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Abstract Incarceration of the appendix within a femoral hernia is a rare condition of abdominal wall hernia about 0.1 to 0.5% in reported femoral hernia [1]. We report a case of a 56-year-old female whose appendix was trapped in the right femoral canal. There are few reports in the literature on entrapment of the appendix within a femoral hernia. The management of this condition includes antibiotics, drainage appendectomy, hernioplasty and mesh repair.

[This corrects the article DOI: 10.1371/journal.pone.0056704.].

Objectives: Trauma is one of the leading causes of death and its incidence increases annually. The “weekend effect” and “holiday season effect” on traumatic injury mortality remain controversial, whereby traumatic injury patients admitted during weekends and/or holiday season have a higher risk of in-hospital death. The present study is aimed to explore the association between “weekend effect” and “holiday season effect” and mortality in traumatic injury population. Materials and Methods: This retrospective descriptive study included patients from the Taipei Tzu Chi Hospital Trauma Database between January 2009 and June 2019. The exclusion criterion was age of < 20 years. The primary outcome was the in-hospital mortality rate. The secondary outcomes included intensive care unit (ICU) admission, ICU re-admission, length of stay (LOS) in the ICU, ICU admission duration ≥ 14 days, total hospital LOS, total hospital LOS ≥ 14 days, need for surgery, and re-operation rate. Results: In this study, 11,946 patients were included in the analysis, and 8143 (68.2%) patients were admitted on weekdays, 3050 (25.5%) on weekends, and 753 (6.3%) on holidays. Multivariable logistic regression revealed that the admission day was not associated with an increased risk of in-hospital mortality. In other clinical outcome analyses, we found no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups. The subgroup analysis showed that the association between holiday season admission and in-hospital mortality was noted only in the elderly and shock condition populations. The holiday season duration did not differ in terms of in-hospital mortality. Longer holiday season duration was also not associated with an increased risk of in-hospital mortality, ICU LOS ≥14 days, and total LOS ≥14 days. Conclusion: In this study, we did not find any evidence that weekend and holiday season admissions in the traumatic injury population were associated with an increased risk of mortality. In other clinical outcome analyses, there was no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups.

Summary: Background: Post-caesarean section analgesia is important physiologically and psychologically for both mothers and infants. Patient-controlled analgesia is a well-established method of administering opioids for postoperative pain. However, to date, no study has systematically investigated the effects of opioids administered through intravenous patient-controlled analgesia (IVPCA) or patient-controlled epidural analgesia (PCEA) in parturients who have undergone caesarean section. Methods: This systematic review and network meta-analysis aimed to evaluate the analgesic and adverse effects of opioids administered via IVPCA or PCEA in parturients who have undergone a caesarean section. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception through 02 10, 2022 for relevant records. Randomised controlled trials (RCTs) that compared opioids administered via IVPCA or PCEA and reported outcomes of interest were included. Studies were excluded if the solution for patient-controlled analgesia contained antiemetics and/or other analgesics in addition to opioids. The methodological quality of RCTs was assessed using the revised Cochrane Risk of Bias Tool. Summary data were extracted from each eligible study. The primary outcome was pain intensity, and the secondary outcomes were opioid-related adverse effects. Frequentist network meta-analyses were performed using a contrast-based random-effects model. This study is registered with PROSPERO, CRD42021254040. Findings: Twenty-three studies with 2589 parturients were included. Compared with IVPCA morphine as a reference treatment, PCEA fentanyl had better analgesic effects at 4 h (mean difference [MD] in the visual analogue scale score, −0.75; 95% confidence interval [CI] [-1.16, −0.34]) and 8 h (MD, −0.93; 95% CI [-1.57, −0.28]) and yielded lower odds of developing nausea/vomiting (odds ratio [OR], 0.27; 95% CI [0.09, 0.80]) and sedation/drowsiness (OR, 0.22; 95% CI [0.11, 0.45]). However, PCEA fentanyl may be more likely to cause pruritus than IVPCA treatments. Interpretation: Considering the analgesic efficacy; opioid-induced nausea, vomiting, and sedation; and the well-being of breastfed infants, PCEA fentanyl may be the treatment of choice for post-caesarean section analgesia. Funding: The Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-111-27)

