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BACKGROUND: CA125 level normalization at different chemotherapy cycles has been reported to be a prognosticator in advanced epithelial ovarian cancer. OBJECTIVE: In the present study, we investigated whether the time (in days) to CA125 normalization or nadir during treatment could be used as markers to predict survival. METHODS: Patients with FIGO stage III–IV epithelial ovarian cancer treated with cytoreductive surgery followed by adjuvant chemotherapy between 2008 and 2016 were enrolled in this retrospective study. Clinicopathological characteristics, changes in CA125 level during treatment, and survival outcomes were analyzed. Time-dependent receiver operating characteristic curve analysis was used to determine the optimal cut-off values of the time to normalization and time to nadir of CA125 levels to predict survival. Univariate and multivariate Cox regression analysis were used to examine the impact of each variable on survival. RESULTS: A total of 106 patients were included in the analysis. The optimal cut-off values for the time to normalization and nadir for predicting survival were 60 and 194 days, respectively. In Kaplan-Meier survival analysis, CA125 level normalization ⩽ 60 days and CA125 ⩽ 35 u/mL after the third cycle, and CA125 level ⩽ 10 u/mL after the sixth cycle of chemotherapy were associated with significantly better 5-year progression-free survival (PFS) and overall survival (OS). In multivariate analysis, only CA125 level normalization > 60 days was significantly associated with poor survival outcomes (PFS, HR 2.62 [95% CI: 1.54, 4.45], p= 0.004; OS, HR 2.40 [95% CI: 1.19, 4.81], p= 0.014). CONCLUSIONS: Normalization of CA125 level within 60 days after cytoreductive surgery followed by adjuvant chemotherapy in patients with advanced ovarian epithelial cancer could be used as a marker to predict survival.

Screening for mismatch repair (MMR) deficiency in unselected patients with endometrial carcinoma (EC) and the clinicopathologic descriptions of ECs with MMR deficiency have been well demonstrated in Western populations, but studies on Asian populations are relatively scarce. In this study, we described the clinicopathologic features of ECs according to MMR status in unselected Taiwanese patients. We also conducted subgroup analysis of MMR-deficient (dMMR) cases according to the presence or absence of MLH1. Patients diagnosed with ECs between January 2017 and February 2020 at our institution were included. Immunohistochemistry analysis of MLH1, PMS2, MSH2, and MSH6 proteins on endometrial primary tumors and clinicopathologic variables were assessed retrospectively. A total of 231 EC patients were enrolled, of whom 50 (21.6%) had dMMR tumors. Of these 50 cases, 39 had tumors that lacked MLH1 expression and 11 were positive for MLH1. The overall dMMR group was significantly related to older age, parity, and high histologic grade compared with the MMR-proficient (pMMR) group. ECs with MLH1 deficiency were obviously associated with several poor pathologic features, including high histologic grade, lymph node metastasis, and lymphovascular space invasion. Moreover, we first reported that parity and the late age at menopause are strongly correlated with MLH1-related dMMR EC group compared with pMMR group. In conclusion, triaging EC patients into pMMR, MLH1-related dMMR and non-MLH1-related dMMR groups by immunohistochemistry analysis may help clinicians to predict disease behavior and guide further management. The strong association between parity and MLH1-related dMMR ECs warrants further investigation on the underlying mechanism.

Hao Lin,1 Wen-Hsin Chen,1 Chen-Hsuan Wu,1,2 Yu-Che Ou,3 Yu-Jen Chen,3 Ying-Yi Chen,1 Yu-Han Lin,4 Hung-Chun Fu1– 3 1Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Lin-Kou, Taiwan; 3Department of Obstetrics and Gynecology, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan; 4Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Hung-Chun FuDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta Pei Road, Niao Sung District, Kaohsiung City, Taiwan, Republic of ChinaTel +886 7 731712Fax +886 7 7322915Email allen133@adm.cgmh.org.twAim: To investigate whether the time interval between primary debulking surgery (PDS) and initiating adjuvant chemotherapy affects survival in patients with epithelial ovarian cancer (EOC).Methods: We retrospectively reviewed FIGO stage IIB to IV EOC patients who received PDS followed by adjuvant chemotherapy in our hospital between January 2008 and December 2016. The optimal cut-off time interval to chemotherapy related to survival was determined using the Contal and O’Quigley method and Cox hazard models. Cox regression analysis was used to identify the independent effect of time interval on survival.Results: A total of 152 patients were identified and divided into three groups based on the time interval between PDS and initiating adjuvant chemotherapy: early (< 23 days), intermediate (23– 43 days) and late (> 43 days). The intermediate group had a significantly better median progression-free survival (PFS, 35.5 months) compared to the early (20 months) and late (22.6 months) groups. After adjustments for confounding factors, time interval was still an independent variable affecting PFS. The intermediate group was associated with a better PFS compared with the early and late groups (hazard ratio 0.27, 95% CI 0.10– 0.83, p=0.002). There was no statistical significance in overall survival (OS) in univariate or multivariate analysis, although there was a trend towards better OS in the intermediate group.Conclusion: Our results provide evidence that the time interval from PDS to chemotherapy influences PFS in patients with advanced EOC. The optimal time to initiate chemotherapy was between 23 and 43 days, within 3– 6 weeks post-operatively. Initiating chemotherapy early (< 23 days) did not appear to benefit PFS.Keywords: time interval, chemotherapy, ovarian cancer

Objectives We investigated hippocampal-sparing lesionectomy (HSL) outcomes in temporal lobe epilepsy (TLE) and the significance of high-frequency oscillations (HFOs) detected by hippocampography in HSL. Methods We retrospectively reviewed data from patients who underwent HSL for lesional TLE. Patients were included when MRI confirmed (i) a lesion limited to the temporal lobe with normal hippocampi preoperatively and (ii) hippocampal integrity postoperatively. Factors possibly related to outcomes were collected. Intraoperative hippocampography was reviewed, and spikes, ripples, and fast ripples were marked. Seizure outcomes were tracked ≥ 2 years. Postoperative neuropsychological tests were performed and analyzed. Results We included 67 patients (35 males/32 females, median age at surgery 28 years, 57 seizure-free). Complete resection was significantly associated with being seizure-free without aura, an outcome achieved by 32 (69.6%) patients with complete resection vs 1 (12.5%) with incomplete resection (p = 0.004). Spikes/ripples/fast ripples appeared frequently in the hippocampus, occurring in 86.4%/82.4%/75.0% of cases before resection and 76.7%/78.1%/63.0% after resection. The presence and rate were unconnected to seizure outcome. Postoperative neuropsychological outcomes in intelligence and visual memory improved overall. Conclusions HSL in lesional TLE can produce satisfactory seizure and cognitive outcomes. Intraoperative hippocampography-guided resection of apparently normal hippocampi should be performed cautiously and might not be necessary. Significance This study provided evidence in decision making for patients with lesional TLE with a radiologically normal hippocampus.

BACKGROUND Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

OBJECTIVES To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to

The origin and fate of renal myofibroblasts is not clear after acute kidney injury (AKI). Here, we demonstrate that myofibroblasts were activated from quiescent pericytes (qPericytes) and the cell numbers increased after ischemia/reperfusion injury–induced AKI (IRI-AKI). Myofibroblasts underwent apoptosis during renal recovery but one-fifth of them survived in the recovered kidneys on day 28 after IRI-AKI and their cell numbers increased again after day 56. Microarray data showed the distinctive gene expression patterns of qPericytes, activated pericytes (aPericytes, myofibroblasts), and inactivated pericytes (iPericytes) isolated from kidneys before, on day 7, and on day 28 after IRI-AKI. Hypermethylation of the Acta2 repressor Ybx2 during IRI-AKI resulted in epigenetic modification of iPericytes to promote the transition to chronic kidney disease (CKD) and aggravated fibrogenesis induced by a second AKI induced by adenine. Mechanistically, transforming growth factor-β1 decreased the binding of YBX2 to the promoter of Acta2 and induced Ybx2 hypermethylation, thereby increasing α-smooth muscle actin expression in aPericytes. Demethylation by 5-azacytidine recovered the microvascular stabilizing function of aPericytes, reversed the profibrotic property of iPericytes, prevented AKI-CKD transition, and attenuated fibrogenesis induced by a second adenine-AKI. In conclusion, intervention to erase hypermethylation of pericytes after AKI provides a strategy to stop the transition to CKD.

