Proxalutamide for the treatment of COVID-19 rebound following Paxlovid treatment: Report of four cases and review of the literature.

BACKGROUND: The pandemic the coronavirus disease 2019 (COVID-19) has created a global health crisis. Although Paxlovid is recommended for the early-stage treatment of mild-to-moderate COVID-19 in patients at increased risk of progression to severe COVID-19, more and more cases are reported a COVID-19 rebound after Paxlovid treatment. Currently, information on the additional treatment for COVID-19 rebound following Paxlovid treatment is limited. CASE REPORT: Here, we present four cases with COVID-19 who were mild on admission. All cases experienced a COVID-19 rebound and progressed to severe COVID-19, following treatment with Paxlovid (300 mg of nirmatrelvir with 100 mg ritonavir, twice daily for 5 days). After being treated with proxalutamide (300 mg/day), all cases finally turned real-time reverse transcription polymerase chain reaction (RT-PCR) negative. CONCLUSION: Our cases suggested that proxalutamide might be an effective remedial treatment option for patients experiencing a COVID-19 rebound after Paxlovid treatment.

Risk factors of delirium in a paediatric intensive care unit: A prospective case series study.

BACKGROUND: Delirium is one of the most common complications in critically ill children. Once delirium occurs, it will cause physical and psychological distress in children and increase the length of their ICU stay and hospitalization costs. Understanding the risk factors for delirium in critically ill children can help develop targeted nursing interventions to reduce the incidence of delirium. AIMS: To investigate the incidence and the risk factors of delirium in the paediatric intensive care unit (PICU). STUDY DESIGN: We performed a prospective observational study in critically ill patients in the PICU between February and July 2020. Delirium was diagnosed by the Cornell Assessment of Paediatric Delirium (CAPD) and the Richmond Agitation Sedation Scale and analysed via univariate analysis and multivariate logistic regression to determine the independent risk factors of delirium in critically ill children. RESULTS: The study enrolled 315 patients ranging in age from 1-202 (65.3-54.3) months, with 56.2% (n = 177) being male. The incidence of delirium was 29.2% (n = 92) according to CAPD criteria. Among them, 33 cases (35.9%) were of hyperactive delirium, 16 cases (17.4%) were of hypoactive delirium, and 43 cases (46.7%) were of mixed delirium. By using stepwise logistic regression, the independent risk factors of delirium included mechanical ventilation (odds ratio [OR], 11.470; 95% confidence interval [CI], 4.283-30.721), nervous system disease (OR, 5.596; 95%CI, 2.445 to 12.809), developmental delay (OR, 5.157; 95% CI, 1.990-13.363), benzodiazepine (OR, 3.359; 95% CI 1.278-8.832), number of catheters (OR, 1.918; 95% CI, 1.425 to 2.582), and age (OR, 0.985; 95% confidence interval CI, 0.976-0.993). CONCLUSIONS: Delirium is a common complication in the PICU. The independent risk factors include mechanical ventilation, nervous system disease, developmental delay, benzodiazepines, higher number of catheters, and younger age. This study may help develop intervention strategies to reduce the incidence of delirium in critically ill children by targeting modifiable risk factors. RELEVANCE TO CLINICAL PRACTICE: Recommendations for practice include paying attention to high-risk children in the ICU who are prone to delirium, removing influencing factors as soon as possible, and providing targeted nursing interventions.

Usage of compromised lung volume in monitoring steroid therapy on severe COVID-19.

BACKGROUND: Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19. METHODS: Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3-7 days); Stage 3 (8-14 days); Stage 4 (15-21 days); and Stage 5 (22-31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, - 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders. RESULTS: Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (- 3.27% [95% CI, - 5.86 to - 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P < 0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P < 0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group (P < 0.05), but not in the low CL group. CONCLUSIONS: Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process. Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247.

CXCL16/CXCR6 is involved in LPS-induced acute lung injury via P38 signalling.

