Do We Need to Administer Fludrocortisone in Addition to Hydrocortisone in Adult Patients With Septic Shock? An Updated Systematic Review With Bayesian Network Meta-Analysis of Randomized Controlled Trials and an Observational Study With Target Trial Emulation.

OBJECTIVES: This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone, compared with placebo in adult patients with septic shock. DATA SOURCES: By extending a prior Cochrane review, databases, including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov , along with other relevant websites, were searched until August 31, 2023. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies using target trial emulation were included. DATA EXTRACTION: The primary outcome was short-term mortality with an emphasis on 28- or 30-day mortality as the main measure and in-hospital or ICU mortality as the nearest surrogate of this measure. Three of the most common adverse events, namely, gastroduodenal bleeding, superinfection, and hyperglycemia, were also considered. DATA SYNTHESIS: A total of 19 studies involving 95,841 patients were included. Hydrocortisone plus fludrocortisone showed the lowest short-term mortality versus placebo (odds ratio [OR]: 0.79; 95% credible interval [CrI], 0.64-0.99; number needed to treat [NNT]: 21, range: 12-500; low certainty of evidence) in terms of informative priors. The surface under the cumulative ranking curve values for hydrocortisone plus fludrocortisone, hydrocortisone alone, and placebo were 0.9469, 0.4542, and 0.0989, respectively. Consistent results were observed in RCTs alone and those using a daily 200-mg dose of hydrocortisone. Although gastroduodenal bleeding or superinfection showed no clear increase, hyperglycemia risk increased. The ORs were 0.53 for placebo versus hydrocortisone plus fludrocortisone and 0.64 for placebo versus hydrocortisone alone, with very low certainty of evidence. CONCLUSIONS: In adults with septic shock, hydrocortisone plus fludrocortisone improved short-term survival with minimal adverse events compared with hydrocortisone alone or placebo. However, these findings are not definitive due to the limited certainty of evidence and wide NNT range. Additional large-scale, placebo-controlled RCTs are needed to provide conclusive evidence.

Blood Purification for Adult Patients With Severe Infection or Sepsis/Septic Shock: A Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis. DATA SOURCES: We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions. STUDY SELECTION: Only randomized controlled trials (RCTs) were selected. DATA EXTRACTION: The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement. DATA SYNTHESIS: We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57-0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42-0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy. CONCLUSIONS: Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification.

Efficacy of brief behavioural therapy for insomnia in older adults with chronic insomnia: a systematic review and meta-analysis from randomised trials.

BACKGROUND: chronic insomnia is a highly prevalent and persistent health concern among older adults, and it has significant adverse effects on cognitive function and physical health. OBJECTIVES: the study aimed to evaluate the efficacy of a brief 4-week behavioural therapy for insomnia (BBTi) on insomnia remission in older adults with chronic insomnia. DESIGN: a systematic review and meta-analysis were conducted. SUBJECTS: adults aged 60 years or older. METHODS: eight electronic databases were systematically searched through the end of March 2022. Studies followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement. RESULTS: four randomised controlled trials (190 subjects) were included. The mean age of the participants was 69.06 (65.10-71.65), and 29.9% (27.3-32.3%) were male. Older adults who received the BBTi showed a significant insomnia remission (standardised mean differences, -1.07; 95% confidence interval, -1.43 to -0.71; I2, 0%). Sleep parameters measured by actigraphy revealed that in older adults, the BBTi program significantly improved total sleep time, wake after sleep onset (WASO), sleep onset latency (SOL) and sleep efficacy (SE) compared to the controls. For the subjective sleep parameters measured the by sleep diary, older adults who received BBTi obtained a more effective improvement in WASO, SE and SOL. The overall risk of bias was mostly low or of some concern due to the difficulty of blinding participants and assessors. CONCLUSIONS: a 4-week BBTi program can be considered an effective and nonselective intervention for insomnia remission among older adults with chronic insomnia and thereby has the potential to ameliorate WASO, SE and SOL.

Effect of exercise on slowing breastfeeding-induced bone loss: A meta-analysis and trial sequential analysis.

