Rate of Sodium Correction and Osmotic Demyelination Syndrome in Severe Hyponatremia: A Meta-Analysis.

Introduction: Current guidelines recommend limiting the rate of correction in patients with severe hyponatremia to avoid severe neurologic complications such as osmotic demyelination syndrome (ODS). However, published data have been conflicting. We aimed to evaluate the association between rapid sodium correction and ODS in patients with severe hyponatremia. Materials and methods: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to November 2023. The primary outcome was ODS and the secondary outcomes were in-hospital mortality and length of hospital stay. Results: We identified 7 cohort studies involving 6,032 adult patients with severe hyponatremia. Twenty-nine patients developed ODS, resulting in an incidence rate of 0.48%. Seventeen patients (61%) had a rapid correction of serum sodium in the first or any 24-hour period of admission. Compared with a limited rate of sodium correction, a rapid rate of sodium correction was associated with an increased risk of ODS (RR, 3.91 [95% CI, 1.17 to 13.04]; I2 = 44.47%; p = 0.03). However, a rapid rate of sodium correction reduced the risk of in-hospital mortality by approximately 50% (RR, 0.51 [95% CI, 0.39 to 0.66]; I2 = 0.11%; p < 0.001) and the length of stay by 1.3 days (Mean difference, -1.32 [95% CI, -2.54 to -0.10]; I2 = 71.47%; p = 0.03). Conclusions: Rapid correction of serum sodium may increase the risk of ODS among patients hospitalized with severe hyponatremia. However, ODS may occur in patients regardless of the rate of serum sodium correction.

A Retrospective Comparison of Diagnostic Tools of Bullous Pemphigoid for Elderly Patients.

BACKGROUND: Older patients who are predisposed to bullous pemphigoid (BP) may exhibit reluctance to undergo skin biopsy due to potential complications. OBJECTIVES: This study aimed to conduct a comparative evaluation among histology, direct immunofluorescence (DIF), and indirect immunofluorescence (IIF) to determine the optimal diagnostic tool in elderly patients. METHODS: A retrospective study was conducted on 841 patients suspected of having BP. All cases were initially classified as BP and non-BP in accordance with the diagnostic criteria. Student's t-test and chi-squared test examined differences between the 2 groups. We evaluated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio detected by the 3 tools. We stratified the analysis by age to compare the performance of the diagnostic tools and examined the risk factors associated with BP using logistic regression. RESULTS: Overall, histology exhibited the highest sensitivity (89.4%), while DIF demonstrated the highest specificity (67.1%). In the elderly, the IIF test exhibited the highest specificity (57.5%), the highest positive likelihood ratio (2.047), and the lowest negative likelihood ratio (0.226). Among patients taking Dipeptidyl Peptidase-4 (DPP-4) inhibitors, IIF demonstrated the highest positive likelihood ratio (3.194) and the second-lowest negative likelihood ratio (0.235). CONCLUSIONS: In cases that elderly patients suspected of having BP are reluctant to undergo skin biopsy, IIF demonstrates the optimal diagnostic method due to its highest positive likelihood ratio, the lowest negative likelihood ratio among the 3 diagnostic measures. Moreover, IIF is found to be a more effective tool for detecting BP in patients using DPP-4 inhibitors.

Therapeutic Potential of Olfactory Ensheathing Cells and Adipose-Derived Stem Cells in Osteoarthritis: Insights from Preclinical Studies.

Olfactory-ensheathing cells (OECs) are known for their role in neuronal regeneration and potential to promote tissue repair. Adipose-derived stem cells (ADSCs), characterized by mesenchymal stem cell (MSC) traits, display a fibroblast-like morphology and express MSC surface markers, making them suitable for regenerative therapies for osteoarthritis (OA). In this study, OECs and ADSCs were derived from tissues and characterized for their morphology, surface marker expression, and differentiation capabilities. Collagenase-induced OA was created in 10-week-old C57BL/6 mice, followed by intra-articular injections of ADSCs (1 × 105), OECs (1 × 105), or a higher dose of OECs (5 × 105). Therapeutic efficacy was evaluated using rotarod performance tests, MRI, histology, and immunohistochemistry. Both cell types exhibited typical MSC characteristics and successfully differentiated into adipocytes, osteoblasts, and chondrocytes, confirmed by gene expression and staining. Transplantation significantly improved rotarod performance and preserved cartilage integrity, as seen in MRI and histology, with reduced cartilage destruction and increased chondrocytes. Immunohistochemistry showed elevated type II collagen and aggrecan in treated joints, indicating hyaline cartilage formation, and reduced MMP13 and IL-1ß expression, suggesting decreased inflammation and catabolic activity. These findings highlight the regenerative potential of OECs and ADSCs in treating OA by preserving cartilage, promoting chondrocyte proliferation, and reducing inflammation. Further research is needed to optimize delivery methods and evaluate long-term clinical outcomes.

