Search Results (1,783)

Background: Supplemental oxygen and aerosol therapy may be used simultaneously to treat neonates suffering from hypoxemia caused by respiratory diseases. Due to the cost and lack of availability of oxygen cylinders in some countries, oxygen concentrators are a reported substitute. We assessed whether an oxygen concentrator compared to low-flow oxygen therapy impacts neonatal aerosol drug delivery. Methods: A vibrating mesh nebulizer (A-VMN; Aerogen Solo) was used to aerosolize a 500 µg dose of salbutamol. The aerosol was delivered via a nasal cannula to a neonate head model in combination with oxygen concentrator at gas flow rates of 0.2, 1.0, and 5.0 L per minute (LPM), and low-flow oxygen therapy at gas flow rates of 1.0, 4.0, and 5.0 LPM. Emitted and tracheal doses were recorded. The impact of A-VMN operation and refill on circuit pressure in both systems was also measured. Results: The oxygen concentrator delivered a higher emitted dose than the low-flow system, the largest emitted dose (%) being 20.58 ± 0.50% and 14.69 ± 0.89%, respectively, at 1.0 LPM, p = 0.018. At 5.0 LPM, the tracheal dose was 11.01 ± 0.29% for the oxygen concentrator compared to 9.66 ± 1.53% for low-flow oxygen therapy, p = 0.073. Refill and operation of the A-VMN did not impact the circuit pressure in either system. Conclusions: This study shows that the system used to provide concurrent aerosol and supplemental oxygen therapy has a significant impact on the quantity of nebulized drug delivered to patients. Full article

Childhood-onset lupus nephritis (cLN) should no longer be framed as a smaller version of adult lupus nephritis. It is a high-stakes pediatric kidney disease in which immune injury, treatment toxicity, growth, puberty, fertility, adherence, and transition to adult care intersect over decades. Approximately 10–20% of systemic lupus erythematosus begins in childhood, and 40–60% of affected children develop lupus nephritis. Regional cohorts report even higher renal involvement in some populations, including 65–73% among Saudi children with SLE. Contemporary guidance has moved from prolonged high-dose glucocorticoids and cyclophosphamide-dominant treatment toward biopsy-driven, treat-to-target care built around mycophenolic acid analogues, hydroxychloroquine, nephroprotection, rapid steroid tapering, and selected belimumab- or calcineurin-inhibitor-based triple therapy. This Viewpoint argues that the central question in cLN is no longer simply how to induce remission, but how to produce a durable kidney response early enough, with sufficiently low cumulative toxicity, to preserve kidney function and childhood development. Pediatric practice must therefore combine adult trial evidence with child-specific caution, explicit adherence strategies, fertility and growth protection, and structured transition planning. The aim should be efficacy without toxicity: not undertreatment, but intelligent, sustainable, developmentally informed treatment. Full article

Background: Oral everolimus (Oral-EVE; EVE, Afinitor^®) is an effective therapy for multiple malignancies, including HR-positive/HER2-negative breast cancer, but its clinical use is limited by low and variable oral bioavailability as well as extensive first-pass metabolism. IV-EVE is a Deciparticle™ intravenous formulation of everolimus developed to bypass gastrointestinal absorption and improve systemic pharmacokinetic (PK) predictability. Methods: In vitro ADME properties were assessed across multiple species. IV-EVE (Intravenous EVE, Sapu003) and EVE demonstrated comparable plasma protein binding, metabolic stability, and CYP-mediated metabolism. Pharmacokinetics, tissue distribution, metabolism, and excretion of IV-EVE were evaluated following intravenous administration in rats, with Oral-EVE as a comparator. Results: Elimination of intact everolimus was minimal following either route of administration and occurred predominantly through metabolic biliary/fecal pathways. Compared with Oral-EVE, IV-EVE produced substantially higher and more consistent systemic exposure while maintaining comparable elimination half-lives. Intravenous administration resulted in broad tissue distribution without the marked gastrointestinal accumulation observed following oral dosing. Repeat-dose toxicology studies in rats demonstrated no treatment-related gastric pathology following intravenous administration. Conclusions: These findings suggest that intravenous administration may overcome limitations associated with oral delivery and support the clinical evaluation of IV-EVE in patients with advanced malignancies. Full article

