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Background Although many studies have investigated iatrogenic radial nerve palsy (RNP) in humerus shaft fracture, there is inconsistent evidence on which approach leads to iatrogenic RNP. Moreover, no meta-analysis has directly compared the anterolateral and posterior approaches regarding iatrogenic RNP. Methods In this systematic review and meta-analysis, the MEDLINE, Embase, and Cochrane Library databases were searched systematically for studies published before March 30, 2021. We included studies that (1) assessed the RNP in the surgical treatment of humerus shaft fracture and (2) directly compared the anterolateral and posterior approaches regarding the RNP. We performed synthetic analyses of the incidence of iatrogenic RNP and the recovery rate of iatrogenic RNP in humerus shaft fracture between the anterolateral and posterior approaches. Results Our study enrolled nine studies, representing 1303 patients who underwent surgery for humerus shaft fracture. After exclusion of traumatic RNP, iatrogenic RNP was reported in 35 out of 678 patients in the anterolateral approach and in 69 out of 497 patients in the posterior approach. Pooled analysis revealed that the incidence of iatrogenic RNP was significantly higher in the posterior approach than in the anterolateral approach (OR = 2.72; 95% confidence interval (CI), 1.70-4.35; P Conclusion In this meta-analysis, the posterior approach showed a higher incidence of iatrogenic RNP than the anterolateral approach in the surgical treatment of humerus shaft fracture. With limited studies, it is difficult to anticipate if any particular approach favors the recovery of iatrogenic RNP.

Cardiovascular disease is one of major causes of deaths, and its incidence has gradually increased worldwide. For cardiovascular diseases, several therapeutic approaches, such as drugs, cell-based therapy, and heart transplantation, are currently employed; however, their therapeutic efficacy and/or practical availability are still limited. Recently, biomaterial-based tissue engineering approaches have been recognized as promising for regenerating cardiac function in patients with cardiovascular diseases, including myocardial infarction (MI). In particular, materials mimicking the characteristics of native cardiac tissues can potentially prevent pathological progression and promote cardiac repair of the heart tissues post-MI. The mechanical (softness) and electrical (conductivity) properties of biomaterials as non-biochemical cues can improve the cardiac functions of infarcted hearts by mitigating myocardial cell death and subsequent fibrosis, which often leads to cardiac tissue stiffening and high electrical resistance. Consequently, electrically conductive hydrogels that can provide mechanical strength and augment the electrical activity of the infarcted heart tissue are considered new functional materials capable of mitigating the pathological progression to heart failure and stimulating cardiac regeneration. In this review, we highlight nanomaterial-incorporated hydrogels that can induce cardiac repair after MI. Nanomaterials, including carbon-based nanomaterials and recently discovered two-dimensional nanomaterials, offer great opportunities for developing functional conductive hydrogels owing to their excellent electrical conductivity, large surface area, and ease of modification. We describe recent results using nanomaterial-incorporated conductive hydrogels as cardiac patches and injectable hydrogels for cardiac repair. While further evaluations are required to confirm the therapeutic efficacy and toxicity of these materials, they could potentially be used for the regeneration of other electrically active tissues, such as nerves and muscles.

Rivaroxaban (RIV; Xarelto; Janssen Pharmaceuticals, Beerse, Belgium) is one of the direct oral anticoagulants. The drug is a strong substrate of cytochrome P450 (CYP) enzymes and efflux transporters. This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model for RIV. It contained three hepatic metabolizing enzyme reactions (CYP3A4, CYP2J2, and CYP-independent) and two active transporter-mediated transfers (P-gp and BCRP transporters). To illustrate the performance of the developed RIV PBPK model on the prediction of drug-drug interactions (DDIs), carbamazepine (CBZ) was selected as a case study due to the high DDI potential. Our study results showed that CBZ significantly reduces the exposure of RIV. The area under the concentration-time curve from zero to infinity (AUC

Since late preterm neonates are physiologically less mature than term neonates, the use of antenatal corticosteroids in the late preterm period has been recommended. The use of tocolytics can also be considered to gain valuable time for using antenatal corticosteroids in the late preterm period. In this study, we examined the efficacy of tocolytics on prolonging pregnancy in the late preterm period, by comparing women who received tocolytics with those who received none.This retrospective cohort study included women who were admitted due to preterm labor after 34 weeks of gestation and delivered in the late preterm period. Primary outcome was time from admission to delivery (days). Secondary outcomes were the proportion of preterm births within 2 days, and within 7 days, completed cycles of antenatal corticosteroids, and the neonatal outcomes. Primary and secondary outcomes were compared according to the use of tocolytics. Propensity score matching was performed to create comparable groups. The maternal age, pre-pregnancy body mass index, nulliparity, history of preterm birth, hypertensive disease during pregnancy, gestational diabetes mellitus, history of preterm labor, gestational age at admission, cervical length, and the number of contractions were the baseline characteristics included in the propensity score.Of 275 women, 44 women received tocolytics (tocolytics group) and 231 women did not (no tocolytics group). We matched 44 women who received tocolytics and 44 women who didn't. The tocolytics group was shown to exhibit a longer time from admission to delivery than the no tocolytics group, with a hazard ratio for tocolytics of 0.4 (95 % confidence interval, 0.2-0.6). In addition, the proportion of preterm births occurring within 2 days and 7 days were lower in those receiving tocolytics compared to those that didn't.In this propensity score matched-study, the use of tocolytics had a significant effect on pregnancy prolongation, which allows more time for use of corticosteroids in women with preterm labor after 34 weeks of gestation.

