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Background/Aims Improving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC. Methods A multicenter, hospital-based, prospective study was performed using a Moderateto- Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later. Results In a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p

Background/aims This study aimed to investigate the perceptions and behaviors of patients with inflammatory bowel disease (IBD) during the early coronavirus disease 2019 (COVID-19) pandemic in the major epidemic area in Korea. Methods Between April and May 2020, a cross-sectional survey was performed at two tertiary hospitals in Daegu, South Korea, on patients' experiences, coping strategies and perceptions. Results Most of the 544 patients participating in the survey strictly adhered to personal protection guidance against COVID-19. In the early COVID-19 crisis, many patients canceled or postponed hospital visits (57.5%) and rescheduled biologics administrations (26.4%). Although 13.6% utilized telemedicine, the frequency of individuals leaving their homes remained unchanged. Although 50.4% were concerned about their susceptibility to COVID-19, 72.2% adhered to their treatment for IBD. In patients taking biologics or Janus kinase inhibitors, 86.8% disagreed that they should discontinue their medication as a preventative measure against COVID- 19, but 21.9% actually discontinued their medications. Of those with discordance between the perception of IBD drug adherence and active behaviors, 5.4% of all and 39.4% of biologics or Janus kinase inhibitors withheld drugs specifically due to fear of COVID-19. Only 7% of all patients discussed drug safety with their physicians. The level of concern for COVID-19 depended on the type of drug used. Conclusions Patients with IBD showed concerns about the increased risk of COVID-19 due to IBD or their medications, and a considerable number of patients withheld their medications without consulting medical staff. Enhanced active communications with patients with IBD and appropriate health-related education should be provided.

Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and HBV infection, little is known about the relevant oncogenic effects. We sought to identify the landscape and mechanism of HBV integration, along with the genomic architecture of HBV-infected iCCA (HBV-iCCA) tumors.We profiled a cohort of 108 HBV-iCCAs using whole-genome sequencing, deep sequencing, and RNA sequencing, together with preconstructed data sets of HBV-infected HCC (HBV-HCC; n = 167) and combined hepatocellular cholangiocarcinoma (HBV-cHCC/CCA; n = 59), and conventional (n = 154) and fluke-related iCCAs (n = 16). Platforms based on primary iCCA cell lines to evaluate the functional effects of chimeric transcripts were also used. We found that HBV had inserted at multiple sites in the iCCA genomes in 45 (41.7%) of the tumors. Recurrent viral integration breakpoints were found at nine different sites. The most common insertional hotspot (7 tumors) was in the TERT (telomerase reverse transcriptase) promoter, where insertions and mutations (11 tumors) were mutually exclusive, and were accompanied by promoter hyperactivity. Recurrent HBV integration events (5 tumors) were also detected in FAT2 (FAT atypical cadherin 2), and were associated with enrichment of epithelial-mesenchymal transition-related genes. A distinctive intergenic insertion (chr9p21.3), between DMRTA1 (DMRT like family A1) and LINC01239 (long intergenic non-protein coding RNA 1239), had oncogenic effects through activation of the mammalian target of rapamycin (mTOR)/4EBP/S6K pathway. Regarding the mutational profiles of primary liver cancers, the overall landscape of HBV-iCCA was closer to that of nonviral conventional iCCA, than to HBV-HCC and HBV-cHCC/CCA.Our findings provide insight into the behavior of iCCAs driven by various pathogenic mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.

Noncerebral vasculitis is a wide-range noninfectious inflammatory disorder affecting the vessels. Vasculitides have been categorized based on the vessel size, such as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. In this document, we cover large-vessel vasculitis and medium-vessel vasculitis. Due to the challenges of vessel biopsy, imaging plays a crucial role in diagnosing this entity. While CTA and MRA can both provide anatomical details of the vessel wall, including wall thickness and enhancement in large-vessel vasculitis, FDG-PET/CT can show functional assessment based on the glycolytic activity of inflammatory cells in the inflamed vessels. Given the size of the vessel in medium-vessel vasculitis, invasive arteriography is still a choice for imaging. However, high-resolution CTA images can depict small-caliber aneurysms, and thus can be utilized in the diagnosis of medium-vessel vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Post-partum galactocele is a common benign disease among breastfeeding women, whereas retromammary and peri-implant galactocele are relatively rare conditions. Herein, a 34-yearold, 1 month-postpartum female, who had augmentation mammoplasty and a 1-month history of breast pump use, presented with left breast enlargement for 2 weeks. An initial left breast US revealed hyperechoic peri-implant fluid collection. Additional US-guided fine needle aspiration was done using a 21G-needle, draining the milk component in the process, and cytologic results revealed numerous crystals, suggestive of galactocele. Various diseases, especially breast implant-associated anaplastic large cell lymphoma, can cause peri-implant fluid collection in an augmented breast. Thus, correlating imaging features with clinical information and cytologic analysis plays an important role in appropriate management.

Background An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. Methods MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. Results Of the 85 patients [age, 54.0 (41.0–65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65–148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02–1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08–1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. Conclusions The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.

Chronic liver disease and liver transplantation are risk factors for poor physical health and quality of life. This meta-analysis aimed to examine whether supervised exercise improves the physical health and quality of life in patients with chronic liver disease and liver transplant. Articles were searched in four databases (MEDLINE, Cochrane, Embase, and the Web of Science) from 1 January 1990 to 6 July 2021. Studies that assessed the change in aerobic capacity and quality of life following supervised exercise in patients with chronic liver disease or in those who had undergone liver transplantation were included in this meta-analysis. The two independent reviewers extracted data and the methodological quality of the included studies was assessed by the Cochrane Handbook for Systematic Reviews of Interventions. The extracted data were statistically analyzed using review management software (RevMan 5.3). The meta-analysis included 11 studies, comprising 159 patients. We observed that aerobic capacity measured as VO2 peak and 6-min walking test improved in patients with chronic liver disease and liver transplant after supervised exercise. Among the parameters of Short-form-36 (SF-36) used for measuring the quality of life, only physical functioning improved after supervised exercise. The other parameters of SF-36 including role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health were not significantly improved after supervised exercise. Supervised exercise seems essential for patients with chronic liver disease and liver transplant. It was found to be helpful in enhancing the aerobic capacity and physical function in these patients.

Background Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment option for acute leukemia. We aimed to identify the comorbidity factors affecting survival outcomes after alloSCT and develop a new comorbidity index tool for predicting overall survival (OS). Methods A Korean nationwide cohort of 3,809 adults with acute leukemia treated with alloSCT between January 2002 and December 2018 was analyzed as the development cohort. A retrospective cohort comprising 313 consecutive adults with acute leukemia who underwent alloSCT between January 2019 and April 2020 was analyzed as the validation cohort. Results In the development cohort, advanced age, male sex, and comorbidities such as previous non-hematologic malignancy, hypertension, and coronary or cerebral vascular disease were significantly related to poor OS. Subsequently, a new comorbidity scoring system was developed, and risk groups were created, which included the low-risk (score ≤0.17), intermediate-risk (0.17< score ≤0.4), high-risk (0.4< score ≤0.55), and very high-risk (score ＞0.55) groups. The 1-year OS rates were discriminatively estimated at 73.5%, 66.2%, 61.9%, and 50.9% in the low-risk, intermediate-risk, high-risk, and very high-risk groups in the development cohort, respectively (P

Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients and are associated with poor prognosis. In this prospective study, we find increased Th17 frequencies in the blood of patients after chemoradiotherapy and a post‐therapeutic ratio of Th17/CD4+ T cells > 8% was associated with early recurrence. Furthermore, Th17 cells promote resistance of cervical cancer cells toward CRT, which was dependent on the AKT signaling pathway. Consistently, patients with high Th17 frequencies in pretherapeutic biopsies exhibit lower response to primary CRT. This work reveals a key role of Th17 cells in CRT resistance and elevated Th17 frequencies in the blood after CRT correspond with early recurrence. Our results may help to explain individual treatment responses of cervical cancer patients and suggest evaluation of Th17 cells as a novel predictive biomarker for chemoradiotherapy responses and as a potential target for immunotherapy in cervical cancer., This study demonstrates that chemoradiotherapy‐treated patients with cervical cancer have increased frequencies of Th17 cells. Th17 frequency was associated with early cancer relapse. Additionally, high pretherapeutic Th17 amounts in situ were correlated to a failed response to chemoradiotherapy. Our work suggests that the evaluation of Th17 cells could serve as a novel predictive biomarker for chemoradiotherapy responses and a potential target for immunotherapy in patients with cervical cancers.

The influence of long-term tacrolimus treatment on cognitive function remains to be elucidated. Using chronic tacrolimus neurotoxicity in mice, we evaluated the influence of tacrolimus on cognitive function, synaptic balance, its regulating protein (Klotho), and oxidative stress in the hippocampus. Compared to vehicle-treated mice, tacrolimus-treated mice showed significantly decreased hippocampal-dependent spatial learning and memory function. Furthermore, tacrolimus caused synaptic imbalance as demonstrated by decreased excitatory synapses and increased inhibitory synapses, and downregulated Klotho in a dose-dependent manner; its downregulation was localized to excitatory hippocampal synapses. Moreover, tacrolimus increased oxidative stress and was associated with the activation of the PI3K/AKT pathway in the hippocampus. The present results indicate that tacrolimus impairs cognitive function via synaptic imbalance, and that these processes are associated with Klotho downregulation at synapses through tacrolimus-induced oxidative stress in the hippocampus.

The coronavirus disease 2019 (COVID-19) pandemic has reduced the ability to prevent or control chronic disease due to the concerns about safety in accessing health care. Inflammatory bowel disease (IBD) is a chronic condition requiring long- term sustained treatment, which is difficult in the current panedemic situation. The Korean Association for the Study of Intestinal Diseases (KASID) has developed an expert consensus statement on the clinical practice management of adult inflammatory bowel disease during the COVID-19 pandemic. This expert consensus statement is based on guidelines and clinical reports from several countries around the world. It provides recommendations to deal with the risk of COVID-19 and medication use in IBD patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and emphasizes the importance of right treatment approach to avoid worsening of the disease condition in IBD patients.

Backgrounds/aims Surgical resection is the only curative treatment for biliary tract cancers; however, most patients undergo palliative chemotherapy because they are contraindicated for surgery. Conversion surgery, a treatment strategy for downsizing chemotherapy and subsequent surgical resection, is feasible for initially unresectable biliary tract cancers following the introduction of effective chemotherapeutic agents. Methods Patients initially diagnosed with unresectable biliary tract cancers, and treated with conversion surgery after palliative chemotherapy between 2013 and 2019, were reviewed retrospectively. Results Twelve patients underwent conversion surgery after palliative chemotherapy for initially unresectable biliary tract cancers. The final pathological diagnosis included six perihilar cholangiocarcinomas, four distal common bile duct cancers, and two gallbladder cancers. Different chemotherapy regimens were used, but all the patients were treated with gemcitabine at some point during their treatment. The median overall survival was 28 months, which was longer than that of patients treated with isolated palliative chemotherapy in previous studies. Conclusions Conversion surgery represents a therapeutic alternative for specific cases of unresectable biliary tract cancers. Palliative chemotherapy for initially unresectable biliary tract cancers is recommended for downsizing the tumor and expanding the indications for surgery. Further studies and clinical trials are required to develop new and effective chemotherapeutic regimens.

Purpose Laparoscopic distal pancreatectomy (LDP) is widely performed but its efficacy and safety are not established for malignant lesions. This study was aimed to compare outcomes of LDP and open distal pancreatectomy (ODP) in pancreatic ductal adenocarcinoma (PDAC). Methods Patients who underwent distal pancreatectomy for PDAC between 2009 and 2017 were enrolled. The preoperative clinical stage was evaluated and propensity score matching (PSM) was performed using age, sex, The American Joint Committee on Cancer 8th clinical T stage, and other organ involvement. Results In 186 patients enrolled, 35 (18.8%) received LDP. The ODP group showed larger tumor size and frequent involvement of other organs in preoperative images. However, after PSM, these differences were balanced. R0 resection (90.5% vs. 94.3%, P = 0.730), harvested lymph nodes (14.3 vs. 12.6, P = 0.380) and pathologic T stage (P = 0.474) were comparable between ODP and LDP groups, respectively. LDP demonstrated shorter operation time, less postoperative pain, and shorter hospitalization (14.4 days vs. 11.1 days, P = 0.026). In terms of long-term oncologic outcomes, median overall survival (32 months vs. 28 months, P = 0.724) and disease-free survival (18 months vs. 19 months, P = 0.926) were comparable. Conclusion LDP demonstrated better short-term outcomes and comparable long-term outcomes compared with ODP. LDP is a safe and feasible procedure for PDAC.

Background Chemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity. Methods Rat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed. Results Five control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01). Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, P P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P P P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P Conclusions Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.

This single-center study aimed to assess the perinatal outcomes and its associated factors in fetuses with twin-to-twin transfusion syndrome (TTTS) treated by fetoscopic laser coagulation (FLC).In this retrospective study, we included fetuses prenatally diagnosed with TTTS at Asan Medical Center, Seoul, Korea, between October 2011 and December 2018. All patients with TTTS stage II or higher and those with stage I TTTS coupled with symptomatic polyhydramnios or cardiac dysfunction were eligible for FLC.A total of 172 cases of monochorionic diamniotic twins and one case of dichorionic triamniotic triplets were prenatally diagnosed with TTTS and treated with FLC. The median gestational ages (GAs) at diagnosis and FLC were 20.3 and 20.5 weeks, respectively. The median GA of survivors at delivery was 32.5 weeks. The overall at least one twin- and double-survival rates within 28 days after birth were 82.1% and 55.5%, respectively. The GAs at diagnosis and FLC, Quintero stage, inter-twin weight discordance, associated selective intrauterine growth restriction (sIUGR), procedure time, volume of amnioreduction, preterm prelabor rupture of membranes (PPROM) within one week after FLC, intraoperative intrauterine bleeding, and chorioamnionitis were significant predictive factors of perinatal death. Associated sIUGR, absent end-diastolic flow of umbilical artery, and abnormal cord insertion were significantly associated with donor demiseFLC is an effective treatment for TTTS. The learning curve reached the acceptable target faster than in previous studies. Several prenatal parameters are identified as predictive factors of fetal survival in TTTS treated with FLC.

