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Background: Transforming growth factor (TGF-β) pathway mediates suppression of anti-tumor immunity, and is associated with poor prognosis in triple-negative breast cancer (TNBC). Methods: In this study, we generated a humanized animal model by transplanting human peripheral blood mononuclear cells into immunodeficient mice followed by inoculation of MDA-MB-231 cells, and subsequently analyzed the role of TGF-β2 in the interaction between human T cells and human tumor cells. Results: Following reconstitution of the human immune system, inhibition of TGF-β signaling by TGF-β2 antisense oligodeoxynucleotide (TASO) resulted in accelerated tumor growth inhibition. TGF-β2 inhibition also resulted in downregulation of peripheral Foxp3+ regulatory T cells (Treg), whereas no effect was seen in the expression of CD8+ cytotoxic T cells. Analysis of the TASO-treated mice serum revealed elevated levels of human IFN-γ and reduced levels of human IL-10 and TGF-β2. Moreover, TGF-β2 inhibition resulted in increased CD8+ T cell infiltration, whereas the reduced infiltration of Tregs into the tumor partly resulted from decreased expression of CCL22. Decreased intra-tumoral Tregs facilitated the activation of cytotoxic T cells, associated with increased granzyme B expression. Conclusion: These results indicate that TASO potentiated T-cell mediated antitumor immunity, and it is proposed that TGF-β2 may be a promising target in the immunotherapeutic strategy of TNBC.

Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.

There have been limited studies on the association between prognosis and body weight change in patients with idiopathic pulmonary fibrosis (IPF). This single-center retrospective observational study evaluated the impact of weight loss on outcomes in Korean patients with IPF receiving pirfenidone at a tertiary medical institution. We analyzed 215 IPF patients prescribed pirfenidone from January 1st, 2015 to December 31st, 2019. The patients were categorized into maintained weight (MW; weight gain or loss P P = 0.221, diffusing capacity of the lung for carbon monoxide [% of predicted]; P = 0.973). The MW group had a lower risk of all-cause mortality (P

The binding mode to TAP (i.e., the peptide transporter associated with antigen processing) from a viral peptide thus far has been unknown in the field of antiviral immunity, but an interfering mode from a virus-encoded TAP inhibitor has been well documented with respect to blocking the TAP function. In the current study, we predicted the structure of the pig TAP transporter and its inhibition complex by the small viral protein ICP47 of the herpes simplex virus (HSV) encoded by the TAP inhibitor to exploit inhibition of the TAP transporter as the host's immune evasion strategy. We found that the hot spots (residues Leu5, Tyr22, and Leu51) on the ICP47 inhibitor interface tended to prevail over the favored Leu and Tyr, which contributed to significant functional binding at the C-termini recognition principle of the TAP. We further characterized the specificity determinants of the peptide transporter from the pig TAP by the ICP47 inhibitor effects and multidrug TmrAB transporter from the Thermus thermophillus and its immunity regarding its structural homolog of the pig TAP. The specialized structure-function relationship from the pig TAP exporter could provide insight into substrate specificity of the unique immunological properties from the host organism. The TAP disarming capacity from all five viral inhibitors (i.e., the five virus-encoded TAP inhibitors of ICP47, UL49.5, U6, BNLF2a, and CPXV012 proteins) was linked to the infiltration of the TAP functional structure in an unstable conformation and the mounting susceptibility caused by the host's TAP polymorphism. It is anticipated that the functional characterization of the pig TAP transporter based on the pig genomic variants will lead to additional insights into the genotype and single nucleotide polymorphism (SNP) in relation to antiviral resistance and disease susceptibility.

Background & Aims: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital. Methods: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death. Results: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p

Background The mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer. Methods From the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC–IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients’ clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed. Results Overall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P P = 0.001, respectively). Multivariate analysis for OS could not be conducted because of the small number of events, although non-endometrioid histology was the only factor associated with worse OS in univariate analysis (adjusted HR, 4.523; P = 0.032). Conclusions NAC-IDS may be a treatment option for unresectable metastatic endometrial cancer. Tumor histology and the possibility of complete cytoreduction are the primary considerations for NAC-IDS.

Background This study aims to evaluate the incidence of and identify risk factors for gastrointestinal (GI) and genitourinary (GU) fistula or perforation formation with or without bevacizumab in patients with recurrent cervical cancer who underwent pelvic radiation therapy (RT). Methods Medical records of patients with recurrent cervical cancer who previously underwent pelvic RT between 2007 and 2020 were retrospectively reviewed. Clinicopathological factors were compared between groups that are stratified according to: 1) fistula/perforation (+) versus (-); and 2) bevacizumab plus conventional chemotherapy (BC) versus chemotherapy alone (C). Univariate and multivariate regression analyses were performed to identify risk factors for fistula/perforation. Overall survival (OS) was compared between the different groups. Results Of 219 participants, fistula/perforation of any grade occurred in 36 patients (16.4%); 27 fistulas and 9 perforations. Bevacizumab was more frequently used in Bevacizumab was more frequently used ( +) group than fistula/perforation (-) group (p = 0.015). Multivariate analysis showed that bevacizumab administration was the only independent risk factor for fistula or perforation (HR, 3.27; 95% CI, 1.18–9.10; P = 0.023). F/P was observed more frequently in women receiving BC (n = 144) than those receiving C (n = 75) (20.8% vs. 8.0%; P = 0.019). During median follow-up of 33.7 months (1.2–185.6 months), no significant OS difference was observed between fistula/perforation ( +) vs. (-) (hazards ratio [HR], 1.78; median 84.2 months [95% CI, 59.3–109.0] vs. 129.5 months [95% CI, 114.1–144.9]; P = 0.065) or BC vs. C (HR, 1.03; median 119.8 months [95% CI, 97.3–142.3] vs. 115.7 months [95% CI, 96.0–135.4]; P = 0.928). Conclusions This study suggests that incorporation of bevacizumab in chemotherapy regimens for treating recurrent cervical cancer in patients who underwent pelvic RT incurs considerable risk for GI/GU fistula or perforation. There were no other independent risk factors for developing GI/GU fistula or perforation in this study population.

