Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: Esophagojejunostomy leakage (EJL) remains one of the most critical complications following total gastrectomy for gastric cancer. This study aimed to evaluate the evolving therapeutic approaches and clinical outcomes of EJL using data from a large-scale multicenter retrospective cohort. Methods: Among 6,577 patients who underwent total gastrectomy or proximal gastrectomy with double tract reconstruction at nine institutions from 2003 to 2024, 196 (3.0%) developed EJL. Of these, 162 patients with comprehensive clinical data were included in the final analysis. The study examined treatment modalities, changes in management over time, patient characteristics, surgical variables, and clinical outcomes. Four groups were defined according to treatment approach: conservative, endoscopic, reoperation, and multimodal (combined) therapy. Results: Endoscopic therapy was first introduced in 2011 and has progressively supplanted reoperation, now comprising 32.5% of cases. The average time to EJL diagnosis was 8.4 days after surgery. Overall in-hospital mortality was 6.1% (10/162). When conservative management was excluded, endoscopic treatment demonstrated the highest rate of therapeutic success (94.3%, p = 0.004). Both the duration until diet resumption and length of hospital stay were notably reduced in the endoscopic and conservative groups compared with reoperation and multimodal therapy (p < 0.001). Moreover, although the highest post-leakage hospitalization costs were observed with multimodal treatment (p < 0.001), overall hospitalization expenses were significantly lower for patients managed conservatively or with endoscopic intervention (p < 0.001). Conclusion Over the past two decades, management of EJL has shifted toward endoscopic approaches. Endoscopic therapies yield superior clinical outcomes and should be considered a primary option for appropriate candidates.

Background: The use of immune checkpoint inhibitors (ICIs) for advanced cancer is increasing, particularly in combination withchemotherapy. However, previous studies have focused on immune-related adverse events (irAEs) in specific organs, with limited re-search on combination therapy. Objective: We aimed to detect signals of adverse drug reaction (ADR) in both ICIs plus chemotherapy and ICIs alone compared to chemotherapy. Methods: We investigated individual case safety reports (ICSRs) between 2014 and 2022using Korea Institute of Drug Safety and Risk Management Korean Adverse Event Reporting System database (KIDS KAERS DB(2304A0076)). We defined adverse events (AEs) and drugs using MedDRA and the national drug code directory provided by the Min-istry of Food and Drug Safety. To detect signals, we performed disproportionality analysis using indices of reporting odds ratio (ROR) and information component (IC). Results: We identified 206,959 ICSRs in the KIDS KAERS DB, of which 5,154 contained ICIs and 201,805 were for chemotherapy. Compared to chemotherapy, radiation pneumonitis (ROR, 2313.6; IC, 5.4), hyperthyroidism (ROR, 53.4; IC, 4.2), and eczema (ROR,18.3; IC, 3.4) were detected as signals for ICIs. For ICIs with chemotherapy, additional signals including heart failure (ROR 9.65; IC 2.45), proteinuria (ROR 28.67; IC 4.16), and urinary tract infections (ROR 3.46; IC 1.03) were detected. Conclusion The study highlights an essential signal of ADRs associated with ICIs, both alone and in combination therapy, with conditions such as hyperthyroidism, hypothyroidism, and pneumonitis. These AEs should be monitored in clinical settings.

Objective: Primary frozen shoulder causes significant pain and progressively restricts shoulder movements. Diagnosis is made clinically based on patient history and physical examination. Management is mainly non-invasive owing to its self-limiting clinical course. However, clinical practice guidelines for frozen shoulder have not yet been developed in Korea. The developed guidelines aim to provide evidence-based recommendations for the diagnosis and treatment of frozen shoulder. Methods: A guideline development committee reviewed the literature from four databases (PubMed, Embase, Cochrane Library, and KMbase). Using the Population, Intervention, Comparator, and Outcome (PICO) framework, the committee formulated two backgrounds and 16 key questions to address common clinical concerns. Recommendations were made using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Diabetes, thyroid disease, and dyslipidemia significantly increase the risk of developing a frozen shoulder. Although frozen shoulder is often self-limiting, some patients may experience long-term functional disabilities. Ultrasound and magnetic resonance imaging should be used as adjunctive tools alongside clinical diagnosis, and rather than as independent diagnostic methods. Noninvasive approaches, such as medications, physical modalities, exercises, electrical stimulation, and manual therapy, may reduce pain and improve shoulder function. Other noninvasive interventions have limited evidence, and their application should be based on clinical judgment. Intra-articular steroid injections are recommended for treatment, and physiotherapy or hydrodilation with steroid injections can also be beneficial. Conclusion These guidelines provide evidence-based recommendations for diagnosing and treating primary frozen shoulder.

