Search Results (238)

Background: Meniscal tears are a common cause of knee pain and functional limitation, yet determinants of pain recovery following rehabilitation remain incompletely understood. Structural imaging findings often show limited correlation with clinical symptoms. This study aimed to evaluate longitudinal pain trajectories after rehabilitation in patients with meniscal tears and to investigate whether synovial fluid characteristics and structural joint degeneration are associated with pain improvement. Methods: This retrospective cohort study included 59 patients with meniscal tears who underwent structured rehabilitation. Structural degeneration was assessed using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Synovial fluid cytology evaluated neutrophil predominance (PNL) and erythrocyte positivity. Pain intensity was measured using the Visual Analog Scale (VAS) at 3 months, 6 months, and 1 year. Longitudinal changes were analyzed using the Friedman test, and predictors of pain improvement (ΔVAS from 3 months to 1 year) were evaluated using multivariable linear regression. Results: VAS scores decreased significantly over time (p < 0.001), indicating sustained pain reduction during follow-up. In the multivariable regression model (F(4, 54) = 2.80, p = 0.035), 17% of the variance in pain improvement was explained (R² = 0.17). Synovial erythrocyte positivity was modestly associated with greater longitudinal pain reduction (β = 0.75, 95% CI 0.15–1.36, p = 0.016). Age was also a significant predictor (β = 0.025, p = 0.043), whereas WORMS score and PNL positivity were not significantly associated with pain improvement. Conclusions: Pain recovery following rehabilitation in patients with meniscal tears appears to be influenced more by intra-articular biological characteristics than by structural imaging severity alone. Synovial erythrocyte positivity may indicate a potentially reversible inflammatory phenotype associated with higher early pain but greater subsequent improvement. These findings support a multidimensional model of knee pain and suggest that synovial characteristics may help improve clinical risk stratification during rehabilitation planning. Full article

Background/Objectives: The neonatal Fc receptor (FcRn) plays a crucial role in extending the systemic half-life of monoclonal antibodies (mAbs), but its influence on ocular distribution remains incompletely understood. This study investigated the impact of FcRn on the ocular disposition of mAbs following systemic administration in rabbits. Methods: New Zealand White rabbits received a single intravenous dose (1 mg/kg) of either wild-type trastuzumab (TS-WT) or its FcRn non-binding variant (IHH). Plasma and ocular tissues (retina, iris–ciliary body, vitreous humor, aqueous humor, cornea, conjunctiva, and tears) were collected at terminal time points up to 336 h for TS-WT and 168 h for IHH. Antibody concentrations were quantified using a validated sandwich ELISA. Pharmacokinetic parameters and antibody biodistribution coefficients (ABC) were calculated to assess the FcRn-mediated effects on ocular distribution. Results: TS-WT demonstrated 2-fold higher systemic exposure compared to IHH. The iris–ciliary body exhibited the highest absolute exposure for both antibodies, with TS-WT showing significantly higher accumulation (ABC_0–168h: 14.95% vs. 8.89%). Retinal distribution remained comparable between antibodies (5.96% vs. 5.51%). Both antibodies were detectable in tears, with ABC value of ~4% reported for TS-WT. TS-WT also demonstrated markedly increased distribution in vitreous humor and tear fluid (3.5- and 5.5-fold higher ABC values, respectively) compared to IHH. The cornea (5.76% vs. 5.57%) and conjunctiva (7.71% vs. 7.21%) showed comparable relative distribution between TS-WT and IHH, while aqueous humor showed minimal differences (0.44% vs. 0.52%). Conclusions: This investigation reveals distinct tissue-specific patterns of FcRn-mediated mAb distribution within the eye. FcRn binding significantly enhanced antibody distribution in ocular tissues, such as the iris–ciliary body, and tears, with less pronounced effects on the retina, cornea, conjunctiva and aqueous humor. These findings provide mechanistic insights for optimizing mAb-based therapeutics for ocular disease and understanding the ocular toxicity of mAb-based therapeutics, such as antibody–drug conjugates. Full article

