Search Results (31)

Brain metastases are the third most common metastatic site in melanoma patients, with 40% of melanoma patients developing melanoma brain metastasis (MBM). Symptomology of MBM ranges from headaches, neurological deficits, cognitive changes, and seizures, resulting from MBM embedding in areas of highest blood flow following the breakdown of the blood–brain barrier (BBB) via genetic, cytokine, and molecular processes. The BBB is highly restrictive, making MBM difficult to treat. Challenges in MBM treatment are evident in adverse therapeutic effects, such as neurocognitive decline with whole-brain radiation therapy (WBRT), increased risk of radiation necrosis with stereotactic radiosurgery (SRS), and reduced penetration into the brain, which can lead to drug resistance with prolonged use of MAPK inhibitors. This review investigates current and novel treatments against MBM, including radiotherapy, chemotherapy, targeted therapies such as BRAF/MAPK inhibitors, and immunotherapy. Full article

Protein-losing enteropathy (PLE) is an uncommon and often underrecognized manifestation of lymphoproliferative disorders and may be difficult to diagnose when conventional gastrointestinal investigations are unrevealing. We present an 82-year-old woman with recurrent hospital admissions initially spanning six months for diarrhea, weight loss, peripheral edema, and persistent hypoalbuminemia. Initial upper gastrointestinal endoscopy was normal, and colonoscopy was deferred due to intercurrent infection. Despite extensive laboratory and radiologic evaluation, including routine biochemical testing and imaging, the etiology of PLE remained unclear. Peripheral blood flow cytometry subsequently identified a small kappa-restricted monoclonal B-cell population compatible with marginal zone lymphoma, later confirmed on bone marrow biopsy, raising suspicion for gastrointestinal involvement. Video capsule enteroscopy demonstrated diffuse erosive and ulcerative disease throughout the small intestine, providing an anatomical explanation for the patient’s protein loss. Following lymphoma-directed therapy, repeat capsule enteroscopy showed complete normalization of the small bowel mucosa. This case highlights the diagnostic value of combining peripheral blood flow cytometry and capsule endoscopy in unexplained protein-losing enteropathy, a rare and diagnostically challenging presentation of indolent lymphoma, and illustrates the role of capsule imaging in both disease localization and treatment monitoring. As a single-case report, these findings are not generalizable, and further studies are required to evaluate the broader applicability of this diagnostic approach. Full article

Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105⁺ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)–cysteine–arginine–glycine–aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies Full article

Background: Meniscal injuries are common athletic injuries, and isolated meniscal repair is a critical procedure for restoring knee function. However, rehabilitation protocols after meniscal repair remain controversial. This systematic review aimed to evaluate rehabilitation protocols to determine the best strategies for enhancing recovery following isolated meniscal repair. Objectives: Analyze current rehabilitation protocols following isolated meniscal repair, focusing on the efficacy of approaches in improving functional outcomes and reducing recovery time. This study also aims to identify gaps in the existing literature and provide recommendations for future studies. Data sources: Search was conducted using PubMed, Scopus, and Web of Science databases, covering studies published between May 2015 and May 2024. Inclusion criteria: Studies reporting on isolated meniscal repair with defined postoperative rehabilitation protocols and quantifiable outcome measures. Data extraction: Focused on patient demographics, meniscal tear types, repair techniques, and rehabilitation outcomes. The methodological quality of the included studies was assessed, and narrative synthesis was conducted. Results: The review included 13 studies with significant variability in rehabilitation protocols and outcomes. Early weight-bearing and range of motion exercises have been associated with improved recovery in some studies for stable meniscal tears. However, conservative approaches have better outcomes in patients with complex tears. The use of adjunctive therapies such as blood flow restriction training has demonstrated potential in enhancing muscle preservation and overall recovery. Conclusions: Rehabilitation protocols after meniscal repair surgery should be individualized. Although innovative protocols show promise, further research is needed to standardize rehabilitation approaches and optimize long-term outcomes. Full article

