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

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

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

Background The benefit of low‐density lipoprotein cholesterol (LDL‐C) levels in chronic kidney disease populations remains unclear. This study evaluated the cardiovascular and renal outcomes in patients with stage 3 chronic kidney disease with different LDL‐C levels during statin treatment. Methods and Results There were 8500 patients newly diagnosed as having stage 3 chronic kidney disease under statin treatment who were identified from the Chang Gung Research Database and divided into 3 groups according to their first LDL‐C level after the index date: 100 mg/dL. Inverse probability of treatment weighting was performed to balance baseline characteristics. Compared with the LDL‐C ≥100 mg/dL group, the 70≤LDL‐C Conclusions Among patients with stage 3 chronic kidney disease, statin users with 70≤LDL‐C100 mg/dL. Moreover, the 70≤LDL‐C

Background: Rigid dietary controls and pill burden make a very-low protein (0.3–0.4 g/kg body weight per day), vegetarian diet supplemented with ketoanalogues of amino acids (sVLPD) hard to follow in the long-term. This study aimed to evaluate whether a ketoanalogue supplemental low-protein diet (sLPD) (0.6 g/kg body weight per day) could also reduce the risks of dialysis among CKD stage 4 patients. Methods: Patients aged >20 years with a diagnosis of stage 4 CKD who subsequently received ketosteril treatment, which is the most commonly used ketoanalogue of essential amino acids, between 2003 and 2018 were identified from the Chang Gung Research Database (CGRD). Then, these individuals were divided into two groups according to the continuation of ketosteril for more than three months or not. The primary outcome was ESKD requiring maintenance dialysis. Results: With one-year follow-up, the continuation group (n = 303) exhibited a significantly lower incidence of new-onset end-stage kidney disease (ESKD) requiring maintenance dialysis (6.8% vs. 10.4%, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41–0.94) in comparison to the discontinuation group (n = 238). Conclusions: This study demonstrated that initiating sLPDs since CKD stage 4 may additionally reduce the short-term risks of commencing dialysis without increasing CV events, infections, or mortality.

Background: High-definition transcranial electrical theta burst superimposing direct current stimulation (HD-tDCS-eTBS) not only incorporates the therapeutic advantages of tDCS and TBS but enhances stimulation focality and practicality. However, the applicability of this innovative neuromodulatory device in post-stroke rehabilitation remains uncertain. Objective: This study aimed to assess the efficacy and safety of the HD-tDCS-eTBS on upper extremity (UE) motor function in patients with chronic stroke. Methods: A patient-blinded, randomized controlled study was conducted. Twenty-four participants were randomly assigned into either the active HD-tDCS-eTBS group or sham HD-tDCS-eTBS group. Both groups received 20 minutes of active/sham HD-tDCS-eTBS combined with 30 minutes of conventional UE rehabilitation each time, 3 times a week for 4 weeks. Outcome measures including the Fugl-Meyer Assessment of Upper Extremity, Wolf Motor Function Test, Jebsen-Taylor Hand Function Test, Finger-Nose Test, and Modified Ashworth Scale were assessed before and immediately after the intervention period. Results: Spasticity of shoulder adductor ( P = .05), elbow extensor ( P = .04), and thumb flexor ( P p2 = 0.06–0.16). No severe adverse events except for slight skin redness under the stimulus electrode was detected after the HD-tDCS-eTBS. Conclusions: Our findings support that HD-tDCS-eTBS is safe and has therapeutic potential for post-stroke UE motor rehabilitation. Trial registration: ClinicalTrials.gov (ID: NCT04278105).

Infective endocarditis (IE) is a serious infection and causes significant morbidity and mortality. However, the benefit of surgery for endocarditis besides antibiotic treatment in dialysis patients remains controversial. We performed a systematic review of studies published between 1960 and February 2022. Meta-analysis was conducted with a random-effects model to explore the in-hospital, 30, 60, 90, 180-d, and 1-year mortality rates in adult dialysis patients with IE. Sensitivity analysis, subgroup analysis, and meta-regression were performed to explore potential sources of heterogeneity. Confidence of evidence was evaluated by the GRADE system. Thirteen studies were included. The pooled odds ratio of in-hospital mortality was 0.62 (95% confidence interval [CI]: 0.30-1.28