Purpose Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and methods Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results Among the recruited patients, 569 (63.9%) with naive HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Introduction:Vascular dementia (VaD), a severe neurologic condition related to aging of the cerebrovascular structure, has been treated with herbal medications and products. In this overview of systematic reviews (SRs) on the effects of herbal medications, we aimed to summarize the current clinical evidence on the benefits of herbal drugs and to propose an evidence map outlining their effects on VaD.Methods:SRs assessing their effects on cognitive function or performance and the associated safety, published until December 2018, were located from PubMed, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, China National Knowledge Infrastructure, and Oriental Medicine Advanced Searching Integrated System. A Measurement Tool to Assess systematic Reviews 2 was used to assess their overall confidence. A bubble plot was proposed to present the depth and width of the current status of the evidence supporting the use of individual herbal drugs.Results:Ten SRs (4 on individual herbal medications and 6 on various herbal drugs) were included. The overall evidence on herbal medicines suggests that they are effective in improving cognitive function and performance. Individual herbal medications including FuFangHaiShe, NaoXinTong, YinDanXing- NaoTong, NaoMaiTai, ShenFuTang, and TongXinLuo showed favourable effects when assessed via a minimal mental state examination score but have limited evidence supporting their effectiveness due to the scarcity of randomized controlled trials. Concerning safety, most SRs did not outline the estimated risk ratio of adverse events.Conclusions:Herbal medications might have benefits for VaD patients but they need to be evaluated further.

Background The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition. Methods A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739). Results Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system (“ASAR”). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570–0.871) in the derivation, 0.700 (95% CI = 0.445–0.905) in the internal validation, and 0.680 (95% CI = 0.652–0.707) in the external validation, respectively. Patients with ASARP P Conclusions ASAR provides refined prognostication for repetition of TACE in patients with unresectable HCC. For Child-Pugh class B patients, a modified model with baseline factors might guide TACE initiation.

Objective Electroacupuncture (EA) is used in the treatment of various diseases through the use of electrical stimulation. Reports of adverse events (AEs) associated with acupuncture are relatively consistent, but the safety of EA has been less well reported. In this systematic review, we provide a summary of the types of AEs related to EA in clinical practice. Methods Twelve electronic databases, including those in English (PubMed, Ovid-EMBASE, CENTRAL), Korean (KMbase, KISS, NDSL, KISTI, OASIS), Chinese (CNKI, Wanfang, Weipu) and Japanese (J-STAGE), were systematically searched for single case studies and case series through April 2018. There were no language restrictions. We included clinical studies in which EA was used as a key intervention and in which AEs that may have been causally related to EA were reported. Results Thirty-seven studies, including 27 single case studies and 10 case series, were evaluated. The most frequently reported AEs were pallor (eight cases), skin pigmentation (eight cases), vertigo (seven cases), chest tightness (six cases), vomiting (six cases) and unconsciousness (five cases). Thirty-one cases (62%) achieved full recovery and three cases (6%) achieved partial recovery. There were also three cases of death (6%). Conclusion AEs related to EA included acupuncture-related AEs and serious AEs induced by electrical stimulation. Currently, specific stimulation conditions associated with EA-specific AEs are not identifiable due to inappropriate reporting. However, skin pigmentation, syncope or spasm, implantable cardioverter-defibrillator shock, cardiac emergencies, electrical burns, and potential internal organ injury are potential EA-specific AEs regarding which physicians should be cautious in clinical practice.

Background Data on clinical characteristics of nonalcoholic fatty liver disease (NAFLD) in patients with chronic kidney disease (CKD) are scarce. We investigated the clinical features and risk factors of NAFLD using noninvasive serum markers in CKD patients and attempted the temporal validation of a predictive model for CKD based on NAFLD. Methods This retrospective cross-sectional study was conducted in a single tertiary center. We enrolled 819 CKD patients and evaluated the predictive performance of relevant clinical and laboratory markers for the presence of NAFLD in both derivation (data from 2011 to 2014, n = 567) and validation (data from 2015 to 2016, n = 252) groups. Results In the derivation group, NAFLD was observed in 89 patients (15.7%; mean body mass index (BMI), 24.6 kg/m2; median estimated glomerular filtration rate (eGFR), 28.0 ml/min). BMI, hemoglobin, serum alanine aminotransferase, eGFR, and triglyceride-glucose index were used to derive a prediction model for the presence of NAFLD. Using the cutoff value of 0.146, the area under the receiver operating characteristic curve (AUROC) for the prediction of NAFLD was 0.850. In the validation group, NAFLD was observed in 51 patients (20.2%; mean BMI, 25.4 kg/m2; median eGFR, 36.0 ml/min). Using the same prediction model and cutoff value, the AUROC was 0.842. NAFLD prevalence in CKD patients was comparable to that in the general population, increasing over time. Conclusions Our model using BMI, renal function, triglyceride-glucose index, serum alanine aminotransferase, and hemoglobin accurately predicted the presence of NAFLD in CKD patients.

BackgroundPHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer.MethodsChk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial.Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101.DiscussionPHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer.Trial registrationClinicalTrials.govIdentifier:NCT04678102.

Background To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). Methods We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). Results A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552–2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621–5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139). Conclusions Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.

Pulmonary blastoma is an extremely rare and highly aggressive tumor. Only a few hundred cases of pulmonary blastoma have been reported. In other cases, a definitive diagnosis is often made through surgical resection. The use of preoperative histopathological sampling in diagnosing was of limited value because of the variety of pulmonary blastoma histology. And there was no literature that the first biopsy was attempted with medical thoracoscopy for diagnosis.A 65-year-old man presented to our hospital with pleural effusion and lung mass.The patient was initially diagnosed with dedifferentiated chondrosarcoma by medical thoracoscopic biopsy but the final diagnosis was pulmonary blastoma through bilobectomy.Medical thoracoscopy, and video-assisted thoracoscopic surgery (bilobectomy) followed by adjuvant chemotherapy.After surgical resection of the tumor, adjuvant chemotherapy has been performed 5 cycles at 3 weeks intervals, and there was no evidence of recurrence on follow-up computed tomography performed 4 months after surgery.Medical thoracoscopy is useful for the diagnosis of indeterminate pleural effusion; however, caution is needed when confirming rare malignancies, such as pulmonary blastoma. Although surgical resection is the treatment of choice, appropriate adjuvant chemotherapy to improve the prognosis may be necessary if there is pleural metastasis.