Although several chemokines play key roles in the pathogenesis of acute lung injury (ALI), the roles of chemokine (C-X-C motif) ligand 16 (CXCL16) and its receptor C-X-C chemokine receptor type 6 (CXCR6) in ALI pathogenesis remain to be elucidated. The mRNA and protein expression of CXCL16 and CXCR6 was detected after lipopolysaccharide (LPS) stimulation with or without treatment with the nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC). Lung injury induced by LPS was evaluated in CXCR6 knockout mice. CXCL16 level was elevated in the serum of ALI patients (n = 20) compared with healthy controls (n = 30). CXCL16 treatment (50, 100, and 200 ng/mL) in 16HBE cells significantly decreased the epithelial barrier integrity and E-cadherin expression, and increased CXCR6 expression, reactive oxygen species (ROS) production, and p38 phosphorylation. Knockdown of CXCR6 or treatment with the p38 inhibitor SB203580 abolished the effects of CXCL16. Moreover, treatment of 16HBE cells with LPS (5, 10, 20 and 50 µg/mL) significantly increased CXCL16 release as well as the mRNA and protein levels of CXCL16 and CXCR6. The effects of LPS treatment (20 µg/mL) were abolished by treatment with PDTC. The results of the luciferase assay further demonstrated that PDTC treatment markedly inhibited the activity of the CXCL16 promoter. In conclusion, CXCL16, whose transcription was enhanced by LPS, may be involved in ROS production, epithelial barrier dysfunction and E-cadherin down-regulation via p38 signalling, thus contributing to the pathogenesis of ALI. Importantly, CXCR6 knockout or inhibition of p38 signalling may protect mice from LPS-induced lung injury by decreasing E-cadherin expression.

Glucocorticoid attenuates acute lung injury through induction of type 2 macrophage.

BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung diseases. Methylprednisolone (MP) is a common drug against inflammation in clinic. In this study, we aim to investigate the protective effect of MP on ALI and potential mechanisms. METHODS: Male BABL/c mice were injected through tail vein using lipopolysaccharide (LPS, 5 mg/kg) with or without 5 mg/kg MP. Lung mechanics, tissue injury and inflammation were examined. Macrophage subsets in the lung were identified by flow cytometry. Macrophages were cultured from bone marrow of mice with or without MP. Then, we analyzed and isolated the subsets of macrophages. These isolated macrophages were then co-cultured with CD4+ T cells, and the percentage of regulatory T cells (Tregs) was examined. The expression of IL-10 and TGF-ß in the supernatant was measured. The Tregs immunosuppression function was examined by T cell proliferation assay. To disclose the mechanism of the induction of Tregs by M2c, we blocked IL-10 or/and TGF-ß using neutralizing antibody. RESULTS: Respiratory physiologic function was significantly improved by MP treatment. Tissue injury and inflammation were ameliorated in the MP-treated group. After MP treatment, the number of M1 decreased and M2 increased in the lung. In in vitro experiment, MP promoted M2 polarization rather than M1. We then induced M1, M2a and M2c from bone marrow cells. M1 induced more Th17 while M2 induced more CD4+CD25+Fxop3+ Tregs. Compared with M2a, M2c induced more Tregs, and this effect could be blocked by anti-IL-10 and anti-TGF-ß antibodies. However, M2a and M2c have no impact on Tregs immunosuppression function. CONCLUSION: In conclusion, MP ameliorated ALI by promoting M2 polarization. M2, especially M2c, induced Tregs without any influence on Tregs immunosuppression function.

Moderate-dose glucocorticoids as salvage therapy for severe pneumonia in renal transplant recipients: a single-center feasibility study.

This study aimed to assess the effectiveness and safety of moderate-dose glucocorticoids (GCs) with mechanical ventilation as salvage therapy for renal transplant recipients with severe pneumonia, which was non-responsive to conventional treatment. A retrospective study was conducted involving renal transplant recipients diagnosed with severe pneumonia and did not respond to conventional treatment. All immunosuppressants were then completely withdrawn, and the patients were initially administered with methylprednisolone at doses of 2.0-2.5 mg/kg/day once every 12 h. This dosage was continued until oxygenation improved, and the treatment was gradually tapered (by 20 mg every 2-3 days) to the previous maintenance dosage. Ten patients were recruited from year 2008 to 2012. Two patients who underwent emergency endotracheal intubation were intubated on days 3 and 8, respectively, another one died from recurrent pneumothorax. The mean PaO2/FiO2 of the nine survivors was significantly increased by the increasing treatment duration; whereas the lung injury scores (LIS) and the sequential organ failure assessment (SOFA) score were both significantly decreased. The use of moderate-dose GCs may play a role as salvage therapy for renal transplant recipients with severe pneumonia. However, further study with larger trials to is needed.

Nursing Care of a Child With Delirium Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Case Report.