Hyalinizing clear cell carcinoma in the nasopharynx: A case report and literature review.

RATIONALE: Hyalinizing clear cell carcinoma (HCCC) arising from a minor salivary gland is a rare malignant neoplasm. Most HCCC has been reported in the palate and tongue base, and only rarely in the nasopharynx. Here, we report a rare case of nasopharyngeal HCCC. PATIENT CONCERNS: A 44-year-old male who complained of otorrhea and aural fullness for 5 years was found to have a nasopharyngeal mass. DIAGNOSES: HCCC by fluorescence in situ hybridization analysis. INTERVENTIONS: Surgical resection plus concurrent chemotherapy and radiation therapy were administered. OUTCOMES: The patient recovered well with symptoms improved at postoperative follow-up. LESSONS: HCCC should be included in the differential diagnosis of nasopharyngeal mass. Overall, the prognosis of HCCC is positive after tumor resection and adequate management.

Associations between body weight trajectories and neurodevelopment outcomes at 24 months corrected age in very-low-birth-weight preterm infants: a group-based trajectory modelling study.

Introduction: This study aimed to explore the relationship between the trajectories of body weight (BW) z-scores at birth, discharge, and 6 months corrected age (CA) and neurodevelopmental outcomes at 24 months CA. Methods: Conducted as a population-based retrospective cohort study across 21 hospitals in Taiwan, we recruited 3,334 very-low-birth-weight (VLBW) infants born between 2012 and 2017 at 23-32 weeks of gestation. Neurodevelopmental outcomes were assessed at 24 months CA. Instances of neurodevelopmental impairment (NDI) were defined by the presence of at least one of the following criteria: cerebral palsy, severe hearing loss, profound vision impairment, or cognitive impairment. Group-based trajectory modeling was employed to identify distinct BW z-score trajectory groups. Multivariable logistic regression was used to assess the associations between these trajectories, postnatal comorbidity, and neurodevelopmental impairments. Results: The analysis identified three distinct trajectory groups: high-climbing, mid-declining, and low-declining. Significant associations were found between neurodevelopmental impairments and both cystic periventricular leukomalacia (cPVL) [with an adjusted odds ratio (aOR) of 3.59; p < 0.001] and belonging to the low-declining group (aOR: 2.59; p < 0.001). Discussion: The study demonstrated that a low-declining pattern in body weight trajectory from birth to 6 months CA, along with cPVL, was associated with neurodevelopmental impairments at 24 months CA. These findings highlight the importance of early weight trajectory and specific health conditions in predicting later neurodevelopmental outcomes in VLBW infants.

Nodal T-Follicular Helper Cell Lymphoma, Angioimmunoblastic-Type, Diagnosed in a Patient with Psoriasis Following COVID-19 Vaccination under Adalimumab Treatment: A Causal Association?

Biologics have expanded the armamentarium for psoriasis, but there has been a growing concern about the risk of lymphoma in patients under tumour necrosis factor (TNF)-α inhibitor and methotrexate. Besides, the mRNA-based coronavirus disease 2019 (COVID-19) vaccination was known to stimulate the proliferation of T-follicular helper cells. We report a case of a patient with psoriasis under adalimumab developing nodal T-follicular helper cell lymphoma, angioimmunoblastic-type following the mRNA-1273 COVID-19 vaccine. We suspect that adalimumab, methotrexate, Epstein-Barr virus (EBV) reactivation, previous reactive lymphoid hyperplasia and psoriasis per se predispose our patient to a lymphoma-prone condition, and the two doses of the mRNA vaccine act as the last straw.

[Determination of sodium cyclamate in Baijiu by pre-column derivatization-high performance liquid chromatography with fluorometric detection].

