Synergistic Effects of Carbon Vacancies in Conjunction with Phosphorus Dopant across Bilayer Graphene for the Enhanced Hydrogen Evolution Reaction.

Bilayer graphene (BLG) exhibits distinct physical properties under external influences, such as torsion and structural defects, setting it apart from monolayer graphene. In this study, we explore the synergistic effects of carbon vacancies, in conjunction with phosphorus dopants, across BLG, focusing on their impact on structural, magnetic, electrical, and hydrogen adsorption properties. Our findings reveal that the substitutional doping of a phosphorus atom into a single carbon vacancy in a graphene layer induces substantial structural distortion in BLG. In contrast, doping phosphorus into a double vacancy maintains the flat structure of graphene layers. These distinct layer structures affect the electron distribution and spin arrangement, leading to varied electronic configurations and intriguing magnetic behaviors. Furthermore, the presence of abundant unsaturated electrons around the vacancy promotes the capture and bonding of hydrogen atoms. Hydrogen adsorption on BLG results in substantial orbital hybridization, accompanied by significant charge transfer. The calculated Gibbs free energies for hydrogen adsorption on BLG range from -0.08 to 0.09 eV, indicating exceptional catalytic activity for the hydrogen evolution reaction. These findings carry implications for optimizing the properties of graphene layers, making them highly desirable for applications such as catalysis.

Establishment of a patient-specific avatar organoid model derived from endoscopic ultrasonography-guided fine needle biopsy for timely clinical application in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, over 80 percent of PDACs are considered surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. The study aimed to establish a patient-derived organoid (PDO) platform from endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous analysis of HTS drug sensitivity test and genomic analysis. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs, compared with in EUS-FNB tissues. The HTS drug sensitivity test showed the clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "Patient Avatar Model" in clinical practice.

Diagnostic Performance of Endoscopic Ultrasound Elastography for Differential Diagnosis of Gallbladder Polyp.

BACKGROUND AND AIMS: It is difficult to differentiate between neoplastic and non-neoplastic gallbladder (GB) polyps before surgery. Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method. The utility of EUS-EG in the differential diagnosis of GB polyps has not been investigated. We aimed to investigate the diagnostic performance of EUS-EG for the differential diagnosis of GB polyps. METHODS: Patients with GB polyps were prospectively enrolled from June 2020 until November 2022. EUS-EG and semi-quantitative evaluation of the strain ratio (SR) were performed for differential diagnosis of GB polyps. Fifty-three eligible patients were divided into two groups based on the final diagnosis after surgery. Patient demographics, EUS characteristics, and SR values were compared. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff SR value that discriminates between neoplastic and non-neoplastic GB polyps. RESULTS: The median SR value for neoplastic polyps (32.93 [interquartile range: 22.37-69.02]) was significantly higher than for non-neoplastic polyps (5.40 [2.36-14.44]; p<0.001). There were significant differences in SR values between non-neoplastic, benign neoplastic (23.38 [13.62-39.04]), and malignant polyps (49.25 [27.90-82.00]). The optimal cut-off SR value to differentiate between neoplastic and non-neoplastic polyps was 18.4. In multivariable logistic regression, SR value >18.4 (odds ratio 33.604, 95% confidence interval 2.588-436.292) was an independent predictor of neoplastic polyps. CONCLUSIONS: EUS-EG and SR values can be used as a supplementary method for evaluating GB polyps.

Bleeding after endoscopic papillectomy and its risk factors: A single center experience of 196 cases.