ObjectivesEarly identification of traumatic brain injury (TBI) patients at a high risk of mortality is very important. This study aimed to compare the predictive accuracy of four scoring systems in TBI, including shock index (SI), modified shock index (MSI), age-adjusted shock index (ASI), and reverse shock index multiplied by the Glasgow Coma Scale (rSIG).Patients and methodsThis is a retrospective analysis of a registry from the Taipei Tzu Chi trauma database. Totally, 1,791 patients with TBI were included. We investigated the accuracy of four major shock indices for TBI mortality. In the subgroup analysis, we also analyzed the effects of age, injury mechanism, underlying diseases, TBI severity, and injury severity.ResultsThe predictive accuracy of rSIG was significantly higher than those of SI, MSI, and ASI in all the patients [area under the receiver operating characteristic curve (AUROC), 0.710 vs. 0.495 vs. 0.527 vs. 0.598], especially in the moderate/severe TBI (AUROC, 0.625 vs. 0.450 vs. 0.476 vs. 0.529) and isolated head injury populations (AUROC 0.689 vs. 0.472 vs. 0.504 vs. 0.587). In the subgroup analysis, the prediction accuracy of mortality of rSIG was better in TBI with major trauma [Injury Severity Score (ISS) ≥ 16], motor vehicle collisions, fall injury, and healthy and cardiovascular disease population. rSIG also had a better prediction effect, as compared to SI, MSI, and ASI, both in the non-geriatric (age < 65 years) and geriatric (age ≥ 65 years).ConclusionrSIG had a better prediction accuracy for mortality in the overall TBI population than SI, MSI, and ASI. Although rSIG have better accuracy than other indices (ROC values indicate poor to moderate accuracy), the further clinical studies are necessary to validate our results.

Energy shortage has become a global issue in the twenty-firt century, as energy consumption grows at an alarming rate as the fossil fuel supply exhausts. Perovskite solar cells (PSCs) are a promising photovoltaic technology that has grown quickly in recent years. Its power conversion efficiency (PCE) is comparable to that of traditional silicon-based solar cells, and scale-up costs can be substantially reduced due to its utilization of solution-processable fabrication. Nevertheless, most PSCs research uses hazardous solvents, such as dimethylformamide (DMF) and chlorobenzene (CB), which are not suitable for large-scale ambient operations and industrial production. In this study, we have successfully deposited all of the layers of PSCs, except the top metal electrode, under ambient conditions using a slot-die coating process and nontoxic solvents. The fully slot-die coated PSCs exhibited PCEs of 13.86% and 13.54% in a single device (0.09 cm2) and mini-module (0.75 cm2), respectively.

Summary: Background: Hearing loss is a common morbidity that requires a hearing device to improve quality of life and prevent sequelae, such as dementia, depression falls, and cardiovascular disease. However, conventional hearing aids have some limitations, including poor accessibility and unaffordability. Consequently, personal sound amplification products (PSAPs) are considered a potential first-line alternative remedy for patients with hearing loss. The main objective of this study was to compare the efficacy of PSAPs and conventional hearing aids regarding hearing benefits in patients with hearing loss. Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases and reference lists were searched from inception to January 12, 2022. Studies including randomised, controlled trials; nonrandomised, controlled trials; or observational studies comparing PSAPs and hearing aids with regard to hearing gain performance (e.g., speech intelligence) were considered eligible. The review was registered prospectively on PROSPERO (CRD42021267187). Findings: Of 599 records identified in the preliminary search, five studies were included in the review and meta-analysis. A total of 124 patients were divided into the PSAP group and the conventional hearing aid group. Five studies including seven groups compared differences for speech intelligence in the signal-noise ratio (SNR) on the hearing in noise test (HINT) between PSAPs and conventional hearing aids. The pooled results showed nonsignificant differences in speech intelligence (SMD, 0.14; 95% CI, -0.19 to 0.47; P = .41; I2=65%), sound quality (SMD, -0.37; 95% CI, -0.87 to 0.13; P = .15; I2=77%) and listening effort (SMD 0.02; 95% CI, -0.24 to 0.29; P = .86; I2=32%). Nonsignificant results were also observed in subsequent analyses after excluding patients with moderately severe hearing loss. Complete sensitivity analyses with all of the possible combinations suggested nonsignificant results in most of the comparisons between PSAPs and conventional hearing aids. Interpretation: PSAPs are potentially beneficial as conventional hearing aids are in patients with hearing loss. The different features among PSAPs should be considered for patients indicated for hearing devices. Funding: This work was supported by grants from Ministry of Science and Technology (MOST-10-2622-8-075-001) and Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST111-G6-11-2 and VGHUST111c-140).

