Search Results (19,999)

Objectives: This study aimed to evaluate the effects of a combined treatment consisting of O₂O₃ injections and McKenzie-based physiotherapy exercises, compared to a Control group treated with O₂O₃ injections and a Back School physiotherapy program, in reducing pain and disability in individuals with chronic non-specific neck pain. Methods: In this prospective double-arm pilot study, patients with chronic non-specific neck pain and a Numerical Rating Scale (NRS) > 4 were enrolled. All patients received eight weekly sessions of O₂O₃ injections (10 μg/mL, 10 mL total, and 2 mL bilaterally into the cervical paravertebral muscles). Patients were then randomly assigned (1:1 ratio) to either an experimental group receiving McKenzie physiotherapy or a Control group undergoing Back School techniques, with five sessions per week over two weeks. Outcome measures included the Neck Disability Index (NDI), NRS, EuroQol-5D-3L (EQ5D3L), and EuroQol Visual Analog Scale (EQ-VAS). Results: A total of 41 patients were included and divided into two groups: Back School (n = 21; mean age: 63.9 ± 13.4 years) and McKenzie (n = 20; mean age: of 57.3 ± 12.9 years). Both groups showed significant improvement in NDI, NRS, EQ5D3L, and EQ-VAS following the O₂O₃ injection cycle (∆T0–T1 p < 0.001). The subsequent addition of physical therapy led to further improvements across all outcomes in both groups (∆T1–T2 p < 0.001), with the McKenzie group showing slightly greater benefits, despite the lack of significant differences. Conclusions: This study demonstrated the effects of combining O₂O₃ injections with either McKenzie or Back School therapy in improving pain, disability, and quality of life in patients with chronic non-specific neck pain. Full article

Background/Objectives: Bronchopulmonary dysplasia (BPD) remains a major morbidity among extremely premature infants, with variability in the application of evidence-based interventions between and within neonatal intensive care units (NICUs). We evaluated a multi-component, risk-guided personalized implementation strategy for BPD prevention in a real-world setting. Methods: We conducted a prospective observational study of infants <29 weeks’ gestation at birth admitted to a quaternary NICU. The intervention combined risk stratification and structured longitudinal care planning rounds (LCPRs) that included standardized documentation, multidisciplinary facilitation, and associated continuous quality improvement strategies. Implementation outcomes were assessed using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. Secondary outcomes included care processes, provider-reported measures, and exploratory clinical outcomes. Results: Over six months, 41 infants were included. Risk stratification was consistently applied and all fifteen high-risk infants received LCPR, demonstrating targeted reach. Multidisciplinary participation was broad, with implementation fidelity reflected by consistent screening, structured documentation, and timely care plan execution. Practice standardization was observed, including consistent corticosteroid use (100%), earlier initiation of systemic postnatal steroids (median 16 days), and selective adjunctive therapy use. Providers reported improved teamwork, care coordination, and confidence. Rates of BPD or mortality were comparable between higher-risk infants receiving LCPR and lower-risk infants, despite greater illness severity in the LCPR group. Respiratory severity scores showed a downward trend after implementation, though this did not reach statistical significance (p = 0.07). Strategy use continued beyond the study period indicating early sustainability. Conclusions: A multi-component, risk-guided implementation strategy can be effectively integrated into routine NICU practice, improving care processes while maintaining clinical outcomes in high-risk infants compared with lower-risk infants. Full article

Wound healing is a complex, multi-stage process governed by tightly regulated molecular mechanisms. However, effective regenerative therapies remain with limitations. This study presents a novel marine-derived biocomposite, JPC-ALG-CT, designed to improve wound healing through synergistic bioactive mechanisms. The material incorporates collagen extracted from the jellyfish Rhizostoma pulmo, chitosan derived from the crab Pachygrapsus mormoratus, and polysaccharide-rich extracts from the green alga Cladophora vagabunda, all sourced from the Black Sea. The study is based on the biochemical analysis of these three marine-derived components, highlighting the collagen content of jellyfish, the polysaccharides present in algae, and the bioactive properties of chitosan. The biochemical and physico-chemical properties of each component were characterized, with particular emphasis on the structural features of jellyfish collagen and the functional bioactivity of chitosan and algal polysaccharides. The research findings are supported by the identification of the collagen type extracted from jellyfish, as well as by the characterization of chitosan and green algal extracts. The resulting composite demonstrated significant antioxidant and antimicrobial activities, indicating its potential to integrate key processes involved in wound repair, including inflammation control and microbial protection. In vitro studies using fibroblast and keratinocyte models showed that the JPC-CT-ALG biocomposite supported cell viability at lower tested concentrations and promoted scratch closure in cell monolayers, suggesting preliminary wound-relevant biological activity. These findings suggest that the combined marine-derived components interact to enchance wound healing at the cellular level. This work evidenced the potential of marine biomaterials as sources for next-generation regenerative therapies and supports further investigation into their molecular mechanisms and in vivo applications for improved wound care. Full article

