Alzheimer's disease (AD) is driven by a self-amplifying interplay between oxidative stress and neuroinflammation, in which mitochondrial DNA (mtDNA) leakage-induced activation of the cGAS-STING pathway plays a central role. Strategies that solely eliminate reactive oxygen species (ROS) are insufficient to suppress downstream inflammatory cascades. Here, we report a pair of chiral dual-functional single-atom nanoagents that can simultaneously scavenge ROS and sequester leaked mtDNA. A diazonium-enabled post-synthetic modification strategy is employed to graft benzoic acid linkers onto a single-atom catalyst, enabling covalent conjugation of nona-arginine peptides with opposite chirality (L-/D-R9). The resulting constructs are further encapsulated by KLVFFAED peptides and tannic acid to yield L-/D-TKRM, conferring blood-brain barrier permeability and mitochondrial targeting. Both L- and D-TKRM effectively scavenge ROS and preserve mitochondrial function in Aβ-stimulated microglia, while D-TKRM exhibits enantioselectively prolonged mtDNA capture, more efficient suppression of cGAS-STING signaling, enhanced M2 microglial polarization, and superior neuroprotection. In vivo studies have demonstrated that these two nanoagents rescue cognitive function in 3 × Tg-AD mice, with D-TKRM showing better efficacy accompanied by reduced amyloid pathology, microglial activation, and neuronal loss. This work highlights diazonium chemistry as a new, versatile single-atom functionalization strategy and underscores that chirality is important for developing effective therapeutic agents for AD treatment.
Metabolically deranged tumor microenvironment (TME) with compromised innate immune signaling induces severe immunosuppression and markedly blunts the efficacy of cancer immunotherapy. Activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway can boost antitumor immunotherapy, and a manganese complex, called TPE-Mn, was developed in this work. Nevertheless, the excess lactate accumulation and poor tumor-targeted delivery jointly restrict the clinical translation of Mn2+-based immune stimulation. Herein, we designed glutathione (GSH)-sensitive nanoparticles (NPMn/Syro) co-loaded with TPE-Mn and the monocarboxylate transporter 1/4 (MCT1/4) inhibitor syrosingopine (Syro) at an optimized ratio to simultaneously remodel tumor metabolism and activate innate immunity. Upon effective intratumoral accumulation, NPMn/Syro concurrently release two payloads: Syro inhibit lactate efflux and elevates intracellular lactate, while TPE-Mn disrupts mitochondrial dynamics. Collectively, these synergistic effects shift the mitochondrial fusion-fission balance toward excessive fission, leading to mitochondrial fragmentation and cytosolic mitochondrial DNA (mtDNA) leakage. The leaked mtDNA activates cGAS, while Mn2+ further amplifies the activation of the STING pathway to boost innate immune responses. Moreover, metabolic disruption and mitochondrial injury cooperatively trigger immunogenic cell death (ICD) and potentiate systemic antitumor immunity. Furthermore, combined with anti-PD-1 antibody (α-PD-1), NPMn/Syro exerts synergistic antitumor efficacy, providing a promising therapeutic strategy for clinical management of tumor. This work presents a metabolic-metal synergistic strategy to augment the cGAS-STING pathway activation and significantly reverse metabolism-mediated immunosuppressive TME.
Despite decades of research, there is still a lack of calibrated data on acoustic leak signatures typical of common types of water supply pipes. This study addresses this gap by providing leak signatures recorded with calibrated, high-sensitivity accelerometers in a controlled laboratory environment. The study also investigates how different leak configurations at nominal static pressures of 2.8-4.2 bars influence the power spectrum of the pipe-wall acceleration. The results show a great variability, i.e., 5 orders of magnitude, in the power spectrum. The amplitude and shape of this spectrum depend on whether the leak is through a valve-controlled nozzle, hole directly drilled in the pipe wall, or a longitudinal or traverse slit. The coherence in the leak signals as a function of the distance between the accelerometers is determined and used to estimate the leak signal attenuation. Crucially, the results reveal that longitudinal slits, which represent the most common failure mode in plastic pipes, produce the weakest acoustic signals, making them difficult to detect and locate using standard acoustic equipment. It is expected that the calibrated data collected from this study will support high-fidelity computer simulations and development of better signal processing algorithms to predict and to detect hidden leaks in water distribution networks in the presence of background noise and high acoustic attenuation. The recorded data are made available to a wider community through a dedicated data depository.