BACKGROUND: Endoscopic papillectomy (EP) is an effective method to remove an ampulla of Vater (AoV) adenoma with minimal invasiveness. We reviewed the clinical outcomes and prognosis of patients undergoing EP, including tumor recurrence and adverse events. METHODS: A total of 196 patients who underwent EP from January 2004 to December 2017 were included. Clinical information was collected through electronic medical records, and risk factors to predict post-procedural bleeding were analyzed using a multivariate logistic regression model. RESULTS: A total of 93.9% patients (184/196) underwent complete resection. During the follow-up period, 14.7% patients (27/184) experienced tumor recurrence, and two of seven surgically resected tumors were malignant. A total of 45.4% patients (89/196) experienced adverse events related to EP. Delayed bleeding occurred in 16.3% of the patients (32/196), and they were all successfully treated with endoscopic hemostasis and conservative management. The most frequent site of delayed bleeding was the distal end of the papillary orifice, and 56.2% (18/32) patients of delayed bleeding were classified as having mild severity, the others had moderate severity. Familial adenomatous polyposis (FAP) [odds ratio (OR) = 3.80, 95% confidence interval (CI): 1.01-14.29; P < 0.05] and male sex (OR = 2.82, 95% CI: 1.04-7.63; P = 0.04) showed statistical significance in predicting delayed post-EP bleeding. CONCLUSIONS: EP for AoV adenoma was a highly effective and safe procedure. The risk of post-EP delayed bleeding was increased in patients with FAP syndrome and male patients, and post-EP bleeding occurred most commonly in the distal part of the AoV.

Prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency through molecular genetic analysis of the CYP21A2 gene.

PURPOSE: Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was performed to investigate the clinical utility of prenatal diagnosis of 21-OHD using molecular genetic testing in families at risk. METHODS: This study included 27 pregnant women who had previously borne a child with 21-OHD. Fetal tissues were obtained using chorionic villus sampling (CVS) or amniocentesis. After the genomic DNA was isolated, Sanger sequencing of CYP21A2 and multiplex ligation-dependent probe amplification were performed. The clinical and endocrinological findings were reviewed retrospectively. RESULTS: A total of 39 prenatal genetic tests was performed on 27 pregnant women and their fetal tissues. The mean gestational age at the time of testing was 11.7 weeks for CVS and 17.5 weeks for amniocentesis. Eleven fetuses (28.2%) were diagnosed with 21-OHD. Among them, 10 fetuses (90.9%) harbored the same mutation as siblings who were previously diagnosed with 21-OHD. Among these, 4 fetuses (3 males and 1 female) identified as affected were born alive. All 4 patients have been treated with hydrocortisone, 9α-fludrocortisone, and sodium chloride since a mean of 3.7 days of life. The male patients did not show hyponatremia and dehydration, although they harbored pathogenic variants associated with the salt-wasting type of 21-OHD. CONCLUSION: This study demonstrated the diagnostic efficacy and clinical consequences of diagnosis by prenatal genetic testing in families at risk for 21-OHD. All patients identified as affected were treated with hydrocortisone and 9α-fludrocortisone early after birth, which can prevent a life-threatening adrenal crisis.

Light emitting diode (LED) irradiation of liposomes enhances drug encapsulation and delivery for improved cancer eradication.

Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.

Elevated white blood cell count and long-term clinical outcomes of patients with vasospastic angina.

OBJECTIVES: Inflammation is known as one of key pathophysiologic mechanisms of coronary artery disease. We aimed to investigate the relationship between white blood cell (WBC) count and long-term clinical outcomes of patients with vasospastic angina (VA). METHODS: A total of 823 patients who were diagnosed as VA without significant coronary lesion by coronary angiography with ergonovine provocation test were enrolled for analysis. Patients were divided according to WBC count tertile at the time of diagnosis: group I, tertile 1 and 2 (n = 546, <7490/ml); group II, tertile 3 (n = 277, ≥7490/ml). Primary outcome was defined as major adverse cardiovascular events (MACE), a composite outcome of all-cause death, cardiac death, myocardial infarction (MI), readmission due to cardiac symptoms, and revascularization. RESULTS: Median follow-up duration was 4.3 years. No significant difference of primary outcome was observed between group I and group II (14.7% vs. 20.2%, hazard ratio (HR) 1.29, confidence interval (CI) 0.90-1.83, P = 0.162), while incidence of cardiac death and MI was significantly higher in group II (1.5% vs. 4.3%, HR 2.86, CI 1.14-7.17), P = 0.025). In multivariate Cox regression model, elevated WBC count at the time of diagnosis of VA was an independent predictor of MI (HR 3.43, CI 1.02-11.59, P = 0.047). CONCLUSION: Elevated WBC count at the time of diagnosis was associated with a significantly increased risk of cardiac death and MI during long-term follow-up in VA patients.