Rotavirus infection has been reported to be associated with neonatal seizures with a diffuse and symmetrical diffusion restriction of periventricular white matter, namely, neonatal rotavirus-associated leukoencephalopathy. The extensive white matter injury seen in this cohort raises concerns about the long-term neurodevelopmental outcomes. In the present study, we prospectively assessed the neurodevelopmental outcomes of 13 patients with neonatal rotavirus-associated leukoencephalopathy at a median age of 26 months (range, 23–68 months). Neurodevelopmental outcomes were evaluated using a neurological examination, developmental evaluations, and magnetic resonance imaging (MRI) of the brain. Overall, 6 of the 13 patients (46%) had abnormal neurodevelopmental outcomes: 1 patient had mental retardation, visual–motor integration (VMI) dysfunction, cerebral palsy, and epilepsy; 1 patient had cerebral palsy and VMI dysfunction; remaining 4 patients had VMI dysfunction. Follow-up MRI in 12 of 13 patients showed an increased signal intensity on periventricular white matter in all patients. These findings suggested that neonatal rotavirus-associated leukoencephalopathy could not be assumed to be benign in long-term neurodevelopment, particularly in VMI function. Early intervention and long-term follow-up are necessary for these patients. Our findings raise caution for rotavirus infection in this vulnerable population for infants.

Although mesoporous silica nanoparticles (MSNs) are widely used as anticancer drug carriers, unmodified MSNs induce off-target effects and at high doses, there are adverse effects of hemolysis because of the interaction with the silanol group on the surface and cells. In this study, we developed doxorubicin (DOX)-loaded MSNs coated with mannose grafted poly (acrylic acid) copolymer (DOX@MSNs-man-g-PAA) to enhance the hemocompatibility and target efficacy to cancer cells. This uniform nanosized DOX@MSNs-man-g-PAA showed sustained and pH-dependent drug release with improved hemocompatibility over the bare MSNs. The uptake of the DOX@MSN-man-g-PAA in breast cancer cells was significantly improved by mannose receptor-mediated endocytosis, which showed significant increasing intracellular ROS and changes in mitochondrial membrane potential. This formulation exhibited superior tumor-suppressing activity in the MDA-MB-231 cells inoculated mice. Overall, the present study suggested the possibility of the copolymer-coated MSNs as drug carriers for cancer therapy.

The impact of 1-month dual antiplatelet therapy (DAPT) followed by aspirin monotherapy according to clinical presentation has not been elucidated.This study aimed to compare the impact of 1-month DAPT followed by aspirin monotherapy after polymer-free drug-coated stent (PF-DCS) implantation (1-month DAPT after PF-DCS) vs 6-12-month DAPT followed by aspirin monotherapy after biodegradable polymer drug-eluting stent (BP-DES) implantation (6-12-month DAPT after BP-DES) according to clinical presentation.This is a post hoc analysis of the One-Month DAPT trial. The primary outcome was the composite of major adverse cardiac and cerebrovascular events (MACCE; a composite of cardiac death, non-fatal myocardial infarction, target vessel revascularisation, and stroke) and major bleeding.Among 1,828 patients with stable coronary artery disease (CAD), 1-month DAPT after PF-DCS resulted in lower rates of the primary outcome than 6-12-month DAPT after BP-DES (3.9% vs 6.5%; hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.39-0.90; p=0.012). However, among 1,192 patients with acute coronary syndrome (ACS), the rates of the primary outcome were not significantly different between the two therapy groups (5.6% vs 3.6%; HR 1.57, 95% CI: 0.91-2.70; p=0.102) and a significant interaction was observed between therapy and clinical presentation regarding the primary outcome (PIn patients undergoing drug-eluting stent implantation for non-complex lesions, the benefits of 1-month DAPT followed by aspirin monotherapy for a composite of ischaemic and bleeding outcomes were found in patients with stable CAD, but not in those with ACS.gov: NCT02513810.

The mechanisms of how cancer cells are selected and evolve to establish distant metastatic colonies remain unclear. Tumor heterogeneity and lack of biomarkers are some of the most difficult challenges in cancer biology and treatment. Here using mouse models for triple-negative breast cancer (TNBC) metastasis, we report heterogeneous expression of DNA methyltransferase 3B (DNMT3B) in both mouse and human primary tumors. High levels of DNMT3B were correlated with poor clinical outcomes in multiple human breast cancer datasets. Mechanistically, clonal cells with high DNMT3B (DNMT3BH) showed higher vimentin (VIM) expression and displayed enhanced epithelial-to-mesenchymal transition capacity. Deletion of VIM diminished the metastatic phenotype of DNMT3BH cells. Importantly, in preclinical mouse models in which the primary tumors were surgically removed, perioperative targeting of DNMT3B in combination with chemotherapy markedly suppressed tumor recurrence and metastasis. Our studies identify DNMT3B-mediated transcription regulation as an important mediator of tumor heterogeneity and show that DNMT3B is critical for tumor invasion and metastasis, reinforcing its potential as a target for treating metastatic disease. Implications: Our findings of transcriptome changes mediated by DNMT3B provide new mechanistic insight for intratumor heterogeneity and chemoresistance, and therapeutic targeting of DNMT3B in combination with chemotherapy offer additional treatment options for metastatic disease especially for patients with TNBC.

