrition is increasingly recognized as a modifiable factor influencing disease activity and symptom management. Despite growing interest, structured dietary guidelines for CD are lacking, and patients often rely on personal experience or fragmented advice. This study aimed to investigate patients’ perceptions of diet, the support they receive, and the psychosocial burden of dietary management in CD. Methods: A nationwide online survey was conducted in Italy from April to May 2025 among individuals diagnosed with CD. The questionnaire, developed in line with the CROSS reporting guidelines, comprised 30 multiple-choice questions across five sections: demographics, disease characteristics, dietary habits during remission, dietary habits during flare-ups, and psychological impact. Invitations were distributed through patient associations, webinars, and gastroenterology professionals. Responses were anonymized. Results: A total of 222 participants completed the survey (59.5% female, most aged 30–39 years). Fatigue was the most common symptom (71.6%), frequently persisting even during remission. Nearly half of respondents reported diet as “very important” in disease management, yet only 32% had received a formal referral to a nutritionist. The most commonly adopted dietary approach was a low-fiber diet, while awareness of evidence-based protocols like the Crohn’s disease exclusion diet (CDED) was limited (11.7%). Social and psychological burdens were significant, with 79.2% reporting anxiety when outside their home. Conclusions: Dietary education and psychological support are unmet needs for CD patients. Improved access to tailored nutritional counseling and greater awareness of validated dietary approaches may enhance disease management and quality of life. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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15 pages, 357 KB  
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 1680
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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17 pages, 4789 KB  
Systematic Review
Efficacy of Combined Oral Isotretinoin and Desloratadine or Levocetirizine vs. Isotretinoin Monotherapy in Treating Acne Vulgaris: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Julia Woźna, Andrzej Bałoniak, Jan Stępka, Adriana Polańska, Ewa Mojs and Ryszard Żaba
Biomedicines 2025, 13(8), 1847; https://doi.org/10.3390/biomedicines13081847 - 30 Jul 2025
Cited by 2 | Viewed by 4309
Abstract
Background/Objectives: Acne vulgaris is a widespread, chronic inflammatory skin condition that significantly impacts patients’ quality of life. Although oral isotretinoin remains the most effective treatment, recent evidence suggests that H1-antihistamines such as desloratadine and levocetirizine may enhance acne therapy. This study [...] Read more.
Background/Objectives: Acne vulgaris is a widespread, chronic inflammatory skin condition that significantly impacts patients’ quality of life. Although oral isotretinoin remains the most effective treatment, recent evidence suggests that H1-antihistamines such as desloratadine and levocetirizine may enhance acne therapy. This study assesses whether combining H1-antihistamines to isotretinoin enhances treatment efficacy in acne vulgaris compared to isotretinoin alone. Methods: Our analysis included 10 randomized controlled trials involving 675 patients collectively, predominantly from Asia and the Middle East. Data were extracted by two independent reviewers, with discrepancies resolved by a third. Risk of bias was assessed using the Cochrane RoB 2 tool. Analyses were performed using RevMan 5.4 with random-effects models, and heterogeneity was evaluated via I2 and Q tests. Sensitivity analyses were conducted to assess result robustness. Results: Combination therapy with isotretinoin and desloratadine showed a significantly greater reduction in GAGS (Global Acne Grading Scale) score by week 12 (p < 0.00001; MD 2.68, 95% CI 1.60 to 3.75; I2 = 0%) while earlier timepoints showed non-significant or borderline results. For inflammatory lesions, significant improvements with desloratadine emerged at weeks 4, 8, and 12 after excluding an influential outlier, with low heterogeneity and consistent direction of effect. Non-inflammatory lesions did not differ significantly at weeks 4 or 8. At week 12, a significant reduction was seen in the desloratadine subgroup (OR 2.61, p = 0.003, I2 = 11%) and in overall pooled analysis (OR 2.77, p < 0.0001, I2 = 2%). Among side effects, acne flare-ups, pruritus, and cheilitis were significantly reduced in the desloratadine group, as well as in pooled analysis. Xerosis did not consistently differ between groups. Overall, desloratadine improved tolerability and reduced mucocutaneous adverse events more than levocetirizine. Conclusions: Current evidence suggests that combining oral antihistamines with isotretinoin may offer therapeutic benefits in acne management, particularly in enhancing tolerability and potentially improving clinical outcomes, as reflected by significant reductions in GAGS scores and mucocutaneous adverse effects such as cheilitis, pruritus, and acne flare-ups. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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20 pages, 770 KB  
Review
Histamine Metabolism in IBD: Towards Precision Nutrition
by Dimitra Kanta, Eleftherios Katsamakas, Anna Maia Berg Gudiksen and Mahsa Jalili
Nutrients 2025, 17(15), 2473; https://doi.org/10.3390/nu17152473 - 29 Jul 2025
Viewed by 6764
Abstract
Patients with Inflammatory Bowel Disease (IBD) exhibit a dysregulated immune response that may be further exacerbated by bioactive compounds, such as histamine. Current dietary guidelines for IBD primarily focus on symptom management and flare-up prevention, yet targeted nutritional strategies addressing histamine metabolism remain [...] Read more.