Nano-chemical priming strategy to enhance TGF-ß resistance and anti-tumor activity of natural killer cells.

Immunotherapy based on adoptive transfer of natural killer (NK) cells is a promising strategy for circumventing the limitations of cancer treatments. However, components of the immunosuppressive tumor microenvironment (TME), such as transforming growth factor-beta (TGF-ß), compromise the therapeutic efficacy of NK cells significantly. To address these limitations, we developed a novel method of engineering NK cells for adaptive transfer. The method is based on nanogels that serve two functions: (1) they overcome the TGF-ß-mediated stress environment of the TME, and (2) they enhance the direct anti-tumor activity of NK cells. Previously, we demonstrated that cationic compounds such as 25 K branched polyethylenimine (25 K bPEI) prime NK cells, putting them in a 'ready-to-fight' state. Based on these findings, we designed nanogels that have two primary characteristics: (1) they encapsulate galunisertib (Gal), which is used clinically to inhibit TGF-ß receptor activity, thereby blocking TGF-ß signaling; and (2) they provide cells with a surface coating of 25 K bPEI. When grown in culture medium containing TGF-ß, nanogel-treated NK cells demonstrated greater migration ability, degranulation activity, and cytotoxicity towards cancer cells than untreated NK cells. Additionally, the in vivo efficacy of nanogel-treated NK cells against PC-3 xenografts was significantly greater than that of Chem_NK cells primed by 25 K bPEI alone. These findings suggest that Gal-loaded 25 K bPEI-coated nanogels exert anti-tumor effects via chemical priming, as well suppressing the effects of TGF-ß on NK cells. We also expect 25 K bPEI-based nanogels to have great potential to overcome the suppressive effects of the TME through their NK cell-priming activity and delivery of the desired chemicals.

Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy.

Intratumor heterogeneity leads to different responses to targeted therapies, even within patients whose tumors harbor identical driver oncogenes. This study examined clinical outcomes according to a patient-derived cell (PDC)-based drug sensitivity test in lung cancer patients treated with targeted therapies. From 487 lung cancers, 397 PDCs were established with a success rate of 82%. In 139 PDCs from advanced non-small-cell lung cancer (NSCLC) patients receiving targeted therapies, the standardized area under the curve (AUC) values for the drugs was significantly correlated with their tumor response (p = 0.002). Among 59 chemo-naive EGFR/ALK-positive NSCLC patients, the PDC non-responders showed a significantly inferior response rate (RR) and progression-free survival (PFS) for the targeted drugs than the PDC responders (RR, 25% vs. 78%, p = 0.011; median PFS, 3.4 months [95% confidence interval (CI), 2.8-4.1] vs. 11.8 months [95% CI, 6.5-17.0], p < 0.001). Of 25 EGFR-positive NSCLC patients re-challenged with EGFR inhibitors, the PDC responder showed a higher RR than the PDC non-responder (42% vs. 15%). Four patients with wild-type EGFR or uncommon EGFR-mutant NSCLC were treated with EGFR inhibitors based on their favorable PDC response to EGFR inhibitors, and two patients showed dramatic responses. Therefore, the PDC-based drug sensitivity test results were significantly associated with clinical outcomes in patients with EGFR- or ALK-positive NSCLC. It may be helpful for predicting individual heterogenous clinical outcomes beyond genomic alterations.

Long-term endocrine sequelae after hematopoietic stem cell transplantation in children and adolescents.