Metabolic syndrome is one factor known to contribute to the development of tendinopathies. The aim of this study was to compare the clinical outcomes of eccentric calf-muscle exercise for treatment of chronic insertional Achilles tendinopathy in patients with or without metabolic syndrome. Twenty-eight patients with chronic insertional Achilles tendinopathy and metabolic syndrome who performed eccentric calf-muscle exercise were retrospectively compared with 28 age- and sex-matched controls without metabolic syndrome. Comparisons between the 2 groups were made by evaluating the Visual Analog Scale for pain, patient satisfaction, and amount of pain medications needed during 3 months of follow-up. Two-way analysis of variance with repeated measures showed that the pain scales in the metabolic syndrome group were higher than those in the control group during the follow-up period (F[1,54] = 24.45, p.001). The patient satisfaction ratings were lower and the amount of required pain medication was higher in the metabolic syndrome group (p.001 and p.001, respectively). Eccentric calf-muscle exercises for chronic insertional Achilles tendinopathy were less effective in patients with metabolic syndrome. Therefore, these patients should be managed with a combination of other treatment modalities rather than eccentric exercise alone.

Oblique lumbar interbody fusion (OLIF) is known as a minimally invasive technique for disc space augmentation. Motor weakness after OLIF has been known to occur in some cases. This study aimed to report the incidence and potential risk factors for motor weakness following OLIF.We enrolled 36 patients and 57 segments who underwent OLIF. Computed tomography was performed before and after OLIF. Clinical data, including age, sex, presenting symptoms, bone mineral density, visual analog scale score, operating segments, and postoperative complications, were collected. We divided the patients into groups with and without neurologic deficit. The disc height was measured and compared between the 2 groups. We also divided the segments into groups with and without neurologic deficit. Foramen height and osteophyte length were measured and compared between the 2 groups.The neurologic deficit group included 3 patients (8%), whereas non-neurologic deficit group included 33 patients (92%). The neurologic deficit group included 5 segments (4%), whereas the non-neurologic deficit group included 109 segments (96%). The disc and foramen heights did not differ significantly between the groups with and without neurologic deficit; however, the osteophyte lengths were longer in the neurologic deficit group.In our study, vertebral osteophyte length was found to be a potential risk factor for motor weakness after OLIF. For patients with long osteophytes, additional laminectomy following OLIF or another surgical approach for direct decompression should be considered.

The prevalence of adrenal insufficiency (AI) is increasing with an increase in the elderly population. Steroid replacement therapy (SRT) is often required in patients with AI because of acute symptoms and complications. The long-term effects of SRT on kidney function have not been well elucidated.Overall, 788 patients diagnosed with AI between 2010 and 2015 at Yonsei University Health System were retrospectively evaluated. SRT was defined when an equivalent dose of ≥5 mg/d of hydrocortisone was initiated within 30 days of AI diagnosis and maintained for30 days. Those not included in the SRT group were identified as the no-SRT group. The primary outcome was 40% reduction in the estimated glomerular filtration rate compared with baseline sustained for ≥30 days or end-stage kidney disease development.The mean age of was 63.1 ± 15.4 years, and 43.0% were men. The SRT group comprised 387 patients. During a median follow-up duration of 4.1 years, the primary outcome occurred in 118 (15.0%) patients. The outcome incidence rate was higher in the SRT group (4.61/100 patient-years) than in the no-SRT group (2.76/100 patient-years). When the subdistribution hazard ratio for kidney outcome was assessed with death as a competing risk, the risk was 67% higher in the SRT group than in the no-SRT group (subdistribution hazard ratio, 1.67; 95% confidence interval, 1.16-2.45; P = .006). This association was maintained with inverse probability of treatment weighting and adjustment for confounding variables.Kidney function decline was more prominent in patients with AI who received SRT. Further prospective evaluations are needed to confirm these findings.

Hepatitis C virus (HCV) infection is the second most common cause of chronic liver disease in South Korea, with a prevalence ranging from 0.6% to 0.8%, and HCV infection incidence increases with age. The anti-HCV antibody test, which is cheaper than the HCV RNA assay, is widely used to screen for HCV infections; however, the underdiagnosis of HCV is a major barrier to the elimination of HCV infections. Although several risk factors have been associated with HCV infections, including intravenous drug use, blood transfusions, and hemodialysis, most patients with HCV infections present with no identifiable risk factors. Universal screening for HCV in adults has been suggested to improve the detection of HCV infections. We reviewed the cost-effectiveness of HCV screening and the methodologies used to perform screening. Recent studies have suggested that universal HCV screening and treatment using direct-acting antivirals represent cost-effective approaches to the prevention and treatment of HCV infection. However, the optimal timing and frequency of HCV screening remain unclear, and further studies are necessary to determine the best approaches for the elimination of HCV infections.

This study aimed to investigate the macrophage migration inhibitory factor (MIF) and associated clinical factors in neonates. Clinical information and blood samples were obtained from 77 neonates. Clinical details were reviewed from medical records, and MIF was measured by enzyme-linked immunosorbent assay using blood samples acquired within a week after birth. Statistical analyses were performed between plasma MIF concentration and clinical factors. Among the 77 newborn infants, 25 were born at34 weeks of gestation (preterm), 25 at 34 to 37 weeks (late preterm), and 27 at term gestation. The mean MIF was 9849.5 ± 7187.8 pg/mL in preterm, 5718.7 ± 4596.4 in late preterm, and 5361.1 ± 3895.7 in term infants (P = .016). Among 25 preterm infants born at34 weeks of gestation, MIF was significantly higher in infants with necrotizing enterocolitis (NEC, 19,478.6 ± 8162.4 pg/mL, n = 5) than that in infants without NEC (feeding intolerance 7173.7 ± 4203.0 pg/mL, n = 12 and others 7844.9 ± 5311.2 pg/mL, n = 8, P = .020). Elevated plasma MIF levels in the transitional period were significantly associated with preterm birth before 34 weeks of gestation and the development of NEC.