Patients with Inflammatory Bowel Disease (IBD) exhibit a dysregulated immune response that may be further exacerbated by bioactive compounds, such as histamine. Current dietary guidelines for IBD primarily focus on symptom management and flare-up prevention, yet targeted nutritional strategies addressing histamine metabolism remain largely unexplored. This narrative review aims to summarize the existing literature on the complex interplay between IBD and histamine metabolism and propose a novel dietary framework for managing IBD progression in patients with histamine intolerance (HIT). Relevant studies were identified through a comprehensive literature search of PubMed/MEDLINE, Google Scholar, ScienceDirect, Scopus, and Web of Science. The proposed low-histamine diet (LHD) aims to reduce the overall histamine burden in the body through two primary strategies: (1) minimizing exogenous intake by limiting high-histamine and histamine-releasing foods and (2) reducing endogenous histamine production by modulating gut microbiota composition, specifically targeting histamine-producing bacteria. In parallel, identifying individuals who are histamine-intolerant and understanding the role of histamine-degrading enzymes, such as diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT), are emerging as important areas of focus. Despite growing interest in the role of histamine and mast cell activation in gut inflammation, no clinical trials have investigated the effects of a low-histamine diet in IBD populations. Therefore, future research should prioritize the implementation of LHD interventions in IBD patients to evaluate their generalizability and clinical applicability. Full article
(This article belongs to the Special Issue Precise Nutrition Therapy to Inflammatory Bowel Diseases)
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14 pages, 1172 KB  
Case Report
A Multimodal Approach to Managing Severe Psoriasis Vulgaris: A Case Report Leveraging Natural Therapies for Flare Control
by Ada Radu, Tunde Jurca, Andrei-Flavius Radu, Teodora Maria Bodog, Ruxandra Florina Bodog and Laura Endres
Life 2025, 15(8), 1186; https://doi.org/10.3390/life15081186 - 25 Jul 2025
Cited by 1 | Viewed by 1501
Abstract
A psoriasis vulgaris flare is characterized by a rapid intensification of symptoms, which is often triggered by various factors that can worsen the condition. The risk factors for these exacerbations are numerous and include obesity, antihypertensive drugs, and psychological stress. Moreover, links have [...] Read more.