Background/Objectives: Discontinuation of long-term denosumab (Dmab) remains a major clinical challenge because of rebound activation of bone remodeling and increased vertebral fracture risk. Intravenous zoledronate (ZOL) is widely recommended as sequential therapy, although evidence after very prolonged Dmab exposure is limited. We report a patient who developed two rare adverse events—acute hepatocellular injury and delayed inflammatory polyarthritis—following a single ZOL infusion administered after 12 years of continuous Dmab treatment. The subsequent management of persistent rebound bone turnover with oral alendronate (ALN) highlights the therapeutic challenges encountered when repeat ZOL administration is not feasible. Methods: A 65-year-old woman with postmenopausal osteoporosis received a single 5 mg ZOL infusion 6 months after her final Dmab injection following 12 years of continuous therapy. Within 24 h, she developed a typical acute phase response. Three days later, marked hepatocellular injury was detected, characterized by substantial elevations in transaminases and gamma-glutamyl transferase, while viral and autoimmune hepatitis were excluded. Liver enzymes normalized within five days with supportive management. Thirty-two days after ZOL administration, she developed inflammatory polyarthritis in the absence of previous rheumatologic disease and with negative immunologic testing. Treatment with low-dose prednisone (5 mg/day) resulted in rapid clinical and biochemical remission. At 6 months, bone turnover markers remained markedly elevated (CTX 0.82 ng/mL, P1NP 95 ng/mL), indicating insufficient suppression of rebound bone turnover after Dmab discontinuation. Because of the adverse events, the patient declined repeat ZOL administration. Results: Weekly oral alendronate (ALN) (70 mg) was initiated and was associated with partial suppression of bone turnover markers. Despite a decline in bone mineral density (BMD) of approximately 5% at both the lumbar spine and total hip over 12 months, BMD remained within the osteopenic range, and no new fragility fractures occurred during follow-up. Conclusions: This case illustrates two rare sequential immune-mediated adverse events following ZOL infusion and underscores the therapeutic challenges of managing Dmab discontinuation after long-term treatment when repeat ZOL administration is contraindicated. Sequential intravenous ZOL and oral ALN therapy was associated with partial suppression of bone turnover markers and protection from incident fractures during follow-up, despite a modest decline in BMD of approximately 5%. Full article

Background/Objectives: Diabetes mellitus type 2 (T2DM) is often associated with hypertension, necessitating treatment with combinations of medications that address both glycemic control and blood pressure. Whether commonly co-prescribed antihypertensives modify the glycemic efficacy of a sulfonylurea remains insufficiently characterized in controlled preclinical models. Methods: One hundred adult male Wistar rats were allocated to ten parallel groups (n = 10): healthy and diabetic untreated controls; glimepiride, bisoprolol or amlodipine monotherapy (in healthy and diabetic animals); and the diabetic combinations glimepiride+bisoprolol and glimepiride+amlodipine. T2DM was induced with a high-fat diet plus low-dose streptozotocin (35 mg/kg, i.p.) and confirmed by fasting blood glucose ≥ 200 mg/dL. Glycated hemoglobin (HbA1c) was measured weekly for 11 weeks. Non-parametric inference (Kruskal–Wallis, Dunn’s with Bonferroni correction, Mann–Whitney U, Wilcoxon signed-rank) was complemented by Random Forest regression and PCA/K-means clustering. Results: Week-11 HbA1c differed markedly across groups (Kruskal–Wallis H = 94.3, p < 0.001). Glimepiride + bisoprolol achieved near-normal control (4.37% ± 0.15), statistically indistinguishable from healthy groups (p ≥ 0.33), and was the only diabetic regimen with a declining trajectory (−0.66 percentage points; Wilcoxon p = 0.004). Adding either antihypertensive to glimepiride did not worsen glycemic control. Amlodipine monotherapy did not attenuate hyperglycemia (8.47% ± 0.20), approaching that of untreated diabetic controls (9.31% ± 0.18), consistent with the absence of intrinsic glucose-lowering activity. All agents showed pronounced disease-state dependence (healthy–diabetic divergence 2.33–3.13 points). Random Forest prediction was accurate (R² = 0.985), and unsupervised clustering separated effective from ineffective regimens, corroborating the statistical findings. Conclusions: In this model, bisoprolol co-administration enhanced and amlodipine co-administration preserved glimepiride-mediated glycemic control. Glimepiride+bisoprolol emerged as the most effective regimen, supporting cardioselective β-blockade as a metabolically favorable antihypertensive partner for sulfonylurea therapy and warranting clinical confirmation. More broadly, these results provide a preclinical, evidence-based rationale for selecting metabolically favorable antihypertensives in patients with coexisting T2DM and hypertension, with the potential to improve glycemic outcomes and reduce the risk of adverse drug–disease interactions during combination therapy. Full article

