Regenerative Peripheral Nerve Interface (RPNI) and Targeted Muscle Reinnervation (TMR) have demonstrated superior outcomes compared to classical amputation in prophylactic prevention of pain, primarily by reducing the incidence of symptomatic neuromas, residual limb pain, and phantom limb pain. However, direct comparisons between these two techniques remain limited. Furthermore, their comparative effectiveness across diverse patient demographics (including age, sex, and comorbidities) and surgical variables (amputation level, etiology, and nerve handling) has not been systematically evaluated. Therefore, the objective of this systematic review and meta-analysis is to synthesize the available evidence to determine the comparative safety and efficacy of primary TMR or RPNI. This review will be conducted following the methodological guidance of the Cochrane Handbook for Systematic Reviews of Interventions. A comprehensive electronic search will be performed in the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, PubMed, and MedRxiv, without language restrictions. We will include randomized controlled trials, quasi-randomized trials, and observational studies. Study selection and data extraction will be managed using Covidence. Two reviewers will independently screen titles and abstracts, assess full-text eligibility, evaluate risk of bias, and extract data. As this systematic review relies on the analysis of secondary data from published studies, ethical approval is not required. Findings will be disseminated through publication in a peer-reviewed journal and presented at relevant conferences. CRD42024617299.
Mesenteric cysts are uncommon lesions whose classification is primarily based on their histological origin. We present the case of a mesenteric cyst diagnosed incidentally during staging investigations for colonic adenocarcinoma. Histological examination revealed a multiloculated cystic lesion lined by non-mucinous columnar epithelium without atypia, associated with mature pancreatic acini. Immunohistochemical analysis showed positivity for CK7, CK19, EMA, and trypsin, and negativity for mesothelial, enteric, and lymphatic markers, thereby excluding the subtypes described in current classifications. This exceptional finding, not previously reported, broadens the histopathological spectrum of mesenteric cysts and suggests pancreatic heterotopia as a possible origin of a subtype not recognised to date.
Management of pain in the canine cervical spine is a challenge where regional anesthesia of the cervical dorsal branches via an interfascial plane approach can improve multimodal analgesia. This study aimed to describe the ultrasound-guided multifidus cervicis plane (US-MCP) approach in dogs and evaluate its distribution and nerve staining. An anatomical and sonoanatomical study was followed by an experimental phase using 15 ultrasound-guided injections performed at the C3 level (0.3 mL kg-1 of a methylene blue, iodinated contrast, and saline mixture) in canine cadavers. Contrast spread and nerve staining were evaluated using computed tomography (CT) and subsequent anatomical dissection. Sonoanatomical landmarks were consistently identified in all cases. CT contrast spread reached the C1-C2 levels cranially and C4-C5 caudally in most cases. Contrast distribution reached the dorsal midline in 12/15 injections. Epidural migration occurred in 4/15 cases, mainly at the C2-C3 level. Dissection confirmed accurate interfascial deposition in all specimens. Nerve staining was 100% effective (15/15) for the dorsal branches of C2 and C3 and 60% in the case of C4 (9/15). However, success rates decreased caudally and staining was observed in 13.3% (2/15) of C5 nerves, and was absent (0/15) at C6. The described US-guided MCP approach is a feasible and highly specific technique for the desensitization of the cranial dorsal cervical region. Consistent staining of the C2 and C3 dorsal branches, and potentially C4, supports its potential as a promising tool for integration into multimodal analgesia protocols. Clinical studies are required to evaluate its safety and analgesic efficacy.
Hemorrhoidal disease is a common condition and may affect quality of life. Although it tends to respond to conservative treatment, some cases require surgery. The present study examined clinical and demographic factors associated with symptom duration in surgically treated patients, with no causal inference or predictive intent. A retrospective, cross-sectional study was conducted at the Hospital Universitario de Puebla on 56 patients who underwent hemorrhoidectomy (2019-2023). The factors of sex, age, smoking, constipation, BMI, and time to surgery were analyzed, employing descriptive statistics, linear regression, and K-Fold cross-validation. There was a significant association between sex and years of disease (p = 0.0427), with men having a mean 4.89 more years of disease than women (β = -4.89, 95% CI -9.61 to -0.17). There was a positive, non-significant association between age and years of disease (p = 0.0907). A significant inverse relation was identified between age at disease onset and years of disease (p < 0.001; β = -0.31, 95% CI -0.46 to -0.15), as well as a significant interaction between sex and age at onset (p < 0.001). Sex and age at disease onset were key factors associated with symptom duration in patients who underwent hemorrhoidectomy. Factors traditionally considered relevant, such as constipation and BMI, showed no significant association, highlighting the importance of considering complex interactions between clinical and demographic variables.