A psoriasis vulgaris flare is characterized by a rapid intensification of symptoms, which is often triggered by various factors that can worsen the condition. The risk factors for these exacerbations are numerous and include obesity, antihypertensive drugs, and psychological stress. Moreover, links have been documented between type II diabetes, hypertension, and psoriasis vulgaris. The present case report describes a 52-year-old female patient who presented at the clinic with disseminated erythematous-squamous plaques and patches covered by thick, white-pearly, easily detachable scales, along with stress, fatigue, anxiety, severe pruritus, irritability, insomnia, and decreased self-esteem. Her past medical regimen included various conventional topical options, including calcipotriol combined with betamethasone, clobetasol, betamethasone combined with salicylic acid, and betamethasone combined with gentamicin, yet the condition remained refractory, with periodic flare-ups. The integrated and personalized therapeutic approach aimed to target both the dermatological issues and the associated systemic and psychological factors contributing to the condition. The therapeutic strategy implemented in this case combined psychological counseling sessions, a very low-calorie ketogenic diet, oral supplementation with anti-inflammatory and antioxidant vitamins and minerals, topical treatments utilizing urea and Dead Sea-mineral-based formulations, and rosemary extract-based scalp care, without requiring additional conventional treatment. This comprehensive approach led to significant improvement, ultimately achieving complete remission of the patient’s psoriasis. The associated comorbidities were well controlled with the specified medication, without any further complications. Thus, the importance of alternative options was emphasized, particularly in the context of an incurable disease, along with the need for continued research to improve the ongoing therapeutic management of psoriasis vulgaris. Such approaches are essential to reducing the risk of flare-ups and to achieving better management of associated risk factors. Full article
(This article belongs to the Section Physiology and Pathology)
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18 pages, 344 KB  
Review
Intestinal Microbiota and Fecal Transplantation in Patients with Inflammatory Bowel Disease and Clostridioides difficile: An Updated Literature Review
by Chloe Lahoud, Toni Habib, Daniel Kalta, Reem Dimachkie, Suzanne El Sayegh and Liliane Deeb
J. Clin. Med. 2025, 14(15), 5260; https://doi.org/10.3390/jcm14155260 - 25 Jul 2025
Cited by 2 | Viewed by 2958
Abstract
Background/Objectives: Inflammatory bowel disease (IBD) is characterized by chronic relapsing and remitting inflammation of the gastrointestinal tract. Fecal microbiota transplantation (FMT) has emerged as an FDA-approved treatment for recurrent Clostridioides difficile infections (CDIs), with promising potential in patients with IBD. This manuscript [...] Read more.
Background/Objectives: Inflammatory bowel disease (IBD) is characterized by chronic relapsing and remitting inflammation of the gastrointestinal tract. Fecal microbiota transplantation (FMT) has emerged as an FDA-approved treatment for recurrent Clostridioides difficile infections (CDIs), with promising potential in patients with IBD. This manuscript aimed to provide a comprehensive and updated review of the available literature on fecal microbiota transplantation, its clinical use in IBD in general, as well as in patients with IBD and CDI. Methods: An extensive literature search was performed from October 2024 to March 2025. All publications available within PubMed, Medline, Embase, Google Scholar, and Cochrane databases were reviewed. All original articles, case reports, review articles, systematic reviews, and meta-analyses were included. Qualitative and quantitative data were both extracted. Discussion: Intestinal microbiota is an integral part of the human body, and dysbiosis (an imbalance in the gut’s microbial community) has been linked with several pathologies. Dysbiosis in IBD is marked by reduced beneficial bacteria and increased pro-inflammatory pathogens, contributing to mucosal damage and immune dysregulation. FMT has emerged as a solution to dysbiosis, with the first case recorded in 1917. FMT has been successful in treating patients with CDI. The diagnostic value of the gut microbiome is currently being explored as a possible therapeutic approach to IBD. Several studies have assessed FMT in patients with IBD and CDI with promising results in both ulcerative colitis (UC) and Crohn’s disease (CD) but varying efficacy based on administration routes, donor selection, and processing methods. In the context of recurrent CDI in patients with IBD, FMT demonstrates a high cure rate and potential benefit in concurrently improving IBD activity. However, risks such as IBD flare-ups post-FMT remain a concern. Conclusions: FMT holds promising potential in the management of CDI in patients with IBD. By restoring microbial diversity and correcting dysbiosis, FMT offers a novel, microbiota-targeted alternative to conventional therapies. While data support its efficacy in improving disease remission, variability in outcomes underscores the need for standardized protocols and additional large-scale, controlled studies. Continued research efforts into donor selection, treatment regimens, and long-term safety will be critical to optimizing FMT’s role in IBD and CDI care as well as improving patient outcomes. Full article
(This article belongs to the Special Issue Emerging Treatment Options in Inflammatory Bowel Disease)
14 pages, 1849 KB  
Article
Objective Treatment Targets and Their Correlation with Patient-Reported Outcomes in Inflammatory Bowel Disease: A Real-World Study
by Panu Wetwittayakhlang, Siripoom Ngampech, Saichol Pattarakulniyom and Peter L. Lakatos
J. Clin. Med. 2025, 14(13), 4733; https://doi.org/10.3390/jcm14134733 - 4 Jul 2025
Cited by 1 | Viewed by 1718
Abstract
Background & Aims: treat-to-target approach is essential for improving outcomes in inflammatory bowel disease (IBD). This study aimed to assess real-world achievement in objective monitoring (clinical, biomarker, and endoscopic assessments) and the correlation between patient-reported outcomes (PROs) and treatment targets. Methods: [...] Read more.