Background/Objectives: Photon re-irradiation in previously treated head and neck cancer (HNC) is constrained by cumulative normal-tissue toxicity. Pencil-beam scanning intensity-modulated proton therapy (PBS-IMPT) allows for a sharper dose conformation than conventional photon techniques, which may widen the therapeutic window in previously irradiated tissue. Methods: Sixty-five patients with recurrent or second primary HNC were enrolled in a prospective single-institution registry and re-irradiated with PBS-IMPT between January 2020 and December 2025. Forty-five were treated with radical intent (69.2%), and 20 were treated postoperatively (30.8%), with a median prescribed dose of 66 Gy (RBE) in 30 fractions. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Locoregional control (LRC), adverse events and the prognostic impact of anatomical extent were secondary endpoints. Results: The median follow-up was 9.3 months. The median OS was 17.2 months (95% CI 13.9–NR), with a 12-month rate of 67.1%. The median PFS was 10.1 months and the median LRC was 28.1 months. Central/skull-base involvement was associated with a non-significant trend toward worse OS (14.3 vs. 35.2 months; p = 0.062) and with significantly worse PFS (9.1 vs. 14.7 months; p = 0.037) than peripheral disease, but LRC did not differ between the groups (p = 0.240). Grade ≥ 3 oral mucositis occurred in 7.7%, with no grade 4–5 acute events. Within a median follow-up of 9.3 months, late osteoradionecrosis affected 6.2%, but late toxicity data remain preliminary given the short follow-up. Ninety-two percent of patients completed treatment. Conclusions: PBS-IMPT re-irradiation provided adequate survival with low acute toxicity. T3–T4 stage at re-irradiation was the only variable retaining significance for PFS on multivariable analysis (HR 4.32, 95% CI 1.24–15.13; p = 0.022). The poor survival observed for central/skull-base disease on Kaplan–Meier curves disappeared after T-stage adjustment, indicating the higher concentration of advanced disease in that compartment. Multicentre prospective data and longer follow-up are needed. Full article

Intranasal corticosteroids (INCS) remain the cornerstone of pharmacologic treatment for allergic rhinitis (AR) because of their well-established anti-inflammatory efficacy and generally favorable benefit–risk profile. Nevertheless, concerns regarding local and systemic corticosteroid-related adverse events (AEs) continue to influence patient adherence, prescribing practices, and long-term treatment acceptance. In routine clinical practice, safety perception and corticosteroid-related concerns frequently influence adherence and formulation selection to a greater extent than differences in clinical efficacy, particularly in pediatric populations and in patients requiring prolonged continuous therapy. Differences in pharmacokinetic and pharmacodynamic properties, including systemic bioavailability, glucocorticoid receptor affinity, lipophilicity, protein binding, and extent of first-pass metabolism, are considered important safety profile determinants of currently available INCS formulations. Available evidence indicates that local AEs, particularly epistaxis, nasal irritation, dryness, and sensory discomfort, represent the most frequently reported treatment-related AEs across INCS formulations, although these events are generally mild, self-limiting, and infrequently treatment-limiting. Clinically significant structural nasal complications, including septal perforation or progressive mucosal injury, appear uncommon in currently available studies. Systemic AEs, including hypothalamic–pituitary–adrenal (HPA) axis suppression, ocular toxicity, growth impairment, or clinically meaningful effects on bone metabolism, have not been consistently demonstrated with currently used low-systemic-exposure formulations administered at recommended therapeutic doses. Although systemic glucocorticoid exposure has been associated with alterations in lipid metabolism, adipose tissue function, and metabolic homeostasis, currently available intranasal corticosteroids demonstrate minimal systemic exposure, making clinically relevant metabolic effects unlikely under recommended therapeutic conditions. Formulations such as mometasone furoate, fluticasone propionate, fluticasone furoate, and ciclesonide exhibit pharmacokinetic characteristics associated with minimal systemic exposure because of extensive first-pass metabolism and low oral bioavailability. Although substantial pharmacokinetic differences exist between currently available INCS formulations, direct comparative evidence demonstrating clinically meaningful superiority in systemic safety outcomes remains limited. Current evidence suggests that formulation-dependent differences are clinically more relevant with respect to local tolerability, sensory characteristics, patient preference, and long-term adherence than major systemic safety outcomes. Pediatric evidence is generally reassuring, although historical concerns regarding growth suppression associated with earlier corticosteroid formulations continue to influence clinical practice. Currently available evidence supports the use of modern INCS as effective and generally well-tolerated therapeutic options across adult and pediatric populations. Full article