ObjectiveAlthough mass eradication ofHelicobacter pylorihas been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear.DesignMass eradication ofH. pyloriinfection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalentH. pyloriinfection. Test positives for the13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively.ResultsAfter six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates ofH. pylorifell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, pH. pylori.ConclusionPopulation-based eradication ofH. pylorihas significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period.Trial registration numberNCT00155389

Background and aim The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. Methods Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. Results Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). Conclusions After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.

Purpose To determine the intensity of corneal pigmented arc in orthokeratology (ortho-k)-treated children and its correlation with wide epithelial thickness map (ETM) obtained through anterior segment optical coherent tomography (AS-OCT). Methods This retrospective case series reviews medical records of children who received ortho-k treatment for myopia control. Intensity of ortho-k-associated pigmented arc after wearing ortho-k lens more than 12 months and its correlation with each sector/zone of wide ETM obtained by AS-OCT was explored. Pigmented arcs were further divided into apparent and unapparent groups, and the clinical differences between groups were determined. Results This study included 57 eyes of 29 children (mean age, 11.4 years, range 9–15); after initiating ortho-k treatment, the incidence of the corneal pigmented arc was 91.2% with mean lens wear duration of 26.1 months. Intensity of pigmented arc was significantly correlated with lens wear duration, target power, baseline degree of myopia, C zone and sectors I2, I3 and IT3 on wide ETM. Comparison between apparent and unapparent groups showed the same significant results except for C zone. After adjusting for lens wear duration and target power, sector I2 has the highest association with pigmented arc severity. Conclusion Children treated with ortho-k are likely to develop ortho-k-associated pigmented arcs. The new wide ETM of AS-OCT can provide important information regarding the intensity of pigmented arc in these children. This can support customized pigmented arc-free ortho-k treatment for children in the future.

Stroke is one of the leading causes of death as well as results in a massive economic burden for society. Stroke is a cerebrovascular disease mainly divided into two types: ischemic stroke and hemorrhagic stroke, which, respectively, refer to the partial blockage and bleeding inside brain blood vessels. Both stroke types lead to nutrient and oxygen deprivation in the brain, which ultimately cause brain damage or death. This study focuses on ischemic stroke in rats with middle cerebral artery occlusion (MCAO) as experimental subjects, and the volumes of infarct and atrophy are calculated based on the brain slice images of rat brains stained with 2,3,5-triphenyl tetrazolium chloride. In this study, a stroke rat brain infarct and atrophy volumes computation system (SRBIAVC system) is developed to segment the infarcts and atrophies from the rat brain slice images. Based on the segmentation results, the infarct and atrophy volumes of a rat brain can be computed. In this study, 168 images of brain slices cut from 28 rat brains with MCAO are used as the test samples. The experimental results show that the segmentation results obtained by the SRBIAVC system are close to those obtained by experts.

Background Human leukocyte antigen‐identical sibling donor (ISD)‐hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for high‐risk pediatric acute myeloid leukemia (AML). A haploidentical donor (HID) is readily available to almost all children. Previous studies have demonstrated that patients with HID‐SCT had similar outcomes compared to ISD‐SCT for pediatric and adult AML. However, the role of HID‐SCT in high‐risk pediatric AML is unclear. Methods To compare the overall survival of high‐risk AML children who underwent either HID‐SCT or ISD‐SCT, we analyzed 179 cases of high‐risk AML patients under 18 years of age treated with either ISD‐SCT (n = 23) or HID‐SCT (n = 156). Granulocyte colony‐stimulating factor plus anti‐thymocyte globulin‐based regimens were used for HID‐SCT. We also analyzed the subgroup data of AML patients at first complete remission (CR1) before SCT with known cytogenetic risk. Results The numbers of adverse cytogenetic risk recipients were 8 (34.8%) and 13 (18.8%) in the ISD‐SCT group and the HID‐SCT group, and the number of patients with disease status beyond CR1 were 6 (26.1%) and 14 (20.3%) in the two groups. The cumulative rates of grades II‐IV acute graft‐versus‐host disease (GVHD) were 13.0% in the ISD‐SCT group and 34.8% in the HID‐SCT group (P = 0.062), with a three‐year cumulative rates of chronic GVHD at 14.1% and 34.9%, respectively (P = 0.091). The relapse rate in the ISD‐SCT group was significantly higher than that in the HID‐SCT group (39.1% vs. 16.4%, P = 0.027); with non‐relapse mortality at 0.0% and 10.6% (P = 0.113), respectively. The three‐year overall survival rates were 73.0% for the ISD‐SCT group and 74.6% for the HID‐SCT group (P = 0.689). In subgroup analysis, the three‐year relapse rate in the ISD‐SCT group was higher than that in the HID‐SCT group (50.0% vs. 9.2%, P = 0.001) and the three‐year DFS in the ISD‐SCT group (50.0%) was lower than that in the HID‐SCT group (81.2%) (P = 0.021). Conclusions Unmanipulated HID‐SCT achieved DFS and OS outcomes comparable to those of ISD‐SCT for high‐risk pediatric AML patients with potentially higher rate but manageable GVHD.

Surgical treatments for skull base meningiomas are challenging. We found that most of these lesions (75%), despite locating at the anterior, middle or posterior fossa, could be dealt with a combo skill—the pretemporal trans-cavernous trans-Meckel’s trans-tentorial trans-petrosal approach (PCMTP), which adopted the same curvilinear skin incision as for the classic pterional approach. Our aim of this study is to validate the application of this technique in treating skull base meningiomas. Patients underwent surgical intervention at our institute during 2010–2018 were retrospectively reviewed. We statistically analyzed the clinical, radiological, and pathological outcomes. In total, 109 patients operated with at least part of the PCMTP combo technique were included. The median follow-up time was 26.6 months. Tumor locations were categorized into: Zone I—sphenoid ridge, olfactory groove, and juxtasellar meningiomas which could be dealt with pterional approach. Zone II—clinoidal and cavernous sinus meningiomas which could be dealt with pretemporal trans-cavernous approach. Zone III—Meckel’s and Incisura meningiomas which could be dealt with trans-Meckel’s trans tentorial approach. Zone IV—petroclival menigiomas which could be dealt with trans-petrosal approach. When an extensive tumor occupied the anterior, middle, and posterior fossa, the whole combination of the PCMTP technique was applied. The mortality rate is 3.7% (4 patients). Three patients (2.8%) suffered from postoperative deterioration and required occasional assistance. The location of tumor was associated with different Simpson grade removal (p = 0.0015) and resection rate (p

Objective: To evaluate differences in hysteroscopic findings between benign endometrial polyps and endometrial cancer. Materials and methods: From January 2012 to December 2016, we extracted 179 cases with endometrial polyps from 3066 women who underwent hysteroscopy followed by dilatation and curettage or transcervical resection, with 154 and 25 cases of benign and malignant endometrial polyps, respectively. Clinical characteristics, histopathological and hysteroscopic findings of the women were evaluated retrospectively. Results: The hysteroscopic findings of malignant polyps were hyper-vascular (72%, 18/25), ulcerative (64%, 16/25) and polyps with irregular surfaces (24%, 6/25). In contrast, pedunculate small growths with smooth surfaces were usually seen in the benign endometrial polyps (38.3%, 59/154). Hyper-vascular (OR: 142.6, 95% CI: 25.98–783.4) and polyps with irregular surfaces (OR: 12.02, 95% CI: 1.765–81.83) in hysteroscopic findings were significant strong predictors of endometrial polyps with endometrial cancer. Hysteroscopic findings of ulcerative changes were most strongly associated with a diagnosis of malignant polyps, with sensitivity, specificity, negative (NPV) and positive (PPV) predictive values of 64.0%, 100%, 94.5%, and 100%, respectively. Conclusion: Women with hysteroscopic findings of endometrial polyps with hyper-vascular, ulcerative, and polyps with irregular surfaces had a high likelihood of endometrial cancer. A target biopsy of the polyps with these specific appearances should be performed to exclude malignant lesions. Keywords: Differential diagnoses, Endometrial cancer, Hysteroscopy, Polyps

