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Abstract Background Systemic amyloidosis is a kind of clinical syndrome in which amyloid is deposited between the cells of various organs in the body, resulting in gradual failure of the function of the affected organs. Depending on the site of amyloid deposition, it may show various clinical symptoms of multiple system involvement. Patient concerns A 44-years-old female with spontaneous giant retroperitoneal hematoma was admitted to the emergency department of Peking Union Medical College Hospital in Mar 2023. Diagnoses She was found with a extremely X-factor deficiency and diagnosed with AL amyloidosis according to pathological findings finally. Interventions and outcomes She received a variety of treatments to improve her coagulation function and underwent chemotherapy for AL in the hematology department which improved her coagulation function and was discharged to her local hospital for follow-up treatment. Conclusion This case provides a new reference for emergency doctors in the diagnosis and treatment of acute severe hemorrhagic diseases.

Abstract The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40–1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79–1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58–1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir.

IntroductionThere is growing evidence that patients with SARS-CoV-2 (The severe acute respiratory syndrome coronavirus 2) may have a variety of cardiovascular complications in the post-acute phase of COVID-19, but these manifestations have not yet been comprehensively characterized.MethodsWe performed a systematic review and meta-analysis of primary research papers which evaluated individuals at least four weeks after confirmed COVID-19 diagnosis and reported on cardiovascular disease prevalence. Systematic search conducted without language restrictions from December 1, 2019 to June 31, 2022 on PubMed, EMBASE, Web of Science, Cochrane library, ProQuest Coronavirus Research Database, COVID-19 Living Overview of the Evidence (L-OVE) subset of Episteminokos and the World Health Organization (WHO) Covid-19 databases. Study was reported according to MOOSE-lists and the PRISMA guidelines. The risk of bias was identified using the Newcastle-Ottawa Scale (NOS) for observational studies. Random-effects meta-analyses examined the pooled risk difference in the prevalence of each symptom or symptom combination in cases with confirmed SARS-coV-2 infection compared with controls.ResultsEight cohort studies were eligible, including nearly 10 million people. Long COVID-19 was associated with a higher risk of thromboembolic disorders [HR 3.12 (1.60, 6.08)], coronary heart disease [HR 1.61 (1.13, 2.31)], stroke [HR 1.71 (1.07,2.72)], arrhythmia [HR 1.60 (1.13, 2.26)], cardiomyopathy [HR 1.71 (1.12, 2.61)], myocarditis [HR 6.11 (4.17,8.94)], hypertension [HR 1.70 (1.56, 1.85)], heart failure [HR 1.72 (1.15,2.59)] and cardiogenic shock [HR 2.09 (1.53,2.86)] compared to non-COVID-19 controls. Pooled risk differences in long COVID cases compared to controls were significantly higher for cardiomyopathy [0.15% (0.06, 0.23)], deep vein thrombosis [0.45% (0.06, 0.83)] and hypertension (0.32%, (0.06, 0.58) but not for thromboembolic disorders, coronary disease, stroke, arrhythmia, cardiomyopathy, myocarditis, hypertension, heart failure or cardiogenic shock.ConclusionThe risk of cardiovascular disease increased significantly four weeks or more after recovering from acute COVID-19. Care for survivors after an acute attack of COVID-19 should include paying close attention to cardiovascular health and disease.Systematic Review RegistrationPROSPERO [CRD42022353965].

Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that is associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) may provide new insight into understanding and identifying SI-AKI. Plasma cfDNA from 82 healthy individuals, 7 patients with sepsis non-acute kidney injury (SN-AKI), and 9 patients with SI-AKI was subjected to genomic methylation sequencing. We deconstructed the relative contribution of cfDNA from different cell types based on cell-specific methylation markers and focused on exploring the association between kidney-derived cfDNA and SI-AKI.Based on the deconvolution of the cfDNA methylome: SI-AKI patients displayed the elevated cfDNA concentrations with an increased contribution of kidney epithelial cells (kidney-Ep) DNA; kidney-Ep derived cfDNA achieved high accuracy in distinguishing SI-AKI from SN-AKI (AUC = 0.92, 95% CI 0.7801–1); the higher kidney-ep cfDNA concentrations tended to correlate with more advanced stages of SI-AKI; strikingly, SN-AKI patients with potential kidney damage unmet by SI-AKI criteria showed higher levels of kidney-Ep derived cfDNA than healthy individuals. The autonomous screening of kidney-Ep (n = 24) and kidney endothelial (kidney-Endo, n = 12) specific methylation markers indicated the unique identity of kidney-Ep/kidney-Endo compared with other cell types, and its targeted assessment reproduced the main findings of the deconvolution of the cfDNA methylome. Our study first demonstrates that kidney-Ep- and kidney-Endo-specific methylation markers can serve as a novel marker for SI-AKI emergence, supporting further exploration of the utility of kidney-specific cfDNA methylation markers in the study of SI-AKI.

Objectives Detection and diagnosis of Chlamydia psittaci (C. psittaci) pneumonia is often overlooked due to conventional methods limitations and similarity to other atypical community acquired pneumonia (CAP). Using mNGS, we aimed to distinguish psittacosis from legionellosis for early C. psittaci pneumonia diagnosis and better prognosis.Methods Thirty-seven patients diagnosed with atypical CAP were enrolled in this retrospective study, including 14 C. psittaci pneumonia and 23 Legionella pneumophila (L. pneumophila) pneumonia. We collected and compared baseline, lab results, radiology imaging, conventional microbiological methods and more importantly, mNGS results of clinical samples, as well as the treatments and prognosis between psittacosis and legionellosis.Results Patients with C. psittaci and L. pneumophila had similar symptoms and were presented with high levels of inflammatory markers. However, patients with C. psittaci pneumonia were more likely to have exposure to birds or parrots [11 (78.6%) vs. 2 (8.7%), p

BackgroundIn sepsis, the lung is one of the worst affected organs, often leading to acute lung injury (ALI). More and more evidence suggests that macrophages are also involved in the pathogenesis of ALI. In our previous study, we successfully synthesized Iron-capsaicin-based nanoparticles (Fe-CAP NPs) and found that it could inhibit the secretion of inflammatory cytokines to alleviate ALI. Here, we further explore the anti-inflammatory mechanism of Fe-CAP NPs.MethodsBone marrow-derived macrophages (BMDM) and C57 mice were divided into four groups: control group, lipopolysaccharide (LPS) group, CAP + LPS group and Fe-CAP + LPS group. Western blot and Immunofluorescence were used to detect the expression of macrophage phenotypic markers CD86 and CD206 in BMDM and lung tissue. Fluorescence microbeads, Transwell and ROS kit were used to detect the phagocytosis, migration and ROS clearing capability of BMDM. Western blot was used to detect the expression of JAK2/STAT3 pathway and apoptosis proteins in BMDM. TUNEL kit and H&E staining were used to evaluate apoptosis and pathological changes in lung tissue.ResultsIn vitro, CD86 expression was increased in LPS, but decreased after Fe-CAP pretreatment. CD206 expression was the opposite. Fe-CAP reduced phagocytosis, migration and scavenged ROS in LPS-treated BMDM. Fe-CAP inhibited P-JAK2 and P-STAT3 expression and reduced apoptosis. In vivo, Fe-CAP improved lung histopathology and reduced apoptosis in lung tissue of LPS group. CD86 expression was increased in lung tissue of LPS group, but decreased in Fe-CAP preconditioning, and CD206 expression was reversed.ConclusionFe-CAP NPs could alleviate sepsis-induced ALI by regulating the polarization and function of macrophages, reducing ROS level and apoptosis.

