Electrochemically Active MoO3/TiN Sulfur Host Inducing Dynamically Reinforced Built-in Electric Field for Advanced Lithium-Sulfur Batteries.

Although various electrocatalysts have been developed to ameliorate the shuttle effect and sluggish Li-S conversion kinetics, their electrochemical inertness limits the sufficient performance improvement of lithium-sulfur batteries (LSBs). In this work, an electrochemically active MoO3/TiN-based heterostructure (MOTN) is designed as an efficient sulfur host that can improve the overall electrochemical properties of LSBs via prominent lithiation behaviors. By accommodating Li ions into MoO3 nanoplates, the MOTN host can contribute its own capacity. Furthermore, the Li intercalation process dynamically affects the electronic interaction between MoO3 and TiN and thus significantly reinforces the built-in electric field, which further improves the comprehensive electrocatalytic abilities of the MOTN host. Because of these merits, the MOTN host-based sulfur cathode delivers an exceptional specific capacity of 2520 mA h g-1 at 0.1 C. Furthermore, the cathode exhibits superior rate capability (564 mA h g-1 at 5 C), excellent cycling stability (capacity fade rate of 0.034% per cycle for 1200 cycles at 2 C), and satisfactory areal capacity (6.6 mA h cm-2) under a high sulfur loading of 8.3 mg cm-2. This study provides a novel strategy to develop electrochemically active heterostructured electrocatalysts and rationally manipulate the built-in electric field for achieving high-performance LSBs.

Establishment of the Foot-and-Mouth Disease Virus Type Asia1 Expressing the HiBiT Protein: A Useful Tool for a NanoBiT Split Luciferase Assay.

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that affects cloven-hoofed animals and causes severe economic losses in the livestock industry. Given that this high-risk pathogen has to be handled in a biosafety level (BSL)-3 facility for safety reasons and the limited availability of BSL-3 laboratories, experiments on FMDV call for more attention. Therefore, we aimed to develop an FMDV experimental model that can be handled in BSL-2 laboratories. The NanoBiT luciferase (Nano-luc) assay is a well-known assay for studying protein-protein interactions. To apply the NanoBiT split luciferase assay to the diagnosis and evaluation of FMD, we developed an inactivated HiBiT-tagged Asia1 Shamir FMDV (AS-HiBiT), a recombinant Asia1 shamir FMDV with HiBiT attached to the VP1 region of Asia1 shamir FMDV. In addition, we established LgBiT-expressing LF-BK cell lines, termed LgBit-LF-BK cells. It was confirmed that inactivated AS-HiBiT infected LgBiT-LF-BK cells and produced a luminescence signal by binding to the intracellular LgBiT of LgBiT-LF-BK cells. In addition, the luminescence signal became stronger as the number of LgBiT-LF-BK cells increased or the concentration of inactivated AS-HiBiT increased. Moreover, we confirmed that inactivated AS-HiBiT can detect seroconversion in sera positive for FMDV-neutralizing antibodies. This NanoBiT split luciferase assay system can be used for the diagnosis and evaluation of FMD and expanded to FMD-like virus models to facilitate the evaluation of FMDV vaccines and antibodies.

Unraveling the Photovoltage Formation Mechanism in Indium-Tin Oxide Branched Nanowires/Poly(3-Hexylthiophene) Photorechargeable Supercapacitors.

Photorechargeable supercapacitors are promising next-generation renewable energy storage devices. Previously, a hybrid structure consisting of indium-tin oxide branched nanowires (ITO BRs) and poly(3-hexylthiophene) (P3HT) was demonstrated as a photorechargeable supercapacitor. However, the formation mechanism of photovoltage has not been studied. Herein, we experimentally investigated the photovoltage-determining parameters in the ITO BRs/P3HT photorechargeable supercapacitor by inserting a polyethylenimine ethoxylated (PEIE) interlayer or adding a phenyl-C61-butyric acid methyl ester (PCBM) electron acceptor. Coating the PEIE interlayer on ITO BRs decreased the work function by 0.5 eV and hindered the hole extraction from P3HT to ITO BRs, leading to interfacial recombination and a decrease in photovoltage. On the other hand, the addition of PCBM promoted the charge transfer of the electrons from P3HT to PCBM, enhanced the redox reaction at the PCBM/electrolyte interface, and reduced the number of accumulated electrons, leading to a decreased photovoltage. From these results, we found that two key parameters determine the photovoltage and charge storage capability; one is the interfacial recombination at the ITO BRs/P3HT interface and the other is the redox reaction at the P3HT/electrolyte interface.

