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Background: Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to efficiently treat desmoid tumor. However, molecular mechanism of why imatinib works remains poorly understood. Here, we describe the potential roles of NOTCH2 and HES1 in association with clinical response to imatinib as in genome and transcriptome levels. Methods: We identified all somatic mutations in coding and non-coding regions via whole genome sequencing using desmoid tumor samples. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale Whole-genome sequencing (WGS) and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response. Results: Among 20 patients, 4 (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥1 year. With gene-wise functional analyses, we detected significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on PCAWG data analyses, NOTCH2 mutations affect its expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders Conclusions: Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, which provides an important therapeutic consideration for desmoid tumor. Trial Registration: ClinicalTrials.gov, NCT02495519, Registered July 13, 2015- Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02495519

Background: The depth of anesthesia is an essential factor in surgical prognosis. The neurotoxic effect of chemotherapeutic drugs affects the sensitivity to anesthetics. This study was conducted to determine whether the effect-site concentration (Ce) of propofol for loss of consciousness (LOC) differs in patients undergoing preoperative chemotherapy. Methods: A total of 60 patients scheduled for surgery for colorectal cancer under general anesthesia were included in this study. Patients who had received chemotherapy comprised the experimental (C) group, and those without a previous history of chemotherapy comprised the control (N) group. Propofol was administered as an effect-site target-controlled infusion, and the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scores were evaluated. When the plasma concentration and Ce were similar, and if the MOAA/S score did not change, the target Ce was increased by 0.2 μg/ml; otherwise, the Ce was maintained for 2 min and then increased. Results: The Ce values of propofol for loss of verbal contact (LVC) in groups C and N were 2.40 ± 0.39 and 2.29 ± 0.39 μg/ml (P = 0.286), respectively, and those for LOC in groups C and N were 2.69 ± 0.43 and 2.50 ± 0.36 μg/ml (P = 0.069), respectively. No significant difference was observed in Ce values between the two groups.Conclusions: Chemotherapy had no effect on the Ce of propofol for LVC and LOC in patients with colorectal cancer. We do not recommend reducing the dose of propofol for the induction of LOC in patients with colorectal cancer undergoing chemotherapy.

The involvement of immune checkpoint regulators (ICs) in alcohol-associated liver diseases (ALDs) is still largely unknown. Here, we analyzed the levels of 16 soluble ICs (sICs) in male patients with ALD to determine their clinical significance. The 16 sICs were measured using a luminex-based multiplex assay in 115 patients with ALD and 47 healthy controls (HCs). The expressions of membrane-type (m) PD-1 and mCTLA-4 on CD4+ and CD8+ T lymphocytes and NK cells of 28 patients with ALD and 8 HCs were also measured. Correlation test and risk assessment were also conducted to evaluate biomarkers of ALD in clinical practice. Our results show that four sICs were upregulated (sCTLA-4, sTIM-3, sCD27, and sGITR) and two sICs were downregulated (sLAG-3 and sHVEM) in ALD. mPD-1 expression was significantly more greatly increased on CD4+T lymphocytes in the ALD group than in the HC group (p = 0.009). sTIM-3 was positively correlated, while sLAG-3 was negatively correlated with non-invasive liver fibrosis markers (AST/ALT, APRI, GPR, and FIB-4) and Maddrey discriminant function score. Risk factor analysis showed that sTIM-3 was consistently associated with ALD severity in both MDF and FIB-4 scores, and sLAG-3 was associated with FIB-4 scores. This study revealed the involvement of sCTLA-4, sTIM-3, sCD27, sGITRL, sLAG-3, and sHVEM in discriminating male patients with ALD. Expressions of sTIM-3 and sLAG-3 were correlated with liver fibrosis markers and significantly associated with ALD severity, which can be further studied as diagnostic markers and therapeutic targets in ALD.

Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that occasionally shares morphologic and immunohistochemical overlap with low- and high-grade endometrial stromal sarcoma (LGESS and HGESS). In this study, we sought to characterize the clinical, morphologic, genetic, and epigenetic features of five uterine sarcomas that display histologic features of LGESS, HGESS, and PEComa. All tumors demonstrated epithelioid cells often associated with a low-grade spindled component resembling LGESS, with both regions expressing CD10, ER, PR, variable HMB45, and Melan-A immunoreactivity, and strong cathepsin K and pS6 expression. Targeted massively parallel sequencing analysis revealed the presence of somatic TSC2 mutations in all five cases, of which four harbored concurrent or consecutive JAZF1-SUZ12 gene fusions. Unsupervised hierarchical clustering analysis of methylation profiles of TSC2-mutant uterine sarcomas (n = 4), LGESS (n = 10), and HGESS (n = 12) demonstrated two clusters consisting of (1) all LGESS and TSC2-mutant uterine sarcomas and (2) all HGESS. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, calcium, and Rap1 signaling. TSC2-mutant uterine sarcomas were responsive to hormone suppression, and mTOR inhibition demonstrated clinical benefit in four patients with these neoplasms. Our results suggest that these tumors represent histologically distinctive LGESS with TSC2 mutations. TSC2 mutations and JAZF1-SUZ12 fusion may help diagnose these tumors and possibly direct effective treatment.

The World Health Organization endorses molecular subclassification of endometrial endometrioid carcinomas (EECs). Our objectives were to test the sensitivity of tumor morphology in capturing p53 abnormal (p53abn) cases and to model the impact of p53abn on changes to ESGO/ESTRO/ESP (European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology) risk stratification. A total of 292 consecutive endometrial carcinoma resections received at Foothills Medical Centre, Calgary, Canada (2019–2021) were retrieved and assigned to ESGO risk groups with and without p53 status. Three pathologists reviewed the representative H&E‐stained slides, predicted the p53 status, and indicated whether p53 immunohistochemistry (IHC) would be ordered. Population‐based survival for endometrial carcinomas diagnosed during 2008–2016 in Alberta was obtained from the Alberta Cancer Registry. The cohort consisted mostly of grade 1/2 endometrioid carcinomas (EEC1/2; N = 218, 74.6%). One hundred and fifty‐two EEC1/2 (52.1% overall) were stage IA and 147 (50.3%) were low risk by ESGO. The overall prevalence of p53abn and subclonal p53 was 14.5 and 8.3%, respectively. The average sensitivity of predicting p53abn among observers was 83.6%. Observers requested p53 IHC for 39.4% with 98.5% sensitivity to detect p53abn (99.6% negative predictive value). Nuclear features including smudged chromatin, pleomorphism, atypical mitoses, and tumor giant cells accurately predicted p53abn. In 7/292 (2.4%), p53abn upgraded ESGO risk groups (2 to intermediate risk, 5 to high risk). EEC1/2/stage IA patients had an excellent disease‐specific 5‐year survival of 98.5%. Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC1/2/stage IA cases.