Dysphagia is one of the main serious issues for amyotrophic lateral sclerosis (ALS) patients because of causing malnutrition and aspiration pneumonia. Early detection and management of dysphagia are essential for the long-term survival. In this study, videofluoroscopic swallowing study (VFSS) results of bulbar and spinal onset ALS patients were compared. VFSS results and revised ALS Functional Rating Scale (ALSFRS-R) score were also analyzed to assess the correlation between dysphagia and functional status of patients. ALS patients with swallowing difficulties who underwent VFSS were recruited retrospectively. Two oral, seven pharyngeal, and two esophageal components of VFSS were evaluated. An ALSRFRS-R bulbar subtype score 9 was used to divide the groups with severe bulbar symptoms. Total 109 Korean ALS patients (39 bulbar vs 70 spinal) were included. Bulbar ALS patients exhibited a significantly longer oral transit time (OTT) then spinal ALS patients, especially in severe bulbar patients with low ALSRFRS-R bulbar subscale. In bulbar ALS patients, penetration (thick liquid), aspiration, OTT, and Penetration-Aspiration Scale (PAS) were significantly correlated with ALSFRS-R bulbar subscale score. However, in spinal ALS patients, only OTT (thin liquid) and aspiration (thick liquid) were significantly correlated with ALSFRS-R bulbar subscale score. Bulbar ALS patients demonstrated significantly longer OTT than spinal ALS patients, and ALSFRS-R bulbar subscale score also correlated well with bulbar ALS patients. Therefore, high vigilance and aggressive treatment for dysphagia especially in bulbar ALS patients rather than spinal ALS patients are mandatory.

Corilagin (CLG) is a hydrolyzable tannin and possesses various pharmacological activities. Here, we investigated the impact of CLG as an anti-tumor agent against human gastric tumor cells. We observed that CLG could cause negative regulation of JAKs-Src-STAT3/5 signaling axis in SNU-1 cells, but did not affect these pathways in SNU-16 cells. Interestingly, CLG promoted the induction of mitogen-activated protein kinases (MAPKs) signaling pathways in only SNU-16 cells, but not in the SNU-1 cells. CLG exhibited apoptotic effects that caused an increased accumulation of the cells in sub-G1 phase and caspase-3 activation in both SNU-1 and SNU-16 cell lines. We also noticed that CLG and docetaxel co-treatment could exhibit significantly enhanced apoptotic effects against SNU-1 cells. Moreover, the combinations treatment of CLG and docetaxel markedly inhibited cell growth, phosphorylation of JAK-Src-STAT3 and induced substantial apoptosis. Additionally, pharmacological inhibition of JNK, p38, and ERK substantially blocked CLG-induced activation of MAPKs, cell viability, and apoptosis, thereby implicating the pivotal role of MAPKs in the observed anti-cancer effects of CLG. Taken together, our data suggest that CLG could effectively block constitutive STAT3/5 activation in SNU-1 cells but induce sustained MAPKs activation in SNU-16 cells.

Background/Aims: The objective of this study was to determine whether the newly developed two-dimensional shear wave elastography (2D-SWE, RS85, Samsung-shearwave imaging) was more valid and reliable than transient elastography (TE) for predicting the stage of liver fibrosis.Methods: The study prospectively enrolled a total of 116 patients with chronic liver disease who underwent 2D-SWE, TE, laboratory testing, and liver biopsy on the same day from two tertiary care hospitals. One patient with unreliable measurement was excluded. The measurement of 2D-SWE was considered acceptable when a homogenous color pattern in a region of interest of at least 10 mm was detected at 10 different sites. Diagnostic performance was calculated using area under the receiver operating characteristic curve (AUROC).Results: Liver fibrosis stages included F0 (18%), F1 (19%), F2 (24%), F3 (22%), and F4 (17%). Interclass correlation coefficient for inter-observer agreement in 2D-SWE was 0.994 (95% confidence interval [CI], 0.988 to 0.997). Overall, the results of 2D-SWE and stages of histological fibrosis were significantly correlated (r = 0.601, p < 0.001). For The 2D-SWE showed good diagnostic ability (AUROC, 0.851; 95% CI, 0.773 to 0.911) comparable to TE (AUROC, 0.859; 95% CI, 0.781 to 0.916) for the diagnosis of significant fibrosis (≥ F2), and the cut-off value was 5.8 kPa. AUROC and optimal cut-off of 2D-SWE for the diagnosis of liver cirrhosis were 0.889 (95% CI, 0.817 to 0.940) and 9.6 kPa, respectively. TE showed similar diagnostic performance in distinguishing cirrhosis (AUROC, 0.938; 95% CI, 0.877 to 0.974; p = 0.08).Conclusions: 2D-SWE is comparable to TE in diagnosing significant fibrosis and liver cirrhosis with high reliability.