AIM: This study systematically reviewed evidence regarding the effectiveness of exercise in slowing breastfeeding-induced bone loss. METHODS: The evidence-based approach of a systematic review (PROSPERO registration No. CRD42019111623) was adopted. The inclusion criteria were randomized controlled trials or observational studies. Study samples were breastfeeding women, the intervention was any form of exercise, and bone mineral density (BMD) of the total body, lumbar spine and hip/femur neck before 6 months and at 1 year were the outcome measures. Meta-analyses were performed using a random effect model, and calculations of mean differences of BMD change and 95% confidence intervals (CIs) were carried out. Studies were further evaluated through trial sequential meta-analysis (TSA), and the 'Grading of Recommendations Assessment, Development and Evaluation' methodology was used to assess the certainty of evidence (CoE). RESULTS: A total of 1049 studies were screened, and 4 met the inclusion criteria. Weight-bearing aerobic exercise and resistance training before the 6-month evaluation slowed breastfeeding-induced bone loss in the lumbar spine (1.62% BMD change [95% CI = 0.53-2.71]; I2 = 8%). The TSA Z-curve revealed crossing of the TSA boundary and line of information size, indicating sufficient sampling and significance. The CoE of exercise benefit in the lumbar spine at 6 months was low, whereas the CoE for other areas ranged from low to very low. CONCLUSION: This first systematic review and meta-analysis provided some evidence of the advantages of exercise for slowing breastfeeding-induced bone loss. However, additional randomized controlled trials are warranted to generate more conclusive evidence.

Comparing fine motor performance among young children with autism spectrum disorder, intellectual disability, attention-deficit/hyperactivity disorder, and specific developmental disorder of motor function.

Objective: The acquisition of fine motor skills is considered to be a crucial developmental milestone throughout early childhood. This study aimed to investigate the fine motor performance of young children with different disability diagnoses. Methods: We enrolled a sample of 1,897 young children under the age of 6 years who were at risk of developmental delays and were identified by a transdisciplinary team. A series of standardized developmental assessments included the Bayley Scales of Infant Development-Third Edition, Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition, Peabody Developmental Motor Scale-Second Edition, and Movement Assessment Battery for Children-Second Edition were used. Retrospective chart reviews were conducted on all children to identify specific developmental disorders. The number of autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), comorbidity, motor dysfunction, and unspecified developmental delays (DD) were 363 (19.1%), 223 (11.8%), 234 (12.3%), 285 (15.0%), 128 (6.7%), and 590 (31.1%), respectively. Results: Young children with ID, comorbidity, and motor dysfunction demonstrated significant difficulty in performing manual dexterity and visual motor integration tasks and scored significantly lower in these areas than children with ASD, ADHD, and unspecified DD. In addition, fine motor performance was associated with cognitive ability in children with different disability diagnoses, indicating that young children showed better fine motor performance when they demonstrated better cognitive ability. Conclusion: Our findings support that differences in fine motor performance differ by disability type. Close links between fine motor performance and cognitive ability in children under the age of 6 years were seen in all disability types.

Prognostic nutritional index as a predictive marker for acute kidney injury in adult critical illness population: a systematic review and diagnostic test accuracy meta-analysis.