Background: Staphylococcus aureus neonatal osteomyelitis (SA-NOm) is a rare condition with the potential for lifelong skeletal morbidity. Available evidence remains scarce and inconsistent, with notable differences in clinical presentation, therapeutic regimens, and reported outcomes, underscoring the need for a systematic evaluation combining clinical experience with existing literature. Methods: We retrospectively reviewed data from all neonates admitted to Regina Margherita Children’s Hospital, Turin, Italy, between 2017 and 2024 with a diagnosis of SA-NOm. A structured narrative review of the pertinent literature published over the past 25 years was conducted to identify additional cases and compare management approaches. Results: Four neonates with SA-NOm were identified at our center (institutional cohort) while a literature review retrieved 38 additional cases (literature cohort) to establish a combined cohort (n = 42). Of these, 78% were born at term, with a male-to-female ratio of 1.6:1 (26 males, 16 females). Approximately half of the combined cohort presented identifiable risk factors for SA-NOm, including neonatal intensive care unit admission, prematurity, sepsis, or maternal complications. Across the combined cohort, the mean age at presentation was 19 days. The most common presenting signs were local swelling and reduced mobility of the affected limb, although systemic symptoms often complicated early recognition. Long bones were most frequently involved—particularly the femur, humerus, and tibia—with equal distribution between upper and lower extremities. The mean intravenous antibiotic duration for the combined cohort was 31.6 days, followed by two to three weeks of oral therapy. Empiric regimens varied, including glycopeptides alone or combined with second- or third-generation cephalosporins, anti-staphylococcal penicillins, or carbapenems. Sequelae rates were rarely reported in the literature, likely due to limited follow-up, whereas extended surveillance in our cohort revealed substantial long-term morbidity, including restricted joint mobility, limb length discrepancy, and persistent radiographic abnormalities. Conclusions: SA-NOm, due to its rarity and potential for long-term skeletal sequelae, requires early diagnosis and timely empiric antibiotic therapy based on local resistance data. Prospective multicenter studies are needed to define standardized diagnostic and therapeutic protocols. Full article

Background: Multimodal rehabilitation represents standard practice in musculoskeletal care, where exercise therapy is routinely combined with manual therapy, electrotherapy, education, and cognitive–behavioral strategies. However, research has largely evaluated these modalities in isolation, and no bibliometric synthesis has characterized multimodal rehabilitation despite its predominance in routine practice. Objective: To characterize global research activity, thematic clusters, and diagnostic patterns underpinning multimodal musculoskeletal rehabilitation and to examine their alignment with contemporary rehabilitation guidelines and practice models. Methods: A bibliometric and altmetric analysis was performed using Web of Science Core Collection (1989–2026). Studies indexed under exercise therapy, manual therapy, electrotherapy, education, and cognitive–behavioral approaches were included. Network analyses (co-occurrence, co-authorship, thematic evolution, and bibliographic coupling) were conducted using Bibliometrix and VOSviewer. Diagnostic subgroups included osteoarthritis, low back pain, chronic musculoskeletal pain, tendinopathy, and shoulder disorders. Results: A total of 409 publications were identified. Five multimodal combinations were recurrent: exercise + education, exercise + cognitive–behavioral therapy, exercise + manual therapy, exercise + electrotherapy, and mixed multimodal programs. Diagnostic subgrouping showed distinct patterns, with osteoarthritis and low back pain clustering around exercise + education, chronic musculoskeletal pain around exercise + CBT/self-management, and tendinopathy/shoulder disorders around exercise + manual therapy. Temporal analyses demonstrated a shift from unimodal electrophysical agents toward guideline-aligned biopsychosocial models. Altmetric signals suggested relevant dissemination and policy attention. Conclusions: Multimodal musculoskeletal rehabilitation is research-intensive, diagnosis-specific, and aligned with guideline recommendations prioritizing exercise, education, self-management, and behavioral strategies. These findings support multimodal rehabilitation as a maturing evidence-based practice model with implications for pragmatic trials, guideline implementation, and clinical service delivery. Beyond research implications, these patterns are relevant for musculoskeletal care pathways, training of rehabilitation professionals and health system planning. Full article