Cryopreserved homograft implantation in the pulmonary position is a common surgical approach for pulmonary valve replacement, although it carries a risk of early failure requiring reintervention. This study aimed to identify clinical, anatomical, surgical, graft, and postoperative factors associated with early failure, defined as reintervention (percutaneous or surgical) within 3 years. In this retrospective cohort study (2017-2024), we included 136 patients (median weight 45.0 [IQR: 25.25-60.00] kg; age 14.11 [8.31-18.09] years) who received a homograft in the pulmonary position. Time-to-event analyses were performed to identify factors associated with early failure, including multivariable Cox proportional hazards regression. The most frequent underlying conditions were tetralogy of Fallot in 44.0% and common arterial trunk in 16.9%. The median homograft size was 22 [19-24] mm, and 15 (11%) were aortic homografts. The median follow-up was 4.15 [1.61-5.00] years. Eighteen patients (13.2%) required reintervention at a median of 1.29 [0.72-1.93] years. Reasons for reintervention included postimplantation due to stenosis (n=8), stenosis and infective endocarditis (n=1), and stenosis and regurgitation (n=9). Interventions included percutaneous pulmonary valve implantation (n=5), homograft dilatation (n=3), stenting (n=3), and surgical replacement or heterograft implantation (n=7). Univariate analysis identified significant associations with fever, fever without documented infection, pericardial/mediastinal collection necessitating reintervention, and elevated RVOT velocity on echo (> 2.1 m/s) at discharge. On multivariable Cox regression analysis, fever without documented infection remained independently associated with earlier reintervention (HR, 4.42; 95%CI, 1.34-14.52; P=.014). Early reintervention is associated with postoperative inflammatory markers and immediate suboptimal homograft function. These findings support and refine previous observations on early homograft dysfunction and may help identify patients who warrant closer postoperative surveillance.
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Weight Recurrence (WR) after bariatric surgery is a common long-term complication, undermining the effectiveness of the procedure and the resolution of comorbidities associated with obesity. The prevalence of WR varies widely, depending on the definition used and follow-up duration. To analyze the current definitions, contributing factors, and management strategies for WR, emphasizing the importance of early detection and comprehensive follow-up. A narrative review of published literature on WR after bariatric surgery was conducted, focusing on epidemiology, pathophysiology, risk factors, and therapeutic approaches, including behavioral, pharmacological, endoscopic, and surgical options. WR can occur in over 70% of patients during long-term follow-up, depending on the criteria used. Key contributors include behavioral factors, lack of adherence to nutritional recommendations, hormonal adaptations, anatomical changes, and insufficient postoperative follow-up. Early detection within the first two years after surgery improves the likelihood of successful interventions. Treatment options range from lifestyle modification and psychological support to advanced endoscopic and surgical techniques, with outcomes varying based on patient-specific factors. WR is a multifactorial issue requiring individualized, multidisciplinary management. Strengthening follow-up protocols and utilizing predictive tools can optimize long-term outcomes for bariatric surgery patients.
To evaluate the association between the operational implementation of a Fast-Track referral pathway for head and neck cancer and changes in care intervals, tumor profile at diagnosis, and overall survival in a real-world tertiary care cohort. Retrospective observational historical cohort study including patients with a primary malignant ENT tumor treated between January 2010 and August 2023. Patients were classified according to diagnostic period as Pre-Fast-Track or Post-Fast-Track, using January 2018 as the operational implementation date. Care intervals, tumor characteristics, route of entry into the pathway, and overall survival were analyzed. A total of 1106 patients were included: 614 in the Pre-Fast-Track period and 492 in the Post-Fast-Track period. After implementation, median referral time decreased from 9 to 5 days, first ENT consultation-to-treatment time from 27 to 21 days, and referral-to-treatment time from 50 to 43 days, all p < 0.001. The Post-Fast-Track period also showed a lower proportion of stage III-IV disease. Among post-implementation patients with available data, 22.8% entered through the Fast-Track pathway. Kaplan-Meier curves showed no significant survival differences between periods (log-rank, p = 0.95). In the multivariable Cox model, the Post-Fast-Track period was not independently associated with overall survival (adjusted HR 0.94; 95%CI 0.77-1.15; p = 0.537). The operational implementation of a Fast-Track pathway was associated with shorter care intervals and a relatively less advanced-stage distribution at diagnosis, but not with improved overall survival. Its clinical impact may depend on pathway penetration and the efficiency of the entire diagnostic-therapeutic process.