Abstract Background Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. Methods We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. Results A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48–5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02–26.02; p

Abstract Background Early, rapid, and accurate pathogen diagnosis can help clinicians select targeted treatment options, thus improving prognosis and reducing mortality rates of severe pneumonia. Metagenomic next-generation sequencing (mNGS) has a higher sensitivity and broader pathogen spectrum than traditional microbiological tests. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes and cost-effectiveness in patients with severe pneumonia have not been evaluated. Methods This is a regional, multi-center, open, prospective, randomized controlled trial to evaluate that whether the combination of mNGS and traditional testing methods could decrease 28-day call-cause mortality with moderate cost-effectiveness. A total of 192 patients with severe pneumonia will be recruited from four large tertiary hospitals in China. Bronchoalveolar lavage fluid will be obtained in all patients and randomly assigned to the study group (mNGS combined with traditional microbiological tests) or the control group (traditional microbiological tests only) in a 1:1 ratio. Individualized antimicrobial treatment and strategy will be selected according to the analysis results. The primary outcome is 28-day all-cause mortality. The secondary outcomes are ICU and hospital length of stay (LOS), ventilator-free days and ICU-free days, consistency between mNGS and traditional microbiological tests, detective rate of mNGS and traditional microbiological tests, turn-out time, time from group allocation to start of treatment, duration of vasopressor support, types and duration of anti-infective regimens, source of drug-resistant bacteria or fungi, and ICU cost. Discussion The clinical benefits of mNGS are potentially significant, but its limitations should also be considered. Trial registration ChineseClinicalTrialRegistry.org, ChiCTR2300076853. Registered on 22 October 2023.

Abstract Objectives This study was conducted to characterize the need for palliative care and its effect on patients with end-stage disease in the emergency department (ED). Design This was a prospective cohort study. A questionnaire survey was administered to patients with end-stage disease who were admitted to the resuscitation room of the ED and expected to live less than 6 months. Results A total of 82 of 2095 patients admitted to the resuscitation room were included. Only 1 (1.22%) patient had ever received palliative care before admission. Nine patients received palliative care consultation after admission, and they were more likely to select medical places of death accompanied by their families and do not resuscitate orders at the end of life after consultation (P

Abstract Background Chylopericardium is a rare condition characterized by the accumulation of chyle in the pericardial space. It is most commonly caused by thoracic duct injury. Chylopericardium following esophagectomy is extremely rare but can cause life-threatening complications. This report presents a case of chylopericardium post-esophagectomy, resulting in cardiac tamponade and cardiac arrest. A systematic literature review was also conducted to facilitate the understanding of this rare condition. Case presentation A 41-year-old male was admitted to our hospital with intermediate to highly differentiated squamous cell carcinoma of the mid-thoracic esophagus (clinical T4NxM0). He underwent thoracoscopic-laparoscopic esophagectomy with cervical anastomosis. On postoperative day 1, patient had a cardiac arrest secondary to cardiac tamponade, requiring emergency ultrasound-guided drainage. The drained fluid was initially serous but became chylous after the administration of enteral nutritional emulsion. As a result of significant daily pericardial drainage, patient subsequently underwent thoracic duct ligation. The amount of drainage was substantially reduced post-thoracic duct ligation. Over a period of 2 years and 7 months, patient recovered well and tolerated full oral diet. A comprehensive literature review was conducted and 4 reported cases were identified. Among these cases, three patients developed pericardial tamponade secondary to chylopericardium post-esophagectomy. Conclusion Chylopericardium is a rare but serious complication post-esophagectomy. Prompt echocardiography and thorough pericardial fluid analysis are crucial for diagnosis. Thoracic duct ligation has been shown to be an effective management approach for this condition.

Abstract Aims We aimed to investigate the independent associations between growth differentiation factor 15 (GDF‐15) level at admission and cardiovascular (CV) death, thrombotic events, heart failure (HF), and bleeding outcomes in patients with coronary artery disease (CAD). Methods and results We measured the plasma concentrations of GDF‐15 centrally in patients from the BIomarker‐based Prognostic Assessment for patients with Stable angina and acute coronary Syndrome (BIPass) registry, which consecutively enrolled patients with CAD from November 2017 to September 2019 at five tertiary hospitals in China. The outcomes included CV death, thrombotic events [myocardial infarction (MI) and ischaemic stroke], HF events [acute HF during hospitalization and hospitalization for HF post‐discharge (A/H HF) and cardiogenic shock], and bleeding outcomes [non‐coronary artery bypass grafting‐related major bleeding and clinically significant bleeding (CSB)] during the 12 month follow‐up period after hospitalization. Among 6322 patients with CAD {65.4% male, median age 63.7 [inter‐quartile range (IQR)] 56.0–70.1 years}, the median concentration of plasma GDF‐15 at admission was 1091 (IQR 790.5–1635.0) ng/L. Higher concentrations of GDF‐15 were associated with an increased risk of CV death [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.35–2.88, P

Abstract Background The inflammatory immune response is involved in the pathophysiology of the post-cardiac arrest syndrome and leads to high mortality. The admission (neutrophil + monocyte) to lymphocyte ratio (NMLR) can help us to assess the immune inflammatory status of patients. We aimed to identify factors that affect the prognosis and explore the association between NMLR and the prognosis of patients after cardiopulmonary resuscitation (CPR). Methods This is a retrospective study based on the MIMIC-IV database. We assessed patients admitted to the ICU after cardiopulmonary resuscitation, included demographic characteristics, peripheral blood cell count and blood gas indicators for the first time after admission to the ICU, developed a multivariate COX proportional-hazards model to explore prognostic factors, and divided patients into High NMLR and Low NMLR groups by cutoff values of NMLR. Propensity score matching (PSM) was used to adjust confounding factors. Results A total of 955 patients were included in the analysis, with 497 surviving and 458 dying during the follow-up period. In a multivariate Cox proportional-hazards model, age (RR 1.007, p = 0.0411), NMLR levels (RR 1.003, p = 0.0381), lactate (RR 1.097, p 14.2) and a low NMLR group (≤ 14.2) based on the optimal threshold for NMLR. Compared to low NMLR group, high NMLR group had higher total vasoactive drugs and lower 28-day survival. After PSM, there were no differences in baseline characteristics. The high NMLR group still had a higher mortality rate (p = 0.001), lower 28-day survival (p = 0.001) and shorter length of stay (p = 0.005) compared to the low NMLR group. Conclusions Age, NMLR levels, lactate levels and hematocrit were independent risk factors for death in patients after CPR. NMLR > 14.2 was associated with higher mortality and was a potential predictor of clinical outcome in patients after CPR.

Background. High-quality chest compression (CC) is the crux of survival for cardiac arrest patients. While, rescuers’ position setting relative to patients during CC was unrecommended in the present guidelines. We aimed to assess the impact of position settings on CC quality during cardiopulmonary resuscitation (CPR) and to test the heterogeneity related to rescuers’ characteristics. Methods. We conducted randomized, crossover, simulation trials with clinical students unfamiliar with CPR. The participants received standard training on performing CC and were divided randomly into two groups. The two groups separately performed CC with standing and kneeling positions in turn, forming the crossover design. The trials were performed with standard manikin models. CC quality indicator data were recorded by the tracking and feedback system automatically. Result. 156 participants finished at least one round of trial, with 126 participants finishing both rounds. Records for CC with kneeling and standing positions showed statistically significant differences in the correct rate, pause happening, average depth, and happening of over-depth compression. Regression analysis also implied that larger compression depths with the standing position were related to larger height and BMI of the participants. Conclusion. When performing CC, the standing position will lead to lower CC quality by larger chance of pause happening and over-depth compression. In addition, compression depth gaps between CC with kneeling and standing position were related with rescuer characteristics including height and BMI, with a threshold effect.