INTRODUCTION: Children receiving extracorporeal membrane oxygenation are prone to delirium. This case report describes the nursing care of a child with delirium who received venoarterial extracorporeal membrane oxygenation. Relevant interventions and precautions are also discussed. CLINICAL FINDINGS: A 6-year-old girl was admitted to the pediatric intensive care unit with a 2-day history of vomiting and fever. The child underwent cannulation for venoarterial extracorporeal membrane oxygenation. DIAGNOSIS: The child was diagnosed with acute fulminant myocarditis, cardiac shock, and ventricular arrhythmia. INTERVENTIONS: On the third day of extracorporeal membrane oxygenation, bedside nurses began using the Cornell Assessment of Pediatric Delirium to assess the child for delirium symptoms. The team of physicians and nurses incorporated a nonpharmacologic delirium management bundle into pediatric daily care. Delirium screening, analgesia and sedation management, sleep promotion, and family participation were implemented. OUTCOMES: During the 18 days of pediatric intensive care unit hospitalization, the child had 6 days of delirium: 1.5 days of hypoactive delirium, 1.5 days of hyperactive delirium, and 3 days of mixed delirium. The child was successfully discharged home on hospital day 22. CONCLUSION: Caring for a child with delirium receiving venoarterial extracorporeal membrane oxygenation required multidimensional nursing capabilities to prevent and reduce delirium while ensuring safe extracorporeal membrane oxygenation. This report may assist critical care nurses caring for children under similar circumstances.

Multidisciplinary intensive care in extensive necrotizing fasciitis.

This is a case report of extensive necrotizing fasciitis (NF). A 65-year-old man presented with high fever, pain, swelling, and redness of the perineum, scrotum, and right lower limb. Based on the clinical symptoms and an imaging examination, a diagnosis of NF was made. The patient underwent an extensive exploration followed by daily bedside debridement. A diversion colostomy and six additional debridement procedures on the right thigh and perineum were subsequently performed. Although the patient had an eventful course, he recovered well under a multidisciplinary treatment regimen. The treatment and hospital course of the patient are described.

Effect of admission time on mortality in an intensive care unit in Mainland China: a propensity score matching analysis.

INTRODUCTION: The relationship between admission time and intensive care unit (ICU) mortality is inconclusive and influenced by various factors. This study aims to estimate the effect of admission time on ICU outcomes in a tertiary teaching hospital in China by propensity score matching (PSM) and stratified analysis. METHODS: A total of 2,891 consecutive patients were enrolled in this study from 1 January 2009 to 29 December 2011. Multivariate logistic regression and survival analysis were performed in this retrospective study. PSM and stratified analysis were applied for confounding factors, such as Acute Physiology and Chronic Health Evaluation II (APACHE II) score and admission types. RESULTS: Compared with office hour subgroup (n = 2,716), nighttime (NT, n = 175) subgroup had higher APACHE II scores (14 vs. 8, P < 0.001), prolonged length of stay in the ICU (42 vs. 24 h, P = 0.011), and higher percentages of medical (8.6% vs. 3.3%, P < 0.001) and emergency (59.4% vs. 12.2%, P < 0.001) patients. Moreover, NT admissions were related to higher ICU mortality [odds ratio (OR), 1.725 (95% CI 1.118-2.744), P = 0.01] and elevated mortality risk at 28 days [14.3% vs. 3.2%; OR, 1.920 (95% CI 1.171-3.150), P = 0.01]. PSM showed that admission time remained related to ICU outcome (P = 0.045) and mortality risk at 28 days [OR, 2.187 (95% CI 1.119-4.271), P = 0.022]. However, no mortality difference was found between weekend and workday admissions (P = 0.849), even if weekend admissions were more related to higher APACHE II scores compared with workday admissions. CONCLUSIONS: NT admission was associated with poor ICU outcomes. This finding may be related to shortage of onsite intensivists and qualified residents during NT. The current staffing model and training system should be improved in the future.

Combination of caspofungin and low-dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients.

Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP-SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP-SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off-label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low-dose TMP-SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related adverse effects.

IL-17A/p38 Signaling Pathway Induces Alveolar Epithelial Cell Pyroptosis and Hyperpermeability in Sepsis-Induced Acute Lung Injury by Activating NLRP3 Inflammasome.