Background Lymph node (LN) metastasis is a well-known poor prognostic factor of pancreatic cancer. LN metastasis, through direct invasion of tumor cell to peritumoral lymph nodes (PTLN), is treated as the same as those which spread through lymphatic channels. This study aimed to evaluate the impact of PTLN invasion on the oncologic outcome of pancreatic cancer. Methods Five hundred and six patients who underwent operation for pancreatic ductal adenocarcinoma from 2012 to 2018 were reviewed. PTLN invasion was defined as direct invasion of tumor cells in contact with main tumor. Results Among the 506 patients, 112 patients (22.1%) had PTLN invasion. PTLN invasion group (PTLNI) showed better disease-free survival than regional LN metastasis group (RLNM) and combined LN metastasis group (CLNM) (PTLNI 21 vs RLNM 11 vs CLNM 12 months, P = .003). There was no significant difference between N0 and PTLNI (PTLNI 21 vs N0 23 months, P = .999). In multivariate analysis, conventional LN metastasis was a significant factor compared to N0, but PTLN invasion was not (hazard ratio 0.786 [0.507-1.220], P = .283). Conclusion Because PTLN invasion does not adversely affect survival in the same way as LN metastasis does, pancreatic cancer-may be overstaged if PTLN invasion were dealt in the same manner as a metastatic LN. Therefore, PTLN invasion should be disregarded from current nodal staging system.

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants. The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

Although hepatocellular carcinomas (HCCs) often recur in patients undergoing hepatectomy, there are no reliable biomarkers of this undesirable event. Recent RNA-based efforts have developed valuable genetic indices prognostic of cancer outcomes. We aimed to identify molecular predictors of early recurrence after resection of HCC, and reveal the genomolecular structure of the resected tumors. Based on the transcriptomic and genomic datasets of 206 HCC samples surgically resected in the Asan Medical Center (AMC), we performed a differential gene expression analysis to identify quantitative markers associated with early recurrence and used the unsupervised clustering method to classify genomolecular subtypes. Differential gene expression profiling revealed that S100P was the highest-ranked overexpressed gene in HCCs that recurred within 2 years of surgery. This trend was reproduced in immunohistochemical studies of the original cohort and an independent AMC cohort. S100P expression also independently predicted HCC-specific mortality post-resection (adjusted hazard ratio 1.09, 95% confidence interval 1.01–1.19; p = 0.042). Validation in a Chinese cohort and in in vitro experiments confirmed the prognostic value of S100P in HCC. We further identified five discrete molecular subtypes of HCC; a subtype with stem cell features (‘AMC-C4’) was associated with the worst prognosis, both in our series and another two Asian datasets, and S100P was most strongly upregulated in that subtype. We identified a promising prognostic biomolecule, S100P, associated with early recurrence after HCC resection, and established the genomolecular architecture of tumors affecting clinical outcomes, particularly in Asian patients. These new insights into molecular mediators should contribute to effective care for affected patients.

Background/aims Nilotinib is used for treating patients with imatinib-sensitive or -resistant chronic myeloid leukemia (CML); however, nilotinib-resistant cases have been observed in recent years. In addition, a considerable number of patients receiving nilotinib developed diabetes. Metformin is a front-line drug for the treatment of type 2 diabetes, and several studies have shown that diabetes patients treated with metformin have reduced incidence of cancer. This study aimed to define the effect of metformin on CML cells to determine whether metformin overcomes nilotinib resistance, and to identify novel targets for the treatment of nilotinib resistance. Methods We observed the effects of metformin and nilotinib on K562 and KU812 human CML cell lines. Nilotinib-resistant CML cell lines were generated by exposing cells to gradually increasing doses of nilotinib. Then, we investigated the driving force that makes resistance to nilotinib and the effect of metformin on the driving force. Results Sub-toxic doses of metformin enhanced nilotinib efficacy by reducing Bcl-xL expression, which induces apoptosis in CML cells. Next, we generated nilotinib-resistant K562 and KU812 cell lines that overexpressed the c-Jun N-terminal kinase (JNK) gene. JNK silencing by a JNK inhibitor restored sensitivity to nilotinib. Furthermore, metformin was effective in decreasing phosphorylated JNK levels, restoring nilotinib sensitivity. Combined treatment with nilotinib and metformin was more effective than combined treatment with nilotinib and a JNK inhibitor in terms of cell proliferation inhibition. Conclusion This study suggested that combination therapy with metformin and nilotinib may have clinical benefits of enhancing antileukemia efficacy and overcoming resistance to nilotinib.

Ankle-foot orthoses (AFOs) are widely prescribed for stroke rehabilitation. We investigated the potential of transcranial magnetic stimulation (TMS) at an early stage, after stroke, to predict the need of using AFOs in stroke patients. We recruited 35 patients who could walk with intermittent support of one person or independently 3 months after onset of stroke. The patients included in the study were classified into two groups: a TMS (+) group (n = 10), in which motor-evoked potential (MEP) in the affected tibialis anterior (TA) was present, and a TMS (-) group (n = 25), in which the MEP in the affected TA was absent. Three months after the onset of stroke, we investigated whether patients were using AFOs or not. We also checked the motor function of the affected lower extremity using the Medical Research Council (MRC) scale. After 3 months of onset of stroke in the TMS (+) group, 4 patients (40%) were using an AFO during ambulation. In the TMS (-) group, 21 patients (84%) were using an AFO. The probability of using AFOs in the 2 groups were significantly different. Additionally, 3 months after the onset of stroke, the MRC scores of ankle dorsiflexor power, on the affected side, were significantly higher in the TMS (+) group. Early TMS evaluation of the corticospinal tract to the TA appears to be useful for predicting the need of using AFOs in stroke patients during the recovery phase.

Objectives Sarcopenia is a common disease in the elderly population that causes disability, poor quality of life, and a high risk of death. In the current study, we conducted a meta-analysis to report basic knowledge about the prevalence of sarcopenia in the elderly in Korea. Methods We searched for articles in the MEDLINE, Cochrane Library, Embase, and Scopus databases published until December 28, 2020. Studies investigating the prevalence of sarcopenia in elderly Koreans aged ≥65 years were included. The methodological quality of the studies was evaluated using the Newcastle-Ottawa scale. Publication bias was evaluated using the Egger test and funnel plots. Results In total, 3 studies and 2922 patients were included in the meta-analysis. All 3 studies used the European Working Group on Sarcopenia in Older People criteria for the diagnosis of sarcopenia. The total prevalence of sarcopenia was 13.1-14.9% in elderly men and 11.4% in elderly women. Conclusions This meta-analysis is the first to estimate the pooled prevalence of sarcopenia in elderly Koreans, and its findings suggest that sarcopenia is common in this population. Therefore, attention should be paid to the prevention and control of sarcopenia.

Purpose Diagnostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) have been used for early detection to reduce its dismal survival rate. However, clinically feasible biomarkers are still rare. Therefore, in this study, we developed an automated multi-marker enzyme-linked immunosorbent assay (ELISA) kit using 3 biomarkers (leucine-rich alpha-2-glycoprotein [LRG1], transthyretin [TTR], and CA 19-9) that were previously discovered and proposed a diagnostic model for PDAC based on this kit for clinical usage. Methods Individual LRG1, TTR, and CA 19-9 panels were combined into a single automated ELISA panel and tested on 728 plasma samples, including PDAC (n = 381) and normal samples (n = 347). The consistency between individual panels of 3 biomarkers and the automated multi-panel ELISA kit were accessed by correlation. The diagnostic model was developed using logistic regression according to the automated ELISA kit to predict the risk of pancreatic cancer (high-, intermediate-, and low-risk groups). Results The Pearson correlation coefficient of predicted values between the triple-marker automated ELISA panel and the former individual ELISA was 0.865. The proposed model provided reliable prediction results with a positive predictive value of 92.05%, negative predictive value of 90.69%, specificity of 90.69%, and sensitivity of 92.05%, which all simultaneously exceed 90% cutoff value. Conclusion This diagnostic model based on the triple ELISA kit showed better diagnostic performance than previous markers for PDAC. In the future, it needs external validation to be used in the clinic.