BackgroundHeterogeneity exists in sepsis-associated acute kidney injury (SA-AKI). This prospective observational cohort study aimed to perform consensus cluster analysis and investigate the clinical relevance of identified sub-phenotypes of critically ill patients with dialysis-requiring SA-AKI.MethodsAll septic patients with dialysis-requiring SA-AKI, defined by the Sepsis-3 and Kidney Disease: Improving Global Outcomes AKI criteria, admitted to an intensive care unit in Taiwan between 2002 and 2018 were included. We employed unsupervised consensus clustering based on 22 clinical variables upon initialising renal replacement therapy. They were observed until death or 90 days after hospital discharge. The outcomes were mortality and being free of dialysis.ResultsIn total, 1,397 patients were enrolled (mean age of 63.8 ± 16.38 years and 69.7% were men). After a median follow-up period of 31 (interquartile range 8-123) days, all-cause mortality occurred in 911 patients (65.12%). Moreover, 133 (9.51%) survivors were dialysis dependent, where 355 (25.38%) survivors were free of dialysis. Unsupervised consensus clustering identified three sub-phenotypes associated with significantly different risks of mortality and being free of dialysis. This strategy led us to reveal that the pre-dialysis hyperlactatemia of ≥ 3.1 mmol/L was an independent predictor of mortality and being free of dialysis according to the competing risk modeling. Our results were validated in an independent multi-center AKI cohort.ConclusionsBy the data-driven clustering analysis, we identified sub-phenotypes in septic patients with dialysis-requiring SA-AKI and revealed pre-dialysis hyperlactatemia as a novel outcome predictor. This result represents a step towards precision medicine for septic patients.

Background Limited treatment options exist for relapsed advanced lung squamous cell carcinoma (SCC), leading to poor outcomes compared with adenocarcinoma. This study aimed to investigate the efficacy of second-line afatinib versus chemotherapy in patients with advanced lung SCC who progressed after first-line chemotherapy. Methods In this retrospective, multisite cohort study, we recruited patients with initial locally advanced or metastatic lung SCC from four institutes in Taiwan between June 2014 and October 2020. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results The present study enrolled 108 patients: 19 received second-line afatinib, and 89 received second-line chemotherapy. The median ages were 71 and 67 years, respectively. PFS was significantly longer among patients who received afatinib than among those who received chemotherapy (median 4.7 months [95% confidence interval (CI), 0.1–7.5] vs. 2.6 months [95% CI, 0.9–6.7]; hazard ratio (HR) 0.53 [95% CI 0.32–0.88], p = 0.013). Compared with the chemotherapy group, OS was longer in the afatinib group but did not reach significance (median 16.0 months [95% CI, 6.1–22.0] vs. 12.3 months [6.2–33.9]; HR 0.65 [95% CI 0.38–1.11], p = 0.112). Conclusions Afatinib offered a longer PFS and comparable OS to chemotherapy in advanced lung SCC patients in a real-world setting, it may be considered as a 2nd line alternative treatment choice for immunotherapy unfit advanced lung SCC patients.

The aim of the study is to determine the effects of monocular 0.125% atropine daily treatment on the longer axial length (AL) eyes in children with pediatric anisometropia. This was a retrospective cohort study. The charts of children with anisometropia (aged 6–15 years) who had a > 0.2-mm difference in AL between the two eyes were reviewed. Children who received monocular treatment of 0.125% atropine in the eye with longer AL were included for final analysis. The main outcome measure was the difference in AL between the two eyes after treatment. Regression analysis was used to model the changes in AL according to the time of treatment in both eyes. Finally, forty eyes in 20 patients (mean age 10.2 years) were included in the analyses. During the treatment period, AL was controlled in the treated eyes (p = 0.389) but elongated significantly in the untreated eyes (p p

Introduction: Cerebral palsy (CP) is the leading cause of childhood-onset physical disability. Children with CP often have impaired upper limb (UL) function. Constraint-induced therapy (CIT) is one of the most effective UL interventions for children with unilateral CP. However, concerns about CIT for children have been repeatedly raised due to frustration caused by restraint of the child’s less-affected UL and lack of motivation for the intensive protocol. Virtual reality (VR), which can mitigate the disadvantages of CIT, potentially can be used as an alternative mediator for implementing CIT. Therefore, we developed a VR-based CIT program for children with CP using the Kinect system.Aims: The feasibility of the Kinect-based CIT program was evaluated for children with unilateral CP using a two-phase study design.Materials and Methods: In phase 1, ten children with unilateral CP were recruited. To confirm the achievement of the motor training goals, maximal UL joint angles were evaluated during gameplay. To evaluate children’s perceptions of the game, a questionnaire was used. In phase 2, eight children with unilateral CP were recruited and received an 8 weeks Kinect-based CIT intervention. Performance scores of the game and outcomes of the box and block test (BBT) were recorded weekly.Results: In phase 1, results supported that the design of the program was CIT-specific and was motivational for children with unilateral CP. In phase 2, game performance and the BBT scores began showing stable improvements in the fifth week of intervention.Conclusion: It suggested the Kinect-based CIT program was beneficial to the motor function of the affected UL for children with unilateral CP. According to the results of this feasibility study, larger and controlled effectiveness studies of the Kinect-based CIT program can be conducted to further improve its clinical utility.Clinical Trial Registration: ClinicalTrials.gov, NCT02808195; Comparative effectiveness of a Kinect-based unilateral arm training system vs. CIT for children with CP

Background We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated. Methods Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed. Findings In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX, ORXR2, pMCH and Gal) in the hypothalami, of lipogenic genes (CD36, SREBP-1c, ChREBP, PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides. Interpretation CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA.

Patients with systemic lupus erythematosus (SLE) are at high risk of tuberculosis (TB) because of their immunocompromised status and the use of immunosuppressive drugs. In endemic regions, TB complicates the diagnosis and treatment of SLE, but the risk factors of mortality in these patients have not been investigated. In this study, we reviewed medical records during 2006–2016. Patients who fulfilled the 1997 American College of Rheumatology SLE criteria and presented with definite TB were enrolled. The primary outcome was mortality during TB treatment. There were 5388 SLE patients screened, and 30 patients were enrolled. Seven patients died during follow-up. Compared with the survival group, patients in the mortality group had significantly more central nervous system involvement of TB, higher Systemic Lupus Erythematosus Disease Activity Index-2000 scores and more cyclophosphamide use before TB, and higher prednisolone dose before and during TB treatment. Cox regression showed that prednisolone dose during TB treatment was an independent risk factor for mortality (per 10 mg/day increase, hazard ratio (HR) 1.61, p = .019). For SLE patients, prednisolone dose during TB treatment is an independent risk factor for mortality. Keeping prednisolone dose at less than 25 mg per day during TB treatment might be a reasonable strategy in these patients.