Congenital duodenal obstruction (CDO) is a common neonatal intestinal obstruction associated with prematurity, low birth weight, and additional anomalies. Postoperative enteral feeding delays, caused by proximal duodenal dysmotility and anastomotic edema, prolong the need for total parenteral nutrition (TPN) and the use of a central venous catheter (CVC). The transanastomotic tube (TAT) bypasses the dysfunctional segment for direct jejunal feeding. This study evaluated effects of TAT on outcomes, TPN/CVC requirements, complications, and hospitalization duration in neonates undergoing CDO repair. Forty-eight CDO patients (January 2012-January 2021) were retrospectively reviewed. After excluding 7 pre-feeding deaths and 5 early TAT removals, 36 patients were analyzed: TAT(+) (n = 21) and TAT(-) (n = 15). Demographic characteristics, obstruction type, surgical technique, anomalies, feeding milestones, TPN duration, CVC use, complications, and hospitalization durations were compared. Groups were comparable for gestational age, birthweight, obstruction type, and associated anomalies. Time to initiation of enteral feeding was significantly shorter in TAT(+) group (3.01 ± 2.05 vs. 11.1 ± 5.4 days, p = 0.001), as was time to full enteral feeding (7.6 ± 3.8 vs. 19.2 ± 15.6 days, p = 0.002). TPN duration was shorter (6.5 ± 4.1 vs. 19.8 ± 12.4 days, p = 0.019) and CVC insertion rate lower (23.8% vs. 73.3%; p = 0.004) in TAT(+) group. Complication rates were 19% vs. 73.3% (p = 0.002); anastomotic leaks/strictures occurred exclusively in TAT(-) group. Hospitalization was shorter in TAT(+) patients (12.6 ± 4.9 vs. 25.2 ± 21.1 days, p = 0.03). TAT placement following CDO repair facilitates earlier enteral feeding, reduces TPN and CVC requirements, decreases complications, and shortens hospitalization. TAT is an effective postoperative nutritional strategy, particularly in high-risk neonates.
International guidelines recommend first-generation cephalosporins for preoperative antibiotic prophylaxis in patients undergoing resection for perihilar cholangiocarcinoma (pCCA). Knowledge on the resistance profile of biliary bacteria and its impact on liver-specific complications is limited. This study aimed to evaluate the biliary microbial spectrum, particularly focusing on the impact of resistant bacteria on liver-specific complications following pCCA resection. This is a retrospective, single-center, observational study. All patients with resected pCCA at the University Hospital Frankfurt from July 2005 to December 2022 were included. The microbial spectrum was analyzed using intraoperative bile swabs. From 118 patients, 104 had an intraoperative bile swab taken. Microorganisms (bacteria, fungi) were detected in 89.4% of cases. 24% of the samples contained clinically relevant antibiotic-resistant bacteria, which were related with more severe postoperative bile leaks requiring relaparotomy (24% versus 8.8%, p = 0.055) and posthepatectomy liver failure (48% versus 25.3%, p = 0.031). 76.9% of the microbial isolates were resistant to in-house standard antibiotic prophylaxis with cefuroxime. Biliary colonization with clinically relevant antibiotic-resistant bacteria is associated with liver-specific complications.
To compare postoperative outcomes of absorbable versus non-absorbable sutures and sutureless versus sutured incisions in pediatric cataract surgery (0-18 years). Pediatric cataract surgery requires precise wound closure to ensure postoperative stability. Identifying the most effective closure method is essential to minimize complications and the need for reintervention under general anesthesia. The review protocol was registered in the International Prospective Register of Systematic Reviews (CRD420251174549). We searched PubMed, Embase, Cochrane, and Web of Science (inception to October 2025). The primary outcome was the overall rate of postoperative complications. Meta analysis utilized Mantel-Haenszel fixed-effects model (Review Manager 5.4); certainty of evidence was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE). Eight studies (four per comparison) evaluated suture material (321 absorbable; 430 non-absorbable) and closure technique (1,127 sutureless; 187 sutured closure). Absorbable sutures were associated with significantly lower odds of overall complications than non-absorbable sutures (OR 2.35; 95% CI 1.38 to 3.99; P=0.002; very low-certainty evidence). Specifically, 10-0 polyglactin 910 outperformed 10-0 nylon (OR 2.18; P=0.005; very low-certainty evidence), though loosening was more frequent (P=0.05). Sutureless closure was associated with significantly lower complication odds than sutured techniques (OR 0.34; 95% CI 0.23 to 0.49; P<0.00001; very low-certainty evidence). No significant differences were found for wound leakage (P=0.60) or endophthalmitis (P=0.10). Absorbable sutures and sutureless techniques are associated with a lower risk of overall complications. However, results are limited by very low-certainty and potential selection bias, as sutures are often reserved for leaking wounds. While non-absorbable sutures provide early wound security, they appear to increase long term ocular surface morbidity. Large scale RCTs are required to establish definitive surgical guidelines.
