Search

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.

Background Cutaneous angiosarcoma (CAS) is a rare but fatal cancer. Established CAS cell lines are necessary for the investigation of their properties and treatment options. Methods Two cell lines, KU-CAS3 and KU-CAS5, were established from human angiosarcoma specimens obtained from the scalp. Flow cytometric assay, tube formation assay, low-density lipoprotein (LDL) uptake assay, immunofluorescence analysis, real-time PCR, tumorigenesis assay, and STR analysis were conducted. Results The cells showed endothelial cell properties, based on the cobblestone appearance upon reaching confluence, CD31 positivity, tube-formation activity, active uptake of acetylated LDL, and vWF expression. The two cell lines expressed relatively high levels of adrenergic β2 receptor, and the VEGF1 and VEGF2 receptors. In the in vivo study, the growing neoplasms, confirmed as CAS, were identified as subcutaneous dark papules. KU-CAS cell lines were considered authentic based on STR profiling. Conclusions KU-CAS3 and KU-CAS5 are the first human CAS cell lines having tumorigenic potential in vivo.

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.

Objective Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. Methods Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). Results Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11–13.64; p I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84–13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD − 13.66; 95% CI − 18.6 to –8.71; p I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD − 1.63; 95% CI − 10.77–7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31–2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression–decompression (ACD) and impedance threshold (ITD) devices. Conclusion In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

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

To evaluate the differences in the pullout strength and displacement of pedicle screws in cadaveric thoracolumbar vertebrae with or without artificial demineralization.Five human lumbar and five thoracic vertebrae from one cadaver were divided into two hemivertebrae. The left-side specimens were included in the simulated osteopenic model group and the right-side bones in a control group. In the model group, we immersed each specimen in HCl (1 N) solution for 40 minutes. We measured bone mineral density (BMD) using dual-energy X-ray absorptiometry and quantitative computerized tomography. We inserted polyaxial pedicle screws into the 20 pedicles of the cadaveric lumbar and thoracic spine after measuring the BMD of the 2 hemivertebrae of each specimen. We measured the pullout strength and displacement of the screws before failure in each specimen using an Instron system.The average pullout strength of the simulated osteopenic model group was 76% that of the control group. In the control and model groups, the pullout strength was 1678.87±358.96 N and 1283.83±341.97 N, respectively, and the displacement was 2.07±0.34 mm and 2.65±0.50 mm, respectively (p.05). We detected positive correlations between pullout strength and BMD in the control group and observed a negative correlation between displacement and BMD in the model group.By providing an anatomically symmetric counterpart, the human cadaveric model with or without demineralization can be used as a test bed for pullout tests of the spine. In the simulated osteopenic model group, pullout strength was significantly decreased compared with the untreated control group.Decreased bone mineral density may significantly reduce the pullout strength of a pedicle screw, even though the range is osteopenic rather than osoteoporotic.

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

The purpose of this study was to evaluate the effects of various emotion regulation (ER) strategies on emotional distress and the urge to self-harm in response to mood induction in individuals who engaged in nonsuicidal self-injury (NSSI). Sixty-one individuals who engaged in NSSI participated in this study were assigned to an experimental ER strategy group (Distraction = 20, Cognitive Reappraisal = 21, Acceptance = 20). Participants completed the Self-Injury Urge Scale (SIUS), State-Trait Anxiety Inventory-State (STAI X-1), and Positive and Negative Affect Scales (PANAS) at several time points: T1) baseline; T2) after watching a film to induce negative mood; and a final time T3) after watching the film again but while using the group-specific ER strategy in response to the induced negative mood. We found that distraction effectively reduced the urge for NSSI after a negative mood induction, as measured using the SIUS. Additionally, cognitive reappraisal and distraction significantly reduced the STAI X-1 and negative affect scale (NAS) scores of the PANAS in individuals with NSSI who underwent negative mood induction. However, acceptance was significantly less effective in relieving unpleasant and undesirable inner experiences in the short term. Our findings suggest that both distraction and cognitive reappraisal are helpful in alleviating negative emotional experiences, and distraction may be useful in dealing with the urge to engage in NSSI. More evidence-based research to test the current findings is required.