Sodium cyclamate in Baijiu is a key item in the China National Food Safety Supervision and Inspection Plan. A simple, economical, sensitive, and reliable method is urgently needed for routine analysis and internal quality control. A method based on high performance liquid chromatography with fluorescence detection (HPLC-FLD) was developed for the determination of sodium cyclamate in Baijiu by o-phthalaldehyde derivatization. First, the sodium cyclamate in the sample solution was converted into amino compounds using the desulfurization reaction under acidic conditions. Next, 400 g/L sodium hydroxide solution was added to the sample solution for neutralization. The amino compounds in the sample solution were then derivatized with o-phthalaldehyde to produce indole-substituted derivatives that are capable of producing fluorescence signals. Separation was carried out on a C18 column (250 mm×4.6 mm, 5 µm) in isocratic elution mode using a mobile phase consisting of acetonitrile and phosphate buffer. Finally, the eluate was monitored using a fluorescence detector, and an external standard method was used for quantification. A good linear relationship was obtained in the range of 0.1-2.0 mg/L, with correlation coefficients greater than 0.999. The average recoveries of sodium cyclamate spiked at levels of 0.1-1.0 mg/kg in Baijiu samples ranged from 90.7% to 100.9%, with relative standard deviations (RSDs) of 3.5%-5.6% (n=6). The limits of detection and quantification were 0.03 and 0.10 mg/kg, respectively. Nine Baijiu samples collected from the market were tested, and the results demonstrated that the contents of sodium cyclamate detected by the developed method were consistent with those obtained using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method described in GB 5009.97-2016 (the third method). The proposed method is economical, sensitive, specific, and accurate; thus, it provides a basic approach for the determination of sodium cyclamate in Baijiu samples and has great potential for routine analysis in foodstuffs.

Survival impact of pre-transplant local treatments in liver transplant recipients with BCLC stage A hepatocellular carcinoma.

This study aimed to evaluate the impact of different pre-transplant local treatments on the survival of liver transplantation (LTx) recipients with BCLC Stage A Hepatocellular Carcinoma (HCC). We analyzed data from the Taiwan Cancer Registry and National Health Insurance Research Databases spanning 2012 to 2018. Employing propensity score matching, patients were categorized into three groups: those receiving local treatments (180 patients), hepatectomy (179 patients), and combined treatments (180 patients). The primary outcomes were overall mortality and HCC-specific death, assessed using time-varying Cox regression models and Kaplan-Meier survival analysis. During a median follow-up period of 3.92 years, all-cause mortality rates were observed as 74.44% for local treatments, 42.46% for hepatectomy, and 65.00% for combined treatments. HCC-specific mortality rates followed a similar pattern at 65.00%, 39.11%, and 59.44%, respectively. Adjusted hazard ratios demonstrated significantly elevated mortality risks associated with local and combined treatments compared to hepatectomy. Notably, the 2-year overall and HCC-specific survival rates were highest in the hepatectomy group, surpassing those observed in both the combined treatment and local treatment groups. The findings of our study highlight that for patients with BCLC Stage A HCC, undergoing hepatectomy prior to LTx is associated with superior survival outcomes compared to solely local treatments. This underscores the importance of considering hepatectomy as a vital component of the treatment strategy in this patient population.

Phospholipid peroxidation in macrophage confers tumor resistance by suppressing phagocytic capability towards ferroptotic cells.

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy.

Polyphenol-stabilized coacervates for enzyme-triggered drug delivery.

Stability issues in membrane-free coacervates have been addressed with coating strategies, but these approaches often compromise the permeability of the coacervate. Here we report a facile approach to maintain both stability and permeability using tannic acid and then demonstrate the value of this approach in enzyme-triggered drug release. First, we develop size-tunable coacervates via self-assembly of heparin glycosaminoglycan with tyrosine and arginine-based peptides. A thrombin-recognition site within the peptide building block results in heparin release upon thrombin proteolysis. Notably, polyphenols are integrated within the nano-coacervates to improve stability in biofluids. Phenolic crosslinking at the liquid-liquid interface enables nano-coacervates to maintain exceptional structural integrity across various environments. We discover a pivotal polyphenol threshold for preserving enzymatic activity alongside enhanced stability. The disassembly rate of the nano-coacervates increases as a function of thrombin activity, thus preventing a coagulation cascade. This polyphenol-based approach not only improves stability but also opens the way for applications in biomedicine, protease sensing, and bio-responsive drug delivery.

Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system.

CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.

Students' core competence performance during fundamental nursing practicum: A cross-sectional survey with importance-performance analysis.