Abstract Background Acute pancreatitis is a serious threat to human health and gastrointestinal dysmotility is a common complication for acute pancreatitis patients, resulting in delayed feeding, oral feeding intolerance, paralytic ileus, and abdominal compartment syndrome. Currently, there are limited treatment for this complication. Neostigmine is known to increase gastrointestinal motility and has been used to treat gastrointestinal dysmotility after surgery. However, research in treating acute pancreatitis with neostigmine is currently limited. Methods This trial is a randomized, placebo-controlled, double-blinded, mono-centric trial that will test the hypothesis that neostigmine can improve gastrointestinal motility in patients with severe acute pancreatitis. Up to 56 patients will be randomized in this study receiving 0.5 mg/1 ml of neostigmine methylsulfate injection twice per day or 1 ml of saline injection twice per day. Defection time (aim 1), mortality and organ failure (aim 2), borborygmus, starting of enteral nutrition and intra-abdominal pressure (aim 3), and length of ICU and hospital stay (aim 4) will be assessed. Discussion Findings from this study will provide data supporting the usage of neostigmine for treating severe acute pancreatitis patients with gastrointestinal dysmotility. Trial registration This study is registered on chictr.org.cn with the identifier as ChiCTR2200058305. Registered on April 5, 2022.

Abstract Background Cardiac arrest is currently one of the leading causes of mortality in clinical practice, and the Charlson Comorbidity Index (CCI) is widely utilized to assess the severity of comorbidities. We aimed to evaluate the relationship between the age-adjusted CCI score and in-hospital mortality in intensive care unit (ICU) patients with the diagnosis of cardiac arrest, which is important but less explored previously. Methods This was a retrospective study including patients aged over 18 years from the MIMIC-IV database. We calculated the age-adjusted CCI using age information and ICD codes. The univariate analysis for varied predictors’ differences between the survival and the non-survival groups was performed. In addition, a multiple factor analysis was conducted based on logistic regression analysis with the primary result set as hospitalization death. An additional multivariate regression analysis was conducted to estimate the influence of hospital and ICU stay. Results A total of 1772 patients were included in our study, with median age of 66, among which 705 (39.8%) were female. Amongst these patients, 963 (54.3%) died during the hospitalization period. Patients with higher age-adjusted CCI scores had a higher likelihood of dying during hospitalization (P

As a hallmark of COVID-19 progression, lymphopenia alongside its subtle immune disturbance has been widely reported, but yet to be thoroughly elucidated. Aiming at exploring clinical immune biomarkers with accessibility in the current and acute omicron epidemic abrupted in China post-control era, we design a real-world prospective observation cohort in Peking Union Medical College Hospital to describe immunological, haematological profiles inducing lymphocyte subsets related to SARS-CoV-2 infection. In this COVID-19 cohort, we enrolled 17 mild/moderate (M/M), 24 severe (S) and 25 critical (C) patients. The dynamics of lymphocytes of COVID-19 demonstrated that the sharp decline of NK, CD8+, and CD4+ T cell counts was the main contributor to lymphopenia in the S/C group, compared to the M/M group. Expressions of activation marker CD38 and proliferation marker Ki-67 both in CD8+ T and NK cells were significantly higher in all COVID-19 patients than that in healthy donors, independent of disease severity. The subsequent analysis showed in contrast to the M/M group, NK and CD8+ T cell counts remained low-level after therapy in the S/C group. CD38 and Ki-67 expressions in NK and CD8+ T cells still stay at a high level, despite active treatment. Targeting relatively elderly patients with SARS-CoV-2 infection, severe COVID-19 features the unreversible reduction of NK and CD8+ T cells with persistent activation and proliferation, which assist clinicians in early recognizing and saving severe or critical COVID-19 patients. Given that immunophenotype, the new immunotherapy improving NK and CD8+ T lymphocyte antiviral efficiency should be considered.

AbstractBackground Pheochromocytomas and paragangliomas (PPGLs) are a group of rare neuroendocrine tumors. Dysglycemia has been observed in patients with PPGLs in some small case series. However, there is limited information available on the factors associated with development and resolution of dysglycemia in these patients.Patients and methods The clinical data of consecutive patients admitted to our hospital with PPGLs between January 2018 and June 2020 were retrospectively analyzed. Clinical characteristics were compared between patients with and without dysglycemia. Logistic regression analysis was used to identify risk factors and receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the variables.Results Among 163 patients, 58.9% had preoperative dysglycemia. Patients with dysglycemia were significantly older at diagnosis (p = 0.01) and were significantly more likely to have hypertension (p = 0.007). White blood cell counts (p = 0.016), 24-hour urinary epinephrine (24hU-E) levels (p

AbstractAim To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori methenamine silver (GMS) staining and serum 1,3-β-d-Glucan (BG) assay.Methods 52 PCP patients and 103 patients with non-pneumocystic jirovecii pneumonia (non-PCP) were enrolled, and comparative analysis was conducted of different diagnostic tests. Clinical features and co-pathogen characteristics were reviewed.Results The diagnostic sensitivity (92.3%) and specificity (87.4%) of mNGS did not show significant differences compared with that of PCR while mNGS had the advantage over PCR in the detection of co-pathogens. Despite its excellent specificity, the sensitivity of GMS staining (9.3%) was inferior to that of mNGS (p

The protein homeostasis (proteostasis) network is a nexus of molecular mechanisms that act in concert to maintain the integrity of the proteome and ensure proper cellular and organismal functionality. Early in life the proteostasis network efficiently preserves the functionality of the proteome, however, as the organism ages, or due to mutations or environmental insults, subsets of inherently unstable proteins misfold and form insoluble aggregates that accrue within the cell. These aberrant protein aggregates jeopardize cellular viability and, in some cases, underlie the development of devastating illnesses. Hence, the accumulation of protein aggregates activates different nodes of the proteostasis network that refold aberrantly folded polypeptides, or direct them for degradation. The proteostasis network apparently functions within the cell, however, a myriad of studies indicate that this nexus of mechanisms is regulated at the organismal level by signaling pathways. It was also discovered that the proteostasis network differentially responds to dissimilar proteotoxic insults by tailoring its response according to the specific challenge that cells encounter. In this mini-review, we delineate the proteostasis-regulating neuronal mechanisms, describe the indications that the proteostasis network differentially responds to distinct proteotoxic challenges, and highlight possible future clinical prospects of these insights.

Background Percutaneous catheter drainage (PCD) has been viewed as first-line treatment for pyogenic liver abscess (PLA), yet detailed guidance is lacking for best practice of PCD. This study investigated characteristics of patients with PLA who had received PCD, identified factors associated with prolonged fever, and aimed to evaluate the relationship between timing of PCD and clinical improvement.Methods This was a retrospective study of patients with PLA who had undergone PCD over a 7-year period. PCD performed when the liquefaction degree of abscesses was less than 30% and/or within 1 week after fever onset was defined as early PCD. Patients were grouped and analysed based on the timing of PCD (early vs. delayed). Factors associated with prolonged fever were also analysed using univariate and multivariate logistic regression.Results Among 231 patients with PLA, 81 treated with PCD were included in the study after exclusion. The size of abscesses ranged from 3.4 to 16 cm in diameter. Interestingly, the abscesses were predominantly multiloculated in this cohort (82.7%). The most common pathogen isolated from pus was Klebsiella pneumoniae (60.5%), followed by Escherichia coli (8.6%). The duration of fever was significantly shortened with early PCD as compared to delayed PCD intervention (p = .042). No statistical differences were found between the two groups with regard to catheter adjustment and salvage drainage. Maximum body temperature and diameter of abscess > 7.5 cm were found to be associated with prolonged fever while early PCD was inversely related to prolonged fever. Multivariate analysis suggested that early PCD treatment was an independent protective factor of prolonged fever (p = .030).Conclusions Large abscesses with loculation could be successfully treated with PCD, and early PCD protected patients with PLA from prolonged fever. Our findings suggest that early intervention should be provided if PCD is indicated in clinical practice.KEY MESSAGESLarge abscesses and multiloculated abscesses can be treated with percutaneous catheter drainage.Early percutaneous catheter drainage is identified as a protective factor of prolonged fever among patients with pyogenic liver abscesses.Early intervention should be provided if percutaneous catheter drainage is indicated for pyogenic liver abscesses.