Duropathies represent a spectrum of disorders associated with spinal dural tears and cerebrospinal fluid (CSF) leaks. Diagnosis and treatment is often complicated by overlapping clinical manifestations. This review aims to synthesize current literature on duropathies, focusing on their clinical, neuroradiological, and pathophysiological features. A comprehensive literature review was conducted, analyzing various conditions classified as duropathies, including spontaneous intracranial hypotension (SIH), superficial siderosis (SS), spinal cord herniation, and, as added issue, arachnoid webs. The review emphasized the importance of imaging techniques such as MRI and CT myelography in diagnosing these conditions. Duropathies can arise from congenital anomalies, trauma, and degenerative changes, with SIH being characterized by orthostatic headaches and neurological deficits. Imaging typically reveals specific patterns, such as a widened dorsal subarachnoid space and ventral displacement of the spinal cord. Syringomyelia was frequently associated with arachnoid webs, and complications like SS and bibrachial amyotrophy were noted in patients with persistent ventral spinal CSF leaks. The unifying concept of duropathies is proposed, emphasizing the need for timely intervention to mitigate long-term neurological consequences. Enhanced diagnostic strategies are crucial for improving patient outcomes, and a multidisciplinary approach is recommended for the management of these complex disorders. Further research is warranted to clarify the pathophysiological mechanisms underlying duropathies and to establish standardized treatment protocols. Full article

Background: Assessing aortic dissection (AD) in its early stages is crucial for cardiovascular surgeons to improve patient outcomes and avoid complications associated with surgical intervention for type A aortic dissection. Initial evaluations rely on patient referrals for computed tomography (CT) scans, which involve measuring the maximum aortic diameter. Objective: This study aimed to improve current diagnostic thresholds for type A aortic dissection by using computational fluid dynamics (CFD) modeling to correlate hemodynamic factors related to the wall shear stress with maximum aortic diameter growth rate, offering insights into predicting AD progression and reassessing current diameter-based diagnostic criteria. Methods: The pre- and post-AD scan data, with an average duration of three and a half years for the 15 patients, were converted into 3D geometries. These geometries were analyzed using the transitional-turbulent CFD model. Wall shear stress (WSS), its derivatives, and the pressure gradient from the pre-AD CT scans were compared across 15 patients, grouped according to the aortic diameter growth per year. Results: For patients in group 1 (nine patients with normal diagnosis), pre-AD time-average wall shear stress (TAWSS) was mostly 2–4 Pa, above physiologic levels. Post-AD, values dropped below 1.5 Pa (stagnant, thrombus-prone), with oscillatory shear index (OSI) elevated (0.24–0.32). In group 2 (n = 6, abnormal diagnosis), post-AD TAWSS was <3 Pa (thrombosis risk), with OSI 0.1–0.31 near tear sites. These findings confirm a dual-risk profile: low TAWSS promotes thrombosis, while high TAWSS drives dissection progression. Conclusions: WSS parameters, such as TAWSS and OSI, can be utilized to assess the development of a dilated ascending aorta, especially for extreme maximum aortic diameter. Pre-AD analysis for some patients revealed a strong negative correlation, indicating that high shear stress in the true lumen (TL) results in a drop in diastolic pressure post-AD at the upward-going section of the aorta. Full article

Cognitive dysfunction and neurodegenerative disorders represent an increasing clinical challenge in aging dogs and cats, while objective and minimally invasive biomarkers for early detection and disease monitoring remain limited. Tear film is a biologically active fluid reflecting both local and systemic processes and offers a practical, non-invasive source of potential biomarkers in geriatric veterinary patients. Proteomic analyses of canine and feline tear film have revealed a complex protein composition, including molecules involved in inflammation, oxidative stress, immune regulation, and cellular homeostasis—processes implicated in neurodegeneration. However, growing evidence from human and veterinary research emphasizes the importance of CNS-specific and mechanistically informative biomarkers, such as markers of axonal injury, synaptic degeneration, and glial activation, which may provide a more precise framework for interpreting peripheral proteomic alterations. This review summarizes current knowledge on tear film proteomics in dogs and cats and discusses its potential relevance to cognitive dysfunction and neurodegenerative processes. Particular attention is given to the integration of tear-derived proteins with validated blood and cerebrospinal fluid biomarkers, as well as to methodological challenges and future research priorities. With appropriate standardization and clinical validation, tear film proteomics may contribute to the development of novel diagnostic and monitoring strategies for neurodegenerative disorders in companion animals. Full article

