The present study aimed to conduct a comprehensive meta-analysis to assess the diagnostic value of fluorometric assays and tandem mass spectrometry (MS/MS) for hyperphenylalaninemia (HPA) and its subtypes. The PubMed, Embase and Cochrane Library databases were searched from inception to October 2023. The present study included studies that reported the newborn screening and genetic features of patients with HPA and excluded duplicate publications, studies without full text, studies with incomplete information, studies from which it was not possible to extract data, animal experiments, reviews and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results revealed that 0.04% [95% confidence interval (CI): 0.019-0.069] of neonatal HPA fluorometric assays and MS/MS. The positive predictive value (PPV) of neonatal HPA screening using fluorometric assays and tandem mass spectrometry was 31.7% (95% CI: 19.6-45.2). Notably, the PPV of neonatal HPA screening using fluorometric assays was 8.3% (95% CI: 7.1-9.6), while the PPV of neonatal HPA screening using tandem mass spectrometry was 31.8% (95% CI: 16.4-49.4). Additionally, the pooled results showed that the incidence of tetrahydrobiopterin deficiency (BH4D) in HPA patients was 12.43% (95% CI: 3.28-25.75) and the incidence of phenylalanine hydroxylase deficiency (PAHD) in HPA patients was 88.65% (95% CI: 78.84-95.86). Newborn screening is an effective method for the early detection of HPA and MS/MS has a greater PPA than fluorometric assays for diagnosing HPA. In addition, in the screening of HPA, the proportion of HPA patients with PAHD was significantly higher than that of patients with BH4D.

The nasal potential difference test (nPD) is an electrophysiological measurement which is altered in patients and animal models with cystic fibrosis (CF). Because protocols and outcomes vary substantially between laboratories, there are concerns over its validity and precision. We performed a systematic literature review (SR) of the nPD to answer the following review questions: A. Is the nasal potential difference similarly affected in CF patients and animal models?\", and B. \"Is the nPD in human patients and animal models of CF similarly affected by various changes in the experimental set-up?\". The review protocol was preregistered on PROSPERO (CRD42021236047). We searched PubMed and Embase with comprehensive search strings. Two independent reviewers screened all references for inclusion and extracted all data. Included were studies about CF which described in vivo nPD measurements in separate CF and control groups. Risk of bias was assessed, and three meta-analyses were performed. We included 130 references describing nPD values for CF and control subjects, which confirmed substantial variation in the experimental design and nPD outcome between groups. The meta-analyses showed a clear difference in baseline nPD values between CF and control subjects, both in animals and in humans. However, baseline nPD values were, on average, lower in animal than in human studies. Reporting of experimental details was poor for both animal and human studies, and urgently needs to improve to ensure reproducibility of experiments within and between species.

UNASSIGNED: Predicting the severity of acute pancreatitis (AP) early poses a challenge in clinical practice. While there are well-established clinical scoring tools, their actual predictive performance remains uncertain. Various studies have explored the application of machine-learning methods for early AP prediction. However, a more comprehensive evidence-based assessment is needed to determine their predictive accuracy. Hence, this systematic review and meta-analysis aimed to evaluate the predictive accuracy of machine learning in assessing the severity of AP.
UNASSIGNED: PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched until December 5, 2023. The risk of bias in eligible studies was assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Subgroup analyses, based on different machine learning types, were performed. Additionally, the predictive accuracy of mainstream scoring tools was summarized.
UNASSIGNED: This systematic review ultimately included 33 original studies. The pooled c-index in both the training and validation sets was 0.87 (95 % CI: 0.84-0.89) and 0.88 (95 % CI: 0.86-0.90), respectively. The sensitivity in the training set was 0.81 (95 % CI: 0.77-0.84), and in the validation set, it was 0.79 (95 % CI: 0.71-0.85). The specificity in the training set was 0.84 (95 % CI: 0.78-0.89), and in the validation set, it was 0.90 (95 % CI: 0.86-0.93). The primary model incorporated was logistic regression; however, its predictive accuracy was found to be inferior to that of neural networks, random forests, and xgboost. The pooled c-index of the APACHE II, BISAP, and Ranson were 0.74 (95 % CI: 0.68-0.80), 0.77 (95 % CI: 0.70-0.85), and 0.74 (95 % CI: 0.68-0.79), respectively.
UNASSIGNED: Machine learning demonstrates excellent accuracy in predicting the severity of AP, providing a reference for updating or developing a straightforward clinical prediction tool.

BACKGROUND: RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial.
METHODS: We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups.
RESULTS: Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47-5.73) and 2.69 (1.82-3.98)] and OS [HRs = 2.66 (1.95-3.65) and 2.45 (1.55-3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (Pinteraction < 0.01 for PFS). Patients with tumors with any mutation in the KRAS/NRAS/BRAF/PIK3CA gene also showed similar results compared with all wild-type tumors (Pinteraction for PFS, OS, and ORR were < 0.01, < 0.01 and 0.01, respectively). While low miR-31-3p expression could predict PFS (Pinteraction = 0.01) and OS (Pinteraction = 0.04) benefit. The prognostic and predictive value regarding PIK3CA mutations, PTEN mutations or deletions, EGFR, EREG/AREG, HER2, HER3, and HER4 expression remains uncertain.
CONCLUSIONS: In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.