Background/Objectives: Regional citrate anticoagulation (RCA) is guideline-preferred for continuous renal replacement therapy (CRRT), yet implementation requires expertise, calcium protocols, and reliable monitoring. Evidence for standardized low-molecular-weight heparin strategies without routine anti-Xa monitoring remains limited. Methods: We retrospectively analyzed adult ICU patients receiving protocolized divided-dose enoxaparin during CRRT from January 2020 to December 2024. Enoxaparin 1.5 mg/kg/24 h was divided into six equal prefilter doses every 4 h. The primary outcome was circuit clotting; death and hemodynamic instability were treated as competing termination events. Safety endpoints were ISTH major bleeding, clinically relevant non-major bleeding (CRNMB), minor bleeding, thrombosis, and suspected heparin-induced thrombocytopenia (HIT). Results: The cohort included 200 patients and 223 CRRT runs, contributing 8829.8 CRRT-hours. Median run duration was 35.0 h (IQR, 27.2–52.1). Circuit clotting occurred in 31 runs (13.9%; 95% CI, 9.6–19.1), equivalent to 0.35 events per 100 CRRT-hours. Kaplan–Meier clotting-free survival at 48 h was 89.8% (95% CI, 84.3–95.2), and the competing-risk cumulative incidence of clotting was 9.0%. Any classified bleeding occurred in 10 runs (4.5%; 95% CI, 2.2–8.1), including one ISTH major bleeding event and one CRNMB event. No thrombotic or HIT events were identified. In a prespecified four-variable Cox model with patient-level cluster-robust standard errors, no predictor was significantly associated with clotting. Conclusions: In a citrate-unavailable or citrate-not-routinely-implemented ICU setting, this standardized divided-dose enoxaparin protocol showed low observed major/clinically relevant bleeding rates and acceptable clotting-free circuit performance. Prospective comparative evaluation is warranted. Full article

Seasonal influenza is not only a respiratory infection but also a clinically relevant trigger of acute cardiovascular events. In adults with established cardiovascular disease, particularly older adults and patients with recent acute coronary syndrome or heart failure, influenza vaccination should be considered a low-risk, evidence-supported component of cardiovascular prevention rather than solely protection against respiratory disease. The evidence addresses three related but distinct questions: influenza infection as a cardiovascular trigger; influenza vaccination versus placebo or no vaccination; and enhanced or high-dose vaccination versus standard-dose vaccination. Randomized trials and meta-analyses support reductions in major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality in higher-risk secondary-prevention populations, with particularly persuasive evidence after myocardial infarction. Recent pragmatic active-comparator trials of high-dose inactivated influenza vaccine, including DANFLU-2 and GALFLU, and the individual-level pooled FLUNITY-HD analysis provide incremental evidence in adults aged 65 years or older, strongest for hospitalization for influenza or pneumonia, cardiorespiratory hospitalization, and heart failure hospitalization. The current priority is implementation: screening, offering, documenting, and communicating vaccination across hospitalization, outpatient cardiology, cardiac rehabilitation, heart failure pathways, primary care, pharmacies, and long-term care. Influenza vaccination should complement, not replace, established guideline-directed cardiovascular therapies. Full article

Objective: This study aimed to evaluate the knowledge and clinical awareness of local anesthetic systemic toxicity (LAST), preventive practices, knowledge of lipid emulsion therapy, and institutional availability among dentists actively practicing in Türkiye, and to examine the demographic and professional factors associated with knowledge level. Methods: This descriptive cross-sectional study was conducted using a 15-item online questionnaire developed by the researchers. The analyses included 369 dentists actively practicing in Türkiye. Data were analyzed using descriptive statistics, the Kruskal–Wallis test, Dunn–Bonferroni pairwise comparisons, Spearman rank correlation, and multinomial logistic regression analysis. Results: Among the participants, 45.8% reported having basic knowledge of LAST, whereas only 2.7% reported detailed knowledge, including the management steps. Although 40.1% stated that they calculated the local anesthetic dose according to the patient’s body weight, only 3.3% reported preparing an emergency response plan for LAST, and 2.2% indicated that they were prepared to use treatment options such as lipid emulsion. Regarding lipid emulsion therapy, 59.1% of participants had low knowledge and 24.4% had superficial knowledge; only 0.5% reported detailed knowledge of the administration steps and dosing protocol. In terms of institutional availability, 45.0% did not know whether lipid emulsion was available at their institution, 40.9% reported that it was unavailable, and 14.1% reported that it was available. Knowledge levels differed according to professional status; however, the effect size was small (H(2) = 13.129; p = 0.001; ε² = 0.030). No statistically significant association was found between years of professional experience and knowledge level (ρ = 0.020; p = 0.702). Conclusions: Although dentists’ self-reported awareness of LAST varied, detailed knowledge of the administration steps and dosing protocol for lipid emulsion therapy, as well as institutional preparedness, remained limited. The findings suggest that strengthening practice-oriented education on the prevention and management of LAST and reviewing lipid emulsion availability and emergency response protocols in clinical institutions may be beneficial. Full article