Purpose: Male breast cancer (maleBC) is an orphan disease. Aside from age, risk factors include genetic mutations and conditions like Klinefelter syndrome or other reasons of hypogonadism. Treatment is based on standards in women, but biological differences may exist, with maleBC exhibiting higher rates of hormone-receptor expression. Limiting data exists regarding the rate of low/ultralow HER2 expression, a predictive biomarker for the antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in HER2-negative disease in women. Materials and Methods: We conducted a retrospective single-center analysis of clinicopathological features of maleBC at a tertiary cancer center. We identified a cohort of 57 maleBC patients, described demographic, pathological, prognostic and surgical and systemic treatment data and evaluated frequencies of low and ultralow HER2 expression. Results: The mean age was 64.3 (SE ± 1.79) years; 94.7% (n = 54) of patients presented with early/nonmetastatic breast cancer and 40.7% (22 of 54) of patients exhibited nodal involvement. Most patients (92.6%, 50 of 54 patients) had luminal disease and approximately one third of patients received chemotherapy. Endocrine therapy was administered in 87.7% (n = 50/57) of cases. For 52 of the patients included, full receptor status data including HER2 IHC scoring and/or histological specimens were available. IHC slides of tumor specimens from 24 patients with either historically reported “HER2 negative” or “HER2 0” expression were available for reassessment; 79.2% (n = 19 of 24) of these tumors exhibited either HER2-low or -ultralow expression. In the whole cohort, rates of HER2-low and -ultralow expression were 75.0% (39 of 52) and 5.8% (3 of 52 patients), respectively. The median follow-up was 7 years. Six deaths occurred in the total population (n = 57). The median event-free survival (EFS) was 8.39 years (95% CI 7.36–11.35). No statistically significant associations were observed between HER2 expression categories and clinicopathological variables including grade, ER status, nodal status, genetic variant status, age, Ki67 index, or overall survival events. Conclusions: In this cohort of maleBC patients, high rates of combined HER2-low and -ultralow expression were observed upon reassessment of tumors with historically negative HER2 status, shedding light on potential ADC eligibility in male breast cancer. Full article

Ferroptosis, an iron-dependent and lipid peroxidation-driven form of regulated cell death, has emerged as a “versatile player” in oncology. It exerts a dual, context-dependent role in cancer, acting as both a potent tumor suppressor and a facilitator of tumor progression and therapeutic resistance. This review systematically delineates the core molecular regulatory networks of ferroptosis, highlighting the intricate balance between its execution mechanisms—driven by polyunsaturated fatty acid (PUFA) oxidation, iron catalysis, and mitochondrial dysfunction—and the robust endogenous defense systems, including the GSH-GPX4, FSP1/DHODH-CoQ10, and GCH1-BH4 axes. We deeply explore the dichotomous nature of ferroptosis in tumorigenesis: while classical tumor suppressors like p53 and CDKN2A harness ferroptosis to halt tumor growth, cancer cells can hijack lipid metabolic reprogramming and specific enzymes (e.g., iPLA2β) to evade cell death and promote distant metastasis. Furthermore, we dissect the multidimensional crosstalk between ferroptosis and the tumor microenvironment (TME), emphasizing its bidirectional immunoregulatory effects. Although CD8+ T cell-derived IFN-γ can sensitize tumor cells to ferroptosis and amplify anti-tumor immunity, aberrant ferroptotic activation can paradoxically foster an immunosuppressive niche. Finally, we summarize the latest translational strategies using small-molecule inducers and synergistic combination therapies, emphasizing that biomarker-guided patient stratification remains the ultimate paradigm for overcoming resistance and realizing precision ferroptosis-targeted cancer therapy. Full article