Background: Common variable immunodeficiency (CVID), the most prevalent symptomatic inborn error of immunity, involves impaired B-cell differentiation and antibody production, causing recurrent infections and the need for life-long immunoglobulin replacement therapy. Methods: This study evaluated the in vitro differentiation of memory B-cells (MBCs) into antibody-secreting cells (ASCs) in CVID patients. Peripheral blood mononuclear cells from 13 CVID patients and 10 healthy controls were stimulated using two protocols: (I) Staphylococcus aureus Cowan Strain I, Pokeweed mitogen, and CpG, or (II) a T-cell-dependent approach using CD40 ligand, interleukin-21, and CpG. B-cell subpopulations were analyzed by flow cytometry, ASC differentiation using ELISpot, and antibody levels in supernatants by ELISA. Results: Despite severely restricted in vivo antibody production, MBCs from all 13 CVID patients differentiated into IgG and IgM ASCs under adequate in vitro stimulation. Protocol II, mimicking T-cell help, was more effective than protocol I. As expected, the patients exhibited reduced class-switched MBCs ex vivo, but the MBCs differentiated and proliferated to an extent similar to those in healthy controls. IgA secretion remained significantly impaired post-stimulation. Specific IgG antibodies against tetanus toxoid and Streptococcus pneumoniae were detected in the patient supernatants, while no double-stranded DNA autoantibodies emerged after in vitro stimulation. Conclusions: These findings indicate that the MBCs of most patients retain functional B-cell differentiation and antigen-specific IgG secretion under T-cell dependent stimulation, though IgA secretion remains impaired. Tailored stimulation protocols could deepen our understanding of how to restore MBC formation in CVID patients in vivo. This methodology provides a platform to investigate antigen-specific functional memory responses like post-vaccination. Full article

Optimal recovery supports health and enhances performance in soccer players, yet the empirical evidence on various recovery strategies in soccer is complex to interpret. This review aimed to summarize the literature on post-exercise recovery modalities in male and female soccer players of all ages and competition levels. Following PRISMA guidelines, PubMed, SPORTDiscuss, and Web of Science were systematically searched until 17 October 2023. Randomized controlled trials or within-subjects crossover design studies that examined the effects of post-exercise recovery interventions on physical, psychological, or performance outcomes in soccer players were included. A single reviewer extracted data and assessed study quality using the Physiotherapy Evidence Database (PEDro) scale. Overall, 41 studies were included in the final review. The recovery strategies represented in these studies were organized into the following categories: active recovery, blood flow restriction, cold water immersion, contrast water therapy, compression garments, active cool-down, cryotherapy, cold garments, sleep and daytime nap, pneumatic cooling, foam rolling, mindfulness interventions, nutritional intervention, and static stretching. The findings demonstrated that cold-water immersion consistently improved jump performance and perceptions of fatigue, soreness, and overall well-being. Other recovery strategies, such as active recovery, compression therapy, sleep interventions, and nutrition supplementation, also positively impacted recovery, albeit with varying levels of effectiveness and evidence. However, the studies exhibited heterogeneity in methods, outcome measures, and recovery intervention protocols, posing challenges for generalizability. This review summarizes recovery strategies for soccer players, emphasizing the need for practitioners, coaches, and athletes to individualize interventions based on athletes’ needs, preferences, and competition level. Full article

Background/Objectives: Anterior cruciate ligament (ACL) injuries continue to present significant clinical and rehabilitative challenges. Despite advances in surgical techniques and rehabilitation protocols, persistent reinjury rates and increased pressure for early return to sport require a critical reassessment of current practices. This narrative review provides a comprehensive overview of the evolution, current standards, and future directions of ACL surgery and rehabilitation. Content: The literature search was conducted primarily in PubMed/MEDLINE and Web of Science using ACLRelated keywords, with emphasis on systematic reviews, randomized controlled trials, registry data, and consensus guidelines published within the past two decades. The evolution of ACL treatment is shaped by the transition from open to arthroscopic and anatomic reconstructions, as well as the refinement of fixation and augmentation techniques. In parallel, rehabilitation concepts shifted from rigid, time-based schedules to criteria-driven, individualized approaches. Key aspects include early mobilization, prehabilitation, and the integration of innovative tools such as anti-gravity treadmill and blood flow restriction training. Evidence on bracing suggests no routine benefit, while structured prevention programs have proven effective. Return-to-play strategies now emphasize objective functional criteria and psychological readiness. Conclusions: ACL therapy has evolved toward personalized, function-oriented rehabilitation. Future developments—including markerless motion analysis, AI-supported rehabilitation, and digital health applications promise for further individualization of care and optimization of long-term outcomes. Full article