Abstract Background Noninvasive ventilation (NIV) is the recommended mode of ventilation used in acute respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Recent data has shown that high-flow nasal cannula (HFNC) treatment can be an alternative for patients with hypercapnic respiratory failure. The purpose of this study is to evaluate HFNC with sequential NIV versus NIV alone as the initial ventilatory strategy in AECOPD. Methods This investigator-initiated, unblinded, single center, randomized controlled trial will be conducted in the emergency department, emergency intensive care unit, or respiratory intensive care unit of a tertiary-care urban teaching hospital. A total of 66 patients will be enrolled and randomized into the intervention group (HFNC with sequential NIV) or the control group (NIV group). The primary endpoint will be the mean difference in PaCO2 from baseline to 24 h after randomization. Secondary endpoints include the mean difference in PaCO2 from baseline to 6, 12, and 18 h, as well as the dyspnea score, overall discomfort score, rate of treatment failure, respiratory rate, rate of endotracheal intubation, length of hospital stay, and mortality. Discussion Taking the advantages of both HFNC and NIV on AECOPD patients into account, we designed this clinical trial to investigate the combination of these ventilatory strategies. This trial will help us understand how HFNC with sequential NIV compares to NIV alone in treating AECOPD patients. Trial registration ChiCTR2100054809.

Abstract Background There is growing evidence that patients recovering after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have a variety of acute sequelae including newly diagnosed diabetes. However, the risk of diabetes in the post-acute phase is unclear. To solve this question, we aimed to determine if there was any association between status post-coronavirus disease (COVID-19) infection and a new diagnosis of diabetes. Methods We performed a systematic review and meta-analysis of cohort studies assessing new-onset diabetes after COVID-19. PubMed, Embase, Web of Science, and Cochrane databases were all searched from inception to June 10, 2022. Three evaluators independently extracted individual study data and assessed the risk of bias. Random-effects models estimated the pooled incidence and relative risk (RR) of diabetes compared to non-COVID-19 after COVID-19. Results Nine studies with nearly 40 million participants were included. Overall, the incidence of diabetes after COVID-19 was 15.53 (7.91–25.64) per 1000 person-years, and the relative risk of diabetes after COVID-19 infection was elevated (RR 1.62 [1.45–1.80]). The relative risk of type 1 diabetes was RR=1.48 (1.26–1.75) and type 2 diabetes was RR=1.70 (1.32–2.19), compared to non-COVID-19 patients. At all ages, there was a statistically significant positive association between infection with COVID-19 and the risk of diabetes: 65 years: RR=1.68 (1.22–2.30). The relative risk of diabetes in different gender groups was about 2 (males: RR=2.08 [1.27–3.40]; females: RR=1.99 [1.47–2.80]). The risk of diabetes increased 1.17-fold (1.02–1.34) after COVID-19 infection compared to patients with general upper respiratory tract infections. Patients with severe COVID-19 were at higher risk (RR=1.67 [1.25–2.23]) of diabetes after COVID-19. The risk (RR=1.95 [1.85–2.06]) of diabetes was highest in the first 3 months after COVID-19. These results remained after taking confounding factors into account. Conclusions After COVID-19, patients of all ages and genders had an elevated incidence and relative risk for a new diagnosis of diabetes. Particular attention should be paid during the first 3 months of follow-up after COVID-19 for new-onset diabetes.

Abstract Background Dexmedetomidine is widely used in patients with sepsis. However, its effect on septic patients remains controversial. The objective of this study was to summarize all randomized controlled trials (RCTs) examining dexmedetomidine use in sepsis patients. Methods This systematic review and meta-analysis included RCTs comparing dexmedetomidine with other sedatives in adult sepsis patients. We generated pooled relative risks (RRs) and standardized mean differences and performed trial sequential analysis and a cumulative meta-analysis. The primary outcome was mortality, and the secondary outcomes were the length of the intensive care unit stay, duration of mechanical ventilation, number of ventilation-free days, incidence of total adverse event, incidence of delirium, and levels of interleukin 6, tumor necrosis factor alpha, and alanine aminotransferase. Results We included 19 RCTs that enrolled 1929 patients. Compared with other sedatives, dexmedetomidine decreased the all-cause mortality (RR 0.83; 95% confidence interval [CI] [0.69, 0.99]) and inflammatory response (interleukin 6 and tumor necrosis factor alpha levels at 24 h: standardized mean difference (SMD) − 2.15; 95% CI [− 3.25, − 1.05] and SMD − 1.07, 95% CI [− 1.92, − 0.22], respectively). Trial sequential analysis showed that it is not up to required information size. The overall risk adverse events was similar between dexmedetomidine and the other sedatives (RR 1.27, 95% CI [0.69, 2.36]), but dexmedetomidine increased the risk of arrhythmias (RR 1.43, 95% CI [0.59, 3.51]). Length of intensive care unit stay (SMD − 0.22; 95% CI [− 0.85, − 0.41]), duration of mechanical ventilation (SMD 0.12; 95% CI [− 1.10, 1.35]), incidence of delirium (RR 0.98; 95% CI [0.72, 1.33]), and levels of alanine aminotransferase and creatinine at 24 h were not significantly reduced. Conclusions Dexmedetomidine in sepsis patients could significantly reduce mortality compared with benzodiazepines but not with propofol. In addition, dexmedetomidine can significantly decrease inflammatory response in patients with sepsis compared with other sedatives. Dexmedetomidine might lead to an increased incidence of arrhythmias, but its safety profile did not show significant differences in the incidence of total adverse events. Future RCTs are needed to determine the sepsis patient population that would benefit most from dexmedetomidine and its optimal dosing regimen.

Abstract. Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022, which has exceeded the past annual incidences of related regions, and has aroused wide concern. Affected patients were predominantly children under 16 years of age, presented with symptoms of acute hepatitis with markedly elevated liver enzymes, and had been ruled out of common viral infections such as hepatitis A, B, C, D, and E. Similar cases have not been reported in China yet. However, considering that the severe acute hepatitis has involved worldwide areas, still with unknown origin, and incidences of severity is relatively high, we formulated this recommendation to standardize diagnosis and treatment of acute severe hepatitis of unknown origin in Peking Union Medical College Hospital, to get fully prepared to the possible public health events.

Abstract Background Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a common type of autoimmune encephalitis. Patients with this condition are frequently very ill but are often misdiagnosed in the Emergency Department (ED). The objective of this study was to analyze the clinical characteristics of anti-NMDAR patients in the ED and to identify any associations with a diagnosis of anti-NMDAR encephalitis. Methods We performed a retrospective analysis of a prospectively obtained cohort of ED patients from May 2011 to December 2017. We identified patients diagnosed with anti-NMDAR encephalitis in this cohort and extracted key patient characteristics and clinical data, including patient gender, age, presentation, modified Rank Score (m-RS), laboratory test results, significant treatments, and mortality. Results Eighty-seven patients with anti-NMDAR encephalitis were identified. 54 (62.1%) were female, 23 (26.4%) were 50% incidence of each symptom in the cohort. The sensitivity of CSF oligoclonal band (OB) testing was 78.9%. 22 (25.3%) were admitted to the ICU, 20 (23.0%) patients were intubated, but only one patient died (1.1%). 47 (54.0%) were misdiagnosed prior to ED arrival. All patients underwent immunotherapy as first-line treatment for anti-NMDAR encephalitis. Conclusions A majority of anti-NMDAR encephalitis patients presenting to the ED were female and were likely to be misdiagnosed prior to arrival. Patients with symptoms of fever, altered mental status, and seizures need a lumbar puncture, including CSF OB testing, for definitive diagnosis.

