Brief Intraoperative Electrical Stimulation (BIES) can enhance axonal regeneration across axotomy sites. Cross-Face Nerve Grafts (CFNG) are typically performed in two stages, with a 6–12-month interval to allow for axonal growth. This provides an opportunity to assess axonal regeneration via biopsy. We describe a protocol to evaluate the effects of a 10-minute BIES on axonal regeneration across CFNG. This is a protocol for a multicenter, double-blind, randomized controlled trial in patients with unilateral facial paralysis undergoing two-stage CFNG. After nerve coaptation, the intervention group will receive 10 minutes of BIES (biphasic current, 2mA amplitude, 100 µsec pulse duration, 16 Hertz) applied proximal to the donor facial to sural nerve coaptation. Controls will undergo standard surgery without stimulation. The primary outcome is the histological count of regenerated myelinated axons from a biopsy obtained during the second stage surgery. Secondary outcomes include patient reported quality of life and objective facial reanimation based on photo analysis. We aim to recruit 20 participants. This protocol evaluates the impact of BIES on histological, patient reported, and objective facial reanimation outcomes in CFNG.
Brain-Computer Interfaces (BCIs) are increasingly used in neurorehabilitation, but the rapid expansion of scientific literature complicates the identification of clinically relevant studies. This study investigated whether expert-defined relevance within BCI rehabilitation literature emerges as a structural property of semantic networks through the integration of graph theory and Principal Component Analysis (PCA). A Lexical Network Analysis Based on Graph Theory (LENGTH) was applied to randomized controlled trials indexed in PubMed over the last decade using the query "brain computer interface" AND rehabilitation. Titles and abstracts were analyzed to construct a semantic network linking articles and lexical terms. Multiple graph-theoretical metrics were calculated and residualized against weighted degree to minimize document-size bias. PCA was subsequently applied to the residualized metrics. Forty-eight studies were included. The network showed a compact and highly interconnected structure, centered on motor and functional recovery concepts. PCA identified two principal components explaining of total variance. Relevant articles tended to occupy regions characterized by higher semantic integration and lower hierarchical influence. Although no clear categorical separation emerged, a consistent positional tendency was observed. These findings suggest that relevance may be represented as a topological property within a multidimensional semantic landscape, supporting the use of semantic-network approaches for literature screening and evidence synthesis.
Hip Tuberculosis (HTB) is a severe form of extrapulmonary Tuberculosis (TB) that can lead to progressive joint destruction, functional impairment, and reduced Quality Of Life (QoL). Optimal management requires timely Antitubercular Therapy (ATT), appropriate surgical intervention, and structured rehabilitation. This case report aims to present a 57-year-old Bulgarian female with advanced HTB, persisting chronic pain, severe functional limitation, and marked restriction in Range Of Motion (ROM) and Muscle Strength (MS). Baseline assessment revealed a Harris Hip Score (HHS) of 56 and pain intensity of 7/10 on the Visual Analogue Scale (VAS). Microbiological confirmation of Mycobacterium tuberculosis was obtained via bone biopsy. Following completion of ATT and normalization of inflammatory markers, the patient underwent Total Hip Arthroplasty (THA) using an anterolateral approach. An individualized Exercise-Based Postoperative Rehabilitation Program (EBRP) was implemented. At 6-Hip Flexion (HF) improved from 25° to 55°, while hip abduction increased from 15° to 40°.MS improved from 2/5 to 4+/5 in key muscle groups (MG). Functional performance improved significantly, with HHS increasing from 56 to 81 (+44.6%), and pain decreasing from 7/10 to 2/10 (−71.4%). No postoperative complications or infection recurrence were observed. This case highlights the importance of appropriate timing of THA after successful infection control with ATT, combined with a structured EBRP. A multidisciplinary approach is essential to optimize functional recovery and minimize complications in patients with HTB.