Blood flow restriction training (BFRT) offers notable advantages, including simplicity and time efficiency. However, no meta-analysis has yet comprehensively evaluated its effects on glucose and lipid metabolism in overweight or obese adults. This meta-analysis examines the potential efficacy of BFRT in improving glycemic and lipid control in overweight/obese adults. The literature was searched in six databases, with the search period up to 31 March 2025. A total of eight randomized controlled trials involving 267 participants were identified. Data were analyzed using Stata 18.0 and RevMan 5.4 with random effects models. Outcomes included fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles, and risk of bias and publication bias (Egger’s test) were assessed. BFRT significantly reduced FBG (Hedges’ g = −1.13, 95% CI: −1.65 to −0.62, p < 0.01; I² = 66.34%) and HOMA-IR (Hedges’ g = −0.98, 95% CI: −1.35 to −0.61, p < 0.01; I² = 17.33%) compared with the controls. However, no significant changes were observed in lipid profiles. Our analysis demonstrates that BFRT exhibits the favorable effect of improving glucose metabolism in overweight/obese adults; however, current evidence does not support significant advantages of BFRT for lipid metabolism improvement. Full article

Background and Objectives: Lymphedema is one of the most important morbid complications of modified radical mastectomy (MRM) surgery. It can cause limb movement restriction and psychosocial deformities in some patients. This study aimed to determine and compare the physiological and pathological changes that develop in the axillary venous structures in patients who underwent axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). Materials and Methods: Patients diagnosed with breast cancer who underwent MRM and breast-conserving surgery (BCS) plus SLNB between 2017 and 2022 were retrospectively examined. The patients’ operation side and contralateral axillary vein diameter and the difference between them, axillary vein flow rate and the difference between them, axillary vein wall thickness and the difference between them, severity of lymphedema, extremity joint restriction examination, and the Nottingham Health Profile (NHP) data were recorded. The relationship of these parameters with the lymph node dissection width and radiotherapy was analyzed. Results: Fifty-eight patients in total were included in the study. In the distribution of lymphedema and lymphedema severity according to ALND groups, there is a statistically significant difference (p < 0.001). A statistically significant difference was determined in the distribution of the difference in the axillary vein blood flow rate and axillary vein diameter difference between the two arms according to the lymph node dissection groups. In the distribution of physical therapy and rehabilitation scales according to the lymph node dissection groups, a significant difference was found in the disabilities of the arm, shoulder, and hand (DASH), shoulder flexion restriction variables, and NHP sleep variables (all p < 0.001). Conclusions: This study demonstrated that ALND leads to more pronounced physiological and pathological changes in axillary venous structures—including increased vein wall thickness, altered flow rates, and diameter differences—compared to SLNB combined with breast-conserving surgery. These changes may be attributed to lymphovenous disruption and postoperative edema. Furthermore, radiotherapy appears to contribute to these changes, though to a lesser extent than ALND. Therefore, SLNB followed by radiotherapy may be preferable in eligible patients to reduce postoperative complications such as lymphedema, joint restriction, and sleep disturbances. Full article

Background/Objectives: Long-distance runners with exercise-induced hypertension (EIH) are at increased risk for cardiovascular complications. Although blood flow restriction (BFR) training has shown promise in improving vascular function, hemodynamic response, and cardiorespiratory fitness, its effects in EIH runners remain understudied. This study aimed to evaluate the effects of BFR training on cardiovascular responses and exercise performance in this population as a potential non-pharmacological therapy. Methods: Middle-aged male long-distance runners aged 40–65 with peak systolic blood pressure (SBP) ≥ 210 mmHg during graded exercise testing were randomly assigned to either a BFR group (n = 18) or a non-BFR control group (n = 15) using a computer-generated random sequence. There were no significant differences in baseline characteristics between the groups. Both groups performed aerobic training at 40–60% HRR for 20 min twice weekly for 8 weeks. SBP, diastolic blood pressure (DBP), rate pressure product (RPP), ventilatory threshold (VT), VO_₂max, and perceived exertion were assessed before and after the intervention at rest, during exercise, and during recovery. Results: Compared to the non-BFR group, the BFR group showed statistically significant reductions in resting and maximal SBP and DBP (p < 0.05), along with significant increases in VO_₂max and VT (p < 0.05). During submaximal exercise and post-exercise recovery, SBP and RPP were significantly lower in the BFR group (p < 0.05). The reductions in maximal SBP and DBP were significantly greater in the BFR group than in the control group. Conclusions: BFR training led to reduced myocardial workload and enhanced cardiovascular efficiency in male runners with EIH. These findings suggest that BFR training may be a viable non-pharmacological therapy for mitigating cardiovascular risks associated with EIH. Future studies should explore the long-term effects of BFR in broader populations and assess its applicability in clinical settings. Full article