AIM: Limited available studies compare the core competence performance of students undertaking their practicum at different level-of-care practicum sites. This study aimed to (1) compare the gaps between the perception of importance for competence and the perceived performance of nursing students at practicum sites involving different level-of-care and (2) identify low competencies that must be prioritized for improvement at different sites during the fundamental nursing practicum. DESIGN: Cross-sectional design. METHODS: A total of 659 students who had passed their fundamental nursing practicum within 1 month from six nursing colleges in Taiwan were recruited. The students completed the 25-item Core Competence in Fundamental Nursing Practicum Scale, wherein both the importance and performance level of each item are indicated. One-way analysis of variance along with the Scheffe post hoc test and importance-performance analysis were used to explore the gaps between the perception of importance for competence and the perceived performance and to identify weak competencies that must be prioritized for improvement, respectively. RESULTS: Compared with nursing students practicing in district hospitals (predominantly caring for chronically ill patients), nursing students practicing in medical centres (predominantly caring for patients with severe and critical conditions) had larger gaps in total scores and the application of nursing processes. Students in medical centres also had larger gaps in professional attitude than their counterparts in long-term care facilities. Importance-performance analysis identified a common shortfall in communication skills among nursing students for all level-of-care practicum sites. Students at long-term facilities had the highest number of weak competencies that required improvement. The results of this study can guide instructors in designing curricular activities focused on the weaker core competencies of the students at a practicum site for each level of care. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contributions.

Cutting-edge pharmacotherapy for hepatitis C virus infection: a comprehensive review.

INTRODUCTION: Pharmacotherapy against hepatitis C virus (HCV) infection has tremendously improved since the advent of interferon (IFN)-free direct-acting antivirals (DAAs). Additionally, fixed-dose pangenotypic DAAs, which are safe, potent, easy for use, and can cover a wide spectrum of patients, have been recommended by professional guidelines for DAA-naïve and DAA-experienced patients with HCV. AREAS COVERED: We review the pharmacokinetics, pharmacodynamics, and potential drug-drug interactions (DDIs) of fixed-dose pangenotypic DAA regimens, including glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Additionally, we summarize the efficacy and safety of these regimens in clinical trials as well as real-world studies for treating different populations. Lastly, we discuss unmet medical needs in managing HCV in the era of fixed-dose pangenotypic DAAs. EXPERT OPINION: Protease inhibitors (PIs), including GLE and VOX, are prone to have more frequent DDIs, compared to the non-structural (NS) 5A and 5B inhibitors. These regimens are generally well tolerated and can be applied to different populations, except for the contraindicated use of PI-containing DAA regimens in decompensated cirrhosis. Using the first-line GLE/PIB and SOF/VEL can eradicate HCV in more than 95% of DAA-naïve patients across different populations. The viral cure usually exceeds 95% when using the rescue SOF/VEL/VOX regimen for prior DAA failures.

Comparison of supraglottic airway device and endotracheal tube in former preterm infants receiving general anesthesia: a randomized controlled trial.

To date, endotracheal tube (ETT) remains the mainstream for preterm infants receiving general anesthesia. We aim to compare the perioperative respiratory adverse events between using supraglottic airway device (SAD) and ETT in former preterm infants receiving general anesthesia. Former preterm infants below 52 weeks of postmenstrual age scheduled for herniorrhaphy were randomized to receive SAD or ETT for general anesthesia. Infants with severe congenital cardiopulmonary disease, prolonged oxygen or mechanical ventilation dependence, and recent respiratory tract infection were excluded. Muscle relaxant agents and opioids were avoided in this study. 40 infants were assigned into SAD or ETT groups. Infants in the SAD group had a much lower rate of intraoperative desaturation than those in the ETT group (21.1% vs. 73.7%, p = 0.003). Incidences of other intraoperative and postoperative 24-h respiratory adverse events were similar between groups, including laryngospasm/bronchospasm, cough and stridor during anesthesia, and postoperative apnea, bradycardia, and supplemental oxygen use. All participants were extubated successfully in the operation room. SAD is recommended in former preterm infants receiving general anesthesia for herniorrhaphy in their early infancy as it much decreases the incidence of intraoperative desaturation compared to ETT.

Developing Microelectrode Arrays for the Point-of-Care Multiplex Detection of Metabolites.

DNA-aptamer-functionalized electrode arrays can provide an intriguing method for detecting pathogen-derived exometabolites. This work addresses the limitations of previous aptamer-based pathogen detection methods by introducing a novel surface design that bridges the gap between initial efforts in this area and the demands of a point-of-care device. Specifically, the use of a diblock copolymer coating on a high-density microelectrode array and Cu-mediated cross coupling reactions that allow for the exclusive functionalization of that coating by any electrode or set of electrodes in the array provides a device that is stable for 1 year and compatible with the multiplex detection of small-molecule targets. The new chemistry developed allows one to take advantage of a large number of electrodes in the array with one experiment described herein capitalizing on the use of 960 individually addressable electrodes.

Predicaments and coping strategies in implementing cancer truth-telling: a qualitative content analysis.

