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17 pages, 758 KB  
Systematic Review
Evaluating the Safety and Efficacy of PD-1 Inhibitors in HIV Patients Diagnosed with Lung Cancer: A Systematic Review
by Helal F. Hetta, Yasser Alatawi, Fawaz E. Alanazi, Abdullah Alattar, Reem Alshaman, Hanan Alshareef, Zinab Alatawi, Majd S. Alatawi, Jumana H. Albalawi, Ghadeer A. Alosaimi, Reem Sayad and Wedad M. Nageeb
Pharmaceuticals 2025, 18(11), 1654; https://doi.org/10.3390/ph18111654 (registering DOI) - 1 Nov 2025
Abstract
Background and Aim: People with HIV (PWH) have historically been excluded from cancer immunotherapy trials due to concerns over immune dysregulation and safety. This systematic review evaluates the safety, efficacy, and immunologic outcomes of Programmed death-1 (PD-1) inhibitors in PWH diagnosed with [...] Read more.
Background and Aim: People with HIV (PWH) have historically been excluded from cancer immunotherapy trials due to concerns over immune dysregulation and safety. This systematic review evaluates the safety, efficacy, and immunologic outcomes of Programmed death-1 (PD-1) inhibitors in PWH diagnosed with non-small-cell lung cancer (NSCLC). Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, Web of Science, and Medline through January 2025. Studies were included if they reported outcomes of ICIs in PWH with NSCLC. Data extraction included progression-free survival (PFS), overall survival (OS), immune-related adverse events (irAEs), antitumor response, HIV viral control, and immunologic parameters. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist. Results: Six cohort studies (n = 762 patients) met inclusion criteria. ICIs used included nivolumab, pembrolizumab, atezolizumab, and durvalumab, with treatment durations ranging from 3.1 to 5.4 months. Median PFS ranged from 3.0 to 6.3 months, and OS ranged from 10.0 to 66.0 months. Overall response rates (ORRs) varied from 13% to 75%, and disease control rates (DCRs) ranged from 47% to 62.5%. irAEs occurred in 25% to 75% of patients, with 6–20% experiencing grade 3–4 events. Corticosteroids were required in 13–29% of patients, and treatment discontinuation due to toxicity occurred in up to 30%. Most patients had controlled HIV, with CD4 counts typically above 300 cells/μL and undetectable viral loads. Conclusions: ICIs appear safe and effective in PWH with NSCLC, with toxicity and efficacy outcomes comparable to the general population. While immunotherapy should not be withheld based solely on HIV status, better standardization in reporting HIV-related variables is needed to optimize patient selection and management. Full article
(This article belongs to the Special Issue Comprehensive Strategies in Cancer Immunotherapy)
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21 pages, 2647 KB  
Systematic Review
Efficacy and Safety of Non-Surgical Treatments for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis
by Mohammed Saad AlQahtani, Bogdan Miutescu, Ielmina Domilescu, Serban Negru, Dorel Popovici and Eyad Gadour
Pharmaceuticals 2025, 18(11), 1650; https://doi.org/10.3390/ph18111650 (registering DOI) - 31 Oct 2025
Abstract
Background: Pancreatic neuroendocrine tumor (pNET) is a rare and complex disease that requires careful management and treatment. Currently, a range of treatments, including surgery, somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy, exist for pNETs. However, determining [...] Read more.
Background: Pancreatic neuroendocrine tumor (pNET) is a rare and complex disease that requires careful management and treatment. Currently, a range of treatments, including surgery, somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy, exist for pNETs. However, determining the optimal treatment strategies remains challenging. Aim: To evaluate the efficacy and safety of non-surgical therapies, such as somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy in treating pNETs. Methods: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science databases for relevant studies published from inception until August 2025. Randomized clinical trials (RCTs), non-randomized clinical trials, and prospective studies were included in this meta-analysis if they evaluated the efficacy and safety of any treatment of interest in patients with pNETs. Results: Thirty-three studies involving 2374 pNET patients were analyzed. Targeted therapies showed modest objective response rates (ORRs) but high disease control rates (DCRs): everolimus (ORR 7%, 95% CI: 3–10%; DCR 81%, 95% CI: 75–87%), sunitinib (ORR 12%, 95% CI: 5–19%; DCR 79%, 95% CI: 70–88%), surufatinib (ORR 19%, 95% CI: 12–27%; DCR 81%, 95% CI: 73–89%). Cytotoxic chemotherapy demonstrated higher ORRs: dacarbazine-based (32%, 95% CI: 21–43%), streptozocin-based (40%, 95% CI: 25–54%), temozolomide-based (42%, 95% CI: 29–55%). PRRT showed varying efficacy: 177Lu-DOTATATE (ORR 36%, 95% CI: 27–44%; DCR 84%, 95% CI: 76–92%), 90Y-DOTATOC (ORR 27%, 95% CI: 18–36%; DCR 73%, 95% CI: 63–83%). SSAs had low ORRs but high DCRs: lanreotide (ORR 0%, DCR 67%, 95% CI: 57–77%), octreotide (ORR 23%, 95% CI: 15–31%; DCR 75%, 95% CI: 66–84%). Immunotherapy with pembrolizumab showed limited efficacy (ORR 7%, 95% CI: 0–14%). Treatment-related adverse events were common across therapies, with specific toxicity profiles for each modality. Conclusions: Cytotoxic chemotherapy offers better response rates than other treatment modalities. However, toxicity management is crucial. PRRT also shows robust antitumor activity and disease control, while SSAs and targeted therapies are effective treatment options for disease stabilization. Immunotherapy demonstrated limited antitumor activity, and further research is needed to establish its role in pNET treatment. Full article
(This article belongs to the Special Issue Drug Treatment of Cancers)
20 pages, 1170 KB  
Systematic Review
Berries and Bone Health: A Systematic Review of Their Polyphenols in Osteoporosis Prevention
by Simone Perna, Giorgia F. Ruina, Asmita Acharya, Giuseppe Mazzola, Mariangela Rondanelli and Patrizia Riso
Nutrients 2025, 17(21), 3440; https://doi.org/10.3390/nu17213440 (registering DOI) - 31 Oct 2025
Abstract
Background: Oxidative stress and inflammation contribute to osteoporosis. Berries provide polyphenols especially anthocyanins that may modulate bone remodeling. This review is the first to synthesize evidence specifically on berries and bone health, integrating human, animal, and in vitro data under the GRADE [...] Read more.
Background: Oxidative stress and inflammation contribute to osteoporosis. Berries provide polyphenols especially anthocyanins that may modulate bone remodeling. This review is the first to synthesize evidence specifically on berries and bone health, integrating human, animal, and in vitro data under the GRADE framework. Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library through 23 April 2025 for human, animal, and in vitro studies on berries or berry-derived compounds and bone outcomes. Risk of bias was assessed with RoB 2.0, ROBINS-I, SYRCLE, and an adapted ToxRTool; certainty of human evidence was appraised with GRADE. Results: Forty-six studies were included (12 human, 20 animal, 14 in vitro). Observational cohorts linked higher anthocyanin intake with greater BMD. Small randomized trials suggested modest benefits of blackcurrant and blueberry on whole-body BMD, bone turnover markers, and calcium retention, while results for biomarkers were mixed. Animal models generally showed attenuation of ovariectomy- or age-related bone loss, and in vitro experiments indicated inhibition of osteoclastogenesis with stimulation of osteoblast activity. By GRADE, certainty was low–moderate for BMD, low for biomarkers, and very low for fractures. Conclusions: Berry polyphenols may support skeletal health via antioxidant and anti-resorptive mechanisms, but current clinical evidence is limited by small samples, heterogeneity, and lack of fracture outcomes. Larger, longer, standardized RCTs with exposure profiling are needed before dietary recommendations can be made. Full article
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23 pages, 2279 KB  
Review
Effects of Gluten-Free Diet in Non-Celiac Hashimoto’s Thyroiditis: A Systematic Review and Meta-Analysis
by Edilene Maria Queiroz Araújo, Claubert Radamés Oliveira Coutinho-Lima, André Silva de Sousa, Lana Mércia Santiago de Souza, Helton Estrela Ramos, Bianca de Almeida-Pititto, Graziela De Luca Canto and Virginia Fernandes Moça Trevisani
Nutrients 2025, 17(21), 3437; https://doi.org/10.3390/nu17213437 (registering DOI) - 31 Oct 2025
Abstract
Background/Objectives: The gluten-free diet (GFD) may be anti-inflammatory in treating Hashimoto’s thyroiditis (HT), but the studies are inconsistent. Methods: To determine the effects of the GFD in non-celiac HT, we included randomized controlled trials from the following databases: Cochrane Central, Embase, [...] Read more.