Previous studies evaluating association between circulating tumor cells (CTCs) and clinical outcomes in hepatocellular carcinoma (HCC) have shown inconsistent results due to suboptimal detection methods and patient heterogeneity. Patients undergoing surgery for early-stage HCC were prospectively enrolled. The CTC numbers were determined using a tapered slit platform, which detects CTCs based on the cell size and morphology. Survival and recurrence were evaluated, and Cox proportional hazards models were used to demonstrate the prognostic significance of CTC. Of 105 patients, 25 had increased CTC numbers after surgery (ΔCTC > 0, defined as positive) and a significantly higher level of recurrence (p = 0.042). A positive ΔCTC was seen to be an independent predictor of recurrence (hazard ratio 2.28), along with hepatitis B virus infection, alanine aminotransferase level, and the presence of satellite nodules (all p

Background: Randomised controlled trials of acupuncture performed using sham interventions to control for the placebo effect have mostly used two types of sham techniques: techniques with minimal insertion of acupuncture needles with no additional stimulation (shallow needling control) and techniques with sham acupuncture devices that do not penetrate the skin (sham device control). To achieve successful blinding, sham device controlled acupuncture trials also use the acupuncture base unit in the verum acupuncture group, but in the shallow needling control trials this is not necessary for the verum acupuncture treatment. Objective: In this study, we analysed the estimated comparative effectiveness of these two verum acupuncture modalities in studies of acupuncture for menopausal hot flashes that used two types of sham control treatments. Methods: We conducted a network meta-analysis that included randomised controlled trials of acupuncture for hot flashes. Electronic databases, including Medline, Embase, Cochrane Library and AMED, were searched through March 2017. Data were extracted using a predefined data extraction tool by two independent reviewers. The risk of bias was assessed using the Cochrane risk of bias tool for randomised controlled trials. A five-node network meta-analysis was conducted based on the frequentist framework. Results: Eight studies were included in this review. From the network meta-analysis, we found that verum acupuncture in the shallow needling controlled trials was more effective than verum acupuncture in the sham device controlled trials (SMD −7.27, 95% CI−9.11 to −5.43). Significant heterogeneity and inconsistency were not observed among the included studies or the comparisons. Conclusions: From this preliminary analysis, we found that different types of verum acupuncture may have different effect sizes with respect to the severity of menopausal hot flashes.

Keeping RNA processing contained Biomolecular condensates that assemble by phase separation are involved in RNA processing. Posttranslational modifications in intrinsically disordered regions of proteins can regulate RNA processing by regulating phase separation. Kim et al. used nuclear magnetic resonance spectroscopy to characterize phase separation in a model system comprising the C-terminal disordered regions of the translational regulators FMRP and CAPRIN1 that repress translation by deadenylating mRNA. Interactions between the proteins involve specific sequences in FMRP and CAPRIN1, and the propensity for mRNA to partition into the condensates depends on the phosphorylation patterns in the disordered regions. This mechanism integrates signaling pathways with the regulation of RNA processing. Science , this issue p. 825

Background Autism spectrum disorder (ASD) is characterized by continuous impairment in communication and social interaction and by limited and repetitive behaviors, interests, or activities. Behavioral, educational, and pharmaceutical interventions have been shown to reduce behavioral disabilities, improve verbal/non-verbal communication, and help patients acquire self-reliance skills. However, there has been a lack of systematic verification and consensus regarding the treatment of the core symptoms of ASD because of its unclear etiology. Ukgansangajinpibanha (UGSJB), a legitimately prescribed herbal medicine for nervousness, insomnia, night crying, and malnutrition in South Korea and Japan, has been used for angry, sensitive, nervous, and unsettled children with ASD. Methods/design This trial is a prospective, multicenter, randomized, double-blinded, placebo-controlled, parallel-group, clinical trial. The 4- to 6-year-old children with ASD will be randomly assigned to following groups:A UGSJB granule with acupuncture, twice daily (n = 120)A placebo group with acupuncture, twice daily (n = 120). The following outcome measures will be used: behavior by the Childhood Autism Rating Scale, Autism Behavior Checklist, and Aberrant Behavior Checklist; social maturity by the Social Maturity Scale; quality of life by the Child Health Questionnaire and EuroQoL Five-dimension Five-level Youth; and parental stress by the Parenting Stress Index at baseline and at 6, 12, and 24 weeks after the beginning of treatment. In addition, to evaluate safety, we will investigate the adverse reactions that may be caused by UGSJB granule. Finally, we will make an economic evaluation of UGSJB for the treatment of ASD. Discussion We prepared a well-designed clinical trial to investigate the safety and effectiveness of UGSJB on ASD symptoms compared with placebo treatment. The results from this study will provide clinical evidence on the safety, effectiveness, and economic value of UGSJB combined with acupuncture in children with ASD. Trial registration Clinical Research Information Service: KCT0003007 (registered on April 5, 2018) Electronic supplementary material The online version of this article (10.1186/s13063-019-3537-7) contains supplementary material, which is available to authorized users.

Background: Cold hypersensitivity in the hands and feet (CHHF) is frequent in Asian countries including Korea. The quality of life can be degraded by the symptoms of CHHF. In particular, gynecological disorders such as menstrual pain, infertility, leucorrhea, and irregular bleeding may be related to CHHF. Sipjeondaebo-tang(SDT) is widely used in the treatment of various diseases including CHHF by balancing Yin and Yang, restoring the deterioration of physiological function, and improving immunity. However, the efficacy of SDT in the treatment of CHHF has not been assessed in clinical trials. Therefore, we aimed to investigate the feasibility of a full randomized clinical trial of SDT for the treatment of CHHF in Korean women through this trial. Methods: This study will be a pilot, randomized, double-blind, two-arm, placebo-controlled, parallel-group, multicenter clinical trial. Women aged 19-59 years who present with CHHF will be recruited from five university hospitals. A total of 60 subjects will be randomly assigned to a treatment group (SDT) or a placebo group at a 1:1 ratio. The subjects will receive 3 g of either SDT or placebo three times daily for 8 weeks. The primary outcome measures will be the Visual Analogue Scale scores of CHHF. The secondary outcome measures will be changes in body temperature in both the hands and the feet as measured by using a thermometer and the Korean version of the World Health Organization Quality of Life Scale Abbreviated Version. Discussion: This will be the first trial to investigate the efficacy and safety of SDT in the treatment of CHHF. This study will provide basic clinical information regarding Korean herbal medicine treatment of CHHF and a clinical basis for designing a full randomized clinical trial. Trial registration: This study is registered at ClinicalTrials.gov, ID: NCT03374345. Registered on (15 February 2018). Keywords: Herbal medicine, Cold Hypersensitivity, Sipjeondaebo-tang, Cold intolerance.