Background Selective amygdalohippocampectomy (SAH) is designed to treat patients with mesial temporal lobe epilepsy (MTLE). Objective To determine the volume and impact of temporal lobe infarction after retractorless transsylvian SAH (en bloc resection of the hippocampus) that have not been reported. Methods A retrospective analysis of patients treated with retractorless transsylvian SAH. Infarctions were detected by magnetic resonance imaging (MRI) within the first week after the operation. Neuropsychological testing was performed preoperatively and 6 mo later. Seizure outcome was evaluated 2 yr after epilepsy surgery. Results Between 2010 and 2014, a total of 30 patients were included in this study. Analysis of postoperative MRI showed the following: (1) mean removal volume of the hippocampus-parahippocampus was 5.72 cm3, and (2) mean volumes of temporal and insular infarctions were 1.71 and 0.25 cm3, respectively. Twenty-five patients (83.3%) were free of disabling seizures (Engel class I) at 2 yr of outcome. Neuropsychological testing revealed improvement in Perceptual Organization Index (P = .036) and verbal paired associates II (P = .014) after the operation. Neither infarction volume nor removal volume was related to epilepsy outcome in linear regression model. Conclusion Transsylvian SAH has comparable seizure outcomes but bears inherent risks of vasospasm/vascular injury. Immediate postoperative small infarction volume around resection cavity or along surgical corridor was noticed after retractorless transsylvian SAH, which did not cause neuropsychological deteriorations, in contrast to previous study with the use of self-sustaining rigid retraction system. Further study should be performed to compare procedure-related infarctions and their impacts on neuropsychological outcomes in different selective approaches.

Background Damage to the endothelium due to ischemia reperfusion injury (IRI) leads to a disruption of the microvasculature, which could be influenced by angiopoietin 1 via its effects on endothelium. We investigated the physiological and therapeutic roles of angiopoietin 1 in renal IRI using angiopoietin 1 knockout and over-expression mice. Methods Renal IRI was induced by clamping the right renal artery seven days after left uninephrectomy for 25 min followed by reperfusion. A whole body angiopoietin 1 knockout was achieved by induction with tamoxifen. The renal tubule over-expression of angiopoietin 1 was induced by doxycycline. Results In the normal mice, the renal expression of angiopoietin 1 increased 7 days to 14 days after IRI. The angiopoietin 1 knockout caused a delay in the recovery of renal function, less tubular regeneration and more residual tubular necrosis. The endothelial density was lower and the VE-cadherin protein loss was greater in the knockout mice. The over-expression of angiopoietin 1 attenuated the tubular necrosis and renal function impairment 1 and 3 days after IRI. The loss of the endothelium was ameliorated in the over-expression mice. This protective effect was associated with the up-regulation of the gene expression of epidermal growth factor, hepatocyte growth factor, and insulin like growth factor-1 and less tubular apoptosis. The over-expression of angiopoietin 1 stimulated tumor necrosis factor-α, C-C chemokine receptor type 2 and CX3C chemokine receptor 1 inflammatory gene expression, but did not influence macrophage infiltration. Conclusions Altogether, the augmentation and downregulation of angiopoietin 1 attenuated renal damage and impaired renal recovery, respectively, by influencing the survival/regeneration of the endothelium. The manipulation of angiopoietin 1 represents a novel therapeutic approach for the treatment of ischemic kidney injury. Electronic supplementary material The online version of this article (10.1186/s10020-019-0072-7) contains supplementary material, which is available to authorized users.

Objective To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Patients and Methods Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. Results Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P

Fertility-sparing progestin therapy is highly effective in selected young women with endometrial cancer. In present study, we attempted to evaluate the role of prolonged medication and identify factors predicting successful treatment, and also assess fertility outcomes among young women with early stage endometrial endometrioid carcinoma (EC).We retrospectively reviewed clinical data from patients aged45 years with well-differentiated EC at presumed stage IA (without myometrial invasion) who wished to preserve fertility. They were managed with oral progestin at Kaohsiung Chang Gung Memorial Hospital between June 2005 and June 2019.Forty-five patients were included with a median follow-up of 53.5 months (range 12-170 months). Forty-one patients (91.1%) had complete remission, the cumulative complete response (CR) rates at 3, 6, 9, 12, and12 months were 17.7%, 48.9%, 60.0%, 68.9% and 91.1%, respectively. Among the 41 responders, 23 attempted to conceive and nine (39.1%) achieved pregnancy with 12 live newborn infants. Eleven (27.5%) responders experienced recurrence at a median of 22 months from CR (range 3-54 months). Multivariate Cox regression analysis revealed that non-diabetes (HR: 4.59; 95% CI: 1.62-12.98) and endometrial thickness2 cm (HR: 0.39; 95% CI: 1.41-17.67) were significantly factors associated with treatment response.We concluded that prolonged oral progestin treatment was possible with a certain proportion of responders (24.4%) being responded after one year. Diabetes controlled on metformin and endometrial thickness2 cm could be used as surrogate markers to predict better treatment response.

Cajanolactone A (CLA) is a stilbenoid isolated from Cajanus canjan (L.) Millsp with the potential to prevent postmenopausal obesity. In this study, the effect of CLA on high-fat diet (HFD)-induced obesity in female C57BL/6 mice was investigated. It was found that, treatment with CLA reduced the energy intake and effectively protected the mice from HFD-induced body weight gain, fat accumulation within the adipose tissues and liver, and impairment in energy metabolism. Further investigation revealed that CLA significantly down-regulated the expression of ORX, ORXR2, pMCH, and Gal in the hypothalamus and antagonized HFD-induced changes in the expression of UCP1, Pgc-1α, Tfam, and Mfn1 in the inguinal white adipose tissue (iWAT); Caveolin-1, MT and UCP3 in the perigonadal white adipose tissue (pWAT); and Pdhb, IRS2, Mttp, Hadhb, and Cpt1b in the liver. CLA also protected the pWAT and liver from HFD-induced mitochondrial damage. However, neither HFD nor CLA showed an effect on the mass of brown adipose tissue (BAT) or the expression of UCP1 in the BAT. In summary, our findings suggest that CLA is a potential drug candidate for preventing diet-induced obesity, at least in females. CLA works most likely by suppressing the hypothalamic expression of orexigenic genes, which leads to reduced energy intake, and subsequently, reduced fat accumulation, thereby protecting the adipose tissues and the liver from lipid-induced mitochondrial dysfunction.

Background: To explore the clinical characteristics of acute myocardial infarction (AMI) with ventricular septal perforation (VSR) and the prognosis comparison of different treatment methods, as well as the analysis of related risk factors.Methods: From January 2006 to February 2020, 29 patients with AMI and VSR diagnosed in the people's Hospital of Peking University were selected as the study object, among them, 16 cases were male (55.2%), 13 cases were female (44.8%), the average age was 64.69 ± 10.32 years old, and they were divided into survival group (n=16) and non-survival group (n=13) according to whether they survive within 30 days of surgical or drug conservative treatment.The clinical characteristics, coronary angiography and treatment of the two groups were summarized, and the prognosis and related risk factors were analyzed.Results: There was no significant difference in the basic clinical characteristics between the two groups(P>0.05)；Compared with the results of coronary angiography in the two groups, the proportion of the culprit vessel which was a simple anterior descending branch in the non-survival group was higher than that in the survival group, there was a statistical difference between the two groups(PConclusions: Whether complete revascularization and recanalization of culprit vessels or not are independent risk factors for 30 day mortality in patients with AMI and VSR；the long-term survival rate of patients after surgery and complete revascularization is significantly higher than that of patients with conservative medical treatment and incomplete revascularization. Surgery and complete revascularization are important factors affecting the long-term prognosis of patients with AMI and VSR.