BACKGROUND: The prognostic nutritional index (PNI), integrating nutrition and inflammation markers, has been increasingly recognized as a prognostic predictor in diverse patient cohorts. Recently, its effectiveness as a predictive marker for acute kidney injury (AKI) in various clinical settings has gained attention. This study aims to assess the predictive accuracy of the PNI for AKI in critically ill populations through systematic review and meta-analysis. METHODS: A systematic review was conducted using the databases MEDLINE, EMBASE, PubMed, and China National Knowledge Infrastructure up to August 2023. The included trials reported the PNI assessment in adult population with critical illness and its predictive capacity for AKI. Data on study characteristics, subgroup covariates, and diagnostic performance of PNI, including sensitivity, specificity, and event rates, were extracted. A diagnostic test accuracy meta-analysis was performed. Subgroup analyses and meta-regression were utilized to investigate the sources of heterogeneity. The GRADE framework evaluated the confidence in the meta-analysis's evidence. RESULTS: The analysis encompassed 16 studies with 17 separate cohorts, totaling 21,239 patients. The pooled sensitivity and specificity of PNI for AKI prediction were 0.67 (95% CI 0.58-0.74) and 0.74 (95% CI 0.67-0.80), respectively. The pooled positive likelihood ratio was 2.49 (95% CI 1.99-3.11; low certainty), and the negative likelihood ratio was 0.46 (95% CI 0.37-0.56; low certainty). The pooled diagnostic odds ratio was 5.54 (95% CI 3.80-8.07), with an area under curve of summary receiver operating characteristics of 0.76. Subgroup analysis showed that PNI's sensitivity was higher in medical populations than in surgical populations (0.72 vs. 0.55; p < 0.05) and in studies excluding patients with chronic kidney disease (CKD) than in those including them (0.75 vs. 0.56; p < 0.01). Overall, diagnostic performance was superior in the non-chronic kidney disease group. CONCLUSION: Our study demonstrated that PNI has practical accuracy for predicting the development of AKI in critically ill populations, with superior diagnostic performance observed in medical and non-CKD populations. However, the diagnostic efficacy of the PNI has significant heterogeneity with different cutoff value, indicating the need for further research.

Beyond traditional therapies: a network meta-analysis on the treatment efficacy for chronic phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear. OBJECTIVE: The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP. EVIDENCE REVIEW: We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events. FINDINGS: The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low). CONCLUSIONS: The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs. PROSPERO REGISTRATION NUMBER: CRD42023455949.

Effectiveness and Adverse Events of Gabapentinoids as Analgesics for Patients with Burn Injuries: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

(1) Background: Pain after a burn injury is difficult to endure, and emerging studies aim to ascertain the effects of gabapentin and pregabalin as non-opioid treatment options. (2) Methods: We searched for randomised controlled trials (RCTs) in six databases. The risk of bias was assessed using the RoB 2.0 tool. We performed meta-analysis and trial sequential analysis and used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology for judging the certainty of evidence (CoE). (3) Results: Five RCTs were included. Compared with placebo, gabapentinoids significantly decreased the pain intensity within 24 h (mean difference (MD) = -1.06, 95% confidence interval (CI): -1.47--0.65) and from 72 h to 9 days (MD = -0.82, 95% CI: -1.16--0.48), but not after 3 weeks (MD = -0.44, 95% CI: -1.31-0.42). Opioid consumption (mg/day) was reduced within 24 h (MD = -13.34, 95% CI: -22.16--4.52) and from 72 h to 9 days (MD = -7.87, 95% CI: -14.82--0.91). Increased risks of drowsiness (risk ratio (RR) = 3.255, 95% CI: 1.135-9.335) and dizziness (RR = 3.034, 95% CI: 1.006-9.147) were observed, but sensitivity analysis using the Bayesian method showed no increased risk. All endpoints were judged as low to very low CoE. (4) Conclusions: Gabapentinoids offer modest analgesic benefits as a component of multimodal pain management for burn injuries of less than 3 weeks. The adverse effects should be carefully monitored. Large-scale RCTs are warranted for the reinforcement of CoE in clinical use.

Can The 'Speed Bump Sign' Be a Diagnostic Tool for Acute Appendicitis? Evidence-Based Appraisal by Meta-Analysis and GRADE.

