Diagnostic performance of metagenomic next-generation sequencing for the detection of pathogens in cerebrospinal fluid in pediatric patients with central nervous system infection: a systematic review and meta-analysis.

BACKGROUND: Detecting pathogens in pediatric central nervous system infection (CNSI) is still a major challenge in medicine. In addition to conventional diagnostic patterns, metagenomic next-generation sequencing (mNGS) shows great potential in pathogen detection. Therefore, we systematically evaluated the diagnostic performance of mNGS in cerebrospinal fluid (CSF) in pediatric patients with CNSI. METHODS: Related literature was searched in the Web of Science, PubMed, Embase, and Cochrane Library. We screened the literature and extracted the data according to the selection criteria. The quality of included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the certainty of the evidence was measured by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) score system. Then, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd's ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) were estimated in Stata Software and MetaDisc. Subgroup analyses were performed to investigate the potential factors that influence the diagnostic performance. RESULTS: A total of 10 studies were included in the meta-analysis. The combined sensitivity was 0.68 (95% confidence interval [CI]: 0.59 to 0.76, I2 = 66.77%, p < 0.001), and the combined specificity was 0.89 (95% CI: 0.80 to 0.95, I2 = 83.37%, p < 0.001). The AUC of sROC was 0.85 (95% CI, 0.81 to 0.87). The quality level of evidence elevated by the GRADE score system was low. CONCLUSIONS: Current evidence shows that mNGS presents a good diagnostic performance in pediatric CNSI. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review.

The circadian rhythm generated by circadian clock genes functions as an internal timing system. Since the circadian rhythm controls abundant physiological processes, the circadian rhythm evolved in organisms is salient for adaptation to environmental change. A disturbed circadian rhythm is a trigger for numerous pathological events. Recently, accumulated data have indicated that kidney stone disease (KSD) is related to circadian rhythm disturbance. However, the mechanism between them has not been fully elucidated. In this narrative review, we summarized existing evidence to illustrate the possible association between circadian rhythm disturbance and KSD based on the epidemiological studies and risk factors that are linked to circadian rhythm disturbance and discuss some chronotherapies for KSD. In summary, KSD is associated with systemic disorders. Metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis are the major risk factors supported by sufficient data to cause KSD in patients with circadian rhythm disturbance, while others including hypertension, vitamin D deficiency, parathyroid gland dysfunction, and renal tubular damage/dysfunction need further investigation. Then, some chronotherapies for KSD were confirmed to be effective, but the molecular mechanism is still unclear.

Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis.

BACKGROUND: Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear. METHODS: A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety. RESULTS: Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81-1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29-0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period. CONCLUSION: TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease: A literature review.

Tumor necrosis factor-α (TNF-α) antagonists, the first biologics approved for treating patients with inflammatory bowel disease (IBD), are effective for the induction and maintenance of remission and significantly improving prognosis. However, up to one-third of treated patients show primary nonresponse (PNR) to anti-TNF-α therapies, and 23%-50% of IBD patients experience loss of response (LOR) to these biologics during subsequent treatment. There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs. This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients. Most predictors remain controversial, and only previous surgical history, disease manifestations, drug concentrations, antidrug antibodies, serum albumin, some biologic markers, and some genetic markers may be potentially predictive. In addition, we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists. Therapeutic drug monitoring plays an important role in treatment selection. Dose escalation, combination therapy, switching to a different anti-TNF drug, or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

The application of metagenomic next-generation sequencing in pathogen diagnosis: a bibliometric analysis based on Web of Science.

Background: Infectious disease is a large burden on public health globally. Metagenomic next-generation sequencing (mNGS) has become popular as a new tool for pathogen diagnosis with numerous advantages compared to conventional methods. Recently, research on mNGS increases yearly. However, no bibliometric analysis has systematically presented the full spectrum of this research field. Therefore, we reviewed all the publications associated with this topic and performed this study to analyze the comprehensive status and future hotspots of mNGS for infectious disease diagnosis. Methods: The literature was searched in the Web of Science Core Collection and screened without year or language restrictions, and the characteristics of the studies were also identified. The outcomes included publication years, study types, journals, countries, authorship, institutions, frontiers, and hotspots with trends. Statistical analysis and visualization were conducted using VOSviewer (version 1.6.16) and CiteSpace (version 6.1. R3). Results: In total, 325 studies were included in the analysis after screening. Studies were published between 2009 and 2022 with a significantly increasing number from 1 to 118. Most of the studies were original articles and case reports. Frontiers in Cellular and Infection Microbiology and Clinical Infectious Disease were the most commonly cited and co-cited journals. Institutions and researchers from China contributed the most to this field, followed by those from the USA. The hotspots and frontiers of these studies are pneumonia, tuberculosis, and central nervous system infections. Conclusion: This study determined that mNGS is a hot topic in the diagnosis of infectious diseases with development trends and provides insights into researchers, institutions, hotspots and frontiers in mNGS, which can offer references to related researchers and future research.

The value of NLR versus MLR in the short-term prognostic assessment of HBV-related acute-on-chronic liver failure.