Background Fluid overload is common in critically ill patients and is associated with worse outcomes. The trends in fluid balance have not been investigated previously. This study used trajectory analysis to investigate the impact of fluid balance trends on patients who had undergone cardiac or aortic surgery. Methods We analyzed patients who underwent cardiac or aortic surgery between August 2005 and March 2015. We excluded patients who died within the first 72 postoperative hours or received chronic dialysis before the surgery. Trajectories of urine and input-output during the first 3 postoperative days were analyzed using a latent class growth model. The primary outcomes were any stage of acute kidney injury (AKI) by Kidney Disease Improving Global Outcomes definition and de novo dialysis. Results The in-hospital mortality was 6.6% (70 of the 1063 patients included). The fluid input-output balance trajectories had better association with the primary outcome than urine output trajectories did. The risk of AKI and de novo dialysis were highest in the group with progressively positive fluid balance adjusted by preoperative body weight (AKI: adjusted odds ratio, 7.10; 95% confidence interval, 2.02-24.93; de novo dialysis: odds ratio, 4.54; 95% confidence interval, 1.12-18.38). Conclusions A progressively positive fluid balance is associated with AKI and de novo dialysis in patients undergoing cardiac or aortic surgery.

Background. Various forms of theta-burst stimulation (TBS) such as intermittent TBS (iTBS) and continuous TBS (cTBS) have been introduced as novel facilitation/suppression schemes during repetitive transcranial magnetic stimulation (rTMS), demonstrating a better efficacy than conventional paradigms. Herein, we extended the rTMS-TBS schemes to electrical stimulation of high-definition montage (HD-TBS) and investigated its neural effects on the human brain. Methods. In a within-subject design, fifteen right-handed healthy adults randomly participated in 10 min and 2 mA HD-TBS sessions: unilateral (Uni)-iTBS, bilateral (Bi)-cTBS/iTBS, and sham stimulation over primary motor cortex regions. A 20-channel near-infrared spectroscopy (NIRS) system was covered on the bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal lobe (PL) for observing cerebral hemodynamic responses in the resting-state and during fast finger-tapping tasks at pre-, during, and poststimulation. Interhemispheric correlation coefficient (IHCC) and wavelet phase coherence (WPCO) from resting-state NIRS and concentration of oxyhemoglobin during fast finger-tapping tasks were explored to reflect the symmetry between the two hemispheres and cortical activity, respectively. Results. The IHCC and WPCO of NIRS data in the SMC region under Bi-cTBS/iTBS showed relatively small values at low-frequency bands III (0.06–0.15 Hz) and IV (0.02–0.06), indicating a significant desynchronization in both time and frequency domains. In addition, the SMC activation induced by fast finger-tapping exercise was significantly greater during Uni-iTBS as well as during and post Bi-cTBS/iTBS sessions. Conclusions. It appears that a 10 min and 2 mA Bi-cTBS/iTBS applied over two hemispheres within the primary motor cortex region could effectively modulate the interhemispheric synchronization and cortical activation in the SMC of healthy subjects. Our study demonstrated that bilateral HD-TBS approaches is an effective noninvasive brain stimulation scheme which could be a novel therapeutic for inducing effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.

Patients with kidney failure who start dialysis have a chance of kidney function recovery. Whether the initial dialysis modality affects the possibility of recovery is not fully understood.We included patients diagnosed with kidney failure requiring dialysis during 2001-2013 from the Taiwan National Health Insurance Research Database. We excluded diabetic and elderly patients. Kidney function recovery was defined as not receiving dialysis therapy for longer than 3 months. The primary outcome was kidney function recovery, and the secondary outcome was all-cause mortality during a 3-year follow up.A total of 12,619 patients was eligible for analysis, with 981 received PD and 11,638 received HD. Total 620 patients had kidney function recovery during a 3-year follow up, which represented 4.9% of the entire cohort. After propensity score matching, the PD groups were more likely to experience kidney function recovery (subdistribution hazard ratio [SHR]: 1.64, 95% confidence interval [CI]: 1.19-2.25). The risk of all-cause mortality between groups did not significantly differ (hazard ratio [HR]: 1.23, 95% CI: 0.89-1.70).The study found that in nonelderly, nondiabetic patients who received inadequate predialysis nephrology care before kidney failure, PD is associated with a higher chance of kidney function recovery.

