It is extensively documented that tumor hypoxia contributes to the failure of chemotherapy and radiotherapy. Recent evidence suggests that hypoxia is also closely involved in the resistance to immunotherapy. In this review, we highlight how immune cells that are essential for the maximized immunotherapy efficacy, including cytotoxic T cells, dendritic cells, and natural killer cells, can adapt to tumor hypoxia. We then outline previous attempts targeting tumor hypoxia (for example, modulators of tumor cell oxygen consumption, perfusion modulators, hypoxia-activated prodrugs, hypoxia-inducible factor inhibitors, and hypoxia-responsive chimeric antigen receptor T cells) discussing how these approaches have resulted in an improvement of the antitumor response to immunotherapy in preclinical or clinical settings. Lastly, we review various non-invasive techniques to detect the tumor hypoxia and immune responses. We believe that an integration of the biological knowledge of immune cell adaptation to tumor hypoxia with the cutting edge non-invasive imaging technologies may ultimately allow us not only to select for patients who would benefit the most from the immunotherapy but also to monitor their responses in a real-time manner so that we can offer them an optimal personalized medicine in the clinic.

Coronary artery calcification (CAC) is highly prevalent in patients with chronic kidney disease (CKD) and is associated with major adverse cardiovascular events and metabolic disturbances. The triglyceride-glucose index (TyGI), a novel surrogate marker of metabolic syndrome and insulin resistance, is associated with CAC in the general population and in patients with diabetes. This study investigated the association between the TyGI and CAC progression in patients with CKD, which is unknown. Methods: A total of 1,154 patients with CKD (grades 1–5; age, 52.8 ± 11.9 years; male, 688 [59.6%]) were enrolled from the KNOWCKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The TyGI was calculated as follows: ln (fasting triglycerides × fasting glucose/2). Patients were classified into tertiles (low, intermediate, high) based on the TyGI. The primary outcome was annualized percentage change in CAC score [(percent change in CAC score + 1)12/follow-up months – 1] of ≥15%, defined as CAC progression. Results: During the 4-year follow-up, the percentage of patients with CAC progression increased across TyGI groups (28.6%, 37.5%, and 46.2% in low, intermediate, and high groups, respectively; p < 0.001). A high TyGI was associated with an increased risk of CAC progression (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.14–3.88; p = 0.02) compared to the low group. Moreover, a 1-point increase in the TyGI was related to increased risk of CAC progression (OR, 1.55; 95% CI, 1.06–1.76; p = 0.02) after adjustment. Conclusion: A high TyGI may be a useful predictor of CAC progression in CKD.

Background: Unlike gestational diabetic mellitus (GDM), which is strictly managed by most patients and physicians, obesity does not have proper management guidelines, and the importance of its management during pregnancy is often ignored. The aim of this study was to compare maternal and neonatal outcomes according to obesity and GDM, alone or in combination. Methods: This was a retrospective cohort study of 3,078 consecutive pregnant women who experienced prenatal care and delivery of a live singleton neonate between January 2016 and December 2020 at our institution. Study participants were categorized into 4 mutually exclusive groups, as follows: group 1, no GDM without obesity; group 2, GDM without obesity; group 3, no GDM with obesity; and group 4, GDM with obesity. Results: Compared to group 2, group 3 had higher rates of pre-eclampsia, cesarean section including emergent cesarean section rate. Also, neonates in group 3 were heavier and had lower glucose levels compared to those in group 2. Of note, there was no significant difference in maternal or neonatal outcomes except the rate of large-for-gestational-age (LGA) between group 1 and group 2. Among the GDM groups, group 4 had higher risks for pre-eclampsia, cesarean section, and LGA infant status than group 2. Conclusion Our data showed that obese women without GDM face higher risk of adverse pregnancy outcomes than women with supervised GDM and non-obese women. We also confirmed that adverse pregnancy outcomes associated with GDM were mainly attributable to obesity among women receiving GDM education.