Sepsis is a syndrome with poor prognosis. Nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and T helper 17 (Th17) cells are involved in the pathogenesis of inflammatory diseases. This study aims to explore their roles and underlying mechanisms in sepsis. The blood and bronchoalveolar lavage fluid are collected from sepsis patients and healthy donors. A sepsis mice model is established by cecal ligation puncture (CLP). The contents of cytokines are detected by ELISA. The amounts of Th17 cells, IL-17A, IL-1ß, IL-18, and lipopolysaccharide is significantly elevated in sepsis patients. The increased differentiation of Th17 cells can promote lung cell pyroptosis and induce hyperpermeability via activating NLRP3 inflammasome and p38 pathway. The inhibitors targeting Th17 cells, NLRP3 inflammasome, and p38 pathway can significantly alleviate lung injury in sepsis mice. Th17 cells can secrete IL-17A to activate NLRP3 inflammasome via p38 signaling pathway, which contributes to the development of sepsis-induced acute lung injury.

The immunomodulation role of Th17 and Treg in renal transplantation.

Kidney transplantation (KT) is an ultimate treatment of end-stage chronic kidney disease, which can meet a lot of complications induced by immune system. With under-controlled immunosuppression, the patient will obtain a good prognosis. Otherwise, allograft disfunction will cause severe organ failure and even immune collapse. Acute or chronic allograft dysfunction after KT is related to Th17, Treg, and Th17/Treg to a certain extent. Elevated Th17 levels may lead to acute rejection or chronic allograft dysfunction. Treg mainly plays a protective role on allografts by regulating immune response. The imbalance of the two may further aggravate the balance of immune response and damage the allograft. Controlling Th17 level, improving Treg function and level, and adjusting Th17/Treg ratio may have positive effects on longer allograft survival and better prognosis of receptors.

The Clinical Impact of Metagenomic Next-Generation Sequencing (mNGS) Test in Hospitalized Patients with Suspected Sepsis: A Multicenter Prospective Study.

Background: Metagenomic Next Generation Sequencing (mNGS) has the potential to detect pathogens rapidly. We aimed to assess the diagnostic performance of mNGS in hospitalized patients with suspected sepsis and evaluate its role in guiding antimicrobial therapy. Methods: A multicenter, prospective cohort study was performed. We enrolled patients with suspected sepsis, collected clinical characteristics and blood samples, and recorded the 30-day survival. Diagnostic efficacy of mNGS test and blood culture was compared, and the clinical impact of mNGS on antibiotic regimen modification was analyzed. Results: A total of 277 patients were enrolled, and 162 were diagnosed with sepsis. The mortality was 44.8% (121/270). The mNGS test exhibited shorter turn-out time (27.0 (26.0, 29.0) vs. 96.0 (72.0, 140.3) hours, p < 0.001) and higher sensitivity (90.5% vs. 36.0%, p < 0.001) compared with blood culture, especially for fungal infections. The mNGS test showed better performance for patients with mild symptoms, prior antibiotic use, and early stage of infection than blood culture, and was capable of guiding antibiotic regimen modification and improving prognosis. Higher reads of pathogens detected by mNGS were related to 30-day mortality (p = 0.002). Conclusions: Blood mNGS testing might be helpful for early etiological diagnosis of patients with suspected sepsis, guiding the antibiotic regimen modification and improving prognosis.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

Early Enteral Nutrition Tolerance in Patients With Cardiogenic Shock Requiring Mechanical Circulatory Support.

Background: Enteral nutrition (EN) is recommended within the first 24-48 h for patients with hemodynamic stability, following admission to an intensive care unit (ICU). However, for patients with approximate stable hemodynamics requiring mechanical circulatory support and vasoactive drugs, the application of early EN remains controversial. We sought to evaluate the tolerance of early EN in patients with cardiogenic shock who required vasoactive drugs and mechanical circulatory support after cardiac surgery. Methods: This single-center, prospective observational study included patients with cardiogenic shock, requiring vasoactive drugs and mechanical circulatory support after cardiac surgery, undergoing EN. The primary endpoint was EN tolerance and secondary endpoints were mortality, length of mechanical ventilation, and length of ICU stay. Results: From February 2019 to December 2020, 59 patients were enrolled, of which 25 (42.37%) developed intolerance within 3 days of starting EN. Patients in the EN intolerant group had a longer median length of mechanical ventilation (380 vs. 128 h, p = 0.006), a longer median ICU stay (20 vs. 11.5 days, p = 0.03), and a higher proportion of bloodstream infections (44 vs. 14.71%, p = 0.018). The median EN calorie levels for all patients in the first 3 days of EN were 4.00, 4.13, and 4.28 kcal/kg/day, respectively. Median protein intake levels of EN in the first 3 days were 0.18, 0.17, and 0.17 g/kg/day, respectively. No significant difference was observed in the median dose of vasoactive drugs between the groups (0.035 vs. 0.05 µg/kg/min, p = 0.306). Conclusions: Patients with cardiogenic shock after cardiac surgery had a high proportion of early EN intolerance, and patients with EN intolerance had a worse prognosis, but no significant correlation was identified between EN tolerance and the dose of vasoactive drugs.