Resistance mechanisms of EGFR tyrosine kinase inhibitors, in EGFR exon 20 insertion-mutant lung cancer.

BACKGROUND: Mobocertinib, an EGFR exon 20 insertion (Ex20ins)-specific tyrosine kinase inhibitor has been used for treatment of advanced/metastatic EGFR Ex20ins-mutant non-small cell lung cancer (NSCLC). However, resistance mechanisms to EGFR Ex20ins-specific inhibitors and the efficacy of subsequent amivantamab treatment is unknown. METHODS: To investigate resistance mechanisms, tissue and cfDNA samples were collected before treatment initiation and upon development of resistance from NSCLC patients with EGFR Ex20ins mutations received mobocertinib, poziotinib, and amivantamab treatments. Genetic alterations were analyzed using whole-genome and targeted sequencing, and in vitro resistant cell lines were generated for validation. RESULTS: EGFR amplification (n = 6, including 2 broad copy number gain) and EGFR secondary mutation (n = 3) were observed at the resistance of mobocertinib. One patient had both EGFR secondary mutation and high EGFR focal amplification. In vitro models harboring EGFR alterations were constructed to validate resistance mechanisms and identify overcoming strategies to resistance. Acquired EGFR-dependent alterations were found to mediate resistance to mobocertinib in patients and in vitro models. Furthermore, two of six patients who received sequential amivantamab followed by an EGFR tyrosine kinase inhibitor had MET amplification and showed partial response. CONCLUSIONS: Our study revealed EGFR-dependent and -independent mechanisms of mobocertinib resistance in patients with advanced EGFR Ex20ins-mutant NSCLC.

A phase II study of osimertinib in patients with NSCLC harboring EGFR exon 20 insertion: A multicenter trial of the Korean Cancer Study Group (LU17-19).

BACKGROUND: Epidermal growth factor receptor (EGFR) exon 20 insertions account for up to 10% of all EGFR mutations. Clinical outcomes in patients receiving approved EGFR exon 20 insertion-specific inhibitors have been variable. Although osimertinib has demonstrated antitumor activity in clinical trials, its clinical efficacy and translational potential remain to be determined in non-small cell lung carcinoma (NSCLC) with EGFR exon 20 insertion. METHODS: In this multicenter phase II study, patients with advanced NSCLC harboring EGFR exon 20 insertions for whom the standard chemotherapy failed received 80 mg osimertinib once daily. The primary endpoint was the investigator-assessed objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety profile. RESULTS: Among 15 patients enrolled at stage 1, the best response was most commonly disease stabilization (73.3 %), which did not meet the stage 1 threshold (objective response ≥ 2/15). As of data cutoff, two patients remained on the treatment. The median PFS and OS were 3.8 (95 % confidence interval [CI] = 1.7-5.5) months and 6.5 (95 % CI = 3.9-not reached) months, respectively. Adverse events (≥grade 3) were anemia, hypercalcemia, and pneumonia (13.3 % each), and asthenia, femur fracture, increased alkaline phosphate, hyperkalemia, bone pain, and azotemia (6.7 % each). Pre-existing EGFR C797S mutation detected in plasma limited the efficacy of osimertinib. CONCLUSION: Osimertinib at 80 mg once daily had limited efficacy and mostly showed disease stabilization with an acceptable safety profile in advanced NSCLC harboring EGFR exon 20 insertions. CLINICALTRIALS: govIdentifier: NCT03414814.

Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM).

PURPOSE: Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs. MATERIALS AND METHODS: In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6. RESULTS: A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set-T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2. CONCLUSION: The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.

Boosted Lithium-Ion Transport Kinetics in n-Type Siloxene Anodes Enabled by Selective Nucleophilic Substitution of Phosphorus.

Doped two-dimensional (2D) materials hold significant promise for advancing many technologies, such as microelectronics, optoelectronics, and energy storage. Herein, n-type 2D oxidized Si nanosheets, namely n-type siloxene (n-SX), are employed as Li-ion battery anodes. Via thermal evaporation of sodium hypophosphite at 275 °C, P atoms are effectively incorporated into siloxene (SX) without compromising its 2D layered morphology and unique Kautsky-type crystal structure. Further, selective nucleophilic substitution occurs, with only Si atoms being replaced by P atoms in the O3≡Si-H tetrahedra. The resulting n-SX possesses two delocalized electrons arising from the presence of two electron donor types: (i) P atoms residing in Si sites and (ii) H vacancies. The doping concentrations are varied by controlling the amount of precursors or their mean free paths. Even at 2000 mA g-1, the n-SX electrode with the optimized doping concentration (6.7 × 1019 atoms cm-3) delivers a capacity of 594 mAh g-1 with a 73% capacity retention after 500 cycles. These improvements originate from the enhanced kinetics of charge transport processes, including electronic conduction, charge transfer, and solid-state diffusion. The approach proposed herein offers an unprecedented route for engineering SX anodes to boost Li-ion storage.

