Search Results (380)

Background/Objectives: Early identification of complicated appendicitis in children remains challenging. We developed and internally validated laboratory-based machine-learning models for severity stratification using age and routine admission laboratory data. Methods: This retrospective study included 628 children with surgically confirmed appendicitis treated between 2020 and 2024. Complicated appendicitis was defined by operative or pathological evidence of perforation, gangrene, abscess, phlegmon, diffuse peritonitis, or comparable advanced inflammation. Fifteen candidate predictors were evaluated using five prespecified models. Models were tuned in the training set and evaluated once on an isolated test set. Pairwise DeLong comparisons, decision curve analysis, SHAP, and permutation importance were performed. Results: Complicated appendicitis occurred in 93 patients (14.8%). The prespecified primary CatBoost model achieved a ROC AUC of 0.867, a precision-recall AUC of 0.677, a sensitivity of 0.750, a specificity of 0.863, a positive predictive value of 0.488, and an F1-score of 0.592. Formal comparisons did not demonstrate statistically significant AUC superiority over the other algorithms after Holm correction. Exploratory decision curve analysis showed a greater net benefit than treat-all and treat-none strategies across threshold probabilities of 0.06–0.35. ESR, age, CRP, and CRP-derived indices were the most influential model features. Conclusions: Routine laboratory data may provide adjunctive information for severity stratification, but the modest event count, limited positive predictive value, and absence of external validation preclude stand-alone clinical use. Full article

Background: Acute appendicitis is a leading pediatric surgical emergency. Timely diagnosis remains challenging, particularly in young children with atypical presentations. Clinical evaluation alone yields variable diagnostic performance, prompting the use of risk stratification tools. Objective: To evaluate and compare the Alvarado score against alternative clinical scoring systems, laboratory biomarkers, and imaging modalities in pediatric acute appendicitis. Methods: A narrative literature review with structured selection elements was conducted across PubMed, Scopus, and Web of Science for studies published between 2016 and 2026. Results: The Alvarado score demonstrates moderate diagnostic accuracy in children, with good sensitivity but limited specificity (57–76%) at standard cut-offs (≥7). Pediatric-specific scores like the Pediatric Appendicitis Score (PAS) offer higher sensitivity, while the Appendicitis Inflammatory Response (AIR) score provides superior specificity and better identifies complicated appendicitis (including gangrene, phlegmon, and perforation). Continuous risk models, notably the Pediatric Appendicitis Risk Calculator (pARC), outperform fixed additive scores in pediatric cohorts. Combining clinical scores with C-reactive protein, neutrophil-to-lymphocyte ratio, and selective ultrasonography enhances diagnostic precision. Computed tomography reserved for equivocal cases further optimizes diagnostic yield. Conclusion: The Alvarado score should not be used as a standalone tool. A structured, stepwise multimodal approach integrating clinical scores (such as pARC or PAS), inflammatory biomarkers, and selective imaging optimizes diagnostic accuracy and supports timely surgical decision-making in children. Full article