Background/Objectives: The gluten-free diet (GFD) may be anti-inflammatory in treating Hashimoto’s thyroiditis (HT), but the studies are inconsistent. Methods: To determine the effects of the GFD in non-celiac HT, we included randomized controlled trials from the following databases: Cochrane Central, Embase, Lilacs, Medline, Scopus, and Web of Science. The study was registered at Prospero (no. CRD42024566034). The outcomes assessed included free triiodothyronine (fT3), free tetraiodothyronine (fT4), thyroid stimulating hormone (TSH), Anti-thyroid Peroxidase (TPO), anti-thyroglobulin (Tg), C-reactive protein (CRP), body weight (BW), body mass index (BMI) and adverse effects. Sensitivity, subgroup, meta-regression, bias risk, and evidence analyses’ certainty were also assessed. Results: Only three studies were meta-analyzed, comprising 110 participants. The pooled data revealed the evidence was very uncertain about the effect of GFD compared to the control group on mean differences (MD) of TSH (MD −0.63 uIU/mL; 95% CI −1.63 to 0.36; p = 0.21), fT3 (MD −0.18 pg/mL; 95% CI −0.50 to 0.14; p = 0.28), fT4 (MD −0.33 ng/dL; 95% CI −0.89 to 0.23; p = 0.24), anti-Tg (MD −10.07 IU/mL; 95% CI −17.73 to −2.42; p = 0.010), anti-TPO (MD 76.19 IU/mL; 95% CI 46.86 to 108.51; p < 0.00001), CRP (MD −0.12 IU/mL; 95% CI −0.30 to 0.07), BW (MD −1.46 kg; 95% CI −6.70 to 3.77), and BMI (MD −1.80 kg/m2; 95% CI −3.30 to −0.31). The quality of evidence was rated as having serious methodological concerns to extremely serious imprecision. Conclusions: The GFD decreased anti-Tg and increased the anti-TPO levels, both significantly. There were no significant results on fT3, fT4, and TSH. Full article
(This article belongs to the Special Issue Effects of Diets and Nutrients on Immunity)
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26 pages, 1421 KB  
Systematic Review
Improving Early Prostate Cancer Detection Through Artificial Intelligence: Evidence from a Systematic Review
by Vincenzo Ciccone, Marina Garofano, Rosaria Del Sorbo, Gabriele Mongelli, Mariella Izzo, Francesco Negri, Roberta Buonocore, Francesca Salerno, Rosario Gnazzo, Gaetano Ungaro and Alessia Bramanti
Cancers 2025, 17(21), 3503; https://doi.org/10.3390/cancers17213503 - 30 Oct 2025
Abstract
Background: Prostate cancer is one of the most common malignancies in men and a leading cause of cancer-related mortality. Early detection is essential to ensure curative treatment and favorable outcomes, but traditional diagnostic approaches—such as serum prostate-specific antigen (PSA) testing, digital rectal examination [...] Read more.
Background: Prostate cancer is one of the most common malignancies in men and a leading cause of cancer-related mortality. Early detection is essential to ensure curative treatment and favorable outcomes, but traditional diagnostic approaches—such as serum prostate-specific antigen (PSA) testing, digital rectal examination (DRE), and histopathological confirmation following biopsy—are limited by suboptimal accuracy and variability. Multiparametric magnetic resonance imaging (mpMRI) has improved diagnostic performance but remains highly dependent on reader expertise. Artificial intelligence (AI) offers promising opportunities to enhance diagnostic accuracy, reproducibility, and efficiency in prostate cancer detection. Objective: To evaluate the diagnostic accuracy and reporting timeliness of AI-based technologies compared with conventional diagnostic methods in the early detection of prostate cancer. Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and Cochrane Library were searched for studies published between January 2015 and April 2025. Eligible designs included randomized controlled trials, cohort, case–control, and pilot studies applying AI-based technologies to early prostate cancer diagnosis. Data on AUC-ROC, sensitivity, specificity, predictive values, diagnostic odds ratio (DOR), and time-to-reporting were narratively synthesized due to heterogeneity. Risk of bias was assessed using the QUADAS-AI tool. Results: Twenty-three studies involving 23,270 patients were included. AI-based technologies achieved a median AUC-ROC of 0.88 (range 0.70–0.93), with median sensitivity and specificity of 0.86 and 0.83, respectively. Compared with radiologists, AI or AI-assisted readings improved or matched diagnostic accuracy, reduced inter-reader variability, and decreased reporting time by up to 56%. Conclusions: AI-based technologies show strong diagnostic performance in early prostate cancer detection. However, methodological heterogeneity and limited standardization restrict generalizability. Large-scale prospective trials are required to validate clinical integration. Full article
(This article belongs to the Special Issue Medical Imaging and Artificial Intelligence in Cancer)
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20 pages, 4360 KB  
Systematic Review
Efficacy and Safety of Fundoplication Sleeve Gastrectomy in Obesity and GERD: A Systematic Review and Meta-Analysis
by Filipe Amorim-Cruz, Diogo Fernandes Lopes, Bernardo Sousa-Pinto and Hugo Santos-Sousa
J. Clin. Med. 2025, 14(21), 7723; https://doi.org/10.3390/jcm14217723 (registering DOI) - 30 Oct 2025
Abstract
Background/Objectives: Laparoscopic sleeve gastrectomy (SG) is the most performed bariatric procedure, providing effective weight loss and comorbidity improvement. However, its association with new-onset or worsening gastroesophageal reflux disease (GERD) remains a limitation. To address this, fundoplication sleeve gastrectomy (FSG) has been proposed [...] Read more.