Acute kidney injury (AKI) is a common complication in acute heart failure (AHF) and is associated with prolonged hospitalization and increased mortality. The aim of this study was to externally validate existing prediction models of AKI in patients with AHF. Data for 10,364 patients hospitalized for acute heart failure between 2008 and 2018 were extracted from the Chang Gung Research Database and analysed. The primary outcome of interest was AKI, defined according to the KDIGO definition. The area under the receiver operating characteristic (AUC) curve was used to assess the discrimination performance of each prediction model. Five existing prediction models were externally validated, and the Forman risk score and the prediction model reported by Wang et al. showed the most favourable discrimination and calibration performance. The Forman risk score had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.696, 0.829, and 0.817, respectively. The Wang et al. model had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.73, 0.858, and 0.845, respectively. The Forman risk score and the Wang et al. prediction model are simple and accurate tools for predicting AKI in patients with AHF.

Introduction: Human lipocalin-2, known as neutrophil gelatinase-associated lipocalin (NGAL), is a widely studied biomarker of acute kidney injury (AKI).Areas covered: NGAL can serve as a predictor of AKI, disease progression, and mortality and can help in differentiating between AKI etiologies. We conducted a systematic review in the PubMed and Medline databases involving the clinical application of NGAL in patients with AKI.Expert opinion: In this review, we explored the usefulness of NGAL for AKI or clinical outcome prediction. The use of urine or blood NGAL levels alone or in combination with a clinical prediction model may facilitate AKI prediction, severity prediction, AKI etiological differentiation, and mortality prediction. For AKI prediction, urine and plasma NGAL levels have an area under the curve (AUC) ranging from 0.71 to 0.90 and from 0.71 to 0.89, respectively, in different populations. The diagnostic performance of NGAL alone for renal replacement therapy or successful discontinuation prediction is suboptimal (AUC range: 0.65-0.81). Sepsis limits the application of NGAL as a clinical predictor, and the prediction performance of NGAL is affected by baseline renal function, timing of sample collection, and underlying comorbidities. The lack of internationally approved reference material also limits the usefulness of NGAL.

Background Dialysis‐requiring acute kidney injury (D‐AKI) is a major complication of cardiovascular surgery that results in worse prognosis. However, the incidence and impacts of D‐AKI in different types of cardiac surgeries have not been fully investigated. Methods and Results Patients admitted for cardiovascular surgery between July 1, 2004, and December 31, 2013, were identified from the National Health Insurance Research Database of Taiwan. The patients were grouped into D‐AKI (n=3089) and non–D‐AKI (n=42 151) groups. The outcome was all‐cause mortality and major adverse kidney event. The long‐term outcomes were worse in the D‐AKI group than the non–D‐AKI group (hazard ratio [HR], 3.89; 95% CI, 3.79–3.99 for major adverse kidney event; HR, 2.89; 95% CI, 2.81–2.98 for all‐cause mortality). Patients who underwent aortic surgery had higher risk for D‐AKI than other types of surgeries, but they were also more likely to recover. The long‐term dialysis rate for the patients who recovered from D‐AKI was also lowest in those who underwent aortic surgery. Among all types of cardiac surgeries with D‐AKI, patients who had heart valve surgery exhibited the greatest risks of all‐cause mortality (HR, 6.04; 95% CI, 5.78–6.32). Conclusions Compared with other heart surgeries, aortic surgery resulted in a higher incidence of D‐AKI but better renal recovery, better short‐term outcome, and lower incidences of long‐term dialysis.

Background It has been a matter of much debate whether the co-administration of furosemide and albumin can achieve better diuresis and natriuresis than furosemide treatment alone. There is inconsistency in published trials regarding the effect of this combination therapy. We, therefore, conducted this meta-analysis to explore the efficacy of furosemide and albumin co-administration and the factors potentially influencing the diuretic effect of such co-administration. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, Medline, and Cochrane databases. Prospective studies with adult populations which comparing the effect of furosemide and albumin co-administration with furosemide alone were included. The outcomes including diuretic effect and natriuresis effect measured by hourly urine output and hourly urine sodium excretion from both groups were extracted. Random effect model was applied for conducting meta-analysis. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity of treatment effects. Results By including 13 studies with 422 participants, the meta-analysis revealed that furosemide with albumin co-administration increased urine output by 31.45 ml/hour and increased urine excretion by 1.76 mEq/hour in comparison to furosemide treatment alone. The diuretic effect of albumin and furosemide co-administration was better in participants with low baseline serum albumin levels (< 2.5 g/dL) and high prescribed albumin infusion doses (> 30 g), and the effect was more significant within 12 hours after administration. Diuretic effect of co-administration was better in those with baseline Cr > 1.2 mg/dL and natriuresis effect of co-administration was better in those with baseline eGFR < 60 ml/min/1.73m2. Conclusion Co-administration of furosemide with albumin might enhance diuresis and natriuresis effects than furosemide treatment alone but with high heterogeneity in treatment response. According to the present meta-analysis, combination therapy might provide advantages compared to the furosemide therapy alone in patients with baseline albumin levels lower than 2.5 g/dL or in patients receiving higher albumin infusion doses or in patients with impaired renal function. Owing to high heterogeneity and limited enrolled participants, further parallel randomized controlled trials are warranted to examine our outcome. Registration PROSEPRO ID: CRD42020211002; https://clinicaltrials.gov/.