Osteoarthritis (OA) is a degenerative joint disease with increasing prevalence due to population aging. Conservative management of knee OA has traditionally focused on pain control, with intra-articular injections widely used for targeted local therapy. This study evaluated the clinical efficacy of a single 4.4 mL intra-articular injection of cross-linked hyaluronic acid compared with hylastan SGL-80 (4 mL) in patients with knee OA. In this interventional cohort study, 120 patients with grade III knee OA (Outerbridge) were allocated to two groups: Group 1 (UP; n=60) received 4.4 mL cross-linked hyaluronic acid, and Group 2 (Normal; n=60) received hylastan SGL-80/4 mL. All patients followed a 15-day NSAID protocol before injection and had no prior knee injections within 6 months. Outcomes were assessed using VAS, KOOS, and SF-12 at baseline and up to 6 months. Analgesic use, complications, and VAS-KOOS correlations were evaluated. Both groups showed a low complication rate (5%). Pain reduction over 6 months was significantly greater in Group 1 (VAS 6.93 to 2.32) than in Group 2 (6.44 to 3.52; p=0.030). Group 1 demonstrated superior KOOS (p=0.017), SF-12 scores (p=0.021), and reduced anti-inflammatory drug use (p=0.026). VAS-KOOS correlation confirmed greater clinical improvement in Group 1 at 180 days (p=0.031). A single 4.4 mL intra-articular injection of cross-linked hyaluronic acid provides significant and sustained improvement in pain, function, and quality of life in patients with knee OA.
Insulin Resistance (IR) is a central pathophysiological mechanism underlying obesity, type 2 diabetes mellitus, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease, with significant implications for skeletal muscle function, exercise capacity, and rehabilitation outcomes. Because skeletal muscle represents the primary site of insulin-stimulated glucose disposal, muscle insulin resistance is a key determinant of both metabolic health and physical performance. Cannabidiol (CBD), a non-intoxicating phytocannabinoid derived from Cannabis sativa, has attracted increasing scientific interest due to its anti-inflammatory, antioxidant, and pleiotropic signaling properties. This narrative review aims to examine the relationship between CBD and insulin resistance, with a particular focus on skeletal muscle biology and its relevance for exercise and rehabilitation medicine. A structured literature search was conducted using major biomedical databases, including PubMed, Scopus, and Web of Science, to identify relevant preclinical and clinical studies. Evidence was synthesized narratively, with emphasis on skeletal muscle insulin resistance, endocannabinoid system signaling, potential mechanisms of CBD action, and clinical outcomes. Preclinical data suggest that CBD may influence several pathways involved in skeletal muscle insulin resistance, including chronic low-grade inflammation, oxidative stress, lipotoxicity, and ceramide accumulation. However, current human studies remain limited and do not demonstrate consistent improvements in glycemic control or insulin sensitivity with CBD alone. Furthermore, evidence regarding its effects on muscle function, exercise performance, or rehabilitation outcomes is lacking. In conclusion, CBD represents a biologically plausible but clinically unproven modulator of skeletal muscle insulin resistance. At present, it should be considered an experimental adjunct rather than an established therapeutic strategy. Future research should focus on well-designed clinical trials integrating metabolic and functional endpoints to determine its potential role alongside exercise-based interventions in rehabilitation medicine.