Background/Aims: Drugs with anticholinergic properties (DAPs) are associated with adverse health outcomes in older patients. The objective of this study was to evaluate the factors that determine the prescribing of more DAPs in long-term care hospitals (LTCHs) in Korea. In addition, the current patterns of DAP prescription were explored using a novel platform, which can collect data from LTCHs.Methods: This was a Health-RESPECT (integrated caRE Systems for elderly PatiEnts using iCT) sub-study, which is a pragmatic, cluster-randomized, controlled trial. The Health-RESPECT platform was used to collect prescribed medication data of 466 patients (aged ≥ 65 years) from seven LTCHs. DAPs were identified using the Korean Anticholinergic Burden Scale (KABS). Physical frailty, cognitive function, functional status, and quality of life were evaluated.Results: Among 466 LTCH patients, 88.8% (n = 414) were prescribed DAPs, and the prevalence of high KABS (≥ 3) was 70.4% (n = 328). The drugs that contributed most to the total KABS were quetiapine (20.7%), chlorpheniramine (19.5%), tramadol (9.8%), cimetidine (5.8%), and furosemide (3.6%). Polypharmacy, higher body mass index, less dependence, better communication and cognitive functions, and poorer quality of life were associated with high KABS.Conclusions: Although the patients with a high burden of DAPs were less dependent and had better cognitive and communication functions, they had poorer quality of life. DAP use in LTCH patients should be monitored carefully, and the risk/ benefit relationship for their use should be considered.

Because of paucity of published data, we evaluated the 2-year major clinical outcomes between early invasive (EI) and delayed invasive (DI) strategies according to the stage of chronic kidney disease (CKD) in patients with non-ST-segment elevation myocardial infarction (NSTEMI), who underwent a successful newer-generation drug-eluting stent (DES) implantation.A total of 8241 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry (KAMIR). Based on baseline estimated glomerular filtration rate (eGFR; ≥90, 60-89, 30-59, and30 mL/min/1.73 mAfter multivariable-adjusted and propensity score-adjusted analyses, the cumulative incidence of MACE (group A, p = 0.139 and p = 0.103, respectively; group B, p = 0.968 and p = 0.608, respectively; group C, p = 0.111 and p = 0.196, respectively; group D, p = 0.882 and p = 0.571, respectively), all-cause death, re-MI, and any repeat revascularization was similar between the EI and DI groups in the 4 different renal function groups.In the era of newer-generation DES, EI and DI strategies showed comparable major clinical outcomes in patients with NSTEMI and CKD during a 2-year follow-up period. However, to confirm these results, further randomized, large-scale, long-term follow-up studies are needed.

Background The Phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control; randomized 2:1 to olaparib or control) in men with homologous recombination repair gene alterations and metastatic castration-resistant prostate cancer whose disease progressed on prior next-generation hormonal agent. Methods We present efficacy and safety data from an exploratory post hoc analysis of olaparib in the PROfound Asian subset. Analyses were not planned, alpha controlled or powered. Of 101 Asian patients enrolled in Japan (n=57), South Korea (n=29) and Taiwan (n=15), 66 and 35 patients received olaparib and control, respectively. Results Radiographic progression-free survival (rPFS) and overall survival (OS) favored olaparib versus control in Cohort A [rPFS 7.2 vs. 4.5 months, HR 0.58, 95% CI 0.29–1.21, P = 0.14 (nominal); OS 23.4 vs. 17.8 months, HR 0.81, 95% CI 0.40–1.74, P = 0.57 (nominal)] and Cohorts A+B [rPFS 5.8 vs. 3.5 months, HR 0.69, 95% CI 0.42–1.16, P = 0.13 (nominal); OS 18.6 vs. 16.2 months, HR 0.96, 95% CI 0.56–1.70, P = 0.9 (nominal)]. Olaparib showed greatest improvement in patients harboring BRCA alterations [rPFS 9.3 vs. 3.5 months, HR 0.17, 95% CI 0.06–0.49, P = 0.0003 (nominal); OS 26.8 vs. 14.3 months, HR 0.62, 95% CI 0.24–1.79, P = 0.34 (nominal)]. Safety data were consistent with the known profile of olaparib, with no new safety signals identified. Conclusion In PROfound, there was a statistically significant improvement in outcomes reported in the global population of patients with metastatic castration-resistant prostate cancer and alterations in homologous recombination repair genes whose disease progressed on prior next-generation hormonal agent compared with control. For the subset of Asian patients reported here, exploratory analysis suggested that there was also an improvement in outcomes versus control. The safety and tolerability of olaparib in Asian patients were similar to that of the PROfound global population. Clinical trial number ClinicalTrials.gov NCT02987543

Ten days after receiving the first dose of coronavirus disease vaccine, a 22-year-old woman in South Korea experienced myocarditis, myopathy, pericarditis, and gastroenteritis; rash subsequently developed. There was no evidence of prior infection with severe acute respiratory syndrome coronavirus 2. The diagnosis was multisystem inflammatory syndrome resulting from coronavirus disease vaccination.

Purpose Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.Materials and Methods Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.Results Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Sonodynamic therapy has shown promise as an effective alternative to conventional photodynamic therapy owing to its ability to treat deep-seated tumors. However, the development of stimuli-responsive sonosensitizers with high biocompatibility faces a significant challenge.

We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 weeks], 11.7 ± 8.2 kPa [96 weeks], 10.09 ± 6.23 [144 weeks], all p Clinical trials registration: ClinicalTrials.gov (NCT02865369).