PEBP1 downregulation is associated to poor prognosis in HCC related to hepatitis B infection.

BACKGROUND & AIMS: Phosphatidylethanolamine-binding protein 1 (PEBP1, also RKIP) plays a pivotal role in cancer by regulating multiple cellular signaling processes and suppressing metastasis in animal models. We examined whether PEBP1 expression in hepatocellular carcinoma (HCC) correlated with the risk of recurrence and survival after resection. METHODS: A randomly selected cohort of 240 Chinese HCC patients, predominantly hepatitis B related, formed the basis of the study. PEBP1 expression levels were evaluated by immunohistochemistry and real-time reverse-transcriptase PCR. Survival analysis was performed by univariate and multivariate analyses. The results were further validated in an independent series of 403 patients. The relevance of PEBP1 to phospho-ERK was determined by Western blot analysis on clinical samples and hepatoma cell lines. RESULTS: PEBP1, prevalently down-regulated in HCC, was significantly associated with tumor invasive characteristics (such as vascular invasion, lack of encapsulation, poor differentiation and large size). Both PEBP1 protein and mRNA levels were independent predictors for tumor recurrence (hazard ratio (HR) = 1.877, p=0.001; HR = 2.633, p = 0.001; respectively), and patient survival (HR = 1.796, p = 0.004; HR = 1.730, p = 0.044; respectively). The prognostic value of PEBP1 was then confirmed in the validation cohort. In addition, Western blot suggested that loss of PEBP1 led to hyperactivity of MAPK signaling. CONCLUSIONS: Down-regulation of PEBP1 in HCC indicated aggressive tumor behaviors and predicted a worse clinical outcome, which may be a useful biomarker to identify the patients at high risk of post-operative recurrence.

Cyclic helix B peptide alleviates sepsis-induced acute lung injury by downregulating NLRP3 inflammasome activation in alveolar macrophages.

Acute lung injury (ALI) exhibits high clinical morbidity and mortality rates. Our previous study has indicated that the novel proteolysis-resistant cyclic helix B peptide (CHBP) exerts an anti-inflammatory effect in mice with AKI. In the present study, we evaluated the effect of CHBP in an in vivo sepsis-induced ALI model and in vitro using lipopolysaccharide (LPS) and ATP stimulated bone marrow-derived macrophages (BMDMs). For in vivo experiments, mice were randomly divided into three groups: 1) sham; 2) LPS; and 3) LPS + CHBP (n = 6). All relevant data were collected after 18 h. Following CHBP treatment, the lung function of the mice was significantly improved compared to the LPS group. CHBP administration inhibited interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production at both the protein and mRNA levels. Additionally, following CHBP treatment, the population of pulmonary macrophages decreased. Simultaneously, the proportion of caspase-1-activated alveolar macrophages was also decreased after CHBP treatment. The protein levels of NLRP3 and cleaved caspase-1 were attenuated in the lung tissue following CHBP treatment. In in vitro experiments, CHBP treatment decreased NLRP3 inflammasome expression and downstream IL-1ß secretion, consistent with the in vivo results. In addition, CHBP reversed nuclear factor (NF)-κB and I-κB phosphorylation with a significant dose-dependent effect. Therefore, these findings suggest the potential of CHBP as a therapeutic agent in sepsis-induced ALI owing to inhibition of the NLRP3 inflammasome via the NF-κB pathway in macrophages.

Neutrophil-to-Lymphocyte Ratio Predicts Mortality in Adult Renal Transplant Recipients with Severe Community-Acquired Pneumonia.