Attenuation of an increase in intraocular pressure (IOP) is crucial to preventing devastating postoperative visual loss following surgery. IOP is affected by several factors, including the physiologic alteration due to pneumoperitoneum and patient positioning and differences in anesthetic regimens. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) and volatile anesthesia on IOP. We searched multiple databases for relevant studies published before October 2019. Randomized controlled trials comparing the effects of propofol-based TIVA and volatile anesthesia on IOP during surgery were considered eligible for inclusion. Twenty studies comprising 980 patients were included. The mean IOP was significantly lower in the propofol-based TIVA group after intubation, pneumoperitoneum, Trendelenburg positioning, and lateral decubitus positioning. Moreover, mean arterial pressure and peak inspiratory pressure were also lower after intubation in the propofol-based TIVA group. Trial sequential analyses for these outcomes were conclusive. Propofol-based TIVA is more effective than volatile anesthesia during surgery at attenuating the elevation of IOP and should be considered, especially in at-risk patients.

BackgroundHearing loss is one of the most common disabilities worldwide and affects both individual and public health. Pure tone audiometry (PTA) is the gold standard for hearing assessment, but it is often not available in many settings, given its high cost and demand for human resources. Smartphone-based audiometry may be equally effective and can improve access to adequate hearing evaluations. ObjectiveThe aim of this systematic review is to synthesize the current evidence of the role of smartphone-based audiometry in hearing assessments and further explore the factors that influence its diagnostic accuracy. MethodsFive databases—PubMed, Embase, Cochrane Library, Web of Science, and Scopus—were queried to identify original studies that examined the diagnostic accuracy of hearing loss measurement using smartphone-based devices with conventional PTA as a reference test. A bivariate random-effects meta-analysis was performed to estimate the pooled sensitivity and specificity. The factors associated with diagnostic accuracy were identified using a bivariate meta-regression model. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. ResultsIn all, 25 studies with a total of 4470 patients were included in the meta-analysis. The overall sensitivity, specificity, and area under the receiver operating characteristic curve for smartphone-based audiometry were 89% (95% CI 83%-93%), 93% (95% CI 87%-97%), and 0.96 (95% CI 0.93-0.97), respectively; the corresponding values for the smartphone-based speech recognition test were 91% (95% CI 86%-94%), 88% (95% CI 75%-94%), and 0.93 (95% CI 0.90-0.95), respectively. Meta-regression analysis revealed that patient age, equipment used, and the presence of soundproof booths were significantly related to diagnostic accuracy. ConclusionsWe have presented comprehensive evidence regarding the effectiveness of smartphone-based tests in diagnosing hearing loss. Smartphone-based audiometry may serve as an accurate and accessible approach to hearing evaluations, especially in settings where conventional PTA is unavailable.

Background: Early trauma team activation (TTA) may improve clinical outcomes through early diagnosis and timely intervention by a dedicated multidisciplinary team. Controversy seems to exist about the effect of establishing trauma team systems in traumatic injury populations. Our aim was to identify factors that may be associated with clinical outcomes in trauma injury and to investigate the effect of trauma team activation. Method: This retrospective descriptive study included all traumatic patients from the Taipei Tzu Chi Hospital Trauma Database. All prehospital vital signs, management, injury type, injury mechanisms, hospitalization history, and clinical outcomes were analyzed, and multivariable logistic regression was used to investigate the association between trauma team activation and clinical outcomes. Subgroups of TTA in minor injury and non-TTA in major injury were also analyzed. Result: In this study, a total of 11,946 patients were included, of which 10,831 (90.7%) patients were minor injury (ISS < 16), and 1115 (9.3%) patients were major injury (ISS ≥ 16). In the minor injury population, TTA had a higher intensive care unit (ICU) admission rate, operation rate, re-operation rate, and prolonged total length of stay (LOS). In the major injury population, TTA had a higher mortality rate, prolonged total LOS, and prolonged ICU LOS. After adjusting for mechanism of injury and injury severity, there was no association between in-hospital mortality and TTA, compared with the non-TTA group. However, the TTA group had a higher risk of ICU admission, prolonged ICU LOS, and prolonged total LOS. The subgroup analysis showed trauma team activation had a higher risk of mortality in the 60- to 80-year-old population, major injury (ISS ≥ 16), consciousness clear population, and non-head injury group. Conclusions: We found there was no significant association between in-hospital mortality and TTA. However, in the TTA group, there was a higher risk of ICU admission, prolonged total, LOS, and prolonged ICU LOS. In the subgroup analysis, TTA had a higher risk of mortality in the 60- to 80-year-old population, major injury (ISS ≥ 16), consciousness clear population, and non-head injury group. Our results reflect TTA-criteria-selected patients with greater ISS and a high risk of mortality.