Background Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock. Methods This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. Results Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61–0.99; p = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44–0.99; p = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64–1.15; p = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. Conclusion Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

Femoral head fracture is a rare type of fracture commonly associated with hip dislocation. Femoral head fracture treatments include conservative treatment, fragment excision, open reduction, internal fixation, and arthroplasty. In cases of young patients, open reduction and internal fixation are preferred over arthroplasty. Pipkin type 2 fractures are treated with open reduction and internal fixation in most cases because the fracture line extends upward of the fovea and includes the femoral head-acetabular weight-bearing joint surface. However, if the fracture is severely comminuted or crushed, good results are difficult to obtain with open reduction and internal fixation.A 23-years-old male patient presented to the emergency room with right hip pain after 4-m fall.In initial image work up, he was diagnosed with right posterior hip dislocation and a Pipkin type 2 femoral head fracture with an ipsilateral superior ramus fracture. After manual reduction, simple radiography and computed tomography showed reduction of the hip joint and a large osteochondral defect of approximately 6 cm2 in the weight-bearing area on the superomedial side of the femoral head.This was treated with a novel surgery named autologous osteochondral transplantation (repositionplasty), devised by the authors.The congruent reduction was confirmed by radiography and computed tomography immediately after the surgery. At 5 years postoperatively, the Harris Hip Score was 100 points and no discomfort, femoral head collapse, osteonecrosis, or traumatic arthritis were observed on follow-up radiographs.We think this method "repositionplasty" will be a good treatment method for young patients with a large defect in the weight-bearing part of the femoral head who cannot undergo open reduction and internal fixation.

BackgroundPrehospital delay is an important contributor to poor outcomes in both acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We aimed to compare the prehospital delay and related factors between AIS and AMI.Methods and ResultsWe identified patients with AIS and AMI who were admitted to the 11 Korean Regional Cardiocerebrovascular Centers via the emergency room between July 2016 and December 2018. Delayed arrival was defined as a prehospital delay of >3 hours, and the generalized linear mixed‐effects model was applied to explore the effects of potential predictors on delayed arrival. This study included 17 895 and 8322 patients with AIS and AMI, respectively. The median value of prehospital delay was 6.05 hours in AIS and 3.00 hours in AMI. The use of emergency medical services was the key determinant of delayed arrival in both groups. Previous history, 1‐person household, weekday presentation, and interhospital transfer had higher odds of delayed arrival in both groups. Age and sex had no or minimal effects on delayed arrival in AIS; however, age and female sex were associated with higher odds of delayed arrival in AMI. More severe symptoms had lower odds of delayed arrival in AIS, whereas no significant effect was observed in AMI. Off‐hour presentation had higher and prehospital awareness had lower odds of delayed arrival; however, the magnitude of their effects differed quantitatively between AIS and AMI.ConclusionsThe effects of some nonmodifiable and modifiable factors on prehospital delay differed between AIS and AMI. A differentiated strategy might be required to reduce prehospital delay.

To analyze the clinical presentation and outcomes of myocarditis after administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccine. Nine case series and 15 case reports (74 patients) of myocarditis after administration of the BNT162b2 or mRNA-1273 vaccine were reviewed from PubMed, Scopus, Embase, and Web of Science. We analyzed clinical manifestations, diagnostic findings, and outcomes. In addition, we performed a pooled analysis and investigated risk factors leading to admission to the intensive care unit and recovery with conservative care. Most patients were male (94.6%), and the median age (range) was 17.6 (14–70) years. Patients who received the BNT162b2 (n = 58, 78.4%) vaccine presented fewer systemic symptoms and left ventricular dysfunction than mRNA-1273 recipients. Although patients under 20 years experienced more fever and myalgia, they had better ejection fraction and less prominent myocardial inflammation in magnetic resonance imaging than older patients. The clinical course of all patients was favorable without mortality, and one-third of patients resolved with conservative care alone. Risk factor analyses revealed that patients with gastrointestinal symptoms required intensive care (odds ratio: 20.3, 95% confidence interval 1.90–217, p = 0.013). The risk of fatality in myocarditis subjected to mRNA vaccination seems to be low. However, patients with gastrointestinal symptoms received more intensive care, and a significant proportion of patients recovered with conservative management.

BACKGROUND AND AIM Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. METHODS This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. RESULTS A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P

People make decisions based on deviations from expected outcomes, known as prediction errors. Past work has focused on reward prediction errors, largely ignoring violations of expected emotional experiences—emotion prediction errors. We leverage a method to measure real-time fluctuations in emotion as people decide to punish or forgive others. Across four studies (N = 1,016), we reveal that emotion and reward prediction errors have distinguishable contributions to choice, such that emotion prediction errors exert the strongest impact during decision-making. We additionally find that a choice to punish or forgive can be decoded in less than a second from an evolving emotional response, suggesting that emotions swiftly influence choice. Finally, individuals reporting significant levels of depression exhibit selective impairments in using emotion—but not reward—prediction errors. Evidence for emotion prediction errors potently guiding social behaviours challenge standard decision-making models that have focused solely on reward. Heffner et al. show that violations of emotion expectations—emotion prediction errors—motivate social choice, such as punishing norm transgressors. Emotion prediction errors often outperformed reward prediction errors in predicting choice and were selectively impaired in those at risk of depression.

Cytochrome P450 1A1 (CYP1A1) is a member of a subfamily of enzymes involved in the metabolism of both endogenous and exogenous substrates and the chemical activation of xenobiotics to carcinogenic derivatives. Here, the effects of nicotine, a major psychoactive compound present in cigarette smoke, on CYP1A1 expression and human hepatocellular carcinoma (HepG2) cell proliferation were investigated. Nicotine stimulated CYP1A1 expression via the transcription factors, activator protein 1, nuclear factor-kappa B, and the aryl hydrocarbon receptor (AhR) signaling pathway. Pharmacological inhibition and mutagenesis studies indicated that p38 mitogen-activated protein kinase, as well as RelA (or p65), mediated the upregulation of CYP1A1 of nicotine in HepG2 cells. The antioxidant compound, N-acetyl-cysteine, abrogated nicotine-activated production of reactive oxygen species and inhibited CYP1A1 expression by nicotine. Furthermore, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was inhibited by diphenyleneiodonium (an NADPH oxidase inhibitor). Thus, these results demonstrated that AhR played an important role in nicotine-induced CYP1A1 expression. Additionally, liver hepatocellular carcinoma HepG2 cells treated with nicotine exhibited markedly enhanced proliferation via CYP1A1 expression and Akt activation.