Background/Purpose: Stereotactic ablative radiotherapy (SABR) is the treatment of choice for medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC). The influence of oncogenic driver alterations and comorbidities are not well known. Here we present treatment outcomes based on clinicopathologic features and molecular profiles. Methods: We retrospectively analyzed patients treated with SABR for inoperable ES-NSCLC. Molecular features of oncogenic driver alterations included EGFR, ALK, and ROS1. Comorbidities were assessed using the age-adjusted Charlson Comorbidity Index (ACCI). Survival was calculated using the Kaplan–Meier method. The Cox regression model was performed for univariate and multivariate analyses of prognostic factors. Competing risk analysis was used to evaluate the cumulative incidence of disease progression. Results: From 2008 to 2020, 100 patients (median age: 82 years) were enrolled. The majority of patients were male (64%), ever-smokers (60%), and had adenocarcinoma (65%). With a median follow-up of 21.5 months, the median overall survival (OS) and real-world progression-free survival were 37.7 and 25.1 months, respectively. The competing-risk-adjusted 3-year cumulative incidences of local, regional, and disseminated failure were 8.2%, 14.5%, and 31.2%, respectively. An ACCI ≥7 was independently associated with inferior OS (hazard ratio [HR] 2.45, p = 0.03). Tumor size ≥4 cm (HR 4.16, p

We aimed to investigate the effect of chronic particulate matter (PM) exposure on bleomycin-induced lung fibrosis in a rat model using chest CT, histopathologic evaluation, and RNA-sequencing. A bleomycin solution was intratracheally administrated to 20 male rats. For chronic PM exposure, after four weeks of bleomycin treatment to induce lung fibrosis, PM suspension (experimental group) or normal saline (control group) was intratracheally administrated for 10 weeks. Chest CT was carried out in all rats, and then both lungs were extracted for histopathologic evaluation. One lobe from three rats in each group underwent RNA sequencing, and one lobe from five rats in each group was evaluated by western blotting. Inflammation and fibrosis scores in both chest CT and pathologic analysis were significantly more aggravated in rats with chronic PM exposure than in the control group. Several genes associated with inflammation and immunity were also upregulated with chronic PM exposure. Our study revealed that chronic PM exposure in a bleomycin-induced lung fibrosis rat model aggravated pulmonary fibrosis and inflammation, proven by chest CT, pathologic analysis, and RNA sequencing.

Backgrounds Neutrophil-to-lymphocyte ratio (NLR), a surrogate marker of systemic response to physiological stress, is used for prognosis prediction in many diseases. However, the usefulness of this marker for predicting acute kidney injury (AKI) progression is unclear. Methods This retrospective study was based on the Chang Gung Research Database. Patients admitted to the intensive care unit with a diagnosis of stage 1 or 2 AKI were identified. The primary outcome was a composite of progression to stage 3 AKI, requirement of renal replacement therapy, or 14-day in-hospital mortality. The association between NLR and the primary outcome was examined using a logistic regression model and multivariable analysis. The nonlinearity and cutoff points of this relationship were determined using a restricted cubic spline model. Results A total of 10,441 patients were enrolled. NLR level at the time of stage 1–2 AKI diagnosis was a marker of adverse outcomes. After adjustment for confounders, NLR was independently associated with the composite outcome of AKI progression, renal replacement therapy, or mortality. The restricted cubic spline model revealed a J-shaped curve, with the lowest odds ratio for an NLR between 7 and 38. Subgroup analysis revealed linear and J-shaped relationships between NLR and the primary outcome in patients admitted to the intensive care unit for medical reasons and for cardiovascular surgery, respectively. Conclusions NLR is an independent marker of AKI progression and in-hospital mortality. Because it is readily available in daily practice, it might be used for risk stratification in the AKI population. Graphic abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40620-021-01162-3.

Background Restless legs syndrome (RLS) is common among patients with end-stage kidney disease (ESKD) and is associated with poor outcomes. Several recently published studies had focused on pharmacological and non-pharmacological treatments of RLS, but an updated meta-analysis has not been conducted. Methods The study population was adult ESKD patients on dialysis with RLS. Randomized controlled trials (RCTs) were selected. The primary outcome was reduction in RLS severity. The secondary outcomes were improvement in sleep quality and treatment-related adverse events. Frequentist standard network meta-analysis (NMA) and additive component NMA were performed. The evidence certainty was assessed using the Confidence in NMA (CINeMA) framework. Results A total of 24 RCTs with 1252 participants were enrolled and 14 interventions were compared. Cool dialysate produced the largest RLS severity score reduction {mean difference [MD] 16.82 [95% confidence interval (CI) 10.635–23.02]} and a high level of confidence. Other potential non-pharmacological interventions include intradialytic stretching exercise [MD 12.00 (95% CI 7.04–16.97)] and aromatherapy massage [MD 10.91 (95% CI 6.96–14.85)], but all with limited confidence of evidence. Among the pharmacological interventions, gabapentin was the most effective [MD 8.95 (95% CI 1.95–15.85)], which also improved sleep quality [standardized MD 2.00 (95% CI 0.47–3.53)]. No statically significant adverse events were detected. Conclusions The NMA supports that cool dialysate is appropriate to treat patients with ESKD and RLS. Gabapentin is the most effective pharmacological intervention and also might improve sleep quality. Further parallel RCTs with sufficient sample sizes are required to evaluate these potential interventions and long-term effects.

Background Non-invasive painless signaling therapy (NPST) is an electro-cutaneous treatment that converts endogenous pain information into synthetic non-pain information. This study explored whether pain improvement by NPST in failed back surgery syndrome (FBSS) patients is related to cerebral modulation. Methods Electroencephalography (EEG) analysis was performed in 11 patients with FBSS. Subjects received daily NPST for 5 days. Before the first treatment, patients completed the Brief Pain Inventory (BPI) and Beck Depression Inventory and underwent baseline EEG. After the final treatment, they responded again to the BPI, reported the percent pain improvement (PPI), and then underwent post-treatment EEG. If the PPI grade was zero, they were assigned to the ineffective group, while all others were assigned to the effective group. We used standardized low-resolution brain electromagnetic tomography (sLORETA) to explore the EEG current-source distribution (CSD) associated with pain improvement by NPST. Results The 11 participants had a median age of 67.0 years, and 63.6% were female. The sLORETA images revealed a beta-2 CSD increment in 12 voxels of the right anterior cingulate gyrus (ACG) and the right medial frontal area. The point of maximal CSD changes was in the right ACG. The alpha band CSD increased in 2 voxels of the left transverse gyrus. Conclusions Pain improvement by NPST in FBSS patients was associated with increased cerebral activity, mainly in the right ACG. The change in afferent information induced by NPST seems to be associated with cerebral pain perception.