Cachexia is a severe wasting syndrome characterized by profound skeletal muscle atrophy that significantly contributes to mortality across various diseases, including cancer. However, its underlying mechanisms remain poorly understood. We previously identified major alterations of iron metabolism in the skeletal muscle of cachectic tumor-bearing mice and in particular a decrease in mitochondrial iron content, resulting in mitochondrial dysfunction. Lipocalin 2 (LCN2), an iron-chelating protein, has been identified as one of the most upregulated genes in various models of skeletal muscle atrophy. Being known the role of glucocorticoids in muscle wasting and that LCN2 is a transcriptional target of the glucocorticoid receptor (GR), we hypothesized its involvement in the dysregulation of iron metabolism during muscle wasting. Firstly, we confirmed the increased expression of LCN2 in the skeletal muscle of both C26 tumor-bearing mice and dexamethasone-treated mice, recapitulating the cachectic phenotype. Consistently, in vitro LCN2 overexpression induced a significant reduction in C2C12 myotube diameter and, oppositely, its silencing was sufficient to prevent dexamethasone-induced atrophy. Moreover, iron supplementation prevented glucocorticoid-induced atrophy in vitro and mitigated the cachectic phenotype in our two mouse models. Importantly, local expression of LCN2 promoted markers of iron deprivation in vivo. These results suggest that iron metabolism acts as a key contributor to skeletal muscle atrophy. Our findings shed light on both cancer and glucocorticoid-induced skeletal muscle wasting mechanisms, highlighting LCN2 as a potential therapeutic target for muscle wasting diseases.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin gene. The lack of functional dystrophin disrupts the dystrophin-glycoprotein complex, leading to progressive structural degeneration and functional impairment of myofibers. Currently, no cure is available. Although AAV-mediated micro-dystrophin (μDys) gene therapy is among the most promising strategies, its efficacy is still limited by the pathological dystrophic muscle environment, characterized by chronic inflammation and sarcolemma fragility, which compromises μDys engraftment and long-term stability. To enhance therapeutic outcomes, we are investigating a combined approach based on μDys gene therapy and pharmacological activation of Sirtuin1 (SIRT1), a NAD-dependent deacetylase involved in muscle homeostasis and regeneration. In previous work, we demonstrated that SRT2104, a clinically advanced SIRT1-activator, improves functional, metabolic, and histological parameters in mdx mice after 12 weeks of treatment. Importantly, we also observed improvements in specific neurocognitive markers, a relevant finding considering the cognitive deficits often associated with DMD. Given its broad effects on DMD-dysregulated pathways, SRT2104 represents a promising candidate to support μDys therapy by improving muscle condition and potentially allowing a reduction in viral vector dose. To explore this synergistic potential, we selected a dose of AAV9-μDys capable of restoring ≥20% of dystrophin expression, and we are currently testing different administration schedules of SRT2104 and μDys to define the optimal therapeutic window. Specifically, a time-course study is ongoing to determine the optimal timing for gene delivery following SRT2104-mediated stabilization of the muscle environment. This strategy aims not only to boost the efficacy of μDys gene therapy but also to reduce the risks associated with high AAV doses, toward a safer, more sustainable DMD treatment.
Volumetric muscle loss (VML) poses a clinical challenge due to the native skeletal muscle's inability to regenerate large tissue defects, often resulting in fibrosis and functional impairment. Despite various approaches, current therapeutic strategies fail to provide a fully effective and durable solution for VML, highlighting the need for innovative regenerative treatments. This study aims to explore the regenerative potential of primary human pericytes embedded in 3D-bioprinted constructs for VML treatment using a swine model. Human pericytes, isolated from muscle biopsies and characterized through immunofluorescence and flow cytometry, demonstrated strong myogenic potential, making them excellent candidates for use. Pericyte-laden hydrogel constructs, fabricated using a custom microfluidic-assisted 3D rotary wet-spinning (RoWS) bioprinting platform with and without an alginate shell, were surgically implanted into an induced VML site in mini-pig limbs. Over a period of 120 days, tissue regeneration was monitored via ultrasound imaging, histological staining, and immunofluorescence analysis of biopsies. Results indicated that constructs containing alginate maintained greater structural integrity over time, promoting vascularization and a more compact tissue architecture. PAN-positive human cells were detected in the biopsies, confirming the survival of implanted pericytes. Myogenic differentiation was evident only at 60 days post-implantation, with the emergence of small fibers. Furthermore, a progressive reduction in macrophage infiltration (MannRpositive area) suggested a resolution of inflammation possibly associated with active tissue remodeling. This work demonstrates that human pericytes, when delivered through a biocompatible 3Dprinted scaffold, can survive in vivo, support neovascularization, and initiate myogenic differentiation in a large animal VML model, offering a promising avenue for translational muscle regenerative therapies.