Objective: To assess whether computed tomography (CT) conversion across different scan parameters and manufacturers using a routable generative adversarial network (RouteGAN) can improve the accuracy and variability in quantifying interstitial lung disease (ILD) using a deep learning-based automated software. Materials and Methods: This study included patients with ILD who underwent thin-section CT. Unmatched CT images obtained using scanners from four manufacturers (vendors A-D), standard- or low-radiation doses, and sharp or medium kernels were classified into groups 1–7 according to acquisition conditions. CT images in groups 2–7 were converted into the target CT sty le (Group 1: vendor A, standard dose, and sharp kernel) using a RouteGAN. ILD was quantified on original and converted CT images using a deep learning-based software (Aview, Coreline Soft). The accuracy of quantification was analyzed using the dice similarity coefficient (DSC) and pixel-wise overlap accuracy metrics against manual quantification by a radiologist. Five radiologists evaluated quantification accuracy using a 10-point visual scoring system. Results: Three hundred and fifty CT slices from 150 patients (mean age: 67.6 ± 10.7 years; 56 females) were included. The overlap accuracies for quantifying total abnormalities in groups 2–7 improved after CT conversion (original vs. converted: 0.63vs. 0.68 for DSC, 0.66 vs. 0.70 for pixel-wise recall, and 0.68 vs. 0.73 for pixel-wise precision; P < 0.002 for all). The DSCs of fibrosis score, honeycombing, and reticulation significantly increased after CT conversion (0.32 vs. 0.64, 0.19 vs. 0.47, and 0.23 vs. 0.54, P < 0.002 for all), whereas those of ground-glass opacity, consolidation, and emphysema did not change significantly or decreased slightly. The radiologists’ scores were significantly higher (P < 0.001) and less variable on converted CT. Conclusion CT conversion using a RouteGAN can improve the accuracy and variability of CT images obtained using different scan parameters and manufacturers in deep learning-based quantification of ILD.

Objectives: It is important that inflammatory bowel disease (IBD) patients adhere to their prescribed medication regimens to avoid the repeat exacerbations, complications, or surgeries associated with this disorder. However, there are few studies on medication adherence in patients with IBD, especially in Asian populations. So, we analyzed the factors associated with medication adherence in Korean IBD patients. Methods: Patients who had been diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) more than 6 months previously and receiving oral medications for IBD were enrolled. Medication adherence was measured using the Medical Adherence Reporting Scale (MARS-5), a self-reported medication adherence measurement tool. Results: Among 207 patients in the final study population, 125 (60.4%) had CD and 134 (64.7%) were men. The mean age was 39.63 years (SD, 13.16 years) and the mean disease duration was 10.09 years (SD, 6.33 years). The mean medication adherence score was 22.46 (SD, 2.86) out of 25, and 181 (87.4%) patients had score of 20 or higher.In multiple linear regression analysis, self-efficacy (β=0.341, P<0.001) and ≥3 dosing per day (β=–0.192 P=0.016) were revealed to be significant factors associated with medication adherence. Additionally, there was a positive correlation between self-efficacy and medication adherence (r=0.312, P<0.001). However, disease related knowledge, depression, and anxiety were not significantly associated with medication adherence. Conclusion To improve medication adherence among patients with IBD, a reduction in the number of doses per day and an improved self-efficacy will be helpful.

Determining blood loss [100% – RBV (%)] is challenging in the management of haemorrhagic shock. We derived an equation estimating RBV (%) via serial haematocrits (Hct1 , Hct2 ) by fixing infused crystalloid fluid volume (N) as [0.015 × body weight (g)]. Then, we validated it in vivo. Mathematically, the following estimation equation was derived: RBV (%) = 24k / [(Hct1 / Hct2 ) – 1]. For validation, nonongoing haemorrhagic shock was induced in Sprague–Dawley rats by withdrawing 20.0%–60.0% of their total blood volume (TBV) in 5.0% intervals (n = 9). Hct1 was checked after 10 min and normal saline N cc was infused over 10 min. Hct 2 was checked five minutes later. We applied a linear equation to explain RBV (%) with 1 / [(Hct1 / Hct2 ) – 1]. Seven rats losing 30.0%–60.0% of their TBV suffered shock persistently. For them, RBV (%) was updated as 5.67 / [(Hct1 / Hct2 ) – 1] + 32.8 (95% confidence interval [CI] of the slope: 3.14–8.21, p = 0.002, R2 = 0.87). On a Bland-Altman plot, the difference between the estimated and actual RBV was 0.00 ± 4.03%; the 95% CIs of the limits of agreements were included within the pre-determined criterion of validation (< 20%). For rats suffering from persistent, non-ongoing haemorrhagic shock, we derived and validated a simple equation estimating RBV (%). This enables the calculation of blood loss via information on serial haematocrits under a fixed N.Clinical validation is required before utilisation for emergency care of haemorrhagic shock.