Goals: We aimed to investigate significant factors influencing the long-term prognosis of patients who survived acute-on-chronic liver failure (ACLF). Background: The mortality of ACLF is predominantly affected by the organ failure severity. However, long-term outcomes of patients who survive ACLF are not known. Study: A cohort of 1084 cirrhotic patients who survived for more than 3 months following acute deterioration of liver function was prospectively followed. ACLF was defined by the European Association for the Study of the Liver Chronic Liver Failure Consortium definition. Results: The mean follow-up duration was 19.4±9.9 months. In the subgroup of patients without previous acute decompensation (AD), ACLF occurrence did not affect long-term outcomes. However, in patients with previous AD, ACLF negatively affected long-term transplant-free survival even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the significant predictive factor of long-term mortality and was independent of the Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ failure severity did not affect transplant-free survival in patients who survived an ACLF episode. Conclusions: A prior history of AD is the most important factor affecting long-term outcomes following an ACLF episode regardless of Model for End-stage Liver Disease score. Prevention of a first AD episode may improve the long-term transplant-free survival of liver cirrhosis patients.

The role of biomolecular condensates in regulating biological function and the importance of dynamic interactions involving intrinsically disordered protein regions (IDRs) in their assembly are increasingly appreciated. While computational and theoretical approaches have provided significant insights into IDR phase behavior, establishing the critical interactions that govern condensation with atomic resolution through experiment is more difficult, given the lack of applicability of standard structural biological tools to study these highly dynamic large-scale associated states. NMR can be a valuable method, but the dynamic and viscous nature of condensed IDRs presents challenges. Using the C-terminal IDR (607 to 709) of CAPRIN1, an RNA-binding protein found in stress granules, P bodies, and messenger RNA transport granules, we have developed and applied a variety of NMR methods for studies of condensed IDR states to provide insights into interactions driving and modulating phase separation. We identify ATP interactions with CAPRIN1 that can enhance or reduce phase separation. We also quantify specific side-chain and backbone interactions within condensed CAPRIN1 that define critical sequences for phase separation and that are reduced by O-GlcNAcylation known to occur during cell cycle and stress. This expanded NMR toolkit that has been developed for characterizing IDR condensates has generated detailed interaction information relevant for understanding CAPRIN1 biology and informing general models of phase separation, with significant potential future applications to illuminate dynamic structure-function relationships in other biological condensates.

and purpose: Although several studies have reported that thread embedding acupuncture (TEA) is effective for lumbar herniated intervertebral disc (LHIVD), the evidence remains limited because previous studies had a high risk of bias. This study aimed to investigate the efficacy and safety of TEA for LHIVD through a rigorously designed trial.This was a randomized, patient-assessor-blinded, sham-controlled trial. Participants were screened according to eligibility criteria, and 70 patients with LHIVD were randomly allocated to the TEA and sham TEA (STEA) groups in a 1:1 ratio. Both groups received TEA or STEA treatment at 23 acupoints once per week for eight weeks. Changes in low back pain, radiating pain, Oswestry disability index, Roland-Morris disability questionnaire, EuroQol 5-Dimensions 5-Levels, and global perceived effect were measured at baseline and at 4, 8, 12, and 16 weeks after screening and compared between the two groups.TEA showed no significant difference in all outcomes compared to STEA immediately after eight weeks of treatment. After an additional eight weeks of follow-up, TEA showed a more significant effect on the low back pain than STEA (p 0.05) and showed a better tendency in maintaining or enhancing the improvement of radiating pain, function, and quality of life even after the end of treatment. No serious adverse events were observed.TEA is effective in improving low back pain in patients with LHIVD and may help improve function and quality of life, especially in the long term.