Mortality of renal transplant recipients with severe community-acquired pneumonia (CAP) remains high, despite advances in critical care management. There is still a lack of biomarkers for predicting prognosis of these patients. The present study aimed to investigate the association between neutrophil-to-lymphocyte ratio (NLR) and mortality in renal transplant recipients with severe CAP. A total of 111 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility between 1 January 2009 and 30 November 2018. Patient characteristics and laboratory test results at ICU admission were retrospectively collected. There were 18 non-survivors (22.2%) among 81 patients with severe CAP who were finally included. Non-survivors had a higher NLR level than survivors (26.8 vs. 12.3, p < 0.001). NLR had the greatest power to predict mortality as suggested by area under the curve (0.88 ± 0.04; p < 0.0001) compared to platelet-to-lymphocyte ratio (0.75 ± 0.06; p < 0.01), pneumonia severity index (0.65 ± 0.08; p = 0.05), CURB-65 (0.65 ± 0.08; p = 0.05), and neutrophil count (0.68 ± 0.07; p < 0.01). Multivariate logistic regression models revealed that NLR was associated with hospital and ICU mortality in renal transplant recipients with severe CAP. NLR levels were independently associated with mortality and may be a useful biomarker for predicting poor outcome in renal transplant recipients with severe CAP.

Prognostic Accuracy of Early Warning Scores for Clinical Deterioration in Patients With COVID-19.

Background: Early Warning Scores (EWS), including the National Early Warning Score 2 (NEWS2) and Modified NEWS (NEWS-C), have been recommended for triage decision in patients with COVID-19. However, the effectiveness of these EWS in COVID-19 has not been fully validated. The study aimed to investigate the predictive value of EWS to detect clinical deterioration in patients with COVID-19. Methods: Between February 7, 2020 and February 17, 2020, patients confirmed with COVID-19 were screened for this study. The outcomes were early deterioration of respiratory function (EDRF) and need for intensive respiratory support (IRS) during the treatment process. The EDRF was defined as changes in the respiratory component of the sequential organ failure assessment (SOFA) score at day 3 (ΔSOFAresp = SOFA resp at day 3-SOFAresp on admission), in which the positive value reflects clinical deterioration. The IRS was defined as the use of high flow nasal cannula oxygen therapy, noninvasive or invasive mechanical ventilation. The performances of EWS including NEWS, NEWS 2, NEWS-C, Modified Early Warning Scores (MEWS), Hamilton Early Warning Scores (HEWS), and quick sepsis-related organ failure assessment (qSOFA) for predicting EDRF and IRS were compared using the area under the receiver operating characteristic curve (AUROC). Results: A total of 116 patients were included in this study. Of them, 27 patients (23.3%) developed EDRF and 24 patients (20.7%) required IRS. Among these EWS, NEWS-C was the most accurate scoring system for predicting EDRF [AUROC 0.79 (95% CI, 0.69-0.89)] and IRS [AUROC 0.89 (95% CI, 0.82-0.96)], while NEWS 2 had the lowest accuracy in predicting EDRF [AUROC 0.59 (95% CI, 0.46-0.720)] and IRS [AUROC 0.69 (95% CI, 0.57-0.81)]. A NEWS-C ≥ 9 had a sensitivity of 59.3% and a specificity of 85.4% for predicting EDRF. For predicting IRS, a NEWS-C ≥ 9 had a sensitivity of 75% and a specificity of 88%. Conclusions: The NEWS-C was the most accurate scoring system among common EWS to identify patients with COVID-19 at risk for EDRF and need for IRS. The NEWS-C could be recommended as an early triage tool for patients with COVID-19.

Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma.

The peritumoral inflammatory environment is critical for the progression of intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resections. Here, we investigated the relevance of peritumoral mast cells (MCs) to HCC outcomes. Peritumoral tryptase(+) MCs in addition to Foxp3(+) T-regulatory cells (Tregs) were evaluated using immunohistochemistry enumeration in tissue microarrays containing 207 randomly selected HCC patients. Clinicopathological factors and postoperative outcomes were compared between high and low subgroups of MCs or Tregs. Compared to low denstiy, higher peritumoral MCs were associated with poorer clinical outcomes, and independently related to elevated 5-year recurrence incidence (54.1%vs 39.2%, P = 0.026). High-dense MCs were especially related to increased probability of early recurrence (within 2 years) (P = 0.004). We also found that peritumoral Tregs were positively correlated with MCs in density (r = 0.353, P < 0.001) and reversely related to HCC outcomes. Notably, MCs in combination with Tregs displayed better prognostic performances than MCs alone (area under curve [AUC](survival) = 0.629 vs 0.589, AUC(recurrence) = 0.632 vs 0.591). Moreover, MCs were positively correlated to alanine aminotransferase, a serum inflammatory marker (P = 0.014). Therefore, peritumoral MCs are promising prognostic parameters for HCC mainly through inflammation response-related mechanisms, and we propose that MCs and Tregs may cooperate with each other and result in poorer prognosis.