Background: Intensive care unit (ICU) admission following a short-term emergency department (ED) revisit has been considered a particularly undesirable outcome among return-visit patients, although their in-hospital prognosis has not been discussed. We aimed to compare clinical outcomes between adult patients admitted to the ICU after unscheduled ED revisits and those admitted during index ED visits. Method: This retrospective study was conducted at two tertiary medical centers in Taiwan from 1 January 2016 to 31 December 2017. All adult non-trauma patients admitted to the ICU directly via the ED during the study period were included and divided into two comparison groups: patients admitted to the ICU during index ED visits and those admitted to the ICU during return ED visits. The outcomes of interest included in-hospital mortality, mechanical ventilation (MV) support, profound shock, hospital length of stay (HLOS), and total medical cost. Results: Altogether, 12,075 patients with a mean (standard deviation) age of 64.6 (15.7) years were included. Among these, 5.3% were admitted to the ICU following a return ED visit within 14 days and 3.1% were admitted following a return ED visit within 7 days. After adjusting for confounding factors for multivariate regression analysis, ICU admission following an ED revisit within 14 days was not associated with an increased mortality rate (adjusted odds ratio (aOR): 1.08, 95% confidence interval (CI): 0.89 to 1.32), MV support (aOR: 1.06, 95% CI: 0.89 to 1.26), profound shock (aOR: 0.99, 95% CI: 0.84 to 1.18), prolonged HLOS (difference: 0.04 days, 95% CI: −1.02 to 1.09), and increased total medical cost (difference: USD 361, 95% CI: −303 to 1025). Similar results were observed after the regression analysis in patients that had a 7-day return visit. Conclusion: ICU admission following a return ED visit was not associated with major in-hospital outcomes including mortality, MV support, shock, increased HLOS, or medical cost. Although ICU admissions following ED revisits are considered serious adverse events, they may not indicate poor prognosis in ED practice.

Background: Delta shock index (SI; i.e., change in SI over time) has been shown to predict mortality and need for surgical intervention among trauma patients at the emergency department (ED). However, the usefulness of delta SI for prognosis assessment in non-traumatic critically ill patients at the ED remains unknown. The aim of this study was to analyze the association between delta SI during ED management and in-hospital outcomes in patients admitted to the intensive care unit (ICU).Method: This was a retrospective study conducted in two tertiary medical centers in Taiwan from January 1, 2016, to December 31, 2017. All adult non-traumatic patients who visited the ED and who were subsequently admitted to the ICU were included. We calculated delta SI by subtracting SI at ICU admission from SI at ED triage, and we analyzed its association with in-hospital outcomes. SI was defined as the ratio of heart rate to systolic blood pressure (SBP). The primary outcome was in-hospital mortality, and the secondary outcomes were hospital length of stay (HLOS) and early mortality. Early mortality was defined as mortality within 48 h of ICU admission.Result: During the study period, 11,268 patients met the criteria and were included. Their mean age was 64.5 ± 15.9 years old. Overall, 5,830 (51.6%) patients had positive delta SI. Factors associated with a positive delta SI were multiple comorbidities (51.2% vs. 46.3%, p < 0.001) and high Simplified Acute Physiology Score [39 (29–51) vs. 37 (28–47), p < 0.001). Patients with positive delta SI were more likely to have tachycardia, hypotension, and higher SI at ICU admission. In the regression analysis, high delta SI was associated with in-hospital mortality [aOR (95% CI): 1.21 (1.03–1.42)] and early mortality [aOR (95% CI): 1.26 (1.07–1.48)], but not for HLOS [difference (95% CI): 0.34 (−0.48 to 1.17)]. In the subgroup analysis, high delta SI had higher odds ratios for both mortality and early mortality in elderly [aOR (95% CI): 1.59 (1.11–2.29)] and septic patients [aOR (95% CI): 1.54 (1.13–2.11)]. It also showed a higher odds ratio for early mortality in patients with triage SBP Conclusion: High delta SI during ED stay is correlated with in-hospital mortality and early mortality in patients admitted to the ICU via ED. Prompt resuscitation should be performed, especially for those with old age, sepsis, triage SBP

Although boron neutron capture therapy (BNCT) is a promising treatment option for malignant brain tumors, the optimal BNCT parameters for patients with immediately life-threatening, end-stage brain tumors remain unclear. We performed BNCT on 34 patients with life-threatening, end-stage brain tumors and analyzed the relationship between survival outcomes and BNCT parameters. Before BNCT, MRI and 18F-BPA-PET analyses were conducted to identify the tumor location/distribution and the tumor-to-normal tissue uptake ratio (T/N ratio) of 18F-BPA. No severe adverse events were observed (grade ≥ 3). The objective response rate and disease control rate were 50.0% and 85.3%, respectively. The mean overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) times were 7.25, 7.80, and 4.18 months, respectively. Remarkably, the mean OS, CSS, and RFS of patients who achieved a complete response were 17.66, 22.5, and 7.50 months, respectively. Kaplan–Meier analysis identified the optimal BNCT parameters and tumor characteristics of these patients, including a T/N ratio ≥ 4, tumor volume &lt, 20 mL, mean tumor dose ≥ 25 Gy-E, MIB-1 ≤ 40, and a lower recursive partitioning analysis (RPA) class. In conclusion, for malignant brain tumor patients who have exhausted all available treatment options and who are in an immediately life-threatening condition, BNCT may be considered as a therapeutic approach to prolong survival.

Background Cataract is a public health concern worldwide that differentially affects rural residents of outlying islands where ultraviolet radiation (UVR) may have greater penetration because of less shading. Objectives To assess the relationships between attitudes and practices of eye protection and eye diseases for residents of an offshore island of Taiwan. Methods Questionnaire survey was administered to local residents (age > 50 years) regarding socio-demographic information, attitudes/practices of eye protection under sun exposure and eye diseases. Results A total of 816 participants (response rate 90.7%, 816/900) completed the questionnaires. Mean age was 63.7 (+ 10.8) years. Among these participants, 44.4%, 15.1% and 8.3% had cataract, dry eye and glaucoma, respectively. Although 86.3% and 88.2% of participants agreed that they should avoid outdoor activities and wear glasses/broad-brimmed hats in harsh daylight, 69.4% and 48.3% of participants never/rarely used glasses or hats/umbrellas in harsh daylight, respectively. Predictors of less practices of eye protection against solar UVR included residents who were male, with lower education level, with longer residence and lack of commercial health insurance. Multivariate logistic regression revealed that practices of eye protection under sun exposure were significantly associated with less cataract, but not glaucoma or dry eye. Participants who did not wear glasses, broad-brimmed hats/use umbrellas or both in harsh sunlight (almost) every time were respectively associated with a 57% (P = 0.028), 45% (P = 0.027) or 70% (P = 0.026) increase of cataract than those who did in harsh sunlight (almost) every time. Conclusions Practices of eye protection under sun exposure is associated with lower risk of cataract.

Objectives: Intraoperative neurophysiological monitoring (IONM) has long been regarded as the “gold standard” when resecting a supratentorial glioma, as it facilitates the goals of maximal tumor resection and preservation of sensorimotor function. The purpose of the present study was to evaluate the ability of motor evoked potentials (MEPs) monitoring or subcortical mapping (SCM), alone or in combination, to predict postoperative functional outcomes in glioma surgery. Materials and Methods: We retrospectively reviewed patients with supratentorial glioma that underwent craniotomy for tumor removal with IONM. Statistical analyses were used to evaluate whether the following criteria correlated with postoperative functional outcomes: Reduced amplitude (>50% reduction) or disappearance of MEPs (criterion 1), SCM with a stimulation intensity threshold less than 3 mA (criterion 2), the presence of both two phenomena (criterion 3), or either one of the two phenomena (criterion 4). Results: Ninety-two patients were included in this study, of whom 15 sustained new postoperative deficits, 4 experienced improved functional status, and 73 were unchanged. Postoperative functional status correlated significantly with all four criteria, and especially with criterion 3 (r = 0.647, P = 0.000). Sensitivity of IONM was better if using criteria 2 and 4, but specificity was better if using criteria 1 and 3. Criterion 3 had the most favorable overall results. Conclusion: Using statistical methodology, our study indicates that concomitant interpretation of MEPs and SCM is the most accurate predictor of functional outcomes following supratentorial glioma surgery. However, accurate interpretations of the monitoring results by experienced neurophysiologists are essential.