Intraocular pressure (IOP) is crucial to the well-being of eyes. During anesthesia, the administration of succinylcholine and endotracheal intubation are associated with an increase in IOP, which may be attenuated by short-acting opioids. However, the drug of choice among the commonly used short-acting opioids is unclear. This study aimed to evaluate the effects of fentanyl, sufentanil, alfentanil, and remifentanil on IOP measured after the administration of succinylcholine and after endotracheal intubation in patients undergoing general anesthesia. Five databases were searched. Randomized controlled trials (RCTs) that compared short-acting opioids and reported at least one of the clinical outcomes of interest were included. Nine RCTs with 357 patients were included. Remifentanil (1 μg kg−1) more effectively alleviated the increase in IOP than the placebo after the administration of succinylcholine [mean difference (MD) of IOP, −3.64; confidence interval (CI), −5.47 to −1.81 and after endotracheal intubation (MD, −9.71; CI, −11.91 to −7.51). Remifentanil (1 μg kg−1) ranked the best in terms of both attenuating the increase in IOP after the administration of succinylcholine [surface under the cumulative ranking curve (SUCRA), 0.91; normalized entropy (NE), 0.47; and after endotracheal intubation (SUCRA, 0.89; NE, 0.54) among all of the treatments. Remifentanil (1 μg kg−1) should be considered the drug of choice in the circumstances where increased IOP is a great concern.

Acute low-tone hearing loss (ALHL) is a common clinical disease and was first proposed by Abe in 1981 as sensorineural hearing loss confined to low frequencies. The best strategy for initiating medication is still unclear, as the superiority of steroids and diuretics is still debated, and combination therapy might yield additional benefits. However, no study regarding combination therapy has been published. The objective of this study was to evaluate the efficacy of steroid therapy versus combination therapy of diuretics with steroids by conducting a systematic review with a meta-analysis and trial sequential analysis (TSA). Studies enrolling patients with a diagnosis of acute low-tone hearing loss were considered eligible. After searching the PubMed, Cochrane Library, Embase, Scopus and Web of Science databases from inception to 31 December 2021, five studies including 433 patients were enrolled. Overall, the comparison between combination therapy with steroids and diuretics and single-modality treatment with steroids (OR, 1.15; 95% CI, 0.51 to 2.59; p = 0.74; I2 = 34%) and the comparison between combination therapy and treatment with diuretics alone (OR, 1.73; 95% CI, 0.93 to 3.23; p = 0.09; I2 = 5%) showed that combination therapy did not confer significant benefits when compared to single-modality treatments. A trial sequential analysis (TSA) showed conclusive nonsignificant results of the comparison between the combination of steroids and diuretics and a single-modality treatment. In conclusion, we reported that the combination of steroids and diuretics did not yield significant benefits when compared to single-modality treatment with steroids or diuretics. We suggest that treatment should be initiated with steroids or diuretics alone to avoid potential adverse effects.