Osteosarcomas (OS), the most common primary malignant bone tumours, are classified as low-grade (characterised by MDM2 amplification) or high-grade (with complex karyotypes). Accurate diagnosis is essential for treatment and prognosis. This study evaluates pre-analytical variables associated with the success or failure of epigenetic analyses in osteosarcoma samples and proposes a standardised preparation protocol. Retrospective cohort study of adult patients with OS diagnosed at our sarcoma reference centre (CSUR) over the past 20 years. Pre-analytical variables: year of diagnosis, histological subtype, tissue type, site of origin, sample type (core needle biopsy or surgical specimen with or without chemotherapy), decalcification method (none, EDTA, or nitric acid), and FISH availability. Five 5-μm sections were obtained from each paraffin block. DNA methylation profiling was performed using the Infinium MethylationEPIC v2.0 platform (Illumina). Univariate and multivariate analyses were performed to identify failure predictors. A total of 103 samples from 79 patients were analysed: 58 conventional OS, 14 extraskeletal, 24 parosteal, and 7 dedifferentiated OS. Of the 95 formalin-fixed, paraffin-embedded (FFPE) samples, 43 (45.2%) were suitable for epigenetic analysis, whereas all frozen samples were adequate (100%). Decalcification affected success rates, although not significantly: nitric acid was associated with the highest failure rate (68.97%), followed by EDTA (57.14%) and non-decalcified samples (46.15%). FFPE samples are suitable for epigenetic studies, although performance depends on pre-analytical factors. Frozen tissue remains the gold standard. Nitric acid should be avoided. A protocol is proposed that prioritises frozen tissue, documents decalcification methods, excludes strong acids, incorporates quality control measures, and favours samples less than five years old.
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Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancerrelated mortality worldwide. Liver transplantation (LT) is a curative option for selected patients; however, recurrence remains the major determinant of post-transplant survival. Most recurrences occur within the first five years, while ultra-late events are exceptionally rare. We describe a 66-year-old male with cirrhosis due to hereditary hemochromatosis and a solitary 4-cm HCC within the Milan criteria, who underwent cadaveric orthotopic LT after bridging therapy with a single session of transarterial chemoembolization. Explant pathology confirmed HCC without microvascular invasion. The postoperative course was uneventful, and the patient remained disease-free for thirteen years. He then presented with rapidly progressive bilateral paraparesis. Magnetic resonance imaging revealed a 30-mm intradural extramedullary lesion at T6 causing severe spinal cord compression. Neurosurgical resection was performed, and histopathology with immunohistochemistry (HepPar-1 positive) confirmed metastatic HCC. This is, to our knowledge, the first reported case of spinal cord metastasis from HCC occurring thirteen years after LT. Conventional tumor markers, including alpha-fetoprotein, remained within normal limits, underscoring the limitations of current surveillance protocols. The exceptionally prolonged disease-free interval and atypical metastatic site challenge the prevailing paradigm that follow-up can be safely limited to the early post-transplant years. Ultra-late recurrence of HCC after LT, though rare, is clinically relevant and may manifest in unusual sites. This case highlights the need for risk-stratified, individualized, and potentially extended surveillance strategies to optimize long-term outcomes in LT recipients. El carcinoma hepatocelular (CHC) es el cáncer primario más frecuente del hígado. El trasplante hepático (TH) constituye un tratamiento curativo en pacientes seleccionados; sin embargo, la recurrencia sigue siendo el principal determinante de la supervivencia postrasplante. Se describe el caso de un hombre de 66 años con cirrosis secundaria a hemocromatosis hereditaria y un CHC solitario de 4 cm dentro de los criterios de Milán, sometido a trasplante hepático ortotópico cadavérico tras terapia de puente con una sesión de quimioembolización transarterial. La anatomía patológica del explante confirmó CHC sin invasión microvascular. La evolución postoperatoria fue favorable y el paciente permaneció libre de enfermedad durante trece años. Posteriormente, consultó por paraparesia bilateral rápidamente progresiva. La resonancia magnética evidenció una lesión intradural extramedular de 30 mm a nivel de T6 con compresión medular grave. Se realizó resección neuroquirúrgica, y el estudio histopatológico con inmunohistoquímica (HepPar-1 positivo) confirmó metástasis de CHC. Este constituye, a nuestro conocimiento, el primer caso reportado de metástasis medular de CHC trece años después de un TH. Los marcadores tumorales convencionales, incluido el alfa-fetoproteína, se mantuvieron en rango normal, lo que evidencia las limitaciones de los protocolos de vigilancia actuales. El intervalo libre de enfermedad extraordinariamente prolongado y la localización atípica cuestionan la noción de que el seguimiento pueda restringirse a los primeros años. La recurrencia ultra-tardía de CHC tras TH, aunque infrecuente, es clínicamente relevante y puede presentarse en sitios inusuales. Este caso resalta la necesidad de estrategias de seguimiento individualizadas, estratificadas por riesgo y posiblemente extendidas en el tiempo.