With advances in the understanding of characteristics of molecules, specific antigens on the surface of hematological malignant cells were identified and multiple therapies targeting these antigens as neoplasm treatments were developed. Among them, chimeric antigen receptor (CAR) T-cell therapy, which got United States Food and Drug Administration (FDA) approval for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) as well as for recurrent acute lymphoblastic leukemia (ALL) within the past five years, and for r/r mantle cell lymphoma (MCL) this year, represents one of the most rapidly evolving immunotherapies. Nevertheless, its applicability to other hematological malignancies, as well as its efficacy and persistence are fraught with clinical challenges. Currently, more than one thousand clinical trials in CAR T-cell therapy are ongoing and its development is changing rapidly. This review introduces the current status of CAR T-cell therapy in terms of the basic molecular aspects of CAR T-cell therapy, its application in hematological malignancies, adverse reactions during clinical use, remaining challenges, and future utilization.

Background We assessed the image quality of endometrial cancer lesions by readout segmentation of long variable echo-trains (RESOLVE) diffusion-weighted imaging (DWI) compared with that by single-shot echo-planar imaging (SS-EPI) DWI, aimed to explore the value of RESOLVE DWI for determining myometrial invasion and clinical stage in endometrial cancer. Materials and methods From April 2017 to March 2018, a total of 30 endometrial cancer patients (mean age 52.8 ± 9.0 years), who had undergone RESOLVE DWI and SS-EPI DWI, were included in the study. The image quality of endometrial carcinoma by two kinds of DWI scanning methods was compared qualitatively and quantitatively. The Spearman rank correlation test was used to assess the correlation of qualitative image quality scores between two readers. The accuracy of two DWI methods in detecting myometrial invasion and staging of endometrial carcinoma was calculated according to postoperative pathological results. The indexes were analyzed including sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). Results The qualitative score of RESOLVE DWI group was superior to SS-EPI DWI group in every aspect of five aspects (all P PP = 0.261). The specificity, accuracy, PPV, and NPV of estimating myometrial invasion by RESOLVE DWI in three cases (intramucosal lesion, P = 0.125). Conclusion RESOLVE DWI can provide higher quality images of endometrial carcinoma than SS-EPI DWI. The high-quality images are helpful for precise assessment of myometrial invasion in endometrial cancer.

AIMS: To compare the annual axial length (AL) changes in myopic children with type 1 diabetes mellitus (T1DM) and those without diabetes. METHODS: There are two groups of myopic children in this retrospective cohort study. Group 1 consisted of myopic children with T1DM (44 eyes of 22 patients). Group 2 comprised age-matched myopic children without diabetes (44 eyes of 22 children). These two groups were compared with regard to their baseline clinical characteristics. A generalized estimating equations (GEE) model was also used to determine the most likely factor that contributed to the results. RESULTS: The average ages of group 1 and group 2 were 14.8 and 14.6 years, respectively. Children in group 1 had significantly slower annual AL changes (0.051 mm/year versus 0.103 mm/year; 50.5% slower, P = 0.011) and shorter baseline AL (23.97 versus 25.19 mm, P < 0.001) than those in group 2. GEE also showed that serum glycosylated hemoglobin (HbA1c) level (B = −0.023, P = 0.039) was the most important factor in reducing AL elongation in group 1 myopic children. CONCLUSIONS: Long-term high HbA1c level may reduce AL elongation. A strict blood sugar control strategy in clinical practice is warranted to axial myopia progression in T1DM children.

Background With the ageing of China’s population, the incidence and mortality of coronary atherosclerotic heart disease (CAD) is increasing year by year, which brings a heavy burden to the family and society [1]. We aimed to analyse the strategy of coronary artery bypass grafting (CABG) in the right coronary artery and to compare the haemodynamic characteristics of the sequential grafts with those of single grafts and to observe the patency rate of those grafts for 1 week after the operation. Methods A total of 242 patients (178 men, mean age 62.6 ± 8.8 years) underwent right coronary artery bypass grafting in our hospital from October 2016 to January 2019. The blood flow (Q, ml/min), pulsatility index (PI) and related parameters of the grafts were measured and recorded by TTFM during the CABG. The patency of the grafts was evaluated by coronary computed tomography (CT) for 1 week after the operation. Results The most common material used for the graft in the right coronary system of CABG is the greater saphenous vein (92.3%), followed by the radial artery (5.5%) and the internal mammary artery (1.9%). The highest frequency target of the right coronary artery is the posterior descending artery (PDA) (47.6%), followed by the right main coronary artery (RCA) (29.1%) and the posterior branch of the left ventricle (PL) (23.3%). The proportion of single grafts was the highest for the right coronary artery in CABG (178 cases, 67.9%), followed by a graft of the PDA-PL (42 cases, 16.0%) and other sequential grafts among the different coronary artery systems (including the system of the left anterior descending artery (LAD) and the left circumflex (LCX)). Whether there were sequential grafts of the PDA-PL or other sequential grafts among the different systems of the coronary artery, the instantaneous flow of a group of sequential grafts was higher than that of a single graft, and the difference had statistical significance (P P = 0.410). Diastolic flow (DF) in the group of sequential grafts of the right coronary system was better than that in the non-sequential group (P P Conclusions In our centre, the most common form of CABG in the right coronary artery system is a non-sequential vein bridge to the PDA. Whether there are sequential grafts of the PDA-PL or other sequential grafts among the different coronary artery systems, the instantaneous flow of a group of sequential grafts is higher than that of a single graft. DF in the group of sequential grafts of the right coronary system was better than that in the non-sequential group.

Chronic kidney disease (CKD) is an emerging disease worldwide. We investigated the relationship between blood pressure (BP) control and parafoveal retinal microvascular changes in patients with CKD. This case–control study enrolled 256 patients with CKD (stage 3–5) and 70 age‐matched healthy controls. Optical coherence tomography angiography showed lower superficial vascular plexus (SVP) vessel density, lower deep vascular plexus (DVP) vessel density, and larger SVP flow void area in the CKD group. The BP parameters at enrollment and during the year before enrollment were collected in patients with CKD. Partial correlation was used to determine the relationship between BP parameters and microvascular parameters after controlling for age, sex, diabetes mellitus, axial length, and intraocular pressure. The maximum systolic blood pressure (SBP) (p = 0.003) and within-patient standard deviation (SD) of SBP (p = 0.006) in 1 year were negatively correlated with SVP vessel density. The average SBP (p = 0.040), maximum SBP (p = 0.001), within-patient SD of SBP (p

Type 2 diabetes mellitus (T2DM) is an important public health issue worldwide. T2DM correlates with cardiovascular disease. Arterial stiffness is also a key factor that can be thought of as a surrogate marker. Nevertheless, it was unclear which harmonic indexes of blood pressure waveforms (BPWs) from subjects' radial artery pulses would be affected by T2DM. Therefore, the objective of this study was to investigate whether and how harmonic indexes can be used to discriminate hemodynamic differences between patients with T2DM and non-T2DM. This helps us to build objective results no matter who conducts the examination instead of pulse diagnosis in traditional way. We enrolled T2DM and non-T2DM patients as experimental and control groups, respectively, from the Department of Family Medicine in the National Taiwan University Hospital and the Department of Internal Medicine in Taipei's Veterans General Hospital from December 2017 to January 2019. ANSWatch® Model TS-0411 was used to capture the BPWs. Amplitude proportions (Cn values) were calculated from harmonics 1–10 of the BPW using fast Fourier transform. Thirty-two T2DM and 15 non-T2DM patients were enrolled. T2DM patients had significant differences in C1 (p = 0.031) and C5 (p = 0.041). The study suggests that analyzing the harmonic characteristics of non-invasively measured BPW of radial artery may be a potential and easy-to-perform approach to discriminate T2DM-induced hemodynamic changes.