The preoperative biliary drainage (PBD) in ampulla of Vater (AoV) cancer is indiscriminately performed without logical backgrounds. This study was performed to evaluate the effect of PBD on short and long-term outcomes in AoV cancer.313 patients who underwent pancreaticoduodenectomy and were pathologically diagnosed as AoV cancer between January 2000 and December 2014 were reviewed.167 patients (53.4%) underwent PBD: Endoscopic drainage was performed in 106 patients (33.9%) and percutaneous drainage in 61 (19.5%). The postoperative complication rate of PBD group was significantly higher than that of upfront surgery group (48.5% vs. 38.4%, p = 0.045). The 5-year disease-free survival rate (5Y-DFSR) was significantly lower in PBD group compared to upfront surgery group (53.8% vs. 74.3%, p 0.001). Worse 5Y-DFSR of PBD group was more evident in T1/T2 stage (59.2% vs. 84.1%, p 0.001). In multivariate analysis with T1/T2 staged patients, PBD was independently associated with worse outcome (hazard ratio 2.145 [95% confidence interval, 1.202-3.826], p = 0.010).For T1/T2 AoV cancer, PBD adversely affected the short-term postoperative complication rate as well as the long-term oncologic outcomes. Therefore, especially in patients with T1/T2 AoV cancer, routine practice of PBD should be refrained and be reserved for selected cases such as cholangitis.

Relapsing polychondritis (RP) is a rare, progressive immune-mediated systemic inflammatory disease of unknown etiology, characterized by recurrent inflammation of cartilaginous structures. Approximately 30% of RP cases are associated with other autoimmune diseases. However, the co-occurrence of RP and Crohn's disease (CD) has rarely been reported. Herein, we present a 35-year-old woman diagnosed with RP and CD, who was refractory to initial conventional medications, including azathioprine and glucocorticoid, but who subsequently responded to infliximab (IFX). For both diseases, remission was sustained with IFX. There has been no previous report regarding the successful treatment of co-existing RP and CD with IFX.

Background/Aims: Many patients uses the internet to obtain information about their diseases. However, there is increasing concern regarding the quality of in ternet information. Thus, we aimed to systematically evaluate the quality of web sites containing educational information about non-alcoholic fatty liver disease (NAFLD) in Korea. Methods: Naver, Daum, and Google search engines were searched using the term “non-alcoholic fatty liver disease” in Korean. Two reviewers independently evalu ated website quality using the quality evaluation instrument (QEI), which award ed websites scores for specific information on various aspects of NAFLD, as well as a five-point Likert scale (1-5), the DISCERN instrument, and a global quality scale (GQS). Results: Forty-seven websites met the inclusion criteria. We found that the quality of the internet information about NAFLD is generally poor. The mean QEI score with standard deviation was 10.31 ± 5.09 (range, 4 to 22), with only 17% of websites scoring higher than 10 points. The median GQS of the websites was 2.0, with no website achieving a score of 4 or 5. The QEI score was highly associated with the GQS score (r = 0.74, p < 0.01). For each DISCERN question from question 1 to ques tion 15, the mean score was less than 3. Conclusions: Overall, the internet health information for patients regarding NA FLD is poor and in need of much improvement. There is a need for institutional support, qualitative regulation of internet information, and development of an accreditation system to provide patients with internet health information of ap propriate quality.

Extra-domain B of fibronectin (EDB-FN) is an alternatively spliced form of fibronectin with high expression in the extracellular matrix of neovascularized tissues and malignant cancer cells. In this study, we evaluated the practicality of using EDB-FN as a biomarker and therapeutic target for malignant gliomas (MGs), representative intractable diseases involving brain tumors. Methods: The microarray- and sequence-based patient transcriptomic database 'Oncopression' and tissue microarray of MG patient tissue samples were analyzed. EDB-FN data were extracted and evaluated from 23,344 patient samples of 17 types of cancer to assess its effectiveness and selectivity as a molecular target. To strengthen the results of the patient data analysis, the utility of EDB-FN as a molecular marker and target for MG was verified using active EDB-FN-targeting ultrasmall lipidic micellar nanoparticles (~12 nm), which had a high drug-loading capacity and were efficiently internalized by MG cells in vitro and in vivo. Results: Brain tumors had a 1.42-fold cancer-to-normal ratio (p < 0.0001), the second highest among 17 cancers after head and neck cancer. Patient tissue microarray analysis showed that the EDB-FN high-expression group had a 5.5-fold higher risk of progression than the EDB-FN low-expression group (p < 0.03). By labeling docetaxel-containing ultrasmall micelles with a bipodal aptide targeting EDB-FN (termed APTEDB-DSPE-DTX), we generated micelles that could specifically bind to MG cells, leading to superior antitumor efficacy of EDB-FN-targeting nanoparticles compared to nontargeting controls. Conclusions: Taken together, these results show that EDB-FN can be an effective drug delivery target and biomarker for MG.

Actinic keratosis (AK) and Bowen's disease (BD) are common premalignant lesions of invasive squamous cell carcinoma that have different pathogenesis and clinical significance. Fatty acid-binding protein 5 (FABP5) is responsible for keratinocyte homeostasis and differentiation; however, no study has revealed its expression in AK and BD. Our study aimed to investigate the differential expression and significance of FABP5 in these lesions. Patients with pathologically confirmed cases of AK (n = 37) and BD (n = 12) were included in this study. FABP5 immunostaining pattern was assessed in the normal skin, AK and BD lesions, with a focus on the staining patterns of basal cells, atypical keratinocytes, and uninvolved epidermal keratinocytes. All patients with AK showed negative FABP5 expression in the atypical cells in the basal layer, whereas the uninvolved upper layers showed diffuse, strong FABP5 expression, regardless of the grade of AK. All patients with BD showed heterogeneous and diffuse FABP5 expression in atypical cells of all layers of the epidermis. This study is the first to investigate the role of FABP5 in premalignant skin lesions. The unique immunohistochemical localization of the FABP5 can be a helpful diagnostic marker, and altered fatty acid metabolism may be the key in understanding the different pathophysiology of AK and BD.