Background & Aims: treat-to-target approach is essential for improving outcomes in inflammatory bowel disease (IBD). This study aimed to assess real-world achievement in objective monitoring (clinical, biomarker, and endoscopic assessments) and the correlation between patient-reported outcomes (PROs) and treatment targets. Methods: This retrospective study included consecutive IBD patients from January 2020 to December 2024. Disease activity was assessed using the Harvey-Bradshaw Index (HBI), partial Mayo score, PRO2, and PRO3, along with C-reactive protein (CRP) levels and endoscopic scores (SES-CD, MES). Clinical outcomes were evaluated at baseline, 1 year, and 2 years. Results: Among 112 IBD patients (55% with CD, median age at diagnosis: 45.2 years), clinical remission rates at baseline, 1 year, and 2 years were; CD: 75.8%, 70.0%, and 55.8%; UC: 84.0%, 79.5%, and 81.4%. CRP normalization rates at the same time points were; CD: 54.8%, 41.7%, and 63.8% UC: 78.0%, 70.5%, and 81.8%. Endoscopic remission rates were; CD: 58.1%, 50.0%, and 50.0%, UC: 71.4%, 64.5%, and 51.7% Flare-ups were more frequent in CD than in UC (32% vs. 20%), with an 8.1% rate of IBD-related surgery. In CD, PRO2 and PRO3 strongly correlated with clinical remission (AUC = 0.885 and 0.881), moderately with biomarkers (AUC = 0.737 and 0.755), and modestly with endoscopic remission (AUC = 0.695 and 0.685). In UC, PRO2 showed a strong correlation with clinical remission (AUC = 0.972) and moderate correlations with biomarkers (AUC = 0.653) and endoscopy (AUC = 0.783). Conclusions: Clinical remission was more frequent in UC than in CD. PROs showed a strong correlation with clinical remission but only moderate associations with biomarkers and endoscopic remission in both CD and UC. Full article
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34 pages, 981 KB  
Review
Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review
by Chloë Hanssens and Jolien Van Cleemput
Pathogens 2025, 14(7), 654; https://doi.org/10.3390/pathogens14070654 - 1 Jul 2025
Viewed by 4832
Abstract
Background: Human herpesviruses are double-stranded DNA viruses of which eight types have been identified at present. Herpesvirus infection comprises an active lytic phase and a lifelong latency phase with the possibility of reactivation. These infections are highly prevalent worldwide and can lead to [...] Read more.
Background: Human herpesviruses are double-stranded DNA viruses of which eight types have been identified at present. Herpesvirus infection comprises an active lytic phase and a lifelong latency phase with the possibility of reactivation. These infections are highly prevalent worldwide and can lead to a broad spectrum of clinical manifestations, ranging from mild symptoms to severe disease, particularly in immunocompromised individuals. Clustered regularly interspaced palindromic repeats (CRISPR)-based therapy is an interesting alternative to current antiviral drugs, which fail to cure latent infections and are increasingly challenged by viral resistance. Objective: This scoping review aimed to summarize the current state of CRISPR-based antiviral strategies against herpesvirus infections, highlighting the underlying mechanisms, study design and outcomes, and challenges for clinical implementation. Design: A literature search was conducted in the databases PubMed and Web of Science, using both a general and an individual approach for each herpesvirus. Results: This scoping review identified five main mechanisms of CRISPR-based antiviral therapy against herpesvirus infections in vitro and/or in vivo. First, CRISPR systems can inhibit the active lytic replication cycle upon targeting viral lytic genes or host genes. Second, CRISPR technologies can remove latent viral genomes from infected cells by targeting viral genes essential for latency maintenance or destabilizing the viral genome. Third, reactivation of multiple latent herpesvirus infections can be inhibited by CRISPR-Cas-mediated editing of lytic viral genes, preventing a flare-up of clinical symptoms and reducing the risk of viral transmission. Fourth, CRISPR systems can purposefully induce viral reactivation to enhance recognition by the host immune system or improve the efficacy of existing antiviral therapies. Fifth, CRISPR technology can be applied to develop or enhance the efficiency of cellular immunotherapy. Conclusions: Multiple studies demonstrate the potential of CRISPR-based antiviral strategies to target herpesvirus infections through various mechanisms in vitro and in vivo. However, aspects regarding the delivery and biosafety of CRISPR systems, along with the time window for treatment, require further investigation before broad clinical implementation can be realized. Full article
(This article belongs to the Special Issue Herpesvirus Latency and Reactivation)
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14 pages, 651 KB  
Article
Safety and Efficacy of Simultaneous Vaccination with Polysaccharide Conjugate Vaccines Against Pneumococcal (13-Valent Vaccine) and Haemophilus Type B Infections in Children with Systemic Juvenile Idiopathic Arthritis: Prospective Cohort Study
by Ekaterina Alexeeva, Tatyana Dvoryakovskaya, Dmitry Kudlay, Anna Fetisova, Ivan Kriulin, Elizaveta Krekhova, Anna Kabanova, Vladimir Labinov, Elizaveta Labinova and Mikhail Kostik
Vaccines 2025, 13(6), 644; https://doi.org/10.3390/vaccines13060644 - 15 Jun 2025
Viewed by 1404
Abstract
Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening [...] Read more.
Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening complications, namely macrophage activation syndrome. Our study aimed to evaluate the efficacy and safety of simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) in children with sJIA. Methods: This study included 100 sJIA patients receiving immunosuppressive therapy who were simultaneously vaccinated against pneumococcal and Haemophilus influenzae type b (Hib) infections. The mean age of disease onset was 5.5 years. The median age at vaccination was 10 ± 4.5 years. Clinical and laboratory parameters of sJIA activity, immunization efficacy, and safety, including anti-SP and anti-Hib IgG antibodies, as well as all vaccination-related adverse events (AEs), were recorded in every patient before, 3 weeks after, and 6 months after vaccination. Results: At the time of vaccination, 29% of patients did not meet the criteria for the inactive disease stage, as defined by C. Wallace: active joints were present in 34.5% of patients, systemic manifestations (rash and/or fever) were present in 41.3%, and 24.2% of patients had solely inflammatory laboratory activity. The protective titer of anti-SP and anti-Hib IgG antibodies was detected in the majority of patients 3 weeks after vaccination (100% and 93%, respectively). The results remained unchanged (99% and 92%, respectively) for 6 months of follow-up, compared to the baseline (91% and 37%, p = 0.000001). Anti-SP IgG and anti-Hib titers raised from 48.3 (18.2; 76.5) and 0.64 (0.3; 3.2) U/mL at the baseline to 103.5 (47.3; 185.4) and 4 (3.5; 4.2) U/mL at D22 and 105 (48.7; 171.8) and 4 (3.8; 4) U/mL (EOS), respectively. Immunosuppressive therapy regimens (combined therapy or biological disease-modifying antirheumatic drug monotherapy) did not influence the immunogenic efficacy of vaccination. The incidence of infectious complications (p = 0.0000001) and antibiotic prescriptions (p = 0.0000001) decreased by more than two times, to 29.9 and 13.8 events per 100 patient months, respectively, within 6 months after vaccination—the average duration of acute infectious events was reduced by five times after immunization (p = 0.0000001). Vaccination did not lead to disease flare: the number of patients with active joints decreased by half compared to the baseline, and the number of patients with systemic manifestations decreased by six times. All vaccine-associated adverse events were considered mild and resolved within 1–2 days. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections in sJIA children is an effective and safe tool that reduces the number and duration of infectious events and does not cause disease flare-ups. Full article
(This article belongs to the Special Issue Pneumococcal Vaccines: Current Status and Future Prospects)
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12 pages, 579 KB  
Article
Salivary Calprotectin as a Biomarker in Early Onset Inflammatory Bowel Disease: A Pilot Study
by Simone Liguori, Gennaro Musella, Daniela Adamo, Erasmo Miele, Noemi Coppola, Federica Canfora, Carmela Del Giudice, Gianrico Spagnuolo, Sandro Rengo, Michele Davide Mignogna and Stefania Leuci
J. Clin. Med. 2025, 14(12), 4232; https://doi.org/10.3390/jcm14124232 - 14 Jun 2025
Cited by 1 | Viewed by 1313
Abstract
Objectives: This study aimed to evaluate the potential of salivary calprotectin (SCP) as a novel biomarker in the management of Early Onset Inflammatory Bowel Disease (EOIBD), comparing EOIBD and healthy controls and differentiating patients based on their history of oral manifestations (OM). We [...] Read more.