AimsTo explore the expression of secretagogin (SCGN) in neuroendocrine carcinoma of the uterine cervix and analyse its relationship with clinicopathological characteristics and prognosis.MethodsFrom January 2010 to December 2017, 44 patients with cervical neuroendocrine carcinoma undergoing surgery were included in the study group, and 55 patients with cervical non-neuroendocrine carcinoma (including 30 cases of cervical squamous cell carcinoma and 25 cases of cervical adenocarcinoma) undergoing surgery were included in the control group. Immunohistochemical staining of SCGN was performed in both groups and compared with three common neuroendocrine markers, chromogranin A, synaptophysin (Syn) and CD56 in the study group. Detailed clinicopathological data of the two groups were analysed, and the patient survival in the study group was followed up.ResultsThe positive expression of SCGN in cervical neuroendocrine carcinoma, cervical adenocarcinoma and squamous cell carcinoma was 65.9% (29/44), 8% (2/25) and 0%, respectively. The positive expression of SCGN in cervical neuroendocrine carcinoma was significantly higher than that in cervical adenocarcinoma and squamous cell carcinoma (χ2=44.5, p0.05 for all). The intensity of SCGN staining in patients with cervical neuroendocrine carcinoma with lymph node metastasis was significantly higher than that in patients without lymph node metastasis (p=0.020). However, there was no significant association between SCGN expression and survival among patients with cervical neuroendocrine carcinoma (p=0.633).ConclusionsSCGN is a new neuroendocrine marker for cervical neuroendocrine carcinoma, whose expression correlates with lymph node metastasis.

BACKGROUND Epithelial ovarian cancer is a highly lethal gynecological malignancy. Accurate and cost-effective predictive tools to estimate the prognosis of patients with epithelial ovarian cancer before treatment are currently lacking. OBJECTIVE The purpose of this study was to evaluate the prognostic significance of pretreatment serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) in primary epithelial ovarian cancer. METHODS Between 2008 and 2016, 326 patients with a diagnosis of primary epithelial ovarian cancer were retrospectively reviewed. We attempted to identify an optimal cut-off value of CEA to predict survival using ROC curve analysis. Cox regression univariate and multivariate analyses were used to evaluate prognostic factors. RESULTS The optimal cut-off value of CEA was 2.6 ng/mL. In univariate and multivariate analyses, FIGO stage and pretreatment CA-125 and CEA levels significantly predicted progression-free and overall survival. The 5-year progression-free survival rate for patients with both a CEA level < 2.6 ng/mL and CA-125 level < 35 U/mL was 84%, compared to only 33% for the patients with higher levels of both markers (p< 0.001). The 5-year cancer specific survival rate was 94% in those with a CEA level < 2.6 ng/mL and CA-125 level < 35 U/mL, and only 39% for those with higher levels of both markers (p< 0.001). CONCLUSIONS In addition to traditional prognostic factors, a pretreatment serum CEA level ⩾ 2.6 ng/mL and CA-125 level ⩾ 35 U/mL were also independent prognostic factors for epithelial ovarian cancer. Patients with an elevated CEA and/or CA-125 level before treatment should be considered to be at high-risk of recurrence and death.

Background Low infection and case-fatality rates have been thus far observed in Taiwan. One of the reasons for this major success is better use of big data analytics in efficient contact tracing and management and surveillance of those who require quarantine and isolation. Objective We present here a unique application of big data analytics among Taiwanese people who had contact with more than 3000 passengers that disembarked at Keelung harbor in Taiwan for a 1-day tour on January 31, 2020, 5 days before the outbreak of coronavirus disease (COVID-19) on the Diamond Princess cruise ship on February 5, 2020, after an index case was identified on January 20, 2020. Methods The smart contact tracing–based mobile sensor data, cross-validated by other big sensor surveillance data, were analyzed by the mobile geopositioning method and rapid analysis to identify 627,386 potential contact-persons. Information on self-monitoring and self-quarantine was provided via SMS, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests were offered for symptomatic contacts. National Health Insurance claims big data were linked, to follow-up on the outcome related to COVID-19 among those who were hospitalized due to pneumonia and advised to undergo screening for SARS-CoV-2. Results As of February 29, a total of 67 contacts who were tested by reverse transcription–polymerase chain reaction were all negative and no confirmed COVID-19 cases were found. Less cases of respiratory syndrome and pneumonia were found after the follow-up of the contact population compared with the general population until March 10, 2020. Conclusions Big data analytics with smart contact tracing, automated alert messaging for self-restriction, and follow-up of the outcome related to COVID-19 using health insurance data could curtail the resources required for conventional epidemiological contact tracing.

Background: With the aging of China's population, the incidence and mortality of coronary atherosclerotic heart disease (CAD) are increasing year by year, which brings a heavy burden to the family and society [1]. To analyse the strategy of Coronary artery bypass grafting(CABG) in right coronary artery. To compare hemodynamic characteristics of the sequential grafts with those of single grafts and observe the patency rate of those grafts for one week after-operation.Methods: A total of 242 patients (178 male, mean age 62.6±8.8 years ) underment the right coronary artery bypass grafting in our hospital from October 2016 to January 2019 were collected. The blood flow (Q, ml/min) and pulsatility index (PI) and related parameters of grafts are measured and recorded by TTFM in CABG.The patency of grafts were evaluated by coronary computed tomography(CT) for one week after operation.Results: The most common material of graft in right coronary system of CABG is great saphenous vein(92.3%), followed by the radial artery and internal mammary artery. The highest frequency target of right coronary artery is posterior descending artery (PDA)(47.6%),followed by the Right main coronary artery (RCA )(29.1%) and Posterior branch of left ventricle (PL)(23.3%).The proportion of single graft is the largest in right coronary artery in CABG(178 cases，67.9%),followed by the proportion of the graft of PDA-PL (42cases，16.0%) and other sequential grafts among the different coronary artery system (including the system of Left anterior descending artery (LAD) and Left Circumflex (LCX)).The research shows that whether the sequential grafts of PDA-PL or with other sequential grafts among the different system of coronary artery the instantaneous flow of group of sequential grafts is higher than that of single graft, and the difference has statistical significance (P < 0.01) .But there was no statistical difference of the flow between groups of sequential grafts (P = 0.410).Diastolic flow (DF) in the group of sequential grafts of right coronary system is better than that in non-sequential group (P < 0.001), and the difference has statistical significance. There was no statistical difference between the DF of groups of other system of sequential grafts and that of right coronary sequential grafts .Coronary artery CT suggests that there was 11 cases existing poor development grafts or stenosis and occlusion in week after operation,and those phenomenon mainly occurred in the group of a single graft.There was only one case which be occluded in the group of other systems of sequential grafts, and statistically significant difference existed between two groups (P < 0.01).Conclusions: The most common form of CABG in right coronary artery system is non-sequential vein bridge to PDA in our center. Whether the sequential grafts of PDA-PL or other sequential grafts among the different coronary artery system the instantaneous flow of group of sequential grafts is higher than that of single graft. DF in the group of sequential grafts of right coronary system is better than that in non-sequential group.

Background A prophylactic antimalarial drug that is both effective for protection and improves compliance is in high demand. Methods We conducted a randomized, placebo-controlled, double-blinded phase 3 trial to evaluate the 1:1 fixed-dose combination of naphthoquine-azithromycin (NQAZ) for safety and protection against Plasmodium infections in villages along the China-Myanmar border. A total of 631 residents, 5–65 years of age, were randomized into the drug group (n = 319) and the placebo group (n = 312) to receive NZAQ and placebo, respectively, as a single-dose monthly treatment. Follow-ups were conducted weekly to monitor for adverse events and malaria infections. Results Of the 531 subjects completing the trial, there were 46 and 3 blood smear–positive Plasmodium infections in the placebo and treatment groups, respectively. For the intent-to-treat analysis, the single-dose monthly NQAZ treatment had 93.62% protective efficacy (95% confidence interval [CI]: 91.72%–95.52%). For the per-protocol analysis, NQAZ treatment provided a 93.04% protective efficacy (95% CI: 90.98%–95.1%). Three smear-positive cases in the NQAZ group were all due to acute falciparum malaria. In comparison, NQAZ treatment provided 100% protection against the relapsing malaria Plasmodium vivax and Plasmodium ovale. The treatment group had 5.6% of participants experiencing transient elevation of liver aminotransferases compared with 2.2% in the placebo group (P > .05). Conclusions Monthly prophylaxis with NQAZ tablets was well tolerated and highly effective for preventing Plasmodium infections. It may prove useful for eliminating P. vivax in areas with a high prevalence of glucose-6-phosphate dehydrogenase deficiency in the population. Clinical Trials Registration ChiCTR1800020140.

