Search Results (29,440)

With the acceleration of global population aging, the incidence of knee osteoarthritis (KOA) has risen significantly, placing unprecedented pressure on healthcare resources and creating an urgent need for automated segmentation technologies to enhance clinical diagnostic efficiency. Therefore, this paper proposes a novel multi-target tissue segmentation network for knee joints, SwMrNet, which integrates improved Swin Transformer units and a proposed multi-scale residual module within the decoder to enhance both segmentation accuracy and robustness. Firstly, a sliding-window mechanism is used to iteratively exchange feature information, allowing for the extraction of global tissue features. Then, features are extracted at multiple scales, with residual connections preserving the fine details of each tissue type. Through the repeated fusion of global and local features, the SwMrNet segmentation performance and robustness are significantly enhanced. Finally, the proposed model was evaluated on a public knee MRI dataset and a local clinical knee MRI dataset. On the public dataset, the model achieved a Dice score of 98.2%, with Dice scores for all segmented tissues exceeding 94%. On the local clinical dataset, the model showed visually consistent segmentation results, suggesting its potential as an efficient multi-tissue segmentation tool for automated knee joint analysis and auxiliary clinical assessment. Full article

Tricuspid regurgitation (TR) is being increasingly recognized in the patient population. It is a common cardiac cause of chronic disability. This pathology is characterized by a heterogeneous and broad spectrum of clinical manifestations with signs and symptoms. The results from various and different analyses and studies suggest that TR-related deaths may have increased over the last 20 years. This trend may justify a greater focus on timely diagnosis and management of TR. For a long time, this problem has been underestimated or treated with only pharmacological therapy (diuretics). The use of the isolated surgical option remains infrequent, especially in patients at high surgical risk, for whom a significant number of patients with TR are still not treated, and a disability remains that is difficult to manage and rehabilitate. To date, there are emerging as an alternative to surgery in high-risk patients with severe TR multiple transcatheter devices that aim to reduce TR through different functional mechanisms. There are numerous minimally invasive treatments for TR, and many devices used for the treatment of this disabling pathology. In fact, there are various treatments with a transcatheter approach using ever-new devices. The use of heterotopic implantation of bioprosthetic valves in the superior and inferior vena cava represents an additional therapeutic armamentarium that, through caval reflux, can constitute an additional resource, too. Starting from a single clinical experience and describing a clinical case report, a narrative review has been undertaken by reviewing the various studies that have investigated this type of approach and their impact on the general, cardiac, and functional sides, to then discuss the cost–benefit ratio in light of knowledge on this specific topic. Full article

Background: Dermoscopy has increased the excision of very small pigmented lesions in routine practice, yet the diagnostic efficiency of excising lesions ≤ 6 mm judged suspicious for melanoma remains incompletely defined. Objectives: The objectives of this study were to quantify melanoma detection yield and number needed to excise (NNE) for pigmented lesions ≤ 6 mm excised after clinical and dermoscopic suspicion of melanoma and to describe melanoma characteristics according to lesion diameter. Methods: We performed a retrospective observational cross-sectional study at a tertiary dermatologic oncology referral center within the Tuscany Regional Health Service, Florence, Italy. All pigmented lesions excised between 1 January 2022 and 31 December 2023 were screened. Consecutive lesions were included if they were excised because melanoma or suspected melanoma was the preoperative clinicodermoscopic diagnosis; lesions removed for benign or cosmetic indications were excluded. Primary outcomes were melanoma yield and number needed to excise, overall and stratified by clinical diameter. Multivariable logistic regression was performed to assess whether lesion diameter was independently associated with melanoma diagnosis after adjustment for age, sex, and anatomical site. Results: Among 2240 included excisions, 609 melanomas were diagnosed, corresponding to an overall yield of 27.2%. Lesions ≤ 6 mm accounted for 1331 excisions and yielded 175 melanomas, with a yield of 13.1% and a number needed to excise of 7.6. Lesions > 6 mm accounted for 909 excisions and yielded 434 melanomas, with a yield of 47.7% and a number needed to excise of 2.1. Thus, 86.9% of excised lesions ≤ 6 mm were benign on histopathology. Melanomas diagnosed in lesions ≤ 6 mm showed a more favorable histopathologic profile than larger melanomas. In multivariable analysis, lesions > 6 mm had significantly higher odds of melanoma than lesions ≤ 6 mm after adjustment for age, sex, and anatomical site (adjusted odds ratio 4.77, 95% confidence interval 3.81–5.97; p < 0.001). Conclusions: In routine practice, excision of dermoscopically suspicious pigmented lesions ≤ 6 mm has markedly lower melanoma yield and higher NNE than excision of larger lesions. These findings support risk-stratified management approaches and careful consideration of excision thresholds for very small lesions. Full article