The outcomes of patients with incident kidney failure who start hemodialysis are influenced by several factors. Whether hemodialysis facility characteristics are associated with patient outcomes is unclear. We included adults diagnosed as having kidney failure requiring hemodialysis during January 1, 2001 to December 31, 2013 from the Taiwan National Health Insurance Research Database to perform this retrospective cohort study. The exposures included different sizes and levels of hemodialysis facilities. The outcomes were all-cause mortality, cardiovascular death, infection-related death, hospitalization, and kidney transplantation. During 2001–2013, we identified 74,406 patients and divided them in to three groups according to the facilities where they receive hemodialysis: medical center (n = 8263), non-center hospital (n = 40,008), and clinic (n = 26,135). The multivariable Cox model demonstrated that a larger facility size was associated with a low mortality risk (hazard ratio [HR] 0.991, 95% confidence interval [95% CI] 0.984–0.998; every 20 beds per facility). Compared with medical centers, patients in non-center hospitals and clinics had higher mortality risks (HR 1.13, 95% CI 1.09–1.17 and HR 1.11, 95% CI 1.06–1.15, respectively). Patients in medical centers and non-center hospitals had higher risk of hospitalization (subdistribution HR [SHR] 1.11, 95% CI 1.10–1.12 and SHR 1.22, 95% CI 1.21–1.23, respectively). Patients in medical centers had the highest rate of kidney transplantation among the three groups. In patients with incident kidney failure, a larger hemodialysis facility size was associated with lower mortality. Overall, medical center patients had a lower mortality rate and higher transplantation rate, whereas clinic patients had a lower hospitalization risk.

Ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are both associated with endometriosis but differ in histologic phenotype, biomarker profile, and survival. Our objectives were to refine immunohistochemical (IHC) panels that help distinguish the histotypes and reassess the prevalence of mismatch repair deficiency (MMRd) in immunohistochemically confirmed OCCC. We selected 8 candidate IHC markers to develop first-line and second-line panels in a training set of 344 OCCC/OEC cases. Interobserver reproducibility of histotype diagnosis was assessed in an independent testing cohort of 100 OCC/OEC initially without and subsequently with IHC. The prevalence of MMRd was evaluated using the testing cohort and an expansion set of 844 ovarian carcinomas. The 2 prototypical combinations (OCCC: Napsin A+/HNF1B diffusely+/PR-; OEC: Napsin A-/HNF1B nondiffuse/PR+) occurred in 75% of cases and were 100% specific. A second-line panel (ELAPOR1, AMACR, CDX2) predicted the remaining cases with 83% accuracy. Integration of IHC improved interobserver reproducibility (κ=0.778 vs. 0.882, P

Chae Hong Lim,1 Sang Eun Yoon,2 Won Seog Kim,2 Kyung-Han Lee,3,4 Seok Jin Kim2,4 1Department of Nuclear Medicine, Soonchunhyang University College of Medicine, Seoul, Korea; 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, KoreaCorrespondence: Seok Jin KimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, KoreaTel +82-2-3410-1766Fax +82-2-3410-1754Email kstwoh@skku.eduKyung-Han LeeDepartment of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, KoreaTel +82-2-3410-2630Fax + 82-2-3410-2638Email khnm.lee@samsung.comPurpose: The clinical value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in intravascular large B-cell lymphoma (IVLBCL) is unknown. This study investigated the association between PET/CT features and prognosis in IVLBCL patients.Patients and Methods: Subjects were 30 newly diagnosed Asian variant IVLBCL patients at a single institution. Baseline PET/CT was analyzed for the distribution and intensity of FDG lesions, and PET/CT pattern groups were compared for the outcome.Results: Eight patients had hypermetabolic lymph node (LN) lesions (Nodal group). The remaining 22 patients with extranodal (EN) involvement were categorized into Deauville score 3– 4 (EN/DS3-4; n = 14) and DS5 groups (EN/DS5; n = 8). First-line therapy resulted in a complete or partial response in 75.0%, 64.3%, and 100% of the respective groups. Treatment-related deaths occurred in one nodal group and three EN/DS3-4 group cases, but none among the EN/DS5 group. During 56 months of follow-up, disease progression or relapse occurred in five, four, and one case of respective groups. Cancer-related death occurred more frequently in the Nodal (n = 6) and EN/DS3-4 groups (n = 7) than the EN/DS5 group (n = 1; P = 0.041). Nodal and EN/DS3-4 groups had worse 5-year event-free survival (EFS; 25.0% and 49.0%, respectively, P = 0.010 and 0.076) and overall survival (OS; 33.3% and 48.2%, P = 0.010 and 0.068) compared to the EN/DS5 group (87.5% EFS and 87.5% OS).Conclusion: In patients with Asian variant IVLBCL, the distribution and intensity of FDG uptake lesions on PET/CT can be useful for predicting treatment outcomes and survival.Keywords: intravascular lymphoma, 18F-fluorodeoxyglucose, PET/CT, prognosis

Objective To examine the treatment effects of repositioning maneuvers with the head turned 45° downwards (Gufoni maneuver) and 45° upwards (Appiani maneuver) in 25 patients with ageotropic horizontal semicircular canal (HSCC) benign paroxysmal positional vertigo (BPPV). Methods Patients were randomly assigned to the Gufoni or Appiani maneuvers, and their immediate and short‐term efficacy was investigated. Results The immediate treatment response was successful in four of 16 patients who were treated with the Appiani maneuver and were not successful in any of the nine patients treated with the Gufoni maneuver. The patients who showed spontaneous resolution during follow‐up outnumbered the patients who showed resolution of ageotropic HSCC BPPV immediately after the repositioning maneuvers. Conclusion This study showed a very low immediate resolution rate of ageotropic HSCC BPPV after the Gufoni maneuver; this may be attributed to the less effectiveness of the Gufoni maneuver against debris that often exists in the canal side of the cupula. Another interesting finding was that the rate of spontaneous resolution during the follow‐up period was higher than that of immediate resolution after the repositioning maneuvers, which may support the recently proposed hypothesis that ageotropic positional nystagmus can also be evoked by causes other than the otolithic attachment on the cupula, such as a slight change in the biochemical composition of the inner ear fluids. Level of Evidence 3.

Magnetic resonance imaging (MRI) plays an important role in diagnosing and classifying axial spondyloarthritis (SpA) and is also useful for appropriate evaluation of disease status owing to its ability to detect inflammation early and reveal structural changes. However, dedicated MRI for the anterior chest wall (ACW) is not routinely considered despite relatively frequent presence of ACW lesions. To date, no study has investigated the imaging findings and clinical features of ACW involvement in Korean SpA patients. Thus, we aimed to show ACW involvement in SpA patients using ACW lesions found by MRI. We describe 20 cases of ACW involvement in which MRI-detected manubriosternal joint lesions. The lesion types included subchondral bone marrow edema, marginal or central bone erosions, subchondral fat infiltration or deposition, and ankylosis, with erosions being the most prevalent finding. We also provide the literature review results describing MRI findings of ACW lesions in SpA patients. (J Rheum Dis 2021;28:159-164)