Background Dietary supplements with ginseng, or ginseng alone, are widely used for a broad range of conditions, including erectile dysfunction. Ginseng is particularly popular in Asian countries. Individual studies assessing its effects are mostly small, of uneven methodological quality and have unclear results. Objectives To assess the effects of ginseng on erectile dysfunction. Search methods We conducted systematic searches on multiple electronic databases, including CENTRAL, MEDLINE, Embase, CINAHL, AMED, and loco‐regional databases of east Asia, from their inceptions to 30 January 2021 without restrictions on language and publication status. Handsearches included conference proceedings. Selection criteria We included randomized or quasi‐randomized controlled trials that evaluated the use of any type of ginseng as a treatment for erectile dysfunction compared to placebo or conventional treatment. Data collection and analysis Two authors independently classified studies and three authors independently extracted data and assessed risk of bias in the included studies. We rated the certainty of evidence according to the GRADE approach. Main results We included nine studies with 587 men with mild to moderate erectile dysfunction, aged from 20 to 70 years old. The studies all compared ginseng to placebo. We found only short‐term follow‐up data (up to 12 weeks). Primary outcomes Ginseng appears to have a trivial effect on erectile dysfunction when compared to placebo based on the Erectile Function Domain of the International Index of Erectile Function (IIEF)‐15 instrument (scale: 1 to 30, higher scores imply better function; mean difference [MD] 3.52, 95% confidence interval [CI] 1.79 to 5.25; I² = 0%; 3 studies; low certainty evidence) assuming a minimal clinically important difference (MCID) of 4. Ginseng probably also has a trivial effect on erectile function when compared to placebo based on the IIEF‐5 instrument (scale: 1 to 25, higher scores imply better function; MD 2.39, 95% CI 0.89 to 3.88; I² = 0%; 3 studies; moderate certainty evidence) assuming a MCID of 5. Ginseng may have little to no effect on adverse events compared to placebo (risk ratio [RR] 1.45, 95% CI 0.69 to 3.03; I² = 0%; 7 studies; low certainty evidence). Based on 86 adverse events per 1000 men in the placebo group, this would correspond to 39 more adverse events per 1000 (95% CI 27 fewer to 174 more). Secondary outcomes Ginseng may improve men's self‐reported ability to have intercourse (RR 2.55, 95% CI 1.76 to 3.69; I² = 23%; 6 studies; low certainty evidence). Based on 207 per 1000 men self‐reporting the ability to have intercourse in the placebo group, this would correspond to 321 more men (95% CI 158 more to 558 more) per 1000 self‐reporting the ability to have intercourse. Ginseng may have a trivial effect on men's satisfaction with intercourse based on the Intercourse Satisfaction Domain of the IIEF‐15 (scale: 0 to 15, higher scores imply greater satisfaction; MD 1.19, 95% CI 0.41 to 1.97; I²=0%; 3 studies; low certainty evidence) based on a MCID of 25% improvement from baseline. It may also have a trivial effect on men's satisfaction with intercourse based on item 5 of the IIEF‐5 (scale: 0 to 5, higher scores imply more satisfaction; MD 0.60, 95% CI 0.02 to 1.18; 1 study; low certainty evidence) based on a MCID of 25% improvement from baseline. No study reported quality of life as an outcome. We found no trial evidence to inform comparisons to other treatments for erectile dysfunction, such as phosphodiesterase‐5 inhibitors. We were unable to conduct any predefined subgroup analyses. Authors' conclusions Based on mostly low certainty evidence, ginseng may only have trivial effects on erectile function or satisfaction with intercourse compared to placebo when assessed using validated instruments. Ginseng may improve men's self‐reported ability to have intercourse. It may have little to no effect on adverse events. We found no trial evidence comparing ginseng to other agents with a more established role in treating erectile dysfunction, such as phosphodiesterase‐5 inhibitors., Plain language summary Ginseng for improving erectile function Review question Does ginseng help men’s ability to have erections? Background Many men have problems with gaining an erection. This can result in low self‐esteem, relationship issues and reduced quality of life. Medication and surgery can help with this problem, but studies also suggest that herbal supplements may help. We reviewed the literature to find out whether certain forms of ginseng, a popular root used in many countries, can help with erection problems. Study characteristics We included nine studies that compared the effects of ginseng against a placebo (dummy drug). These studies included 587 participants with mild to moderate difficulty in erection, aged 20 to 70 years old. All information we found was limited to a short follow‐up period of 12 weeks or fewer. Key results Compared to a dummy drug, ginseng may have a trivial effect on erectile function, as assessed by two questionnaires specially developed for this purpose. It may also have little to no effect on unwanted side effects. It may also have a trivial effect on men's satisfaction with intercourse based on responses to two specialized questionnaires. When men were simply asked whether their erections improved (without using a specialized questionnaire), the results of this systematic review show that ginseng may improve the ability to have intercourse. Certainty of evidence The certainty of evidence for most outcomes was low. This means that the true effect may be substantially different from what this review shows.

Background The dropout rate is an important determinant of outcomes in randomized controlled trials (RCTs) and should be carefully controlled. This study explored the current dropout rate in studies of Korean medicine (KM) interventions by systematic evaluation of RCTs conducted in the past 10 years. Methods Three clinical trial registries (Clinical Research Information Service, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform) were searched to identify RCT protocols for KM interventions, such as acupuncture, herbal medicine, moxibustion, or cupping, and studies of mixed interventions, registered in Korea from 2009 to 2019. The PubMed, Embase, and OASIS databases were searched for the full reports of these RCTs, including published journal articles and theses. Dropout rates and the reasons for dropping out were analyzed in each report. The risk of bias in each of the included studies was assessed using the Cochrane risk of bias tool. The risk difference for dropping out between the treatment and control groups was calculated with the 95% confidence interval in a random effects model. Results Forty-nine published studies were included in the review. The median dropout rate was 10% in the treatment group (interquartile range 6.7%, 17.0%) and 14% in the control group (interquartile range 5.4%, 16.3%) and was highest in acupuncture studies (12%), followed by herbal medicine (10%), moxibustion (8%), and cupping (7%). Loss to follow-up was the most common reason for dropping out. The risk difference for dropping out between the intervention and control groups was estimated to be 0.01 (95% confidence interval − 0.02, 0.03) in KM intervention studies. Conclusions This review found no significant difference in the dropout rate between studies according to the type of KM intervention. We recommend allowance for a minimum dropout rate of 15% in future RCTs of KM interventions. Review protocol registration PROSPERO CRD42020141011

Small- and intermediate-conductance Ca2+-activated K+ channels, KCa2.3 and KCa3.1, are involved in cellular signaling processes associated with inflammation and fibrosis. KCa2.3 and KCa3.1 are upregulated by proinflammatory cytokines and profibrotic growth factors. Cyclic AMP, which downregulates KCa2.3 and KCa3.1, is elevated by modafinil in cells; accordingly, we investigated whether modafinil exerts anti-inflammatory and anti-fibrotic responses via KCa2.3- and KCa3.1-mediated pathways in high-fat diet (HFD)- or thioacetamide-induced liver disease models in mice. Modafinil was administered orally in the form of a racemate, (R)-isomer, or (S)-isomer. We also determined whether the treatment targeted the profibrotic activity of hepatic stellate cells using immortalized human hepatic stellate cells (LX-2 cells). Modafinil improved HFD- or thioacetamide-induced changes compared to the control, leading to a reduced inflammatory response, collagen deposition, and α-smooth muscle actin expression both in vivo and in vitro. However, modafinil did not relieve HFD-induced steatosis. There were no significant differences in the effects of the (R)- and (S)-isomers of modafinil. KCa2.3 and KCa3.1 were upregulated and catalase was downregulated in liver tissues from thioacetamide- or HFD-induced liver disease models or in TGF-β-treated LX-2 cells. TGF-β-induced upregulation of KCa2.3, KCa3.1, collagen, and α-smooth muscle actin and downregulation of catalase were reversed by modafinil, polyethylene glycol catalase, N-acetylcysteine, siRNA against KCa2.3 or KCa3.1, and Epac inhibitors. Our investigation revealed that modafinil attenuated inflammatory and fibrotic progression via KCa2.3- and KCa3.1-mediated pathways in nonalcoholic hepatitis, suggesting that inhibiting KCa2.3- and KCa3.1-mediated signaling may serve as a novel therapeutic approach for inflammatory and fibrotic liver diseases.