BACKGROUND: Systemic inflammation is associated with the development and progression of hepatitis B-associated acute-on-chronic liver failure (HBV-ACLF). The neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic biomarker in patients with HBV-ACLF. However, the role of the monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in multiple diseases is rarely mentioned in HBV-ACLF. METHODS: We included a total of 347 patients with HBV-ACLF who met the definition of the Chinese Guidelines for the Diagnosis and Treatment of Liver Failure (2018 edition). Among them, 275 cases were included retrospectively, and 72 cases were collected prospectively. Clinical characteristics and laboratory examination data were collected from medical records within 24 h after diagnosis to calculate MLR and NLR levels, and lymphocyte subpopulation counts were collected in prospectively included patients. RESULTS: Of the 347 patients with HBV-ACLF, 128 patients in the non-surviving group had a mean age of 48.87 ± 12.89 years; 219 patients in the survival group had a mean age of 44.80 ± 11.80 years and a combined 90-day mortality rate of 36.9%. The median MLR was higher in the non-survivors than in the survivors (0.690 vs 0.497, P < 0.001). MLR values were significantly associated with 90-day mortality in HBV-ACLF (OR 6.738; 95% CI 3.188-14.240, P < 0.001). The AUC for the predictive power of the combined MLR and NLR analysis for HBV-ACLF was 0.694, and the calculated MLR threshold was 4.495. In addition, in the analysis of peripheral blood lymphocyte subsets in HBV-ACLF, a significant decrease in the number of circulating lymphocytes was found in HBV-ACLF patients in the non-surviving group (P < 0.001), with a predominant decrease in the number of CD8 + T cells and no significant difference in the number of CD4 + T cells, B cells or NK cells. CONCLUSION: Increased MLR values are associated with 90-day mortality in patients with HBV-ACLF, and the MLR may serve as a potential prognostic indicator for patients with HBV-ACLF. Decreased CD8 + T-cell counts may be associated with poor survival in patients with HBV-ACLF.

Easily readable? Examining the readability of lay summaries published in Autism Research.

Communicating science to the general public could sometimes be problematic partly because the language used in scientific writing was difficult to understand for people outside the scientific community. Against this backdrop, lay summaries were introduced to the research community. Lay summaries are short, non-technical summaries of scientific articles that are aimed at a lay audience. Despite the increasing attention on the roles that lay summaries play in scientific communication, it remains unclear whether they are comprehensible to the lay audience. To address the foregoing concerns, this study examines the readability of lay summaries published in Autism Research. It was found that lay summaries were more readable than traditional abstracts but were not easy enough to read for the lay audience. Possible explanations for these findings are discussed.

Crisis communication in the WHO COVID-19 press conferences: A retrospective analysis.

OBJECTIVES: The objective of this study is to investigate, from a longitudinal perspective, how WHO communicated COVID-19 related information to the public through its press conferences during the first two years of the pandemic. METHODS: The transcripts of 195 WHO COVID-19 press conferences held between January 22, 2020 and February 23, 2022 were collected. All transcripts were syntactically parsed to extract highly frequent noun chunks that were potential topics of the press conferences. First-order autoregression models were fit to identify "hot" and "cold" topics. In addition, sentiments and emotions expressed in the transcripts were analyzed using lexicon-based sentiment/emotion analyses. Mann-Kendall tests were performed to capture the possible trends of sentiments and emotions over time. RESULTS: First, eleven "hot" topics were identified. These topics were pertinent to anti-pandemic measures, disease surveillance and development, and vaccine-related issues. Second, no significant trend was captured in sentiments. Last, significant downward trends were found in anticipation, surprise, anger, disgust, and fear. However, no significant trends were found in joy, trust, and sadness. CONCLUSIONS: This retrospective study provided new empirical evidence on how WHO communicated issues pertaining to COVID-19 to the general public through its press conferences. With the help of the study, members of the general public, health organizations, and other stake-holders will be able to better understand the way in which WHO has responded to various critical events during the first two years of the pandemic.

Flipped classroom improves student learning outcome in Chinese pharmacy education: A systematic review and meta-analysis.