Duchenne Muscular Dystrophy (DMD) is a severe genetic disease causing progressive muscle degeneration, inflammation, and fibrosis. While gene and cell therapies offer promising therapeutic avenues, their complexity makes pharmacological approaches more accessible. Histone deacetylases (HDACs) are a family of epigenetic regulators found deregulated in DMD patients. Indeed, the modulation of HDACs has emerged as a key strategy with Givinostat, a pan-HDAC inhibitor, recently being approved by the FDA. However, the use of pan inhibitors has been associated with many side effects. Indeed, the treatment with selective compounds might reduce the off-targets, while maintaining the therapeutic effects. Specifically, inhibiting HDAC8 with PCI-34051 restores the muscle function, acting on the stabilization of the cytoskeleton, while the activation of SIRT1 with SRT2104 improves the energy metabolism and muscle regeneration, acting on the mitochondrial biogenesis. In our study, we evaluated a novel combination therapy involving HDAC8 inhibition and SIRT1 activation. In dmd zebrafish embryos, the co-administration of PCI-34051 and SRT2104 restores the muscle loss and reduces the inflammation. Importantly, the combination therapy allowed for lower doses of each compound, maximizing therapeutic effects while minimizing potential side effects. These findings underline the potential of HDAC8 inhibition and SIRT1 activation as an interesting therapeutic strategy to be exploited for DMD patients, both in single and in combination settings.
Smooth muscle cells play a critical role in the physiology of the human vagina, especially in conditions such as the menopause, in which the decline of sex hormones levels can cause effects such as thinning of the epithelium and decreased muscle tone, impairing tissue elasticity and human vaginal smooth muscle cells (hvSMC) contractility. Elucidating the membrane proteins that regulate their activity is essential for the comprehension of the mechanisms underlying vaginal physiology and pathophysiology. Among these, Transient Receptor Potential (TRP) channels are transmembrane protein complexes acting as nonselective cation channels which can be modulated by sex hormones. They are widely expressed in several tissues, playing a pivotal role in processes as mechano-transduction, flogosis and thermal nociception. Although TRP channels have emerged as key modulators of calcium signaling and smooth muscle contractility, their effective role in hvSMCs remain largely unexplored. In this study we aimed to evaluate the expression and functionality of TRP channels in hvSMCs, considering that their activity could be disturbed following hormonal changes occurring in the menopause. We first evaluated the TRP channels expression in hvSMCs by RT-PCR and immunohistochemical analyses. The functionality of the channels was assessed by the wholecell patch clamp technique, using chemical and thermal stimuli for their activation. Our analyses showed a high expression of mRNA related to TRPV1 and TRPA1, whereas the expression of TRPM8 resulted significantly lower. The electrophysiological analyses showed that chemical and thermal stimuli were able to activate the three channels, causing an increase in current amplitude proportional to their expression. In conclusion, our results show for the first time that TRP channels are widely expressed and functional in isolated hvSMCs, and can represent a potential therapeutic target for the treatment of gynecological diseases.
Neuromuscular junction (NMJ) dysfunction contributes to muscle wasting in numerous neuromuscular diseases such as ALS and age-related sarcopenia. Interestingly, in the last few years it has become clear that skeletal muscle fibers play a critical role to maintain a proper connection between nerve and muscle, and inhibition of muscle-specific protein synthesis leads to rapid presynaptic degeneration. mTORC1 is a key regulator of muscle protein homeostasis, and we previously showed that its activity in muscle fibers is essential to maintain NMJ structure and function. To understand the underlying mechanisms, we generated two novel tissue-specific mouse models; musclespecific RiboTag mice that allow us to observe the expression of the ribosomal protein RPL22 exclusively in skeletal muscle, and muscle-specific MetRS mice which permit the labelling and tracking of de novo synthesized muscle proteins. RiboTag mice labelling revealed increased-ribosomal protein RPL22 expression arou nd the NMJ, suggestive of increased ribosome content and, consequently, elevated translational activity. RNA sequencing of RiboTag-derived mRNA identified a strong enrichment of mTORC1 pathway components at the NMJ, suggesting a role for localized mTORC1 signaling. Furthermore, the MetRS model revealed muscle-derived proteins within the sciatic nerve and spinal cord, supporting muscle-to-nerve communication. Using musclespecific RiboTag Raptor knockout and AKT overexpression models, we observed altered translation of NMJ-related genes, reinforcing the regulatory role of mTORC1 in the NMJ translatome. Finally, we are implementing a sciatic nerve crush model to study the dynamics of muscle reinnervation and functional recovery, aiming to elucidate the contribution of mTOR signaling to this regenerative process. Together, our findings highlight the importance of mTORC1-dependent translational control in NMJ maintenance and muscle-nerve interaction.