UNASSIGNED: Neutrophil gelatin lipase carrier protein (NGAL) has been used as an early biomarker to predict acute kidney injury (AKI). However, the predictive value of NGAL in urine and blood in children with acute kidney injury in different backgrounds remains unclear. Therefore, we conducted this systematic review and meta-analysis to explore the clinical value of NGAL in predicting AKI in children.
UNASSIGNED: Computerized databases were searched for relevant the studies published through August 4th, 2022, which included PUBMED, EMBASE, COCHRANE and Web of science. The risk of bias of the original included studies was assessed by using the Quality Assessment of Studies for Diagnostic Accuracy (QUADA-2). At the same time, subgroup analysis of these data was carried out.
UNASSIGNED: Fifty-three studies were included in this meta-analysis, involving 5,049 patients, 1,861 of whom were AKI patients. The sensitivity and specificity of blood NGAL for predicting AKI were 0.79 (95% CI: 0.69-0.86) and 0.85 (95% CI: 0.75-0.91), respectively, and SROC was 0.89 (95% CI: 0.86-0.91). The sensitivity and specificity of urine NGAL for predicting AKI were 0.83 (95% CI: 0.78-0.87) and 0.81 (95% CI: 0.77-0.85), respectively, and SROC was 0.89 (95% CI: 0.86-0.91). Meanwhile, the sensitivity and specificity of overall NGAL (urine and blood NGAL) for predicting AKI in children were 0.82 (95% CI: 0.77-0.86) and 0.82 (95% CI: 0.78-0.86), respectively, and SROC was 0.89 (95% CI: 0.86-0.91).
UNASSIGNED: NGAL is a valuable predictor for AKI in children under different backgrounds. There is no significant difference in the prediction accuracy between urine NGAL and blood NGAL, and there is also no significant difference in different measurement methods of NGAL. Hence, NGAL is a non-invasive option in clinical practice. Based on the current evidence, the accuracy of NGAL measurement is the best at 2 h after cardiopulmonary bypass (CPB) and 24 h after birth in asphyxiated newborns.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022360157.

To calculate the predictive value and thus the clinical usefulness of transvaginal ultrasound (US) imaging for the management of deep endometriosis, knowing that the positive predictive value (PPV) varies with the prevalence and probably with the volume and location of the disease.
After registration on PROSPERO (CRD42022366323), PubMed was searched for all reports describing the diagnostic accuracy of US imaging for deep endometriosis published between January 1, 2000, and October 20, 2022.
The 536 articles on \"endometriosis AND US And diagnosis\" were hand searched, and 30 reports describing sensitivity and specificity of deep endometriosis were found. Besides sensitivity and specificity, the prevalence, localization, and size of deep endometriosis lesions were collected.
Prevalences of deep endometriosis were reported only twice as 12% and 32% by ultrasonographers. In women undergoing surgery, prevalences vary between 40% and 100% because of the variable inclusion criteria. Specificity is higher than sensitivity for all locations: rectovaginal (97% [86-100] vs 74% [31-95], p = .0002), rectosigmoid (97% [63-100] vs 88% [37-97], p = .0082), vesicouterine (100% [97-100] vs 63% [22-100], p = .0021), and uterosacrals (91% [77-99] vs 68% [18-83], p = .0005). Notwithstanding improved equipment, accuracy did not vary over the last 20 years. Sensitivities or specificities have not been stratified by the size of the lesion, and thus, the lower detection limits are not known. In the absence of blinding, the usefulness for surgery could not be established.
The reported sensitivities and specificities of transvaginal US are not only those of imaging but include symptoms and clinical examinations. In referral centers, the reported PPVs are high (94%-100%) given that prevalences are >10% and specificities are >95%. However, the extrapolation of the clinical use before surgical interventions should be considered with care, given that PPVs for smaller lesions and the lower detection limit are unknown and surgeons were not blinded to US results.

Awareness and prompt recognition of sepsis are essential for nurses working in the emergency department (ED), enabling them to make an initial assessment of patients and then to sort them according to their condition s severity. The aim of this systematic review was to investigate prognostic accuracy in detecting sepsis in the emergency department by comparing the previous sepsis-2 screening tool, the Systemic Inflammatory Response Syndrome (SIRS) and the current sepsis-3 screening tool, the Quick Sequential Organ Failure Assessment (qSOFA).
This systematic review used the guideline by Bettany-Saltikov and McSherry and was reported according to the Preferred Reporting Items for Systematic Reviews and meta-Analyses (PRISMA) 2020 checklist. The protocol was registered in PROSPERO. A systematic search was conducted using the CINAHL, EMBASE and MEDLINE databases. Study selection and risk of bias was performed independently by pair of authors.
Five articles were included. Overall, SIRS showed higher sensitivity than qSOFA, while qSOFA showed higher specificity than SIRS. The positive predictive value for qSOFA was superior, while there was a minor deviation in negative predictive value between qSOFA and SIRS.
The overall recommendation based on the included studies indicates that qSOFA is the better-suited screening tool for prognostic accuracy in detecting sepsis in the emergency department.