This study reviewed the pattern of malocclusion among orthodontic patients in East Coast of Sabah and the type of treatment indicated for the patients. A total of 138 pre-treatment orthodontic records of patients who attended the orthodontic consultation clinic in year 2018 were included in this cross-sectional retrospective study. Data taken were demographic data, source of referral, BSI (British Standards Institutes) incisor classification, skeletal pattern, and type of treatment. All data were analysed descriptively using Stata 15. Based on the results, mean age of the patients was 16.89 ± 0.37 years. More females sought orthodontic treatment (n=101, 73.19%) than males. Majority of the patients were Chinese (n=68, 49.28%) and Bumiputera Sabah (n=55, 39.86%). Main source of referral was from dental officers (n=128, 92.75%). The distribution of malocclusion showed high percentage of Class II division 1 (n=56, 40.58%), followed by Class III (n=45, 32.61%), Class I (n=34, 24.64%) and Class II division 2 (n=3, 2.17%). For skeletal pattern, more patients presented with Class II (n=54, 39.13%), while the number of patients presented with Class I and Class III were equal (n=42, 30.43%). Class III malocclusion (n=29, 42.65%) and Class III skeletal pattern (n=29, 42.65%) were more common in Chinese patients. Treatment indicated was mostly fixed orthodontic appliance (n=120, 86.96%). In conclusion, Class II Division 1 malocclusion and Class II skeletal pattern were most common among the patients. Class III malocclusion and Class III skeletal pattern were typical features among the Chinese patients. Fixed orthodontic appliance was the most common treatment method. DOI : http://dx.doi.org/10.17576/JSKM-2021-1902-06

Objective. To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods. We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. Results. In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion. Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN. (J Rheum Dis 2021;28:150-158)

Background Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers. Methods This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap. Results On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer. Conclusions Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.

Currently, antibiotics are commonly used to treat coccidiosis, a severe protozoal disease in chickens. However, due to growing concerns about the antibiotic residue in meat and eggs, phytogenic formulations are becoming an attractive approach to manage this disease. In this study, we investigated the anti-coccidial function and mechanism of phytogenic formulations composed of Bidens pilosa, Artemisia indica, and both used in combination. We found that these formulations increased the survival rate and reduced body weight loss, the feed conversion ratio, oocyst excretion, bloody stools, and gut lesions of chickens. Mechanistic studies showed that A. indica, but not B. pilosa, reduced the survival of Eimeria oocysts. Accordingly, they both inhibited oocyst sporulation and sporozoite invasion into Madin-Darby bovine kidney (MDBK) cells. Overall, we demonstrate that these formulations protect chickens against coccidiosis. Moreover, a combination of B. pilosa and A. indica has an additive effect on coccidiosis control and growth performance in chickens compared to either one used alone.

AIMS Genomic inactivation of ARID1B in ARID1A-inactivated tumour and genomic inactivation of SMARCB1 represent two recurrent mechanisms, core SWItch/sucrose non-fermentable (SWI/SNF) complex inactivation, that are associated with de-differentiation in endometrial carcinoma. Approximately one-third of dedifferentiated/undifferentiated endometrial carcinomas (DDEC/UEC) show loss of ARID1B expression with a minor subset showing loss of SMARCB1 expression, but little is known regarding the specificity of ARID1B or SMARCB1 loss in gynaecological tract tumours in general. The aim of this study was to examine the frequency of ARID1B and SMARCB1 loss by immunohistochemistry in a series of gynaecological tract epithelial/mesenchymal neoplasms. METHODS AND RESULTS We evaluated 1849 tumours that included 748 endometrial carcinomas, 101 uterine carcinosarcomas/adenosarcomas, 64 uterine sarcomas, 221 cervical carcinomas and 715 ovarian carcinomas/borderline tumours by tissue microarrays (TMA). We observed ARID1B loss in 35 of 86 (41%) and SMARCB1 loss in three of 86 (3%) DDEC/UEC, but not in any other uterine tumour types examined. ARID1B-deficient DDEC/UEC also showed concurrent loss of ARID1A expression. All SMARCB1-deficient tumours showed loss of MLH1 and PMS2, while 29 of 35 ARID1B-deficient tumours showed loss of MLH1 and PMS2 or loss of MSH6. All ovarian carcinomas/borderline tumours and cervical carcinomas showed intact expression of ARID1B and SMARCB1. CONCLUSION Our findings indicate that the loss of expression of ARID1B or SMARCB1 by immunohistochemistry is highly specific for undifferentiated carcinoma among tumours of the upper gynaecological tract and cervix, and therefore can be used to identify these highly aggressive malignant tumours.

Malignant mesothelioma is a neoplasm of serosal surfaces, most commonly affecting the pleura. The peritoneum, pericardium, and tunica vaginalis are less frequently involved. Malignant mesothelioma with EWSR1-ATF1 fusion in young adults was recently reported in the literature. Here, we present two pediatric cases of EWSR1-ATF1 translocation-associated malignant mesothelioma in the peritoneum and pericardium respectively. Both cases lacked a known exposure history. Microscopy in both cases showed predominantly epithelioid morphology with ample eosinophilic cytoplasm, and immunohistochemistry was positive for pan-keratin, calretinin, and WT1. Both cases showed EWSR1-ATF1 gene rearrangement by RNA sequencing, which was instrumental in confirming the diagnosis of malignant mesothelioma and to exclude more common pediatric sarcomas, especially in the context of limited sampling.

Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.

Immune checkpoint blockade (ICB) therapy has substantially improved the outcomes of patients with many types of cancers, including renal cell carcinoma (RCC). Initially studied as monotherapy, immunotherapy-based combination regimens have improved the clinical benefit achieved by ICB monotherapy and have revolutionized RCC treatment. While biomarkers like PD-L1 and tumor mutational burden (TMB) are FDA approved as biomarkers for ICB monotherapy, there are no known biomarkers for combination immunotherapies. Here, we describe the clinical outcomes and genomic determinants of response from a phase Ib/II clinical trial on patients with advanced RCC evaluating the efficacy of lenvatinib, a multi-kinase inhibitor mainly targeting VEGFR and FGFR plus pembrolizumab, an anti-PD1 immunotherapy. Concurrent treatment with lenvatinib and pembrolizumab resulted in an objective response rate of 79% (19/24) and tumor shrinkage in 96% (23/24) of patients. While tumor mutational burden (TMB) did not predict for clinical benefit, germline HLA-I diversity strongly impacted treatment efficacy. Specifically, HLA-I evolutionary divergence (HED), which measures the breadth of a patient's immunopeptidome, was associated with both improved clinical benefit and durability of response. Our results identify lenvatinib plus pembrolizumab as a highly active treatment strategy in RCC and reveal HLA-I diversity as a critical determinant of efficacy for this combination. HED also predicted better survival in a separate cohort of patients with RCC following therapy with anti-PD-1–based combination therapy. Implications: These findings have substantial implications for RCC therapy and for understanding immunogenetic mechanisms of efficacy and warrants further investigation.