BACKGROUND Among various prognostic factors of pancreatic cancer, preoperative clinical information is obtained by imaging modality. This study aimed to evaluate clinical usefulness of preoperative carbohydrate antigen and preoperative standard uptake value in 18F-fluorodeoxyglucose positron emission tomography as predictive biological markers for resectable pancreatic ductal adenocarcinoma. METHODS A total of 189 patients with PDAC who underwent preoperative PET-computed tomography were evaluated. Patients underwent neoadjuvant chemotherapy, and R2 resection was excluded. The correlation between SUVmax and clinicopathologic parameters was analyzed. The C-tree statistical method was used to estimate cutoff values of logCA19-9 and SUVmax for survival rate. A multivariate analysis was conducted to identify prognostic factors for overall survival. RESULTS The median duration of OS was 26 months, and the 5-year survival rate was 22.4%. The optimal cutoff values for CA19-9 level was 150 U/mL and SUVmax was 5.5. When subjects were divided into three groups according to the combination of CA19-9 level and SUVmax from C-tree (high-risk group, CA19-9 > 150 U/mL and SUVmax > 5.5; intermediate-risk group, CA19-9 ≤ 150 U/mL and SUVmax > 5.5 or CA19-9 > 150 U/mL and SUVmax ≤ 5.5; and low-risk group, CA19-9 ≤ 150 U/mL and SUVmax ≤ 5.5), there was a significant 5YSR difference (5.6%, 24.3%, and 36.5%, P < .001). The multivariate analysis revealed high SUVmax, high preoperative CA19-9 level, venous invasion, and adjuvant chemotherapy were prognostic factors of OS. CONCLUSIONS CA19-9 and SUVmax are strong prognostic biological factors in resectable PDAC. Moreover, patients with high CA19-9 level and SUVmax are not indicated for upfront surgery.

Doppler ultrasonography (US) is widely used for the differential diagnosis of thyroid nodules, metastatic cervical lymph nodes in patients with thyroid cancer, and diffuse parenchymal disease, as well as for guidance in various US-guided procedures, including biopsy and ablation. However, controversies remain regarding the appropriate use and interpretation of Doppler US. Therefore, the Korean Society of Thyroid Radiology organized a taskforce to develop a consensus statement on the clinical use of Doppler US for thyroid disease. The review and recommendations in this article are based on a comprehensive analysis of the current literature and the consensus of experts.

Background To compare admission lactate and base deficit (BD), which physiologically reflect early hemorrhagic shock, as outcome predictors of pediatric trauma. Methods We reviewed the data of children with trauma who visited a Korean academic hospital from 2010 through 2018. Admission lactate and BD were compared between children with and without primary outcomes. The outcomes included in-hospital mortality, early (≤24 h) transfusion, and early surgical interventions for the torso or major vessels. Subsequently, performances of lactate and BD in predicting the outcomes were compared using receiver operating characteristic curves. Logistic regressions were conducted to identify the independent associations of the two markers with each outcome. Results Of the 545 enrolled children, the mortality, transfusion, and surgical interventions occurred in 7.0%, 43.5%, and 14.9%, respectively. Cutoffs of lactate and BD for each outcome were as follows: mortality, 5.1 and 6.7 mmol/L; transfusion, 3.2 and 4.9 mmol/L; and surgical interventions, 2.9 and 5.2 mmol/L, respectively. No significant differences were found in the areas under the curve for each outcome. Of the two markers, a lactate of >5.1 mmol/L was associated with mortality (adjusted odds ratio, 6.43; 95% confidence interval, 2.61-15.84). A lactate of >3.2 mmol/L (2.82; 1.65-4.83) and a BD of >4.9 mmol/L (2.32; 1.32-4.10) were associated with transfusion, while only a BD of >5.2 mmol/L (2.17; 1.26-3.75) was done with surgical interventions. Conclusions In pediatric trauma, lactate is more strongly associated with mortality. In contrast, BD may have a marginally stronger association with the need for hemorrhage-related procedures.

Summary Background and aims Since there is a shortage of liver donors, we investigated recurrence patterns and outcomes after liver resection (LR) to determine the feasibility of salvage liver transplantation (SLT). Methods We analyzed 468 patients with hepatocellular carcinoma (HCC) within the Milan criteria (MC) who were mainly associated with Hepatitis B virus infection (76.3%) and had undergone curative LR as an initial treatment. Results The overall survival (OS) rates were 86.6% and 67.4% at 5 and 10 years after LR, respectively. During a median follow-up of 59 months, 211 patients experienced recurrences including 175 (37.4%) within MC and 36 (7.7%) beyond MC. Survival was lowest in patients with beyond MC-recurrence followed by within MC- and no-recurrence groups (26.5%, 86.6%, and 94.7% at 5 years, respectively, P Conclusion Curative LR achieved a 5-year survival of > 85% in patients with transplantable HCC, but early SLT after recurrence within MC is advocated because of poor survival and high risk of progression thereafter. Further, prophylactic LT could be considered for those with high risk of recurrence.

Growth charts are essential for monitoring the postnatal growth of preterm infants. The preterm postnatal follow-up study (PPFS) of the Intergrowth-21st Project provides new growth standards based on a longitudinal study. This study was conducted to investigate the prevalence of extrautrine growth restriction (EUGR) and the associated factors of EUGR in preterm infants, using the PPFS charts and the Fenton charts. Data of 1,356 infants with gestational age (GA) less than 28 weeks from the Korean Neonatal Network were analysed. The prevalence of small for gestational age (SGA) of weight and length was higher with the Intergrowth charts than with the Fenton charts. EUGR in weight and length was more prevalent when using the Fenton charts. Multivariate analysis showed that low GA, high birthweight z score, male, treated patent ductus arteriosus (PDA), necrotizing enterocolitis, intraventricular haemorrhage and duration of parenteral nutrition (PN) were associated with EUGR in weight by the Intergrowth charts. High birthweight z score, treated PDA and PN duration were associated with EUGR defined by the Fenton charts. Conclusion: Compared to the Fenton charts, SGA was more defined and EUGR was less prevalent in extremely low gestational infants, while EUGR defined by the Intergrowth charts categorized infants with adverse clinical courses more elaborately.What is Known:• Preterm infants are at risk of postnatal growth restriction (PGR), although optimal postnatal growth is important for the long-term outcomes.• Growth charts are essential tools to monitor the postnatal growth of preterm infants.What is New:• PGR of weight and length were less defined with the Intergrowth charts than the Fenton charts.• PGR defined by the Intergrowth preterm postnatal follow-up study (PPFS) chart categorized preterm infants with morbidities more elaborately than the Fenton charts. Electronic supplementary material The online version of this article (10.1007/s00431-020-03796-0) contains supplementary material, which is available to authorized users.

Background Bronchiolitis obliterans syndrome (BOS) is a rare, progressive and irreversible airway disease associated with significant mortality after allogeneic hematopoietic stem-cell transplantation (HSCT). In this study, we investigated the therapeutic effect of high-dose budesonide/formoterol (320/9 µg bid) in patients with BOS after HSCT already using low-dose budesonide/formoterol (160/4.5 µg bid). Methods After a retrospective chart review, patients who were initially treated with budesonide/formoterol 160/4.5 µg bid and increased their dose to 320/9 µg bid between March 2009 and February 2019 were enrolled. Pulmonary function test (PFT) and COPD assessment test (CAT) were performed before and after changing the drug dose. Efficacy was assessed within 3 months after increasing the drug dose; the primary variable was changes in forced expiratory volume in 1 second (FEV1) and CAT score. Safety was assessed as the incidence of pneumonia within 3 months after increasing the drug dose. Results Seventy-seven patients were treated with budesonide 160 µg plus formoterol 4.5 µg twice a day for more than 3 months and the dose was increased to budesonide 320 µg plus 9.0 µg twice a day. After treatment with high-dose ICS/LABA (budesonide 320 µg plus formoterol 9.0 µg twice a day for 12 weeks), there were no significant differences in FEV1 (before treatment 1.59 L vs. after treatment 1.65 L, P=0.182) or FVC (before treatment 2.93 L vs. after treatment 2.96 L, P=0.519) compared to before starting the high dose treatment. There were no significant differences in the total CAT score. Of all patients, 34.2% of patients had an increase in FEV1 ≥100 mL and 35.3% of patients showed a decrease ≥2 points in CAT score. In safety assessment, there were no significant differences between the two periods. Conclusions Our study failed to show superior effect of high-dose budesonide/formoterol (320/9 µg) compared with low-dose. However, high-dose budesonide/formoterol was safe and there was no lung function deterioration.