Background/Objectives: Laparoscopic sleeve gastrectomy (SG) is the most performed bariatric procedure, providing effective weight loss and comorbidity improvement. However, its association with new-onset or worsening gastroesophageal reflux disease (GERD) remains a limitation. To address this, fundoplication sleeve gastrectomy (FSG) has been proposed by combining SG with an anti-reflux procedure. This systematic review and meta-analysis evaluates the efficacy and safety of FSG in patients with severe obesity. Methods: PubMed, Scopus, and Web of Science were systematically searched up to December 2023. Eligible studies included adults with BMI ≥ 40 kg/m2 or ≥35 kg/m2 with comorbidities undergoing FSG or SG with ≥12 months of follow-up. Random-effects meta-analysis compared FSG and SG in terms of weight loss, postoperative GERD, and complications. Results: Twelve studies (n = 543) were included; five contributed to the meta-analysis. Pooled analysis showed no significant difference in percentage of excess weight loss (%EWL) between FSG and SG (Hedges’ g = −0.11; 95% CI: −0.99–0.76; I2 = 86%), and similar %TWL outcomes (Hedges’ g = −0.28; 95% CI: −0.70–0.13). FSG demonstrated a significantly lower postoperative GERD prevalence (RR = 0.08; 95% CI: 0.01–0.47) and greater GERD resolution (RR = 1.86; 95% CI: 0.80–4.20), but higher complication (RR = 2.95; 95% CI: 1.02–8.50) and reoperation rates (RR = 4.39; 95% CI: 1.47–13.12). Conclusions: FSG achieves weight loss comparable to SG and may reduce postoperative GERD prevalence, but carries an increased complication and reoperation risk. Further randomized trials with standardized GERD definitions and longer follow-up are required. Full article
(This article belongs to the Special Issue New Approaches in Bariatric Surgery)
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24 pages, 1838 KB  
Systematic Review
Promising, but Not Completely Conclusive—The Effect of l-Theanine on Cognitive Performance Based on the Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Trials
by Rebeka Olga Mátyus, Zsóka Szikora, Diána Bodó, Bettina Vargáné Szabó, Éva Csupor, Dezső Csupor and Barbara Tóth
J. Clin. Med. 2025, 14(21), 7710; https://doi.org/10.3390/jcm14217710 - 30 Oct 2025
Viewed by 3
Abstract
Background: Green tea (Camellia sinensis) has been consumed for centuries, and its beneficial effects on human health have been studied in recent decades. l-theanine, an active ingredient in green tea, has been used to improve cognition and mood. Although the [...] Read more.
Background: Green tea (Camellia sinensis) has been consumed for centuries, and its beneficial effects on human health have been studied in recent decades. l-theanine, an active ingredient in green tea, has been used to improve cognition and mood. Although the effects of l-theanine on cognition have been investigated in clinical trials that have reported various results, these studies have not yet been critically evaluated in meta-analyses. Objectives: Our objective was to systematically evaluate the efficacy of l-theanine on cognitive functions compared to a placebo, in a meta-analysis based on randomized controlled trials (RCTs). Methods: PubMed, the Cochrane Central Register of Controlled Trials, Embase and Web of Science were searched for relevant studies until 31 July 2024 and registered in PROSPERO (registration number: CRD42024575122). Placebo-controlled clinical trials investigating the efficacy of l-theanine in healthy adults were included. Conference abstracts, study protocols and reports of non-RCTs were excluded. For risk of bias assessment, the Cochrane Risk of Bias Tool (version 2.0) was used. A random effects model was applied to conduct the meta-analysis. Mean differences (MD) with 95% confidence intervals (CIs) were calculated. Results: Based on the included five RCTs involving 148 healthy adults, l-theanine had a dose-dependent effect on cognitive function based on rapid visual information processing and recognition visual reaction time (MD: −15.20 ms; 95%-CI [−28.99; −1.41]). The effects of l-theanine were non-significant on reaction time to a simple stimulus (MD: −0.46 ms; 95% [CI: −15.65; 14.73]) and in the Stroop test (MD: −37.38 ms; 95%-CI [−86.39; 11.62]). Conclusions: The beneficial effects of l-theanine on cognitive performance could not be confirmed by all test methods. The contradictory results could be explained by the fact that l-theanine only affects certain cognitive domains, but also by the low number of trials and the heterogeneity of the test preparations. Further trials using standardized products with larger sample sizes are required for the accurate assessment of efficacy. Full article
(This article belongs to the Section Mental Health)
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18 pages, 2310 KB  
Systematic Review
Is Ti-Coated PEEK Superior to PEEK for Lumbar and Cervical Fusion Procedures? A Systematic Review and Meta-Analysis
by Julia Kincaid, Richelle J. Kim, Akash Verma, Ryan W. Turlip, David D. Liu, Daksh Chauhan, Mert Marcel Dagli, Richard J. Chung, Hasan S. Ahmad, Yohannes Ghenbot, Ben Gu and Jang Won Yoon
J. Clin. Med. 2025, 14(21), 7696; https://doi.org/10.3390/jcm14217696 - 30 Oct 2025
Viewed by 142
Abstract
Background/Objectives: Utilization of polyetheretherketone (PEEK) cages for spinal fusion has surged in the U.S., yet comprehensive comparisons evaluating its postoperative effectiveness with alternative materials remain limited. This systematic review investigates the efficacy of PEEK cages against traditional fusion materials across various surgery [...] Read more.