A systematic meta-analysis was conducted to examine gender differences in self-efficacy and self-management among adults with Type 2 Diabetes Mellitus (T2DM). Twenty studies (2000–2025) with gender-disaggregated data were analyzed according to PRISMA 2020 guidelines. The meta-analysis used standardized mean differences (Hedges’ g; men minus women) and a multilevel random-effects model, with moderator and sensitivity analyses for behavioral domains, measurement types, regions, and study quality. The pooled effect size was small and positive (g = 0.37, 95% CI: −0.11 to 0.85), but the confidence interval included zero and heterogeneity was substantial (I² = 95.3%), indicating considerable between-study variability. Moderator analyses showed no significant differences by behavioral domain, measurement method, region, or publication year. Evidence of small-study effects and wide prediction intervals further reduced certainty in the findings. Domain-specific results (e.g., dietary self-management) were also positive but imprecise. Importantly, the certainty of evidence was rated low to very low due to imprecision, inconsistency, and potential publication bias, as assessed by the GRADE framework. Therefore, these findings should be interpreted as provisional and hypothesis-generating rather than definitive. In summary, gender differences in self-efficacy and self-management in T2DM are small, inconsistently estimated, and of low certainty, with a tendency to favor men. These results suggest that gender is not a robust determinant of diabetes self-management, and that contextual and psychosocial factors likely contribute to variability across studies. Interventions should aim to enhance self-efficacy for all individuals with T2DM using context-sensitive and gender-responsive approaches. Future research should use standardized measures, report gender-disaggregated data, and include broader geographic samples.
Chronic pain is increasingly recognized as a multidimensional condition sustained by interacting cognitive, behavioral, emotional, attentional, and metacognitive processes. Within this framework, physical exercise has gained relevance as a non-pharmacological intervention that may influence psychological mechanisms involved in pain persistence and disability. This narrative review provides an updated synthesis of recent evidence on the effects and mechanisms of physical exercise on cognitive, behavioral, emotional, and metacognitive dimensions of chronic pain. A structured literature search was conducted across PubMed/MEDLINE, Scopus and Web of Science, focusing on peer-reviewed studies published between January 2016 and December 2025. Evidence was synthesized narratively across mechanistic domains, integrating findings from rehabilitation science and clinical psychology. The literature suggests that exercise may act as an active experiential intervention capable of targeting several psychosocial factors in chronic pain. Across studies, exercise was associated with reductions in catastrophizing and maladaptive pain beliefs, improvements in pain self-efficacy, and attenuation of kinesiophobia. Exercise may also modulate attentional bias and hypervigilance, and psychologically informed exercise approaches appear particularly relevant for metacognitive processes, including reduced rumination, increased decentering, and improved non-reactive awareness of bodily sensations. In parallel, exercise shows beneficial effects on emotional aspects of chronic pain, likely mediated by both neurobiological and psychosocial mechanisms pathways. Overall, physical exercise should be conceptualized as a comprehensive intervention capable of acting on cognitive, behavioral, emotional, and metacognitive processes that sustain chronic pain. Future research should clarify modality-specific mechanisms, identify moderators of response and incorporate process-based outcomes to support personalized exercise prescriptions.