Although previous studies have shown that the administration of fibroblast growth factor 21 (FGF21) reverses hepatic steatosis, the mechanism by which FGF21 exerts a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) is not yet entirely understood. We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable target for NAFLD. We investigated the mechanism underlying the therapeutic effect of recombinant FGF21 on NAFLD, focusing on the involvement of hepatic STAMP2. In this study, we used human nonalcoholic steatosis patient pathology samples, C57BL/6 mice for a high-fat diet (HFD)-induced in vivo NAFLD model, and used human primary hepatocytes and HepG2 cells for oleic acid (OA)-induced in vitro NAFLD model. We observed that recombinant FGF21 treatment ameliorated hepatic steatosis and insulin resistance through the upregulation of STAMP2 expression. We further observed hepatic iron overload (HIO) and reduced iron exporter, ferroportin expression in the liver samples obtained from human NAFLD patients, and HFD-induced NAFLD mice and in OA-treated HepG2 cells. Importantly, recombinant FGF21 improved HIO through the hepatic STAMP2-mediated upregulation of ferroportin expression. Our data suggest that hepatic STAMP2 may represent a suitable therapeutic intervention target for FGF21-induced improvement of NAFLD accompanying HIO.

The metabolic properties of tumor microenvironment (TME) are dynamically dysregulated to achieve immune escape and promote cancer cell survival. However, in vivo properties of glucose metabolism in cancer and immune cells are poorly understood and their clinical application to development of a biomarker reflecting immune functionality is still lacking. Methods: We analyzed RNA-seq and fluorodeoxyglucose (FDG) positron emission tomography profiles of 63 lung squamous cell carcinoma (LUSC) specimens to correlate FDG uptake, expression of glucose transporters (GLUT) by RNA-seq and immune cell enrichment score (ImmuneScore). Single cell RNA-seq analysis in five lung cancer specimens was performed. We tested the GLUT3/GLUT1 ratio, the GLUT-ratio, as a surrogate representing immune metabolic functionality by investigating the association with immunotherapy response in two melanoma cohorts. Results: ImmuneScore showed a negative correlation with GLUT1 (r = -0.70, p < 0.01) and a positive correlation with GLUT3 (r = 0.39, p < 0.01) in LUSC. Single-cell RNA-seq showed GLUT1 and GLUT3 were mostly expressed in cancer and immune cells, respectively. In immune-poor LUSC, FDG uptake was positively correlated with GLUT1 (r = 0.27, p = 0.04) and negatively correlated with ImmuneScore (r = -0.28, p = 0.04). In immune-rich LUSC, FDG uptake was positively correlated with both GLUT3 (r = 0.78, p = 0.01) and ImmuneScore (r = 0.58, p = 0.10). The GLUT-ratio was higher in anti-PD1 responders than nonresponders (p = 0.08 for baseline; p = 0.02 for on-treatment) and associated with a progression-free survival in melanoma patients who treated with anti-CTLA4 (p = 0.04). Conclusions: Competitive uptake of glucose by cancer and immune cells in TME could be mediated by differential GLUT expression in these cells.

Objective: To develop a novel approach for tissue engineering of soft-tissue flaps suitable for free microsurgical transfer, using an injectable nanofiber hydrogel composite (NHC) vascularized by an arteriovenous (AV) loop. Approach: A rat AV loop model was used for tissue engineering of vascularized soft-tissue flaps. NHC or collagen-elastin (CE) scaffolds were implanted into isolation chambers together with an AV loop and explanted after 15 days. Saphenous veins were implanted into the scaffolds as controls. Neoangiogenesis, ultrastructure, and protein expression of SYNJ2BP, EPHA2, and FOXC1 were analyzed by immunohistochemistry and compared between the groups. Rheological properties were compared between the two scaffolds and native human adipose tissue. Results: A functional neovascularization was evident in NHC flaps with its amount being comparable with CE flaps. Scanning electron microscopy revealed a strong mononuclear cell infiltration along the nanofibers in NHC flaps and a trend toward higher fiber alignment compared with CE flaps. SYNJ2BP and EPHA2 expression in endothelial cells (ECs) was lower in NHC flaps compared with CE flaps, whereas FOXC1 expression was increased in NHC flaps. Compared with the stiffer CE flaps, the NHC flaps showed similar rheological properties to native human adipose tissue. Innovation: This is the first study to demonstrate the feasibility of tissue engineering of soft-tissue flaps with similar rheological properties as human fat, suitable for microsurgical transfer using an injectable nanofiber hydrogel composite. Conclusions: The injectable NHC scaffold is suitable for tissue engineering of axially vascularized soft-tissue flaps with a solid neovascularization, strong cellular infiltration, and biomechanical properties similar to human fat. Our data indicate that SYNJ2BP, EPHA2, and FOXC1 are involved in AV loop-associated angiogenesis and that the scaffold material has an impact on protein expression in ECs.

This study aimed to investigate the relationship between aerobic capacity and health-related quality of life (HRQOL) in men with cerebral palsy (CP) by measuring aerobic capacity and using the Health-Related Quality of Life questionnaire. The subjects were ambulant men with CP (N = 34), with a mean age, height, weight, and body mass index of 36.6 ± 9.2 years, 163.9 ± 8.9 cm, 58.6 ± 9.1 kg, and 21.6 ± 2.9 kg·m-2, respectively. Aerobic capacity was measured during a graded exercise test and shuttle run test. Quality of life was evaluated using the Health-Related Quality of Life (Medical Outcomes Study Short Form-36 [SF-36]). The analysis performed using the physical scale of HRQOL as the dependent variable revealed that the contribution rate of physical functioning was 46.3%, role physical was 21.8%, bodily pain was 7.5%, general health was 27.3%, and physical component summary was 36.1%; the aerobic capacity differed significantly in terms of physical functioning, role physical, general health, and physical component summary (p < .05). Peak oxygen uptake was a particularly significant explanatory variable for role physical, and role physical (p < .05). However, the analysis performed using the mental scale of HRQOL as the dependent variable revealed that the contribution rate of vitality was 13.0%, social functioning was 17.3%, role emotional was 14.9%, mental health was 8.1%, and mental component summary was 15.3%; the aerobic capacity showed no significant difference. The aerobic capacity representing the athletic performance level of men with CP positively affected physical health satisfaction but not mental health satisfaction.