Background/Objectives: Utilization of polyetheretherketone (PEEK) cages for spinal fusion has surged in the U.S., yet comprehensive comparisons evaluating its postoperative effectiveness with alternative materials remain limited. This systematic review investigates the efficacy of PEEK cages against traditional fusion materials across various surgery types, elucidating PEEK’s impact on fusion rates, postoperative outcomes, and long-term success. Methods: A systematic search of PubMed, CINAHL, Scopus, Embase, and Web of Science was conducted through 14 October 2024. Included studies were randomized controlled trials (RCTs) comparing PEEK cages with titanium, silicon nitride, and metal-coated PEEK cages for anterior cervical discectomy and fusion (ACDF), posterior lumbar interbody fusion (PLIF), and transforaminal lumbar interbody fusion (TLIF). Article quality was assessed using GRADE criteria. Results: From 288 initially screened articles, 25 RCTs involving 2046 patients (mean follow-up 23.1 ± 18.2 months) met inclusion criteria and were determined as moderate (n = 21) or high (n = 4) quality. Fusion rates by cage material for PEEK (n = 1041), Ti-PEEK (n = 291), and titanium (n = 53) were 85.63 ± 18.00%, 80.05 ± 19.9%, and 92.75 ± 11.31%, respectively. In ACDF, titanium cages achieved higher fusion rates than PEEK (100% vs. 94%). In PLIF and TLIF, coated PEEK outperformed uncoated PEEK (75% vs. 71% and 94% vs. 84%, respectively). Uncoated PEEK achieved fusion rates of 94.04 ± 5.04% for ACDF, 71.21 ± 21.93% for PLIF, and 83.50 ± 24.66% for TLIF, with titanium outperforming PEEK in early fusion outcomes. Coated PEEK demonstrated potential improvements in fusion rates over uncoated PEEK in PLIFs and TLIFs. Conclusions: Selection of cage material for spinal fusions should be tailored to surgical requirements and patient needs. While titanium and PEEK are effective, their performance varies across contexts. New materials and surface modifications may enhance these outcomes further, warranting future research in long-term studies and development of novel materials. These findings can help surgeons choose cage materials according to procedure type, patient characteristics, and imaging needs. Full article
(This article belongs to the Special Issue Clinical Advances in Spinal Neurosurgery)
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18 pages, 315 KB  
Review
Antibiotics for Rheumatologic Diseases: A Critical Review
by Matthew E. Falagas, Panagiotis Stathopoulos, Dimitrios S. Kontogiannis and Iva D. Tzvetanova
Int. J. Mol. Sci. 2025, 26(21), 10527; https://doi.org/10.3390/ijms262110527 - 29 Oct 2025
Viewed by 105
Abstract
Antibiotics have been traditionally used to treat patients with infectious diseases. However, recent investigations have highlighted their immunomodulating features. Additionally, they have been used to treat patients with rheumatologic diseases of proven infectious etiology. Thus, an emerging body of literature is developing on [...] Read more.
Antibiotics have been traditionally used to treat patients with infectious diseases. However, recent investigations have highlighted their immunomodulating features. Additionally, they have been used to treat patients with rheumatologic diseases of proven infectious etiology. Thus, an emerging body of literature is developing on the potential role of antibiotics in managing patients with rheumatologic diseases, which are primarily characterized by autoimmune-driven inflammation. We critically review the potential use of antibiotics in rheumatology, focusing on both their direct antimicrobial actions and immunomodulatory effects. We also examine the potential clinical applications, underlying pharmacological mechanisms, controversies, and future research directions. Databases of biomedical research (PubMed, Scopus, Web of Science, and Cochrane) and Google Scholar were searched. The critical evaluation of the available data suggests that antibiotics should be used only for patients with rheumatologic diseases with a clear infectious etiology. These indications are the treatment and prevention of recurrence of rheumatic fever, Whipple’s disease, and early Lyme disease. Additionally, antibiotics may be considered for early administration in patients with reactive arthritis. Until data from robust clinical trials support the consideration of antibiotics in other rheumatologic diseases, beyond those with a clear infectious etiology, clinicians should follow the internationally relevant guidelines and avoid their use in treating such diseases in this patient population. Further studies may offer additional data for using antibiotics in treating patients with additional rheumatologic diseases, especially in cases where conventional treatments have inadequate effectiveness or are associated with considerable adverse events. Full article
(This article belongs to the Special Issue Drug Treatment for Bacterial Infections)
24 pages, 1072 KB  
Systematic Review
The Role of the Oral Microbiome and Dental Caries in Respiratory Health: A Systematic Review
by Łukasz Zygmunt, Sylwia Kiryk, Kamil Wesołek, Jan Kiryk, Izabela Nawrot-Hadzik, Zbigniew Rybak, Klaudia Sztyler, Agata Małyszek, Jacek Matys and Maciej Dobrzyński
J. Clin. Med. 2025, 14(21), 7670; https://doi.org/10.3390/jcm14217670 - 29 Oct 2025
Viewed by 226
Abstract
Objectives: This systematic review aimed to evaluate the association between oral health—particularly dental caries and dysbiosis of the oral microbiome—and respiratory diseases across different age groups and clinical settings, with emphasis on microbial overlap, clinical outcomes, and preventive strategies. Methods: A systematic search [...] Read more.