Background and Objectives: This retrospective cohort study aimed to analyze the surgical evolution, clinical outcomes, and adoption of uterus-preserving techniques in placenta previa (PP) and placenta accreta spectrum (PAS) cases managed by a single senior surgeon over an uninterrupted 13-year period. Materials and Methods: A total of 324 patients who underwent cesarean section by a single experienced surgeon with a diagnosis of placenta previa between 1 January 2013 and 1 January 2026 were included in the study. The demographic and obstetric characteristics of the patients, the surgical methods applied, perioperative blood product requirements, complications, and neonatal outcomes were evaluated retrospectively. Uterus-preserving surgical methods included a temporary uterine tourniquet, intrauterine hemostatic sutures, bilateral internal iliac artery ligation (IIAL), Bakri balloon tamponade, B-Lynch suture, uterine lower segment resection, and uterine packing, applied in a stepwise manner. The perioperative hemoglobin change (ΔHb) was calculated as an objective indicator of blood loss. Results: Placenta previa constituted a substantial proportion of all cesarean sections performed by the same surgeon during the study period. Total previa was the predominant type, and almost half of the operations were carried out under emergency conditions. Peripartum hysterectomy was required in a minority of patients, and placenta accreta spectrum was histopathologically confirmed in most of these hysterectomy specimens. The proportion of cases managed with uterus-preserving techniques increased progressively across the series, rising from none in the first year to the great majority of cases in the later years, while the peripartum hysterectomy rate declined correspondingly. On multivariable analysis, a greater number of previous cesarean sections independently increased, and operation during the later years of the series independently reduced the likelihood of peripartum hysterectomy. Perioperative transfusion of at least one blood product was required in more than half of the patients, whereas intensive care admission and perioperative complications were infrequent; bladder perforation was the most common complication. Compared with women whose uterus was preserved, those undergoing hysterectomy were older and had markedly longer operative times, greater blood product consumption, longer hospital stays, and a substantially higher complication rate. No maternal death occurred throughout the 13-year period. Conclusions: In this 13-year single-surgeon experience, the gradual adoption of uterus-preserving techniques was sustainably associated with low maternal morbidity and zero maternal mortality. The markedly higher complication burden observed in the hysterectomy group compared with the uterus-preserving group demonstrates that a standardized step-up surgical approach offers an applicable and effective management strategy even in resource-limited centers. Full article

Basilar trunk aneurysms (BTAs) are rare intracranial aneurysms. These aneurysms pose substantial clinical risk because they are located close to vital cranial structures and perfusion-sensitive perforating arteries. In addition, outcomes from BTA repair are dependent upon several factors, which include proximity to the brainstem, preservation of perforators, corridor access to the aneurysm, successful clipping of the aneurysm through reconstruction, the need for intraoperative rescue manoeuvres and the ability of the patient to recover from complications. Many previous studies have documented the outcomes associated with BTA repair; however, few studies have examined how the anatomy of the BTA directly relates to surgical decisions made by surgeons. Therefore, we developed an explainable AI framework for documenting surgeon reasoning regarding the open microsurgical treatment of BTAs. The primary objective was to develop and internally evaluate an explainable microsurgical intelligence framework for structuring surgeon reasoning during open microsurgical treatment of BTAs. The secondary objectives were to explore the relationships between the proposed constructs and postoperative pontine infarction, angiographic occlusion, functional outcome, hidden disability, operative difficulty, and composite technical-safety failure. Methods: We retrospectively analysed the cases of 31 adult patients who underwent open microsurgical treatment of a basilar trunk aneurysm at our hospital between October 1999 and March 2025. The cohort included 18 women (58.1%) and 13 men (41.9%), with a median age of 55 years (interquartile range, 44–63 years); 14 patients (45.2%) presented with ruptured aneurysms. A database containing more than 300 variables collected information about each patient’s imaging studies, operative strategies employed during surgery, intraoperative events encountered during surgery, intraoperative angiographic verification, occurrence of new injuries or complications resulting from surgery, and degree of recovery in each patient. Temporally separated scores were generated to quantify perforator-aware hazard, compression burden imposed by proximity to the brainstem, constraints imposed by corridors available for clipping of the BTA, burden imposed by clip reconstruction, degree of surgical precision adjusted based on the need for rescue manoeuvres, degree of dataset/model readiness, and degree of case-level learning density. The framework was evaluated internally using methods that included leave-one-out cross-validation, Firth regression modelling, Bayesian modelling, bootstrap optimism correction, calibration assessments using Brier score, decision-curve analysis, evaluations of explainability, conformal uncertainty estimation, and retrieval of similar cases. Results: Complete occlusion of the aneurysm was successfully achieved in 27 patients (87.1%), whereas residual neck or sac remained in four patients (12.9%). New pontine infarction occurred in six patients (19.4%), including four perforator-related infarctions (12.9%). A favourable last-follow-up modified Rankin Scale (mRS) score of 0–2 was achieved in 25 patients (80.6%); however, hidden disability was noted in 11 of these 25 patients (44.0%). Mortality was 6.5% and was limited to two patients with high-grade rupture. PAH-S-pre predicted pontine infarction (OR, 1.19 for every five-point increase; leave-one-out cross-validated AUC, 0.92). The composite technical-safety failure model had an ROC AUC of 0.91, optimism-corrected AUC of 0.88, calibration slope of 0.96, Brier score of 0.10, and permutation p < 0.001. Explainability indicated that PAH-S-pre, BPCI, and CCR represented the most important features. Conformal prediction resulted in abstention from prediction in four patients (12.9%). Conclusions: Expert microsurgical thought processes involved in repairing BTAs can be systematised and recorded into time-relevant and clinically meaningful measures that preserve anatomical interpretability. Clinical use will require external validation before implementation; however, this framework may provide a clinically interpretable foundation for risk-adapted planning, verification, surveillance, education, and future decision-support research for complex neurovascular surgery. Full article