Background/Objectives: Periodontitis is a highly prevalent inflammatory disease and a major cause of tooth loss worldwide. Accurate diagnosis requires integration of clinical and radiographic findings, but interpretation of panoramic radiographs is subject to variability. Artificial intelligence (AI) has emerged as a promising adjunct for radiographic assessment. This systematic review evaluated the diagnostic performance of AI-based models for detecting periodontitis using panoramic radiographic images. Methods: A systematic search of PubMed, Scopus, and Web of Science identified studies published between 1 January 2015 and 1 March 2026. Eligible studies assessed AI models for periodontitis detection on panoramic radiographs and used either clinically confirmed periodontal diagnosis or expert radiographic annotation as the reference standard. Data extraction and quality assessment were performed independently by two reviewers using the QUADAS-2 tool. Owing to heterogeneity in AI architectures, datasets, and outcome measures, a narrative synthesis was conducted. Results: Nine studies met the inclusion criteria, comprising more than 20,000 radiographs. AI models included convolutional neural networks (CNNs), segmentation-based systems, and hybrid architectures. Sensitivity ranged from 0.795 to 1.00, specificity from 0.784 to 0.99, and AUC values from 0.843 to 0.967. Studies using clinical periodontal diagnosis as the reference standard generally reported lower performance than those relying solely on expert annotation. Only four studies performed external validation, and dataset sizes varied widely. One study combining panoramic and periapical radiographs showed moderate diagnostic performance. Conclusions: AI-based diagnostic models demonstrate promising performance for detecting periodontitis on panoramic radiographs, with several studies reporting high sensitivity and AUC values. However, heterogeneity in reference standards, limited external validation, and inconsistent dataset quality restrict generalizability. AI should be considered an adjunct to, rather than a replacement for, comprehensive clinical periodontal examination. Standardized datasets and robust external validation are needed to support clinical implementation. Full article

A 66-year-old female patient was referred to the oral surgery unit for the enucleation of a radicular cyst centered at the apex of the necrotic tooth 12. Initial panoramic and intraoral periapical radiographs suggested a persistent periapical cystic lesion despite previous root canal treatment. However, cone-beam computed tomography (CBCT) revealed the coexistence of two distinct lesions within the same anatomical region: a periapical lesion associated with tooth 12, radiographically suggestive of a radicular cyst, and a second well-defined lesion centered within the nasopalatine canal, consistent with a nasopalatine duct cyst and not detectable on conventional radiographs. This unusual association represented a significant diagnostic challenge, as the clinical and two-dimensional radiographic findings initially suggested a single persistent endodontic lesion. Surgical enucleation of both lesions was performed. Histopathological examination confirmed the diagnosis of a nasopalatine duct cyst for the lesion located within the incisive canal, whereas the periapical lesion was confirmed as a radicular cyst. Postoperative follow-up at 10 days, 3 months, 6 months, and 1 year demonstrated satisfactory healing without recurrence or complications. This case highlights the diagnostic value of CBCT in the identification of coexisting odontogenic and non-odontogenic lesions of the anterior maxilla, particularly when conventional radiography is insufficient to distinguish separate pathologies. Full article