Abstract Aims Norepinephrine is recommended as a first‐line vasopressor agent in the haemodynamic stabilization of cardiogenic shock. The survival benefit of norepinephrine therapy has not been demonstrated in clinical practice, however. This study aimed to explore the relationship between norepinephrine use and outcomes in cardiogenic shock patients in real‐world conditions. Methods and results We conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care III (MIMIC‐III) database. Cardiogenic shock patients were enrolled and categorized into a norepinephrine group or a non‐norepinephrine group. Propensity score matching (PSM) was used to control for confounders. Cox proportional‐hazards models and multivariable logistic regression were used to investigate the relationship between norepinephrine treatment and mortality. A total of 927 eligible patients were included: 552 patients in the norepinephrine group and 375 patients in the non‐norepinephrine group. After PSM, 222 cases from each group were matched using a 1:1 matching algorithm. Thirty day mortality for patients treated with norepinephrine was significantly higher than for those in the non‐norepinephrine group (41% vs. 30%, OR 1.61, 95% CI 1.09–2.39, P = 0.017; HR 1.50, 95% CI 1.09–2.06, P = 0.013). In the multivariable analysis, there was no significant difference between norepinephrine therapy and long‐term (90 day, 180 day, or 1 year) mortality (90 day (OR 1.19, 95% CI 0.82–1.74, P = 0.363), 180 day (OR 1.17, 95% CI 0.80–1.70, P = 0.418), 1 year (OR 1.14, 95% CI 0.79–1.66, P = 0.477). Patients in the norepinephrine group required more mechanical ventilation (84% vs. 67%, OR 2.67, 95% CI 1.70–4.25, P

Abstract Background Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection. In non-HIV immunocompromised patients with PCP, a standard second-line treatment has not been established up to now. Methods Non-HIV immunocompromised patients with confirmed PCP between April 2013 and December 2020 were included. Their PCP treatment history was tracked. Factors related to first-line trimethoprim/sulfamethoxazole (TMP/SMX) and second-line treatment failure were identified. Different second-line treatment strategies were compared. Results Among the 220 patients, 127 (57.73%) did not respond to first-line TMP/SMX treatment. Risk factors related to treatment failure included symptom triad with breathlessness at rest, persistent fever and cough (85% in the treatment failure group versus 74% in the treatment success group, P = 0.034), treatment with invasive mechanical ventilation (67 vs. 19%, P

BackgroundPheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors, most of which are characterized by the release of catecholamine, and range in diameters from less than 1 cm to 10 cm or more. However, knowledge of the differences in clinical features between small and large PPGLs is insufficient.MethodsA retrospective analysis of patients with PPGLs treated at our institution between January 2018 and June 2020 was performed. The clinical characteristics of patients were investigated, and comparisons were made between patients with large and small PPGLs. The logistic regression analysis was used to confirm the risk factors, and the receiver operating characteristic curve was used to evaluate the diagnostic performance of the variables.ResultsTotally 263 patients were included, including 110 patients in small tumor group and 153 patients in large tumor group. There were more male patients in the large tumor group (p=0.009). More patients had hypertension (p

Objective: Cardiac dysfunction caused by sepsis, usually termed sepsis-induced cardiomyopathy (SIC), is one of the most serious complications of sepsis, and ferroptosis can play a key role in this disease. In this study, we identified key cuproptosis- and ferroptosis-related genes involved in SIC and further explored drug candidates for the treatment of SIC.Methods: The GSE79962 gene expression profile of SIC patients was downloaded from the Gene Expression Omnibus database (GEO). The data was used to identify differentially expressed genes (DEGs) and to perform weighted correlation network analysis (WGCNA). Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Then, gene set enrichment analysis (GSEA) was applied to further analyze pathway regulation, with an adjusted p-value

Abstract Identifying critically ill patients is a key challenge in emergency department (ED) triage. Mis-triage errors are still widespread in triage systems around the world. Here, we present a machine learning system (MLS) to assist ED triage officers better recognize critically ill patients and provide a text-based explanation of the MLS recommendation. To derive the MLS, an existing dataset of 22,272 patient encounters from 2012 to 2019 from our institution’s electronic emergency triage system (EETS) was used for algorithm training and validation. The area under the receiver operating characteristic curve (AUC) was 0.875 ± 0.006 (CI:95%) in retrospective dataset using fivefold cross validation, higher than that of reference model (0.843 ± 0.005 (CI:95%)). In the prospective cohort study, compared to the traditional triage system’s 1.2% mis-triage rate, the mis-triage rate in the MLS-assisted group was 0.9%. This MLS method with a real-time explanation for triage officers was able to lower the mis-triage rate of critically ill ED patients.

Pneumonia is the fourth leading cause of death globally, and the reason for the high mortality rate of patients with severe community-acquired pneumonia (SCAP) remains elusive. Corticosteroid treatment reduces mortality in adults with SCAP but can cause numerous adverse events. Therefore, novel therapeutic targets need to be explored and new adjunctive immune drugs are urgently required. We analyzed the transcriptome data of peripheral blood leukocytes from patients with SCAP and healthy controls from three perspectives: differentially expressed genes, predicted functions of differentially expressed long non-coding RNAs, and transcriptional read-through. We discovered that the NETosis pathway was top-ranked in patients with SCAP caused by diverse kinds of pathogens. This provides a potential therapeutic strategy for treating patients. Furthermore, we calculated the correlation between the expression of genes involved in NETosis and the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We identified four novel potential therapeutic targets for NETosis in patients with SCAP, including H4C15, H3-5, DNASE1, and PRKCB. In addition, a higher occurrence of transcriptional read-through is associated with a worse outcome in patients with SCAP, which probably can explain the high mortality rate of patients with SCAP.

Background Cardiopulmonary resuscitation (CPR) skills may decay over time after conventional instructor-led BLS training. The Resuscitation Quality Improvement® (RQI®) program, unlike a conventional basic life support (BLS) course, is implemented through mastery learning and low-dose, high-frequency training strategies to improve CPR competence. We facilitated the RQI program to compare the performance of novices vs those with previous BLS training experience before RQI implementation and to obtain their confidence and attitude of the RQI program. Methods A single-center observational study was conducted from May 9, 2021 to June 25, 2021 in an emergency department of a tertiary hospital. The performance assessment data of both trainees with a previous training experience in conventional BLS course (BLS group) and the novice ones with no prior experience with any BLS training (Non-BLS group) was collected by RQI cart and other outcome variables were rated by online questionnaire. Outcome measurements included chest compression and ventilation in both adult-sized and infant-sized manikins. Results A total of 149 participants were enrolled. Among them, 103 participants were in BLS group and 46 participants in Non-BLS group. Post RQI training, all the trainees achieved a passing score of 75 or more, and obtained an improvement in CPR performance. The number of attempts to pass RQI for compression and ventilation practice was lower in the BLS group in both adult and infant training sessions (P < 0.05). Although the BLS group had a poor baseline, it had fewer trials and the same learning outcomes, and the BLS group had better self-confidence. Trainees were well adapted to the innovative training modality, and satisfaction among all of the participants was high. Only the respondents for non-instructor led training, the satisfaction was low in both groups (72.8% in BLS group vs 65.2% in No-BLS group, strongly agreed). Conclusion Among novices, RQI can provide excellent CPR core skills performance. But for those who had previous BLS training experience, it was able to enhance the efficiency of the skills training with less time consumption. Most trainees obtained good confidence and satisfaction with RQI program, which might be an option for the broad prevalence of BLS training in China.