The presence of tumor deposits (TDs) in colorectal cancer is associated with a poor prognosis. In patients with the concomitant presence of both TDs and lymph nodes (LNs), there is no staging option except for the number of positive LNs alone. Therefore, to determine the prognostic value of TDs in patients with stage III colorectal cancer, meta-analyses of survival outcomes of patients with TDs were performed comparing different subgroups based on the lymph node status. PubMed, EMBASE, and the Cochrane Library were searched. Data were pooled, and overall effect size was calculated using random-effect models. Outcome measures were 5-year overall survival (OS) and 5-year disease-free survival (DFS). We included in the analysis 18 nonrandomized studies and 1 prospective study that examined 90,455 patients. N1c patients (TD + LN-) had worse 5-year DFS than TDs-negative stage III patients (TD-LN +) with a RR of 1.30 (95% CI 1.06–1.61, I2 = 47%). In subgroup analysis, N1c patients had worse 5-year DFS (RR = 1.60, 95% CI = 1.25–2.05, I2 = 40%) compared with TDs-negative N1 patients (TD-N1) whereas N1c patients had better 5-year OS (RR = 0.72, 95% CI = 0.62–0.83, I2 = 0%) and 5-year DFS (RR = 0.75, 95% CI = 0.57–0.99, I2 = 0%) compared with TDs-negative N2 patients (TD-N2). These results may suggest that current nodal staging for colorectal cancer needs modification. The presence of TDs may have more adverse oncologic outcomes than TDs-negative N1 patients. More studies are warranted to further verify these results.

Owing to the increasing trend of preserving fertility in adenomyomectomy, the need for laparoscopic adenomyomectomy has increased. This study aimed to introduce a new surgical technique, an advanced laparoscopic adenomyomectomy technique, and to evaluate its efficacy, benefits, and safety in focal uterine adenomyosis.From February 1, 2019 to February 29, 2020, 47 patients who underwent laparoscopic adenomyomectomy using the new surgical technique were enrolled in the study. The inclusion criteria were: (1) Focal-type adenomyosis, diagnosed by ultrasound or magnetic resonance imaging that was refractory to medical treatments. (2) A strong desire to preserve the uterus. All the operations were performed by a single surgeon with a uniform technique.The mean patient age was 40.53 ± 5.93 years (median 38.5, range 32-47). The mean diameter of the adenomyoma lesions was 4.57 ± 1.21 cm and the mean weight of the excised lesions was 40.53 ± 35.65g (range, 15-209 g). The mean total operation time was 70.11 ± 15.05 minutes. The mean estimated blood loss was 88.88 ± 20.0 mL (20 - 500 ml). There was no conversion to laparotomy or major complications requiring reoperation. At the seven-month follow-up, there was complete remission of dysmenorrhea and menorrhagia in 97.4% and 88.9% of the patients, respectively.The new advanced laparoscopic adenomyomectomy technique with a three-step approach could be a safe and effective therapeutic method.

Background Prolonged emergency department length of stay (EDLOS) in critically ill patients leads to increased mortality. This nationwide study investigated patient and hospital characteristics associated with prolonged EDLOS and in-hospital mortality in adult patients admitted from the emergency department (ED) to the intensive care unit (ICU). Methods We conducted a retrospective cohort study using data from the National Emergency Department Information System. Prolonged EDLOS was defined as an EDLOS of ≥ 6 h. We constructed multivariate logistic regression models of patient and hospital variables as predictors of prolonged EDLOS and in-hospital mortality. Results Between 2016 and 2019, 657,622 adult patients were admitted to the ICU from the ED, representing 2.4% of all ED presentations. The median EDLOS of the overall study population was 3.3 h (interquartile range, 1.9–6.1 h) and 25.3% of patients had a prolonged EDLOS. Patient characteristics associated with prolonged EDLOS included night-time ED presentation and Charlson comorbidity index (CCI) score of 1 or higher. Hospital characteristics associated with prolonged EDLOS included a greater number of staffed beds and a higher ED level. Prolonged EDLOS was associated with in-hospital mortality after adjustment for selected confounders (adjusted odds ratio: 1.18, 95% confidence interval: 1.16–1.20). Patient characteristics associated with in-hospital mortality included age ≥ 65 years, transferred-in, artificially ventilated in the ED, assignment of initial triage to more urgency, and CCI score of 1 or higher. Hospital characteristics associated with in-hospital mortality included a lesser number of staffed beds and a lower ED level. Conclusions In this nationwide study, 25.3% of adult patients admitted to the ICU from the ED had a prolonged EDLOS, which in turn was significantly associated with an increased in-hospital mortality risk. Hospital characteristics, including the number of staffed beds and the ED level, were associated with prolonged EDLOS and in-hospital mortality.