OBJECTIVES: The 'speed bump sign' is a clinical symptom characterised by aggravated abdominal pain while driving over speed bumps. This study aimed to perform a diagnostic meta-analysis, rate the certainty of evidence (CoE) and analyse the applicability of the speed bump sign in the diagnosis of acute appendicitis. MATERIALS AND METHODS: Four databanks and websites were systemically searched, and the Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias. Meta-analysis was assessed by MIDAS commands in Stata 15. Grading of Recommendations, Assessment, Development and Evaluation methodology was applied to examine the CoE. RESULTS: Four studies with 343 participants were included. The pooled sensitivity and specificity were 0.94 (95% CI (confidence interval) = 0.83-0.98; I2 = 79%) and 0.49 (95% CI = 0.33-0.66; I2 = 67%), respectively. The area under the summary receiver operating characteristic curve was 0.78 (95% CI = 0.74-0.81). The diagnostic odds ratio was 14.1 (95% CI = 3.6-55.7). The pooled positive and negative likelihood ratios (LR (+) and LR (-)) were 1.84 (95% CI = 1.30-2.61) and 0.13 (95% CI = 0.04-0.41), respectively. According to Fagan's nomogram plot, when the pretest probabilities were 25%, 50% and 75%, the related posttest probabilities increased to 38%, 65% and 85% calculated through LR (+), respectively, and the posttest probabilities were 4%, 12% and 28% calculated through LR (-), respectively. The overall CoEs were low and very low in sensitivity and specificity, respectively. CONCLUSION: Current evidence shows that the speed bump sign is a useful 'rule-out' test for diagnosing acute appendicitis. With good accessibility, the speed bump sign may be added as a routine part of taking the history of patients with abdominal pain.

Should We Use High-Flow Nasal Cannula in Patients Receiving Gastrointestinal Endoscopies? Critical Appraisals through Updated Meta-Analyses with Multiple Methodologies and Depiction of Certainty of Evidence.

(1) Background: High-flow nasal cannula (HFNC) therapy or conventional oxygen therapy (COT) are typically applied during gastrointestinal (GI) endoscopic sedation. (2) Methods: We conducted a rigorous systematic review enrolling randomized controlled trials (RCTs) from five databases. Risk of bias was assessed using Cochrane's RoB 2.0 tool; certainty of evidence (CoE) was assessed using GRADE framework. Meta-analysis was conducted using inverse-variance heterogeneity model and presented as relative risk (RR) with 95% confidence interval (CI). Trial sequential analysis was performed, and sensitivity analysis was conducted with Bayesian approach. (3) Results: Eight RCTs were included. Compared to COT, HFNC did not reduce the overall incidence of hypoxemia (RR 0.51; 95% CI 0.24-1.09; CoE: very low) but might reduce the incidence of hypoxemia in patients at moderate to high risk for hypoxemia (RR 0.54; 95% CI 0.31-0.96; and CoE: very low). HFNC might reduce the incidence of severe hypoxemia (RR 0.38; 95% CI 0.20-0.74; and CoE: low). HFNC might not affect the need of minor airway interventions (RR 0.31; 95% CI 0.08-1.22; and CoE: very low) and had no effect on procedure duration (CoE: very low); (4) Conclusions: During GI endoscopic sedation, HFNC might reduce the incidence of hypoxemia in patients at moderate to high risk for hypoxemia and prevent severe hypoxemia.

Should we believe the benefit of intravenous erythromycin in critically ill adults with gastric feeding intolerance? Reinspecting the pieces of evidence from a series of meta-analyses.

BACKGROUND: In critically ill adults, unachieved nutrition targets owing to feeding intolerance are associated with poor outcomes. Erythromycin, a macrolide of antibiotics, exerts its gastrointestinal prokinetic as a motilin receptor agonist and subsequently promotes bowel movement. The application of erythromycin has been mentioned in the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline with a grade B recommendation and strong consensus based on significant results from a meta-analysis of only three randomized controlled trials in a Mantel-Haenszel random-effects model. METHODS: We reinspected the evidence by a random-effects model of meta-analyses through the frequentist approach with the Hartung-Knapp-Sidik-Jonkman (HKSJ) method, trial sequential analysis (TSA), and Bayesian inference. RESULTS: The results analyzed by the HKSJ method showed a risk ratio (RR) of 0.50 (95% confidence interval, 0.19-1.33; I2 = 74.55%). TSA indicated the false-positive results with insufficient cases. Bayesian inference showed a RR of 0.38 (95% credible interval, 0.04-1.62). CONCLUSIONS: The effect of intravenous erythromycin in feeding intolerance for critically ill adults remained inconclusive, with very low certainty of evidence. Further large-scale randomized controlled trials with increased rigor are warranted to provide a solid conclusion.

