CHA University Bundang Medical Center

Abstract Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced cancers. However, the tumor microenvironment (TME) functions as a formidable barrier that severely impairs the efficacy of ICIs. While the crosstalk between tumor vessels and immune cells determines the nature of anti-tumor immunity, it is skewed toward a destructive cycle in growing tumors. First, the disorganized tumor vessels hinder CD8 + T cell trafficking into the TME, disable effector functions, and even kill T cells. Moreover, VEGF, the key driver of angiogenesis, interferes with the maturation of dendritic cells, thereby suppressing T cell priming, and VEGF also induces TOX-mediated exhaustion of CD8 + T cells. Meanwhile, a variety of innate and adaptive immune cells contribute to the malformation of tumor vessels. Protumoral M2-like macrophages as well as T H 2 and Treg cells secrete pro-angiogenic factors that accelerate uncontrolled angiogenesis and promote vascular immaturity. While CD8 + T and CD4 + T H 1 cells suppress angiogenesis and induce vascular maturation by secreting IFN-γ, they are unable to infiltrate the TME due to malformed tumor vessels. These findings led to preclinical studies that demonstrated that simultaneous targeting of tumor vessels and immunity is a viable strategy to normalize aberrant vascular-immune crosstalk and potentiate cancer immunotherapy. Furthermore, this combination strategy has been evidently demonstrated through recent pivotal clinical trials, granted approval from FDA, and is now being used in patients with kidney, liver, lung, or uterine cancer. Overall, combining anti-angiogenic therapy and ICI is a valid therapeutic strategy that can enhance cancer immunity and will further expand the landscape of cancer treatment.

OBJECTIVE: The 'Atrial fibrillation Better Care' (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with atrial fibrillation (AF). We performed a systematic review of current evidence for the use of the ABC pathway on clinical outcomes. METHODS AND RESULTS: We performed a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched for studies reporting the prevalence of ABC-pathway-adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Meta-analysis of odds ratio (OR) was performed with random-effects models; subgroup analysis and meta-regression were performed to account for heterogeneity. Among the eight studies included, we found a pooled prevalence of ABC-adherent management of 21% (95% confidence interval, CI: 13-34%), with a high grade of heterogeneity, explained by the increasing adherence to each ABC criterion. Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR: 0.42; 95% CI: 0.31-0.56), cardiovascular death (OR: 0.37; 95% CI: 0.23-0.58), stroke (OR: 0.55; 95% CI: 0.37-0.82) and major bleeding (OR: 0.69; 95% CI: 0.51-0.94), with moderate heterogeneity. Prevalence of comorbidities was moderators of heterogeneity for all-cause and cardiovascular death, while longer follow-up was associated with increased effectiveness for all outcomes. CONCLUSION: Adherence to the ABC pathway was suboptimal, being adopted in one in every five patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes.

BACKGROUND: Procedural results for percutaneous coronary intervention (PCI) in coronary vessels with chronic total occlusion (CTO) have improved in recent years, and PCI strategies have moved toward more complete revascularization with more liberal use of CTO-PCI. However, evidence evaluating CTO-PCI is limited to observational studies and small clinical trials. METHODS: In this open-label, multicenter, randomized, noninferiority trial, PCI-eligible patients were assigned to receive either 1 of 2 strategies: PCI or no PCI for the qualifying de novo CTO lesion with the option for PCI of obstructive non-CTO lesions at the discretion of the operator. The primary end point was a composite of death, myocardial infarction, stroke, or any revascularization. Health-related quality of life was assessed at baseline and at 1, 6, 12, 24, and 36 months. Because of slow recruitment, the trial was stopped before completion of the 1284 planned enrollments. RESULTS: Between March 2010 and September 2016, 834 patients were randomly assigned to the CTO-PCI (n=417) or no CTO-PCI (n=398) strategy. Among the patients assigned to the no CTO-PCI strategy, 78 (19.6%) crossed over to receive staged CTO-PCI within 3 days of randomization. The overall CTO-PCI success rate was 90.6%. Serious nonfatal complications associated with CTO-PCI occurred in 3 patients (1 stroke, 1 cardiac tamponade, and 1 patient with recurrent episodes of ventricular tachyarrhythmia induced by intracoronary thrombus). Approximately half of the patients in each group underwent PCI for an average of 1.3 non-CTO lesions, resulting in a comparable residual SYNTAX score (Synergy Between PCI With TAXUS and Cardiac Surgery; 3.7±5.4 versus 4.0±5.9, P=0.42) confined to non-CTO vessels. During a median follow-up of 4.0 years (interquartile range, 2.4 to 5.1 years), there was no significant difference between the CTO-PCI and the no CTO-PCI strategies in the incidence of the primary end point (22.3% versus 22.4%, hazard ratio, 1.03; 95% CI, 0.77 to 1.37; P=0.86). Both CTO-PCI and no CTO-PCI strategy were associated with significant improvements but without between-group differences in disease-specific health status that was sustained through 36 months. CONCLUSIONS: CTO-PCI was feasible with high success rates. There was no difference in the incidence of major adverse cardiovascular events with CTO-PCI versus no CTO-PCI, but the study was limited by low power for clinical end points and high crossover rates between groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01078051.

Embryonic stem cells hold great promise for various diseases because of their unlimited capacity for self-renewal and ability to differentiate into any cell type in the body. However, despite over 3 decades of research, there have been no reports on the safety and potential efficacy of pluripotent stem cell progeny in Asian patients with any disease. Here, we report the safety and tolerability of subretinal transplantation of human embryonic-stem-cell (hESC)-derived retinal pigment epithelium in four Asian patients: two with dry age-related macular degeneration and two with Stargardt macular dystrophy. They were followed for 1 year. There was no evidence of adverse proliferation, tumorigenicity, ectopic tissue formation, or other serious safety issues related to the transplanted cells. Visual acuity improved 9-19 letters in three patients and remained stable (+1 letter) in one patient. The results confirmed that hESC-derived cells could serve as a potentially safe new source for regenerative medicine.

Deregulation of the cyclin D-CDK4/6-INK4-RB pathway leading to uncontrolled cell proliferation, is frequently observed in breast cancer. Currently, three selective CDK4/6 inhibitors have been FDA approved: palbociclib, ribociclib and abemaciclib. Despite promising clinical outcomes, intrinsic or acquired resistance to CDK4/6 inhibitors has limited the success of these treatments; therefore, the development of various strategies to overcome this resistance is of great importance. We highlight the various mechanisms that are directly or indirectly responsible for resistance to CDK4/6 inhibitors, categorizing them into two broad groups; cell cycle-specific mechanisms and cell cycle-nonspecific mechanisms. Elucidation of the diverse mechanisms through which resistance to CDK4/6 inhibitors occurs, may aid in the design of novel therapeutic strategies to improve patient outcomes. This review summarizes the currently available knowledge regarding mechanisms of resistance to CDK4/6 inhibitors, and possible therapeutic strategies that may overcome this resistance as well.

Tumor cells escape the immune surveillance system of the host through a process called immune tolerance. Immunotherapy targets molecules that serve as checks and balances in the regulation of immune response. Indoleamine-2,3-dioxygenase (IDO) is an intracellular enzyme, which through the process of tryptophan depletion exerts an immunosuppressive effect, facilitating immune escape of tumors. This review summarizes our current knowledge on IDO expression in malignancies, the IDO inhibitors that are currently available and those under clinical development.

Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.

Bone marrow‐derived mesenchymal stem cell (BM‐MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM‐MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy‐two patients with baseline biopsy‐proven alcoholic cirrhosis who had been alcohol‐abstinent for more than 6 months underwent a multicenter, randomized, open‐label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM‐MSC groups that underwent either one‐time or two‐time hepatic arterial injections of 5 × 10 7 BM‐MSCs 30 days after BM aspiration. A follow‐up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child‐Pugh score, and Model for End‐stage Liver Disease score. Outcomes were analyzed by per‐protocol analysis. In terms of fibrosis quantification (before versus after), the one‐time and two‐time BM‐MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively ( P < 0.001). In the intergroup comparison, two‐time BM‐MSC transplantation in comparison with one‐time BM‐MSC transplantation was not associated with improved results in fibrosis quantification ( P > 0.05). The Child‐Pugh scores of both BM‐MSC groups (one‐time 7.6 ± 1.0 versus 6.3 ± 1.3 and two‐time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM‐MSC transplantation ( P < 0.05). The proportion of patients with adverse events did not differ among the three groups. Conclusion : Autologous BM‐MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (H epatology 2016;64:2185‐2197)

The stimulator of interferon genes (STING) signaling pathway is a critical link between innate and adaptive immunity, and induces anti-tumor immune responses. STING is expressed in vasculatures, but its role in tumor angiogenesis has not been elucidated. Here we investigated STING-induced tumor vascular remodeling and the potential of STING-based combination immunotherapy. Endothelial STING expression was correlated with enhanced T-cell infiltration and prolonged survival in human colon and breast cancer. Intratumoral STING activation with STING agonists (cGAMP or RR-CDA) normalized tumor vasculatures in implanted and spontaneous cancers, but not in STING-deficient mice. These were mediated by upregulation of type I/II interferon genes and vascular stabilizing genes (e.g., Angpt1, Pdgfrb, and Col4a). STING in non-hematopoietic cells is as important as STING in hematopoietic cells to induce a maximal therapeutic efficacy of exogenous STING agonist. Vascular normalizing effects of STING agonists were dependent on type I interferon signaling and CD8+ T cells. Notably, STING-based immunotherapy was maximally effective when combined with VEGFR2 blockade and/or immune checkpoint blockade (αPD-1 or αCTLA-4), leading to complete regression of immunotherapy-resistant tumors. Our data show that intratumoral STING activation can normalize tumor vasculature and the tumor microenvironment, providing a rationale for combining STING-based immunotherapy and anti-angiogenic therapy.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder with an unknown etiology. IBD is composed of two different disease entities: Crohn's disease (CD) and ulcerative colitis (UC). IBD has been thought to be idiopathic but has two main attributable causes that include genetic and environmental factors. The gastrointestinal tract in which this disease occurs is central to the immune system, and the innate and the adaptive immune systems are balanced in complex interactions with intestinal microbes under homeostatic conditions. However, in IBD, this homeostasis is disrupted and uncontrolled intestinal inflammation is perpetuated. Recently, the pathogenesis of IBD has become better understood owing to advances in genetic and immunologic technology. Moreover, new therapeutic strategies are now being implemented that accurately target the pathogenesis of IBD. Beyond conventional immunesuppressive therapy, the development of biological agents that target specific disease mechanisms has resulted in more frequent and deeper remission in IBD patients, with mucosal healing as a treatment goal of therapy. Future novel biologics should overcome the limitations of current therapies and ensure that individual patients can be treated with optimal drugs that are safe and precisely target IBD.

The waist-to-height ratio (WHtR), calculated by dividing the waist circumference (WC) by height, has recently gained attention as an anthropometric index for central adiposity. It is an easy-to-use and less age-dependent index to identify individuals with increased cardiometabolic risk. A WHtR cutoff of 0.5 can be used in different sex and ethnic groups and is generally accepted as a universal cutoff for central obesity in children (aged ≥6 years) and adults. However, the WHtR has not been validated in preschool children, and the routine use of WHtR in children under age 6 is not recommended. Prospective studies and meta-analysis in adults revealed that the WHtR is equivalent to or slightly better than WC and superior to body mass index (BMI) in predicting higher cardiometabolic risk. In children and adolescents, studies have shown that the WHtR is similar to both BMI and WC in identifying those at an increased cardiometabolic risk. Additional use of WHtR with BMI or WC may be helpful because WHtR considers both height and central obesity. WHtR may be preferred because of its simplicity and because it does not require sex- and age-dependent cutoffs; additionally, the simple message 'keep your WC to less than half your height' may be particularly useful. This review article summarizes recent publications on the usefulness of using WHtR especially when compared to BMI and WC as a screening tool for obesity and related cardiometabolic risks, and recommends the use of WHtR in clinical practice for obesity screening in children and adolescents.

PURPOSE: To evaluate functional and radiographic results of arthroscopic suture anchor repair for posterior root tear of the medial meniscus (PRTMM) and compare with pullout suture repair. METHODS: From December 2006 to August 2008, 51 consecutive patients underwent arthroscopic repair of PRTMM at our hospital. The repair technique was switched over time from pullout suture repair (group 1) to suture anchor repair (group 2). Of the patients, 6 were lost to follow-up, leaving a study population of 45 patients, with 22 menisci (48.9%) in group 1 and 23 (51.1%) menisci in group 2. The mean follow-up duration was 25.9 months (range, 24 to 27 months) in group 1 and 26.8 months (range, 24 to 28 months) in group 2. Compared variables included International Knee Documentation Committee criteria, Kellgren-Lawrence grade, gap distance at PRTMM, structural healing, meniscal extrusion, and cartilage degeneration of the medial femoral condyle. RESULTS: At 2 years postoperatively, both groups showed significant improvements in function (P < .05) and did not show significant differences in Kellgren-Lawrence grade (P > .05) compared with preoperatively. On magnetic resonance imaging, the gap distance at PRTMM was 3.2 ± 1.1 mm in group 1 and 2.9 ± 0.9 mm in group 2 preoperatively (P > .05). Complete structural healing was seen in 11 cases in group 1 and 12 cases in group 2 (P > .05). Mean meniscal extrusion of 4.3 ± 0.9 mm (group 1) and 4.1 ± 1.0 mm (group 2) preoperatively was significantly decreased to 2.1 ± 1.0 mm (group 1) and 2.2 ± 0.8 mm (group 2) postoperatively (P < .05). Regardless of repair technique, incompletely healed cases showed progression of cartilage degeneration (4 cases in group 1 and 2 cases in group 2). CONCLUSIONS: For PRTMM, our results show significant functional improvement in both the suture anchor repair and pullout suture repair groups. Reduction of meniscal extrusion seems to be appropriate to preserve its protective role against progression of cartilage degeneration after complete healing at PRTMM. LEVEL OF EVIDENCE: Level III, prospective therapeutic comparative study.

, based on a significant increase in obesity-related diseases. A waist circumference of ≥90 cm in men and ≥85 cm in women are defined as abdominal obesity, which is also correlated with obesity-related diseases. These diagnostic criteria are the same as in the previous version; however, the updated guidelines put greater emphasis on the use of morbidity as the basis for obesity and abdominal obesity diagnoses. These new guidelines will help to identify and manage high-risk groups for obesity-related comorbidities among Korean adults.

Abstract Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT , AKT1 , PIK3CA , and EIF1AX were frequently co-mutated with driver genes ( BRAF V600E and RAS ) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A ) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS -positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.

The committee systematically collected and reviewed the international and domestic literature published in PubMed, MEDLINE, KoreaMed, and other databases. The literature was limited to research papers published in the English and Korean languages. The keywords used were 'nonalcoholic fatty liver disease,' 'nonalcoholic fatty liver,' 'nonalcoholic steatohepatitis,' 'fatty liver,' 'hepatic steatosis,' and 'steatohepatitis.' In addition, keywords related to specific clinical questions were included.

Introduction: One of the most common sleep disorders, insomnia is a significant public health concern. Several psychiatric disorders, such as anxiety disorders and depression, have shown strong relationships with insomnia. However, the clinical impact of the combination of these two conditions on insomnia severity and sleep quality remains unknown. We investigated the relationship between sleep disturbance and psychiatric comorbidities in subjects with high risk for insomnia. Methods: We analyzed data from a nation-wide cross-sectional survey of Korean adults aged 19~69 years conducted from November 2011 to January 2012. The survey was performed via face-to-face interviews using a structured questionnaire. We used the insomnia severity index (ISI) to evaluate insomnia and defined respondents with ISI scores of ≥10 as subject having a high risk for insomnia. To diagnose anxiety and depression, we used the Goldberg anxiety scale (GAS) and Patient Health Questionnaire-9 (PHQ-9), respectively. Results: Of the 2,762 respondents, 290 (10.5%) were classified as subjects with high risk for insomnia; anxiety (odds ratio [OR], 9.8; 95% confidence interval [CI]. 7.3 - 13.1) and depression (OR, 19.7; 95% CI ,13.1 - 29.6) were more common in this population than in participants without insomnia. Of the participants with insomnia, 152 (52.4%) had neither anxiety nor depression, 63 (21.7 %) only had anxiety, 21 (7.2%) only had depression, and 54 (18.6%) had both anxiety and depression. The group with both anxiety and depression was associated with worse scores on sleep-related scales than the other groups (high ISI, Pittsburgh Sleep Quality Index [PSQI], and Epworth Sleepiness Scale). The relationship between outcome measures (ISI and PSQI) and psychiatric problems was significant only when anxiety and depression were present. The PSQI has a significant mediation effect on the relationship between psychiatric comorbidities and insomnia severity. Conclusion: Among the respondents with insomnia, psychiatric comorbidities may have a negative impact on daytime alertness, general sleep quality, and insomnia severity, especially when the two conditions are present at the same time. Clinicians should therefore consider psychiatric comorbidities when treat insomnia.

Autophagy is an evolutionarily conserved process that cells use to degrade and recycle cellular proteins and remove damaged organelles. During the past decade, there has been a growing interest in defining the basic cellular mechanism of autophagy and its roles in health and disease. However, the functional role of autophagy in kidney fibrosis remains poorly understood. Here, using GFP-LC3 transgenic mice, we show that autophagy is induced in renal tubular epithelial cells (RTECs) of obstructed kidneys after unilateral ureteral obstruction (UUO). Deletion of LC3B (LC3(-/-) mice) resulted in increased collagen deposition and increased mature profibrotic factor TGF-β levels in obstructed kidneys. Beclin 1 heterozygous (beclin 1(+/-)) mice also displayed increased collagen deposition in the obstructed kidneys after UUO. We also show that TGF-β1 induces autophagy in primary mouse RTECs and human renal proximal tubular epithelial (HK-2) cells. LC3 deficiency resulted in increased levels of mature TGF-β in primary RTECs. Under conditions of TGF-β1 stimulation and autoinduction, inhibition of autolysosomal protein degradation by bafilomycin A1 increased mature TGF-β protein levels without alterations in TGF-β1 mRNA. These data suggest a novel intracellular mechanism by which mature TGF-β1 protein levels may be regulated in RTECs through autophagic degradation, which suppresses kidney fibrosis induced by UUO. The dual functions of TGF-β1, as an inducer of TGF-β1 autoinduction and an inducer of autophagy and TGF-β degradation, underscore the multifunctionality of TGF-β1.

AIMS: Atrial fibrillation (AF) is generally regarded as a risk factor for dementia, though longitudinal studies assessing the association between AF and dementia have shown inconsistent results. This study aimed to determine the effect of AF on the risk of developing dementia using a longitudinal, community-based, and stroke-free elderly cohort. METHODS AND RESULTS: The association of incident AF with the development of incident dementia was assessed from 2005 to 2012 in 262 611 dementia- and stroke-free participants aged ≥60 years in the Korea National Health Insurance Service-Senior cohort. Incident AF was observed in 10 435 participants over an observational period of 1 629 903 person-years (0.64%/year). During the observational period, the incidence of dementia was 4.1 and 2.7 per 100 person-years in the incident AF and propensity score-matched AF-free groups, respectively. After adjustment, the risk of dementia was significantly increased by incident AF with a hazard ratio (HR) of 1.52 [95% confidence interval (CI) 1.43-1.63], even after censoring for stroke (1.27, 95% CI 1.18-1.37). Incident AF increased the risk of both Alzheimer (HR 1.31, 95% CI 1.20-1.43) and vascular dementia (HR 2.11, 95% CI 1.85-2.41). Among patients with incident AF, oral anticoagulant use was associated with a preventive effect on dementia development (HR 0.61, 95% CI 0.54-0.68), and an increasing CHA2DS2-VASc score was associated with a higher risk of dementia. CONCLUSION: Incident AF was associated with an increased risk of dementia, independent of clinical stroke in an elderly population. Oral anticoagulant use was linked with a decreased incidence of dementia.

PURPOSE: To evaluate the diagnostic performance of gray-scale ultrasonography (US) and elastography in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study with waiver of informed consent. A total of 703 solid thyroid nodules in 676 patients (mean age, 49.7 years; range, 18-79 years) were included; there were 556 women (mean age, 49.5 years; range, 20-74 years) and 120 men (mean age, 50.7 years; range, 18-79 years). Nodules with marked hypoechogenicity, poorly defined margins, microcalcifications, and a taller-than-wide shape were classified as suspicious at grayscale US. Findings at elastography were classified according to the Rago criteria and the Asteria criteria. The diagnostic performances of gray-scale US and elastography were compared. For comparison between the diagnostic performances of gray-scale US and the combination of gray-scale US and elastography, three sets of criteria were assigned: criteria set 1, nodules with any suspicious grayscale US feature were assessed as suspicious; criteria set 2, Rago criteria were added as suspicious features to criteria set 1; and criteria set 3, Asteria criteria were added as suspicious features to criteria set 1. The diagnostic performances of gray-scale US, elastography with Rago criteria, and elastography with Asteria criteria, and odds ratios (ORs) with 95% confidence intervals for predicting thyroid malignancy were compared using generalized estimating equation analysis. RESULTS: Of 703 nodules, 217 were malignant and 486 were benign. Sensitivity, negative predictive value (NPV), and OR of gray-scale US for the 703 nodules were 91.7%, 94.7%, and 22.1, respectively, and these values were higher than the 15.7% and 65.4% sensitivity, 71.7% and 79.1% NPV, and 3.7 and 2.6 ORs found for elastography with Rago and Asteria criteria, respectively. Specificity, positive predictive value, and accuracy for criteria set 1 were significantly higher than those for criteria sets 2 and 3 for most of the nodule subgroups that were considered. CONCLUSION: Elastography alone, as well as the combination of elastography and gray-scale US, showed inferior performance in the differentiation of malignant and benign thyroid nodules compared with gray-scale US features; elastography was not a useful tool in recommending fine-needle aspiration biopsy.

Immune checkpoint blockade is promising for treating non-small-cell lung cancer (NSCLC). We used multipanel markers to predict the response to immune checkpoint inhibitors (ICIs) by characterizing gene expression signatures or individual genes in patients who showed durable clinical benefit to ICIs. Twenty-one patients with NSCLC treated with single-agent anti-programmed cell death protein (PD)-1 antibody were analyzed and their clinicopathological characteristics and response to ICIs were characterized. Nine (43%) showed a durable clinical benefit (DCB), while the remaining 12 (57%) patients showed non-durable benefit (NDB). The M1 and peripheral T cell signatures showed the best performance for discriminating DCB from NDB (sensitivity, specificity, accuracy = 0.89, 1.0, 0.95, respectively). Progression-free survival (PFS) was significantly longer in patients with high M1 signature or high peripheral T cell signature scores. CD137 and PSMB9 mRNA expression was higher in the DCB group than in the NDB group. Patients with high PSMB9 expression showed longer PFS. M1 signature, peripheral T cell signature and high mRNA expression level of CD137 and PSMB9 showed better predictive performance than known biomarkers, such as PD-L1 immunohistochemistry, tumor mutation burden, or tumor-infiltrating lymphocytes.