Background Ureteral reconstruction is required after surgical resection of the tumor invading the urinary tract in ovarian cancer with low incidence. There are no currently reported surgical outcomes of ureteral reconstruction during cytoreductive surgery. The aim of the study is to investigate the clinical features and surgical outcomes of ureteral reconstruction during primary, interval and secondary cytoreductive surgery for ovarian cancer. Methods A total of 3226 patients who underwent primary, interval or secondary cytoreductive surgery for ovarian cancer between January 2000 and May 2021 were reviewed. Fifty-six patients who underwent ureteral reconstruction during cytoreductive surgery were included in the analysis. Results Ureteral reconstruction was required in 1.7% (56/3226) of ovarian cancer patients. Of the 56 patients who underwent ureteral reconstruction during cytoreductive surgery, 35 (62.5%) had primary ovarian cancer, and 21 (37.5%) had recurrent ovarian cancer. The median tumor size invading the lower urinary tract was 2.0 cm (range, 0.4–9.5 cm). Ureteroneocystostomy with direct implantation (51.8%) and psoas hitch (8.9%), transureteroureterostomy (7.1%), and ureteroureterostomy (32.1%) were required as part of cytoreductive surgery. Complete cytoreduction with ureteral reconstruction was achieved in 83.9% (47/56) and the rest of the patient population (16.1%) achieved a gross residual tumor size of less than 1 cm. All complications, including hydronephrosis (33.9%), were managed, none resulting in long-term sequelae. In primary ovarian cancer, the 5-year disease-free survival and overall survival were 50.0% and 89.5%, respectively. In patients with recurrent ovarian cancer, the 5-year disease-free survival and overall survival were 23.6% and 64.0%, respectively. Conclusions Ureteral reconstruction as a part of cytoreductive surgery for ovarian cancer could be performed with acceptable morbidities. Complete cytoreduction by a multidisciplinary surgical team, including urologic oncologists, should be pursued for the surgical management of ovarian cancer. Trial registration Retrospectively registered.

BACKGROUND In elderly patients, spinal anesthesia-induced hypotension (SAH) can be frequently caused by reduced preload and stiff ventricles. The primary purpose of this study was to investigate the ability of ultrasonographic carotid artery flow measurements during the passive leg raise (PLR) test to predict SAH in elderly patients. The correlation between preoperative transthoracic echocardiography (TTE) measurements and SAH was also investigated. MATERIAL AND METHODS The patients aged over 65 years scheduled for elective surgery under spinal anesthesia were recruited. Preoperative TTE was performed in all patients. Corrected carotid flow time and carotid blood flow were measured in the supine, semirecumbent, and PLR positions. Ultrasonographic carotid artery flow and preoperative TTE measurements were compared between patients who developed SAH and those who did not. Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to test the association with SAH. RESULTS SAH occurred in 17 of 50 patients. Carotid blood flow in the semirecumbent position and preoperative mitral inflow E velocity could predict SAH, showing an area under the ROC curve of 0.754 (95% CI, 0.612-0.865) and 0.775 (95% CI, 0.634-0.881), respectively. However, according to the multivariate analysis, the independent risk factor for SAH was mitral inflow E velocity (OR 0.918, 95% CI 0.858-0.982, P=0.013). CONCLUSIONS In elderly patients, ultrasonographic carotid artery flow measurements failed to predict the occurrence of SAH. Only preoperative mitral inflow E velocity of TTE was selected as an independent risk factor for SAH.

Methicillin-resistant

Background DAX1 mutations are related to the X-linked form of adrenal hypoplasia congenita (AHC) in infancy and to hypogonadotropic hypogonadism (HH) in puberty. We report a male patient affected by X-linked AHC who presented with central diabetes insipidus and schwannoma in adulthood, which has not been described in association with AHC. Case presentation A 36-day-old male infant who presented with severe dehydration was admitted to the intensive care unit. His laboratory findings showed hyponatremia, hyperkalemia, hypoglycemia, and metabolic acidosis. After hormonal evaluation, he was diagnosed with adrenal insufficiency, and he recovered after treatment with hydrocortisone and a mineralocorticoid. He continued to take hydrocortisone and the mineralocorticoid after discharge. At the age of 17, he did not show any signs of puberty. On the basis of a GnRH test, a diagnosis of HH was made. At the age of 24, he was hospitalized with thirst, polydipsia and polyuria. He underwent a water deprivation test for polydipsia and was diagnosed with central diabetes insipidus. By quantitative polymerase chain reaction analysis, we identified a hemizygous frameshift mutation in DAX1 (c.543delA). Conclusions We suggest that DAX1 mutations affect a wider variety of endocrine organs than previously known, including the posterior pituitary gland.

There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI.Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed.Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMIAIS; for EMS use, AMIAIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI.Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Objectives Ginkgolide C (GGC) isolated from Ginkgo biloba (Ginkgoaceae) leaf can demonstrate pleiotropic pharmacological actions. However, its anti-oncogenic impact in non-small cell lung cancer (NSCLC) model has not been reconnoitered. As signal transducer and activator of transcription 3 (STAT3) cascade can promote tumour growth and survival, we contemplated that GGC may interrupt this signalling cascade to expend its anti-cancer actions in NSCLC. Methods The effect of GGC on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation and apoptosis was examined. The in-vivo effect of GGC on the growth of human NSCLC xenograft tumours in athymic nu/nu female mice was also investigated. Key findings GGC attenuated the phosphorylation of STAT3 and STAT3 upstream kinases effectively. Exposure to pervanadate modulated GGC-induced down-regulation of STAT3 activation and promoted an elevation in the level of PTPε protein. Indeed, silencing of the PTPε gene reversed the GGC-promoted abrogation of STAT3 activation and apoptosis. Moreover, GGC exposure significantly reduced NSCLC tumour growth without demonstrating significant adverse effects via decreasing levels of p-STAT3 in mice tissues. Conclusions Overall, the findings support that GGC may exhibit anti-neoplastic actions by mitigation of STAT3 signalling cascade in NSCLC.