Natural and human-induced disasters can cause significant loss of life and property, particularly at the building level, highlighting the need for effective early detection, real-time monitoring, and rapid post-disaster response. Current disaster management approaches largely rely on citizen reports and manual observations, which may lead to delays and inefficient resource allocation, especially in large-scale events. This study proposes a secure, modular, multi-layer disaster monitoring and decision-support architecture that integrates sensor-based building-edge monitoring units deployed at both the building and apartment levels with a central emergency monitoring system. The architecture comprises three main layers: edge sensing, secure cellular communication, and central decision-making. Building-edge monitoring units collect data related to structural motion and inclination indicators, fire, flooding, and gas leaks, perform preliminary processing, and transmit aggregated data securely to the central system. Communication security is ensured through a certificate-based authentication mechanism supported by a dedicated certificate authority, reducing the risk of unauthorized access and fraudulent data injection. The central system performs automated event detection and separately evaluates physical building condition and communication status, enabling prioritized response planning. To evaluate feasibility, a two-building prototype was implemented and tested through scenario-based experiments involving two independently operating building-edge monitoring units connected to the same central monitoring system. The prototype demonstrated concurrent secure data acquisition and central aggregation from two buildings; however, district- and regional-scale performance requires further validation through larger-scale controlled load tests and field deployments. Under laboratory conditions, the prototype demonstrated sensor-data acquisition, authenticated transmission, and centralized event classification. End-to-end latency and building-edge monitoring unit power consumption were also measured; however, the prototype was not validated under environmental conditions representative of real disasters. Overall, the findings suggest that sensor-based, secure, and centralized monitoring systems may complement traditional disaster management approaches.
Surgical management of esophageal atresia/tracheoesophageal fistula (EA/TEF) in extremely low birth weight (ELBW) neonates remains challenging and controversial. This study systematically reviews surgical strategies and outcomes in this population. Following PRISMA guidelines, Cochrane, Embase, MEDLINE, Scopus, and Web of Science (2004-2024) were searched in February 2025 for studies on surgical management of ELBW neonates with EA/TEF (PROSPERO CRD42025636228). Fatal chromosomal abnormalities were excluded. Demographics, comorbidities, surgical techniques, and complications were analyzed descriptively. Risk of bias was assessed. Eleven publications (five case reports and six case series) comprising 30 patients (Gross type B/C = 1/29) met the eligibility criteria. Mean gestational age was 28.1 (23-34) weeks, and mean birth weight was 760.4 (422-995) g. Twelve primary repairs (PR) and 18 delayed primary repairs (DPR) were performed, including staged repair (n=11), lower esophageal banding (n=4), and other techniques (n=3). Postoperatively, four anastomotic leaks were managed conservatively, six strictures and one recurrent TEF required endoscopic intervention, three fundoplications and two aortopexies were reported (follow-up: 1-198 months, n=19). Overall mortality was 30% (PR: 8.3%; DPR: 44.4%). Mortality was 60% among neonates with major congenital heart defects (CHD) and 40% among those with VACTERL association. EA/TEF-related complications contributed to 33.3% of deaths. Mortality in this cohort remains high, particularly with major CHD, and is largely unrelated to EA/TEF-specific complications. In selected cases, PR appears feasible as an alternative to DPR, although conclusions are limited by the small sample size and heterogeneous studies.