Background: Due to the serious side effects and the resistant phenotype acquired by tumors, cisplatin has limited clinical efficacy. The current study aims to investigate the potential of disulfide-bridged phthalocyanines to make breast cancer cells (MCF-7) more sensitive to cisplatin. For this purpose, a novel disulfide-bridged dimeric phthalocyanine complex with a therapeutically active wavelength absorbance value that is activatable in cancer cells was synthesized and encapsulated in liposome nanoparticles. Methods: The synthesized phthalocyanine was characterized using FTIR, UV–visible, and MALDI-TOF-MS techniques; liposome nanoparticles containing the synthesized phthalocyanine were characterized using a particle size analyzer and were tested on MCF-7 breast cancer cell lines using MTT and flow cytometric assays. Results: The results have illustrated that GSH cleavages disulfide bonds of the synthesized disulfide-bridged dimeric phthalocyanine complex with quite favorable characteristics for photodynamic therapy, such as a therapeutically active wavelength absorbance value (685 nm), and disulfide-bridged phthalocyanine (ASG20)-containing liposome nanoparticles have quite favorable characteristics (average size of 167.6 nm and polydispersity index of 0.108) for biomedical applications. As evidenced by MTT and flow cytometric assays, by causing extra decreases in the viability of breast cancer cells (p < 0.01), pre-treatment of the breast cancer cells with photodynamic therapy using the activatable liposome nanoparticles significantly (p < 0.01) enhanced the anticancer activity of cisplatin in high and low doses. Conclusions: In conclusion, the activatable liposome nanoparticles containing disulfide-bridged dimeric phthalocyanine complexes can enable much more effective cisplatin-based therapies for breast cancer by overcoming the handicaps of cisplatin, drug resistance (by decreasing intracellular GSH levels), and serious side effects (by enabling the usage of lower doses of cisplatin in chemotherapy). Full article

Skeletal safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains uncharted, with emerging evidence suggesting a divergence between mono- and dual-agonist therapies. GLP-1RA monotherapy appears bone-neutral, with modest or no adverse effects on bone mineral density (BMD), whilst dual agonists may confer a relatively higher risk of osteoporosis and fractures, plausibly mediated by greater weight loss magnitude and concomitant reductions in lean body mass (LBM) rather than direct osteotoxicity. Intensified surveillance is warranted in susceptible phenotypes, including older adults and postmenopausal women with low baseline BMD under conditions of rapid weight loss. Osteoporosis risk is further amplified by pre-existing osteopenia, nutritional deficiencies, and concomitant exposure to bone-active agents. Given the limitations of serial dual-energy X-ray absorptiometry (DXA), including cumulative radiation exposure and limited sensitivity to early remodeling changes, biochemical markers potentially depict bone turnover more dynamically. Measurement of dynamic bone resorption markers enables early identification of skeletal disturbances, supporting proactive adjustment of therapeutic strategy, dosing, and duration. Specifically, deoxypyridinoline (DPD), a bone-specific collagen crosslink, is a highly sensitive and rapidly responsive urine biomarker of osteoclastic activity. Incorporating DPD urine testing into monitoring frameworks potentially facilitates individualized therapeutic modulation, optimizing the metabolic efficacy of GLP-1RAs while safeguarding skeletal integrity. Full article

Background: Artemisia absinthium (A. absinthium) is a perennial plant valued for its antibacterial, antioxidant, and anti-inflammatory properties, exhibiting broader therapeutic potential. Given the need to deliver low doses of A. absinthium extract, mesoporous silica nanoparticles have attracted considerable attention as promising nanocarriers due to their distinctive physical and chemical properties. Methods: Physicochemical characterization of the materials was performed and biological assays were conducted to investigate the ROS, antibacterial and antioxidant activity of A. absinthium extract encapsulated within cerium- and calcium-doped mesoporous silica nanoparticles (MNSiCaCe) against both aerobic and anaerobic bacteria. Results: FTIR, SEM, and BET analysis confirmed successful synthesis of the MNSiCaCe. Phytochemical profiling of Artemisia absinthium extract using HPLC revealed the presence of artemisinin and a rich composition of phenolic and flavonoid constituents, with a total phenolic content of 182 ± 3.6 mg GAE/100 g dry plant material and a total flavonoid content of 42.5 ± 0.6 mg QE/100 g. Quantitative drug loading profiling demonstrated that while plain MNSi nanocarriers achieved a loading capacity of 16.96%, the MNSiCaCe enhanced this threshold to 43.11%. The in vitro controlled-release kinetics exhibited a highly prolonged and slow-release profile of the MNSiCaCe. The materials demonstrated excellent hemocompatibility and high mitochondrial activity with human periodontal ligament cells (hPDLCs). Elevated ROS generation was observed under conditions where antibacterial activity was most pronounced. While the artemisinin-doped nanoparticles showed notable antibacterial effects, the complete Artemisia absinthium-loaded nanoparticles achieved a significantly greater reduction in bacterial viability probably due to the synergistic interaction between artemisinin and the extract’s rich polyphenol profile. Conclusions: These findings highlight MNSiCaCe as a promising and safe nanocarrier system for drug delivery, with strong antibacterial potential, offering valuable applications in antibacterial therapies. Full article

Musculoskeletal (MSK) disorders—osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, tendinopathy, and skeletal muscle injury—contribute the largest share of years lived with disability worldwide. Conventional therapy relies on systemic dosing or repeated intra-articular and peri-tissue injections, which suffer from off-target toxicity, poor lesional bioavailability, and low adherence. Polymer microneedles (MNs)—micron-scale projections of biodegradable, dissolving, hydrogel-forming, or composite polymers—have rapidly matured into a versatile platform for minimally invasive, spatially localized, and temporally programmable delivery of small molecules, biologics, nucleic acids, extracellular vesicles, and cells to MSK tissues. This review synthesizes 2018–2026 advances in polymer MN systems engineered specifically for MSK regeneration. We classify dominant polymer chemistries and MN architectures; map fit-for-purpose across bone, cartilage, joint, intervertebral disc, tendon, and skeletal muscle; and survey “smart” MN designs that exploit reactive oxygen species, pH, mechanical, triboelectric, optogenetic, and ultrasonic triggers. We close with a concise conclusion and forward perspective that identifies the key design levers—hybrid MN–scaffold combination products, stimuli-responsive platforms tuned to the MSK micro-environment, and cell- and EV-loaded formats—most likely to have clinical impact. Full article

Background: COVID-19 has been linked to musculoskeletal complications, including femoral head avascular necrosis (AVN). Both COVID-19–related hypercoagulability and corticosteroid therapy have been proposed as contributing factors. This systematic review synthesizes current evidence on the occurrence, clinical characteristics, timing, and risk factors for femoral head AVN following COVID-19. Methods: A PRISMA-compliant systematic search of PubMed, Embase, and Scopus identified observational studies and case series (≥10 patients) reporting femoral head AVN in adults or adolescents with confirmed COVID-19. Data on epidemiology, symptom onset, imaging findings, and corticosteroid exposure were narratively synthesized due to heterogeneity. Results: Fifteen eligible studies described patients with post-COVID femoral head AVN. Symptom onset ranged from days to >12 months after infection. Early MRI often revealed asymptomatic or low-grade disease. Corticosteroid exposure was common and strongly associated with AVN severity; however, several studies reported AVN in patients without steroid use, whether this reflects an independent contribution of COVID-19 or unrecognized confounding cannot be determined from the available uncontrolled data. Higher cumulative steroid doses, severe pulmonary involvement, and elevated inflammatory markers were consistently linked to more advanced AVN stages. Conclusions: Femoral head AVN is an emerging post-COVID complication with variable timing and presentation. Corticosteroid exposure remains the principal risk factor; whether COVID-19 contributes independently of corticosteroids is unproven, and current evidence supports an association rather than a causal relationship. Awareness of this potential complication is warranted, although the role of early MRI screening remains to be established in prospective studies. Full article