Abstract Background Hypoxia is one of the life-threatening complications of endotracheal intubation. Supplemental oxygen and ventilation play a vital role in preventing hypoxia. Bag-valve mask (BVM) ventilation is frequently used before intubation, and its ability to improve oxygenation was recently confirmed. It is still unclear if positive end-expiratory pressure (PEEP) added to BVM ventilation can further reduce hypoxia during intubation. Methods This will be a prospective, randomized, double-blind trial to determine if PEEP combined with BVM ventilation can reduce the incidence of hypoxia during intubation compared with conventional BVM ventilation. The lowest oxygen saturation and incidence of complications will be compiled to verify the comparative effectiveness and safety of the two groups. Discussion BMV ventilation with PEEP is hoped to further reduce the incidence of hypoxia during intubation. Trial registration Chinese Clinical Trial Registry ChiCTR2000035156 . Registered on August 2, 2020. It had begun enrollment after passing ethical review but before registration.

Sepsis-associated acute kidney injury (SA-AKI) is a severe and life-threatening condition with high morbidity and mortality among emergency patients, and it poses a significant risk of chronic renal failure. Clinical treatments for SA-AKI remain reactive and non-specific, lacking effective diagnostic biomarkers or treatment targets. In this study, we established an SA-AKI mouse model using lipopolysaccharide (LPS) and performed proteomics and metabolomics analyses. A variety of bioinformatic analyses, including gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), protein and protein interactions (PPI), and MetaboAnalyst analysis, were conducted to investigate the key molecules of SA-AKI. Integrated proteomics and metabolomics analysis revealed that sepsis led to impaired renal mitochondrial function and metabolic disorders. Immune-related pathways were found to be activated in kidneys upon septic infection. The catabolic products of polyamines accumulated in septic kidneys. Overall, our integrated analysis provides a multidimensional understanding of SA-AKI and identifies potential pathways for this condition.

Abstract Background Over the past decades, Klebsiella pneumoniae (K. pneumoniae) infections have been increasing and affected immunocompromised patients nosocomially and communally, with extended-spectrum β-lactamase (ESBL) production becoming a major concern. Patients with rheumatic autoimmune diseases, mostly receiving immunosuppressive therapy, are vulnerable to various infections, including K. pneumoniae. However, few have investigated K. pneumoniae infections in this specific population. This study aimed to identify factors associated with ESBL production and mortality of K. pneumoniae pneumonia among patients with rheumatic autoimmune diseases in the Emergency Department. Methods We retrospectively investigated patients with rheumatic diseases who were diagnosed with K. pneumoniae pneumonia. The diagnosis of K. pneumoniae pneumonia was based on clinical manifestations, radiological findings and microbiological testing results. Prognostic factors and risk factors for ESBL production were determined with univariate and multivariate logistic regression analysis. Empirical therapy and antimicrobial susceptibility data were also collected. Results Of 477 K. pneumoniae pneumonia patients, 60 were enrolled into this study. The in-hospital mortality was 28.3%. Septic shock, ICU admission, the need for mechanical ventilation and change of antibiotics due to clinical deterioration, all related to mortality, were included as unfavorable clinical outcomes. Multivariate analysis suggested that ESBL production (OR, 6.793; p = 0.012), initial PCT ≥ 0.5 ng/ml (OR, 5.024; p = 0.033) and respiratory failure at admission (OR, 4.401; p = 0.046) predicted increased mortality. ESBL production was significantly associated with dose of corticosteroids (OR, 1.033; p = 0.008) and CMV viremia (OR, 4.836; p = 0.032) in patients with rheumatic autoimmune diseases. Abnormal leukocyte count (OR, 0.192; p = 0.036) was identified as a protective factor of ESBL-producing K. pneumoniae pneumonia. The most commonly used empirical antibiotic was ceftazidime, while most isolates showed less resistance to carbapenems and amikacin in susceptibility testing. Conclusions K. pneumoniae pneumonia could be life-threatening in patients with rheumatic autoimmune diseases. Our findings suggested that ESBL production, initial PCT ≥ 0.5 ng/ml and respiratory failure at admission were independent factors associated with poor prognosis. Dose of corticosteroids and CMV viremia, predicting ESBL production in K. pneumoniae pneumonia, may help make individualized antibiotic decisions in clinical practice.

Abstract We evaluated the serum levels of (1–3)-beta-d-glucan (BG) and lactate dehydrogenase (LDH) as a tool to support pneumocystis pneumonia (PCP) diagnostic procedures in non-HIV patients. We retrospectively collected non-HIV (human immunodeficiency virus) patients presenting clinical features of PCP between April 1st, 2013, and December 31st, 2018. A total of 225 included patients were tested for Pneumocystis jirovecii by polymerase chain reaction (PCR) and methenamine silver staining. Based on different exclusion criteria, 179 cases were included in the BG group, and 196 cases were included in the LDH group. In each group, cases with positive immunofluorescence (IF) microscopy and PCR were considered proven PCP, while cases with only positive PCR were considered probable PCP. Fifty patients with negative IF and PCR results and proven to be non-PCP infection were chosen randomly as the control group. The cut-off levels of BG and LDH to distinguish non-PCP from probable PCP were 110 pg/mL and 296 U/L with 88% sensitivity and 86% specificity, and 66% sensitivity and 88% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven PCP were 285.8 pg/mL and 379 U/L with 92% sensitivity and 96% specificity, and 85% sensitivity and 77% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven/probable PCP were 144.1 pg/mL and 363 U/L with 90% sensitivity, 86% specificity and 80% sensitivity, 76% specificity respectively. BG and LDH are reliable indicators for detecting P. jirovecii infection in HIV-uninfected immunocompromised patients.

BackgroundBlood products are commonly transfused in patients with acute upper gastrointestinal bleeding (UGIB). There exists considerable practice variation and less evidence to guide fresh frozen plasma transfusion in patients with UGIB. The aim of this study was to explore any association between fresh frozen plasma transfusion following acute UGIB and clinical outcomes.MethodsThis was a prospective, observational, multicenter study conducted at 20 tertiary hospitals in China. Patients with acute UGIB with an international normalized ratio ≤ 2.0 at emergency department admission were included. Multivariate logistic regression models were used to examine and quantify any clinical associations.ResultsA total of 976 patients (61.57 ± 15.79 years old, 73.05% male) were included, of whom 17.42% received fresh frozen plasma transfusion. The overall 90-day mortality and rebleeding rates were 10.20 and 12.19%, respectively. After adjusting for confounding factors, transfusion of fresh frozen plasma during hospitalization was associated with higher 90-day mortality [odd ratio (OR), 2.36; 95% confidence interval (CI), 1.36–4.09; p = 0.002] but not rebleeding (OR, 1.5; 95% CI; 0.94-2.54; p = 0.085). In a subgroup analysis, patients with an international normalized ratio

Abstract Background Klebsiella pneumoniae (K. pneumoniae) invasive liver abscess syndrome (ILAS) with purulent meningitis was rarely identified the mainland of China. Last winter, we received 3 cases of K. pneumoniae meningitis and all of them died in a short time. We report these cases in order to find the reason of high mortality and discuss effective effort to improve these patients’ prognosis. Case presentation Three patients with uncontrolled diabetes developed live abscess and purulent meningitis. Upon admission, the clinical manifestations, laboratory result of blood and cerebrospinal fluid (CSF) and imaging examinations were compatible with K. pneumoniae ILAS which had metastasis infection of meningitis. Even with timely adequate antibiotic therapy and strict glycemic control, all of the patients’ condition deteriorated rapidly and died in a short time. Conclusion The reason of patients’ poor prognosis might be the absence of liver abscess drainage, high level of CSF protein which indicates severe inflammation and unknown special but stronger virulence factors of K. pneumoniae the patients’ living place Zhangjiakou. Strict glycemic control, early drainage of liver abscess and appropriate antibiotic application are recommended for treating this condition, further progress on the pathogenesis and treatment of K. pneumoniae meningitis may help patients gain a better prognosis.