Traditional otoscopy has some limitations, including poor visualization and inadequate time for evaluation in suboptimal environments. Smartphone-enabled otoscopy may improve examination quality and serve as a potential diagnostic tool for middle ear diseases using a telemedicine approach. The main objectives are to compare the correctness of smartphone-enabled otoscopy and traditional otoscopy and to evaluate the diagnostic confidence of the examiner via meta-analysis. From inception through 20 January 2022, the Cochrane Library, PubMed, EMBASE, Web of Science, and Scopus databases were searched. Studies comparing smartphone-enabled otoscopy with traditional otoscopy regarding the outcome of interest were eligible. The relative risk (RR) for the rate of correctness in diagnosing ear conditions and the standardized mean difference (SMD) in diagnostic confidence were extracted. Sensitivity analysis and trial sequential analyses (TSAs) were conducted to further examine the pooled results. Study quality was evaluated by using the revised Cochrane risk of bias tool 2. Consequently, a total of 1840 examinees were divided into the smartphone-enabled otoscopy group and the traditional otoscopy group. Overall, the pooled result showed that smartphone-enabled otoscopy was associated with higher correctness than traditional otoscopy (RR, 1.26; 95% CI, 1.06 to 1.51; p = 0.01; I2 = 70.0%). Consistently significant associations were also observed in the analysis after excluding the simulation study (RR, 1.10; 95% CI, 1.00 to 1.21; p = 0.04; I2 = 0%) and normal ear conditions (RR, 1.18; 95% CI, 1.01 to 1.40; p = 0.04; I2 = 65.0%). For the confidence of examiners using both otoscopy methods, the pooled result was nonsignificant between the smartphone-enabled otoscopy and traditional otoscopy groups (SMD, 0.08; 95% CI, -0.24 to 0.40; p = 0.61; I2 = 16.3%). In conclusion, smartphone-enabled otoscopy was associated with a higher rate of correctness in the detection of middle ear diseases, and in patients with otologic complaints, the use of smartphone-enabled otoscopy may be considered. More large-scale studies should be performed to consolidate the results.

Pulmonary tuberculosis (TB) is a difficult-to-eliminate disease. Although the Bacille Calmette–Guérin (BCG) vaccine against Mycobacterium tuberculosis (MTB) has been available for decades, its efficacy is variable and has lessened over time. Furthermore, the BCG vaccine no longer protects against newly emerged Beijing strains which are responsible for many current infections in adults. Development of a novel vaccine is urgently needed. In this study, we first tested the efficacy of our recombinant BCG vaccines rBCG1 and rBCG2, compared to parental BCG, against MTB strain H37Ra in mice. Both the bacterial load and the level of lymphocyte infiltration decreased dramatically in the three groups treated with vaccine, especially rBCG1 and rBCG2. Furthermore, the Th1 and Th17 responses increased and macrophage numbers rose in the vaccination groups. Th1-mediated production of cytokines TNF-α, IFN-γ, and MCP-1 as well as M1-polarized cells all increased in lung tissue of the rBCG1 and rBCG2 groups. Clodronate-induced depletion of macrophages reduced the level of protection. Based on these results, we conclude that rBCG vaccines induce a significant increase in the number of M1 macrophages, which augments their potential as TB vaccine candidates.

Abstract Background Increasing evidence indicates a pathogenic role of deregulated autophagy in rheumatoid arthritis (RA). We examined the relationship between autophagy and inflammatory parameters in patients with RA receiving biologic therapy. Methods In 72 patients with RA and 20 healthy control subjects (HC), autophagosome levels were determined by the mean fluorescence intensity (MFI) of autophagosomotropic dye incorporated into circulating immune cells, and p62 expression levels in immune cells were measured by flow cytometry. We used immunoblotting to examine protein expression of LC3-II and p62 in peripheral blood mononuclear cells. Results Patients with RA had significantly higher levels of autophagosome reflected by MFI of Cyto-ID in circulating lymphocytes, monocytes, and granulocytes (median values, 3.6, 11.6, and 64.8, respectively) compared with HC (1.9, 6.0, and 35.8; respectively) (all p