Feline conjunctivitis is a common ocular disorder; however, the molecular composition of feline tear fluid and its alterations during ocular surface inflammation remain poorly characterized. This pilot study aimed to explore the tear proteome of cats with conjunctivitis using matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI–TOF/TOF MS) and to compare findings with those from clinically healthy cats. Tear samples were collected using Schirmer tear test strips from healthy cats and cats diagnosed with conjunctivitis. Total protein concentration was measured by ultraviolet absorbance spectrophotometry, and tear proteins were separated by SDS–polyacrylamide gel electrophoresis, followed by in-gel trypsin digestion and MALDI–TOF/TOF MS analysis. Nine distinct tear proteins were identified, including antimicrobial and immune-related components such as lactoperoxidase, lactotransferrin, albumin, and immunoglobulin A constant region. Lactoperoxidase and SBP1 were identified in feline tear fluid for the first time. No proteins uniquely associated with conjunctivitis were detected. The mean total tear protein concentration was numerically higher in cats with conjunctivitis (13.06 ± 0.75 mg/mL) than in healthy cats (9.69 ± 0.67 mg/mL); however, this difference did not reach statistical significance (p = 0.095) and should be interpreted cautiously given the limited sample size. This pilot study provides preliminary insights into tear protein profiles in cats with conjunctivitis and highlights the need for larger quantitative investigations. These findings provide a preliminary framework for future studies aimed at further characterizing molecular alterations associated with feline ocular surface disorders. Full article

Primary acquired nasolacrimal duct obstruction (PANDO) is a common cause of epiphora in adults, yet the biochemical environment within the nasolacrimal duct (NLD) remains poorly understood. This study aimed to characterize the proteomic composition of NLD lavage fluid and identify subtype-specific molecular features distinguishing membranous and mucinous obstruction. Paired tear and NLD lavage fluid (NLD-LF) samples were collected from patients undergoing dacryoendoscopic recanalization, and proteomic profiling was performed using LC–MS/MS. A total of 1345 proteins were identified in NLD-LF and 767 in tear fluid, revealing a distinct NLD-specific proteome. Although the membranous and mucinous subtypes shared broadly similar protein compositions, differentially expressed proteins highlighted divergent biochemical pathways. The membranous subtype showed enrichment of keratinization-related processes involving KRT1, KRT9, and KLK13, suggesting epithelial remodeling and cornification. In contrast, the mucinous subtype exhibited upregulation of proteins involved in lipid metabolism, carboxylic acid biosynthesis, and sulfur compound metabolism, including ALOX15B, LCAT, and GSTM4, indicating metabolic conditions that promote mucin–lipid interactions, glycan sulfation, and redox-dependent mucin cross-linking. These findings provide new insights into the protein composition of NLD lavage fluid and suggest molecular differences between the membranous and mucinous obstruction subtypes. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial condition affecting the ocular surface. It is characterized by tear film instability, hyperosmolarity, inflammation, and oxidative stress. First-line treatment for DED relies on lubricating and hydrating eye drops, usually containing hyaluronic acid (HA), which supports tear film stability and epithelial healing. However, HA alone cannot correct oxidative stress, a key driver of cellular damage and inflammation in DED. Accordingly, this study aimed to evaluate the antioxidant capacity of Malva sylvestris tincture (MalvaT) and its physicochemical properties in experimental eye-drop formulations containing HA. Methods: The antioxidant activity of reconstituted MalvaT lyophilisate (Malva) was assessed in cell-free assays against several oxygen radicals and in cell-based assays using the human HaCat keratinocyte cell line. The refractive index was measured in eye-drop formulations containing 0.15% or 0.3% HA and 0.5% MalvaT. Surface tension was assessed in eye-drop formulations containing 0.15% HA and increasing concentrations (0.25–2.0%) of MalvaT. Results: Malva showed potent oxygen radical scavenging activity in both cell-free and cell-based assays, indicating its antioxidant capacity and the efficient cellular uptake of antioxidant components. The refractive indices of experimental eye-drop solutions containing HA and MalvaT were close to that of tear fluid (1.334). The surface tension of the experimental eye-drop formulations, while not impacted by 0.15% HA, was significantly reduced by increasing concentrations of MalvaT (p < 0.0001). At the concentration of 0.5% MalvaT, the mean surface tension was reduced from 68.17 mN/m (HA control) to 59.80 mN/m (HA + MalvaT), thereby bringing it closer to that of tear fluid. Conclusions: This pre-clinical study suggests that combining the antioxidant properties of Malva tincture with the lubricating and hydrating effects of HA in eye-drop formulations exhibiting optimal rheological characteristics may offer a promising therapeutic approach for managing DED. Full article