Objectives: This systematic review aimed to evaluate the association between oral health—particularly dental caries and dysbiosis of the oral microbiome—and respiratory diseases across different age groups and clinical settings, with emphasis on microbial overlap, clinical outcomes, and preventive strategies. Methods: A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, and the Cochrane Library up to June 2025. Eligible studies included randomized controlled trials, cohort, case–control, and cross-sectional investigations examining the relationship between oral diseases or microbiome alterations and respiratory outcomes. Data on study design, population, oral health parameters, microbial taxa, and respiratory endpoints were extracted. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT, 2018). Results: Twenty studies met the inclusion criteria, encompassing pediatric, adult, and elderly populations. Poor oral health, reflected by higher caries indices and periodontal inflammation, was consistently associated with increased risk of lower respiratory tract infections (LRTI), aspiration events, ventilator-associated pneumonia (VAP), and impaired pulmonary function. Oral microbiome analyses revealed enrichment of Veillonella, Prevotella, Klebsiella, and Pseudomonas species in both oral and airway samples, supporting the oral cavity as a reservoir for respiratory pathogens. Interventional evidence from intensive care and nursing home settings demonstrated that structured oral care—particularly daily toothbrushing and chlorhexidine-based plaque control—significantly reduced pneumonia incidence. Conclusions: This review confirms a clinically relevant and biologically plausible link between oral dysbiosis, dental caries, and respiratory disease. Oral biofilms contribute to infection risk through microaspiration and microbial seeding of the lower airways. Integrating oral screening, hygiene maintenance, and treatment of active oral disease into respiratory care pathways may reduce respiratory morbidity and mortality, particularly among high-risk populations such as ICU patients, older adults, and individuals with chronic lung disease. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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23 pages, 3451 KB  
Systematic Review
Effect of Neurokinin-1 Receptor Antagonists on Experimental Postoperative Adhesion: A Systematic Review and Meta-Analysis with Trial Sequential Analysis of Preclinical Studies
by Hyeon Joung Hwang, Geun Joo Choi, Yoo Shin Choi, Beom Gyu Kim and Hyun Kang
Medicina 2025, 61(11), 1933; https://doi.org/10.3390/medicina61111933 - 28 Oct 2025
Viewed by 124
Abstract
Background and Objectives: Postoperative adhesions are a major surgical concern. Preclinical studies of neurokinin-1 receptor antagonists (NK-1RAs) have reported inconsistent findings. We conducted a systematic review and meta-analysis with trial sequential analysis (TSA) to evaluate whether NK-1RAs prevent postoperative adhesions. Materials and [...] Read more.
Background and Objectives: Postoperative adhesions are a major surgical concern. Preclinical studies of neurokinin-1 receptor antagonists (NK-1RAs) have reported inconsistent findings. We conducted a systematic review and meta-analysis with trial sequential analysis (TSA) to evaluate whether NK-1RAs prevent postoperative adhesions. Materials and Methods: We searched MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, and Google Scholar for animal studies assessing NK-1RAs applied to the surgical site. The primary outcome was macroscopic adhesion score; secondary outcomes were tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) mRNA expression in peritoneal tissue and t-PA activity in peritoneal tissue. Results: Nine studies including 331 animals (162 NK-1RA; 169 control) met the criteria. Macroscopic adhesion scores were significantly lower with NK-1RAs than control (standardized mean difference [SMD] 1.474; 95% confidence interval [CI] 1.030 to 1.918; Pchi2 = 0.001; I2 = 63.8%; τ = 0.619; 95% predictive interval [PrI] 0.133 to 2.815). TSA showed the cumulative Z-curve crossed both the conventional and trial sequential monitoring boundaries for the macroscopic adhesion score. t-PA activity was higher with NK-1RAs (SMD −1.219; 95% CI −2.379 to −0.058; Pchi2 < 0.001; I2 = 77.66%; τ = 1.453; PrI −4.655 to 2.217). There was no evidence of a difference in t-PA or PAI-1 mRNA expression. Conclusions: NK-1RAs reduced postoperative adhesions by macroscopic scoring and increased t-PA activity in preclinical models. Full article
(This article belongs to the Section Surgery)
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12 pages, 936 KB  
Protocol
Using Citizen Science to Address Out-of-Pocket Healthcare Expenditure with Aboriginal Communities in the Far West of South Australia: A Protocol
by Courtney Ryder, Ray Mahoney, Patrick Sharpe, Georga Sallows, Karla Canuto, Andrew Goodman, Julieann Coombes, Odette Pearson, Jaquelyne T. Hughes, Marlien Varnfield, Candice Oster, Jonathan Karnon, Claire Drummond, James A. Smith, Shanti Omodei-James, Lavender Otieno, Ali Soltani and Billie Bonevski
Int. J. Environ. Res. Public Health 2025, 22(11), 1640; https://doi.org/10.3390/ijerph22111640 - 28 Oct 2025
Viewed by 191
Abstract
Out-of-pocket health expenditure (OOPHE) significantly impacts people with chronic and complex diseases (CCDs) and injuries. Aboriginal communities experience a higher burden of CCDs and injury, along with greater OOPHE inequities. This project aims to develop and implement a social prescribing digital platform (Web [...] Read more.