Neuroendocrine tumors of the gallbladder are included among neuroendocrine tumors of uncommon location. Because they are non-functioning tumors, they usually do not produce symptoms and are often discovered at advanced stages. Their main differential diagnosis, due to gallbladder wall thickening, is acute cholecystitis. If imaging findings do not improve despite appropriate treatment, this entity should be considered in the differential diagnosis to achieve early treatment. Histopathological examination is the key to diagnosis. Small-cell neuroendocrine tumors with a high Ki-67 index have a poor prognosis and high short-term morbidity and mortality.
To analyze the prevalence of depressive symptomatology in the population between 15 and 104 years of age in Spain to study whether there are factors that may be associated with and related to its presence. To this end, data from the 2020 European Health Interview Survey (EHIS) were collected. Analytical cross-sectional study, based on secondary information obtained from this survey. General population residing in Spain, in a community context. A total of 22,072 subjects residing in family homes in the national territory in 2019, of which 47.1% were men and 52.9% women. Prevalence of depressive symptomatology (PHQ-8). Sociodemographic and behavioural factors analysed: physical activity, tobacco and alcohol consumption, frequency of use of health services, chronic diseases and functional limitations. The overall prevalence of positive depression screening in the sample was 8.7%. The multivariate analysis identified the presence of chronic diseases, physical limitations, physical inactivity, and former smoking status as the main associated factors. Likewise, subjects with depressive symptomatology had a higher frequency of use of health services. There are several modifiable behavioural factors associated with depressive symptomatology. The promotion of physical activity and the comprehensive approach to chronicity and functional capacity could be key strategies to improve the state of mental health in the population. Analizar la prevalencia de sintomatología depresiva en la población de España entre los15 y 104 años, para estudiar la existencia de factores que puedan estar asociados y relacionados con su presencia. Para ello, se recogieron datos de la Encuesta Europea de Salud (European Health Interview Survey [EHIS]) de 2020. Estudio transversal analítico, basado en la información secundaria obtenida de dicha encuesta. Población general residente en España, en un contexto comunitario. Un total de 22.072 sujetos residentes en viviendas familiares en territorio nacional en el año 2019, de los cuales el 47,1% eran hombres y el 52,9% mujeres. Prevalencia de sintomatología depresiva (PHQ-8). Factores sociodemográficos y de comportamiento analizados: actividad física, consumo de tabaco y alcohol, frecuencia de uso de servicios sanitarios, enfermedades crónicas y limitaciones funcionales. La prevalencia global de cribado positivo de depresión en la muestra fue del 8,7%. El análisis multivariante identificó como principales factores asociados la presencia de enfermedades crónicas, las limitaciones físicas, la inactividad física y el estatus de exfumador. Asimismo, los sujetos con sintomatología depresiva presentaron una mayor frecuencia de utilización de servicios sanitarios. Existen diversos factores de comportamiento modificables asociados a la sintomatología depresiva. El fomento de la actividad física y el abordaje integral de la cronicidad y la capacidad funcional podrían ser estrategias clave para mejorar el estado de salud mental en la población.