Purpose: As the survival rate for pediatric cancers increases significantly with advances in treatment modalities, long-term endocrine complications have also risen. This study investigated the frequencies and risks of endocrine sequelae of childhood cancer survivors after hematopoietic stem cell transplantation (HSCT). Methods: This study included 200 pediatric patients who underwent HSCT. Clinical and endocrinological findings were collected retrospectively. Median follow-up duration after HSCT was 14 years. Results: Endocrine complications occurred in 135 patients (67.5%). Children who underwent HSCT at pubertal age (n = 100) were at higher risk of endocrine complications than prepubertal age (79% vs. 56%, P = 0.001). The most common complication was hypogonadism (40%), followed by dyslipidemia (22%). Short stature and diabetes mellitus were more prevalent in the prepubertal group, whereas hypogonadism and osteoporosis were more common in the pubertal group. Female, pubertal age at HSCT, and glucocorticoid use were predictors of increased risk for any complication. Radiation exposure increased the risk of short stature and hypothyroidism. Hypogonadism was significantly associated with female, pubertal age at HSCT, and high-dose radiation. Pubertal age at HSCT also increased the risks of osteoporosis and dyslipidemia. Conclusion: This study demonstrated that long-term endocrine complications are common after HSCT in children and adolescents. Age at HSCT is a critical factor for endocrine complications after HSCT. These findings suggest that surveillance strategies for endocrine complications in childhood cancer survivors should be specified according to age at HSCT.

Prolonged progression-free survival achieved by gemcitabine, cisplatin, and albumin-bound paclitaxel for the treatment of advanced biliary tract cancers.

Background: A regimen of gemcitabine, cisplatin, and nab-paclitaxel (GPA) has shown promising results in patients with advanced biliary tract cancer (aBTC). Objectives: This study aimed to evaluate the benefit of GPA compared to a regimen of gemcitabine plus cisplatin (GP) in patients with aBTC. Design: Retrospective study. Methods: Patients with aBTC who received first-line chemotherapy with GPA or GP regimen at the Samsung Medical Center between July 2020 and June 2022 were included. The primary endpoint was progression-free survival (PFS). Results: In all, 37 patients were treated with GPA and 43 patients with GP. The GPA group showed significantly longer median PFS [12.0 months (95% CI, 7.2-16.8)] compared to the GP group [5.5 months (95% CI, 3.7-7.4; p = 0.007)]. The median overall survival (OS) was also longer in the GPA group [18.7 months (95% CI, 13.7-23.7)] than in the GP group [10.7 months (95% CI, 1.5-19.9); p = 0.021]. First-line chemotherapy with GPA was associated with longer PFS, while metastatic disease at initial diagnosis and post-treatment increase in CA 19-9 level were associated with worse PFS. Conclusion: The GPA regimen improved the PFS of patients with aBTC compared to the GP regimen but showed no significant benefit in terms of OS after adjusting for confounding variables. Further large-scale studies are required to establish optimal indications for GPA.

Comparing new and standard chemotherapy treatments for advanced biliary tract cancer: a study of effectiveness and survival In this study, researchers at Samsung Medical Center investigated the effectiveness of two chemotherapy regimens for advanced biliary tract cancer (aBTC) from July 2020 to June 2022. The study compared a new treatment combination, gemcitabine, cisplatin, and nab-paclitaxel (GPA), against the standard treatment of gemcitabine and cisplatin (GP). The main focus was on progression-free survival (PFS) ­ the time patients lived without their cancer worsening, and overall survival (OS) ­ the total lifespan after treatment. A total of 37 patients received the GPA treatment, while 43 received the GP treatment. The results showed that patients on the GPA regimen had a longer median PFS of 12.0 months, compared to 5.5 months for those on the GP regimen. This significant difference suggested that GPA might be more effective in slowing cancer progression. Moreover, the median OS was also longer for patients treated with GPA (18.7 months) than for those with the GP regimen (10.7 months). These findings indicated that GPA not only delayed the progression of cancer but also potentially increased the overall survival time of patients. However, when accounting for other factors that could influence the results, the advantage of GPA in terms of overall survival became less clear. This suggests that while GPA is effective in delaying disease progression, its impact on extending the overall life expectancy of patients with aBTC is not definitive. Despite these promising findings, the researchers cautioned that the benefits of the GPA regimen in extending overall survival need further investigation. The study underscores the potential of GPA in improving outcomes for aBTC patients but also highlights the necessity for more comprehensive studies. These future studies are needed to confirm the optimal treatment for this challenging cancer type. This research is a step towards better understanding and managing aBTC, a cancer that currently has limited treatment options.