Background We determined the relationships among the subjective symptoms of sleep apnea and daytime sleepiness, depressive symptoms, and anxiety in adults with obstructive sleep apnea (OSA). Methods We developed the Subjective Apnea Severity Questionnaire (SASQ) to measure subjective OSA symptoms during the night and on waking in the morning. Construct validity and reliability were assessed. The Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and State Scale of State Trait Anxiety Inventory (STAI-S) were applied. Multiple linear regression analyses were performed, and the results were adjusted for several confounders. Results A total of 337 OSA patients were included. The SASQ consists of eight items with three domains. Cronbach's α for the SASQ was 0.657. The mean SASQ score was 1.35 ± 0.59. Symptoms related to nocturnal breathing difficulties were associated with polysomnographic (PSG) respiratory parameters. In the adjusted models, total SASQ scores were associated with ESS scores but not with BDI or STAI-S scores. Unlike other symptom groups, nocturnal breathing difficulties tended toward a positive relationship with ESS scores (p = 0.076), but were negatively related to BDI scores (p = 0.003) and STAI-S scores (p = 0.012). Symptoms related to nocturnal awakening or morning waking were either positively related or unrelated to ESS, BDI, and STAI-S scores. Conclusions The subjective OSA symptoms measured via the SASQ were associated with daytime sleepiness in adults with OSA, but not with depressive symptoms or anxiety. Nocturnal breathing difficulties were positively related to daytime sleepiness, but negatively related to depressive symptoms and anxiety.

Purpose Serous cystic neoplasm (SCN) of the pancreas is considered benign in most cases. However, some SCN patients undergo surgical resection because lesions could not be differentiated preoperatively. This study evaluated causes of resection for SCN, investigated clinical and radiological features of surgically resected SCNs, and compared characteristics of SCNs diagnosed accurately and those misdiagnosed. Methods One hundred patients, who underwent surgery for pancreatic cystic tumors with pathological confirmation of SCN between 2000 and 2014 were retrospectively analyzed. Results The mean patient age was 52.9 years, 67 (67%) were female, and most lesions (72%) were located in the pancreatic body or tail. Fifty-one (51%) pathologically confirmed SCNs were preoperatively diagnosed as non-SCNs. Patients underwent surgery due to uncertain diagnosis (58%) or symptomatology (18%). According to radiological examination, most lesions were macrocystic (85%), exhibited septation (58%), or were enhancing lesions (48%). Compared with preoperatively diagnosed non-SCNs, accurately diagnosed SCNs exhibited septation (75.5% vs. 41.2%, P = 0.001) and central scar (36.7% vs. 11.8%, P = 0.003) more frequently in radiological examinations. In terms of macrocystic tumors (n = 85), most parameters did not differentiate preoperative diagnoses, although lesions accurately diagnosed as SCN exhibited septation more frequently than those preoperatively misdiagnosed as mucinous cystic neoplasm or intraductal papillary mucinous neoplasm (70.7% vs. 38.9% vs. 33.3%, respectively, P = 0.009). Conclusion It is difficult to accurately distinguish macrocystic SCNs from other cystic tumors using conventional radiological methods. For more accurate diagnosis, new biomarkers and/or other diagnostic modalities are needed and warrant further investigation.

Objective: The purpose of this study was to determine the effect of vaginal progesterone for luteal phase support (LPS) on the clinical pregnancy rate (CPR) in natural frozen embryo transfer (FET) cycles via a meta-analysis.Methods: We performed a meta-analysis of randomized controlled trials (RCTs) and retrospective studies that met our selection criteria. Four online databases (PubMed, Embase, Medline, and the Cochrane Library) were searched between January 2017 and May 2017. Studies were selected according to predefined inclusion criteria and meta-analyzed using R software version 2.14.2. The main outcome measure was CPR.Results: A total of 18 studies were reviewed and assessed for eligibility. One RCT (n=435) and three retrospective studies (n=3,033) met the selection criteria. In a meta-analysis of the selected studies, we found no significant difference in the CPR (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.60–1.55) between the vaginal progesterone and control groups. An analysis of the two retrospective cohort studies that reported the live birth rate (LBR) following FET showed a significantly higher LBR in the vaginal progesterone group (OR, 1.72; 95% CI, 1.21–2.46). A subgroup meta-analysis of FET conducted 5 days after injection of human chorionic gonadotropin showed no significant differences between the two groups with regard to the CPR (OR, 1.18; 95% CI, 0.90–1.55) or miscarriage rate (OR, 0.73; 95% CI, 0.36–1.47).Conclusion: The results of this meta-analysis of the currently available literature suggest that LPS with vaginal progesterone in natural FET cycles does not improve the CPR.

Early diagnosis of hepatocellular carcinoma (HCC) increases the chances of curative treatment and long-term survival.1 2 We read with interest the analytical study by Zhang et al presenting nomogram models predicting recurrence-free survival and guiding therapeutic decisions in a patient-tailored approach to treatment of early-stage HCC within Milan criteria.3 The refined Barcelona Clinic Liver Cancer (BCLC) guidelines no longer limit the size of solitary nodules in the definition of stage A HCC. However, there is continuing debate about the need to restrict the maximum diameter of single HCCs to inside the Milan limit (≤5 cm).4–6 In a survival-based confirmatory investigation, we primarily used a Korean nationwide cancer registry database of 10 510 new HCC cases. These cases were randomly sampled and registered in 54 hospitals, and investigated by the Korea Liver Cancer Study Group and the governmental organisation of the Korea Central Cancer Registry in 2008–2014. We included in the final analysis 1610 asymptomatic HCC subjects with BCLC stage A or stage B who had preserved liver function levels referred to as Child-Pugh class A without ascites and who initially received standard treatments as per BCLC stage (online supplemental figure S1).4 The population was divided into four groups: group 1, stage A disease fulfilling Milan criteria undergoing liver resection or transplantation, or local ablation; group 2, potential stage A with single nodules >5 cm undergoing resection; group 3, potential stage B with single nodules >5 cm undergoing transarterial chemoembolisation (TACE); and group 4, stage B undergoing TACE. Five-year overall survival (OS) rates were significantly different across the four groups (p

Background Nongestational choriocarcinoma is a rare ovarian malignancy with a prognosis worse than that of gestational choriocarcinoma. Debulking surgery is the primary treatment for ovarian carcinoma. However, fertility preservation is important in young women. Case A 15-year-old girl with no sexual experience was admitted for abnormal uterine bleeding. Ultrasonography showed a solid mass in the right ovary and her serum β-human chorionic gonadotrophin levels were markedly elevated. We performed right oophorectomy, omentectomy, and peritoneal washing cytology. The uterus and left adnexa were preserved. She was diagnosed with nongestational choriocarcinoma, stage IIA. She received adjuvant chemotherapy (etoposide, methotrexate, actinomycin, cyclophosphamide, and oncovin regimen) and has been disease-free for more than 5 years. Summary and Conclusion Fertility-sparing surgery combined with chemotherapy is an acceptable treatment option for young patients with locally advanced nongestational choriocarcinoma.