This study proposes a novel friction-based beam-to-column shear connection designed to behave as a nominally pinned joint while avoiding any perforation of the connected members. The connection relies on frictional resistance to transfer shear forces, enabling full reversibility and preserving the integrity of the structural elements for future reuse. A comprehensive design methodology is first introduced, addressing key parameters such as clamping force, friction coefficient, and slip resistance. Subsequently, an extensive numerical investigation is carried out using refined finite-element models, i.e., considering multiple geometric configurations and loading conditions. The local behaviour of the connection is hence assessed in terms of stiffness, strength, and slip capacity. Results show that—with proper sizing—plastic deformation localises in the beam while the joint remains elastic and slip is limited, confirming the conservativeness of the approach. The joints behave as nominally pinned in terms of resistance while showing moderate stiffness. Derived findings highlight the feasibility of adopting friction-based, non-invasive connections as a viable alternative for circular steel construction, contributing to the ongoing transition toward more sustainable structural systems. Full article

Background/Objectives: Pediatric spontaneous or non-traumatic extrahepatic bile duct perforation (SBDP) is a rare cause of bile ascites and biliary peritonitis. We aimed to characterize presentation, diagnosis, management, outcomes, and summarize practical management considerations. Methods: A systematic review was performed in accordance with PRISMA 2020, we searched PubMed/MEDLINE, EMBASE, and Google Scholar from inception to February 2026, and completed backward citation tracking in June 2026. We included pediatric SBDP cases and excluded traumatic, iatrogenic, isolated gallbladder, and perforated choledochal cyst cases. Case-level data were extracted when available, and exploratory subgroup analyses were performed by age and management approach. Results: A total of 139 studies reported 208 cases; with one institutional case, final cohort of 209 patients. Median age was 3.0 months (IQR, 1.15–15.0; n = 174), and 70.5% of patients were ≤1 year old (124/176). Bilious ascites or bile-stained fluid was confirmed in 95.2%. The cystic duct–CHD/CBD junction was the most frequently reported site (82/180, 45.5%), and biliary anomalies were reported in 39.7% (83/209). A step-up initial management was used in 60.3% and immediate surgery in 38.8%. Reported survival was 97.0% (197/203), although publication bias limits interpretation. Clinical complications and reinterventions were reported in 75/198 (37.9%) and 66/209 (31.6%), respectively. Conclusions: Pediatric SBDP is age-dependent and anatomy-driven; infants more often presented with cholestatic-ascitic features, whereas older children more often had acute-abdominal features. Bilious ascites is an important diagnostic clue. Management should prioritize stabilization and source control, followed by anatomical definition and selective reconstruction. Full article