Background: Children with IBD are at increased risk of suboptimal maintenance of vaccine-induced immunity, particularly when the MMR vaccination course is incomplete before diagnosis and initiation of immunosuppressive therapy. We conducted a prospective study to evaluate the durability of antibody responses to measles, mumps, and rubella in pediatric IBD patients and to determine how completeness of MMR vaccination influences long-term antibody persistence over 12 months. Methods: Sixty children with IBD were included. Demographic characteristics, clinical disease activity (PUCAI/PCDAI), inflammatory markers (CRP, ESR), and fecal calprotectin were extracted from electronic medical records. Vaccination completeness was ascertained from documented immunization history. Serum antibodies to measles, rubella, and mumps were measured at baseline and after 12 months. Seroprotection was defined using standard laboratory thresholds. Antibody decay over time was assessed with paired non-parametric tests, and time to loss of seroprotection was analyzed using Cox proportional hazards models. In addition, Bayesian ANOVA modeling was applied to quantify evidence for differences in antibody concentrations and decay kinetics according to vaccination status. Results: Overall, 66.7% of patients had completed the full MMR vaccination course. At baseline, seroprotection rates were 48.3% for measles, 76.7% for rubella, and 70% for mumps. After 12 months, median antibody concentrations declined significantly for all three antigens. Corresponding seroprotection rates changed to 46.7% for measles (p = 0.414), 70% for rubella (p = 0.046), and 66.7% for mumps (p = 0.157). Incomplete MMR vaccination was identified as a major modifiable risk factor for accelerated antibody waning in children with IBD. Cox regression demonstrated that incompletely vaccinated patients had a 2.13-fold higher risk of losing measles seroprotection (95% CI 1.07–4.24; p = 0.032), a 5.27-fold higher risk for rubella (95% CI 1.86–14.95; p = 0.002), and a 4.82-fold higher risk for mumps (95% Cl 1.68–13.85; p = 0.004). Bayesian analyses provided decisive evidence that vaccination completeness strongly influences baseline antibody levels. Conclusions: Incomplete MMR vaccination is associated with markedly reduced durability of vaccine-induced immunity to measles, mumps, and rubella in children with IBD. These findings underscore the need for systematic prevaccination screening, timely completion of age-appropriate vaccination before initiation of immunosuppressive therapy when feasible, and individualized serological monitoring to identify patients at highest risk of vaccine-preventable infections. Full article

The identification of microRNAs (miRNAs) has resulted in significant advancements in research, particularly regarding their utilization as diagnostic and therapeutic targets. This has generated enthusiasm for exploring the potential of non-coding RNAs (ncRNAs) in treating cancer and other diseases, with miRNAs and long non-coding RNAs (lncRNAs) showing particular promise. Over the past twelve years, there has been significant research into RNA-based treatments. Antisense oligonucleotides and small interfering RNAs are the most commonly used. Certain products have received Federal and Drug Administration approval. Notably, the findings from clinical trials have been inconsistent, with certain investigations indicating notable effectiveness and others reporting only minimal efficacy or safety concerns. Consequently, clinical trials are currently underway to evaluate the efficacy of novel treatment options, including antimiRNAs, in addressing these challenges. There is an increasing interest in the use of long non-coding RNA (lncRNA)-based therapies. The potential for drugs developed using this technology is significant. Significant advancements in preclinical and clinical trials have emerged, indicating promising potential for future developments. MiRNAs are playing an increasingly important role in the diagnosis and prediction of acute coronary syndrome manifestations. Its utilization, whether as a comprehensive approach or in conjunction with existing biomarkers, may be implemented in the foreseeable future, especially in instances of uncertainty regarding diagnosis. The primary objective of this review is to deliver a thorough and detailed assessment of recent progress in the field of microRNA detection and characterization. A key focus of this assessment will be on their clinical translation. Secondly, an exploration of the prevailing knowledge in the field of RNA therapies as potential targets for diagnosis and treatment in the cardiovascular system will be conducted. The most recent challenges and perspectives on the road to clinical application are presented herein. The aim of the present seminar is to furnish a thorough report on the recent advancements in the detection and characterization of miRNAs and lncRNAs, with specific emphasis on their clinical translation. In summary, the paper herein presents an exploration of the most recent challenges and perspectives on the road to clinical application. Full article

Structural atrophy and metabolic dysfunction provide complementary biomarkers for Alzheimer’s disease (AD), and their joint modeling may support diagnostic assessment and cognitive score estimation. However, many multimodal methods rely on global fusion and insufficiently enhance cross-modal consistency before interaction, limiting the discriminative quality and clinical relevance of learned representations. We propose CGMF-Net, a cross-modal gated learning framework for joint AD classification and clinical score estimation using paired structural MRI (sMRI) and fluorodeoxyglucose PET (FDG-PET) data. CGMF-Net extracts multi-scale representations from both modalities, introduces a Cross-Modal Similarity Gate to strengthen consistent structural–metabolic responses before fusion, and employs bi-directional cross-attention to capture complementary interactions. The shared representation is optimized with classification supervision, MMSE-based auxiliary regression, and HSIC regularization to improve discriminability and reduce redundant coupling between directional representations. Experiments on ADNI demonstrate that CGMF-Net achieves the best overall classification performance among the compared methods, with 94.22% ACC and 97.74% AUC for AD vs. CN, and 86.67% ACC and 94.84% AUC for AD vs. MCI, while also showing favorable ADNI-2 to ADNI-1 generalization and competitive estimation of ADAS13, CDRSB, and MMSE. These results suggest that cross-modal gated learning provides clinically relevant multimodal representations for AD diagnosis and cognitive score estimation. Full article