Clinical Outcomes of Secondary Duodenal Self-Expandable Metallic Stenting for Duodenal Stent Dysfunction in Patients with Malignant Duodenal Obstruction: A Retrospective Multicenter Study.

Background/Aims: Malignant duodenal obstruction has become more common with the development of palliative therapies.The outcomes of endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) are comparable to those of surgical gastrojejunostomy or duodenal stenting. However, EUS-GJ is technically challenging. Duodenal self-expandable metallic stent (SEMS) placement is popular; however, obstructions are common. Duodenal SEMS obstruction can be managed with the insertion of a second SEMS in a stent-in-stent manner. Therefore, we aimed to analyze the clinical outcomes of secondary duodenal SEMS placement in patients with malignant duodenal obstruction. Methods: We retrospectively analyzed the data of patients who underwent secondary duodenal stent insertion for duodenal stent dysfunction between January 2016 and December 2021. The primary outcome was stent patency. The secondary outcomes were clinical success, factors associated with dysfunction, patient survival, and adverse events. Results: A total of 109 patients were included. The mean age was 64.4±11.2 years, and 63 patients (57.8%) were male. Ninety-two patients (84.4%) had pancreaticobiliary cancer. Clinical success was achieved in 94 cases (86.2%). Twenty-three patients experienced stent dysfunction with 231 days of median stent patency (95% confidence interval [CI], 169 to not available). After a multivariable Cox hazard analysis of stent patency, the Eastern Cooperative Oncology Group performance status (hazard ratio [HR], 2.13; 95% CI, 1.20 to 3.81; p=0.010) and the first stent patency ≥6 months (HR, 0.33; 95% CI, 0.11 to 0.95; p=0.050) remained significant associated factors. Adverse events occurred in five patients (4.6%). Conclusions: Secondary duodenal stent insertion is a viable option for first duodenal stent obstruction. Further comparative studies involving surgery or EUS-GJ for obstructed duodenal stents are warranted.

Comparison of the different versions of NCCN guidelines for predicting margin-negative resection of pancreatic cancer in patients undergoing upfront surgery.

OBJECTIVES: The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement. METHODS: This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics. RESULTS: R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91). CONCLUSION: The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines.

Analytical Method Development and Dermal Absorption of 4-Amino-3-Nitrophenol (4A3NP), a Hair Dye Ingredient under the Oxidative or Non-Oxidative Condition.

The chemical 4-amino-3-nitrophenol (4A3NP) is classified as an amino nitrophenol and is primarily utilized as an ingredient in hair dye colorants. In Korea and Europe, it is exclusively used in non-oxidative or oxidative hair dye formulations, with maximum allowable concentrations of 1% and 1.5%, respectively. Despite this widespread use, risk assessment of 4A3NP has not been completed due to the lack of proper dermal absorption data. Therefore, in this study, both the analytical method validation and in vitro dermal absorption study of 4A3NP were conducted following the guidelines provided by the Korea Ministry of Food and Drug Safety (MFDS). Before proceeding with the dermal absorption study, analytical methods were developed for the quantitation of 4A3NP through multiple reaction monitoring (MRM) via liquid chromatography-mass spectrometry (LC-MS) in various matrices, including swab wash (WASH), stratum corneum (SC), skin (SKIN, comprising the dermis and epidermis), and receptor fluid (RF). These developed methods demonstrated excellent linearity (R2 = 0.9962-0.9993), accuracy (93.5-111.73%), and precision (1.7-14.46%) in accordance with the validation guidelines.The dermal absorption of 4A3NP was determined using Franz diffusion cells with mini-pig skin as the barrier. Under both non-oxidative and oxidative (6% hydrogen peroxide (H2O2): water, 1:1) hair dye conditions, 1% and 1.5% concentrations of 4A3NP were applied to the skin at a rate of 10 µL/cm2, respectively. The total dermal absorption rates of 4A3NP under non-oxidative (1%) and oxidative (1.5%) conditions were determined to be 5.62 ± 2.19% (5.62 ± 2.19 µg/cm2) and 2.83 ± 1.48% (4.24 ± 2.21 µg/cm2), respectively.