Background/Objectives: Transcrestal sinus floor elevation (TSFE) includes several surgical approaches that differ in access, instruments, and force delivery. Existing meta-analyses often combine these approaches. This umbrella review examined methodological quality, primary-study overlap, and the limits of clinical interpretation across three decisions: short implants versus sinus floor elevation, transcrestal versus lateral access, and technique choice within transcrestal elevation. Methods: Following the Cochrane Handbook and PRISMA 2020 reporting standards, eligible meta-analyses on TSFE published between 2015 and April 2026 were identified through a three-phase systematic search across PubMed, EMBASE, Cochrane CENTRAL, Web of Science, and Scopus. Methodological quality was assessed using AMSTAR 2 with verbatim per-item evidence; primary-study overlap was quantified using the Corrected Covered Area. Results: Thirty meta-analyses met the inclusion criteria. AMSTAR 2 confidence was MODERATE in nine reviews, LOW in 11, and CRITICALLY LOW in 10; none was rated HIGH. Pool-level Corrected Covered Area was 0.92%, while cluster-level overlap reached 10.90% in the graftless osteotome cluster. Implant survival was generally high across the reviewed comparisons. Data on membrane perforation, benign paroxysmal positional vertigo (BPPV), and patient-reported outcomes were less complete and were reported inconsistently. Within the limited technique-specific evidence, BPPV was reported mainly with osteotome-based procedures, including one case among 24 patients (4.17%) in the osteotome group reported by Cobo-Vázquez et al. Conclusions: The available meta-analytic evidence supports high implant survival across the main treatment options, but it does not support a simple ranking of techniques. Clinical interpretation should follow the decision being made: whether sinus elevation is needed, whether transcrestal or lateral access is appropriate, and which transcrestal technique fits the case. Signals for BPPV and other complications with osteotome-based procedures are suggestive, but event reporting is sparse and certainty is limited. Biomechanical explanations should therefore be treated as clinical context rather than as causal findings of this umbrella review. Full article

Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in preterm infants, yet it remains one of the most challenging neonatal diagnoses to establish with certainty. No single clinical, laboratory, or radiographic finding is pathognomonic, and the modified Bell’s staging system is limited because features such as abdominal distension, bloody stools, pneumatosis intestinalis, and portal venous gas are common in preterm infants or are mimicked by other conditions. A wide range of disorders in preterm and term neonates can therefore resemble NEC, including spontaneous intestinal perforation, sepsis-associated ileus, dysmotility of prematurity, malrotation with or without volvulus, cow’s milk protein allergy, Hirschsprung-associated enterocolitis, cardiogenic colitis, viral enterocolitis, intussusception, neonatal appendicitis, meconium obstruction, incarcerated inguinal hernia, and food protein-induced enterocolitis syndrome. Misclassification of these mimics leads to over- and under-estimation of NEC incidence, contaminates outcome data, and may delay surgical intervention. This review summarizes the epidemiology, risk factors, pathophysiology, and distinguishing clinical, radiographic, and histopathological features of the common mimics of NEC, with particular emphasis on spontaneous intestinal perforation. We also highlight the inherent diagnostic challenges and future directions, including the need for reliable biomarkers and the evolving role of artificial intelligence. Full article

Gastric cancer complicated by free perforation is a rare but life-threatening oncological emergency, accounting for 0.3% ~ 3.9% of all gastric cancer cases. This review summarizes current evidence on the epidemiology, diagnosis, surgical management, and prognostic determinants of perforated gastric cancer, with emphasis on stage-adapted treatment strategies. It should be noted, however, that the available evidence is derived exclusively from retrospective studies, and all recommendations should be interpreted in the context of this inherent limitation. Relevant studies addressing perforation patterns, perioperative outcomes, one-stage versus two-stage gastrectomy, repair-only approaches, and management of metastatic disease were reviewed. Perforation typically arises from tumors located on the anterior wall or greater curvature, where transmural invasion creates direct communication with the peritoneal cavity, resulting in diffuse peritonitis and substantial postoperative mortality. Available pooled evidence suggests that radical resection, when oncologically and physiologically feasible, is associated with better survival than repair-only strategies. Comparative retrospective data suggest that two-stage gastrectomy may be associated with higher R0 resection rates and lower in-hospital mortality compared with emergency one-stage resection, without compromising long-term survival when curative resection is ultimately achieved; however, these findings should be interpreted with caution given the exclusively retrospective evidence base and the inherent patient selection bias in all published comparisons. In patients with stage IV disease or confirmed distant metastases, stomach-preserving source control followed by systemic chemotherapy may be a rational alternative. Prognosis is primarily determined by TNM stage and R0 resection status, similar to non-perforated gastric cancer. Individualized treatment based on tumor stage, resectability, peritoneal contamination, and physiological reserve is essential. Full article