Recently, both Clarivate and Scopus announced improved metrics for the European Journal of Translational Myology (EJTM), bringing its Impact Factor to 2.0 and its CiteScore to 4.1. I am proud of these achievements and share the credit with the entire PAGEpress staff. Furthermore, many organizers and moderators for the "Padua Days on Muscle and Mobility Medicine" 2027 (2027 Pd3m) have accepted their roles and proposed improvements for the event, which will take place at the Euganean Thermal Baths (Padua, Italy) from March 9 to 12, 2027. The program remains open to numerous additional speakers. On the downside, rising operating costs are affecting both digital publishing and event organization; it is hoped that these increases will not negatively impact the submission of contributions to the EJTM and the 2027 Pd3m conference. Those interested can find further information and forms for active participation (registration, accommodation, abstract template, and participation details) at the following address: www.paduamuscledays.it. Undoubtedly, the 2027 Pd3m promises to be an engaging event, on par with all previous editions of the "Padua Days on Muscle and Mobility Medicine."
Ramp lesions, tears involving the peripheral attachment of the posterior horn of the medial meniscus, significantly impact knee stability and function, particularly in association with anterior cruciate ligament injuries. However, evidence regarding optimal treatment strategies remains inconclusive. This systematic review and meta-analysis aimed to evaluate and compare the clinical efficacy of various treatment modalities for ramp lesions. A comprehensive systematic search was conducted across major electronic databases, including PubMed, Scopus, and Web of Science, up to June 2025. Studies were included based on predefined eligibility criteria. Data extraction was performed and meta-analytic synthesis was conducted using random-effects models. A total of 17 studies met inclusion criteria. The pooled mean difference demonstrated significant improvements in both IKDC (MD=28.5 points; 95% CI: 27.9-29.2) and Lysholm scores (MD=28.5 points; 95% CI: 27.9-29.2). Subgroup analyses revealed notable effectiveness for AIR compared to CM and PM, with statistically significant subgroup differences (p<0.05). The overall treatment success rate was 87% (95% CI: 83-92%). Across techniques, patient-reported outcomes improved markedly (IKDC fixed-effect pooled Mean Difference [MD] 28.8 points, 95% CI 28.2-29.4; random-effects overall effect significant; I²=98%). In anterior vs posterior all-inside subgroups, IKDC showed no robust between-approach difference on the random-effects test (χ²=0.51, p=.48), with a small fixed-effect difference (χ²=4.34, p=.04). Lysholm scores also improved substantially (fixed-effect pooled MD 28.0 points, 95% CI 27.3-28.7), and the between-approach difference was significant, favoring the posterior subgroup on the fixed-effect model. The pooled clinical success proportion was 90% without a significant difference between approaches (p=.10). The findings indicate that surgical interventions, particularly All-inside repair has effectively improved knee function and patient-reported outcomes following ramp lesions compared to conservative management and partial meniscectomy. However, no.
Aging is associated with declines in muscle strength and functional capacity, driven by both neuromuscular and cardiovascular changes. In parallel, ageing is accompanied by reduced nitric oxide (NO) bioavailability and potentially a reduced efficacy of the nitrate (NO₃-)-nitrite (NO₂-)-NO pathway, a route for NO generation that supports vascular and skeletal-muscle function. Thus, the aim of the present study was to examine the effects of acute ingestion of 70 mL of nitrate-rich beetroot juice (6.4 mmol NO₃-) versus 70 mL placebo (0.04 mmol NO₃-) on strength and functional performance in healthy older women aged between 70-80 years. Nine healthy women (75.4±4.0 years) participated in this randomized, double-blind, placebo-controlled crossover experiment. Participants completed a physical performance test consisting of 6-m walk test, isometric handgrip strength (i.e., dominant and non-dominant hand), Timed Up-and-Go Test (TUG), and sit-to-stand (STS) muscle power test along with cardiovascular assessments (systolic/diastolic blood pressure, heart rate response and 6-minutes' walk performance) after ingesting either 70 mL of beetroot juice (6.4 mmol NO₃-) or 70 mL of placebo (0.04 mmol NO₃-) in a randomized order. Beetroot juice ingestion resulted in significant improvement vs. placebo in isometric dominant handgrip strength (9.6%, p=0.046, ES=0.78), with no changes observed in the non-dominant hand (1.2%, p=0.553, ES=0.11). No differences were found in beetroot juice vs placebo for 6-m walk performance (-3.3%, p=0.306, ES=-0.19), TUG (-5.0%, p=0.225, ES=-0.17), STS leg extensor muscle power (5.0%, p=0.121, ES=-0.25), or 6-minute walk performance (-7.7%, p=0.110, ES=-0.48). Acute ingestion of nitrate-rich beetroot juice led to increased isometric handgrip strength in healthy older women, with no significant effects observed in functional performance (TUG), lower limb STS power, cardiovascular responses, or short-term (6-m) as well as long-term (6-min) walking performance compared with placebo conditions.