BACKGROUND Spontaneous spinal epidural hematoma is a rare neurosurgical emergency. CASE SUMMARY A 53-year-old healthy woman suffered from complete paraplegia in both legs and loss of all sensation below the xiphoid process. She was diagnosed as acute spontaneous thoracic epidural hematoma caused by an intraspinal lymphangioma. The primary lab survey showed all within normal limits. Presence of a posteriorly epidural space-occupying lesion at the T4-T8 level of the spinal canal was confirmed on magnetic resonance imaging. A decompressive laminectomy was performed from the T4 to T7 levels at the sixth hour following abrupt onset of complete paraplegia. The lesion was confirmed as lymphangioma. This patient recovered well within one month. CONCLUSION This study reports a case of acute spontaneous thoracic epidural hematoma caused by an intraspinal lymphangioma with well recovery after surgical intervention.

Introduction Point-of-care (POC) ultrasound protocols are commonly used for the initial management of patients with cardiac arrest in the emergency department (ED). However, there is little published evidence regarding any mortality benefit. We compared and studied the effect of implementation of the modified SESAME protocol in terms of clinical outcomes and resuscitation management. Methods This was a single-center retrospective observational study. We conducted a pre- and post-intervention study to evaluate changes in patient outcomes and management after educating emergency medicine residents and the faculty about the modified SESAME protocol. The pre-intervention period lasted from March 2018 to February 2019, and the post-intervention period lasted from May 2019 to April 2020. The modified SESAME protocol education was initiated in March 2019. Multivariate logistic regression analyses were performed to examine the associations between independent variables and outcomes. Results A total of 334 patients were included in this study during a 24-month period. We found no significant differences between the two groups for the primary outcome of survival to hospital admission (pre-intervention group 28.9% versus post-intervention group 28.6%; P = 0.751), survival to hospital discharge (12.1% vs. 12.4%; P = 0.806), and good neurologic outcome at discharge (6.0% vs. 8.1%; P = 0.509). The proportion of resuscitation procedures of thrombolysis, emergency transfusion, tube thoracotomy, and pericardiocentesis during resuscitation increased from 0.6% in the pre-intervention period to 4.9% in the post-intervention period (P = 0.016). Conclusion We did not discover any significant survival benefits associated with the implementation of the modified SESAME protocol; however, early diagnosis of specific pathologies (pericardial effusion, possible pulmonary embolism, tension pneumothorax, and hypovolemia) and accordingly a direct increase in the resuscitation management were seen in this study. Future studies with larger sample sizes are required to examine the clinical outcomes as well as to identify the most effective POC ultrasonography protocols for non-traumatic cardiac arrests.

High-grade endometrial stromal sarcoma (HGESS) may harbor YWHAE-NUTM2A/B fusion, ZC3H7B-BCOR fusion, and BCOR internal tandem duplication (ITD). NTRK3 upregulation and pan-Trk expression were reported in soft tissue lesions that share similar morphology and genetic abnormalities. To confirm these findings in HGESS, differential expression analysis was performed at gene level comparing 11 HGESS with 48 other uterine sarcomas, including 9 low-grade endometrial stromal sarcomas, 23 undifferentiated uterine sarcomas, and 16 leiomyosarcomas, using targeted RNA sequencing data. Pan-Trk immunohistochemistry was performed on 35 HGESS, including 10 tumors with RNA expression data, with genotypes previously confirmed by targeted RNA sequencing, fluorescence in situ hybridization, and/or genomic PCR. Unsupervised hierarchical clustering of the top 25% of differentially expressed probes identified three molecular groups: (1) high NTRK3, FGFR3, RET, BCOR, GLI1, and PTCH1 and low ESR1 expression; (2) low NTRK3, FGFR3, RET, BCOR, GLI1, and PTCH1 and high ESR1 expression; and (3) low NTRK3, FGFR3, RET, BCOR, GLI1, PTCH1, and ESR1 expression. Among HGESS, 64% of tumors clustered in group 1, while 27% clustered in group 2. Cytoplasmic and/or nuclear pan-Trk staining of variable extent and intensity was seen in 91% of HGESS regardless of cyclin D1 and/or BCOR positivity. ER and PR expression was seen in 44% of HGESS despite ESR1 downregulation. Two patients with ER and PR positive but ESR1 downregulated stage I HGESS were treated with endocrine therapy, and both recurred at 12 and 36 months after primary resection. By RNA expression, HGESS appear homogenous and distinct from other uterine sarcomas by activation of kinases, including NTRK3, and sonic hedgehog pathway genes along with downregulation of ESR1. Most HGESS demonstrate pan-Trk staining which may serve as a diagnostic biomarker. ESR1 downregulation is seen in some HGESS that express ER and PR which raises implications in the utility of endocrine therapy in these patients.

Objective This study analyzed trends in foodborne and waterborne diseases in South Korea between 2015 and 2019. Methods The data consisted of information on outbreaks of waterborne and foodborne infectious diseases reported through the Korea Centers for Disease Control and Prevention (KCDC) system. We analyzed the trends and epidemiological aspects of outbreaks by month, place of occurrence, and causative pathogens in this observational study. Results The number of outbreaks has steadily increased over the last 5 years, but the number of cases per outbreak has followed a decreasing trend. Incidence at daycare centers and preschools has been steadily increasing over consecutive years. Conclusion The steady number of patients and decreasing number of cases per outbreak, even as the number of outbreaks has been increasing, suggest that the KCDC's professional management system is operating effectively. It is necessary to continue improving the objectivity and efficiency of the management system and to carefully examine the increasing number of outbreaks in smaller-scale group catering facilities, such as daycare centers and preschools. Outbreaks can be prevented by closely examining those caused by unidentified pathogens and group outbreaks caused by other diseases, identifying problems, and supplementing the management system.

Background/Objectives: Ghrelin is an orexigenic hormone that increases food intake, adiposity, and insulin resistance through its receptor Growth Hormone Secretagogue Receptor (GHS-R). We previously showed that ghrelin/GHS-R signaling has important roles in regulation of energy homeostasis, and global deletion of GHS-R reduces obesity and improves insulin sensitivity by increasing thermogenesis. However, it is unknown whether GHS-R regulates thermogenic activation in adipose tissues directly. Methods: We generated a novel adipose tissue-specific GHS-R deletion mouse model and characterized the mice under regular diet (RD) and high-fat diet (HFD) feeding. Body composition was measured by EchoMRI. Metabolic profiling was determined by indirect calorimetry. Response to environmental stress was assessed using a TH-8 temperature monitoring system. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Tissue histology was analyzed by hematoxylin/eosin and immunofluorescent staining. Expression of genes involved in thermogenesis, angiogenesis and fibrosis in adipose tissues were analyzed by real-time PCR. Results: Under RD feeding, adipose tissue-specific GHS-R deletion had little or no impact on metabolic parameters. However, under HFD feeding, adipose tissue-specific GHS-R deletion attenuated diet-induced obesity and insulin resistance, showing elevated physical activity and heat production. In addition, adipose tissue-specific GHS-R deletion increased expression of master adipose transcription regulator of peroxisome proliferator-activated receptor (PPAR) γ1 and adipokines of adiponectin and fibroblast growth factor (FGF) 21; and differentially modulated angiogenesis and fibrosis evident in both gene expression and histological analysis. Conclusions: These results show that GHS-R has cell-autonomous effects in adipocytes, and suppression of GHS-R in adipose tissues protects against diet-induced obesity and insulin resistance by modulating adipose angiogenesis and fibrosis. These findings suggest adipose GHS-R may constitute a novel therapeutic target for treatment of obesity and metabolic syndrome.