Clinical Significance of Venous Thromboembolism in Patients with Advanced Cholangiocarcinoma.

Background/Aims: Patients with active cancer frequently develop venous thromboembolism (VTE). However, there is little data about VTE in patients with advanced cholangiocarcinoma (CCA). Therefore, we investigated the clinical significance of VTE in patients with advanced CCA. Methods: We analyzed the data of a total of 332 unresectable CCA patients diagnosed between 2010 and 2020 in this retrospective study. We investigated the incidence and risk factors for VTE, and its effect on survival in patients with advanced CCA. Results: During a median follow-up of 11.6 months, 118 patients (35.5%) developed VTE. The cumulative incidence of VTE was 22.4% (95% confidence interval [CI], 0.18 to 0.27) at 3 months and 32.8% (95% CI, 0.27 to 0.38) at 12 months. Major vessel invasion was an independent risk factor for VTE (hazard ratio, 2.88; 95% CI, 1.92 to 4.31; p<0.001). Patients who developed VTE during follow-up had shorter overall survival than patients who did not (11.50 months vs 15.83 months, p=0.005). In multivariable analysis, VTE (hazard ratio, 1.58; 95% CI, 1.23 to 2.02; p<0.001) was associated with poor overall survival. Conclusions: Major vessel invasion is related to the occurrence of VTE in advanced CCA. The development of VTE significantly decreases the overall survival and is an important unfavorable prognostic factor for survival.

Monolithic Integration of Ultraslim Flow Sensor and Medical Guidewire by Laser Filament Scanning Sintering for In Vivo Diagnostics of Cardiovascular Diseases.

In this study, an ultraslim thermal flow sensor system integrated onto a 340 µm diameter medical guidewire was developed using a laser filament scanning sintering method for the early diagnosis of cardiovascular diseases. The proposed system is a calorimetric-based micro thermal flow sensor comprising a microheater and two thermistors. Prior to fabrication, the sensor design was optimized through flow simulation, and the patterned sensor was successfully implemented on a thin and curved surface of the medical guidewire using a laser patterning method with Ag nanoparticles. The performance of the ultraslim thermal flow sensor-on-guidewire system (SoW) was evaluated under pulsatile flow by using an artificial heartbeat simulator with differentially induced fluid flow velocities of up to 60 cm/s. The resulting electrical signals generated by the temperature difference between the two thermistors caused by the fluid flow were measured across different velocity ranges. Based on the obtained data, a calibration curve was derived to establish the relationship between the fluid velocity and the sensor output voltage. Furthermore, the SoW was tested on living animals, whereby the measured blood flow velocities were 60-90 cm/s in the left coronary artery of pigs. This research demonstrates the potential of ultraslim microsensors, such as the developed thermal flow sensor system, for various industries, particularly in the medical field.

Impact of Early Diagnostic and Therapeutic Interventions and Clinical Course in Children and Adolescents with Multiple Endocrine Neoplasia Types 1 and 2.