Glucagon-like peptide-1 (GLP-1) receptor agonist use is associated with reduced mortality and improved cardiovascular outcomes in the general population with diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used antidiabetic agents for patients with advanced-stage chronic kidney disease (CKD). The association of these 2 drug classes with outcomes among patients with diabetes and advanced-stage CKD or end-stage kidney disease (ESKD) is not well understood.To assess whether use of GLP-1 receptor agonists in a population with diabetes and advanced-stage CKD or ESKD is associated with better outcomes compared with use of DPP-4 inhibitors.This retrospective cohort study used data on patients with type 2 diabetes and stage 5 CKD or ESKD obtained from the National Health Insurance Research Database of Taiwan. The study was conducted between January 1, 2012, and December 31, 2018. Data were analyzed from June 2020 to July 2021.Treatment with GLP-1 receptor agonists compared with treatment with DPP-4 inhibitors.All-cause mortality, sepsis- and infection-related mortality, and mortality related to major adverse cardiovascular and cerebrovascular events were compared between patients treated with GLP-1 receptor agonists and patients treated with DPP-4 inhibitors. Propensity score weighting was used to mitigate the imbalance among covariates between the groups.Of 27 279 patients included in the study, 26 578 were in the DPP-4 inhibitor group (14 443 [54.34%] male; mean [SD] age, 65 [13] years) and 701 in the GLP-1 receptor agonist group (346 [49.36%] male; mean [SD] age, 59 [13] years). After weighting, the use of GLP-1 receptor agonists was associated with lower all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.63-0.98) and lower sepsis- and infection-related mortality (HR, 0.61; 95% CI, 0.40-0.91). Subgroup analysis demonstrated a lower risk of mortality associated with use of GLP-1 receptor agonists compared with DDP-4 inhibitors among patients with cerebrovascular disease (HR, 0.33; 95% CI, 0.12-0.86) than among those without cerebrovascular disease (HR, 0.89; 95% CI, 0.71-1.12) (P = .04 for interaction).Treatment with GLP-1 receptor agonists was associated with lower all-cause mortality among patients with type 2 diabetes, advanced-stage CKD, and ESKD than was treatment with DPP-4 inhibitors. Additional well-designed, prospective studies are needed to confirm the potential benefit of GLP-1 receptor agonist treatment for patients with advanced CKD or ESKD.

Risk and prognostic factors for acute kidney injury (AKI) have been published in various studies across various populations. We aimed to explore recent advancements in and provide updated recommendations on AKI risk stratification and information about local AKI risk factors. The Taiwan Acute Kidney Injury Task Force reviewed relevant recently published literature and reached a consensus after group meetings. Systemic review and group discussion were performed. We conducted a meta-analysis according to the PRISMA statement for evaluating the diagnostic performance of the furosemide stress test. Several risk and susceptibility factors were identified through literature review. Contrast-associated AKI prediction models after coronary angiography were one of the most discussed prediction models we found. The basic approach and evaluation of patients with AKI was also discussed. Our meta-analysis found that the furosemide stress test can be used as a prognostic tool for AKI progression and to identify patients with AKI who are at low risk of renal replacement therapy. Factors associated with de novo chronic kidney injury or renal non-recovery after AKI were identified and summarized. Our review provided practical information about early identification of patients at high risk of AKI or disease progression for Taiwan local clinics.