The role of advanced glycation end products (AGEs) is not limited to diabetes and diabetes-related complications. There are multiple modulators, including the receptor for advanced glycation end products, high mobility group box 1, glyoxalase 1, nuclear factor-kappa B, tumor necrosis factor-α, chronic unpredictable stress, reactive oxygen species, and inflammatory cytokines, which interact with AGE signaling and control diabetes, modulating these interacting modulators. The progression of diabetes, as well as related complications, can be controlled and treated. Natural products rich in bioactive constituents can interact with AGEs and their related mediators through various signaling cascades, thereby controlling and preventing the progression of diabetes. This review provides a deeper assessment of the signaling pathway, interactions between phytochemicals and AGEs, and its mediators, to develop a multifold therapeutic approach to prevent and treat diabetes and its related complications.

The relationship between changes in body components and the risk of nonalcoholic fatty liver disease (NAFLD) is not fully understood. We investigated the effects of body components and subsequent changes on incident NAFLD at follow-up ultrasound scanning in a longitudinal cohort. We included 9967 participants without NAFLD at baseline who underwent serial health examinations. Sex-specific, weight-adjusted skeletal muscle index (SMI_Wt) was used. Mean follow-up duration was 48.5 ± 33.5 months. NAFLD developed in 2395 participants (24.0%). Body composition was measured using bioelectrical impedance analysis. The following baseline body components were significantly associated with incident NAFLD: the lowest and middle SMI_Wt tertiles in the normal-weight group (adjusted hazard ratio [aHR] = 2.20 and 1.54, respectively), and fat percentage in the normal-weight (aHR = 1.12), overweight (aHR = 1.05), and obese groups (aHR = 1.03) (all P _Wt increase between the first and second examinations was an independent protective factor against incident NAFLD in non-obese groups (P P

Final publication is available from Mary Ann Liebert, Inc., publishers https://doi.org/10.1089/acm.2020.0032. Background: Acupuncture is one of the fastest developing evidence bases in Complementary Medicine and is one of the leading therapies included within integrative health care. This narrative review includes two separate parts: the first is about evaluation of the current evidence status in reviews on acupuncture and the second examines and gives examples of available recommendations on acupuncture in treatment guidelines from health care experts and public health organizations recommending acupuncture as a viable treatment in patients in palliative care. Methods: Electronic searches were performed in PubMed using the terms “acupuncture” + “palliative” and adding the term “safety” to find review articles documenting safety and evidence of effectiveness of acupuncture for treatment of symptoms in palliative care patients. Treatment guidelines that recommend use of acupuncture for symptom control in palliative care were found by searching through a database currently under construction by the lead author. Results: Acupuncture shows emerging evidence for 17 indications in palliative care. Examples were found and presented of publications recommending acupuncture for treatment of symptoms for patients in palliative care from Government, public health, oncology, and medical expert sources. The most publications are in oncology, but other conditions were found and a number were found in pediatric care. Conclusions: While the evidence for use of acupuncture to treat symptoms in palliative care patients is relatively weak, the evidence base is growing. Experts worldwide are also increasingly recommending acupuncture as a treatment for symptoms in palliative care. Since acupuncture is a safe, nonpharmacological treatment but with small, clinically significant effects, these recommended uses appear as pragmatic efforts to bridge the gap of treatment options available to this patient group.

Many studies have suggested the possibility of using functional near-infrared spectroscopy (fNIRS) devices as neuroimaging tools in various patients. We aimed to evaluate whether fNIRS to measure the prefrontal cortex (PFC fNIRS) is suitable as a screening tool for cognitive impairments. Sixty participants, divided into normal, mild cognitive impairment, and dementia groups, were instructed to wear an fNIRS device during cognitive assessments to assess whether there is a significant difference in the PFC activity between the groups. A significant difference in PFC activity between the groups was observed during the verbal fluency test. Moreover, the PFC activity during the verbal fluency test significantly correlated with the existing cognitive screening tool score. These results suggested that PFC fNIRS can be used as a cognitive impairment screening tool for mild cognitive impairment and dementia. A larger sample size is needed to validate the potential of PFC fNIRS as a cognitive impairment screening tool.

Background/aim Although ginseng seed oil (GSO) appears to have various roles in the body, its anti-cancer effect has not been investigated. Tamoxifen is widely used to treat estrogen receptor-positive (ER+) breast cancer but shows adverse effects with drug resistance. This study investigated the effect of GSO in ER+ breast cancer cell growth. Materials and methods Cell viability assays, western blots and Annexin V staining were conducted to examine cell viability and apoptosis. The synergistic effect of tamoxifen in combination with GSO or oleic acid (OA) was determined. Results GSO and OA caused apoptosis of MCF-7 ER+ breast cancer cells and had synergistic effects with tamoxifen in inhibiting tamoxifen-resistant MCF-7 (MCF-7TAMR) ER+ breast cancer cell growth. Conclusion GSO may block ER+ breast cancer recurrence in combination with tamoxifen.

In this work, the influence of parylene N film on the spheroid formation of osteoblast-like cells (MG-63) was determined and compared with that of high-hydrophilicity microenvironments, such as hydrophilic culture matrix and ultraviolet-treated parylene N film. To elucidate the change in cell properties due to the microenvironment of parylene N film, global gene expression profiles of MG-63 cells on parylene N film were analyzed. We confirmed the upregulated expression of osteoblast differentiation- and proliferation-related genes, such as Runx2, ALPL, and BGLAP and MKi67 and PCNA, respectively, using the real-time polymerase chain reaction. In addition, the differentiation and proliferation of osteoblast cells cultured on parylene N film were validated using immunostaining. Finally, the formation of spheroids and regulation of differentiation in human mesenchymal stem cells (MSCs) on parylene N film was demonstrated. The results of this study confirm that the microenvironment with the controlled hydrophobic property of parylene N film could effectively trigger the bone differentiation and maintains the proliferation of MSCs, similar to MG-63 cells without any scaffold structures or physical treatments.