The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean − 18.2 ± 48.1; 95% confidence interval − 24.9 to − 11.5,p 208) dropped from 23.5 to 10% (p

The purpose of this retrospective study was to investigate the role in staging and prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma without high-grade transformation (HT). We retrospectively reviewed 115 consecutive patients with histopathologically confirmed gastric MALT lymphoma without HT who underwent pretherapeutic F-18 FDG PET/CT. Kaplan–Meier and Cox proportional-hazards regression analyses were used to identify independent prognostic factors for disease free survival (DFS) among 13 clinical parameters and three PET parameters. In two of 115 patients (1.7%), the clinical stage appeared higher according to F-18 FDG PET/CT. In univariate analysis, Helicobacter pylori (HP) infection (P = 0.023), treatment modality (P

Background The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. Methods We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. Results During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). Conclusions This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12–16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

Whether reduced-dose prasugrel has a better efficacy or safety than standard-dose clopidogrel remains unknown in patients undergoing percutaneous coronary intervention (PCI).A systematic search of PubMed, EMBASE, Google Scholar, and Cochrane Library from database inception to May 1, 2020 was performed to compare the clinical outcomes in patients with acute coronary syndrome or stable coronary artery disease undergoing PCI between those treated with reduced-dose prasugrel and clopidogrel. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using the fixed-effect or random-effect model if significant heterogeneity was observed. The primary efficacy endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, myocardial infarction (MI), or ischemic stroke. The primary safety endpoint was all bleeding events.Overall, seven studies with 32,951 patients with PCI were included in the analysis. Reduced-dose prasugrel was associated with a lower risk of MACE than clopidogrel (OR 0.80, 95% CI 0.67-0.97). Except for MI (OR 0.74, 95% CI 0.56-0.98), the secondary efficacy endpoints of CV death, ischemic stroke, all-cause death, and stent thrombosis were similar. For the primary safety endpoint of all bleeding events, there was no significant difference between reduced-dose prasugrel and clopidogrel (OR 1.31, 95% CI 0.87-1.98), but the risk of minor bleeding was significantly higher in reduced-dose prasugrel (OR 1.73, 95% CI 1.25-2.41).In patients undergoing PCI, a lower risk of MACE was found in patients receiving reduced-dose prasugrel than in those with clopidogrel, but a higher risk of minor bleeding events was noted.

Most breast tumors are primary to this site; breast metastasis of endometrial origin is extremely rare. Low-grade endometrioid endometrial carcinomas can undergo dedifferentiation to undifferentiated carcinoma but such transformation at a metastatic site has been reported previously in only 2 cases. We report a case of dedifferentiation occurring in an isolated solitary breast metastasis of a low-grade endometrioid endometrial carcinoma. A 64-yr-old woman presented with a breast mass 2 yr after initial diagnosis of a grade 1 FIGO stage IIIA endometrioid endometrial carcinoma. Ultrasound guided biopsy of the breast mass showed a grade 1 endometrioid carcinoma which was diffusely estrogen receptor and PAX8-positive, consistent with metastasis from the previous endometrial carcinoma. The tumor initially responded to Letrozole therapy but then abruptly increased in size. Mastectomy revealed a poorly differentiated malignant tumor with morphology and immunophenotype (including loss of ARID1A and ARID1B immunoreactivity) consistent with undifferentiated endometrial carcinoma with no residual low-grade component. Awareness of the phenomenon of dedifferentiation of endometrial carcinoma in a metastatic site is important to avoid misdiagnosis as a primary breast cancer or metastasis from another primary site.

There have been no reports regarding nystagmus observed immediately after the end of an acute vertiginous attack in patients with Meniere’s disease. The aim of this study was to demonstrate positional direction-changing nystagmus in patients with Meniere’s disease, and to discuss the mechanism that underlies this nystagmus. Video-nystagmography was recorded in two patients with definite Meniere’s disease, who showed positional direction-changing nystagmus during the period immediately after a vertigo attack. In one patient, video-nystagmographic recording was conducted 5 h after an episode of vertigo attack, and it showed very weak, persistent positional geotropic direction-changing nystagmus. In the other patient, video-nystagmographic recording was conducted 23 h after an episode of vertigo attack, and it showed very weak, persistent positional apogeotropic direction-changing nystagmus. Our patients exhibited very weak, persistent positional direction-changing nystagmus, which was geotropic in one and apogeotropic in the other. This type of positional nystagmus has been reported in other inner ear disorders and it cannot be clearly explained by typical benign paroxysmal positional vertigo. The change in chemical composition and/or electrolyte concentration of the inner ear fluid, although still unclear, may underlie the production of this characteristic nystagmus in these patients.

Although reduced port laparoscopic surgery (RPLS), defined as laparoscopic surgery performed with the minimum possible number of ports and/or small-sized ports, is less invasive than conventional laparoscopic surgery by reducing the number of surgical wounds, an extension of the incision is still needed for specimen extraction, which can undermine the merits of RPLS. To determine the impact of natural orifice specimen extraction (NOSE) in patients undergoing RPLS for colorectal cancer. The endpoints were perioperative outcome and oncologic safety at 3 years. Single-center experience (2013–2019). We retrospectively analyzed our prospectively collected patient records (American Joint Committee on Cancer (AJCC) stage I–III sigmoid or upper rectal cancer (tumor diameter ≤ 5 cm) who underwent curative anterior resection via RPLS. We excluded patients who did not undergo intestinal anastomosis. Perioperative and oncologic outcomes were compared between patients undergoing natural orifice (RPLS-NOSE) or conventional (mini-laparotomy) specimen extraction (RPLS-CSE). Patients were matched by propensity scores 1:1 for tumor diameter, AJCC stage, American Society of Anesthesiologists score and tumor location. Of 119 eligible patients, 104 were matched (52 RPLS-NOSE; 52 RPLS-CSE) by propensity scores. Compared with RPLS-CSE, RPLS-NOSE was associated with longer operative time (223.9 vs. 188.7 min; p = 0.003), decreased use of analgesics (morphine dose 33.9 vs. 43.4 mg; p = 0.011) and duration of hospital stay (4.2 vs. 5.1 days; p = 0.001). No statistically significant difference was found in morbidity or wound-related complication rates between the two groups. After a median follow-up of 34.3 months, no local recurrence was observed in RPLS-NOSE. The 3-year disease-free survival did not differ statistically significantly between groups (90.9 vs. 90.5%; p = 0.610). NOSE enhances the advantages of RPLS by avoiding the need for abdominal wall specimen extraction in patients with tumor diameter ≤ 5 cm. Surgical and oncologic safety are comparable to RPLS with CSE.