Compact malaria detectors for microcontrollers are almost always benchmarked on the NIH Malaria dataset with a per-cell random split. This leaks slide identity because the cells come from only about 200 slides and a random split mixes same-slide cells across training and testing. The leakage also distorts architectural conclusions: under a leakage-free slide-disjoint protocol, per-module ablation gains collapse to seed noise and an apparent cross-site robustness variant loses most of its advantage. Headline accuracy falls from 97.1% to 95.6%, a gap that sits within the cross-seed noise, and all eight tested architectures move the same way. The evidence is this unanimous direction, not the size of any single gap. This benchmarking finding is our main contribution. Two results survive. First, MalariaNet, our 21 K-parameter detector, reaches about 95.6% accuracy at 23.5 KB of INT8 weights, with a numerically faithful on-chip forward on an STM32H743 at a 1.2 FPS triage rate. Second, it is among the most interference-robust of the eight networks and the most robust microcontroller-deployable model. Scope is limited to single P. falciparum thin-smear cells. Slide-disjoint evaluation should become standard, and we provide MalariaNet as the first leakage-free, on-device-validated point-of-care malaria reference.
Spontaneous cerebrospinal fluid (s-CSF) leaks and encephaloceles pose significant challenges in diagnosis, treatment, and long-term management. Although their association with idiopathic intracranial hypertension (IIH), obesity, and obstructive sleep apnoea is increasingly recognized, predictors of recurrence remain unclear. This study analyses a large multi-institutional cohort of patients with s-CSF leaks, with a specific focus on recurrent cases. A multicenter retrospective cohort study was performed. Patients with confirmed s-CSF leaks who underwent surgical repair were included. Demographic, clinical, radiological, and surgical data were collected. A total of 468 patients were included, predominantly women (70.7%) with elevated BMI (> 25 in 82.1%). The olfactory cleft was the most common leak site (39.9%), followed by the sphenoid sinus (27.8%) and the ethmoidal roof (23.3%). Radiological signs suggestive of IIH were present in 64.7% of patients. Endoscopic endonasal repair was performed in 95.5% of cases, with intrathecal fluorescein used in 55.1% and lumbar drain in 3.6%. Postoperative complications occurred in 8.1%, and recurrence was documented in 7.9% of cases. In only 37.8% of recurrent cases, the leak recurred at the same anatomical site. No clinical, surgical, or radiological variable was significantly associated with recurrence. s-CSF leaks are predominant in obese women with radiological features of IIH. Despite this strong association, no independent predictors of recurrence were identified, highlighting the complexity of the underlying mechanisms. Long-term prospective studies are required to better define prognostic factors and optimize management strategies.
Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by mucosal inflammation and epithelial barrier disruption. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, the principal cytosolic DNA-sensing axis, has emerged as a critical node in UC pathogenesis. This review elucidates the cGAS/STING signaling network in UC, from its upstream activation triggered by exogenous stimuli and leaked endogenous DNA to its downstream effects. We discuss how this pathway modulates distinct lines of intestinal defense, including the mechanical, chemical, and immunological barriers, while integrating its bidirectional crosstalk with the microbial barrier. Rather than exerting purely detrimental effects, cGAS/STING functions as a double-edged sword that coordinates both barrier homeostasis and inflammatory pathogenesis. Crucially, we summarize current pharmacological interventions, highlighting synthetic small molecules and bioactive natural products that target and modulate this axis to restore intestinal equilibrium. This framework provides a theoretical foundation for future precision therapies in UC.
Dry age-related macular degeneration (AMD) can progress to wet AMD when leaking capillaries grow under the macula. Although rare, this transition holds significant risk as it causes more rapid and severe vision loss. Oxidative stress is damaging to cellular components and plays a pivotal role in chronic diseases. We aim to determine whether oxidative stress in retinal pigment epithelial (RPE) cells elicits a proangiogenic microenvironment. We exposed human primary RPE cells to hydrogen peroxide (H2O2), and we analyzed their metabolic activity, and the production of reactive oxygen species (ROS) and angiogenic factors. In addition, we evaluated the potential of RPE cell-conditioned medium (CM) to induce HUVEC cell tube formation. RPE cells exposed to H2O2 displayed a dose-dependent decrease in their metabolic activity, and increased ROS levels. The analysis of the CM of exposed RPE cells revealed differential expression of a panel of proangiogenic factors. Notably, the expression of the major angiogenic factors (VEGF, FGF) was increased. Exposure of HUVEC cells to the CM of H2O2-exposed RPE cells promoted tube formation suggestive of microvessel formation. Our findings bring new insights into the role of oxidative stress in altering RPE cell behavior that might have consequences in the progression of AMD towards the exudative form.