PURPOSE: Multiple endocrine neoplasia types 1 (MEN1) and 2 (MEN2) are inherited endocrine tumor syndromes caused by mutations in the MEN1 or RET genes. This study aimed to investigate clinical outcomes and molecular characteristics among children with MEN. METHODS: This study included eight patients from seven unrelated families. Data on clinical course, biochemical findings, and radiologic studies were collected by retrospective chart review. All diagnoses were genetically confirmed by Sanger sequencing of MEN1 in three MEN1 patients and RET in four patients with MEN2A and one patient with MEN2B. RESULTS: Three patients with MEN1 from two families presented with hypoglycemia at a mean age of 11±2.6 years. Four patients with MEN2A were genetically diagnosed at a mean of 3.0±2.2 years of age by family screening; one of them was prenatally diagnosed by chorionic villus sampling. Three patients with MEN2A underwent prophylactic thyroidectomy from 5 to 6 years of age, whereas one patient refused surgery. The patient with MEN2B presented with a tongue neuroma and medullary thyroid carcinoma at 6 years of age. Subsequently, he underwent a subtotal colectomy because of bowel perforation and submucosal ganglioneuromatosis at 18 years of age. CONCLUSION: This study described the relatively long clinical course of pediatric MEN with a mean follow-up duration of 7.5±3.8 years. Insulinoma was the first manifestation in children with MEN1. Early diagnosis by family screening during the asymptomatic period enabled early intervention. The patient with MEN2B exhibited the most aggressive clinical course.

Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant Non-Small Cell Lung Cancer.

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC. MATERIALS AND METHODS: This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling. RESULTS: A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor ß, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS. CONCLUSION: NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.

Treatment-related cardiovascular events in patients with non-small cell lung cancer: Evidence from real-world data with a competing risks approach.

BACKGROUND: Understanding cancer treatment-related cardiovascular (CV) events is important for cancer care; however, comprehensive evaluation of CV events in patients with lung cancer is limited. This study aimed to assess the cumulative incidence and associated risks of various CV event types in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 7868 individuals aged 40 years and older, recently diagnosed with NSCLC (2007-2018), were assessed with data obtained from the National Cancer Center, Korea. This study included nine types of CV events. A 2-year cumulative incidence function (CIF) of CV events was estimated, with death as a competing event. The associated risks were assessed by subdistribution hazard ratio (sHR) in the Fine-Gray competing risks model. RESULTS: CV events were observed in 7.8% of patients with NSCLC, with the most frequently observed types being atrial fibrillation and flutter (AF) (2.7%), venous thromboembolic disease (2.0%), and cerebrovascular disease (CeVD) (1.5%). Overall, all CV events were highest in the group treated with systemic therapy (CIF, 10.6%; 95% confidence interval [CI], 9.5%-11.8%), followed by those treated with surgery (CIF, 10.0%; 95% CI, 8.6%-11.6%); the incidence of AF (CIF, 5.7%; 95% CI, 4.6%-7.0%) was highest in patients treated with surgery. Individuals treated with systemic therapy were found to exhibit a higher CeVD risk than those treated with surgery (sHR, 4.12; 95% CI, 1.66-10.23). Among the patients who underwent surgery, those with lobectomy and pneumonectomy had a higher AF risk (vs. wedge resection/segmentectomy; sHR, 7.79; 95% CI, 1.87-32.42; sHR, 8.10; 95% CI, 1.60-40.89). CONCLUSIONS: These findings revealed treatment-related CV event risks in patients with NSCLC, which suggests that the risk of AF in surgery and CeVD in systemic therapy should be paid more attention to achieve a better prognosis and improve cancer survivorship outcomes. PLAIN LANGUAGE SUMMARY: Atrial fibrillation and flutter (AF) is the most common cardiovascular event, particularly at a high risk in patients with non-small cell lung cancer (NSCLC) undergoing surgery. Patients receiving surgery with poor performance status, diagnosed with regional stage, and undergoing lobectomy or pneumonectomy are at a high risk of AF. Systemic/radiotherapy is associated with cerebrovascular and ischemic heart disease in patients with NSCLC.

Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells.

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Treatment Outcomes of Proton Beam Therapy for Esophageal Squamous Cell Carcinoma at a Single Institute.