Background: Early detection of severe infections in burn patients is difficult due to confounding sterile inflammation. Previous research has shown that Pancreatic Stone Protein (PSP) is less affected by trauma and surgery. Therefore, this study investigated whether longitudinal PSP trends can distinguish sterile post-burn inflammation from clinically relevant infections and indicate response to antimicrobial therapy. Methods: This prospective pilot cohort study included 10 consecutive adult patients with moderate to severe burn injuries admitted to a specialized burn intensive care unit. PSP levels were measured using bedside testing (abioSCOPE^®) daily over a 14-day observation period. Clinical parameters, burn severity as assessed by the Abbreviated Burn Severity Index (ABSI), and the occurrence of severe infectious complications, including pneumonia and bacteremia, were systematically recorded. PSP measurements were not used to guide clinical decision-making. Results: Patients who developed severe infectious complications (pneumonia and/or bacteremia; mean ABSI 8.5) showed a consistent and characteristic increase in PSP levels (>350 ng/mL) over time, with elevations preceding the clinical diagnosis of infection (24–120 h). In contrast, patients without pneumonia or bacteremia (mean ABSI 6) exhibited low and stable PSP (<150 ng/mL) concentrations throughout the observation period, despite the presence of burn-related injury and the expected sterile inflammatory response. Conclusions: In this exploratory cohort study distinct PSP trajectory patterns, with persistently low levels in non-infected patients and rising levels preceding clinically diagnosed infection in several cases, were observed. These preliminary findings suggest that longitudinal PSP monitoring may provide potential utility for infection surveillance in burn ICU patients. However, due to the exploratory design and very limited sample size, the findings should be interpreted cautiously and require validation in larger prospective multicenter studies before conclusions regarding clinical decision-making or patient outcomes can be drawn. Full article

Background: Cardiac calcified amorphous tumours (CATs) are rare non-neoplastic intracardiac masses characterized by calcified nodules within an amorphous fibrinous matrix and may clinically mimic thrombi or cardiac neoplasms. We report two uncommon cases of right atrial CAT occurring in young women and provide a narrative review of the literature. Methods: Two patients with right atrial CAT underwent multimodality imaging evaluation, including echocardiography, computed tomography, and cardiac magnetic resonance, followed by surgical excision and histopathological examination. A narrative review of published cases identified through PubMed and Embase between 1972 and 2025 was also performed. Results: The first patient presented with a calcified right atrial mass extending into the superior vena cava, associated with superior vena cava syndrome and autoimmune disease. The second patient, affected by end-stage renal disease on hemodialysis and thrombophilia, presented with a large calcified right atrial mass associated with a retained dialysis catheter fragment. Histopathological examination confirmed CAT in both cases. The literature review identified 112 published reports comprising 143 patients, including the two cases presented herein, highlighting frequent associations with end-stage renal disease, mitral annular calcification, and embolic complications. Conclusions: Cardiac CAT remains a rare and likely underrecognized entity with heterogeneous clinical presentation and significant embolic potential. Multimodality imaging is essential for diagnosis and surgical planning, while early surgical excision should be considered in symptomatic or high-risk patients. Full article