Importance: A comprehensive analysis of childhood cancer and cancer predisposition syndromes (CPSs) incidence can provide insights that lead to improvements and modifications in treatment protocols through personalized therapy, thereby reducing toxicity. Purpose: This study aimed to analyze age-specific hospital-based childhood cancer rates and the distribution of CPSs in a 20-year pediatric cohort from the region. Materials: A total of 2190 patients, aged from birth to 17 years, diagnosed with any type of neoplasm classified by ICD-10 codes at Karol Jonscher’s Clinical Hospital of Poznan University of Medical Sciences (KJCH PUMS) between 1 January 2000, and 31 December 2019, were included, with 193 (8.8%) having an underlying CPS. Results: The pediatric population of the Greater Poland Region has declined over the past two decades. The most common diagnoses can be grouped into three main categories: (1) leukemias, involving 704 patients (32.1%); (2) central nervous system (CNS) tumors, represented by 382 children (17.4%); and (3) lymphomas, including 279 patients (12.7%), together accounting for 1353 cases (61.8%). The age-specific hospital-based case rate for childhood cancer (all types combined) peaked in the 0–28 days age group at 71.8 per 100,000 person-years (95% CI: 52.2–96.4), with a trend to decrease with age and a slight increase among adolescents aged 16–17 years (13.6 per 100,000, 95% CI: 12.0–15.4). The age-specific incidence of CPS-positive cancers declined from 18.0 (95% CI: 8.2–29.4) per 100,000 person-years in the first month of life to 0.7 (95% CI: 0.3–1.2) in 16–17-year-olds. CPS-positive children were diagnosed at significantly younger ages for four cancer types: liver and intrahepatic bile duct tumors (C22: A = 0.097, adjusted p < 0.001), myeloid leukemia (C92: A = 0.179, adjusted p < 0.001), lymphoid leukemia (C91: A = 0.309, adjusted p = 0.007), and renal tumors (C64: A = 0.335, adjusted p = 0.013). Conclusions: CPSs likely play a significant and underestimated role in pediatric cancers, especially during early childhood. Improving access to genetic testing could greatly enhance risk assessment, personalized treatment, and long-term outcomes in pediatric oncology. Full article

Mucormycosis is a rare, invasive fungal infection associated with high mortality. This retrospective study evaluated adult mucormycosis cases followed in our clinic between 2015 and 2025. A total of 13 patients were included, with a mean age of 50.92 ± 20.65 years (range, 20–83), and 10 (76.9%) were male. The most frequent symptom was facial pain (100%). Four (30.8%) of the patients had rhino-sinusitis, and three (23%) had rhino-orbito-cerebral involvement. Seven (53.9%) of the patients had hematological malignancy, three (23%) had diabetes mellitus (DM), two (15.4%) had a history of COVID-19 pneumonia, and one (7.7%) had a history of both DM and COVID-19 pneumonia. All had elevated C-reactive protein levels. Rhizopus spp. grew in nasal/tissue cultures of three (23%) patients, and so did Mucor spp. Surgery was performed in 11 (84.6%) patients, and fungal hyphae were observed in tissue histopathology. All patients showed radiological findings of mucormycosis on imaging. All patients received Liposomal Amphotericin B, and nine (69.2%) patients received sequential posaconazole therapy. Recurrence occurred in two (15.4%) patients. A total of eight (61.5%) patients, including three (23%) patients with intracranial involvement, died. Mucormycosis is a severe infection, especially in patients with hematological malignancies or DM, despite early diagnosis and combined antifungal and surgical treatments. Full article