Global hyperperfusion after successful endovascular thrombectomy is linked to worse outcome in acute ischemic stroke.

Patients with stroke may develop hyperperfusion after a successful endovascular thrombectomy (EVT). However, the relationship between post-EVT hyperperfusion and clinical outcomes remains unclear and requires further clarification. We reviewed consecutive patients with anterior circulation occlusion who were successfully recanalized with EVT. Based on post-EVT arterial spin-labeling images, hyperperfusion was categorized as follows: global hyperperfusion (GHP), increased cerebral blood flow (CBF) in ≥ 50% of the culprit vessel territory; focal hyperperfusion (FHP), increased CBF in < 50% of the culprit vessel territory; no hyperperfusion (NHP), no discernible CBF increase. Factors associated with hyperperfusion were assessed, and clinical outcomes were compared among patients under different hyperperfusion categories. Among 131 patients, 25 and 40 patients developed GHP and FHP, respectively. Compared to other groups, the GHP group had worse National Institutes of Health Stroke Scale score (GHP vs. NHP/FHP, 18.1 ± 7.4 vs. 12.3 ± 6.0; p < 0.001), a larger post-EVT infarct volume (98.9 [42.3-132.7] vs. 13.5 [5.0-34.1] mL; p < 0.001), and a worse 90-day outcome (modified Rankin Scale, 3 [1-4] vs. 2 [0-3]; p = 0.030). GHP was independently associated with infarct volume (B = 0.532, standard error = 0.163, p = 0.001), and infarct volume was a major mediator of the association of GHP with unfavorable outcomes (total effect: ß = 0.176, p = 0.034; direct effect: ß = 0.045, p = 0.64; indirect effect: ß = 0.132, p = 0.017). Patients presenting with post-EVT GHP had poorer neurological prognosis, which is likely mediated by a large infarct volume.

Rain, rain, go away, come again another day: do climate variations enhance the spread of COVID-19?

The spread of infectious diseases was further promoted due to busy cities, increased travel, and climate change, which led to outbreaks, epidemics, and even pandemics. The world experienced the severity of the 125 nm virus called the coronavirus disease 2019 (COVID-19), a pandemic declared by the World Health Organization (WHO) in 2019. Many investigations revealed a strong correlation between humidity and temperature relative to the kinetics of the virus's spread into the hosts. This study aimed to solve the riddle of the correlation between environmental factors and COVID-19 by applying RepOrting standards for Systematic Evidence Syntheses (ROSES) with the designed research question. Five temperature and humidity-related themes were deduced via the review processes, namely 1) The link between solar activity and pandemic outbreaks, 2) Regional area, 3) Climate and weather, 4) Relationship between temperature and humidity, and 5) the Governmental disinfection actions and guidelines. A significant relationship between solar activities and pandemic outbreaks was reported throughout the review of past studies. The grand solar minima (1450-1830) and solar minima (1975-2020) coincided with the global pandemic. Meanwhile, the cooler, lower humidity, and low wind movement environment reported higher severity of cases. Moreover, COVID-19 confirmed cases and death cases were higher in countries located within the Northern Hemisphere. The Blackbox of COVID-19 was revealed through the work conducted in this paper that the virus thrives in cooler and low-humidity environments, with emphasis on potential treatments and government measures relative to temperature and humidity. HIGHLIGHTS: • The coronavirus disease 2019 (COIVD-19) is spreading faster in low temperatures and humid area. • Weather and climate serve as environmental drivers in propagating COVID-19. • Solar radiation influences the spreading of COVID-19. • The correlation between weather and population as the factor in spreading of COVID-19.

Detection and Characterization of the Metabolites of Ciwujianoside B in Rats Based on UPLC-Fusion Lumos Orbitrap Mass Spectrometry.

We previously conducted a systematic study on the metabolic process and products of hederasaponin B in rats. We hypothesized that the sugar chain structures play a key role in the metabolism of triterpenoid saponins. To verify this hypothesis, we conducted metabolic research on ciwujianoside B ascribed to the same sugar chains and a distinct aglycone and compared it with hederasaponin B. Specifically, we collected feces, urine, and plasma of rats after gavage with ciwujianoside B and identified 42 metabolites by UPLC-Fusion Lumos Orbitrap mass spectrometry. Finally, ciwujianoside B metabolism and hederasaponin B metabolism were compared, reaching the following conclusions: (i) more than 40 metabolites were identified in both, with the majority of metabolites identified in feces; (ii) the corresponding metabolic pathways in vivo were basically similar, including deglycosylation, acetylation, hydroxylation, glucuronidation, oxidation, and glycosylation; and (iii) deglycosylation was considered the main metabolic reaction, and its metabolites accounted for approximately 50% of all metabolites. Overall, this study provides a foundation for further research on the metabolism of triterpenoid saponins.

Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study.

PURPOSE: Lorlatinib improved progression-free survival (PFS) and intracranial activity versus crizotinib in patients with previously untreated, advanced, ALK-positive non-small cell lung cancer (NSCLC) in the phase III CROWN study. Here, we report long-term outcomes from CROWN after 5 years of follow-up. METHODS: Two hundred ninety-six patients with ALK-positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses. RESULTS: With a median follow-up for PFS of 60.2 and 55.1 months, respectively, median PFS was not reached (NR [95% CI, 64.3 to NR]) with lorlatinib and 9.1 months (95% CI, 7.4 to 10.9) with crizotinib (hazard ratio [HR], 0.19 [95% CI, 0.13 to 0.27]); 5-year PFS was 60% (95% CI, 51 to 68) and 8% (95% CI, 3 to 14), respectively. Median time to intracranial progression was NR (95% CI, NR to NR) with lorlatinib and 16.4 months (95% CI, 12.7 to 21.9) with crizotinib (HR, 0.06 [95% CI, 0.03 to 0.12]). Safety profile was consistent with that in prior analyses. Emerging new ALK resistance mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment. CONCLUSION: After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced ALK-positive NSCLC and set a new benchmark for targeted therapies in cancer.

A noradrenergic pathway for the induction of pain by sleep loss.

An epidemic of sleep loss currently affects modern societies worldwide and is implicated in numerous physiological disorders, including pain sensitization, although few studies have explored the brain pathways affected by active sleep deprivation (ASD; e.g., due to recreation). Here, we describe a neural circuit responsible for pain sensitization in mice treated with 9-h non-stress ASD. Using a combination of advanced neuroscience methods, we found that ASD stimulates noradrenergic inputs from locus coeruleus (LCNA) to glutamatergic neurons of the hindlimb primary somatosensory cortex (S1HLGlu). Moreover, artificial inhibition of this LCNA→S1HLGlu pathway alleviates ASD-induced pain sensitization in mice, while chemogenetic activation of this pathway recapitulates the pain sensitization observed following ASD. Our study thus implicates activation of the LCNA→S1HLGlu pathway in ASD-induced pain sensitization, expanding our fundamental understanding of the multisystem interplay involved in pain processing.

Long-term Outcomes of Ampullary Adenoma According to Resected Margin Status after Endoscopic Papillectomy.

Background/Aims: : Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the long-term outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes. Methods: : This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean follow-up duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis. Results: : Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021). Conclusions: : Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

Age-Related Variations in Patterns of Patent Foramen Ovale-Stroke versus Other Cryptogenic Stroke.

INTRODUCTION: Patent foramen ovale (PFO)-stroke, a form of cryptogenic stroke, has certain identifying clinical and imaging features. However, data describing this stroke type remain inconsistent. This study examined the potential variations in PFO-stroke features, depending on age. METHODS: From a hospital registry, cryptogenic stroke patients were retrospectively selected, and PFO-strokes were identified by the presence of >10 microembolic signals on transcranial Doppler saline agitation test. Cryptogenic strokes were grouped according to age (<70 as young, ≥70 as elderly). Clinical and imaging variables of PFO-strokes and non-PFO-strokes were compared, with and without age considered. RESULTS: Of the 462 cryptogenic patients, 30.5% (141/462) were PFO-strokes, while majority (321/462) had no PFO. When cryptogenic strokes were analyzed by age, the significant difference was noted in the lesion number, pattern, and side. A single (72.8 vs. 57.9%, p = 0.020) and a small single lesion (51.1 vs. 35.5%, p = 0.039) were frequently seen in the younger PFO-strokes than the non-PFO counterpart, while mixed territory lesions identified the elderly PFO-strokes (30.6 vs. 8.9%, p = 0.001). A multivariate logistic regression analysis of PFO-strokes further showed that age was independently associated with lesion side (OR 1.12 [1.05-1.20], p < 0.001) and lesion number (OR 1.06 [1.02-1.10], p = 0.005). CONCLUSIONS: Incorporating age-specific imaging criteria in the identification of PFO-strokes may be of additional value. Further, PFO may remain contributory to the stroke risk in the elderly, in association with vascular risk factors.

Full endoscopic surgery for calcium pyrophosphate deposition disease (CPPD) in the cervical ligamentum flavum: report of two cervical myelopathy cases.

Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative.