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Abstract We investigated the multi-domain states of a multiferroic La-doped BiFeO3 (BLFO) thin film by examining diffraction patterns in optical second-harmonic generation (SHG) measurement. By directing a laser onto the domain wall within the domain-patterned sample, we observed clear diffraction signatures of SHG waves generated from two ferroelectric domains. We explained the experimental results of the diffraction patterns, including the intensity distribution and the polarization characteristics, using Fresnel propagation of SHG waves. From this, we could determine the amplitude and phase of the SHG waves generated from each domain, and figure out not only the polarization direction of each ferroelectric domain but also the phase related to the complex-valued second-order susceptibility tensor. Consequently, we could present SHG diffractometry as an effective measurement method to reveal the phase details of electric polarization of the multi-domain states of ferroic materials.

Objective This study investigated the associations between paraspinal muscle measurements on chest computed tomography and clinical outcomes of elderly patients with community-acquired pneumonia (CAP). Methods This single-center, retrospective, observational study analyzed elderly patients (≥65 years) with CAP hospitalized through an emergency department between March 2020 and December 2022. We collected their baseline characteristics and laboratory data at the time of admission. The paraspinal muscle index and attenuation were calculated at the level of the 12th thoracic vertebra using chest computed tomography taken within 48 hours before or after admission. Univariable and multivariable logistic regression analyses were conducted to evaluate the association between paraspinal muscle measurements and 28-day mortality. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were used to evaluate the prognostic predictive power. Results Of the 338 enrolled patients, 60 (17.8%) died within 28 days after admission. A high paraspinal muscle index was associated with low 28-day mortality in elderly patients with CAP (adjusted odds ratio, 0.994; 95% confidence interval, 0.992–0.997). The area under the ROC curve for the muscle index was 0.75, which outperformed the pneumonia severity index and the CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥65 years) metric, both of which showed an AUC of 0.64 in predicting mortality. Conclusion A high paraspinal muscle index was associated with low 28-day mortality in patients aged 65 years or older with CAP.

Abstract With the rapid emergence of artificial intelligence (AI) technology and the exponential growth in data generation, there is an increasing demand for high-performance and highly integratable optical modulators. In this work, we present an ultra-compact exciton-polariton Mach–Zehnder (MZ) modulator based on WS2 multilayers. The guided exciton-polariton modes arise in an ultrathin WS2 waveguide due to the strong excitonic resonance. By locally exciting excitons using a modulation laser in one arm of the MZ modulator, we induce changes in the effective refractive index of the polariton mode, resulting in modulation of transmitted intensity. Remarkably, we achieve a maximum modulation of −6.20 dB with an ultra-short modulation length of 2 μm. Our MZ modulator boasts an ultra-compact footprint area of ~30 μm² and a thin thickness of 18 nm. Our findings present new opportunities for the advancement of highly integrated and efficient photonic devices utilizing van der Waals materials.

Not available.

Abstract Background The hospitalist system has been introduced to improve the quality and safety of inpatient care. As its effectiveness has been confirmed in previous studies, the hospitalist system is spreading in various fields. However, few studies have investigated the feasibility and value of hospitalist-led care of patients with cancer in terms of quality and safety measures. This study aimed to evaluate the efficacy of the Hospitalist-Oncologist co-ManagemEnt (HOME) system. Methods Between January 1, 2019, and January 31, 2021, we analyzed 591 admissions before and 1068 admissions after the introduction of HOME system on January 1, 2020. We compared the length of stay and the types and frequencies of safety events between the conventional system and the HOME system, retrospectively. We also investigate rapid response system activation, cardiopulmonary resuscitation, unplanned intensive care unit transfer, all-cause in-hospital mortality, and 30-day re-admission or emergency department visits. Results The average length of stay (15.9 days vs. 12.9 days, P

Abstract Background Achondroplasia is an autosomal dominant disorder mainly affecting bony growth, typically resulting in markedly short stature. From a neurosurgical viewpoint, patients sometimes develop spinal cord compression at the narrowed foramen magnum and hydrocephalus. This study aims to construct growth references for height, weight, and head circumference (HC) of young achondroplasia patients in Korea and to evaluate the predictability of the necessity and timing of neurosurgical procedures through growth patterns. Methods Growth data were collected from achondroplasia patients who visited our institution between January 2002 and August 2022. First, we constructed percentile growth curves of height, weight, and HC for the patients under 3 years of age with the generalized additive model for location, scale, and shape (GAMLSS). Second, the growth patterns of the patients with hydrocephalus who underwent neurosurgical procedures such as foramen magnum decompression (FMD) and ventriculoperitoneal (VP) shunt were analyzed. Results There were 125 achondroplasia patients, including 67 males and 58 females. Among 125 patients, 46 underwent FMD, and 5 underwent VP shunt. As short stature and macrocephaly were typical characteristics of achondroplasia, the height of achondroplasia was lower than that of the general population, and HC in achondroplasia showed accelerated growth postnatally. There were no significant changes in HC in hydrocephalus patients before they underwent neurosurgical procedures. The influence of hydrocephalus on the growth patterns of HC in achondroplasia seemed insignificant. Conclusion Growth references for height, weight, and HC in young achondroplasia patients were constructed. It is the first report of growth patterns of achondroplasia in Korea. Unlike other pediatric patients, the diagnosis of hydrocephalus and the necessity of neurosurgical procedures are hard to be predicted with HC in achondroplasia. Neuroimaging should be considered for achondroplasia patients with neurological symptoms.

Abstract Background The prognostic nutritional index (PNI) is known to be correlated with clinical outcomes in non‐small cell lung cancer (NSCLC) patients. However, its role has not been studied in patients who have undergone postoperative radiotherapy (PORT). This study aimed to investigate the relationship between PNI and survival and recurrence in NSCLC patients with PORT. Methods We reviewed 97 stage I–III NSCLC patients who received PORT between January 2006 and December 2016 at our institution. We obtained PNI values for both pre‐RT (within 1 month before PORT) and post‐RT (within 2 months after PORT) by using serum albumin and lymphocyte count. A cutoff value for PNI was determined by the receiver operating characteristic curve (ROC). The median follow‐up period was 52.8 months. Results The ROC curve of post‐RT PNI exhibited a higher area under the curve (AUC 0.68, cut‐off: 47.1) than that of pre‐RT PNI (AUC 0.55, cutoff: 50.3), so the group was divided into high post‐RT PNI (> 47.1) and low post‐RT PNI (≤ 47.1). The five‐year overall survival rate (OS) was 66.2% in the high post‐RT group, compared with 41.8% in the low post‐RT PNI group (p = 0.018). Those with both low pre‐RT and low post‐RT PNI had the worst five‐year OS of 31.1%. Post‐RT PNI (HR 0.92, p = 0.003) was an independent risk factor for mortality. Conclusions PNI after PORT was significantly associated with survival. This finding suggests that PNI can be used as a prognostic marker.

Background Semi-rigid neck collars to protect the cervical spine can limit the extent of neck movement and mouth opening; this may further complicate orotracheal intubation. We aimed to compare intubation environments obtained with videolaryngoscopy using the technique of gliding a blade under the epiglottis and that obtained using the conventional Macintosh blade technique of blade tip placement on the vallecula. Methods This prospective randomized study included patients aged ≥ 20 years with American Society of Anesthesiologists physical status I–III scheduled for cervical spine surgery between October 2020 and August 2021. Patients were divided into two groups according to the placement of the blade of the McGrathTM videolaryngoscope: the gliding and conventional groups. The percentage of glottic opening (POGO) score was the primary endpoint. We also recorded the time to obtain the optimal laryngoscopic view, intubation duration, and ease and satisfaction of the researcher performing intubation. Results Among 176 patients, the POGO scores were significantly higher in the gliding group than in the conventional group (88.9 ± 14.7 vs. 63.8 ± 27.4, P < 0.001). The time to achieve the optimal glottic view for intubation and duration of intubation were also shorter, and ease and satisfaction in performing intubation were better in the gliding group than in the conventional group. Conclusion Our findings demonstrated a superior glottic view and more favorable intubation environments when the blade tip was placed under the epiglottis than using the conventional Macintosh technique in patients with immobilized cervical spine.

Background Since the onset of the coronavirus disease 2019 pandemic, virtual simulation has emerged as an alternative to traditional teaching methods as it can be employed within the recently established contact-minimizing guidelines. This prospective education study aimed to develop a virtual reality simulator for a lumbar transforaminal epidural block (LTFEB) and demonstrate its efficacy. Methods We developed a virtual reality simulator using patient image data processing, virtual X-ray generation, spatial registration, and virtual reality technology. For a realistic virtual environment, a procedure room, surgical table, C-arm, and monitor were created. Using the virtual C-arm, the X-ray images of the patient’s anatomy, the needle, and indicator were obtained in real-time. After the simulation, the trainees could receive feedback by adjusting the visibility of structures such as skin and bones. The training of LTFEB using the simulator was evaluated using 20 inexperienced trainees. The trainees’ procedural time, rating score, number of C-arm taken, and overall satisfaction were recorded as primary outcomes. Results The group using the simulator showed a higher global rating score (P = 0.014), reduced procedural time (P = 0.025), reduced number of C-arm uses (P = 0.001), and higher overall satisfaction score (P = 0.007). Conclusions We created an accessible and effective virtual reality simulator that can be used to teach inexperienced trainees LTFEB without radiation exposure. The results of this study indicate that the proposed simulator will prove to be a useful aid for teaching LTFEB.

Abstract Ferroelectric materials are promising candidates for neuromorphic computing synaptic devices due to the nonvolatile multiplicity of spontaneous polarization. To ensure a sufficient memory window, ferroelectric materials with a large coercivity are urgently required for practical applications in highly scaled multi‐bit memory devices. Herein, a remarkable reliability of intermediate ferroelectric polarization states is demonstrated in a textured Al0.66Sc0.34N thin film with a coercive field of 2.4 MV cm−1. Al0.66Sc0.34N thin films are prepared at 300 °C on Pt (111)/Ti/SiO2/Si substrates using a radio frequency reactive sputtering method. Al0.66Sc0.34N thin films exhibit viable ferroelectricity with a large remanent polarization value of >100 µC cm−2. Through the conventional current–voltage characteristics, polarization switching kinetics, and temperature dependence of coercivity, the reproducibility of multiple polarization states with apparent accuracy is attributed to a small critical volume (3.7 × 10−28 m3) and a large activation energy (3.3 × 1027 eV m−3) for nucleation of the ferroelectric domain. This study demonstrates the potential of ferroelectric Al1‐xScxN for synaptic weight elements in neural network hardware.

Abstract Background Preclinical data have shown the immunomodulatory effects of metformin and dipeptidyl peptidase 4 (DPP4) inhibitors in patients with diabetes. However, its clinical impact remains unclear in lung cancer. Methods Between 2017 and 2021, 466 patients received ICI monotherapy. Patients were categorized into concurrent (MET; metformin or combination of metformin and DPP4 inhibitor) and without concomitant (NMET; nonmetformin/DPP4 inhibitors) administration of metformin and DPP4 inhibitors groups at least 8 weeks before and during ICI therapy. The primary objectives were the objective response rate (ORR) and progression‐free survival (PFS). The second objective was to evaluate the overall survival (OS) and the occurrence of immune‐related adverse events (irAEs). Results Among 466 patients, 89 (19.0%) and 377 (81%) were categorized into the MET and NMET groups, respectively. MET group had a significantly higher ORR (MET group: 24.7% vs. NMET group: 14.8%, p = 0.025) and longer PFS than those in the NMET group (MET group 5.1 month vs. NMET group 2.8 months, p = 0.018). After patients were stratified based on the prior line of therapy and PD L1 expression status, the PFS of the second‐line therapy and PD L1 ≥50 was significantly higher in the MET than in the NMET group. The proportion of patients experiencing all‐grade irAEs was numerically higher in the MET group (19.1%) than in the NMET group (14.3%), without statistical significance (p = 0.382). Conclusions Concurrent use of metformin and DPP4 inhibitors with ICIs significantly improved the clinical outcomes without increasing the incidence of irAEs in NSCLC.

Context Pinus densiflora Siebold & Zucc. (Pinaceae) needle extracts ameliorate oxidative stress, but research into their anti-inflammatory effects is limited.Objective To investigate antioxidant and anti-inflammatory effects of a Pinus densiflora needles (PINE) ethanol extract in vitro and in vivo.Materials and methods We measured levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at various PINE concentrations (25, 50 and 100 μg/mL; but 6.25, 12.5 and 25 μg/mL for interleukin-1β and prostaglandin E2 (PGE2)). Thirty ICR mice were randomized to six groups: vehicle, control, PINE pre-treatment (0.1, 0.3 and 1 mg/left ear for 10 min followed by arachidonic acid treatment for 30 min) and dexamethasone. The posttreatment ear thickness and myeloperoxidase (MPO) activity were measured.Results PINE 100 μg/mL significantly decreased ROS (IC50, 70.93 μg/mL, p

BackgroundAccording to a 2020 study by the American Cancer Society, colorectal cancer (CRC) represents the third leading cause of cancer both in incidence and death in the United States. Nonetheless, CRC screening remains lower than that for other high-risk cancers such as breast and cervical cancer. Risk calculators are increasingly being used to promote cancer awareness and improve compliance with CRC screening tests. However, research concerning the effects of CRC risk calculators on the intention to undergo CRC screening has been limited. Moreover, some studies have found the impacts of CRC risk calculators to be inconsistent, reporting that receiving personalized assessments from such calculators lowers people’s risk perception. ObjectiveThe objective of this study is to examine the effect of using CRC risk calculators on individuals’ intentions to undergo CRC screening. In addition, this study aims to examine the mechanisms through which using CRC risk calculators might influence individuals’ intentions to undergo CRC screening. Specifically, this study focuses on the role of perceived susceptibility to CRC as a potential mechanism mediating the effect of using CRC risk calculators. Finally, this study examines how the effect of using CRC risk calculators on individuals’ intentions to undergo CRC screening may vary by gender. MethodsWe recruited a total of 128 participants through Amazon Mechanical Turk who live in the United States, have health insurance, and are in the age group of 45 to 85 years. All participants answered questions needed as input for the CRC risk calculator but were randomly assigned to treatment (CRC risk calculator results immediately received) and control (CRC risk calculator results made available after the experiment ended) groups. The participants in both groups answered a series of questions regarding demographics, perceived susceptibility to CRC, and their intention to get screened. ResultsWe found that using CRC risk calculators (ie, answering questions needed as input and receiving calculator results) has a positive effect on intentions to undergo CRC screening, but only for men. For women, using CRC risk calculators has a negative effect on their perceived susceptibility to CRC, which in turn reduces the intention to sign up for CRC screening. Additional simple slope and subgroup analyses confirm that the effect of perceived susceptibility on CRC screening intention is moderated by gender. ConclusionsThis study shows that using CRC risk calculators can increase individuals’ intentions to undergo CRC screening, but only for men. For women, using CRC risk calculators can reduce their intentions to undergo CRC screening, as it reduces their perceived susceptibility to CRC. Given these mixed results, although CRC risk calculators can be a useful source of information on one’s CRC risk, patients should be discouraged from relying solely on them to inform decisions regarding CRC screening.

Abstract Electrons in crystals interact closely with quantized lattice degree of freedom, determining fundamental electrodynamic behaviors and versatile correlated functionalities. However, the strength of the electron–phonon interaction is so far determined as an intrinsic value of a given material, restricting the development of potential electronic and phononic applications employing the tunable coupling strength. Here, it is demonstrated that the electron–phonon coupling in SrRuO3 can be largely controlled by multiple intuitive tuning knobs available in synthetic crystals. The coupling strength of quasi‐2D SrRuO3 is enhanced by ≈300‐fold compared with that of bulk SrRuO3. This enormous enhancement is attributed to the non‐local nature of the electron–phonon coupling within the well‐defined synthetic atomic network, which becomes dominant in the limit of the 2D electronic state. These results provide valuable opportunities for engineering the electron–phonon coupling, leading to a deeper understanding of the strongly coupled charge and lattice dynamics in quantum materials.

The radiation emitted during radiological examinations can be harmful to the human body, but the technique is still used because it is helpful to the patient. Therefore, radiologic examinations must follow radiation protection principles such as justification and optimization, and only minimal required re-examinations should be performed. Proper use of radiation in the medical field can be achieved by proper education of individuals from multiple medical fields.

Background: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities strongly associated with risks of cardiovascular diseases. However, a relationship between MetS and aneurysmal disease as compared with occlusive disease has not been confirmed. Therefore, correlations of MetS and abdominal aortic aneurysm (AAA) were evaluated. Methods: Between March 2011 and February 2020, 354 patients diagnosed with AAA were enrolled and divided into the MetS (n = 164) and the no-MetS (n = 190) groups. Individual components of MetS, characteristics of AAA, rupture rate, and survival rate were evaluated for both groups. Additionally, correlations between MetS and AAA were evaluated with focusing on effects of diabetes mellitus (DM). Results: The size of AAA was significantly larger in the MetS group compared with the no-MetS group (P 0.05). Conclusions: Although larger prospective studies are necessary, we suggest that MetS proportionally aggravates the status of AAA and survival rate. Therefore, surveillance for MetS and individual components may help to restrict the expansion of AAA.

Abstract Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand. The aim of this study was to investigate the effects of baseline plasma AREG levels in KRAS, NRAS, and BRAF wild-type metastatic colorectal cancer (CRC) on treatment outcome with palliative first-line cetuximab + FOLFIRI chemotherapy. Chemotherapy outcomes were analyzed based on baseline plasma AREG levels. The clinical findings were further validated using an in vitro model of CRC. Among 35 patients, the progression-free survival (PFS) was significantly inferior in patients with high AREG than in those with low AREG levels: 10.9 vs. 24.2 months, respectively (p = 0.008). However, after failure of first-line chemotherapy, AREG levels were associated with neither PFS (4.8 vs. 11.6 months; p = 0.215) nor overall survival (8.4 vs. 13.3 months; p = 0.975). In SNU-C4 and Caco-2 cells which were relatively sensitive to cetuximab among the seven CRC cell lines tested, AREG significantly decreased the anti-proliferative effect of cetuximab (p

Abstract Background Inflammation is recognized as a critical process in expansion of abdominal aortic aneurysm (AAA). A relationship between effects of cholesterol and statin in this process have been suggested, but remain untested. Therefore, current study aimed to examine the effects of hypercholesterolism on expansion of AAA in a rat model. Methods A total of 16 male rats were divided into 4 groups as follows: group I, normocholesterol diet and saline infusion, group II, normocholesterol diet and porcine pancreatic elastase (PPE) infusion, group III, hypercholesterol diet and PPE infusion, and group IV, hypercholesterol diet, PPE infusion and statin administration. At the 3rd week, saline was infused intraluminally in group I and PPE in groups II-IV to induce AAA. At the 5th week, blood and aortic tissue were obtained from each rat for evaluation of lipid profiles, aortic diameters (ADs), and characteristics of stains. Results Post-procedural aortic diameter (AD3) and AD3/pre-procedural aortic diameter (AD1) were significantly different among four groups (P = 0.042, P = 0.028, respectively). AD3 was significantly larger in group II than group I, and group III than group IV (P = 0.012, P = 0.043, respectively). AD3/AD1 was significantly higher in group II than group I, and group III than group II (P = 0.008, P = 0.030, respectively). Group III showed the highest cellularity for inflammatory cells. Conclusions Though larger experimental and clinical studies are necessary, authors suggest that hypercholesterolism can aggravate expansion of AAA, and that statin therapy can reduce it. Therefore, monitoring for hypercholesterolism and instituting statin therapy may be helpful to suppress expansion of AAA.

We aimed to elucidate the evolutionary trajectories of gallbladder adenocarcinoma (GBAC) using multi-regional and longitudinal tumor samples. Using whole-exome sequencing data, we constructed phylogenetic trees in each patient and analyzed mutational signatures. A total of 11 patients including 2 rapid autopsy cases were enrolled. The most frequently altered gene in primary tumors was ERBB2 and TP53 (54.5%), followed by FBXW7 (27.3%). Most mutations in frequently altered genes in primary tumors were detectable in concurrent precancerous lesions (biliary intraepithelial neoplasia [BilIN]), but a substantial proportion was subclonal. Subclonal diversity was common in BilIN (n=4). However, among subclones in BilIN, a certain subclone commonly shrank in concurrent primary tumors. In addition, selected subclones underwent linear and branching evolution, maintaining subclonal diversity. Combined analysis with metastatic tumors (n=11) identified branching evolution in nine patients (81.8%). Of these, eight patients (88.9%) had a total of 11 subclones expanded at least sevenfold during metastasis. These subclones harbored putative metastasis-driving mutations in cancer-related genes such as SMAD4, ROBO1, and DICER1. In mutational signature analysis, six mutational signatures were identified: 1, 3, 7, 13, 22, and 24 (cosine similarity >0.9). Signatures 1 (age) and 13 (APOBEC) decreased during metastasis while signatures 22 (aristolochic acid) and 24 (aflatoxin) were relatively highlighted. Subclonal diversity arose early in precancerous lesions and clonal selection was a common event during malignant transformation in GBAC. However, selected cancer clones continued to evolve and thus maintained subclonal diversity in metastatic tumors.

Tucidinostat (formerly known as chidamide) is an orally available, novel benzamide class of histone deacetylase (HDAC) inhibitor that selectively blocks class I and class IIb HDAC. This multicenter phase IIb study aimed to investigate the efficacy and safety of tucidinostat, 40 mg twice per week (BIW), in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). The primary endpoint was overall response rate (ORR) assessed by an independent overall efficacy review committee. Between March 2017 and March 2019, 55 patients were treated, and 46 and 55 were evaluated for efficacy and safety, respectively. Twenty-one of 46 patients achieved objective responses with an ORR of 46% (95% confidence interval : 30.9-61.0), including five patients with complete response (CR). Responses were observed across various PTCL subtypes. In angioimmunoblastic T-cell lymphoma, there were two CR and five partial responses (PR) among eight patients, achieving an ORR of 88%. The disease control rate (CR + PR + stable disease) was 72% (33/46). The median progression-free survival, duration of response, and overall survival were 5.6 months, 11.5 months, 22.8 months, respectively. The most common adverse events (AE) (all grades) were thrombocytopenia, neutropenia, leukopenia, anemia, and diarrhea. The grade ≥3 AE emerging in ≥20% of patients included thrombocytopenia (51%), neutropenia (36%), lymphopenia (22%), and leukopenia (20%). Importantly, most of the AE were manageable by supportive care and dose modification. In conclusion, the favorable efficacy and safety profiles indicate that tucidinostat could be a new therapeutic option in patients with R/R PTCL (clinicaltrials gov. Identifier: NCT02953652).

Abstract Predicting difficult laryngoscopy is an essential component of the airway management. We aimed to evaluate the use of anterior neck soft tissue measurements on computed tomography for predicting difficult laryngoscopy and to present a clear measurement protocol. In this retrospective study, 281 adult patients whose tracheas were intubated using a direct laryngoscope for thyroidectomy were enrolled. On computed tomography, the distances from the midpoint of the thyrohyoid membrane to the closest concave point of the vallecular (membrane-to-vallecula distance; dMV), and to the most distant point of the epiglottis (membrane-to-epiglottis distance; dME) were measured, respectively. The extended distances straight to the skin anterior from the dMV and dME were called the skin-to-vallecula distance (dSV) and skin-to-epiglottis distance (dSE), respectively. Difficult laryngoscopy was defined by a Cormack-Lehane grade of > 2. Difficult laryngoscopy occurred in 40 (14%) cases. Among four indices, the dMV showed the highest prediction ability for difficult laryngoscopy with an area under the receiver operating characteristic curve of 0.884 (95% confidence interval 0.841–0.919, P

Abstract Background Immune checkpoint inhibitors (ICIs) are an established treatment for non‐small cell lung cancer (NSCLC) that have demonstrated durable clinical benefits (DCBs). Previous studies have suggested NY‐ESO‐1 and LAG‐3 to be surrogate markers of ICI responses in NSCLC; therefore, we explored the predictive value of their expression in NSCLC. Methods We retrospectively reviewed the records of 38 patients with advanced NSCLC treated with anti‐PD‐1 monoclonal antibodies from 2013 to 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital after failed platinum‐based chemotherapy. Tumor tissues from each patient were subjected to immunohistochemical analysis to determine NY‐ESO‐1, LAG‐3, and PD‐L1 expression, whose ability to predict progression‐free survival (PFS) and overall survival (OS) was then analyzed alongside their positive (PPV) and negative (NPV) predictive values. Results NY‐ESO‐1 or LAG‐3 expression was detected in all tumor samples from patients with high PD‐L1 expression and was significantly associated with favorable outcomes, unlike PD‐L1 expression. Patients with both NY‐ESO‐1‐ and LAG‐3‐expressing tumors had a high DCB rate and those with triple‐positive PD‐L1, LAG‐3, and NY‐ESO expression had a superior median OS and PFS than those with triple‐negative expression. Furthermore, LAG‐3 and NY‐ESO‐1 co‐expression was an independent predictor of both PFS and OS, while LAG‐3 displayed a good NPV. Conclusions Patients with NSCLC who co‐express NY‐ESO‐1 or LAG‐3 with PD‐L1 exhibit greater DCBs and improved long‐term survival following anti‐PD‐1 therapy. Moreover, NY‐ESO‐1 and LAG‐3 could be novel predictive biomarkers of survival and should be considered in the future use of ICIs.

Abstract Background The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity. Methods We studied 2471 participants (50.9 % women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT. Results Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P

Abstract Although immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months [95% confidence interval (CI), 13.4 to not reached (NR)], 11.7 months [95% CI, 9.5–21.1], and 5.4 months [95% CI, 2.6-NR], respectively, P

This study evaluated the diagnostic performance of the AccuPower® TB&MDR Real-Time PCR (TBMDR®) and AccuPower® XDR-TB Real-Time PCR Kit-A (XDRA®) to detect multidrug-resistant (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) in comparison with phenotypic drug susceptibility testing (DST) using MGIT 960 on 234 clinical Mycobacterium tuberculosis isolates. Discrepant results were confirmed by direct-sequencing. Sensitivity and specificity of TBMDR and XDRA for cultured isolates were 81.2% and 95.8% for isoniazid (INH) resistance, 95.7% and 95.7% for rifampicin (RIF) resistance, 84.1% and 99.1% for fluoroquinolone (FQ) resistance, and 67.4% and 100% for second-line injectables resistance. The sensitivities of each drug were equivalent to other molecular DST methods. High concordance was observed when compared to direct-sequencing. We also found that TBMDR and XDRA assays can detect INH, RIF and FQ resistance in isolates with low level resistance-associated mutations which were missed by phenotypic DST. Our study showed TBMDR and XDRA assays could be the useful tools to detect MDR-TB and pre-XDR-TB.

Previous studies are limited to modulate oxygen octahedral rotation angles within the same pattern, and engineering the pattern remains a challenge. Here, the authors demonstrate a designed nonequilibrium oxygen octahedral rotation pattern leads to room-temperature ferroelectricity in CaTiO3.

Background The long-term outcomes of patients discharged from the hospital after successful care in intensive care unit (ICU) are not briskly evaluated in Korea. The aim of this study was to assess long-term mortality of patients treated in the ICU and discharged alive from the hospital and to identify predictive factors of mortality. Methods In 3,679 adult patients discharged alive from the hospital after ICU care between 2006 and 2011, the 1-year mortality rate (primary outcome measure) was investigated. Various factors were entered into multivariate analysis to identify independent factors of 1-year mortality, including sex, age, severity of illness (APACHE II score), mechanical ventilation, malignancy, readmission, type of admission (emergency, elective surgery, and medical), and diagnostic category (trauma and non-trauma). Results The 1-year mortality rate was 13.4%. Risk factors that were associated with 1-year mortality included age (hazard ratio: 1.03 [95% CI, 1.02–1.04], P < 0.001), APACHE II score (1.03 [1.01–1.04], P < 0.001), mechanical ventilation (1.96 [1.60–2.41], P < 0.001), malignancy (2.31 [1.82–2.94], P < 0.001), readmission (1.65 [1.31–2.07], P < 0.001), emergency surgery (1.66 [1.18–2.34], P = 0.003), ICU admission due to medical causes (4.66 [3.68–5.91], P < 0.001), and non-traumatic diagnostic category (6.04 [1.50–24.38], P = 0.012). Conclusions The 1-year mortality rate was 13.4%. Old age, high APACHE II score, mechanical ventilation, malignancy, readmission, emergency surgery, ICU admission due to medical causes, and non-traumatic diagnostic category except metabolic/endocrinologic category were associated with 1-year mortality.

Abstract Background Plants have been used as an important source of indispensable bioactive compounds in various cosmetics, foods, and medicines. However, the subsequent functional annotation of these compounds seems arduous because of the largely uncharacterized, vast metabolic repertoire of plant species with known biological phenotypes. Hence, a rapid multi-parallel screening and characterization approach is needed for plant functional metabolites. Results Fifty-one species representing three plant families, namely Asteraceae, Fabaceae, and Rosaceae, were subjected to metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultrahigh-performance liquid chromatography quadrupole orbitrap ion trap tandem mass spectrometry (UHPLC-Q-orbitrap-MS/MS) as well as multivariate analyses. Partial least squares discriminant analysis (PLS-DA) of the metabolite profiling datasets indicated a distinct clustered pattern for 51 species depending on plant parts (leaves and stems) and relative phylogeny. Examination of their relative metabolite contents showed that the extracts from Fabaceae plants were abundant in amino acids, fatty acids, and genistein compounds. However, the extracts from Rosaceae had higher levels of catechin and ellagic acid derivatives, whereas those from Asteraceae were higher in kaempferol derivatives and organic acids. Regardless of the different families, aromatic amino acids, branch chain amino acids, chlorogenic acid, flavonoids, and phenylpropanoids related to the shikimate pathway were abundant in leaves. Alternatively, certain amino acids (proline, lysine, and arginine) as well as fatty acids levels were higher in stem extracts. Further, we investigated the associated phenotypes, i.e., antioxidant activities, affected by the observed spatial (leaves and stem) and intra-family metabolomic disparity in the plant extracts. Pearson’s correlation analysis indicated that ellagic acid, mannitol, catechin, epicatechin, and quercetin derivatives were positively correlated with antioxidant phenotypes, whereas eriodictyol was positively correlated with tyrosinase inhibition activity. Conclusions This work suggests that metabolite profiling, including multi-parallel approaches and integrated bioassays, may help the expeditious characterization of plant-derived metabolites while simultaneously unraveling their chemodiversity.

BackgroundWe aimed to investigate the performance of clinician prediction of survival (CPS) and the association between CPS and the prognostic confidence of clinicians in ambulatory medical oncology outpatients.MethodsEight medical oncologists estimated the expected survival of their patients in a prospective cohort study. They were asked to provide a temporal type of CPS in weeks, together with their level of confidence for each prediction (0-100%). We analyzed the accuracy of CPS, the association between CPS and the prognostic confidence, and the characteristics of patients showing inaccurate CPS.ResultsA total of 200 advanced cancer patients were enrolled and the median overall survival was 7.6 months. CPS was accurate in 67 (33.5%) patients, underestimated in 87 (43.5%), and overestimated in 46 (23.0%). The overall accuracy of CPS for 12-week, 24-week, 36-week, and 48-week survival was 83.0%, 72.0%, 75.5%, and 74.0%, respectively. The specificity was highest for 12-week survival (90.2%) and the sensitivity was highest for 48-week survival (96.1%). The sensitivity of 12-week CPS was 51.4% and the area under the receiver operating characteristic (AUROC) curve was 0.79 (95% confidence interval [CI] 0.71-0.87). The prognostic confidence of clinicians was not significantly associated with the accuracy of prediction (P = 0.359). Patients with overestimated survival had significantly poorer global health status and physical/role/emotional functioning in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Additionally, they showed significantly higher levels of fatigue, nausea/vomiting, pain, dyspnea, and loss of appetite.ConclusionThe overall accuracy of CPS in predicting 12-week to 48-week survival was high in medical oncology outpatients. However the sensitivity of 12-week CPS was low and prognostic confidence was not associated with the accuracy of CPS. Patients with overestimated CPS showed poorer quality of life and higher symptom burden.

PurposeSplanchnic vein thrombosis (SpVT) in solid tumors has not been well investigated. Therefore, the treatment guidelines for SpVT are not well established. We aimed to conduct this prospective study to investigate the clinical characteristics and risk factors influencing survival in patients with gastrointestinal cancer with SpVT.Materials and methodsFifty-one patients with gastrointestinal cancer diagnosed with SpVT were prospectively enrolled. The clinical characteristics and courses of SpVT were analyzed.ResultsSpVT occurred in various clinical situations (at the time of initial cancer diagnosis or tumor recurrence after curative therapy, in the postoperative period, during chemotherapy, or in the period of end-of-life care). Among the total patients, 90.2% had no SpVT-related symptoms at initial SpVT diagnosis, and 82.4% did not receive any anticoagulation therapy. The clinical course of SpVT during the follow-up varied: (1) spontaneous resorption without any anticoagulation (47.1%), (2) resorption with anticoagulation (3.9%), (3) persistent thrombosis without progression (17.6%), and (4) SpVT extension (31.4%). Although the SpVT showed extension in some cases, most of them did not cause symptoms or had little impact on the patient's cancer treatment course. During the follow-up period, 23 patients died, all of which were caused by tumor progression. In the multivariable analysis, performance status and clinical situation at the time of SpVT diagnosis were significant prognostic factors.ConclusionsClinicians could adopt a strategy of close observation for incidentally detected SpVT in patients with gastrointestinal cancer. Anticoagulation should be considered only for SpVT cases selected strictly, weighing the risks and benefits.

The new polyketides lopouzanones A and B, as well as the new 1-O-acetyl and 2-O-acetyl derivatives of dendrodochol B, were isolated from the sponge-derived marine fungus Lopadostoma pouzarii strain 168CLC-57.3. Moreover, six known polyketides, gliorosein, balticolid, dendrodolide G, dihydroisocoumarine, (–)-5-methylmellein, and dendrodochol B, were identified. The structures of the isolated compounds were determined by a combination of NMR and ESIMS techniques. The absolute configurations of the lopouzanones A and B were determined using the Mosher’s method. The cytotoxicity of the isolated compounds against human prostate cancer cells PC-3 and normal rat cardiomyocytes H9c2 was investigated. Gliorosein showed weak DPPH radical-scavenging activity and in vitro cardioprotective effects toward rotenone toxicity and CoCl2-mimic hypoxia.

Abstract Background In-hospital cardiopulmonary resuscitation (CPR) is one of undesirable situations. We tried to identify and characterize a potentially avoidable CPR in cancer patients who were hospitalized in hematology and oncology wards. Methods A potentially avoidable CPR was determined based on chemotherapy setting, disease status and clinical situation at the time when a cardiopulmonary arrest occurred, by using a consensus-driven medical records review of two physicians. Results One hundred thirty-seven patients among 12,437 patients hospitalized at hematology and oncology wards between March 2003 and June 2015 (1.1%) underwent a CPR. Eighty-eight patients (64.2%) were men. The majority of patients with a CPR had lung cancer (41, 29.9%), hematologic malignancy (24, 17.5%), stomach cancer (23, 16.8%) or lymphoma (20, 14.6%). A potentially avoidable CPR was identified in 51 patients (37.2%). In a multivariate analysis, advanced diseases and certain tumor types (e.g., lung cancer, lymphoma) were significant risk factors for a potentially avoidable CPR. Of patients who received a potentially avoidable CPR, 29 patients (56.9%) did not have a do-not-resuscitate documentation. A first return of spontaneous circulation rate (ROSC) and in-hospital survival rate (IHSR) were much lower in patients with a potentially avoidable CPR than those with a CPR that was not avoidable (ROSC: 39.2% vs 53.5%, P = 0.106; IHSR: 2.0% vs 12.8%, P = 0.032, respectively). Conclusions A potentially avoidable CPR was common at hematology and oncology wards. A potentially avoidable CPR frequently occurred in advanced diseases and certain tumor types. Furthermore, cancer patients who received a potentially avoidable CPR showed the worse prognosis.

Abstract Background Despite recent advances in treating non‐small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs), their role in ALK‐positive NSCLC patients is unclear. We investigated the efficacy of ICIs in patients with ALK‐positive NSCLC. Methods Between 2011 and 2018, a total of 14 ALK‐positive NSCLC patients treated with ICIs were evaluated retrospectively. Clinicopathologic features including age, PD‐L1 expression, and treatment outcomes were analyzed. RNA expression level and cytolytic activity by ALK positivity were analyzed using The Cancer Genome Atlas (TCGA) and National Cancer Center Research Institute (NCCRI) data sets. Results A total of 13 patients (92.9%) received ALK inhibitors. Patients received a median of three (range 2–8) courses of therapy. The study included nine patients (64.3%) who were PD‐L1‐high (>50%) and four (28.6%) who were PD‐L1‐low (

Purpose We investigated the sensitivity of various evaluating modalities in predicting a pathologic complete response (pCR) after preoperative chemoradiation therapy (PCRT) for locally advanced rectal cancer (LARC). Methods From a population of 2,247 LARC patients who underwent PCRT followed by surgery at Asan Medical Center, Seoul, Korea from January 2007 to June 2016, we retrospectively analyzed 313 patients (14.1%) who showed a pCR after surgery. Transrectal ultrasound (TRUS), high-resolution magnetic resonance imaging (MRI), abdominopelvic computed tomography (AP-CT), and endoscopy were performed within 2 weeks prior to surgery. Results Of the 313 patients analyzed, 256 (81.8%) had a pCR after radical surgery and 57 (18.2%) showed total regression after local excision. Preoperative TRUS, MRI, and AP-CT were performed in 283, 305, and 139 patients, respectively. Among these 3 groups, a prediction of a pCR of the primary tumor was made in 41 (14.5%), 51 (16.7%), and 27 patients (19.4%), respectively, before surgery. A prediction of a clinical N0 stage was made in 204 patients (88.3%) using TRUS, 130 (52.2%) using MRI, and 78 (65.5%) using AP-CT. Of the 211 patients who underwent endoscopy, 87 (41.2%) had a mention of clinical CR in their records. A prediction of a pathologic CR was made for 124 patients (39.6%) through at least one diagnostic modality. Conclusion The various evaluation methods for predicting a pCR after PCRT show a predictive sensitivity of 0.15–0.41 for primary tumors and 0.52–0.88 for lymph nodes. Endoscopy is a relatively superior modality for predicting the pCR of the primary tumor of LARC patients.

Background The older population (≥65 years) has rapidly increased in size in recent years. Among them, the middle-to-oldest-old (≥75 years) tend to have a poor health status. Therefore, subdivision and evaluation of older patients with traumatic injury are required. We focused on the risk of femoral intertrochanteric fractures occurring in older adults due to minor falls and compared young-old and middle-to-oldest-old populations. Methods The medical records of patients who visited the emergency center due to hip injuries between March 2017 and March 2019 were retrospectively analyzed. Patients were divided into older adult (≥65 years) and non-older (age 18–64 years) groups; the older adult group was subdivided into young-old (65–74 years), middle-old (75–84 years), and oldest-old (≥85 years) groups. This study investigated the occurrence rate of femoral intertrochanteric fractures and related factors. Results The older adult group had a higher incidence of femoral intertrochanteric fractures than that in the non-older adult group (95.3% vs. 4.7%, p

Purpose To evaluate the differences in opinion among radiologists working in different types of medical institutions in Korea, through questionnaires. Materials and Methods Korean board-certified radiologists who participated in the survey in 2017. Results Of the 316 radiologists who responded to the survey, 46.1, 20.3, 16.3, and 10.1% were working in university hospitals, general hospitals, hospitals, and clinics, respectively. More than half the radiologists (52.1%) considered teleradiology necessary, and the most-cited reason was a flexible work style. On the contrary, poor quality of radiology reports was the most-cited reason for considering teleradiology unnecessary. Although regulations for image quality, work environment, and radiology reports were considered necessary, the smaller the size of medical institution, the lower was the agreement rate. Among all responders, most radiologists thought that teleradiology would reduce the scope of radiology. However, most radiologists working in clinics thought that teleradiology would expand the field of radiology. Most responders (94.2%) required teleradiology guidelines provided by the Korean Society of Radiology. Conclusion The results of this survey showed radiologists’ perspective on various aspects of teleradiology. There were significant differences in opinion among radiologists working in different types of medical institutions.

Purpose Teleradiology has been widely used nationwide in various ways. In order to prepare a guideline, it was recognized that a survey on the actual condition of teleradiology in Korea was necessary. Materials and Methods The questionnaires were administered to training hospitals. Interviews were also conducted with teleradiology centers and teleradiologists. The bid records of Government e-Procurement System (Narajangteo) was examined. Results The main reason for requesting teleradiology was manpower shortage. The contracts were made on a per-case basis and all were interpreted with the reading radiolgists’ names on the report. The report seemed to be delivered timely and access to clinical information was possible in some cases. The teleradiology fees collected from the e-procurement system were lower than those from other subjects, which is thought to be the result of the lowest bid method. Conclusion Guidelines for teleradiology should be developed on legitimate interpretations. In addition, continuous efforts to solve the problem of quality deterioration of teleradiology will be needed.

Abstract Background Preoperative chemoradiotherapy (pre-CRT) followed by total mesorectal excision (TME) is currently a standard therapy for locally advanced mid-to-low rectal cancer. Less aggressive, organ-preserving option such as local excision (LE) or watchful wait can alternatively be used for patients who respond well to pre-CRT. High-resolution rectal magnetic resonance imaging (MRI) is one of the most useful methods to assess pre-CRT response, and the MERCURY group has shown that the MR tumor regression grade (mrTRG) correlated with the pathologic TRG. The aim of this study is to compare postoperative complication and oncologic outcomes between LE and TME in mid-to-low rectal cancer patients whose tumors are mrTRG grade 1 (radiological complete remission) or 2 (predominant fibrosis; near-complete remission) after pre-CRT. Methods A prospective, double-arm, randomized, open-labeled, single center, clinical trial will be conducted in patients with mid-to-low rectal cancer whose tumors are mrTRG 1/2 after pre-CRT at the Asan Medical Center, Seoul, Korea, after approval from the Institution Review Board. Patient medical records will be de-identified using a serial number to protect personal information. Inclusion criteria will include rectal adenocarcinoma with an inferior border 20, and provision of informed consent. Postoperative complications will be assessed by Clavien-Dindo Classification Grade. Oncologic and functional outcomes will be collected and risk factors related to these outcomes will be investigated. Discussion We believed that the rate of postoperative complication of LE will be comparable to that of TME in mid-to-low advanced rectal cancer patients with a favorable response after pre-CRT. Trial registration KCT0002579 (https://cris.nih.go.kr) Dec-2017.

Abstract Background We aimed to compare intra- and extracranial responses to immune checkpoint inhibitors (ICIs) in lung cancer with brain metastases (BM), and to explore tumor microenvironments of the brain and lungs focusing on the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Methods Two cohorts of lung cancer patients with BM were analyzed. Cohort 1 included 18 patients treated with nivolumab or pembrolizumab, and intra- and extracranial responses were assessed. Cohort 2 comprised 20 patients who underwent both primary lung surgery and brain metastasectomy. Specimens from cohort 2 were subjected to immunohistochemical analysis for the following markers: CD3, CD4, CD8, FOXP3, and PD-1 on tumor infiltrating lymphocytes (TIL) and PD-L1 on tumor cells. Results Seven patients (38.9%) in cohort 1 showed progressive disease in both primary and intracranial lesions. Although the other 11 patients exhibited a partial response or stable disease in the primary lesion, eight showed a progression in BM. Interestingly, PD-1+ TILs were significantly decreased in BM (P = 0.034). For fifteen patients with adenocarcinoma, more distinctive patterns were observed in CD3+ (P = 0.078), CD8+ (P = 0.055), FOXP3+ (P = 0.016), and PD-1+ (P = 0.016) TILs. Conclusions There may be discordant responses to an ICI of lung cancer between primary lung lesion and BM based on discrepancies in the tumor microenvironment. The diminished infiltration of PD-1+ TILs in tumor tissue within the brain may be one of the major factors that hinder the response to anti–PD-1 antibody in BM.

Background The programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors.Methods Patients (aged ≥18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab’s safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay.Results Between May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1–2 severity; anemia (4.9%) was the most common grade 3–4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab 200 mg intravenous every 3 weeks was the dose and schedule recommended to be taken into subsequent clinical trials.Conclusions Tislelizumab monotherapy demonstrated an acceptable safety/tolerability profile. Durable responses were observed in heavily pretreated patients with advanced solid tumors, supporting the evaluation of tislelizumab 200 mg every 3 weeks, as monotherapy and in combination therapy, for the treatment of solid tumors and hematological malignancies.Trial registration number NCT02407990.

Abstract Background Antitumor immune response of programmed cell death ligand (PD-L1) has shown clinical value not only in Hodgkin lymphoma and EBV-associated lymphomas but also in EBV-negative diffuse large B cell lymphoma (DLBCL) of non-germinal center B cell-like (non-GCB) subtype. Signal transducer and activator of transcription 3 (STAT3) is known to induce PD-L1 in immune cells and its activated form, phosphorylated STAT3 (pSTAT3), is also frequently expressed in non-GCB DLBCL. Herein, we investigated associations between PD-L1 expression/gene alteration, pSTAT3 expression and clinicopathologic variables in EBV-negative DLBCL. Methods In 107 cases of DLBCLs with non-GCB subtype (67%; 72/107), GCB subtype (25%; 27/107) and unclassifiable cases (8%; 8/107), we performed PD-L1 and pSTAT3 immunohistochemistry and fluorescence in situ hybridization for PD-L1 gene translocation and copy number gain/amplification. Results PD-L1 was expressed in tumor cells (PD-L1t) in 21% (23/107; 30% cutoff), immune cells (PD-L1i) in 36% (38/107; 20% cutoff), and pSTAT3 in tumor nuclei in 41% (44/107; 40% cutoff). PD-L1 gene alteration was observed in 10% (10/102) including translocation in 6% (6/102) and copy number gain/amplification in 4% (4/102). Non-GCB subtype was associated with PD-L1t and pSTAT3 (p = 0.006 and p = 0.042), and tended to have PD-L1 gene alteration (p = 0.058). Tumoral PD-L1 expression without gene alteration (PD-L1t+ GA−) correlated with pSTAT3-positive tumor cell proportions (%) (p = 0.033). In survival analysis, pSTAT3 expression independently predicted shorter PFS in total cohort (p = 0.017) and R-CHOP-treated group (p = 0.007), and in pSTAT3-negative R-CHOP-treated subset, PD-L1 expression in immune cells (PD-L1i) correlated with shorter PFS (p = 0.042). Conclusions Gene alteration and protein expression of PD-L1 and pSTAT3 expression were closely related in DLBCL and constituted features of non-GCB subtype. In addition to known clinical significance of pSTAT3, immune cell expression of PD-L1 (PD-L1i) had also clinical value in pSTAT3-dependent manner. These findings may provide an insight into immunotherapeutic strategy and risk stratification in DLBCL patients.

Background Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. Methods Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. Results In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. Conclusion Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.

Background : Suicide lethality and intent are known potential determinants of hospitalization, and high degrees of these factors are discriminating characteristics of elderly suicide attempters. We evaluated their ability to predict hospitalization in elderly suicide attempters. Methods : Via medical charts and interview questionnaires, data were collected retrospectively on suicide attempters aged 65 years and older who presented to the Emergency Department (ED) from January 2012 to December 2016. Subjects were divided into hospitalization and discharge groups. Degrees of suicide lethality and intent were evaluated using the Risk-Rescue Rating Scale (RRRS) and the Suicide Intent Scale (SIS), respectively. The predictive abilities of these scales for hospitalization were assessed using logistic regression analysis and compared with the area under the receiver operating characteristic curve. Results : Of 168 patients, 110 (65%) were hospitalized. The RRRS and SIS scores for hospitalized patients were significantly higher; both scales were identified as independent predictors of hospitalization. The predictive performance of the RRRS for hospitalization was significantly superior to that of the SIS. Among SIS subscales, only the SIS part 2 was found to be an independent predictor of hospitalization. Its performance tended to be higher than the SIS, and comparable to the RRRS. The RRRS and SIS part 2 had greater sensitivity for predicting hospitalization than specificity. Conclusion : For elderly suicide attempters in the ED, the RRRS is a useful predictor of hospitalization. Further investigations based on the feasibility of the SIS part 2 as a predictor are needed.