Objectives: This study aimed to evaluate the potential of salivary calprotectin (SCP) as a novel biomarker in the management of Early Onset Inflammatory Bowel Disease (EOIBD), comparing EOIBD and healthy controls and differentiating patients based on their history of oral manifestations (OM). We correlated SCP and fecal calprotectin (FCP) in EOIBD and assessed the prognostic accuracy of SCP in predicting disease relapses. Methods: A sample of stimulated saliva was collected at baseline by 27 EOIBD and 9 healthy controls and then processed by ELISA for SCP determination. At sampling, a stool specimen was also provided by each patient for routine FCP assessment. Clinical disease activity was measured through Pediatric Ulcerative Colitis Activity Index (PUCAI) or Pediatric Crohn’s Disease Activity Index (PCDAI) at baseline and during follow-up at 4, 8 and 12 weeks. Results: A history of OM was described by 13 EOIBD. EOIBD with OM reported significantly higher SCP than EOIBD without OM (p < 0.01**) and controls (p < 0.05*). When evaluating the correlation between SCP and FCP in EOIBD with OM, positive FCP values (>120 mg/kg) were found to be associated with higher SCP concentrations (p < 0.05*), while in EOIBD without OM, a negative correlation was described (p < 0.05*). Lastly, EOIBD with OM who reported higher SCP were found to have significantly increased risk of relapse (p < 0.05*). Conclusions: In EOIBD with OM SCP was significantly more elevated and was correlated to intestinal inflammation and flare-up risk. Our results suggest the potential use of SCP as prognostic biomarker in children with intestinal and oral disease. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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18 pages, 6412 KB  
Article
Geochemistry and Zircon U-Pb Chronology of West Kendewula Late Paleozoic A-Type Granites in the East Kunlun Orogenic Belt: Implications for Post-Collision Extension
by Bang-Shi Dong, Wen-Qin Wang, Gen-Hou Wang, Pei-Lie Zhang, Peng-Sheng Li, Zhao-Lei Ding, Ze-Jun He, Pu Zhao, Jing-Qi Zhang and Chao Bo
Appl. Sci. 2025, 15(12), 6661; https://doi.org/10.3390/app15126661 - 13 Jun 2025
Viewed by 983
Abstract
The Late Paleozoic granitoids widely distributed in the central section of the East Kunlun Orogenic Belt (EKOB) are responsible for the constraints on its post-collisional extensional processes. We report the whole-rock geochemical compositions, zircon U-Pb ages, and zircon Hf isotope data of granites [...] Read more.
The Late Paleozoic granitoids widely distributed in the central section of the East Kunlun Orogenic Belt (EKOB) are responsible for the constraints on its post-collisional extensional processes. We report the whole-rock geochemical compositions, zircon U-Pb ages, and zircon Hf isotope data of granites in the western Kendewula area. The granites, dated between 413.7 Ma and 417.7 Ma, indicate emplacement during the Early Devonian period. The granite is characterized by high silicon content (72.45–78.96 wt%), high and alkali content (7.59–9.35 wt%), high 10,000 × Ga/Al values, and low Al2O3 (11.29–13.32 wt%), CaO (0.07–0.31 wt%), and MgO contents (0.16–0.94 wt%). The rocks exhibit enrichment in large-ion lithophile element (LILE) content and high-field-strength element (HFSE) content, in addition to strong losses, showing significant depletion in Ba, Sr, P and Eu. These geochemical characteristics correspond to A2-type granites. The values of Rb/N and Ba/La and the higher zircon saturation temperature (800~900 °C) indicate that the magma source is mainly crustal, with the participation of mantle materials, although limited. In addition, the zircon εHf(t) values (−4.3–3.69) also support this view. In summary, the A2-type granite exposed in the western Kendewula region formed against a post-collisional extensional setting background, suggesting that the Southern Kunlun Terrane (SKT) entered a post-orogenic extensional phase in the evolution stage since the Early Devonian. The upwelling of the asthenospheric mantle of the crust, triggered by crustal detachment and partial melting, likely contributed to the flare-up of A2-type granite during this period. By studying the nature of granite produced during orogeny, the evolution process of the formation of orogenic belts is discussed, and our understanding of orogenic is enhanced. Full article
(This article belongs to the Special Issue Technologies and Methods for Exploitation of Geological Resources)
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