Out-of-pocket health expenditure (OOPHE) significantly impacts people with chronic and complex diseases (CCDs) and injuries. Aboriginal communities experience a higher burden of CCDs and injury, along with greater OOPHE inequities. This project aims to develop and implement a social prescribing digital platform (Web App) to reduce OOPHE. It is grounded in citizen science approaches that value the lived experience and knowledge of Aboriginal people in shaping solutions. The project uses a citizen science methodology adapted for these communities, using knowledge interface methodology to weave together Indigenous and Western knowledges. Research methods (Indigenous, quantitative, qualitative) explore the relational nature of OOPHE risks and protective factors through co-design and workshops with Aboriginal participants to develop the Web App. A community-centric developmental evaluation guides the trial and refinement of the platform, allowing for ongoing learning and adaptation. Process measures inform a national scale-up and evaluation framework. Addressing OOPHE is essential to improving health and wellbeing for Aboriginal and Torres Strait Islander individuals and families living with or at risk of CCDs. This initiative aims to reduce the impact of OOPHE through digital social prescribing, there by connecting people with essential community services to access healthcare, offering a scalable approach to addressing health inequities nationwide. Full article
(This article belongs to the Section Global Health)
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42 pages, 5104 KB  
Systematic Review
Tai Chi Exercise and Bone Health in Women at Perimenopausal and Postmenopausal Stages: A Systematic Review and Meta-Analysis
by Wenhui Yin, Zhuo Zeng, Wenyan Yin, Long Xi, Dong Wu and Fengjie Qiao
Life 2025, 15(11), 1678; https://doi.org/10.3390/life15111678 - 28 Oct 2025
Viewed by 191
Abstract
This study systematically examined the effects of Tai Chi exercise on bone health in menopausal women, with subgroup analyses of potential moderators. A systematic search was conducted across nine databases (PubMed, Web of Science, Cochrane Library, EBSCO-Medline, EBSCO-Sportdiscus, Embase, CNKI, VIP and Wanfang [...] Read more.
This study systematically examined the effects of Tai Chi exercise on bone health in menopausal women, with subgroup analyses of potential moderators. A systematic search was conducted across nine databases (PubMed, Web of Science, Cochrane Library, EBSCO-Medline, EBSCO-Sportdiscus, Embase, CNKI, VIP and Wanfang Data) on June 1 and updated on 14 September 2025 to identify controlled trials evaluating perimenopausal or postmenopausal women. A three-level meta-analysis was performed to pool effect estimates, reported as standardized mean differences (SMDs), with heterogeneity further explored through subgroup analyses. Across 16 studies involving 1091 participants aged 49–64 years, Tai Chi interventions led to significant improvements in bone health. Training protocols ranged from 6 to 104 weeks, with sessions lasting 30 to 90 min. Bone mineral density (BMD) improved significantly at the femoral neck (SMD = 0.50), greater trochanter (SMD = 0.61), and lumbar spine L2–L4 (SMD = 0.81), with stronger effects observed in perimenopausal women. Bone mineral content (BMC) also increased significantly in menopausal women (SMD = 1.63, I2 = 91.46%), although heterogeneity was substantial, and no significant differences were detected in subgroup moderators. In contrast, no significant effects were found for bone mineral metabolism (p = 0.38) or bone turnover markers (p = 0.25). According to GRADE assessments, the certainty of evidence ranged from low to moderate across these outcomes. In conclusion, while Tai Chi has been shown to improve BMD and BMC in menopausal women, the relatively high heterogeneity observed for BMC necessitates cautious interpretation of these particular outcomes. In contrast, no statistically significant effects were observed on bone mineral metabolism (BMM) and bone turnover markers (BTMs). Notably, given the significant differences observed between perimenopausal and postmenopausal women, future well-designed studies that stratify participants by menopausal status and possess adequate statistical power are needed to further explore the potential differential effects of Tai Chi on bone health. Full article
(This article belongs to the Special Issue Biomarker Analysis for Sports Performance and Health)
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24 pages, 5039 KB  
Article
Diet Reconstruction Under Limited Prior Information: Dietary Contributions and Isotopic Niche of Metridium senile in the North Yellow Sea
by Yongsong Zhao, Xiujuan Shan, Guangliang Teng, Shiqi Song, Yunlong Chen and Xianshi Jin
Biology 2025, 14(11), 1508; https://doi.org/10.3390/biology14111508 - 28 Oct 2025
Viewed by 275
Abstract
Biomass of the plumose anemone Metridium senile has surged in the benthic ecosystem of the North Yellow Sea in recent years. Understanding its diet and the proportional contributions of food sources is essential for assessing the ecological consequences of this expansion. The species [...] Read more.