Background: Bilateral facial nerve palsy (BFNP) is a rare clinical entity in children and is more often associated with systemic or infectious diseases than unilateral facial palsy. Epstein–Barr virus (EBV) infection is an uncommon but recognized cause of facial nerve palsy and may present with bilateral involvement. Case presentation: We report the case of a 3-year-old boy who presented with progressive bilateral facial weakness following a febrile illness with pharyngitis and cervical lymphadenopathy. Neurological examination revealed complete bilateral facial paralysis (House–Brackmann grade VI). Laboratory investigations showed lymphocytosis and confirmed acute EBV infection through positive viral capsid antigen IgM and detectable EBV DNA in peripheral blood. Cerebrospinal fluid analysis demonstrated mild pleocytosis with negative EBV DNA. Brain magnetic resonance imaging revealed unilateral enhancement of the left facial nerve. Audiologic evaluation supported peripheral facial nerve dysfunction. The patient was treated with systemic corticosteroids, vitamin B complex supplementation, artificial tears, and speech therapy, resulting in gradual and substantial clinical improvement over five months. Discussion: A review of the pediatric literature identified only six previously reported cases of EBV-associated BFNP. The pathogenesis may involve either direct viral neurotropism or a post-infectious immune-mediated mechanism. Diagnostic evaluation is essential to exclude other serious causes of BFNP, particularly Lyme disease and Guillain–Barré syndrome. Conclusions: EBV infection should be considered in the differential diagnosis of BFNP in children. Prognosis is generally favorable, although recovery may be prolonged. Further studies are needed to clarify optimal diagnostic and therapeutic approaches. Full article

(1) Purpose: The study investigated the correlation between variations in body mass index (BMI) and tear crystallization class according to the Masmali classification. Moreover, it examined the potential diagnostic value of a patterning test within the population affected by obesity. (2) Methods: A total of 61 patients were investigated, with ages ranging from 25 to 72 years (median age [interquartile range] = 39.0 [26] years). BMI values ranged from 19.1 to 47.5 kg/m², with a median BMI (interquartile range) of 29.3 (12.1) kg/m². (3) Results: The Kruskal–Wallis test was used to assess differences in BMI across the Masmali classes and revealed statistically significant disparities between at least two groups (p = 0.024). The rank η² value of 0.094 shows a small-to-moderate effect size, suggesting that approximately 9% of the variance in rank distributions is explained by the Masmali classification. The post hoc Dunn test with Bonferroni and Holm corrections showed that patients classified as Masmali grade 2 exhibited a significantly higher BMI compared to those in grade 0 (p = 0.009), whereas no statistically significant differences were identified between grades 0 and 1 or between grades 1 and 2. The analysis of variance (ANOVA) revealed a statistically significant difference among Masmali Classes 0, 1, and 2 with respect to the number of branching structures in dried tear samples analyzed at a brightness threshold of 220. The effect size (η² = 0.263) shows that approximately 26% of the variability in branching number can be attributed to the severity of tear film dysfunction as defined by the Masmali classification. Accordingly, as the Masmali score increases, the number of branches decreases significantly, particularly among patients with elevated BMI. (4) Conclusion: The findings suggest that when classified according to the Masmali scale the dry eye syndrome exhibits a distinct crystallization pattern in patients with excess body weight. Specifically, higher BMI values are associated with a marked decrease in the number of fern-like branches identified in the tear ferning test. Full article

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article

Objectives: The study examined tear and serum alterations using the ferning test and quantified the number of branches formed during the controlled drying of these biological fluids (tears and serum), in order to identify a potential diagnostic patterning test in individuals with obesity. Methods: A total of 61 patients aged between 25 and 72 years were enrolled (median age [interquartile range] = 39.0 [26] years). BMI values ranged from 19.1 to 47.5 kg/m², with a median BMI (interquartile range) of 29.3 (12.1) kg/m². Results: The Kruskal–Wallis test showed statistically significant differences among at least two Schirmer classes with respect to the number of branches observed in dried tears at a brightness threshold of 220 (H(2) = 8.485, p = 0.014). According to the Dunn post hoc test, Schirmer Class 1 showed a markedly lower number of branches compared with Classes 2 and 3 (p < 0.031 and p < 0.021), whereas no significant difference was found between Classes 2 and 3. The Kruskal–Wallis test further suggested the presence of statistically significant differences in the number of branches in dried serum, quantified using ImageJ2 at a brightness threshold of 190, across visceral fat classes (H(2) = 9.583, p = 0.008). Dunn’s post hoc tests revealed that the number of branches in serum analyzed at a brightness threshold of 190 was significantly higher in visceral fat class 3 compared to class 1 (p_holm = 0.006), while no statistically significant differences were observed between classes 1 and 2 or between classes 2 and 3 (p_holm > 0.05). Conclusions: In addition to other obesity-specific complications patients with obesity exhibit an increased risk of developing dry eye syndrome. The combined assessment of DPT in both the tear film and serum may represent a new method for analyzing obesity-associated biomarkers. Further studies are required to determine the sensitivity and specificity of these approaches in diagnosing systemic alterations induced by excess adipose tissue. Full article