At present, surgical resection of primary intramedullary spinal cord tumors is the mainstay of treatment. However, given the dimensional constraints of the narrow spinal canal and dense organization of the ascending and descending tracts, intramedullary spinal cord tumor resection carries a significant risk of iatrogenic neurological injury. Intraoperative neurophysiological monitoring (IONM) and mapping techniques have been developed to evaluate the functional integrity of the essential neural pathways and optimize the surgical strategies. IONM can also inform on impending harm to at-risk structures and can correlate with postoperative functional recovery if damage has occurred. Direct waves (D-waves) will provide immediate feedback on the integrity of the lateral corticospinal tract. In the present review, we have provided an update on the utility of D-waves for spinal cord tumor resection. We have highlighted the neuroanatomical and neurophysiological insights from the use of D-wave monitoring, the technical considerations and limitations of the D-wave technique, and multimodal co-monitoring with motor-evoked potentials and somatosensory-evoked potentials. Together with motor-evoked potentials, D-waves can help to guide the extent of tumor resection and provide intraoperative warning signs and alarm criteria to direct the surgical strategy. D-waves can also serve as prognostic biomarkers for long-term recovery of postoperative motor function. We propose that the use of D-wave IONM can contribute key findings for clinical decision-making during spinal cord tumor resection.

UNASSIGNED: Patients with severe acute kidney injury (AKI) may require renal replacement therapy (RRT), such as hemodialysis and peritoneal dialysis. Neutrophil gelatinase-associated lipocalin (NGAL) is a sensitive indicator for early diagnosis and recognition of AKI; however, its predictive value of AKI-associated need for RRT needs further evaluation.
UNASSIGNED: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, relevant articles were systematically searched and selected from seven databases. The random effects model was applied to evaluate the predictive performance of NGAL for AKI requiring RRT. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of each included study.
UNASSIGNED: A total of 18 studies including 1,787 patients with AKI and having an average NOS score of 7.67 were included in the meta-analysis. For plasma/serum NGAL, the pooled sensitivity and specificity with corresponding 95% confidence interval (CI) were 0.75 (95% CI: 0.68-0.81) and 0.76 (95% CI: 0.70-0.81), respectively. The pooled positive likelihood ratio (PLR) was 2.9 (95% CI: 2.1-4.1), and the pooled negative likelihood ratio (NLR) was 0.34 (95% CI: 0.25-0.46). Subsequently, the pooled diagnostic odds ratio (DOR) was 9 (95% CI: 5-16) using a random effects model, and the area under the curve (AUC) of summary receiver operating characteristic to summarize predictive accuracy was 0.82 (95% CI: 0.79-0.85). For urine NGAL, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC values were 0.78 (95% CI: 0.61-0.90), 0.77 (95% CI: 0.65-0.85), 3.4 (95% CI: 2.4-4.8), 0.28 (95% CI: 0.15-0.52), 12 (95% CI: 6-24), and 0.84 (95% CI: 0.80-0.87), respectively.
UNASSIGNED: Plasma/serum and urine NGAL levels performed comparably well in predicting AKI requiring RRT. Our findings suggested that NGAL is an effective predictive biomarker for the AKI-associated need for RRT. Nevertheless, more pieces of high-quality evidence and future trials with larger sample sizes are needed for further improvement of patient outcomes.
UNASSIGNED: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022346595], identifier [CRD42022346595].

The diagnostic accuracy of cell-free fetal DNA in screening for rare autosomal trisomies is uncertain. We conducted a systematic review and meta-analysis aiming to determine the predictive value of cell-free DNA in screening for rare autosomal trisomies.
PubMed, Embase, and Web of Science were searched from inception to January 2022.
All studies that reported on the diagnostic accuracy of cell-free DNA in the detection of rare autosomal trisomies were included. Case series were included if they contained at least 10 cases with diagnostic test results or postnatal genetic testing.
Study appraisal was completed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed using random-effects meta-analysis of double-arcsine transformed proportions of confirmed results in the fetus out of the positive tests to obtain a pooled estimate of the positive predictive value.
The search identified 7553 studies, of which 1852 were duplicates. After screening 5701 titles and abstracts, 380 studies proceeded to the full-text screen; 206 articles were retrieved for data extraction, of which another 175 articles were excluded. A total of 31 studies, with a total of 1703 women were included for analysis. The pooled positive predictive value of cell-free DNA for the diagnosis of rare autosomal trisomies was 11.46% (95% confidence interval, 7.80-15.65). Statistical heterogeneity was high (I2=82%). Sensitivity analysis restricted to 5 studies at low risk of bias demonstrated a pooled positive predictive value of 9.13% (95% confidence interval, 2.49-18.76). There were insufficient data to provide accurate ascertainment of sensitivity and specificity because most studies only offered confirmatory tests to women with high-risk results.
The positive predictive value of cell-free DNA in diagnosing rare autosomal trisomies is approximately 11%. Clinicians should provide this information when offering cell-free DNA for screening of conditions outside of common autosomal trisomies.