Objectives: The purpose of this study is to quantitatively evaluate the combined effects of sports massage, blood flow restriction (BFR), and cold therapy on quadriceps recovery in mixed martial arts (MMA) athletes following eccentric exercise, focusing on muscle biomechanical properties, pain, and strength. Methods: This randomized, single-blind clinical trial involved 36 men and women MMA-trained participants, divided into three groups: massage (n = 12) received massage, BFR/cool (n = 12) received combined BFR and cooling, and control (n = 12) received passive rest as a control. The fatigue protocol involved MMA fighters performing five sets of plyometric jumps on a 50 cm box until exhaustion, with 1-min breaks between sets. After that, the massage group received a 20-min massage overall using standardized techniques; BFR/cool underwent a 20-min alternating blood flow restriction (200 mmHg) and cooling treatment with ice bags on the quadriceps; and the final group served as the control group with passive rest and no intervention. Participants were assessed four times—before exercise, immediately after exercise, 24 h post-exercise (after two recovery sessions), and 48 h post-exercise (after four recovery sessions)—for perfusion unit (PU), muscle elasticity, pressure pain threshold (PPT), reactive strength index (RSI), and total quality recovery (TQR). Results: The statistical analysis revealed significant effects of both massage and BFR/cooling interventions across key recovery outcomes, with large effect sizes for time-related changes in RSI (p < 0.0001; η² = 0.87), elasticity (p < 0.0001; η² = 0.84), and PPT (p < 0.0001; η² = 0.66). Notably, post-exercise 48 h values for RSI, elasticity, PU, and TQR were significantly improved in both the massage and BFR/cool groups compared to control (p < 0.05)), while no significant group differences were observed for PPT. Conclusions: The study concludes that both massage and combined blood flow restriction with cooling interventions significantly enhance post-exercise recovery—improving muscle perfusion, elasticity, reactive strength, and perceived recovery—compared to passive rest. Full article

Objective: Low-Load Blood Flow Restriction Training (LLBFRT) is an emerging approach in order to increase muscle endurance and muscle volume, as well as decrease pain in the early rehabilitation phase. The purpose of this review was to analyze the published literature on the effects of this intervention on musculoskeletal postsurgical rehabilitation. Methods: Six electronic databases (Cochrane Library, PubMed, SPORTDiscus, SCOPUS, CINAHL, and Web of Science) were searched from 2004 to 2024. Articles including adults who underwent any type of musculoskeletal surgery were screened. The Risk of Bias and Quality of Evidence were assessed using the Cochrane Risk-of-Bias Tool (RoB 2) and GRADE-CERQual scale. A meta-analysis was performed on the identified studies using RevMan version 5.4. The analysis model was synthesized as a random effects model, and the standard mean difference (SMD) was used as the effect measure. Results: Thirteen articles fulfilled the selection criteria and were included in this review. Muscle strength, muscle volume, and perceived pain had positive results in almost all studies; however, the meta-analysis reported a lack of overall effect in favor of LLLBFRT vs. control interventions in both lower and upper limb evaluations. Conclusions: Although some studies indicate positive effects of LLBFRT on strength, muscle size, and pain perception in operated lower and upper limbs, these results must be interpreted carefully since the overall effects are unclear. Nonetheless, the selected studies did not report discomfort claims; therefore, the LLBFRT could be a safe recovery strategy to use when rehabilitation programs need to gain variety. Full article

Chronic wounds pose a significant healthcare challenge, impacting millions of patients worldwide and burdening healthcare systems substantially. These wounds often occur as comorbidities and are prone to infections. Such infections hinder the healing process, complicating clinical management and proving recalcitrant to therapy. The environment within the wound itself poses challenges such as lack of oxygen, restricted blood flow, oxidative stress, ongoing inflammation, and bacterial presence. Traditional systemic treatment for such chronic peripheral wounds may not be effective due to inadequate blood supply, resulting in unintended side effects. Furthermore, topical applications are often impervious to persistent biofilm infections. A growing clinical concern is the lack of effective therapeutic modalities for treating chronic wounds. Additionally, the chemically harsh wound microenvironment can reduce the effectiveness of treatments, highlighting the need for drug delivery systems that can deliver therapies precisely where needed with optimal dosages. Compared to cell-based therapies, exosome-based therapies offer distinct advantages as a cell-free approach for chronic wound treatment. Exosomes are of endosomal origin and enable cell-to-cell communications, and they possess benefits, including biocompatibility and decreased immunogenicity, making them ideal vehicles for efficient targeting and minimizing off-target damage. However, exosomes are rapidly cleared from the body, making it difficult to maintain optimal therapeutic concentrations at wound sites. The hydrogel-based approach and development of biocompatible scaffolds for exosome-based therapies can be beneficial for sustained release and prolong the presence of these therapeutic exosomes at chronic wound sites. Engineered exosomes have been shown to possess stability and effectiveness in promoting wound healing compared to their unmodified counterparts. Significant progress has been made in this field, but further research is essential to unlock their clinical potential. This review seeks to explore the benefits and opportunities of exosome-based therapies in chronic wounds, ensuring sustained efficacy and precise delivery despite the obstacles posed by the wound environment. Full article