Biomass of the plumose anemone Metridium senile has surged in the benthic ecosystem of the North Yellow Sea in recent years. Understanding its diet and the proportional contributions of food sources is essential for assessing the ecological consequences of this expansion. The species is often characterized as a passive suspension feeder, yet laboratory feeding trials have documented shrimp consumption. Because prior dietary information from the region is scarce, conventional stable isotope approaches are poorly constrained. We developed an integrative framework coupling trophic position estimation, isotopic niche metrics, spatial point pattern analysis, and a Bayesian mixing model to improve diet attribution under limited prior information and to test whether M. senile preys on small-bodied and juvenile teleosts and invertebrates under natural conditions. Our analyses showed that: (i) M. senile occupied a high trophic position (TP = 3.09 ± 0.25), exceeding those estimated for putative predators in our dataset, implying weak top-down control; (ii) in isotopic niche analyses, M. senile showed high posterior probabilities of occurring within the niches of cephalopods and medium-sized fishes (78.30% and 63.04%, respectively), consistent with shared prey and inconsistent with a strictly suspension-feeding strategy; (iii) mixing space diagnostics informed by spatial point pattern analysis indicated that including small-sized fishes and shrimps as sources was necessary to reconcile the elevated TP; and (iv) the Bayesian mixing model estimated that small-bodied and juvenile teleosts and invertebrates supplied most long-term nutrition (posterior mean ≈ 0.65), with the remainder from suspension-derived sources, consistent with an opportunistic generalist rather than a strict suspension feeder. Sustained predation on small-bodied and juvenile teleosts and invertebrates could suppress early fish recruitment, impose top-down control on forage species, and alter the local food web structure. Management should monitor M. senile (size structure, population density, and co-occurrence with juveniles and forage biota) and consider targeted removals and seafloor litter cleanups in priority habitats. The framework is applicable to diet studies with limited prior information; adding δ34S, compound-specific amino-acid isotopes (CSIA-AA), and DNA-based dietary evidence should further sharpen source discrimination. Full article
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13 pages, 987 KB  
Systematic Review
The Effects of Virtual Reality Interventions on Motor Function Rehabilitation in Lower-Limb Amputees: A Systematic Review and Metanalysis
by Jade Paillet, Manuel del Valle Rodríguez, Javier Herranz Vázquez, Francisco Javier Ruiz-Matas Contreras, Julia Raya-Benítez, María Granados Santiago and Marie Carmen Valenza
Bioengineering 2025, 12(11), 1170; https://doi.org/10.3390/bioengineering12111170 - 28 Oct 2025
Viewed by 223
Abstract
Background: Lower-limb amputation is a complex condition that profoundly affects motor function and patients’ quality of life. Physical therapists are key in managing lower-limb amputees, and emerging technologies such as virtual reality offer promising tools to further enhance motor function. This review aims [...] Read more.
Background: Lower-limb amputation is a complex condition that profoundly affects motor function and patients’ quality of life. Physical therapists are key in managing lower-limb amputees, and emerging technologies such as virtual reality offer promising tools to further enhance motor function. This review aims to assess the effectiveness of virtual reality-based rehabilitation in improving motor function in lower-limb amputees. Method: A systematic review was conducted using the PubMed, Scopus, and Web of Science databases, covering all studies published from their inception to July 2025. The study population consisted of adult lower-limb amputees receiving virtual reality-based rehabilitation, either alone or combined with other interventions. The search strategy included key terms such as “amputee,” “limb loss,” and “virtual reality,” with no date restrictions. Results: Six studies, all randomized controlled trials, were included and featured a variety of protocols. Meta-analysis showed no significant improvement in walking capacity in the experimental group when compared with controls (p > 0.05). In contrast, postural stability demonstrated significant improvement in the experimental group, with high consistency across studies (I2 = 0%). Conclusions: Current evidence suggests that virtual reality may be an effective approach to improving motor function in lower-limb amputees. However, the studies exhibit methodological limitations, highlighting the need for further research to standardize protocols and evaluate long-term benefits. Full article
(This article belongs to the Special Issue Musculoskeletal Function in Health and Disease)
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