For a long time, cisplatin-based chemotherapy had been viewed as first-line chemotherapy for advanced and metastatic urothelial carcinoma (UC). However, many patients with UC had been classified as cisplatin-ineligible who can only receive alternative chemotherapy with poor treatment response, and the vast majority of the cisplatin-eligible patients eventually progressed, even those with objective response with cisplatin-based chemotherapy initially. By understanding tumor immunology in UC, immune checkpoint inhibitors, targeting on programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) pathways, had been proven as first-line treatment for cisplatin-ineligible metastatic UC and as second-line treatment for patients with platinum-refractory metastatic UC by the U.S Food and Drug Administration (FDA). In 2020, JAVEIN bladder 100 further reported that PD-L1 inhibitors showed benefits on prolonged survival and progression-free survival as maintenance therapy. Besides targeting on immune checkpoint, manipulation of the tumor microenvironment by metabolic pathways intervention, including inhibition on tumor glycolysis, lactate accumulation and exogenous glutamine uptake, had been investigated in the past few years. In this comprehensive review, we start by introducing traditional chemotherapy of UC, and then we summarize current evidences supporting the use of immune checkpoint inhibitors and highlight ongoing clinical trials. Lastly, we reviewed the tumor metabolic characteristic and the anti-tumor treatments targeting on metabolic pathways.

BackgroundThis study analyzed the survival and protective predictors of in-hospital cardiopulmonary cerebral resuscitation (CPCR) to potentially help physicians create effective treatment plans for End-stage kidney disease (ESKD) patients.MethodsWe extracted the data of 7,116 ESKD patients who received their first in-hospital CPCR after initial dialysis between 2004 and 2012 from the National Health Insurance Research Database. The primary outcome was the survival rate during the first in-hospital CPCR. The secondary outcome was the median post-discharge survival.ResultsFrom 2004 through 2012, the incidence of in-hospital CPCR decreases from 3.97 to 3.67 events per 1,000 admission days (P for linear trend ConclusionThe incidence of in-hospital CPCR and the duration post-discharge among ESKD patients improved despite there being no significant difference in the survival rate of ESKD patients after CPCP. Either ICD or CRT-D implantation may be advisable for ESKD patients with a high risk of sudden cardiac death.

Much of the work in alpha NFT has focused on evaluating changes in alpha amplitude. However, the generation mechanism of training-induced alpha activity has not yet been clarified. The present study aimed to identify sources of training-induced alpha activity through four temporal/spectral analytic techniques, i.e., the max peak average (MPA), positive average (PA), negative average (NA) and event-related spectral perturbation average (ERSPA) methods. Thirty-five healthy participants were recruited into an alpha group receiving feedback of 8–12-Hz amplitudes, and twenty-eight healthy participants were recruited into a control group receiving feedback of random 4-Hz amplitudes from the range of 7 to 20 Hz. Twelve sessions were performed within 4 weeks (3 sessions per week). The control group had no change in the amplitude spectrum. In contrast, twenty-nine participants in the alpha group showed significant alpha amplitude increases exclusively and were identified as “responders”. A whole-head EEG was recorded for the “responders” after NFT. The epochs of training-induced alpha activity from whole-head EEG were averaged by four different methods for equivalent current dipole source analysis. High agreement and Cohen’s kappa coefficients on dipole source localization between each method were observed, showing that the dipole clusters of training-induced alpha activity were consistently located in the precuneus, posterior cingulate cortex (PCC) and middle temporal gyrus. The residual variance (goodness of fit) for dipole estimation of the MPA was significantly smaller than that of the others. Our findings indicate that the precuneus, PCC and middle temporal gyrus play important roles in enhancing training-induced alpha activity. The four averaging methods (especially the MPA method) were suitable for investigating sources of brainwaves. Additionally, three dipoles can be used for dipole source analysis of training-induced alpha activity in future research, especially the training sites are around the central regions.

Background The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated. Results We identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74–0.87) and 0.88 (95% CI 0.82–0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96–7.50), the pooled negative LR was 0.26 (95% CI 0.19–0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00–51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72–0.91) and 0.77 (95% CI 0.64–0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06–4.86) and 0.25 (95% CI 0.14–0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74–32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1–2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51–13.33). Conclusion The FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.