Background Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. The only drug currently approved for clinical use in the treatment of advanced HCC is sorafenib. However, many patients with HCC show reduced sensitivity to sorafenib during treatment. SIRT3, a member of the mammalian sirtuin family, is a tumor suppressor in certain tumor types. However, only few studies have investigated the effects of SIRT3 on tumor prognosis and sorafenib sensitivity in patients with HCC. Here, we aimed to investigate the correlation between SIRT3 expression and glucose metabolism and proliferation in HCC and discover effective compounds that increase endogenous SIRT3 modulation effect of sorafenib. Methods To determine the correlation between SIRT3 and glucose related proteins, immunostaining was performed with liver cancer tissue using various antibodies. To investigate whether the expression of SIRT3 in HCC is related to the resistance to sorafenib, we treated sorafenib after the modulation of SIRT3 levels in HCC cell lines (overexpression in Huh7, knockdown in HepG2). We also employed PD0332991 to modulate the SIRT3 expression in HCC cell and conducted functional assays. Results SIRT3 expression was downregulated in high glycolytic and proliferative HCC cells of human patients, xenograft model and HCC cell lines. Moreover, SIRT3 expression was downregulated after sorafenib treatment, resulting in reduced drug sensitivity in HCC cell lines. To enhance the anti-tumor effect of sorafenib, we employed PD0332991 (CDK4/6-Rb inhibitor) based on the correlation between SIRT3 and phosphorylated retinoblastoma protein in HCC. Notably, combined treatment with sorafenib and PD0332991 showed an enhancement of the anti-tumor effect in HCC cells. Conclusions Our data suggest that the modulation of SIRT3 by CDK4/6 inhibition might be useful for HCC therapy together with sorafenib, which, unfortunately, has limited efficacy and whose use is often associated with drug resistance.

Background/aim The aim of the present study was to investigate the mechanism through which kisspeptin inhibits colorectal cancer metastasis. Materials and methods Colorectal cancer cells were treated with kisspeptin and then subjected to assays for cell viability, migration, invasion and anchorage-independent growth. Kisspeptin receptor (KISS1R) requirement was examined by siRNA-based gene silencing followed by western blot and invasion assays. Kisspeptin regulation of PKR and PP2A was examined by treating cells with inhibitors for PKR or PP2A. Results Kisspeptin inhibited colorectal cancer cell invasiveness without affecting cell proliferation. Kisspeptin required activation of KISS1R and resulted in activation of PKR and PP2A. PKR inhibitor blocked kisspeptin-induced PP2A phosphorylation, while PP2A inhibitor failed to block kisspeptin-induced PKR phosphorylation. Conclusion Kisspeptin-mediated activation of PKR-PP2A inhibited colorectal cancer cell invasiveness.

Graves’ disease (GD) is the most common cause of hyperthyroidism. Anti-thyroid drugs, including methimazole, are the most commonly selected treatment option for this condition. But for decades, no additional drug option has been added. Anemarrhena Bunge has been used in many herbal decoctions for patients who had hyperthyroidism-like symptoms, such as sweating, heat intolerance, and anxiety. In this case study, a patient with GD who had once achieved therapeutic goals with methimazole but then re-developed hyperthyroidism was treated with only herbal decoctions, and achieved euthyroidism, normalization of T3, T4 levels for 13 months and maintenance of thyroid stimulating hormone (TSH) levels for 8 months and TSH binding inhibitory immunoglobulins (TBII)-negative status for 13 months (TSH and TBII level before treatment: 0.01 μIU/mL, 10.94 IU/L; TSH level normalization after 14 months from the initiation of the treatment: 0.75 μIU/mL, TBII level normalization after 9 months from the initiation of the treatment: 0.8 IU/L). The patient did not report any adverse effects related to this treatment. A herbal decoction with Anemarrhena Bunge might be effective in patients who are resistant to methimazole treatments, a finding which needs further investigation in future.

As positive evidence emerges for the use of an intervention to treat a health problem, the intervention gradually becomes incorporated into treatment guidelines (TGs) or clinical practice guidelines (CPGs) that are related to that health problem. To assess whether this general hypothesis can apply to acupuncture, 96 health problems were identified for which positive conclusions in systematic reviews and meta-analyses regarding the effectiveness of acupuncture have been made and then searched for TGs or CPGs that have recommended the use of acupuncture.Through August 31, 2017, searches were performed in relevant medical databases and Google using "treatment guideline," "clinical practice guideline," and the names of the 96 medical conditions as search terms. A "snow-balling" search approach was adopted. All positive recommendations were added into the registry.A total of 1311 publications were found that recommended using acupuncture published between 1991 and 2017. The number per year reached 50 in 2005 and 100 in 2009. In addition, 2189 positive recommendations were found for the use of acupuncture. Of these, 1486 were related to 107 pain indications and 703 were related to 97 nonpain indications. These recommendations were made by a wide range of groups, such as government health institutions, national guideline, and medical specialty groups. The recommendations came from around the world but were especially abundant in North America, Europe, and Australasia.Considerably more recommendations were found for the use of acupuncture than are known within the acupuncture or medical communities. A trend by year was also found; a rise in the number of positive statements about acupuncture was typically followed by a rise in the number of recommendations of acupuncture. Thus, the recommendations followed the emergent evidence for acupuncture. Better implementation plans need to be developed for the CPG/TG recommendations about acupuncture to be more effective/efficient.