Background A high number of focal lesions (FL) detected using PET/CT at diagnosis were found to be associated with adverse prognosis along with Revised International Staging System (R-ISS). In present study, we combined R-ISS with FL using PET/CT to design a reliable and easily applicable risk stratification system in patients with newly diagnosed MM (NDMM). Methods In training cohort, the data of 380 patients with NDMM who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis from 10 hospitals of the Korean Multiple Myeloma Working Party were retrospectively analyzed. All patients were classified by R-ISS and were treated by frontline therapy with proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD). The K-adaptive partitioning algorithm was adopted to develop the new risk groups with homogeneous survival. Sixty-seven patients in external validation cohort were additionally collected to confirm reproducibility of the new risk groups. Results In the training cohort, 199 patients (52.4%) showed FL > 3 using PET/CT at diagnosis. R-ISS stages I, II, and III were 78 patients (20.5%), 230 (60.5%), and 72 (18.9%), respectively. The combined R-ISS with PET/CT newly allocated NDMM patients into four groups: R-ISS/PET stage I (n=30; R-ISS I with FL≤3), stage II (n=149; R-ISS I with FL>3 and R-ISS II with FL≤3), stage III (n=166; R-ISS II with FL>3 and R-ISS III with FL≤3), and stage IV (n=35; R-ISS III with FL>3). The new R-ISS/PET showed significantly pronounced survival differences according to stages. Two-year overall survival (OS) rates were 96.6%, 89.5%, 75.0%, and 57.9% (p < 0.001), and 2-year progression-free survival (PFS) rates were 86.9%, 65.1%, 41.9%, and 15.2% (p < 0.001) in stages I, II, III, and IV, respectively. The prognostic role of the R-ISS/PET for survival outcomes was also confirmed in different subgroups classified by transplant eligibility and by types of treatments. In the external validation cohort, the new R-ISS/PET was successfully implemented. Two-year OS rates for were 100%, 89.9%, 82.6%, and 42.0% for R-ISS/PET I, II, III, and IV, respectively (p = 0.001). PFS rates at 2 years for each R-ISS/PET were 100%, 74.5%, 57.9%, and 25.6%, respectively (p = 0.004). In the multivariate Cox analysis for survival outcome, R-ISS/PET was a significant factor and could predict long-term outcomes with regard to OS: stage II vs. I (HR 2.50, p = 0.215), (ii) stage III vs. I (HR 5.11, p = 0.025), and (iii) stage IV vs. I (HR 10.3, p = 0.003) and PFS: (i) stage II vs. I (HR 2.21, p = 0.005), (ii) stage III vs. I (HR 4.57, p < 0.001), and (iii) stage IV vs. I (HR 9.48, p < 0.001). Conclusion The new R-ISS/PET had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely. Thus, R-ISS/PET is applicable for identifying heterogeneous manifestation of clinical MM. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: There have been no studies evaluating the glymphatic system function in patients with migraine. In this study, we evaluated the alterations in glymphatic system function in patients with migraine compared to healthy controls using a diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS) method. We also investigated the differences in glymphatic system function between migraine patients with and without aura using the ALPS method.Methods: We prospectively enrolled patients with migraine and healthy controls. All brain magnetic resonance imaging (MRI), including DTI, in participants, patients with migraine, and healthy controls were obtained using the same MRI scanner. We calculated the ALPS index and compared the differences in the ALPS index between patients with migraine and healthy controls, and between migraine patients with and without aura. In addition, we conducted a correlation analysis between glymphatic system function and the clinical characteristics of migraine.Results: We enrolled 92 patients with migraine and 80 healthy controls. There were no significant differences in the ALPS index between patients with migraine and healthy controls (1.655 vs. 1.713, p = 0.233), and between migraine patients with and without aura (1.690 vs. 1.645, p = 0.601). There were no significant correlations between the ALPS index and clinical characteristics of migraine, including age (r = -0.070, p = 0.507), age of onset (r = 0.066, p = 0.552), disease duration (r = -0.115, p = 0.306), attack frequency (r = -0.049, p = 0.668), and headache intensity (r = -0.003, p = 0.976).Conclusions: There was no glymphatic system dysfunction in patients with migraine. In addition, there were no differences in glymphatic system function between migraine patients with and without aura. We also demonstrated the feasibility of the ALPS method, which can be used for further research on various neurological diseases.

Background Endoscopic assessment of disease activity is a key parameter in the management of ulcerative colitis. Whether sigmoidoscopy alone is sufficient to evaluate the disease activity in ulcerative colitis lacks studies. Methods We retrospectively analyzed the medical records and endoscopic results of patients with ulcerative colitis followed by colonoscopy in seven tertiary hospitals between January 2012 and December 2018. Endoscopic disease activity was scored using the Mayo endoscopic subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for each segment from the colonoscopy images. Concordance was evaluated by comparing the highest MES and UCEIS in the rectosigmoid and proximal regions to confirm the usefulness of sigmoidoscopy. Results A total of 500 colonoscopic examinations from 333 patients were enrolled. Only in 7.6% [k(kappa): 0.893, r(Spearman): 0.906, p 0.001] and 8.6% [k(kappa): 0.890, r(Spearman): 0.914; p 0.001] of cases, MES and UCEIS scored more severely in the proximal colon. Comparison of active disease (MES ≥ 2) in the rectosigmoid area and the entire colon showed a high concordance rate [k(kappa): 0.899, r(Spearman): 0.904, p 0.001]. Endoscopic healing (MES = 0) also showed a high concordance rate [k(kappa): 0.882, r(Spearman): 0.887, p 0.001]. In 38 cases (7.6%) of patients with a higher MES in the proximal area, it was significantly higher in patients with previous extensive colitis. Conclusions Sigmoidoscopy and colonoscopy showed a high concordance rate. Therefore, sigmoidoscopy is considered a sufficient substitute for colonoscopy. However, colonoscopy should be considered in patients with previous extensive colitis.

Background Many patients with complex regional pain syndrome (CRPS) experience refractory pain with severe restrictions in the activities of daily living. Oral prednisolone is commonly used to treat these patients. Purpose To review previous studies assessing the effects of prednisolone in CRPS patients. Methods and materials Articles published from January 1, 1980 to July 23, 2021 in the PubMed database were searched using the following key phrases: (prednisolone OR corticosteroid OR steroid) AND (complex regional pain syndrome OR reflex sympathetic dystrophy OR shoulder hand syndrome OR causalgia). Specifically, we included those articles in which oral prednisolone or corticosteroids were used to control the CRPS symptoms. Results In total, 11 articles were included, comprising 3 randomized trials, 5 single-arm prospective observational studies, and 3 retrospective studies. Nearly all previous studies reported that oral prednisolone can effectively control the CRPS symptoms. Moreover, though 30-100 mg/day of oral prednisolone was initially administered in these studies, 30 mg/day was also found to be effective in controlling the symptoms. Although prednisolone was usually administered for 1-3 months, short-term treatment for 1-2 weeks was also reportedly effective. Furthermore, only 0-30% of the patients in these studies had minor side effects after prednisolone treatment. Conclusions Our review showed that prednisolone may be effective in alleviating the CRPS symptoms. To determine higher levels of evidence, a full systematic review with more highly-qualified studies, such as randomized controlled trials, should be conducted in the future.

Chemotherapy is a mainstream cancer treatment, but has a constant challenge of drug resistance, which consequently leads to poor prognosis in cancer treatment. For better understanding and effective treatment of drug-resistant cancer cells, omics approaches have been widely conducted in various forms. A notable use of omics data beyond routine data mining is to use them for computational modeling that allows generating useful predictions, such as drug responses and prognostic biomarkers. In particular, an increasing volume of omics data has facilitated the development of machine learning models. In this mini review, we highlight recent studies on the use of multi-omics data for studying drug-resistant cancer cells. We put a particular focus on studies that use computational models to characterize drug-resistant cancer cells, and to predict biomarkers and/or drug responses. Computational models covered in this mini review include network-based models, machine learning models and genome-scale metabolic models. We also provide perspectives on future research opportunities for combating drug-resistant cancer cells.