Artificial intelligence (AI) is expected to bring greater efficiency in radiology by performing tasks that would otherwise require human intelligence, also at a much faster rate than human performance. In recent years, milestone deep learning models with unprecedented low error rates and high computational efficiency have shown remarkable performance for lesion detection, classification, and segmentation tasks. However, the growing field of AI has significant implications for radiology that are not limited to visual tasks. These are essential applications for optimizing imaging workflows and improving noninterpretive tasks. This article offers an overview of the recent literature on AI, focusing on the musculoskeletal imaging chain, including initial patient scheduling, optimized protocoling, magnetic resonance imaging reconstruction, image enhancement, medical image-to-image translation, and AI-aided image interpretation. The substantial developments of advanced algorithms, the emergence of massive quantities of medical data, and the interest of researchers and clinicians reveal the potential for the growing applications of AI to augment the day-to-day efficiency of musculoskeletal radiologists.

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.

Introduction As most patients with polytrauma or open fractures are converted from temporary external fixation to definite stabilization, the prevention of complications such as infection is especially important. To overcome the high risk of infection associated with the use of the conventional bicortical pin for temporary external fixation, the authors developed a novel unicortical pin and analyzed it in a biomechanical study. Methods The unicortical pin consisted of an inner screw, purchasing the cortical bone, and an outer sleeve with 6 spikes. A bicortical pin was used for the purpose of comparison. A fracture gap model was stabilized using a monoplanar configuration. Both the unicortical pins (Uni group) and bicortical pins (Bi group) underwent axial compressive and torsional load testing using a servo-hydraulic testing machine. Stiffness, load to failure, and mode of failure were documented. Results Stiffness and load to failure of the Uni group (average, 40.5 N/mm and 1098.4 N, respectively) were greater than that of the Bi group (average, 33.7 N/mm and 968.6 N, respectively) in the axial compressive load test (P = 0.008 and 0.032). Stiffness and load to failure of the Uni group (average, 1.2 Nm/degree and 1.7 Nm, respectively) were also significantly higher than those of the Bi group (average, 0.8 Nm/degree and 0.6 Nm, respectively) in the torsional load test (P = 0.008 and 0.016). All pins in the Bi group were bent at the pin-synthetic bone interface without synthetic bone failure. Contrarily, the Uni group did not show any pin bending or failure. However, in the axial compression test, partial cracks in the synthetic bone were found at the interface with spikes in the outer shell. In addition, in the torsion test, incomplete fractures were seen through the inner screws' holes. Conclusion Compared with the conventional bicortical pin, the newly designed unicortical pin significantly increased fracture stability under both axial compressive and torsional loads. The unicortical pin can be considered an alternative biomechanical solution to obtain adequate stability when performing external fixation of fractures.

Summary Background Despite advances in the first-line treatment of metastatic renal cell carcinoma (RCC), there is an unmet need for options to address disease progression during or after treatment with immune checkpoint inhibitors (ICIs). Pembrolizumab and lenvatinib are active as monotherapies in RCC; thus, we aimed to evaluate the combination of lenvatinib plus pembrolizumab in these patients. Methods We report results of the metastatic RCC cohort from an open-label phase 1b/2 study of lenvatinib plus pembrolizumab in patients aged at least 18 years with selected solid tumours and an Eastern Cooperative Oncology Group performance status of 0–1. Oral lenvatinib at 20 mg was given once daily along with intravenous pembrolizumab at 200 mg once every 3 weeks. Patients remained on study drug treatment until disease progression, development of unacceptable toxicity, or withdrawal of consent. Efficacy was analysed in patients with clear cell metastatic RCC receiving study drug by previous therapy grouping: treatment naive, previously treated ICI naive (previously treated with at least one line of therapy but not with an anti-PD-1 or anti-PD-L1 ICI), and ICI pretreated (ie, anti-PD-1 or anti-PD-L1) patients. Safety was analysed in all enrolled and treated patients. The primary endpoint was the objective response rate at week 24 per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) by investigator assessment. This trial is registered with ClinicalTrials.gov ( NCT02501096 ) and with the EU Clinical Trials Register (EudraCT2017-000300-26), and is closed to new participants. Findings Between July 21, 2015, and Oct 16, 2019, 145 patients were enrolled in the study. Two patients had non-clear cell RCC and were excluded from the efficacy analysis (one in the treatment-naive group and one in the ICI-pretreated group); thus, the population evaluated for efficacy comprised 143 patients (n=22 in the treatment-naive group, n=17 in the previously treated ICI-naive group, and n=104 in the ICI-pretreated group). All 145 enrolled patients were included in the safety analysis. The median follow-up was 19·8 months (IQR 14·3–28·4). The number of patients with an objective response at week 24 by irRECIST was 16 (72·7%, 95% CI 49·8–89·3) of 22 treatment-naive patients, seven (41·2%, 18·4–67·1) of 17 previously treated ICI-naive patients, and 58 (55·8%, 45·7–65·5) of 104 ICI-pretreated patients. Of 145 patients, 82 (57%) had grade 3 treatment-related adverse events and ten (7%) had grade 4 treatment-related adverse events. The most common grade 3 treatment-related adverse event was hypertension (30 [21%] of 145 patients). Treatment-related serious adverse events occurred in 36 (25%) patients, and there were three treatment-related deaths (upper gastrointestinal haemorrhage, sudden death, and pneumonia). Interpretation Lenvatinib plus pembrolizumab showed encouraging antitumour activity and a manageable safety profile and might be an option for post-ICI treatment of metastatic RCC. Funding Eisai and Merck Sharp & Dohme.