To evaluate long-term postoperative symptoms, recovery and treatment responses at least 12 months after surgical repair of spinal CSF leaks in patients with spontaneous intracranial hypotension (SIH) and iatrogenic CSF leaks. This cross-sectional, self-report, online survey was conducted from January to April 2025, with participants recruited through international patient support groups. Descriptive analyses included 92 individuals with SIH and 136 with iatrogenic CSF leaks. The questionnaire assessed pre- and postoperative symptoms, functional recovery, complications and the perceived effectiveness of pharmacological and interventional treatments. Among 228 respondents, complete recovery was reported by 13.6% (12/92) of patients with SIH and 5.8% (8/136) of those with iatrogenic CSF leaks. Orthostatic headache showed the greatest postoperative improvement, whereas fatigue, cognitive impairment and tinnitus improved only moderately. The median duration of sick leave was eight months, and 18% of participants remained on medical leave at the time of assessment. Clinician-diagnosed long-term complications were reported by 14.9% of respondents, including peripheral nerve injury. Acetazolamide was the most effective treatment for rebound high-pressure headache, particularly in patients with SIH. Occipital nerve blocks and therapeutic lumbar punctures provided moderate benefit in selected patients, while most other pharmacological treatments showed limited effectiveness. Many patients in this self-report cohort experience persistent symptoms years after undergoing surgery to repair spinal CSF leaks. These findings emphasise the importance of structured, multidisciplinary and long-term postoperative care.
Short peripheral catheters (SPCs) are the most frequently used vascular access devices in neonates but are associated with complications and limited dwell times. International guidelines recommend using the smallest appropriate catheter gauge, yet 24G SPCs remain the default choice in many neonatal intensive care units (NICUs) while 26G SPCs are less often used because of concerns about flow adequacy particularly during blood transfusions. Evidence directly comparing these gauges in neonates is limited. We conducted a retrospective cohort study in a tertiary NICU and national referral centre for high-risk neonatal care in Doha, Qatar. Data were collected between 1 August 2018 and 31 December 2023. Eligible participants were neonates (0-28 days) who received at least one SPC insertion. Data extracted included demographics, catheter characteristics, dwell time, complications and reasons for removal. Analyses were performed at the catheter episode level. Dwell times were analysed using Kaplan-Meier survival curves with log-rank testing, and group comparisons were performed with parametric or non-parametric tests as appropriate. A total of 45 753 SPC episodes were analysed: 10 531 (23.0%) 24G and 35 222 (77.0%) 26G. Baseline characteristics were comparable between the groups. The mean dwell time was slightly longer for 26G than for 24G (35.1 vs 32.6 hours, p<0.001), although the absolute difference was small. Therapy completion rates were nearly identical (42.6% vs 42.0%, p=0.286). First-attempt success was higher with 26G (79% vs 74%, p<0.001), representing a clinically relevant improvement. The complication profile showed a trade-off: 26G SPCs had fewer leaks (11.9% vs 14.4%, p<0.001) and occlusions (4.0% vs 4.8%, p<0.001), but a slightly higher rate of phlebitis (4.6% vs 4.2%, p<0.001). Severe infiltration and extravasation rates were comparable. Overall complication rates were not significantly different between the groups. In the transfusion subgroup, 26G SPCs were used most frequently, and outcomes were not clinically different from those of 24G, with no excess complications observed, supporting their clinical feasibility for blood administration. In this large neonatal cohort, 26G SPCs were associated with a statistically longer dwell time than 24G SPCs, although the absolute difference was small. Therapy completion and complication rates were comparable between the groups, whereas first-attempt insertion success rates were higher with 26G SPCs.
Peri-device leak after left atrial appendage closure has emerged as a clinically relevant finding, which has been associated with residual thromboembolic risk. Strategies to achieve complete seal after left atrial appendage closure (LAAC), including coil- and plug-based approaches, are increasingly being used in selected anatomies. An 82-year-old woman with paroxysmal atrial fibrillation underwent prior LAAC. Follow-up cardiac computed tomography and transesophageal echocardiography demonstrated a skirt leak caused by incomplete sealing of the inferior aspect of the device, with persistent communication between the left atrium and distal appendage lobes. Given concern for residual embolic risk, she underwent transcatheter leak closure under transesophageal echocardiography and fluoroscopic guidance using detachable coils (Ruby Coils; Penumbra). The final fluoroscopic appearance was a compact ball-like coil mass within the appendage, with complete angiographic occlusion. Multimodality imaging defined the mechanism of residual leak and guided selection of coil embolization over focal plug-based closure. In selected anatomies, coil closure alone may provide an effective solution for persistent peri-device leak. Residual peri-device leak after LAAC should be characterized mechanistically, not only by size. In anatomically selected skirt leaks, coil embolization can achieve durable closure with excellent imaging and clinical follow-up.