Blood-based biomarkers have emerged as promising, minimally invasive tools for the diagnosis, prognostic stratification, and treatment monitoring of non-small cell lung cancer (NSCLC), including markers of tumor burden, tumor dissemination, immune signaling, and post-transcriptional regulation. However, evidence across biomarker classes remains fragmented. This study aimed to synthesize published evidence on major blood-based biomarkers relevant to diagnosis, prognosis, treatment stratification, and monitoring in NSCLC. PubMed was searched for systematic reviews and meta-analyses of blood-based biomarkers in NSCLC. Of 356 screened records, 82 underwent full-text review, and 57 systematic reviews/meta-analyses were included. Biomarkers were grouped into four categories: circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), cytokines/soluble immune proteins, and non-coding RNAs (ncRNAs). Reported pooled effect estimates were extracted by biomarker class and evidence domain, and the methodological quality of included reviews was assessed using AMSTAR 2. Evidence was unevenly distributed across biomarker classes and evidence domains. Circulating ncRNAs were mainly represented in diagnostic and prognostic evidence; selected diagnostic ncRNAs, including miR-145, miR-25, and circRNAs, showed reported AUCs ranging from 0.83 to 0.85. ctDNA was represented across diagnostic, prognostic, treatment-stratification, and dynamic monitoring evidence, with ctDNA positivity associated with poorer survival or recurrence outcomes and ctDNA clearance or decline associated with improved outcomes. CTC evidence was primarily prognostic, with CTC positivity associated with worse overall survival and disease-free survival. Soluble immune biomarker evidence was also primarily prognostic, with elevated soluble PD-L1 and IL-6 associated with adverse survival outcomes and limited exploratory monitoring evidence for exosomal PD-L1. Overall, the evidence suggested distinct but complementary roles across biomarker classes, although direct head-to-head comparisons were lacking. Blood-based biomarkers show potential to support diagnosis, prognosis, and longitudinal monitoring in NSCLC, but their reported utility differs by biomarker class and clinical context. In the available review-level evidence, ncRNAs were mainly represented in diagnostic and prognostic evidence, while ctDNA was represented across diagnostic, prognostic, treatment-stratification, and dynamic monitoring evidence. CTCs were mainly represented in prognostic evidence, and soluble immune biomarkers were primarily represented in prognostic evidence, with limited exploratory evidence for dynamic monitoring. Further assay standardization, prospective validation, and direct comparative studies are needed before these biomarkers can be routinely integrated into clinical practice. Full article

Clostridioides difficile infection (CDI) is a leading healthcare-associated infection worldwide, causing significant morbidity, mortality, healthcare burden, and costs. Clinical manifestations range from mild, self-limiting diarrhea to severe, life-threatening complications such as toxic megacolon and septic shock. Early identification of patients at high risk of severe disease is essential to guide clinical decision-making and optimize therapy. This narrative review summarizes recent epidemiological data, current trends, and known risk factors as clinical context for severity prediction and then examines the utility and limitations of biomarkers that may predict CDI severity, including inflammatory, hematological, fecal, renal, and immune-response biomarkers. While some markers are already used in guideline-based assessment or routine clinical practice (e.g., C-reactive protein, white blood cell count, serum creatinine), they have limited specificity. Other markers emerging from CDI research, including procalcitonin, interleukins, and presepsin, may provide complementary prognostic information. The key challenge is not simply to identify additional biomarkers but to determine which biomarkers are clinically useful, at which stage of CDI progression, and in which patients they add value beyond conventional severity criteria. Validated predictive models integrating combinations of these biomarkers with clinical and microbiological data are needed to support early risk stratification and therapeutic decision-making at the time of diagnosis. Full article

Background/Objectives: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, is a serious complication of hematopoietic stem cell transplantation (HSCT), particularly in high and very high-risk pediatric patients. Despite known risk factors, U.S. data remain limited. The benefit of prophylactic defibrotide is uncertain, with prior trials yielding inconclusive results. This study evaluates its use and association with SOS incidence, healthcare burden, and outcomes. Methods: We performed a retrospective cohort study of 10,250 pediatric HSCT encounters using the Pediatric Health Information System. Patients were stratified as high-risk (n = 9584) or very high-risk (n = 666) per HARMONY criteria. Prophylactic defibrotide was used in 344 encounters; 9906 received none (therapeutic use allowed after SOS diagnosis). Outcomes included SOS incidence, length of stay (LOS), ICU admission, mortality, acute GVHD, and costs. Mixed-effects logistic regression models with patients as a random intercept were used (p < 0.05). Results: SOS incidence differences between the defibrotide prophylaxis and non-prophylaxis groups were not statistically significant in either risk category (high-risk: 26% [n = 79/302] vs. 7.1% [n = 663/9282] p = 0.495, OR 1.457, 95% CI 0.494–4.296; very high-risk: 31.0% [n = 13/42] vs. 21.6% [n = 135/624], p = 0.970, OR 1.081, 95% CI 0.019–60.769). The extremely wide confidence intervals indicate that the data are consistent with both benefit and harm of prophylaxis. Median LOS was longer in the prophylactic group (40 vs. 33 days, p < 0.001; 56 vs. 49 days, p = 0.296, respectively). ICU admissions (50.7% vs. 32.8%; 69.0% vs. 50.8%), mortality (7.9% vs. 3.5%; 23.8% vs. 10.9%), and costs ($443,537 vs. $205,325; p < 0.001) were also higher in the prophylaxis group. Acute GVHD incidence differences were not statistically significant, with contradictory directions between risk subgroups. Conclusions: Prophylactic defibrotide was not associated with reduced SOS incidence and was associated with higher ICU use, longer LOS, increased mortality, and greater costs. These findings represent associations, not causation, and likely reflect residual confounding by indication—as defibrotide prophylaxis was preferentially administered to patients perceived to be at highest clinical risk. Prospective studies with appropriate confounding adjustment are needed to clarify the role of defibrotide in SOS prevention. Full article