To address the bottlenecks of conventional resonant sound-absorbing structures—namely, fixed frequency bands, single functionality, and inapplicability to light-limited spaces—this paper designs and fabricates a composite-perforated Janus acoustic metamaterial using transparent SLA resin. By integrating acoustic impedance theory, parametric finite-element simulations, and impedance-tube experiments, we systematically investigate the sound absorption mechanisms under forward and reverse incidences, as well as the regulatory effects of aperture diameters and spacing on both sides. Results demonstrate that under forward conventional perforation incidence, the structure achieves near-unity low-frequency narrowband absorption at 322 Hz, with coefficients exceeding 0.8 across 308–337 Hz. Under reverse micro-perforated incidence, the absorption peak shifts to 658 Hz with a substantially broader effective band, maintaining coefficients above 0.8 from 611 to 710 Hz. The close agreement among simulations, theory, and experiments validates the reliability of our numerical models. Parametric studies reveal that the front-side perforations primarily tune the Helmholtz resonance frequency with marginal impact on peak magnitude, whereas the rear-side micro-perforations exhibit high sensitivity to aperture size, enabling independent and flexible tuning of absorption bands via bilateral geometric decoupling. By integrating two distinct absorption mechanisms within a single unit cell, this Janus architecture overcomes the limitations of narrowband low-frequency performance and functional singularity. Coupled with its optical transparency, it offers a novel noise-control solution for light-transmitting equipment and industrial pipelines, while providing a valuable reference for the design of multifunctional asymmetric acoustic metamaterials. Full article

Background/Objectives: Pancreatic metastases are uncommon, and local treatment is reserved for selected patients with limited disease. Surgery remains the standard option when feasible, but may be inappropriate in patients with small, multifocal, anatomically challenging, or medically high-risk lesions. This study evaluated endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) as an organ-preserving local treatment for pancreatic metastases. Methods: Consecutive adult patients undergoing EUS-RFA for histologically confirmed pancreatic metastases at a tertiary endoscopy center between February 2021 and December 2025 were included. All cases were discussed in a multidisciplinary setting. EUS-RFA was performed using a 19G internally cooled RFA needle under real-time EUS guidance. The primary endpoint was initial complete radiological response, defined as complete ablation on first follow-up imaging. Secondary endpoints included technical success, radiological response, repeat EUS-RFA, adverse events, follow-up, and survival. Results: Eleven patients were treated; the mean age was 72.4 ± 6.4 years, and 7/11 (63.6%) were women. Primary tumors included renal cell carcinoma in 7/11 (63.6%), breast cancer in 2/11 (18.2%), melanoma in 1/11 (9.1%), and colorectal cancer in 1/11 (9.1%). Median lesion size was 10.5 mm. Technical success was achieved in 11/11 patients (100%). Initial complete radiological response at first follow-up was observed in 10/11 patients (90.9%); the remaining patient achieved complete response after repeat EUS-RFA. Adverse events occurred in 3/11 patients (27.3%), all mild and conservatively managed. No bleeding, perforation, pancreatic duct stenosis, pancreatic collection, or procedure-related death occurred. Median follow-up was 338 days. Conclusions: EUS-RFA appears feasible and generally well tolerated in carefully selected patients with pancreatic metastases, particularly small, well-visualized lesions when surgery is not feasible or an organ-preserving strategy is preferred. Larger prospective multicenter studies are needed. Although formal subgroup comparisons were not possible in this small cohort, lesion size, anatomical location, and primary tumor biology are likely to influence technical difficulty, local response, and the need for staged or repeat treatment. Full article