La anemia y la deficiencia de hierro (DH) son condiciones frecuentes en pacientes con enfermedades cardiovasculares y se asocian a mayor morbimortalidad en cirugía cardíaca. Sin embargo, no existen datos sobre cómo es abordada esta problemática en Iberoamérica. Debido a ello, desde la Sociedad Interamericana de Cardiología nos propusimos explorar conocimientos, actitudes y conductas de médicos latinoamericanos involucrados en el perioperatorio de cirugía cardíaca. Se realizó un estudio transversal mediante una encuesta electrónica anónima distribuida entre enero y agosto de 2025, utilizando un muestreo tipo «bola de nieve». Se incluyeron médicos con actividad asistencial que involucre la atención de pacientes previa a cirugía cardíaca. Respondieron la encuesta 881 médicos de 23 países. Si bien el 83,7% manifestó que tamizaba la presencia de anemia de forma rutinaria, solo el 43,7% expresó evaluar la DH. Un 18,2% manifestó contar con protocolos institucionales sobre este tópico. El manejo terapéutico mostró notables diferencias: solo el 11,8% indicó administrar hierro endovenoso (EV) ante el diagnóstico de anemia o DH. El 46,9% de los participantes expresó tener acceso rutinario a hierro EV; sin embargo, solo el 26,6% de ellos refirió haber indicado esta intervención a pacientes en el preoperatorio de cirugía cardíaca en los 6 meses previos a responder la encuesta. Además, el 54,8% de los encuestados no había recibido formación específica y se sentía solo moderadamente preparado para manejar estas condiciones. Nuestros datos sugieren que existen brechas significativas entre la evidencia disponible y la práctica clínica en el manejo preoperatorio de anemia y DH, destacando la necesidad de protocolos institucionales y mayor educación médica especializada. Anaemia and iron deficiency (ID) are common in patients with cardiovascular disease and are associated with increased morbidity and mortality in cardiac surgery. However, no data are available on how this issue is addressed in Ibero-America. We therefore sought, under the auspices of the Inter-American Society of Cardiology, to explore the knowledge, attitudes, and practices of Latin American physicians involved in the perioperative care of patients undergoing cardiac surgery. We conducted a cross-sectional study using an anonymous electronic survey distributed between January and August, 2025, through snowball sampling. Physicians engaged in clinical practice involving the care of patients prior to cardiac surgery were eligible for inclusion. A total of 881 physicians from 23 countries responded. Although 83.7% reported routinely screening for anaemia, only 43.7% indicated that they assessed iron deficiency. Institutional protocols addressing this topic were reported by 18.2% of respondents. Marked heterogeneity was observed in therapeutic management: only 11.8% reported administering intravenous iron when anaemia or ID was diagnosed. While 46.9% of participants stated that they had routine access to intravenous iron, only 26.6% of these reported prescribing this intervention for patients in the preoperative cardiac surgery setting within the 6 months preceding the survey. Furthermore, 54.8% of respondents had not received specific training and felt only moderately prepared to manage these conditions. Our findings suggest substantial gaps between the available evidence and clinical practice in the preoperative management of anaemia and iron deficiency, underscoring the need for institutional protocols and enhanced specialised medical education.
Myotonia permanens (MP), a life-threatening condition, is prevalent in Chile, and is frequently associated with the SCN4A p.Gly1306Glu variant (exon 22), likely due to a founder effect in this population. Low clinical suspicion and the high cost of genetic testing contribute to delayed diagnosis and impaired quality of life. This study aimed to develop a clinical prediction rule (CPR) for early MP-p.Gly1306Glu detection specially in Chile, and confirm diagnosis through genetic testing. This cross-sectional study was conducted at five Chilean hospitals and included healthy controls and patients with non-dystrophic myotonia (NDM). Participants were classified as controls, MP-p.Gly1306Glu, or non-permanens myotonia (NPM). Diagnosis was confirmed by SCN4A exon 22 sequencing or a gene panel (SCN4A, CLCN1). Fisher's exact test and logistic regression were used to identify clinical predictors of MP. A total of 19 controls and 17 patients with NDM (MP-p.Gly1306Glu/NPM = 8/9; mean age: 36 years) were included. Four predictors of MP-p.Gly1306Glu were identified: eyelid myotonia before age 2 (predictive value [PV] = 100%), myotonic discharges ≥28/30 s (PV = 95%), laryngospasm before age 2 (PV = 94%), and generalized myotonia before age 5 (PV = 88%). If all four predictors are present, MP-p.Gly1306Glu is highly probable and SCN4A exon 22 sequencing is recommended. If one to three predictors are present, targeted sequencing or a gene panel is advised, depending on clinical context. This CPR may facilitate early diagnosis of MP-p.Gly1306Glu and improve clinical outcomes, especially in Chile, and possibly other resource-limited settings, by guiding timely genetic confirmation and management. These predictors may support diagnostic criteria for MP/NPM, and guide future clinical trial design.