Purpose To determine the prognostic value of peritumoral edema identified at preoperative breast magnetic resonance (MR) imaging for disease recurrence in patients with invasive breast cancer. Materials and Methods Between January 2011 and December 2012, 353 women (median age, 49 years; range, 27-77 years) with invasive breast cancer who had undergone preoperative MR imaging and mastectomy or breast-conserving surgery were identified. Two radiologists independently reviewed peritumoral edema on the basis of the degree of the signal intensity surrounding the tumor on T2-weighted images. The association of disease recurrence with peritumoral edema and clinical-pathologic features was assessed by using the multivariate Cox proportional hazards model and the integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI) indexes. Results Twenty-four patients (6.8%) had disease recurrence after 27.2 months of median follow-up. At multivariate analysis, higher N stage (hazard ratio = 4.84, P = .002) and the presence of lymphovascular invasion (hazard ratio = 2.48, P = .044) and peritumoral edema (hazard ratio = 2.77, P = .022) were independent factors associated with disease recurrence. IDI and continuous NRI showed significant improvement in the accuracy of the association with disease recurrence when peritumoral edema was added to established clinical-pathologic features (IDI = 0.061, P < .001; continuous NRI = 0.334, P = .012). Conclusion Peritumoral edema identified at preoperative MR imaging is independently associated with disease recurrence. Peritumoral edema assessment may provide better prognostication in patients with invasive breast cancer. © RSNA, 2018.

Acute compartment syndrome (ACS) after tibial fracture carries a risk of various complications, including infection, delayed union, nonunion, nerve damage, and poor prognosis. For the treatment of fractures with ACS, fasciotomy is conducted, and the method to stabilise the fracture has to be considered. Thirty-five patients who underwent surgery for ACS with tibial shaft fractures were evaluated, and the results of initial internal fixation (Group I, 20 patients) and initial external fixation (Group II, 15 patients) were analysed. The mean age was 41 years. Five patients needed additional surgery for bone union. Complications occurred in 4 cases, but no deep infection was reported. The time to bone union, the need for additional surgery, and the incidence of complications in Group I and Group II were not statistically different. For the treatment of ACS with tibial fracture, immediate internal fixation and changing from external fixation to internal fixation did not affect the clinical course.

Background/Aims Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks. Methods Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P

ObjectiveHeart rate control is important to prevent adverse outcomes in patients with heart failure (HF). However, postdischarge activity may worsen heart rate control, resulting in readmission. This study aimed to explore the implications of the heart rate differences between discharge and the first outpatient visit (D-O diff).MethodsWe retrospectively identified 458 patients (male: 46%; mean age: 72 years) discharged after HF. The heart rates at admission, discharge and first outpatient visit were analysed. The primary outcome was a composite of cardiovascular (CV) death and readmission of non-fatal myocardial infarction (MI), non-fatal stroke or non-fatal HF over a mean follow-up of 16 months.ResultsDuring follow-up, the clinical outcomes were noted in 223 patients (49%): HF, 199; stroke, 9; MI, 6; CV death, 9. The heart rate at the first outpatient visit (r=−0.311, PConclusionsA decreased D-O diff was related to the adverse outcomes of HF. The failure of heart rate control within more than 15 beats/min at the first outpatient visit was an independent factor for CV events.

Background Pediatric patients with olecranon fractures are uncommon. The tension band suture technique was introduced to reduce the burden of implant removal and other complications. However, to our knowledge, early range of motion (ROM) exercise has not been introduced in this population of patients. Double Vicryl loops and knots with 2 cross-pins are used to maintain the benefits of the tension band suture technique and to enhance fixation tensile strength. We believe that early ROM exercises could be achieved without nonunion or fixation failure. Methods Twelve pediatric patients with olecranon fractures were treated with tension band suture with double loops and knots between 2004 and 2015. Vicryl No. 1 was used for wiring. ROM exercises were initiated 1 week postoperatively with a customized functional brace. Early functional outcomes were evaluated by the Mayo Elbow Performance Score at every visit after 8 weeks postoperatively. Results Nine boys and 3 girls (average age, 10.6 years; range, 5 years 7 months–16 years 2 months) were included in the study. Initial displacement and angulation of the fractures were 5 mm (2-7 mm) and 12° (4°-25°), respectively. Two cases had radial neck fractures of the ipsilateral elbow. All patients had a perfect Mayo Elbow Performance Score after 8 weeks postoperatively. Pin removals were performed at 13.1 weeks. No complications, including growth arrest, were observed. Discussion/Conclusion Tension band suture with double loops and knots, combined with early ROM exercise, may be a complete alternative to tension band wiring.

Hepatic angiosarcoma is a mesenchymal tumor originating from liver sinusoidal endothelial cells. It is an extremely rare malignant neoplasm accounting for less than 1% of primary malignant liver tumors. The deregulated coagulopathy that can be seen in hepatic angiosarcoma fulfills the clinical diagnostic criteria of disseminated intravascular coagulation. However, the mechanism that governs this coagulopathy has been poorly understood. This case report provides histological evidence of the consumption of coagulation factors along with trapped platelets occurring within the tumor, which is the foundation for the concept of Kasabach-Merritt syndrome (KMS). KMS is characterized by thrombocytopenia and hyperconsumption of coagulation factors within a vascular tumor. However, KMS associated with angiosarcoma has not been well recognized. This case report describes, for the first time, the histological evidence of KMS that occurred in an extremely rare mesenchymal malignant tumor of the liver.

Intrinsically disordered proteins (IDPs) or regions of intrinsic disorder in otherwise folded proteins (IDRs) play important roles in many different biological processes, including formation of biological condensates via liquid-liquid phase separation. NMR spectroscopy is a powerful tool for obtaining site-specific structural and dynamical information on IDPs/IDRs, and recent efforts have focused on the development of experiments for atomic-resolution studies of these molecules. These include triple-resonance experiments that are based on 13CO-direct detection of magnetization, exploiting increased sensitivity of cryogenically cooled probes. In order to evaluate the different classes of experiment for studies of IDRs or IDPs in both dilute and phase-separated environments, in particular at neutral and higher pHs where many of these proteins phase separate, we compared 13CO-detect versus 1Hα-detect experiments, showing that significant sensitivity gains are achieved via proton detection under the conditions of our experiments. A suite of 1Hα-detect experiments was subsequently developed for studies of IDPs/IDRs and applied to the dilute phase of a 103-residue disordered region of CAPRIN1 that phase separates at neutral pH. Residue-specific chemical shifts derived from our study enable the accurate prediction of the importance of the N-terminal Arg-containing region of this construct for promoting phase separation relative to other Arg-rich stretches of sequence, subsequently confirmed by mutagenesis. Our study emphasizes that the sequence positions of key residues can be a critical factor in controlling phase separation and highlights the unique role of NMR in establishing the relations between amino acid sequence and phase-separation propensity.