BACKGROUND: Previous studies have shown that reduced levels of lung function, characterized by forced expiratory volume in 1 second (FEV(1)), are associated with higher respiratory events and mortality in general population and some chronic lung diseases. Chronic pulmonary aspergillosis (CPA) is a destructive, fatal lung disease caused by Aspergillus infection in non-immunocompromised patients with suboptimal pulmonary function. However, there is limited information on the status and features of CPA according to FEV(1). METHODS: We performed a retrospective observational study to investigate the FEV(1) and airflow limitation in patients with CPA between March 2017 and February 2019 at a tertiary hospital in South Korea. RESULTS: Of the 144 CPA patients, 104 underwent spirometry, demonstrating median forced vital capacity (FVC) and FEV(1) of 2.35 L (68%) and 1.43 L (62%), respectively. Among them, 56 patients had airflow limitation on PFT, with median FVC, and FEV(1) of 2.47 L (73%) and 1.11 L (47%), respectively. Low body mass index (BMI) (20.1 vs. 22.1 kg/m(2); P=0.011), breathlessness (60% vs. 20%; P=0.002), and bilateral pulmonary lesions (33.3% vs. 4%; P=0.006) were more common in patients with moderate to very severe airflow limitation than in those with normal to mild airflow limitation. CONCLUSIONS: Moderate to very severe airflow limitation was observed in 43.3% of patients with CPA. Additionally, low BMI, breathlessness, and bilateral pulmonary lesions contributing to poor prognosis were more common in patients with moderate to very severe airflow limitation than in those with normal to mild airflow limitation. Our findings suggest that airflow limitation can be associated with the prognosis of CPA. Further investigations are needed to demonstrate the clinical significance of this association.

Background Immune checkpoint blockade has made a significant impact on the clinical outcomes of patients with metastatic urothelial carcinoma (UC). However, evidence for this approach in patients with non‐UC of the urinary tract is limited. Methods This was a phase II open‐label study of durvalumab 1500 mg and tremelimumab 75 mg every 4 weeks for four cycles followed by durvalumab 1500 mg every 4 weeks. Eligible patients had metastatic non‐UC with ECOG PS 0–1 regardless of prior therapy (except small cell carcinoma who were pretreated). The primary endpoint was overall response rate per RECIST v1.1. A Simon's minimax two‐stage design was employed, with 13 patients planned for stage one. Pre‐treatment tumors underwent PD‐L1 staining and next‐generation sequencing. Results Thirteen patients were treated, including seven small cell carcinoma, three squamous cell carcinoma, and three adenocarcinoma. Eleven patients had visceral metastases. No responses were observed; 11 patients had PD and 2 patients had SD. Median PFS was 1.8 months (95% CI, 1.25‐not reached [NR]) with a median follow‐up of 7.38 months (range, 5.23–21.99 months). Median OS was 6.97 months (95% CI, 4.34‐NR). One patient's tumor was PD‐L1 positive and all sequenced tumors (n = 8) were microsatellite stable. Grades 3–4 treatment‐related adverse events occurred in 38.4% of patients. Conclusions In a poor prognosis cohort of patients with non‐UC, durvalumab and tremelimumab lacked clinical activity while demonstrating a manageable safety profile., Metastatic, non‐UC tumors of the urinary tract have an aggressive clinical course and dismal prognosis. This phase II trial evaluating durvalumab and tremelimumab demonstrated a manageable safety profile but lack of clinical activity.

Background Alterations in fibroblast growth factor receptor 3 (FGFR3) occur in ∼15% of muscle-invasive bladder cancers (MIBCs) and metastatic urothelial carcinomas (mUCs). Objective To determine the association between FGFR3 status and response to platinum-based chemotherapy in patients with MIBC or mUC. Design, setting, and participants The authors conducted a retrospective review and comparison of patients having (1) MIBC treated with neoadjuvant chemotherapy (NAC), (2) mUC treated with first-line platinum-based chemotherapy (M1 cohort), and (3) MIBC who were from The Cancer Genome Atlas (TCGA). Intervention Platinum-based chemotherapy. Outcome measurements and statistical analysis Pathologic response, recurrence-free (RFS) or progression-free (PFS) survival, and overall survival (OS) were compared between patients with FGFR3 alteration (FGFR3alt) and those without it (FGFR3wild type [FGFR3wt]) in the three cohorts. Results and limitations Nine of 72 NAC patients (13%) had FGFR3alt, of whom none had pathologic complete response and three had residual non-MIBC (carcinoma in situ, n = 1; pT1, n = 2). FGFR3alt was associated with shorter RFS (hazard ratio, 2.74; p = 0.044) but not OS. Among TCGA patients who underwent adjuvant chemotherapy (n = 74), FGFR3alt patients had shorter RFS as well. Conversely, among chemotherapy-naive TCGA patients, FGFR3alt was associated with longer RFS and OS. In the M1 cohort (FGFR3alt, n = 27; FGFR3wt, n = 81), FGFR3alt was associated with higher rates of pulmonary metastases and nonregional lymphadenopathy. Despite lower response rates among FGFR3alt patients (37% vs 49%; p = 0.056), PFS and OS were not significantly different from FGFR3wt patients. Conclusions FGFR3 status is associated with lower responses to platinum-based chemotherapy, which may prompt exploration of nonchemotherapeutic approaches for perioperative management of FGFR3alt urothelial cancers. Patient summary Approximately 15% of bladder cancers harbor mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Our findings suggest that FGFR3 mutations might be associated with lower responses and shorter time to recurrence among patients with muscle-invasive bladder cancer who received perioperative platinum-based chemotherapy. FGFR3 status does not significantly impact response to chemotherapy among those with metastatic urothelial cancers.

Purpose The zinc finger protein, ZBTB48, is a telomere-associated protein. It was renamed as telomeric zinc finger-associated protein (TZAP) binding to elongated telomeres. However, its expression level was not measured in cancers. Patients and Methods We analyzed TZAP mRNA levels in 60 colorectal cancers (CRC) and its correlation with telomere length and TERT was studied. Results TZAP mRNA in CRC was higher statistically than that in paired non-cancerous tissues (p = 0.033). Higher TZAP was found in carcinoembryonic antigen (CEA)-positive CRCs (>5 ng/mL) (p = 0.012). Shorter telomere was found in CRCs with high TZAP expression than that with low TZAP expression (p = 0.010). According to quantitative correlation analysis, TZAP has a correlation with age (r = −0.349, p = 0.007), TERT (r = 0.279, p = 0.041) and telomere length (r = −0.305, p = 0.021). TZAP expression did not harbor prognostic value in CRC. Inhibition of TZAP expression by siRNA suppresses cell growth in HT29 cells; however, it resulted in increased cell viability in HCT116 cells. TZAP inhibition induces a decrease in mRNA levels of TERT in both HT29 and HCT116 cells. TCGA data analysis showed higher expression of TZAP showed poorer overall survival in colon cancer (p = 0.001); however, it did not have a significance in rectal cancer (p = 0.951). Conclusion We suggested that TZAP may be a possible biomarker for CRC.