Understanding temporal patterns of Leishmania infection in sand fly populations is essential for assessing transmission risk and improving surveillance and control in endemic regions. This study investigated infection dynamics in natural populations of Phlebotomus perniciosus and Phlebotomus ariasi, two established vectors of Leishmania infantum in the western Mediterranean and evaluated the utility of pooled sampling for vector surveillance. Sand flies were tested for Leishmania infection using a TaqMan real-time kinetoplast PCR either individually or in pools. Infection rates from pooled samples were estimated using maximum likelihood methods and analyzed alongside individual infection data using mixed-effects regression models to assess the influence of seasonality and female reproductive status on infection probability. Both individual and pooled analyses showed similar seasonal trends. Infection probability peaked in late summer, likely reflecting high parasite prevalence in reservoir hosts, and was highest in gravid females, suggesting cumulative parasite acquisition as sand flies age and complete successive gonotrophic cycles. Individual testing, although more resource-intensive, provided additional resolution by revealing species-specific patterns, with P. ariasi exhibiting higher infection rates than P. perniciosus, offering a deeper understanding of parasite circulation and species-specific infection patterns. We conclude that pooled sampling combined with appropriate statistical modelling can reliably capture seasonal infection patterns. Integrating reproductive status indicators with molecular surveillance represents a novel approach to refine transmission risk assessments and support more targeted and effective vector monitoring strategies in Leishmaniosis-endemic regions.
To evaluate the hemodynamic effects of intravenous maropitant in dogs under general anaesthesia premedicated with dexmedetomidine or acepromazine. Prospective randomized clinical study. Twenty-six healthy Spanish Greyhounds. Dogs were randomly premedicated with dexmedetomidine (DEX; 4 μg/kg) or acepromazine (ACP; 20 μg/kg), both combined with methadone (0.3 mg/kg) administered intramuscularly. Anesthesia was induced with propofol and midazolam and maintained with sevoflurane. Once a stable anesthetic plane was achieved, maropitant (1 mg/kg IV) or saline was administered, resulting in four groups: DEX-M, ACP-M, DEX-C, and ACP-C. Invasive arterial blood pressure (systolic, diastolic, mean) and heart rate were recorded at baseline and for 20 min after administration. Changes over time were analyzed and compared with baseline values using the Friedman test (p < 0.05). In the DEX-M group, diastolic arterial pressure decreased significantly at 2 min, accompanied by a transient increase in heart rate. In the ACP-M group, systolic, diastolic and mean arterial pressures decreased significantly at 2 min, also with an increase in heart rate. Clinically relevant hypotension (mean arterial pressure 51 ± 7 mmHg) occurred only in ACP-M dogs. All changes were transient. Intravenous maropitant administration appears to be hemodynamically well tolerated in healthy dogs under general anesthesia premedicated with dexmedetomidine. In contrast, when acepromazine is used for premedication, maropitant administration results in more pronounced hemodynamic effects, including clinically relevant hypotension. These findings suggest that alternative routes of administration should be considered in the perioperative setting.
To review and assess published imaging evidence for optic nerve stretch (ONS) in patients with dysthyroid optic neuropathy (DON), evaluating its prevalence, measurement methods, and potential association with disease pathophysiology. PubMed, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov were searched using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, for computerized tomographic or magnetic resonance imaging studies of ONS in thyroid eye disease. Data were extracted on imaging modality, ONS definition, and association with DON. Pooled proportions were calculated using random-effects models with logit transformation, and heterogeneity assessed with I2. Sixteen studies, comprising 1,277 orbits (508 DON and 769 non-DON), met the inclusion criteria. Five noncomparative studies, mostly earlier papers, report ONS in 43% (0%-100%) of 75 DON orbits. Eleven studies (1,202 orbits) compared orbits with and without DON: 6 studies examined optic nerve contour (317 DON and 435 non-DON) and reported ONS in 66% of DON and 37% of non-DON orbits. Only 2 studies reported ONS as being significantly associated with DON (74% and 64% of orbits), and both reported marked apical crowding (70% and 67%). The pooled ONS proportion was 56% (95% confidence interval: 37%-74%) in orbits with DON and 31% (95% confidence interval: 12%-59%) in non-DON orbits, with high heterogeneity (I2 > 80%). While optic-nerve stretch is frequently observed in DON, current evidence does not establish it as an independent cause. ONS may reflect geometric changes due to orbital soft-tissue expansion, and the principal mechanism for DON probably remains apical compression and microvascular ischemia of the optic nerve.
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