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 Various systemic immunomodulating therapies have been investigated to treat nail psoriasis, but the efficacy remains unclear. Objective To perform a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. Methods Eligible studies in online databases were identified until March 10, 2020. To assess the efficacy of small molecule inhibitors and biologics, network meta-analyses with surface under the cumulative ranking curve of improvement in nail score at 10 to 16 and at 24 to 26 weeks, as well as 100% improvement of Nail Psoriasis Severity Index (NAPSI), were performed. Results Thirty-nine studies with a total of 13 treatment arms involving 15,673 patients with nail psoriasis were included. An network meta-analysis showed that tofacitinib (weighted mean difference, 56.67; 95% confidence interval [CI], 35.87-77.48) and ixekizumab (weighted mean difference, 59.40; 95% CI, 45.87-72.93) presented the most improvement of nail score at 10 to 16 weeks and 24 to 26 weeks, respectively. For 100% improvement of the Nail Psoriasis Severity Index, ixekizumab showed the best efficacy among all treatments (odds ratio, 2.98; 95% CI, 1.74-5.10). Limitations Insufficiency of eligible data and no long-term follow-up data. Conclusion Tofacitinib and ixekizumab presented the best efficacy for treating nail psoriasis in 10 to 16 weeks and 24 to 26 weeks, respectively.

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.

Purpose This study investigated 18F-FDG PET/CT features of adenovirus-vectored vaccination against COVID-19 in healthy subjects. Patients and methods Thirty-one health care workers had been vaccinated Vaxzevria and underwent FDG PET/CT as an optional test for a cancer screening program. Size and FDG uptake of the hypermetabolic lymph nodes were measured. Uptake value of spleen was also measured with liver for comparison. Results All examinees who underwent FDG PET/CT within 14 days' interval showed hypermetabolic lymphadenopathies ipsilateral to vaccine injection. All examinees with hypermetabolic lymphadenopathy had simultaneous muscular uptakes until 23 days' interval. Among 12 examinees who underwent FDG PET/CT more than 15 days after vaccination, only 3 male examinees did not show hypermetabolism in the axillary lymph nodes. There was no female examinee with negative hypermetabolic lymphadenopathy until 29 days after vaccination. Conclusions Hypermetabolic reactive lymphadenopathy in the ipsilateral axillary area with or without supraclavicular area is most likely to occur in a healthy person with recent adenovirus-vectored COVID-19 vaccination on FDG PET/CT.

Eosinophils influence antitumor immunity and may predict response to treatment with immune checkpoint inhibitors (ICIs). To examine the association between blood eosinophil counts and outcomes in patients with advanced or metastatic urothelial carcinoma (mUC) treated with ICIs, we identified 2 ICI-treated cohorts: discovery (n=60) and validation (n=111). Chemotherapy cohorts were used as comparators (first-line platinum-based chemotherapy, n=75; second-line or more pemetrexed, n=77). The primary endpoint was overall survival (OS). Secondary endpoints were time on treatment (ToT) and progression-free survival. Univariate and multivariate analyses were performed using Cox proportional hazard models. Associations between changes in eosinophil count at weeks 2/3 and 6 after the start of ICI treatment were analyzed using landmark analyses. Baseline characteristics of the ICI cohorts were similar. In the discovery cohort, an optimal cutoff for pretreatment eosinophil count was determined [Eos-Lo

The purpose of this study is to explore authorship trends within the musculoskeletal radiology subspecialty-focused journal, Skeletal Radiology, from inception to 2020. Skeletal Radiology articles published in 1976, 1986, 1996, 2006, 2016, and 2020 were reviewed. For each article, the number of authors, the number of distinct institutions, the names of first and last authors, the country of the first author, the article length, and the number of article references were recorded. A total of 885 articles passed the exclusion criteria to be included in the study. Since inception, there has been a significant increase in the number of SR articles published (P = 0.02), the mean number of authors per article (P

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.