Background: The application of flipped classroom (FC) pedagogy has recently become increasingly popular in Chinese pharmacy education. However, its effectiveness in improving student learning has not yet been assessed. This study aimed to evaluate the effects of teaching with such pedagogical approach by examining studies that compare the FC approach with the traditional lecture-based learning (LBL) module through a systematic review and meta-analysis. Methods: Seven databases, including the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Wanfang database, and China Biomedical Literature Database, were searched from the inception to 30 June 2021, to identify eligible articles of randomized controlled studies. The primary outcomes included the theoretical and experimental test scores, and the secondary outcomes were the results from questionnaires about the number of students who preferred the FC or endorsed its improving effects on their learning enthusiasm, self-learning ability, thinking skills, communication skills, and learning efficiency. The quantitative synthesis was conducted with Revman V.5.3 software following the Cochrane Reviewer's Handbook guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results: Eleven eligible studies published from 2017 to 2020 enrolling 1,200 students were included in this meta-analysis. The quantitative synthesis demonstrated that the FC module presented an overall more significant effectiveness over traditional LBL approach for Chinese pharmacy education in improving student academic performance as measured by theoretical test scores (SMD = 1.08, 95% CI: 0.60-1.56, p < 0.00001) and experimental test scores (MD = 6.62, 95% CI: 4.42-8.82, p < 0.00001). Further sub-group analysis revealed that the preferable effectiveness of FC was also evident in both theory-oriented (SMD = 0.77, 95% CI: 0.10-1.45, p < 0.00001) and experiments-oriented courses (MD = 6.52, 95% CI: 3.48-9.56, p < 0.00001) for both undergraduate (SMD = 0.84, 95% CI: 0.31-1.37, p < 0.00001) and 3-year junior-college students (MD = 8.17, 95% CI: 6.44-9.89, p < 0.00001). Additionally, analysis on the questionnaire outcomes revealed that more respondents preferred for FC and endorsed its improvement effects on developing students' learning enthusiasm, self-learning ability, thinking skills, communication skills, and learning efficiency. Conclusion: Current evidence suggests that FC pedagogical approach can effectively improve student learning outcomes and is applicable to Chinese pharmacy education.

A case report and literature review: diagnosis and treatment of human immunodeficiency virus coinfected with visceral leishmania by metagenomic next-generation sequencing in China.

Background: human immunodeficiency virus (HIV) can disrupt the body's immune system, increasing the chance of various opportunistic infections. The risk of misdiagnosis and underdiagnosis is high for HIV and Leishmania coinfection. Visceral leishmaniasis (VL) has become a significant opportunistic infection in HIV type 1 (HIV-1)-infected patients in the epidemic region. Co-infection is difficult to diagnose, especially in non-endemic areas. Case Description: This study presents a case of VL in a middle-aged male patient with HIV coinfection, where the diagnosis was circuitous and complex. The patient was a 44-year-old male who was hospitalized due to fever. We considered common pathogen infection or hemophagocytic syndrome, so we did various etiological examinations and bone marrow biopsy smears, but no positive pathogens were found. Then we used a variety of empirical treatment, but the patient's temperature did not drop significantly. After the final diagnosis of VL using metagenomic next-generation sequencing (mNGS), we read the bone marrow smear and biopsy specimens again, and ultimately the Leishman-Donovan body and tissue intracellular pathogens were found. The patient responded well to treatment with sodium stibogluconate (SSG), his temperature gradually recovered from hyperthermia to normal, liver and spleen size gradually decreased, hemoglobin and platelet count rebounded, and weight increased by 1.5 kg after discharge from the hospital. We hope to deepen clinicians' understanding of mNGS for VL diagnosis and provide a review of the literature. Conclusions: For patients with HIV coinfection, mNGS-a test that can detect multiple pathogens simultaneously-can be used routinely when multiple pathogen tests showed no positive results, multiple empiric anti-infective therapies failed, and hospital technology and the patient's economy are adequate. While giving highly active antiretroviral therapy (HAART), liposomal amphotericin B (L-AMB) is highly recommended because of its better efficacy and lower side effects. Not only is the treatment of leishmaniasis critical but also follow-up at a later stage is essential. After discharged, the patient had no significant discomfort and no increase in body temperature, his hemoglobin and platelets increased further. He demonstrated a further reduction in liver and spleen size and a weight gain of 1.5 kg.

A case report and literature review: subcutaneous panniculitis-like T-cell lymphoma with liver failure as the main manifestation.

Background: Subcutaneous lipofuscinosis-like T-cell lymphoma (SPTCL) is a rare cutaneous lymphoma that often presents as recurrent subcutaneous nodules and may progress to hemophagocytic syndrome with fever and hepatic impairment in some patients. However, no cases of progression to hepatic failure have been reported. Here, we present a case of an adult diagnosed with fever and liver failure as the main manifestation, which was eventually confirmed as SPTCL by skin biopsy, but the patient eventually died due to disease progression. Case Description: This study retrospectively reports a rare case of SPTCL in a 34-year-old female patient who was admitted with scleral jaundice for 1 month and fever for 20 days. Examination revealed multiple small subcutaneous nodules on the skin of the chest and tibial surface and an enlarged liver and spleen. Laboratory tests revealed hepatic impairment, and common causes of liver failure (viral infection, fatty liver, immune liver damage, etc.) were excluded. We continued to refine the positron emission tomography-computed tomography (PET-CT) examination, which revealed multiple flocculent and nodular hyperdense shadows with increased metabolism in the subcutaneous fat interstices. And then, we performed a skin biopsy and the final pathological diagnosis was SPTCL, but the patient died 1 month after diagnosis due to poor treatment outcome because the disease progressed too rapidly. With this case report, we hope to improve clinicians' understanding of liver injury caused by SPTCL. A review of the literature revealed that this is the first case report in the literature of SPTCL leading to severe liver failure. Conclusions: For patients presenting with fever and liver injury, primary liver disease cannot simply be assumed, as this presentation may be a manifestation of some extra-hepatic diseases, including SPTCL. For this condition, early detection and early diagnosis may improve the prognosis of patients.