Abstract Background Post-extubation stridor (PES) is one of the most common complications of invasive respiratory support, with severe cases leading to possible extubation failure (reintubation within 48 h) and increased mortality. Previous studies confirmed that prophylactic corticosteroids play an important role in reducing the risk of PES and extubation failure. However, few studies have looked at the efficacy of corticosteroids on preventing PES in patients after an emergency intubation. Aim To evaluate whether a single dose of methylprednisolone given over a set timeframe before extubation is effective in preventing PES in patients after an emergency intubation. Methods A multicenter, randomized, placebo-controlled trial will be performed in an emergency department (ED) setting. The trial will include 132 patients who fail a cuff-leak test (CLT) prior to the intervention. Patients will be randomly assigned to either intravenous methylprednisolone (40 mg) or placebo 4 h prior to extubation. Other eligible patients who pass the CLT will be included in a non-intervention (observation) group. The primary endpoint is the incidence of PES within 48 h after extubation. Secondary endpoints include oxygen therapy, respiratory support requirements, reintubation secondary to PES, adverse effects within 48 h after extubation, hospital length of stay, and hospital mortality. Discussion Patients who are intubated on an emergency basis have a higher risk of intubation-related complications. Previous studies have examined treatment regimens involving more than 10 different variations on corticosteroid treatments for PES prevention, while for ED therapy, only a simple and effective treatment would be appropriate. Corticosteroid administration is usually accompanied by adverse effects; thus, this study will be important for further risk stratification among intubated ED patients. Trial registration Chictr.org.cn ChiCTR2000030349 . Registered on 29 February 2020.

Background: Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed the characteristics of different respiratory viral infections. Methods: Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in a fever clinic. Results: Overall, 1860 patients were screened, and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infections, respectively. The COVID-19 group had a higher rate of contact with the epidemic area within 14 days and of clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever to the highest temperature was higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had a lower white blood cell count and neutrophil count than Flu A virus and RSV infection groups, but higher lymphocyte count than Flu A and B virus infection groups. The COVID-19 group (83.33%) had a higher rate of pneumonia in chest CT scans than Flu A and B virus infection groups. Conclusions: Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of a specific respiratory virus; however, epidemic history was significant for the screening of COVID-19.

Abstract Background Reversible splenial lesion syndrome (RESLES) is a clinico-radiological syndrome characterized by the presence of reversible lesions specifically involving the splenium of the corpus callosum (SCC). The cause of RESLES is unknown. However, infectious-related mild encephalitis/encephalopathy (MERS) with a reversible splenial lesion remains the most common cause of reversible splenial lesions. Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthetic pathway. It can affect the autonomic, peripheral, and central nervous system. Result In this study, we report a 20-year-old woman with AIP who presented with MRI manifestations suggestive of RESLES, she had a novel HMBS nonsense mutation, a G to A mutation in base 594, which changed tryptophan to a stop codon (W198*). Conclusion: To the best of our knowledge, this is only one published case of RELES associated with AIP.

BackgroundCatecholamine excess arising from pheochromocytomas and paragangliomas (PPGLs) can cause a wide spectrum of cardiac manifestations. Although there are reviews of reported cases, these reviews lack detailed data, which makes it impossible to perform an accurate analysis. In this study, we conducted a comprehensive analysis of cardiovascular complications (CCs), including PPGL-related myocardial injury, cardiogenic shock, and arrhythmias requiring antiarrhythmic therapy, in a large cohort of patients with PPGL.MethodsWe retrospectively analyzed the clinical data of consecutive patients with PPGL admitted between January 2018 and June 2020. The prevalence and the characteristics of patients with CCs were investigated. Moreover, comparisons were made between patients with and without CCs.ResultsCompared with the non-CC group, the percentage of men was significantly lower (14/41 vs.92/175, 34.1% vs. 52.6%, p = 0.034) and the proportion of patients with paroxysmal hypertension was significantly higher (13/41 vs.29/173, 31.7% vs.16.8%, p = 0.03) in the CC group. More patients showed excessive sweating (19/41 vs 64/175, 46.3% vs. 24.0%, p = 0.004) and PPGL crisis (7/41 vs. 10/175, 17.1% vs.5.7%, p=0.035) in the CC group. In terms of laboratory findings, higher white blood cell [7.36 (6.49, 20.23) vs. 5.95 (5.1, 6.97)×109/L, p

Immunosuppression and host vulnerability play a key role in non-tuberculous mycobacteria (NTM) pathogenesis. The objective of this study was to compare the clinical characteristics and mortality of NTM infections in immunocompromised and immunocompetent patients. We used a retrospective dataset obtained from our large, tertiary, urban, teaching hospital which is the medical records of hospitalized patients with NTM infections between January 1, 2013 to December 31, 2020. The information including clinical manifestations, imaging, and NTM etiological data were obtained from the hospital's clinical data system. A total of 480 patients with NTM infections completed species identification. 118 hospitalized NTM patients who met ATS/IDSA NTM diagnostic criteria and had complete medical records were included in the study. The average age was 49.4 years, 57 (48.3%) were female, and 64 (54.2%) were immunosuppressed hosts. In our study, the most common species in order of frequency were: M. intracellulare, M. abscessus, M. avium, and M. kansasii among NTM patients. The most common comorbidity was history of previous tuberculosis (30.5%). Besides malignancy, the most common immunodeficiencies were adult-onset immunodeficiency induced by anti-interferon-gamma autoantibody, SLE, and vasculitis. The immunocompromised patients with NTM had more clinical symptoms, comorbidities and lower lymphocyte counts compared to immunocompetent patients. The mortality we observed in immunocompromised patients of NTM disease was significantly higher than that of immunocompetent patients (HR 3.537, 95% CI 1.526–8.362). Immunosuppressed NTM patients with lower B and CD4+ T lymphocyte counts may more frequently present with disseminated NTM infections, clinical exacerbations, and higher mortality than immunocompetent patients.

BackgroundWhether heart failure (HF) is an independent risk factor of ischemic stroke (IS) and hemorrhagic stroke remains controversial. We employed a multivariable Mendelian randomization (MR) to further investigate the causal effects of HF on the risk of stroke and stroke subtypes.MethodsGenetically predicted HF was selected as an instrumental variable (IV) from published genome-wide association studies (GWAS) meta-analyses. Stroke data with different etiologies were extracted as outcome variables from another two GWAS meta-analyses. The random-effects inverse variance-weighted (IVW) model was applied as the main method, along with sensitivity analysis. Atrial fibrillation (AF), coronary heart disease (CHD), and systolic blood pressure (SBP) were controlled for mediating effects in multivariable MR.ResultsGenetically predicted HF was significantly associated with any IS [odds ratio (OR), 1.39; 95% CI, 1.12–1.74; p = 0.03], large artery stroke (LAS; OR, 1.84; 95% CI, 1.27–2.65; p = 0.001), and cardioembolic stroke (CES; OR, 1.73; 95% CI, 1.21–2.47; p = 0.003), but without small vessel stroke (SVS; OR, 1.1; 95% CI, 0.80–1.52; p = 0.56) and intracerebral hemorrhage (ICH; OR, 0.86; 95% CI, 0.41–1.83; p = 0.699) in univariable MR. However, these significant associations were attenuated to the null after adjusting for confounding factor in multivariable MR.ConclusionThere was no direct causal association between HF and stroke in our study. The association between HF and IS can be driven by AF, CHD, and SBP.