Background/Aims: Although pediatric ulcerative colitis (UC) has a different phenotype and clinical course than adult UC, its clinical features and outcomes are poorly defined, especially in Asian populations. This study investigated the clinical features and long-term outcomes of pediatric UC in a Korean population. Methods: We retrospectively analyzed 208 patients aged <18 years diagnosed with UC between 1987 and 2013. The patient characteristics at diagnosis according to the Paris classification and the clinical course were analyzed. Results: The male-to-female ratio was 1.3:1, and the median patient age was 15.5 years. At diagnosis, 28.8% of patients had proctitis (E1), 27.8%, left-sided colitis (E2); 5.2%, extensive colitis (E3); and 38.2%, pancolitis (E4). The cumulative probabilities of extension after 5, 10, 15, and 20 years were 32.7%, 40.4%, 52.5%, and 65.8%, respectively. Eighteen patients underwent colectomy, and three patients had colorectal cancer. The cumulative probabilities of colectomy after 5, 10, 15, and 20 years were 7.1%, 8.9%, 12.6%, and 15.6%, and those of colorectal cancer after 10, 15, and 20 years were 0%, 2.1%, and 12.0%, respectively. The disease extent, Pediatric Ulcerative Colitis Activity Index severity, and systemic corticosteroid therapy were significant risk factors for colectomy. The development of primary sclerosing cholangitis was significantly associated with colorectal cancer. Conclusions This study provides detailed information on the disease phenotype and long-term clinical outcomes in a large cohort of Korean children with UC. They have extensive disease at diagnosis, a high rate of disease extension, and a low rate of cumulative colectomy.

Objective: This study aimed to explore the myelin volume change in patients with mild traumatic brain injury (mTBI) with post-concussion syndrome (PCS) using a multidynamic multiecho (MDME) sequence and automatic whole-brain segmentation. Materials and Methods: Forty-one consecutive mTBI patients with PCS and 29 controls, who had undergone MRI including the MDME sequence between October 2016 and April 2018, were included. Myelin volume fraction (MVF) maps were derived from the MDME sequence. After three dimensional T1-based brain segmentation, the average MVF was analyzed at the bilateral cerebral white matter (WM), bilateral cerebral gray matter (GM), corpus callosum, and brainstem. The Mann–Whitney U-test was performed to compare MVF and myelin volume between patients with mTBI and controls. Myelin volume was correlated with neuropsychological test scores using the Spearman rank correlation test. Results: The average MVF at the bilateral cerebral WM was lower in mTBI patients with PCS (median [interquartile range], 25.2% [22.6%–26.4%]) than that in controls (26.8% [25.6%–27.8%]) (p = 0.004). The region-of-interest myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (1.87 cm3 [1.70–2.05 cm3 ] vs. 2.21 cm3 [1.86– 3.46 cm3 ]; p = 0.003) and brainstem (9.98 cm3 [9.45–11.00 cm3 ] vs. 11.05 cm3 [10.10–11.53 cm3 ]; p = 0.015). The total myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (0.45 cm3 [0.39–0.48 cm3 ] vs. 0.48 cm3 [0.45–0.54 cm3 ]; p = 0.004) and brainstem (1.45 cm3 [1.28–1.59 cm3 ] vs. 1.54 cm3 [1.42–1.67 cm3 ]; p = 0.042). No significant correlation was observed between myelin volume parameters and neuropsychological test scores, except for the total myelin volume at the bilateral cerebral WM and verbal learning test (delayed recall) (r = 0.425; p = 0.048). Conclusion MVF quantified from the MDME sequence was decreased at the bilateral cerebral WM in mTBI patients with PCS. The total myelin volumes at the corpus callosum and brainstem were decreased in mTBI patients with PCS due to atrophic changes.

Background/Aims: We aimed to investigate the oral beclomethasone dipropionate’s (BDP) efficacy as an add-on therapy and to clarify the predictive factor for response to oral BDP in Korean ulcerative colitis (UC) patients. Methods: Patients with a stable concomitant drug regimen with exposure to oral BDP (5 mg/day) within 30 days before BDP initiation were included. Partial Mayo score (pMS) was used to evaluate response to oral BDP. Clinical remission (CREM) was defined as a post-treatment pMS ≤ 1 point. Clinical response (CRES) was defined as an at least 2-point decrease in post-treatment pMS and an at least 30% decrease from baseline pMS. Patients without CREM or CRES were considered nonresponders (NRs). Results: Of all, 37 showed CREM, 19 showed CRES, and 44 were NRs. The CREM group included more patients with mild disease activity (75.7% vs. 43.2%, p = 0.011) than NRs. In contrast to NRs, CREM and CRES patients showed significant improvement of post-treatment erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (ESR with p = 0.001, CRP with p = 0.004, respectively). Moreover, the initial rectal bleeding subscore (RBS) was significantly different between CREM and CRES, or NR (both with p < 0.001). In multivariate analyses, initial stool frequency subscore (SFS) of 0 and RBS of 0 were predictive factors for CREM (odds ratio [OR], 15.359; 95% confidence interval [CI], 1.085 to 217.499; p = 0.043 for SFS, and OR, 11.434; 95% CI, 1.682 to 77.710; p = 0.013 for RBS). Conclusions Oral BDP is an efficacious add-on therapy in Korean UC patients. Patients with initial SFS or RBS of 0 may be particularly good candidates for oral BDP.