OBJECTIVES Chronic kidney disease (CKD) impairs the elimination of fluids, electrolytes and metabolic wastes, which can affect the outcomes of extracorporeal membrane oxygenation (ECMO) treatment. This study aimed to elucidate the impact of CKD on in-hospital mortality and mid-term survival of adult patients who received ECMO treatment. METHODS Patients who received first-time ECMO treatment between 1 January 2003 and 31 December 2013 were included. Those with CKD were identified and matched to patients without CKD using a 1:2 ratio and were followed for 3 years. The study outcomes included in-hospital outcomes and the 3-year mortality rate. A subgroup analysis was conducted by comparing the dialytic patients with the non-dialytic CKD patients. RESULTS The study comprised 1008 CKD patients and 2016 non-CKD patients after propensity score matching. The CKD patients had higher in-hospital mortality rates [69.5% vs 62.2%; adjusted odds ratio 1.41; 95% confidence interval (CI) 1.15–1.72] than the non-CKD patients. The 3-year mortality rate was 80.4% in the CKD group and 68% in the non-CKD group (adjusted hazard ratio 1.17; 95% CI 1.06–1.28). The subgroup analysis showed that the 3-year mortality rates were 84.5% and 78.4% in the dialytic and non-dialytic patients, respectively. No difference in the 3-year mortality rate was noted between the 2 CKD subgroups (P = 0.111). CONCLUSIONS CKD was associated with increased risks of in-hospital and mid-term mortalities in patients who received ECMO treatment. Furthermore, no difference in survival was observed between the patients with end-stage renal disease and non-dialytic CKD patients.

The aim of this study was to enhance the effectiveness of photo thermal therapy (PTT) in the targeting of superficial bladder cancers using a green light laser in conjunction with gold nanoparticles (GNPs) conjugated to antibody fragments (anti-EGFR). GNPs conjugated with anti-EGFR-antibody fragments were used as probes in the targeting of tumor cells and then exposed to a green laser (532nm), resulting in the production of sufficient thermal energy to kill urothelial carcinomas both in vitro and in vivo. Nanoparticles conjugated with antibody fragments are capable of damaging cancer cells even at relatively very low energy levels, while non-conjugated nanoparticles would require an energy level of 3 times under the same conditions. The lower energy required by the nanoparticles allows this method to destroy cancerous cells while preserving normal cells when applied in vivo. Nanoparticles conjugated with antibody fragments (anti-EGFR) require less than half the energy of non-conjugated nanoparticles to kill cancer cells. In an orthotopic bladder cancer model, the group treated using PTT presented significant differences in tumor development.

Neurofeedback training (NFT) of the alpha rhythm has been used for several decades but is still controversial in regards to its trainability and effects on working memory. Alpha rhythm of the frontoparietal region are associated with either the intelligence or memory of healthy subjects and are also related to pathological states. In this study, alpha NFT effects on memory performances were explored. Fifty healthy participants were recruited and randomly assigned into a group receiving a 8-12-Hz amplitude (Alpha) or a group receiving a random 4-Hz amplitude from the range of 7 to 20 Hz (Ctrl). Three NFT sessions per week were conducted for 4 weeks. Working memory was assessed by both a backward digit span task and an operation span task, and episodic memory was assessed using a word pair task. Four questionnaires were used to assess anxiety, depression, insomnia, and cognitive function. The Ctrl group had no change in alpha amplitude and duration. In contrast, the Alpha group showed a progressive significant increase in the alpha amplitude and total alpha duration of the frontoparietal region. Accuracies of both working and episodic memories were significantly improved in a large proportion of participants of the Alpha group, particularly for those with remarkable alpha-amplitude increases. Scores of four questionnaires fell in a normal range before and after NFT. The current study provided supporting evidence for alpha trainability within a small session number compared with that of therapy. The findings suggested the enhancement of working and episodic memory through alpha NFT. Hum Brain Mapp 37:2662-2675, 2016. © 2016 Wiley Periodicals, Inc.