Background/Objectives: Thoracic minimally invasive spine surgery (MISS) offers reduced tissue trauma and faster recovery compared with open approaches, but its adoption remains limited due to technical complexity and uncertainty regarding complication rates. This study aimed to synthesize the available evidence on overall and approach-specific complications of thoracic MISS using tubular, uniportal endoscopic, and biportal endoscopic techniques. Methods: Following PRISMA guidelines (PROSPERO CRD42024594316), PubMed, Medline, Embase, and Cochrane Library were searched from January 2013 to March 2024 for studies reporting complication rates after thoracic MISS in adults. Eligible studies included tubular, uniportal, or biportal approaches. Study quality was assessed using the Newcastle–Ottawa Scale. Complication data were extracted and summarized descriptively, with reported rates stratified by surgical approach. Results: Nine studies (234 patients) were included, all retrospective with moderate risk of bias. Across included studies, reported overall complication rates following thoracic MISS ranged from 0% to 42.9%. Stratified by surgical approach, reported complication rates ranged from 0% to 11.8% across six tubular studies, 9.7% to 20.0% across two uniportal endoscopic studies, and 42.9% in a single small biportal endoscopic study. Neural injuries and dural tears were the most frequently reported complications, with reported rates ranging from 0% to 14.3% and 0% to 3.6%, respectively. Symptomatic cerebrospinal fluid leaks and revision surgeries were less common, with reported rates ranging from 0% to 11.8% and 0% to 3.2%, respectively. Conclusions: Thoracic MISS demonstrates a low overall complication rate, particularly for tubular approaches. However, findings should be interpreted with caution given the small number of included studies, retrospective designs, and clinical heterogeneity. Larger comparative investigations are needed to better define safety profiles and support broader adoption of thoracic MISS techniques. Full article

A constantly increasing incidence of chronic diseases is a challenge for healthcare worldwide, being directly associated with physical inactivity, which is considered an important cause of most chronic diseases. In contrast, physical exercise has been proven as a powerful instrument of healthcare to protect individuals against health-to-disease transition and against disease progression. Nonetheless, a number of studies warn against inappropriate high-intensity and/or unaccustomed exercise that exceeds an individual’s physical capacity. Indeed, extensive cardiac activity during prolonged exercise leads to significantly increased cardiac dimensions, triggering cardiac complications that may result in arrhythmogenic sudden cardiac death. The remarkable plasticity of mitochondria allows these organelles to sense and adapt to a variety of stressors and respond to stimuli by molecular signalling, regulating bioenergetics and cellular homeostasis, decisive for repair processes, proliferation, apoptosis, and tissue regeneration to combat degeneration, with whole body outcomes. Mitochondria act as biosensors in the human body; they are reactive to stimuli and protective against health-to-disease transition. To perform this life-important function throughout life, mitochondria need supportive measures, including physical activity, considered an essential pillar of mitochondrial medicine. This article highlights reciprocity between the quality of mitochondrial health and homeostasis on one hand and physical fitness and exercise intervention on the other hand. The proposed novelty relates to the monitoring of mitochondrial homeostasis, which is strongly recommended for creating individualised training programmes, and monitoring exercise efficacy during and after the programme is completed. To this end, a patient-friendly non-invasive approach is already established, utilising tear fluid multi-omics, mitochondria as the vital biosensors, and AI-based multi-professional data interpretation. Full article

We aimed to validate the feasibility of combining ultra-widefield (UWF) fundus photography with targeted swept-source optical coherence tomography (SS-OCT) for clinical decision-making regarding a prophylactic laser therapy. For this purpose we enrolled 119 patients (135 eyes) who, basis on fundus examination, were eligible for prophylactic photocoagulation of degenerative retinal lesions. Eyes were classified into two groups: (1) justified laser, when SS-OCT confirmed vitreoretinal traction and/or subretinal fluid beneath the neurosensory retina; and (2) non-justified laser, when SS-OCT did not confirm these criteria. Using this SS-OCT-guided UWF approach, we found that 25.1% of eyes that initially qualified for laser based on clinical examination did not meet the SS-OCT criteria. Patients in the justified laser group were significantly younger than those in the non-justified group. Horseshoe retinal tears, lattice degeneration and snail-track degenerations, multiple lesions, and lesions located in the far and mid-periphery were significantly more frequent in the justified laser group than in the non-justified group. By contrast, the prevalence of operculated holes, bilateral lesions, and degenerative lesions in patients with a retinal detachment in the fellow eye did not differ between groups. Our findings suggest the SS-OCT-guided UWF imaging may refine patient selection for prophylactic laser therapy. Full article