This narrative review examines acute and chronic kidney injury following COVID-19 infection and vaccination, discussing the mechanism of SARS-CoV-2 entry into host cells through the ACE2 receptor - highly expressed in renal tissues - facilitating the viral invasion. Viral RNA has been detected in the urine of patients infected with SARS-CoV-2, suggesting direct renal involvement. The incidence of Acute Kidney Injuriy (AKI) among hospitalized COVID-19 patients was particularly higher in the early stages of the pandemic and largely varied by 29%-46%, depending on population studied and COVID-19 wave. Pathological findings include Acute Tubular Injury (ATI), collapsing glomerulopathy, and focal segmental glomerulosclerosis. Major risk factors for AKI comprise older age, male sex, diabetes, hypertension, cardiovascular disease, and preexisting Chronic Kidney Disease (CKD). AKI significantly increases mortality of COVID-19 patients, particularly in advanced stages of renal failure. CKD is also associated with severe COVID-19 outcomes, including increased hospitalization, intensive care admission, and mortality. Patients with CKD show a dose-dependent relationship between disease stage and adverse patient outcomes. This review further addresses renal complications following COVID-19 vaccination, which, although rare, encompass various immune-mediated glomerular diseases. Minimal Change Disease (MCD) is most frequently reported after COVID-19 vaccination, followed by IgA nephropathy, membranous nephropathy, anti-glomerular basement membrane (anti-GBM) nephritis, and ANCA-associated vasculitis. These conditions commonly present with hematuria, proteinuria, or nephrotic syndrome, and many respond to corticosteroid or immunosuppressive therapy. Other less frequent renal complications include thrombotic microangiopathy, acute tubulointerstitial nephritis, and IgG4-related nephritis. In conclusion, both COVID-19 infection and vaccination can be associated with a spectrum of renal manifestations ranging from AKI to CKD and immune-mediated glomerulopathies. Awareness, early detection, and multidisciplinary management are essential to reduce renal morbidity and improve patient outcomes.
When conservative treatment of osteoarthritis is not effective, patients may undergo total joint replacement. Postoperative rehabilitation is a crucial component of recovery, and early rehabilitation plays a particularly important role in optimizing outcomes, with the aim of enabling patients to return to independence and work as soon as possible. The aim of this paper is to summarize the role of early rehabilitation after total knee and hip joint replacement, including its main goals, key components, optimal timing, potential risks, and the evidence comparing early with delayed rehabilitation. Current evidence indicates that early inpatient rehabilitation contributes to faster recovery of mobility, improved joint range of motion and muscle strength, fewer postoperative complications, and shorter hospital stays. Early outpatient rehabilitation initiated soon after discharge may further support recovery by increasing daily physical activity, improving joint mobility, and reducing rehabilitation costs. Although some studies report similar clinical outcomes between early and delayed physiotherapy, earlier initiation may allow patients to achieve comparable functional recovery sooner. Overall, early rehabilitation represents a safe and effective approach that should be integrated into standard postoperative care pathways.