We aimed to find the best machine learning (ML) model using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for evaluating metastatic mediastinal lymph nodes (MedLNs) in non-small cell lung cancer, and compare the diagnostic results with those of nuclear medicine physicians. A total of 1329 MedLNs were reviewed. Boosted decision tree, logistic regression, support vector machine, neural network, and decision forest models were compared. The diagnostic performance of the best ML model was compared with that of physicians. The ML method was divided into ML with quantitative variables only (MLq) and adding clinical information (MLc). We performed an analysis based on the 18F-FDG-avidity of the MedLNs. The boosted decision tree model obtained higher sensitivity and negative predictive values but lower specificity and positive predictive values than the physicians. There was no significant difference between the accuracy of the physicians and MLq (79.8% vs. 76.8%, p = 0.067). The accuracy of MLc was significantly higher than that of the physicians (81.0% vs. 76.8%, p = 0.009). In MedLNs with low 18F-FDG-avidity, ML had significantly higher accuracy than the physicians (70.0% vs. 63.3%, p = 0.018). Although there was no significant difference in accuracy between the MLq and physicians, the diagnostic performance of MLc was better than that of MLq or of the physicians. The ML method appeared to be useful for evaluating low metabolic MedLNs. Therefore, adding clinical information to the quantitative variables from 18F-FDG PET/CT can improve the diagnostic results of ML. • Machine learning using two-class boosted decision tree model revealed the highest value of area under curve, and it showed higher sensitivity and negative predictive values but lower specificity and positive predictive values than nuclear medicine physicians. • The diagnostic results from machine learning method after adding clinical information to the quantitative variables improved accuracy significantly than nuclear medicine physicians. • Machine learning could improve the diagnostic significance of metastatic mediastinal lymph nodes, especially in mediastinal lymph nodes with low 18F-FDG-avidity.

BACKGROUND In this study, we aimed to evaluate and compare the treatment indication for patients with glucocorticoid-induced osteoporosis (GIOP) in various clinical practice guidelines. METHODS We searched for potentially relevant studies conducted from January 2000 to March 2020 using online databases, including PubMed, Ovid-EMBASE, Guidelines International Network, National Institute for Health and Clinical Excellence, KoreaMed, KMbase, and KoMGI. We reviewed and analyzed the guidelines that included recommendations on GIOP and fulfilled the inclusion criteria. RESULTS A total of 94 articles were selected based on review of the title and abstract; 14 guidelines were assessed upon reviewing the full text. The bone mineral density score for therapeutic intervention of GIOP in postmenopausal women was presented in 7 guidelines, among which 3 guidelines set a T-score of -2.5 or lower and the other 4 guidelines proposed a less stringent cut-off point of -1.5 or lower. Among the 10 guidelines published since 2012 after the emergence of the fracture risk assessment tool (FRAX), 6 guidelines included FRAX in their criteria for defining intervention thresholds. However, they were further divided into fixed-probability (n=3) and age-dependent (n=3) thresholds based on the country. CONCLUSIONS Recently developed guidelines use FRAX as the criterion for establishing the treatment of patients with GIOP. However, these intervention thresholds need to be adapted for each country.

Purpose We aimed to identify the anterolateral ligament (ALL) tears in anterior cruciate ligament (ACL)-deficient knees using standard 1.5-Tesla magnetic resonance imaging (MRI). Methods We included all patients who underwent primary ACL reconstruction at our center between 2012 and 2015. Exclusion criteria included patients with multiple ligament injuries, lateral collateral ligament, posterolateral corner, and infections, and patients who underwent MRI more than 2 months after their injury. All patients (n = 148) had ACL tears that were subsequently arthroscopically reconstructed. The magnetic resonance (MR) images of the injured knees performed within 2 months of injury were reviewed by a musculoskeletal radiologist and an orthopedic surgeon. The patients were divided into two groups. The first group of patients had MRI performed within 1 month of injury. The second group of patients had MRI performed 1–2 months after the index injury. Both assessors were blinded and the MR mages were read separately to assess the presence of ALL, presence of a tear and the location of the tear. Based on their readings, interobserver agreement (kappa statistic (K)), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were compared. Results The ALL was identified in 100% of the patients. However, there was a discrepancy of up to 15% in the identification of tear of the ALL. In the first group in which MRI scans were performed within 1 month of injury, the ALL tear was identified by the radiologist in 92% of patients and by the surgeon in 90% of patients (Κ = 0.86). In the second group in which MRI scans were performed within 1–2 months of the injury, the ALL tear was identified by the radiologist in 78% of patients and by the surgeon in 93% of patients (K = 0.62). Conclusion The ALL can be accurately identified on MRI, but the presence and location of ALL tear and its location cannot be reliably identified on MRI. The accuracy in identification and characterization of a tear was affected by the interval between the time of injury and the time when the MRI was performed. Level of evidence Diagnostic, level IIIb, retrospective.

IntroductionInflammation is associated with the development and progression of ischemic stroke. In this study, we tested the diagnostic ability of procalcitonin (PCT) to C-reactive protein (CRP) ratio (PC ratio; ×10-6) to predict 90-day mortality in ischemic stroke patients.Material and methodsWe retrospectively collected the medical records of patients with a diagnosis of ischemic stroke from February 2008 to January 2018. We analyzed the data of study patients with both PCT and CRP results, and evaluated the relationship between PC ratio and 90-day mortality. Logistic regression was adjusted for confounders and survival analysis was conducted using the Kaplan-Meier estimation.ResultsA total of 333 patients were analyzed in this study. As compared with the lowest PC ratio quartile (0–2.1), the odds ratios for 90-day mortality were; 1.47 (95% CI: 0.62–4.20) for the 2nd quartile (2.2–6.3, p = 0.440), 2.54 (95% CI: 0.95–5.91) for the 3rd quartile (6.4–19.6, p = 0.048), and 4.10 (95% CI: 1.73–9.80) for the 4th quartile (≥ 19.7, p = 0.002), after adjusting for age, sex, medical history, and laboratory results. A higher PC ratio (≥ 2.2) was associated with higher mortality (p < 0.05) in ischemic stroke patients in Kaplan-Meier estimation, and this was confirmed by the log-rank test (p < 0.001).ConclusionsProcalcitonin to C-reactive protein ratio was found to be positively associated with 90-day mortality in ischemic stroke patients. Our findings indicate that PC ratio may be a useful marker for predicting mortality after ischemic stroke. Further prospective studies are required to investigate and validate the use of PC ratio in clinical practice.