Objectives This study sought to examine the hypothesis that cardiac autonomic function (CAF) is altered in pre-hypertensive subjects and normotensive subjects with a family history of hypertension (FHH). Background The findings on the FHH effect in CAF have been inconsistent, and little is known about altered CAF in pre-hypertensive subjects under The Seventh Report of the Joint National Commission on High Blood Pressure criteria of normotension and pre-hypertension. Methods A total of 1,436 community dwellers were classified as having normotension without FHH (NT[−]), normotension with FHH (NT[+]), pre-hypertension, and hypertension. Cardiac autonomic function was determined by standard deviation of RR intervals (SDNN), power spectrum in low frequencies (LF) and high frequencies (HF) and LF/HF ratio in supine position for 5 min, the ratio between the longest RR interval at approximately the 30th beat and the shortest RR interval at approximately the 15th beat after standing (30 max/15 min ratio), and the ratio between the longest RR interval during expiration and the shortest RR interval during inspiration (E/I ratio). Results There was a significant difference in all CAF indexes among subjects with NT(−), NT(+), pre-hypertension, and hypertension. Multivariate analyses with an analysis of covariance model showed that 30 max/15 min ratio, E/I ratio, and HF power decreased in subjects with NT(+), pre-hypertension, and hypertension when compared with NT(−) subjects. Pre-hypertensive and hypertensive subjects displayed higher square roots of LF/HF ratios. Only pre-hypertensive subjects had higher LF power. Conclusions Our study provides evidence that CAF plays a role in pre-hypertension and that altered autonomic function is already present in subjects with FHH. An autonomic imbalance shifting with augmented sympathetic tone was more enhanced in pre-hypertension.

Context: Autonomic dysfunction is present in diabetes mellitus (DM), but no study is available on alteration in cardiac autonomic function (CAF) across different glycemic statuses including normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and DM. Objective: Our objective was to examine whether CAF is altered in subjects with IGT and isolated IFG. Design and Setting: The study was a stratified systematic cluster sampling design within the general community. Participants: A total of 1440 subjects were classified as NGT (n 983), isolated IFG (n 163), IGT (n 188), and DM (n 106). Main Outcome Measure: CAF was determined by 1) standard deviation of normal-to-normal (SDNN) or RR interval, power spectrum in low and high frequency (LF, 0.04–0.15 Hz; HF, 0.15–0.40 Hz), and LF/HF ratio in supine position for 5 min; 2) ratio between 30th and 15thRRintervalafterstandingfromsupineposition(30/15ratio);and 3) average heart rate change during breathing of six deep breaths for 1 min (HRDB). Results: Univariate analysis showed significant differences in SDNN,30/15ratio,HRDB,HFpower,andLF/HFratioamongsubjects with NGT, isolated IFG, IGT, and DM. In multivariate analysis, none oftheindicesofCAFwasrelatedtoisolatedIFGinthereferencegroup of NGT. IGT and DM were negatively associated with 30/15 ratio and HF power but positively associated with LF/HF ratio. In addition, DM was also related to a lower SDNN. Conclusions: DM and IGT subjects had an impaired CAF independent of other cardiovascular risk factors. The risk of altered CAF is not apparent in subjects with isolated IFG. (J Clin Endocrinol Metab 92: 3885–3889, 2007)

This study aimed to investigate the effects of harmine hydrochloride (HMH) on digestive tumor cells in vitro and its molecular mechanism. MTT assays showed that HMH inhibited the proliferation of some human cancer cell lines and had no obvious inhibitory effects on human LO2 cells. Flow cytometry assays showed that HMH trigged G2 phase arrest in MGC-803 cells and SMMC-7721 cells, while the expression of cyclin A, cyclin B, p21, Myt1, and p-cdc2 (Tyr15) was upregulated. Flow cytometry assays also showed that the percentages of apoptotic cells were increased, the mitochondrial transmembrane potential (ΔΨm) decreased, and the cleavage of caspase-9, caspase-3, and poly (Adenosine diphosphate ribose) polymerase (PARP) were observed, the expression of Bad increased, phospho-Bad (S112) decreased, pro-caspase-8 was cleaved, and Bid (22 kDa) was cleaved. The expression of p-ERK decreased in both cells. In conclusion, these results demonstrated that HMH upregulates the expression of p21, activates Myt1 and inhibits cdc2 by phospho-cdc2 (Y15), and triggers G2 phase arrest in both MGC-803 cells and SMMC-7721 cells. It can also activate the mitochondria-related cell apoptosis pathway through the caspase-8/Bid pathway, inhibiting the ERK/Bad pathway and promoting apoptosis in both of these two cell types.