Purpose: We present a case of central anticholinergic syndrome following the administration of atropine eye drops.Case summary: A 60-year-old male presented with decreased visual acuity in his left eye and was diagnosed with intraocular lens dislocation. Preoperatively, Isopto atropine® eye drops (1 drop at 15-minutes intervals) were used for pupil dilation. Within an hour of the first instillation, the patient exhibited drowsiness, disorientation, agitation, and urinary retention. Laboratory tests and computed tomography of the brain were unremarkable. Considering the recent administration of atropine eye drops, a diagnosis of central anticholinergic syndrome was made. The surgery was postponed and the patient recovered fully after 3 hours of observation. He remained asymptomatic during an additional day of hospitalization. Conclusions A small dose of atropine eye drops even at a therapeutic dose can induce central anticholinergic syndrome. Therefore, ophthalmologists should be aware of this rare and severe complication.

Ectopic pregnancy (EP) is diagnosed based on laboratory values and ultrasonography (US) findings. Evaluation for suspected EP should begin with a quantitative measurement of the serum β-human chorionic gonadotropin levels and transvaginal US. MR imaging is not preferentially performed in the evaluation of EP; however, if the findings of transvaginal US are uncertain, MR imaging can be used, as it has the advantages of superior soft-tissue contrast resolution and a wide scanning range. Identifying the exact location of implantation transfer using MR imaging can help in the diagnosis and establishment of treatment strategies for ectopic pregnancies, including laparoscopy. In particular, as the incidence of heterotopic pregnancy has increased with the recent increase in use of assisted reproductive technology, the scope of application of MR imaging is expected to expand further. This pictorial essay describes the various manifestations of EP and related conditions on MR imaging and US. Familiarity with the clinical setting and the US and MR imaging features of EP and associated conditions can lead to a more accurate diagnosis and treatment.

Purpose: This study aimed to evaluate the effectiveness of using the severity of hyperechoic pancreas (HP) observed on preoperative ultrasonography (US) as a predictor of clinically relevant postoperative pancreatic fistula (CR-POPF). Methods: A retrospective study was conducted with 94 patients who underwent pancreatectomy between April 2006 and March 2021. The severity of HP on US was classified into two categories (normal to mild vs. moderate to severe [obvious HP]). Multiple preoperative and intraoperative parameters were analyzed to predict CR-POPF. Results: Out of the 94 patients, CR-POPF occurred in 21 (22%) patients, and obvious HP was observed in 30 (32%). Univariate analysis revealed that moderate to severe HP (obvious HP) was significantly associated with an increased incidence of CR-POPF (P<0.001). Factors such as the absence of pancreatitis, a small main pancreatic duct (<3 mm), intraoperative soft pancreas, increased body mass index, and lower pancreatic attenuation and attenuation index were also associated with CR-POPF (all P<0.05). Multivariate analysis showed that obvious HP and soft pancreatic texture were independent predictors of CR-POPF, with odds ratios of 11.53 (P=0.001) and 14.12 (P=0.003), respectively. The combination of obvious HP and soft pancreatic texture provided the most accurate prediction for CR-POPF. Conclusion The severity of HP, as observed on preoperative US, was significantly associated with CR-POPF. Severe HP may serve as a clinically useful predictor of POPF, especially when evaluated alongside the intraoperative pancreatic texture.

Purpose: BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. DaBRAFenib and trametinib showed promising antitumor activity in patients with BRAFV600E-mutated metastatic melanoma and non–small cell lung cancer. This study aimed to evaluate the efficacy and safety of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer. Materials and Methods: This was a retrospective study to evaluate the efficacy of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated PTC. The patients received daBRAFenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of daBRAFenib and trametinib. Results: Between December 2019 and January 2022, 27 PTC patients including eight patients with poorly differentiated or anaplastic transformation, received daBRAFenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients. Conclusion DaBRAFenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAFV600E-mutated metastatic PTC required a dose reduction.