Systemic Glucocorticoid (GC) therapy is integral to managing various paediatric conditions, including inflammatory muscle and neuromuscular diseases. However, prolonged GC use in children poses a significant risk for severe ocular Adverse Drug Reactions (ADRs), notably Posterior Subcapsular Cataract (PSCC) and Steroid-Induced Ocular Hypertension (SIOH). These ADRs can lead to irreversible visual impairment, creating a substantial burden, particularly for paediatric patients already managing chronic conditions. Identifying specific risk factors and precise exposure thresholds is crucial for optimizing GC treatment and guiding timely ophthalmic monitoring. This retrospective case–control study analyzed data from 305 children with kidney disease, who received oral or intravenous GCs between December 2020 and December 2022. Participants were grouped into PSCC, SIOH, or control (no ocular ADRs). Logistic regression assessed risk factors, and Receiver Operating Characteristic (ROC) analysis determined critical thresholds for cumulative dose and duration. Results indicated seven significant risk factors for PSCC: younger age, longer GC duration, hypertension, growth retardation, vitamin D deficiency, immunosuppressant use, and oral methylprednisolone. Critical thresholds for cataract onset were identified as GC treatment duration >5.6 months or a cumulative dose >5,888 mg. For SIOH, higher daily GC dosage (>0.59 mg/kg/day), oral methylprednisolone, and growth retardation were significant risk factors. These findings elucidate key risk factors and establish quantitative GC exposure thresholds for ocular ADRs in children. They provide evidence-based guidance for ophthalmic screening and intervention timing, particularly relevant for paediatric patients with muscle and neuromuscular diseases requiring long-term GC therapy. Proactive monitoring and tailored GC management are essential to mitigate vision-threatening complications and improve long-term patient outcomes.
Telerehabilitation is increasingly used in knee osteoarthritis, but its effectiveness compared with structured home exercise and the role of physical therapist contact remain unclear. To address this, we aimed to investigate whether the clinical effectiveness of telerehabilitation for knee osteoarthritis is primarily attributable to the digital platform itself or to the extent and quality of physical therapist engagement within that platform. In this single-centre Randomised Controlled Trial (RCT), 118 patients with knee OA (Kellgren-Lawrence grade I-III) were allocated 1:1 to a 12-week telerehabilitation (TR; n=57) or booklet-based exercise programme (BB; n=61). Within the telerehabilitation group, participants were retrospectively stratified into those with Physical Therapist Contact (TR-C) and those without contact (TR-NC) for an exploratory analysis. Outcomes included knee pain (NRS, Numerical Rating Scale), Range Of Motion (ROM), WOMAC, physical activity (IPAQ), and health-related quality of life (SF-12). A post-hoc exploratory subgroup analysis was conducted and looked at the impact of a physical therapist with and without contact. A key component of the analysis was an exploratory subgroup comparison examining the role of physical therapist contact within the telerehabilitation group. Primary outcomes were analysed using mixed-model ANOVA, with exploratory subgroup comparisons. Both groups showed significant within-group improvements in pain, ROM, and WOMAC scores (all p ≤0.001), with no significant group × time interactions (p >0.05). Exploratory analysis identified significant differences based on physical therapist contact, with greater improvements in pain (p=0.009), knee flexion (p=0.041), and WOMAC Pain (p=0.047) among participants who engaged with the physical therapist. Participants without contact showed the smallest improvements. When stratified by physical therapist contact, participants receiving contact demonstrated greater improvements than those without contact, who showed the smallest gains. Telerehabilitation and booklet-based exercise programme provide comparable clinical outcomes at the group level. However, physical therapist engagement appears to be a key determinant of treatment response. These findings suggest that the effectiveness of TR depends more on clinical interaction than on digital delivery alone. Physical therapist contact may represent an important component influencing the effectiveness of telerehabilitation. It remains unclear whether telerehabilitation effectiveness stems from the digital platform, exercise content, or physical therapist guidance.