Movement-based mind-body interventions for cardiac rehabilitation: An updated systematic review of randomized controlled trials.

This study aimed to assess evidence for the effect of movement-based mind-body interventions (MMBIs) for cardiac rehabilitation (CR). Six databases were searched from January 1995 to September 2020. All randomized controlled trials (RCTs) evaluated the effect of MMBIs on heart disease (HD) patients' physical and psychological outcomes. Two reviewers independently assessed the quality of all the included studies using the revised Cochrane risk-of-bias tool for RCTs. Sixteen RCTs (5160 participants) published between 1996 and 2020 met all inclusion criteria. In total, these studies investigated the effect of MMBIs for CR. Outcome measures that emerged in these studies included physical and psychological, and/or biochemical parameters to comprehensively evaluate the effects of MMBIs on HD patients. Overall, these studies suggest that MMBIs seem to be an alternative with the optimal CR option.

Comparison between Prehospital Mechanical Cardiopulmonary Resuscitation (CPR) Devices and Manual CPR for Out-of-Hospital Cardiac Arrest: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.

In pre-hospital settings, efficient cardiopulmonary resuscitation (CPR) is challenging; therefore, the application of mechanical CPR devices continues to increase. However, the evidence of the benefits of using mechanical CPR devices in pre-hospital settings for adult out-of-hospital cardiac arrest (OHCA) is controversial. This meta-analysis compared the effects of mechanical and manual CPR applied in the pre-hospital stage on clinical outcomes after OHCA. Cochrane Library, PubMed, Embase, and ClinicalTrials.gov were searched from inception until October 2021. Studies comparing mechanical and manual CPR applied in the pre-hospital stage for survival outcomes of adult OHCA were eligible. Data abstraction, quality assessment, meta-analysis, trial sequential analysis (TSA), and grading of recommendations, assessment, development, and evaluation were conducted. Seven randomized controlled and 15 observational studies were included. Compared to manual CPR, pre-hospital use of mechanical CPR showed a positive effect in achieving return of spontaneous circulation (ROSC) and survival to admission. No difference was found in survival to discharge and discharge with favorable neurological status, with inconclusive results in TSA. In conclusion, pre-hospital use of mechanical CPR devices may benefit adult OHCA in achieving ROSC and survival to admission. With low certainty of evidence, more well-designed large-scale randomized controlled trials are needed to validate these findings.

Effective Perturbations by Phenobarbital on INa, IK(erg), IK(M) and IK(DR) during Pulse Train Stimulation in Neuroblastoma Neuro-2a Cells.

Phenobarbital (PHB, Luminal Sodium®) is a medication of the barbiturate and has long been recognized to be an anticonvulsant and a hypnotic because it can facilitate synaptic inhibition in the central nervous system through acting on the γ-aminobutyric acid (GABA) type A (GABAA) receptors. However, to what extent PHB could directly perturb the magnitude and gating of different plasmalemmal ionic currents is not thoroughly explored. In neuroblastoma Neuro-2a cells, we found that PHB effectively suppressed the magnitude of voltage-gated Na+ current (INa) in a concentration-dependent fashion, with an effective IC50 value of 83 µM. The cumulative inhibition of INa, evoked by pulse train stimulation, was enhanced by PHB. However, tefluthrin, an activator of INa, could attenuate PHB-induced reduction in the decaying time constant of INa inhibition evoked by pulse train stimuli. In addition, the erg (ether-à-go-go-related gene)-mediated K+ current (IK(erg)) was also blocked by PHB. The PHB-mediated inhibition on IK(erg) could not be overcome by flumazenil (GABA antagonist) or chlorotoxin (chloride channel blocker). The PHB reduced the recovery of IK(erg) by a two-step voltage protocol with a geometrics-based progression, but it increased the decaying rate of IK(erg), evoked by the envelope-of-tail method. About the M-type K+ currents (IK(M)), PHB caused a reduction of its amplitude, which could not be counteracted by flumazenil or chlorotoxin, and PHB could enhance its cumulative inhibition during pulse train stimulation. Moreover, the magnitude of delayed-rectifier K+ current (IK(DR)) was inhibited by PHB, while the cumulative inhibition of IK(DR) during 10 s of repetitive stimulation was enhanced. Multiple ionic currents during pulse train stimulation were subject to PHB, and neither GABA antagonist nor chloride channel blocker could counteract these PHB-induced reductions. It suggests that these actions might conceivably participate in different functional activities of excitable cells and be independent of GABAA receptors.

Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats.

BACKGROUND: Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE). Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. METHODS: We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7) rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. RESULTS: Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. CONCLUSION: These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

Estimation of the secondary attack rate of COVID-19 using proportional meta-analysis of nationwide contact tracing data in Taiwan.

Crude secondary attack rate (SAR) of COVID-19 in Taiwan was 0.84% using nationwide contact-tracing data till April 8, 2020. The random-effect Bayesian metaanalysis yielded 95% credible intervals of 0.42%-1.69% and 0.08%-8.32%, respectively, for estimated SAR pooling from 15 case series and for predicted SAR in the future if pandemic continues.

Can preoperative neutrophil-to-lymphocyte ratio predict in-hospital mortality in postoperative patients with Stanford type A aortic dissection? Evidence-based appraisal by meta-analysis and GRADE.

OBJECTIVES: In-hospital mortality in postoperative patients with type A aortic dissection (AAD) is high. Neutrophil-to-lymphocyte ratio (NLR) is a novel predictor of adverse outcomes in many cardiovascular diseases. We examine NLR as a predictive tool in AAD in this meta-analysis. MATERIALS AND METHODS: We systematically searched in four databanks. Risk of bias was appraised using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The midas and metandi commands in Stata 15 were used for the meta-analysis. The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation methodology (GRADE). RESULTS: Four studies with 502 cases in total were included. Pooled sensitivity and specificity were 0.71 (95% confidence interval [CI] = 0.52-0.79) and 0.64 (95% CI = 0.55-0.71), respectively. Area under the hierarchical summary receiver operating characteristic curve yielded 0.73 (95% CI = 0.68-0.76). The diagnostic odds ratio was 4.42 (95% CI = 2.56-7.62). Pooled positive and negative likelihood ratios yielded 1.98 (95% CI = 1.53-2.55) and 0.45 (95% CI = 0.32-0.62), respectively. When the pretest probabilities were 25%, 50%, and 75%, the positive posttest probabilities were 40%, 66%, and 86%, and the negative posttest probabilities were 13%, 31%, and 57%, respectively, according to the Fagan's nomogram plot. The overall certainty of evidence in GRADE was low and very low in sensitivity and specificity, respectively. CONCLUSION: The pooled diagnostic values of preoperative NLR, an inexpensive and routine laboratory examination, provide a practicable help for predicting in-hospital mortality for patients with postoperative AAD in our meta-analysis.

Identification of miR-203a, mir-10a, and miR-194 as predictors for risk of lymphovascular invasion in head and neck cancers.

Lymphovascular invasion (LVI) is an important prognostic indicator of lymph node metastasis and disease aggressiveness but clear molecular mechanisms mediating this in head and neck cancers (HNSC) remain undefined. To identify important microRNAs (miRNAs) in HNSC that associate with and are also predictive of increased risk of LVI, we used a combination of clustering algorithms, multiple regression analyses and machine learning approaches and analyzed miRNA expression profiles in the TCGA HNSC database. As the first step, we identified miRNAs with increased association with LVI as a binary variable. In order to determine whether the identified miRNAs would show functional clusters that are also indicative of increased risk for LVI, we carried out unsupervised as well as supervised clustering. Our results identified distinct clusters of miRNAs that are predictive of increased LVI. We further refined these findings using a Random forest approach, and miR-203a-3p, mir-10a-5p, and miR-194-5p to be most strongly associated with LVI. Pathway enrichment analysis showed these miRNAs targeted genes involved in Hippo signaling and fatty acid oxidation pathways that are mediators of lymph node metastasis. Specific association was also identified between the miRNAs associated with LVI and expression of several lymphangiogenic genes that could be critical for determination of therapeutic strategies.