Deep vein thrombosis (DVT) of the lower extremities, as part of venous thromboembolism disorder, is the third leading cause of acute cardiovascular syndrome after heart attack and stroke. It can result in disability due to pulmonary embolism (PE) and post-thrombotic syndrome (PTS), particularly in cases where the thrombosis extends to the iliofemoral veins. Anticoagulation therapy is effective in preventing thrombus propagation and embolism but may not be sufficient for thrombus degradation and venous patency restoration. Up to 50% of patients with iliofemoral DVT develop PTS, mainly due to venous outflow obstruction or valvular incompetence. To date, the advent of new devices that enables rapid thrombus elimination and the restoration of deep venous patency, known as the “OPEN VEIN hypothesis”, may prevent valvular damage and reflux, cutting down the rate of PTS. Similarly, chronic venous disease could be related to a stenosis or occlusion of a major vein that can restrict blood flow. In this setting, intravascular ultrasound (IVUS) is an essential tool for correct diagnostic and therapeutic planning in acute and chronic vein disease. Only angiography in vein disease can limit the procedure’s efficacy, with a high rate of stenosis misdiagnosed; IVUS provides further imaging that complements traditional angiographic study, and its role is now established by different international guidelines. If compared to angiography, IVUS allows for the evaluation of major axial veins in a 360-degree ultrasound image of the lumen and of the vessel wall structure. At the same time, the precise location and size of the major lower extremity veins allow for the placement of the stent to be more straightforward with a precise dimension of the vein in all of its diameters; moreover, other abnormalities should be visualized as acute or chronic thrombus, fibrosis, or trabeculations. This review aims to provide an in-depth analysis of IVUS findings in acute and chronic lower extremity DVT, emphasizing its diagnostic and therapeutic implications. Full article

The aim of this study was to investigate the inhibitory effect of nintedanib (BIBF) on glioblastoma (GBM) cells and its mechanism of action and to optimize a drug delivery strategy to overcome the limitations posed by the blood–brain barrier (BBB). We analyzed the inhibition of GBM cell lines following BIBF treatment and explored its effect on the autophagy pathway. The cytotoxicity of BIBF was assessed using the CCK-8 assay, and further techniques such as transmission electron microscopy, Western blotting (WB), and flow cytometry were employed to demonstrate that BIBF could block the autophagic pathway by inhibiting the fusion of autophagosomes and lysosomes, ultimately limiting the proliferation of GBM cells. Molecular docking and surface plasmon resonance (SPR) experiments indicated that BIBF specifically binds to the autophagy-associated protein VPS18, interfering with its function and inhibiting the normal progression of autophagy. However, the application of BIBF in GBM therapy is limited due to restricted drug penetration across the BBB. Therefore, this study utilized poly-lactic-co-glycolic acid (PLGA) nanocarriers as a drug delivery system to significantly enhance the delivery efficiency of BIBF in vivo. In vitro cellular experiments and in vivo animal model validation demonstrated that PLGA-BIBF NPs effectively overcame the limitations of the BBB, significantly enhanced the antitumor activity of BIBF, and improved therapeutic efficacy in a GBM BALB/c-Nude model. This study demonstrated that BIBF exerted significant inhibitory effects on GBM cells by binding to VPS18 and inhibiting the autophagy pathway. Combined with the PLGA nanocarrier delivery system, the blood–brain barrier permeability and anti-tumor effect of BIBF were significantly enhanced. Targeting the BIBF-VPS18 pathway and optimizing drug delivery through nanotechnology may represent a new strategy for GBM treatment, providing innovative clinical treatment ideas and a theoretical basis for patients with GBM. Full article