We investigated the incidence of tympanic membrane (TM) perforations induced after intratympanic steroid injection (ITSI) in patients with sudden sensorineural hearing loss (SSNHL) through a systematic review and meta-analysis.PubMed, Embase, and MEDLINE.Primary database searches were performed, and 1901 records were identified. After removal of 1802 articles through abstract screening, the remaining 99 full-text journals were assessed for eligibility to be included in the study. Fifty-eight studies that used either ventilation tubing (VT) or tympanocentesis (TC) for ITSI were selected for analysis. The subjects were divided into VT and TC groups. The rate of TM perforation after ITSI in 2 groups, sites of ITSI, needle gauge, and influence on residual hearing were investigated.The cohorts comprised patients who underwent VT (n = 257, 9.6%) and TC (n = 2415, 90.4%). The proportion of TM perforation after ITSI in each group was 0.073 (95% CI, 0.0469-0.1113) and 0.010 (95% CI, 0.0045-0.0215), respectively, which suggested that the VT group showed a significantly higher TM perforation rate than the TC group (ITSI via VT may have a significantly higher risk of TM perforation than ITSI via TC, although those are relatively small overall. ITSI should be performed in the direction to minimize possible adverse effects.

Monoclonal antibodies (mAb) have been used as therapeutic agents for various diseases, and immunoglobulin G (IgG) is mainly used among antibody isotypes due to its structural and functional properties. So far, regardless of the purpose of the therapeutic antibody, wildtype IgG has been mainly used, but recently, the engineered antibodies with various strategies according to the role of the therapeutic antibody have been used to maximize the therapeutic efficacy. In this review paper, first, the overall structural features and functional characteristics of antibody IgG, second, the old and new techniques for antibody discovery, and finally, several antibody engineering strategies for maximizing therapeutic efficacy according to the role of a therapeutic antibody will be introduced.

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.

Objectives The aim of this study is to examine the effect of particulate autogenous tooth graft removed with organic matter and type I collagen addition on bone regeneration and to validate the possibility of useful allograft material for jaw defects. Material and methods Autogenous tooth bone maker (Korean Dental Solution® KOREA) made particulate autogenous tooth not including organic matter. We used to the developed tooth grafts for experiment. Cell adhesion test with hemacytometer and energy dispersive X-ray spectroscopy (Supra40 VP®, Carl Zeiss, Germany) analysis about the particulate autogenous tooth and type I collagen were performed. Rabbits were divided into three groups: bone graft with organic matter (OM) removing particulate autogenous tooth group, bone graft with OM removing particulate autogenous tooth and type I collagen group, and a control group. Bone grafting was performed in rabbit’s calvaria. The rabbits were sacrificed at different interval at 1, 2, 4, and 6 weeks after bone grafting for the histopathologic observation and observed the effect of bone regeneration by SEM, H-E & Masson stains, osteocalcin IHC staining. Result In vitro cytopathological study showed affinity for cells, cell attachment pattern, and cell proliferation in the order of control group, OM-removed and collagen-treated group, OM-removed particulate autogenous tooth group. The results of the degree of mineralization were opposite to those of the previous cell experimental results, and the OM-removed group, OM-removed group and collagen-treated group were relatively higher than the control group. Histopathologic analysis showed that vascularization and neonatal bone formation were higher in particulate autogenous tooth group with removing OM and with addition of collagen than control group and group of OM removed only. Immunohistochemical analysis showed that osteocalcin (OSC) expression was not observed in the control group, but at 4 weeks groups, OSC expression was observed the OM removed and OM-removed-collagen-treated particulate autogenous tooth, and the degree of expression was somewhat stronger in group of the OM removed and collagen additionally treated particulate autogenous tooth. Conclusion Particles that do not contain organic matter, the saint tooth, was responsible for sufficient bone graft material through the role of space maintenance and bone conduction, and further improved bone formation ability through additional collagen treatment. Therefore, research on various extracellular substrates and autologous bone grafting materials is necessary, and through this, it is possible to lay the foundation for a new type of autologous bone grafting material with excellent academic and technical utility.