The shock index (SI) is a useful tool for predicting the injury severity and mortality in patients with trauma. However, pediatric physiology differs from that of adults. In the pediatric trauma population, the shock status may be obscured within the normal range of vital signs. Pediatric age-adjusted SI (SIPA) is reported more accurately compared to SI. In our study, we conducted a 10 year retrospective cohort study of pediatric trauma population to evaluate the SI and SIPA in predicting mortality, intensive care unit (ICU) admission, and the need for surgery. This retrospective cohort study included 1265 pediatric trauma patients from January 2009 to June 2019 at the Taipei Tzu Chi Hospital, who had a history of hospitalization. The primary outcome of this investigation was in-hospital mortality, and the secondary outcomes were the length of hospital and ICU stay, operation times, and ICU admission times. The SIPA group can detect changes in vital signs early to reflect shock progression. In the elevated SIPA group, more severe traumatic injuries were identified, including high injury severity score (ISS), revised trauma score (RTS), and new injury severity score (NISS) scores than SI > 0.9. The odds ratio of elevated SIPA and SI (>0.9) to predict ISS ≥ 16 was 3.593 (95% Confidence interval [CI]: 2.175–5.935, p < 0.001) and 2.329 (95% CI: 1.454–3.730, p < 0.001). SI and SIPA are useful for identifying the compensatory phase of shock in prehospital and hospital settings, especially in corresponding normal to low-normal blood pressure. SIPA is effective in predicting the mortality and severity of traumatic injuries in the pediatric population. However, SI and SIPA were not significant predictors of ICU admission and the need for surgery analysis.

Study Objective: Tinnitus is a common disorder characterized by sound in the ear in the absence of external or internal stimuli. Low-level laser therapy (LLLT) was discovered enhancing tissue repair via increasing the blood microcirculation and cell proliferation in 1960s. In the last two decades, LLLT delivered to the cochlea has frequently been used to reduce the severity of tinnitus. However, whether LLLT effectively attenuates the severity of tinnitus remains controversial. We aimed to evaluate the efficacy of low-level laser therapy on adult patients with complaints of tinnitus. Design: Systematic review and meta-analysis with trial sequential analysis. Interventions: Low-level laser therapy (LLLT). Measurements: Tinnitus Handicap Inventory (THI) score; improvement rates of the visual analog scale (VAS), verbal rating scale (VRS) and numeric rating scale (NRS) scores. Methods: We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from inception through 17 September 2020. Randomized control trials that involved adult patients with complaints of tinnitus, compared LLLT to a placebo and provided sufficient information for meta-analysis were considered eligible. Main Results: Overall, 11 studies involving 670 patients were included. No significant difference in the overall effect according to the THI score (mean difference (MD), −2.85; 95% CI, −8.99 to 3.28; p = 0.362; I2 = 0%) and the rating scale score improvement rate (risk ratio (RR), 1.35; 95% CI, 0.81 to 2.27; p = 0.250; I2 = 67%) was demonstrated between patients receiving LLLT and those receiving a placebo. None of the subgroup analyses showed significant differences, regardless of underlying sensorineural hearing loss, the number of irradiation sessions or the wavelength used. Conclusions: Our meta-analysis suggests that the value of LLLT in controlling the severity of tinnitus remains unclear, in part due to the relatively small number of patients and underlying heterogeneity. More large-scale investigations of LLLT for tinnitus related to inner ear disease are required to further elucidate the therapeutic effects.

The diagnostic performance of the bispectral index (BIS) to early predict neurological outcomes in patients achieving return of spontaneous circulation (ROSC) after cardiac arrest (CA) remained unclear. We searched PubMed, EMBASE, Scopus and CENTRAL for relevant studies through October 2019. Methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analysis was performed using a linear mixed-effects model to the log-transformed data with a logistic distribution assumption. Bivariate meta-regression was performed to explore heterogeneity. In total, 13 studies with 999 CA adult patients were included. At the optimal threshold of 32, BIS obtained within 72 h of ROSC elicits a pooled sensitivity of 84.9% (95% confidence interval (CI), 71.1% to 92.7%), a pooled specificity of 85.9% (95% CI, 71.2% to 93.8%) and an area under the curve of 0.92. Moreover, a BIS cutoff < 12 yielded a pooled specificity of 95.0% (95% CI, 77.8% to 99.0%). In bivariate meta-regression, the timing of neurological outcome assessment, the adoption of targeted temperature management, and the administration of sedative agents or neuromuscular blocking agents (NMBA) were not identified as the potential source of heterogeneity. BIS retains good diagnostic performance during targeted temperature management (TTM) and in the presence of administrated sedative agents and NMBA. In conclusion, BIS can predict poor neurological outcomes early in patients with ROSC after CA with good diagnostic performance and should be incorporated into the neuroprognostication strategy algorithm.