The SARS-CoV-2 non-structural proteome remains the most clinically validated and strategically important landscape for direct-acting small-molecule antiviral drug discovery. The success of inhibitors targeting the main protease (M^pro, Nsp5) and RNA-dependent RNA polymerase (RdRp, Nsp12) has firmly established viral replication enzymes as tractable, druggable, and therapeutically relevant targets, while setting clear benchmarks for translational antiviral development. Building on this foundation, a second wave of non-structural protein (Nsp) targets has emerged with increasing translational promise, including the papain-like protease (PL^pro), the bifunctional Nsp14 proofreading and capping machinery, Nsp16 2′-O-methyltransferase, Nsp13 helicase, and Nsp15 endoribonuclease. In parallel, additional components such as Nsp1 and the Mac1 domain of Nsp3 continue to expand the antiviral design space, although they remain at earlier stages of chemical validation. In this review, we comprehensively assess SARS-CoV-2 non-structural proteins through a medicinal chemistry and translational lens, with an emphasis on structural tractability, mechanism of action, quality of chemical matter, cellular and in vivo antiviral evidence, evolutionary conservation, resistance liabilities, and developability. Particular attention is given to the features that distinguish tool compounds from genuinely actionable leads and to the opportunities for rational combination regimens that extend beyond first-generation protease- and polymerase-centred therapy. Collectively, the non-structural proteome offers the strongest foundation for next-generation and potentially broader-spectrum coronavirus antivirals with improved resilience to viral evolution. Full article

Advanced filariasis-induced lymphedema causes irreversible fibrosis, severe disability, recurrent infections, and major psychosocial burden, often with poor response to conservative therapy. Surgical management in this type of lymphedema is rarely addressed. We conducted a PRISMA 2020-guided systematic review evaluating surgical interventions versus conservative management or no intervention in adults with filarial lymphedema, involving various anatomical locations. Of 580 records identified, 29 studies were included for qualitative synthesis. The evidence base predominantly consisted of case reports, with surgical indications frequently involving disabling elephantiasis or diagnostic excision of filarial masses. While ablative procedures (excisional debulking) remained the primary salvage strategy, specific studies documented physiological techniques, including nodovenous shunts and vascularized lymph node transfer (VLNT). Quantitative limb-volume reduction was sparsely reported; however, qualitative assessments demonstrated significant improvements in ambulation, cosmesis, and patient-reported quality of life. Postoperative complications, primarily superficial surgical site infections, were generally low and manageable. Ablative surgical procedures appear to be the most common salvage strategy for advanced filarial lymphedema, but the evidence base remains limited to low-level, heterogeneous observational data. However, with the emergence of physiological lymphatic surgery, a combination of ablative procedures and physiological procedures should be considered. Prospective controlled studies with standardized outcomes are urgently needed. Full article

Alzheimer’s disease (AD) is undergoing a profound paradigm shift, transitioning from a localized, monolithic proteinopathy into a complex, multisystem disorder. This critical review synthesizes recent mechanistic, translational, and clinical insights to dismantle the traditional linear amyloid cascade hypothesis. We explore the synergistic interplay between amyloid-β (Aβ) and tau propagation, positioning chronic neuroinflammation, endolysosomal failure, and metabolic starvation—often framed as “Type 3 Diabetes”—as fundamental disease drivers. Crucially, we highlight the emerging biological bridge of CNS-PNS crosstalk, where central neurodegeneration and peripheral neuropathies are linked by systemic immune activation and microbiota–gut–brain axis dysbiosis. The recent validation of disease-modifying therapies (DMTs) confirms Aβ clearance as a viable pharmacological target; however, the marginal clinical gains and severe radiological risks, such as Amyloid-Related Imaging Abnormalities (ARIA), expose the profound limitations of monotherapy. Ultimately, we argue that isolated amyloid clearance is merely an induction phase. The future of AD therapeutics mandates a sequential combination approach—pairing early plaque debulking with lifelong metabolic and neuroimmune maintenance. Supported by scalable fluid biomarkers (e.g., plasma p-tau217) and the expanded ATN(I) framework, the field must embrace proactive precision medicine and inclusive clinical trial designs to successfully transform AD into a manageable chronic condition. Full article