Glucose production (GP) and glucose disposal (Rd) are two decisive and fundamental parameters in glucose turnover and in glucose homeostasis regulation. In conventional theory, GP and Rd were responsive to regulatory factors respectively and independently of each other. Even though GP and Rd responded in reverse to insulin, GP for suppression and Rd for elevation, these inverse alterations used to be attributed to insulin multiple functions both on hepatic GP, directly or indirectly, and on whole-body glucose Rd. However, in the present study, we found GP and Rd were inversely coupled intrinsically no matter which side was the target of insulin by comparison of Rd and GP data pairs between peripheral vein insulin infusion protocol and portal vein insulin infusion protocol in rats. Furthermore, neither circulating NEFA nor HFD induced resistance broke the GP-Rd inverse coupling, but both of them reduced the responses of both GP and Rd to insulin. In conclusion, we provide the evidence that GP and Rd are two coupled parameters in vivo and they alter in reverse simultaneously, the mechanism under which needs further investigation but we tend to believe an inter-organ neural reflex was involved.

Introduction The objective of our study was to demonstrate planned conservative management of placenta increta and percreta in a single tertiary center. Methods From April 2005 to July 2019, patients with placenta increta and percreta were managed conservatively at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. The severity of placenta invasion was diagnosed by magnetic resonance imaging (MRI). After delivery of the neonate, prophylactic transcatheter arterial embolization (TAE) was performed immediately. The placenta was left in situ and prophylactic antibiotics were administered during hospitalization. The patient profiles, outcomes, and complications were retrospectively reviewed. Results Based on the MRI findings, twenty-one patients with placenta increta or percreta were included. With prophylactic TAE, the mean surgical blood loss was 854.7 ± 478.2 mL. The mean natural resorption time of residual placenta was 4.69 ± 1.65 months. Regarding maternal complications, 4 patients (19%) had delayed postpartum hemorrhage (PPH), 12 patients (57.1%) developed postpartum infections, 3 patients (14.3%) progressed to sepsis, 4 patients (19%) underwent surgical evacuation, and 4 patients (19%) underwent hysterectomy. No maternal mortality was reported. Main neonatal complications were prematurity and respiratory distress. Regarding fertility, 16 (76.1%) patients had return of menstruation, and one (4.7%) had a subsequent pregnancy resulting in a live birth. Discussion Planned conservative management with prophylactic TAE and leaving placenta in situ is feasible and safe for women with placenta increta or percreta who desire fertility preservation. Delayed PPH and postpartum infection are common complications after conservative treatment.

Background Visceral obesity and fatty liver are prevalent in postmenopausal women. The stilbene-rich extract of Cajanus cajan (L.) Millsp. has been reported to prevent ovariectomy-induced and diet-induced weight gain in animal models, and stilbenoids from C. cajan are thought to have the potential to prevent postmenopausal obesity and fatty liver. Purpose Cajanolactone A (CLA) is the main stilbenoid from C. cajan with osteoblastogenic promoting activity. This study investigated the potential of CLA to prevent postmenopausal obesity and fatty liver. Underlying mechanisms were also investigated. Method Ovariectomized C57BL/6 mice fed a regular diet were used as mimics of postmenopausal women and given 10, 20, or 40 mg/kg/d of CLA, 0.1 mg/kg/d of estradiol valerate (EV, positive control), or vehicle (OVX) orally for 16 weeks. Mice of the same age subjected to a sham operation were used as control (Sham). Body weights were recorded every 2 weeks for 16 weeks. Body compositions were analyzed via micro-CT. Serum levels of lipids, adipocytokines and aminotransferases were measured using the relevant kits. mRNA levels of genes of interest were detected by RT-qPCR. Proteomic study of perigonadal white adipose tissue (pWAT) was performed using tandem-mass-tags-based proteomic technology combined with Parallel-Reaction-Monitoring (PRM) validation. Results CLA showed potential equivalent to that of EV to prevent ovariectomy-induced overweight, obesity, dyslipidemia, liver steatosis and liver dysfunction, but did not prevent uterine atrophy. In the liver, CLA significantly inhibited ovariectomy-induced upregulation in expression of lipogenic genes SREBP-1c and ChREBP, and stimulated the mRNA expression of apolipoprotein B gene ApoB. In pWAT, CLA reversed, or partially reversed ovariectomy-induced downregulation in the expression of a number of metabolism- and mitochondrial-function-related proteins, including Ndufa3, Pcx, Pdhb, Acly, Acaca, Aldh2, Aacs and Echs1. In addition, ovariectomy-inhibited mRNA expression of Pdhb, Aacs, Acsm5, Echs1, and Aldh2 genes in pWAT was also reversed. Conclusion CLA was demonstrated to be a potential non-estrogen-like drug candidate for prevention of postmenopausal obesity and fatty liver. The underlying mechanism might involve the inhibition of lipogenesis and promotion of triglycerides output in the liver, and the promotion of metabolism and mitochondrial functions of visceral white adipose tissue.

Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a highly invasive cervical cancer. The immunohistochemical criteria is an important aspect for assistant diagnosis of SCNECC. However, which markers can be appropriate selection for diagnosing SCNECC were not determined. The aim was to systematically evaluate expression levels of four neuroendocrine markers (containing synaptophysin (Syn), neural cell adhesion molecules (CD56), neuron-specific enolase (NSE) and chromograninA (CgA)) and to find out the appropriate selection for diagnosing SCNECC. Four English and three Chinese libraries were retrieved between 1984 and 2020. 23 studies about NSE, 36 studies about Syn, 23 studies about CD56 and 36 studies about CgA (all studies containing 581 patients) were eligible for meta-analyses. The pooled positive expression percentages (95% CI; I2) were as follows: 84.84% (79.41–90.27%; 76.7%) for Syn, 84.53% (79.43–89.96%; 37.5%) for CD56, 77.94% (69.13–86.76%; 83.5%) for NSE, and 72.90% (67.40–78.86%; 59.7%) for CgA. The positive proportions (95% CI; I2) ranked top three of simultaneous expressions of two markers were 87.75% (82.03–93.87%, 33.3%) for Syn and CD56, 70.92% (50.50–87.68%, 82.7%) for Syn and NSE, 65.65% (53.33–76.98%, 73.5%) for Syn and CgA. This confirms that Syn and CD56 are reliable indicators for diagnosing SCNECC.

Objective In recent years, the Status Epilepticus Severity Score (STESS) has been widely used to predict survival conditions of patients with status epilepticus (SE). However, the diagnostic value of STESS has not yet been evaluated. We therefore performed this meta-analysis to assess the overall diagnostic accuracy of STESS for predicting survival condition of patients with SE. Methods Systemic searches for relevant published studies were conducted in EMBASE, PubMed, Web of Science, and Cochrange databases up to July 2, 2017. Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was used to evaluate the quality of included studies. All statistical analyses were performed using Stata12.0 and Meta-DiSc software. Results A total of 11 studies including 12 observations with 1356 patients were included in this meta-analysis. Summary estimates of the diagnostic value of STESS for survival condition of patients with SE were listed as follows: sensitivity, 0.81 (95% confidence intervals (CI): 0.76–0.85); specificity, 0.53 (95% CI: 0.50–0.56); positive likelihood ratio (PLR), 1.86 (95% CI: 1.57–2.21); negative likelihood ratio (NLR), 0.38 (95% CI: 0.30–0.48); diagnostic odds ratio (DOR), 5.24 (95% CI: 3.49–7.87); and area under the curve (AUC), 0.81. Metaregression analysis showed that ethnicity, study design, publish year, and sample size did not significantly influence the diagnostic performance statistically (all P > 0.05). Conclusions The STESS is a promising candidate for predicting survival condition of patients with SE. However, the potential tool should be validated in well-designed studies with larger sample sizes.