This meta-analysis evaluated the effects of methylphenidate (MPH) on cognitive outcome and adverse events in adults with traumatic brain injuries (TBI). We searched PubMed, EMBASE, and PsycINFO for randomized controlled trials (RCTs) published before July 2019. Studies that compared the effects of MPH and placebos in adults with TBI were included. The primary outcome was cognitive function, while the secondary outcome was adverse events. Meta-regression and sensitivity analysis were conducted to evaluate heterogeneity. Seventeen RCTs were included for qualitative analysis, and ten RCTs were included for quantitative analysis. MPH significantly improved processing speed, measured by Choice Reaction Time (standardized mean difference (SMD): −0.806; 95% confidence interval (CI): −429 to −0.182, p = 0.011) and Digit Symbol Coding Test (SMD: −0.653; 95% CI: −1.016 to −0.289, p < 0.001). Meta-regression showed that the reaction time was inversely associated with the duration of MPH. MPH administration significantly increased heart rate (SMD: 0.553; 95% CI: 0.337 to 0.769, p < 0.001), while systolic or diastolic blood pressure did not exhibit significant differences. Therefore, MPH elicited better processing speed in adults with TBI. However, MPH use could significantly increase heart rate. A larger study is required to evaluate the effect of dosage, age, or optimal timing on treatment of adults with TBI.

Resveratrol (RSV), a phenolic component, is found in grape skins, peanuts, pistachios and red wine. RSV has protective activities in atherosclerosis, yet the detailed mechanisms are not fully elucidated. In the present study, we observed that RSV inhibited oxLDL-mediated lipid accumulation through the enhancement of cholesterol efflux in THP-1-derived macrophages and explored the possible underlying mechanisms. RSV dose-dependently enhanced the mRNA and protein levels of ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) but had no effect on the mRNA expression of scavenger receptor class BI (SR-BI) in cholesterol homeostasis. Additionally, the functional inhibition of ABCA1 and ABCG1 with short hairpin RNA abrogated the effects of RSV on lipid accumulation. The upregulation of ABCA1 and ABCG1 by RSV depended on LXRα, as evidenced by an increase in the nuclear levels of LXRα through the induction of nuclear translocation. The functional inhibition of LXRα with a pharmacological inhibitor, geranylgeranyl pyrophosphate (GGPP), abolished the RSV-mediated protective effects in macrophages. These findings suggest that LXRα-dependent upregulation of ABCA1 and ABCG1 might mediate the beneficial effects of RSV, which ameliorated the oxLDL-mediated lipid accumulation in the process of lipid-laden foam cells formation.

Infection with influenza virus is a major public health problem, causing serious illness and death each year. Emergence of drug-resistant influenza virus strains limits the effectiveness of drug treatment. Importantly, a dual H275Y/I223R mutation detected in the pandemic influenza A 2009 virus strain results in multidrug resistance to current neuraminidase (NA) drugs. Therefore, discovery of new agents for treating multiple drug-resistant (MDR) influenza virus infections is important. Here, we propose a parallel screening strategy that simultaneously screens wild-type (WT) and MDR NAs, and identifies inhibitors matching the subsite characteristics of both NA-binding sites. These may maintain their potency when drug-resistant mutations arise. Initially, we analyzed the subsite of the dual H275Y/I223R NA mutant. Analysis of the site-moiety maps of NA protein structures show that the mutant subsite has a relatively small volume and is highly polar compared with the WT subsite. Moreover, the mutant subsite has a high preference for forming hydrogen-bonding interactions with polar moieties. These changes may drive multidrug resistance. Using this strategy, we identified a new inhibitor, Remazol Brilliant Blue R (RB19, an anthraquinone dye), which inhibited WT NA and MDR NA with IC(50) values of 3.4 and 4.5 µM, respectively. RB19 comprises a rigid core scaffold and a flexible chain with a large polar moiety. The former interacts with highly conserved residues, decreasing the probability of resistance. The latter forms van der Waals contacts with the WT subsite and yields hydrogen bonds with the mutant subsite by switching the orientation of its flexible side chain. Both scaffolds of RB19 are good starting points for lead optimization. The results reveal a parallel screening strategy for identifying resistance mechanisms and discovering anti-resistance neuraminidase inhibitors. We believe that this strategy may be applied to other diseases with high mutation rates, such as cancer and human immunodeficiency virus type 1.