Summary: The protein homeostasis (proteostasis) network (PN) encompasses mechanisms that maintain proteome integrity by controlling various biological functions. Loss of proteostasis leads to toxic protein aggregation (proteotoxicity), which underlies the manifestation of neurodegeneration. How the PN responds to dissimilar proteotoxic challenges and how these responses are regulated at the organismal level are largely unknown. Here, we report that, while torsin chaperones protect from the toxicity of neurodegeneration-causing polyglutamine stretches, they exacerbate the toxicity of the Alzheimer’s disease-causing Aβ peptide in neurons and muscles. These opposing effects are accompanied by differential modulations of gene expression, including that of three neuropeptides that are involved in tailoring the organismal response to dissimilar proteotoxic insults. This mechanism is regulated by insulin/IGF signaling and the transcription factor SKN-1/NRF. Our work delineates a mechanism by which the PN orchestrates differential responses to dissimilar proteotoxic challenges and points at potential targets for therapeutic interventions.

BackgroundTracheal intubation is a necessary but risky procedure performed in emergency departments (EDs) around the world. Relatively high morbidity has been encountered in Chinese EDs, which has raised concerns about peri-intubation ED management. This study aimed to investigate intubation procedures and identify any areas for improvement in Chinese EDs.MethodsThis was a questionnaire-based survey lasting 1 month (March 2021) in 41 tertiary-care hospital EDs in mainland China. The primary outcome was complications associated with intubation. Secondary outcomes were the first-pass success rate and blood pressure variations during intubation. Univariate and binary logistic regression analyses were used to find possible risk factors for first-pass intubation failure.ResultsIn total, 1,020 replies were analyzed out of 1,080 surveys submitted (94.4% response rate). Most patients were elderly men with severe medical conditions like cardiac arrest (24.8%). In total, 97.2% of patients were given preoxygenation, and 48.1% received some form of pretreatment. Induction drugs (e.g., etomidate and ketamine) were less often used: 39.9% of intubations used sedatives, 5.5% used analgesics, and only 5.3% used muscle relaxants. The overall first-pass intubation success rate was 85.7% and was accompanied by a 19.8% adverse event rate. A marked decrease in blood pressure after intubation was also identified.ConclusionThis survey found an 85.7% tracheal intubation first-pass success rate (which is relatively high compared to other countries) and a 19.8% adverse event rate (which is also relatively high). Given the very low rate of using induction medications (5.3% used muscle relaxants), future education should focus on induction drugs and traditional intubation techniques.

Background: Cardiac paragangliomas (CPGLs) are rare neuroendocrine tumors that are easily overlooked and difficult to diagnose. Detailed comprehensive data regarding CPGL diagnosis and outcome are lacking.Methods: We retrospectively analyzed a cohort of 27 CPGL patients. This cohort represents the largest such cohort reported to date.Results: The prevalence of trilogy symptoms (concurrent palpitations, hyperhidrosis, and headache) was frequent (9/27, 33.3%). Sensitivity of echocardiography and contrast-enhanced computed tomography for localization of CPGL were 81.8% and 87%, respectively. Octreotide scintigraphy showed 100% sensitivity for detecting GPCLs, while sensitivity of I131-metaiodoben-zylguanidine scintigraphy was only 32.9%. Multiple tumors were found in 29.6% of patients. Most CPGLs originated from the epicardium or root of the great vessels (92.9%) and were mostly supplied by the coronary arteries and their branches (95.7%). Twenty-four patients underwent surgical treatment. Although local invasion was present in 40.0% of patients, it did not affect long-term outcome. Mean follow-up was 6.9 ± 3.6 years. Biochemical remission was achieved in 85% of patients. The recurrence rate was 15%.Conclusions: Manifestations of CPGLs are non-specific and they can be difficult to detect on imaging examinations. Octreotide scintigraphy should be performed in patients with suspected paragangliomas to screen for multiple lesions. Surgical resection of CPGLs can achieve symptom relief and biochemical remission.

Objective: The study aims to develop a mechanical learning model as a predictive model for predicting the appearance of sepsis-associated encephalopathy (SAE).Materials and Methods: The prediction model was developed in a primary cohort of 2,028 sepsis patients from June 2001 to October 2012, retrieved from the Medical Information Mart for Intensive Care (MIMIC III) database. Least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction and feature selection. The model was developed using multivariable logistic regression analysis. The performance of the nomogram has been evaluated in terms of calibration, discrimination, and clinical utility.Results: There were nine particular features in septic patients that were significantly associated with SAE. Predictors of individualized prediction nomograms included age, rapid sequential evaluation of organ failure (qSOFA), and drugs including carbapenem antibiotics, quinolone antibiotics, steroids, midazolam, H2-antagonist, diphenhydramine hydrochloride, and heparin sodium injection. The area under the curve (AUC) was 0.743, indicating good discrimination. The prediction model showed calibration curves with minor deviations from the ideal predictions. Decision curve analysis (DCA) suggested that the nomogram was clinically useful.Conclusion: We propose a nomogram for the individualized prediction of SAE with satisfactory performance and clinical utility, which could aid the clinician in the early detection and management of SAE.

ABSTRACTConfirmative diagnosis of SARS-CoV-2 infections has been challenged due to unsatisfactory positive rate of molecular assays. Here we identified a family cluster of SARS-CoV-2 infections, with five of six family members were SARS-CoV-2-specific immunoglobin serology testing positive, while molecular assays only detected two of this five patients even repeated twice. We comprehensively analyzed this familial cluster of cases based on the clinical characteristics, chest CT images, SARS-CoV-2 molecular detection results, and serology testing results. At last, two patients were diagnosed with COVID-19, two were suspected of COVID-19, and two were considered close contacts. Our results emphasized the significance of serology testing to assist timely diagnosis of SARS-CoV-2 infections, especially for COVID-19 close contacts screening.

Abstract Background It is widely agreed that triglyceride (TG)-lowering therapy is imperative in early hypertriglyceridemia-induced acute pancreatitis (HTG-AP). Intravenous insulin with or without heparin, and plasmapheresis are available regimens. However, there is no consensus on first-line therapy. Methods/design The Bi-TPAI trial is a multicenter, parallel group, randomized, controlled, non-inferiority trial in patients with early HTG-AP. The Bi-TPAI trial will include 220 patients with HTG-AP from 17 large tertiary hospitals in China. Patients assigned to the intensive insulin group will be administered an intravenous continuous infusion of regular human insulin at a rate of 0.1 units/kg·h and up to 0.3 units/kg·h. Patients allocated to the plasmapheresis group will receive standard-volume plasmapheresis. The primary endpoint is the time it takes for the TG level to reduce to 500 mg/dl. The secondary endpoints are ICU and hospital lengths of stay, 28-day mortality, severity of HTG-AP, incidence of hypoglycemia, HTG-AP complications, and cost-effectiveness. Discussion The Bi-TPAI trial will prove that intensive insulin therapy is non-inferior to plasmapheresis. Intensive insulin therapy should be an effective, safe, available, and cheaper triglyceride-lowering therapy for hypertriglyceridemia-induced acute pancreatitis. Trial registration ClinicalTrials.gov, NCT03342807. Registered on 5 Nov 2017.