Objective. To kill urothelial cancer cells while preserving healthy cells, this study used photothermal therapy (PTT). PTT techniques target urothelial cancer cells using gold nanoparticles (GNPs) and a green light laser.Materials and Methods. The GNPs were conjugated with anti-Mucin 7 antibodies, which acted as a probe for targeting tumor cells. Conjugated GNPs were exposed to a green light laser (532 nm) with sufficient thermal energy to kill the transitional cell carcinomas (TCCs).Results. According to our results, nanoparticles conjugated with Mucin 7 antibodies damaged all types of cancer cells (MBT2, T24, 9202, and 8301) at relatively low energy levels (i.e., 500 laser shots at 10 W/cm2in power, 1.6 Hz in frequency, and 300 ms in duration). Nonconjugated nanoparticles required 30 W/cm2or more to achieve the same effect. Cell damage was directly related to irradiation time and applied laser energy.Conclusions. The minimally invasive PTT procedure combined with Mucin 7 targeted GNPs is able to kill cancer cells and preserve healthy cells. The success of this treatment technique can likely be attributed to the lower amount of energy required to kill targeted cancer cells compared with that required to kill nontargeted cancer cells. Our in vitro pilot study yielded promising results; however, additional animal studies are required to confirm these findings.

Electroencephalogram (EEG) signal artifacts occur often in children, but an EEG valid rate (VR), constructed by excluding the artifacts, might be meaningful to evaluate children's neuropsychological functions. The aim of this study was to develop an easy screening index, the EEGVR, and to investigate attention function in children using this index.The EEG was carried out during a 4 min simple reaction time (SRT) task as standard procedure in 50 children, consisting of 26 with attention-deficit-hyperactivity disorder (ADHD; mean age, 9.8 years; range, 8-11.3 years) and 24 without (mean age, 10.1 years; range, 7.8-12 years). An easy index was derived from the valid rate (VR) of EEG using area under the receiver operating characteristic curve. The index was applied to regroup the 50 children into high VR (HVR) and low VR (LVR) groups, while the Comprehensive Non-verbal Attention Test (CNAT) and four behavioral questionnaires were compared between the two groups in order to investigate the validity of this index.The EEGVR at 75% was optimal to identify HVR and LVR (sensitivity, 0.769; specificity, 0.792). The LVR group had significantly lower scores on both CNAT and the behavioral questionnaires, although the demographic variables and full-scale intelligence quotient (FSIQ) were similar between the two groups.The EEGVR in an SRT task might be an easy and effective index to screen the attention function of children, and could consequently contribute to the early diagnosis of ADHD.

Background Previous studies on the change of cardiac autonomic function and insulin resistance in metabolic syndrome recruited subjects with cardiovascular-related disease and defined metabolic abnormality with a more severe cutoff. We explored the alteration of cardiac autonomic function and insulin resistance in predisease community dwellers with different numbers of metabolic abnormalities. Methods A total of 1298 subjects were classified as none (n=539), one (n=378), 2 (n=218), and 3 or more metabolic abnormalities (n=154). Insulin resistance was calculated by homeostatic model assessment. Cardiac autonomic function included 5-minute standard deviation of R-R interval, low- and high-frequency power spectrum, and low-/high-frequency power spectrum ratio, the ratio of the longest R-R interval around the 30th beat and the shortest R-R interval around the 15th beat after standing, and the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing. Results Subjects with a single metabolic abnormality or more had a lower standard deviation of R-R interval and expiratory/inspiratory ratio than subjects without metabolic abnormality in multivariate analysis. Subjects with 3 or more metabolic abnormalities had a higher low-/high-frequency power spectrum ratio, but a lower high-frequency power. Insulin resistance was higher in groups with 2 metabolic abnormalities or more, but not in the group with one metabolic abnormality, than those without metabolic abnormality. Conclusions Cardiac autonomic function altered in predisease subjects with one or more metabolic abnormalities, while insulin resistance existed in subjects with 2 or more metabolic abnormalities. Thus, autonomic function change may precede insulin resistance in the initiation of metabolic syndrome.

Spasticity is often seen in patients with central nervous system lesion, such as stroke. It hinders functional movement and may induce pain. Current measures for assessing Spasticity are either quantitative but not convenient to use or convenient to use in clinics but lack of objective quantification. We developed a manual spasticity evaluator (MSE) to evaluate the spasticity quantitatively and potentially suitable for a clinical setting. Joint position and torque from 10 subjects with right hemiplegia and 9 healthy subjects were measured conveniently and used to evaluate spasticity and determine the catch angle. EMG signal was obtained from the biceps brachii and triceps brachii to corroborate the mechanical measurement of the MSE. Results showed that the MSE provided a convenient and quantitative measurement of spasticity, including presence of catch angle, increase in joint stiffness, and decrease in joint range of motion in the stroke patients, as compared with healthy subjects. EMG signals corroborated MSE assessment of the catch angle.