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Frontal sinus fractures account for 5% to 11% of craniofacial traumas in the United States, and up to 40% of them involve the posterior table. Moderate to severe displacement or comminution of posterior table fractures has traditionally been addressed with cranialization. However, noncranialization surgical strategies, endoscopic surgical repair or observation have been proposed as alternative treatment options. A systematic review and meta-analysis were performed to evaluate complication rates and outcomes for cranialization versus noncranialization strategies or endoscopic or observation management of displaced posterior table fractures. A comprehensive literature search on PubMed, Scopus, and Web of Science yielded 10,254 articles. Following screening and full-text review, 55 studies met the inclusion criteria. A total of 2263 patients with displaced posterior table fractures were included. Cranialization was utilized in 56.6% (n=1280) of cases, noncranialization in 20.2% (n=457), endoscopic repair in 6.0% (n=135), or observation in 17.1% (n= 386). The overall complication rate was highest in patients managed with cranialization. For cranialization, the total complication rate was 13.0%, with meningitis and sinusitis being the most common complications (8.59%), followed by cerebrospinal fluid (CSF) leaks (3.28%), and mucocele (0.86%). Contrastingly, the noncranialization strategy demonstrated the lowest complication rate of 5.93%, with infection (3.56%) and mucocele (0.95%) being the most frequent complications. Endoscopic therapy yielded a total complication rate of 6.67%, with CSF leak (3.70%) and infection (2.22%) being the most common. The complication rate in the observation group was 6.48%. However, there was no statistical difference between the complication rates among the different management strategies. Therefore, cranialization remains the most common strategy for managing moderate to severe posterior table fractures. However, other strategies offer potentially promising, less invasive alternatives.
Total proctocolectomy with ileal pouch-anal anastomosis serves as the standard surgical treatment for medically refractory ulcerative colitis, yet long-term pouch failure remains a significant clinical challenge. This study aimed to identify independent predictors of pouch failure and to develop a practical clinical nomogram for individualized risk assessment. A retrospective cohort study was conducted utilizing a prospectively maintained database at a European tertiary referral center, analyzing procedures performed between December 2005 and June 2025. The study included 851 adult patients with a confirmed histologic diagnosis of ulcerative colitis who underwent restorative surgery. The primary outcome was pouch failure, defined as permanent pouch excision or indefinite fecal diversion. Independent predictors were identified using penalized logistic regression modeling to build a predictive risk tool. Over a median follow-up of 37.0 months for the entire cohort, pouch failure occurred in 4.7% of patients (n = 40). Among patients who experienced pouch loss, the median time to failure was 29.4 months. The majority of these failures manifested after 12 months and were primarily driven by severe fistulae and chronic leaks. Preoperative biologic therapy emerged as the sole independent predictor of pouch failure. Handsewn anastomoses and non-standard pouch configurations also demonstrated strong associations with failure. A five-variable clinical nomogram was constructed to provide individualized failure probabilities. While overall pouch failure rates remain low in specialized centers, exposure to preoperative biologic therapy significantly elevates this risk. The newly developed nomogram provides a valuable, evidence-based tool for tailored surgical counseling and personalized patient management.
Description Esophageal perforation is a life-threatening condition requiring prompt diagnosis and effective management. While self-expanding metal stents (SEMS) are a first-line treatment, persistent leaks often necessitate adjunctive endoscopic interventions. A structured, multimodal approach is critical for optimizing outcomes and avoiding surgical intervention. A 44-year-old man developed an iatrogenic esophageal perforation following surgical leiomyoma enucleation. Initial treatment with overlapping fully covered self-expanding metal stents (FC-SEMS) failed to achieve closure, necessitating endoscopic suturing for defect reinforcement. Despite suturing, persistent leakage required placement of a larger-diameter FC-SEMS, secured with an endoscopic fixation system to prevent migration. Serial imaging confirmed successful defect closure, allowing the patient to recover without the need for surgical intervention. This case underscores the importance of a stepwise, individualized endoscopic approach in managing complex esophageal perforations. A combination of SEMS, endoscopic suturing, and fixation techniques can enhance closure success and prevent complications, reducing the need for surgery.