Background/Objective: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with limited therapeutic options and poor survival outcomes. Recent advances in molecular oncology have highlighted the significance of isocitrate dehydrogenase 1 (IDH1) mutations as potential therapeutic targets. However, data on the prevalence and prognostic implications of IDH1 mutations in patients with iCCA are scarce. This study aimed to retrospectively investigate the IDH1 mutation rate, histopathological features, and survival outcomes of patients with iCCA. Methods: We retrospectively analyzed 88 patients diagnosed and treated between 2005 and 2025 at two tertiary oncology centers. Clinical, pathological, and survival data were obtained from the institutional oncology archives and national population databases. IDH1 mutation status was evaluated using polymerase chain reaction and next-generation sequencing of paraffin-embedded tissue samples. Results: A total of 88 patients with iCCA were included, with a median age of 62 years, and 62.5% were male. Abdominal pain was the most common presenting symptom (67%). The most frequent stages at diagnosis were stage IB and stage IIIB (22.7% each). Histopathologically, the small-duct subtype (55.7%), nodular morphology (67.0%), and solitary tumors (79.5%) predominated. IDH1 mutation was detected in 2.3% of patients. Curative surgery was performed in 78.2% of cases and was more common in early-stage disease. Gemcitabine–capecitabine was the most frequently used adjuvant regimen, whereas gemcitabine–cisplatin was the most common palliative treatment regimen. Median overall survival differed significantly by albumin-bilirubin (ALBI) grade, with 40.1, 11.1, and 4.4 months for grades 1, 2, and 3, respectively (p < 0.001). Conclusions: In this multicenter cohort, iCCA was characterized by diverse clinicopathological features and treatment approaches. Surgical resection remains the main treatment modality for patients with localized disease, whereas systemic therapies are more frequently used in advanced stages. The findings highlight the prognostic relevance of baseline clinical and biochemical characteristics and may improve risk stratification in patients with iCCA. Full article

Introduction: Biallelic pathogenic variants in DNAJC30 cause an autosomal recessive form of Leber hereditary optic neuropathy (LHONAR1), traditionally considered a mitochondrially transmitted disorder. The phenotypic spectrum of diseases linked to DNAJC30 includes isolated optic neuropathy, Leigh syndrome spectrum (LSS), and atypical LHON-plus. Case description: Here, we report a 13-year-old boy presenting symptoms of area postrema syndrome (APS), with recurrent vomiting, vertigo, nystagmus, and subacute visual deterioration with central scotoma. Ophthalmological examination revealed bilateral papilledema with telangiectatic vessels, while visual evoked potentials demonstrated severe bilateral optic pathway dysfunction. Brain magnetic resonance imaging (MRI) showed T2/FLAIR hyperintense lesions involving the area postrema and enhancement of the optic nerves, strongly suggesting seronegative neuromyelitis optica spectrum disorder (NMOSD). Extensive immunological and cerebrospinal fluid studies, including anti-aquaporin-4 (AQP4) and anti-MOG antibodies, were negative. High-dose corticosteroids and intravenous immunoglobulins resulted in only transient and incomplete improvement, followed by further visual decline. Additionally, laboratory tests detected elevated lactate plasma levels. Hence, whole-exome sequencing was performed, which identified a homozygous pathogenic DNAJC30 c.152A>G, p.(Tyr51Cys) variant, associated with LHONAR1. After initiation of idebenone therapy, the patient showed significant improvement in visual function, normalization of lactate levels, and complete resolution of the brainstem lesions on follow-up MRI. Conclusions: This case further expands the neuro-ophthalmic spectrum associated with DNAJC30 variants and suggests that DNAJC30-related disease may closely mimic seronegative NMOSD. We highlight that early genetic diagnosis is essential, as recognition of this mitochondrial etiology enables targeted therapy and may substantially improve clinical outcomes. Full article