Background: Sphingolipids are essential structural and signaling lipids that support membrane integrity and govern cell fate decisions. While the consequences of chronic sphingolipid inhibition have been extensively explored, the immediate cellular responses to acute suppression of sphingolipid synthesis remain poorly defined. Methods: We analyzed subcellular proteomic changes following an acute reduction in sphingolipid levels induced by myriocin, an inhibitor of de novo sphingolipid synthesis. We then evaluated the cytotoxicity of co-treatment with myriocin and inhibitors of the altered pathways in cancer cells. Results: We found that de novo sphingolipid synthesis is sensitive to myriocin, an inhibitor of serine palmitoyltransferase (SPT), and can be efficiently inhibited within 4 h of treatment. Cells respond to reduced sphingolipid levels by rapidly remodeling their proteome. Mass spectrometry analysis revealed changes in the abundance of hundreds of proteins across the membrane, cytosolic, and nuclear fractions. Gene set enrichment analysis revealed alterations in the proteome across several pathways involved in protein and lipid homeostasis and stress responses, including upregulation of cholesterol homeostasis and lysosome. Co-treatment with myriocin and cholesterol synthesis or lysosomal function inhibitors synergistically reduced cancer cell viability by promoting apoptosis rather than other forms of programmed cell death. Conclusions: Together, our work provides insights into how cells rapidly rewire the abundance of certain protein classes in response to reduced sphingolipid levels and identifies signaling and metabolic pathways that can be exploited for therapeutic intervention. Full article

The tumor microenvironment of breast cancer presents high complexity and resistance to conventional therapies. Ferroptosis, a programed cell death that is dependent on iron and characterized by lipid peroxidation, arises as a promising therapeutic goal. This scoping review mapped evidence on the exogenous use of iron and selenium, in conventional or nano-particulated forms, in the modulation of ferroptosis as therapeutic strategy for breast cancer treatment, identifying knowledge gaps and opportunities for future research. We performed a scoping review and the methodology followed the guidelines of the Joanna Briggs Institute (JBI) and PRISMA-ScR. We made a systematic search in five data bases (Embase, Lilacs, PubMed (MEDLINE), Scopus, and Web of Science) between the years 2012 and 2025. Among 2.723 identified publications, we selected 48 studies. The results revealed predominance of nanoplatforms of iron (97.9%), focused on the Fenton reaction. The modulation of selenium for inactivation of GPX4 was shown to be effective, though still little-explored (n = 1). We evidenced that the induction of ferroptosis potentializes tumor immunogenicity and the effectiveness of combined therapies. We conclude that the field is under development; thus, the diversification of metabolic targets and trials of chronic toxicity are fundamental steps for future clinical research. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most complex and aggressive disease with the worst rates of unresectable or metastatic disease at diagnosis, resistance to systemic therapy, and case fatality rate (CFR) among leading cancers. In non-metastatic disease, neoadjuvant treatment with modern chemotherapeutic regimens followed by surgical resection and/or adjuvant mFOLFIRINOX has significantly improved oncological outcomes. However, recurrence rates remain alarmingly high, while immune checkpoint inhibitors (ICIs) or molecularly targeted therapy have not yet demonstrated clinical benefits. Comprehensive genomic profiling through NGS-based approved assays such as TruSight Oncology 500 (TSO500) could guide targeted therapy. Rapidly evolving mRNA cancer vaccines and circulating tumor DNA (ctDNA)-based prediction of minimal residual disease (MRD) and recurrence risk hold great promise towards the realization of rational combination therapy to improve recurrence-free survival (RFS) and overall survival (OS). More recently, single-cell multiomics (SC MO), spatial proteomics and transcriptomics (SPT), artificial intelligence (AI), and systems biology have revolutionized cancer research, enabling holistic tumor microenvironment (TME) analysis. In this comprehensive review, we describe the latest advances and unmet needs in the standard of care of PDAC. Moreover, we discuss the expectations of ongoing randomized clinical trials of adjuvant mRNA vaccine-based therapy and ctDNA MRD testing as prognostic biomarkers, towards personalized treatment to improve RFS and OS in a medium-term perspective. With a longer perspective, we explore how harnessing SC MO, SPT, AI, and systems biology can reveal the 3D spatial organization of interacting cancer, immune, and stromal cells. Multi-dimensional TME-, TSO500- and ctDNA-based framework of dynamic biomarkers are of paramount importance to achieve an optimal patient-specific perioperative multimodal treatment combining precision immunotherapy, targeted drugs, and modern chemotherapy, translated into future practice-changing clinical trials, that could eliminate MRD towards recurrence prevention. Full article