PURPOSE: The patient-centered communication principles in Western countries are widely esteemed. In Eastern countries, a family-centered approach to medical decision-making is preferred. However, the predicaments faced by attending physicians and their coping strategies in the process of truth-telling about cancer are unknown. Therefore, this study aimed to understand attending physicians' predicaments and coping strategies in implementing truth-telling for cancer in Taiwan. METHODS: This study used a qualitative description approach to conduct in-depth interviews with attending physicians. Data were collected from two medical centers in Taiwan. Purposive sampling was also conducted. A total of 17 attending physicians participated in individual semi-structured interviews. All interviews were audio recorded and transcribed verbatim. Inductive content analysis was used to analyze and develop the subcategories, generic categories, and main categories. RESULTS: Four main categories emerged: (1) Causing harm to the patient: Family members' cooperation is needed. (2) Family members' request to conceal the truth: Physicians should judge based on the patient's disease condition. (3) Delayed treatment: Physicians should prioritize establishing confidence. (4) Delivering bad news about relapse: Physicians have different coping strategies. CONCLUSION: Physicians in Taiwan face challenges but prioritize family-centered care despite having coping strategies to protect patients. When faced with a scenario in which family members request concealment of truth, most physicians cooperate with them to determine the level and method of disclosing unfavorable news to patients. Physicians should prioritize patients' psychological needs when they experience relapse or metastasis or face strong negative emotions.

Dendritic cell vaccine for glioblastoma: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Dendritic cell (DC) vaccine is an emerging immunotherapy that could potentially improve glioblastoma survival. The first phase III clinical trial of DC vaccine was recently published. This meta-analysis aims to update and reappraise existing evidence on the efficacy of DC vaccine in patients with glioblastoma. METHODS: We searched PubMed, Embase, and Cochrane Library for clinical trials of DC vaccine for glioblastoma. The quality of the studies was assessed using the RoB 2.0 and ROBINS-I tools. The results of overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Summary effects were evaluated using random effects models. Trial sequential analysis (TSA) was performed. RESULTS: Seven clinical trials involving 3,619 patients were included. DC vaccine plus standard care was associated with significantly improved OS (HR = 0.71; 95% CI, 0.57 - 0.88) and PFS (HR = 0.65; 95% CI, 0.43 - 0.98). In the subgroup of newly diagnosed glioblastoma, DC vaccine was associated with improved PFS (HR = 0.59; 95% CI, 0.39 - 0.90). TSA of OS showed that the cumulative z-score line for the DC vaccine crossed the benefit boundary and reached the required sample size. TSA of PFS and subgroup analysis of newly diagnosed glioblastoma showed that the required sample size was not reached. CONCLUSIONS: This updated meta-analysis, which included the first phase III trial of a DC vaccine for glioblastoma, demonstrated that the DC vaccine was associated with improved OS. Moreover, TSA showed that the required sample size was reached, indicating a true-positive result. Future studies are required for patient subgroups with newly diagnosed and recurrent glioblastoma.

Clinical performance of Bladder EpiCheck™ versus voided urine cytology for detecting recurrence of nonmuscle invasive bladder cancer: Systematic review and meta-analysis.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) has a favorable prognosis but has high propensity for recurrence. Recent development in one of the urinary biomarker tests, Bladder EpiCheck™, offers a noninvasive and accurate method to detect NMIBC recurrence. In this study, we aimed to compare the diagnostic performance of Bladder EpiCheck™ with urine cytology to detect NMIBC recurrence. METHODS: We performed a systematic review search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to July 2023. Diagnostic accuracy was defined by sensitivity, negative predictive value (NPV), specificity, and positive predictive value (PPV). RESULTS: A total of 6 studies involving 1588 patients were included. Bladder EpiCheck™ has a sensitivity and specificity of 0.81 (95% CI: 0.63-0.91; I2: 43%) and 0.87 (95% CI: 0.83-0.91; I2: 20%), respectively. On the other hand, urine cytology has a sensitivity and specificity of 0.63 (95% CI: 0.29-0.87; I2: 61%) and 0.97 (95% CI: 0.78-1.00; I2: 79%), respectively. EpiCheck™ has a higher NPV (0.94 (95% CI: 0.87-0.97) vs. 0.84 (95% CI: 0.80-0.87) though a lower PPV (0.62 (95% CI: 0.45-0.76) vs. 0.87 (95% CI: 0.56-0.97) than urine cytology. In our subgroup analysis, the sensitivity of Bladder EpiCheck™ for detecting high-grade tumors improved to 0.90 (95% CI: 0.83-0.94) while that for urine cytology improved to 0.72 (95% CI: 0.50-0.87). CONCLUSION: Bladder EpiCheck™ has a high sensitivity and NPV for detecting recurrence among patients with NMIBC.