Recently, proton beam therapy (PBT) has gathered attention for improving outcomes and reducing toxicities in various cancers; however, the evidence for esophageal squamous cell carcinoma (ESCC) is lacking. Our study retrospectively evaluated the outcomes of PBT for ESCC patients at a single institute. The patients treated with PBT between November 2015 and February 2022 were included in the study, excluding those with distant metastases or those that had undertaken prior treatment for esophageal cancer (EC). The 3 year overall survival (OS) and progression-free survival (PFS) rates were calculated based on stage grouping. The patterns of failure, salvage treatment outcomes, and toxicity profiles were analyzed. The median follow-up was 35.1 months, and 132 patients were analyzed. The 3 year OS and PFS rates for the stages I, II, and III disease cases were 81.0%, 62.9%, and 51.3%; and 70.6%, 71.8%, and 39.8%, respectively. Nineteen patients presented isolated local progression, ten patients underwent appropriate salvage procedures, and nine were successfully salvaged. One patient with isolated regional progression was also salvaged. No cases of grade ≥ 4 lymphopenia were observed. One patient had grade 4 pericardial effusion and esophageal fistula. For the patients with ESCC, PBT is an effective treatment in terms of the survival outcomes and toxicities.

Sex-Based Outcomes of P2Y12 Inhibitor Monotherapy After Three Months of Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in the SMART-CHOICE trial, P2Y12 inhibitor monotherapy after three months of dual antiplatelet therapy (DAPT) achieved clinical outcomes comparable to those of 12 months of DAPT. Nonetheless, the effects of sex on these outcomes remain unknown. METHODS: This open-label, non-inferiority, randomized study, conducted in 33 hospitals in South Korea, included 2,993 patients undergoing PCI with drug-eluting stents. Patients were randomly assigned to receive DAPT (aspirin plus a P2Y12 inhibitor) for three months then P2Y12 inhibitor alone for nine months, or DAPT for the entire 12 months. The primary endpoints were major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) 12 months after the index procedure. The bleeding endpoints were Bleeding Academic Research Consortium (BARC) bleeding types 2 to 5. RESULTS: Of the patients, 795 (26.6%) were women, who were older and had a higher prevalence of hypertension, diabetes, and dyslipidemia than men. The sexes exhibited comparable primary endpoints (adjusted hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.55-1.55; P = 0.770) and bleeding endpoints (adjusted HR, 1.07; 95% CI, 0.63-1.81; P = 0.811). P2Y12 inhibitor monotherapy vs DAPT was associated with lower risk of BARC type 2 to 5 bleeding in women (adjusted HR, 0.40; 95% CI, 0.16-0.98; P = 0.045) but the difference was not statistically significant when using the Bonferroni correction. The primary endpoints were similar between treatment groups in both sexes. CONCLUSION: In both sexes undergoing PCI, P2Y12 inhibitor monotherapy after three months of DAPT achieved similar risks of the primary endpoints and the bleeding events compared with prolonged DAPT. Therefore, the benefits of early aspirin withdrawal with ongoing P2Y12 inhibitors may be comparable in women and men. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02079194.

Optimal Follow-up of Incidental Pancreatic Cystic Lesions without Worrisome Features: Clinical Outcome after Long-term Follow-up.

Background/Aims: : The optimal duration and interval of follow-up for cystic lesions of the pancreas (CLPs) is not well established. This study was performed to investigate the optimal duration and interval of follow-up for CLPs in clinical practice. Methods: : Patients with CLPs without worrisome features or high-risk stigmata underwent follow-up with computed tomography at 6, 12, 18, and 24 months and then every 12 months thereafter. A retrospective analysis of prospectively collected data was performed. Results: : A total of 227 patients with CLPs detected from 2000 to 2008 (mean initial diameter, 1.3±0.6 cm) underwent follow-up for a median of 120 months. Twenty-two patients (9.7%) underwent surgery after a median of 47.5 months. Malignancies developed in four patients (1.8%), one within 5 years and three within 10 years. One hundred and fourteen patients (50.2%) were followed up for more than 10 years. No malignancy developed after 10 years of follow-up. During surveillance, 37 patients (16.3%) experienced progression to surgical indication. In patients with CLPs less than 2 cm in diameter, development of surgical indications did not occur within 24 months of follow-up. Conclusions: : CLPs should be continuously monitored after 5 years because of the persistent potential for malignant transformation of CLPs. An interval of 24 months for initial follow-up might be enough for CLPs with initial size of less than 2 cm in clinical practice.