While colonoscopies are generally benign procedures, rare complications such as colonic perforation may result in life-threatening consequences. A 15-year-old neutered male British Shorthair cat underwent colonoscopy for investigation of chronic gastrointestinal signs and persistent tenesmus. During endoscopic evaluation of a distal colonic stricture, the cat developed sudden tachycardia, severe hypoxaemia, and a dramatic decline in end-tidal carbon dioxide (EtCO₂), accompanied by diffuse subcutaneous emphysema. Intestinal perforation was suspected, and venous blood gas analysis revealed a markedly enlarged EtCO₂–PvCO₂ gradient, consistent with severe ventilation–perfusion mismatch and contributing to a presumptive diagnosis of pulmonary air embolism. Anaesthetic management focused on ventilatory adjustments, including an increased respiratory rate and initially high, then moderate peak inspiratory pressures, aimed at reducing EtCO₂ and improving oxygenation. However, improvements in oxygen saturation were limited and the cat was euthanised. Contrast-enhanced post-mortem computed tomography confirmed a distal colonic perforation with extensive air dissemination, including pneumoretroperitoneum, pneumomediastinum, pneumothorax, and subcutaneous emphysema. Full article

The injection of CO₂ into mature natural gas reservoirs is widely recognised for its potential to store carbon dioxide while simultaneously enhancing natural gas recovery. However, across all reservoir pressure and temperature ranges, CO₂ and natural gas are miscible, leading to contamination of the produced gas and increasing surface processing costs. Although miscibility has been a limiting factor in deploying CO₂-EGR-based projects, several strategies have been proposed to mitigate it. In this study, we have analysed the inclusion of water in the CO₂ injection process to reduce mixing, improve natural displacement, and improve carbon dioxide storage security through solubility and residual trapping mechanisms. The simulation was conducted in a 3D reservoir using the CMG-GEM simulator. The results show that the inclusion of water injection improves natural gas recovery by up to 8.04% compared with when only CO₂ was injected. The CO₂ breakthrough time increased by up to 931 days, while the hysteresis and solubility trapped CO₂ were improved by 2.68% and 3.06%, respectively. EGR and CO₂ storage security were found to be affected by reservoir heterogeneity, injection rate, and the perforation depths of injector and producer wells. Full article

Self-ear cleaning is widespread in Saudi Arabia, yet public knowledge about proper ear hygiene and associated risks remains variable. This study aimed to assess knowledge, attitudes, and practices regarding self-ear cleaning among adults in the Northern Border Region and to situate the findings within the context of previous studies from other Saudi regions. A cross-sectional online survey was conducted among 534 adults (ages 18–60) residing in the Northern Border Region of Saudi Arabia. Data were collected using a validated questionnaire that assessed sociodemographic characteristics, knowledge, attitudes, practices, and self-reported complications related to self-ear cleaning. Knowledge was evaluated using 8 items, with 1 point per correct response (total score 0–8), and good knowledge was defined as ≥5 correct responses. Most participants (89.1%) reported practicing self-ear cleaning, predominantly using cotton buds (73.7%). Although many recognized potential harms (81.4% believed cotton buds could push wax deeper and 78.1% were aware of the risk of eardrum perforation), 64.1% still believed regular self-ear cleaning was necessary, indicating a knowledge–practice gap. Reported complications included otitis externa (50.6%), pain (44.0%), and bleeding (18.9%). In multivariable logistic regression, higher knowledge was independently associated with postgraduate education, healthcare employment, non-smoking status, and a history of hearing problems. Comparative synthesis with previous surveys from other Saudi regions revealed broadly similar prevalence, preferred tools, and complications, suggesting that self-ear cleaning is a common and often risky behavior nationwide. In conclusion, self-ear cleaning is prevalent in the authors’ region despite substantial awareness of its risks, and a persistent knowledge–practice gap was observed. While the cross-sectional, convenience-sample design limits causal inference and generalizability, these region-specific findings may help inform targeted educational messages and future interventional studies aimed at promoting safer ear hygiene and reducing avoidable ear-related morbidity in similar settings. 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