Sensitive and rapid identification of pathogens by droplet digital PCR in a cohort of septic patients: a prospective diagnostic study.

BACKGROUND: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. METHODS: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. RESULTS: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. CONCLUSIONS: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients.

High concentrations of nirmatrelvir/ritonavir in critically ill patients receiving continuous renal replacement therapy.

OBJECTIVES: Nirmatrelvir/ritonavir is a highly efficacious agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although dose adjustment is recommended in patients with renal impairment according to the package insert for Paxlovid (Pfizer), there is no dose recommendation for patients with severe renal impairment who require continuous renal replacement therapy (CRRT). METHODS: To characterise the features of nirmatrelvir/ritonavir in critically ill Chinese patients undergoing CRRT, therapeutic drug monitoring of nirmatrelvir/ritonavir was performed by high-performance liquid chromatography tandem mass spectrometry assay in eight patients. RESULTS: Nirmatrelvir trough concentrations ranged from 3325.34 ng/mL to 15 625.46 ng/mL. Concentrations were up to 7-fold higher compared with patients with normal renal function and 2-fold higher compared with patients with end-stage renal disease undergoing haemodialysis. CONCLUSIONS: These results suggest that a dose reduction should be implemented in the treatment of patients with CRRT.

Prognostic value of APTT combined with fibrinogen and creatinine in predicting 28-Day mortality in patients with septic shock caused by acute enteric perforation.

BACKGROUND: Septic shock is one of the leading causes of mortality in intensive care units. This retrospective study was carried out to evaluate the association of clinical available factors with 28-day mortality. PATIENTS AND METHOD: In this observational study, patients with perioperative septic shocks secondary to intra-abdominal infection caused by enteric perforation were included. A total of 328 sepsis patients were admitted to the surgical intensive care units from January 2012 to December 2016. A total of 138 patients met the enrolment criteria and were included in the study. The data of demographic, clinical and laboratory were all recorded. RESULT: All these 138 patients received abdominal surgery prior to surgical intensive care units caused by acute enteric perforation. These patients were all met the diagnostic criteria of septic shock according to Sepsis-3. Statistical analysis showed that lactic acid, blood platelet, fibrinogen, creatinine and activated partial thromboplastin time were found to be associated with 28-day mortality. A combination of serum activated partial thromboplastin time combined with fibrinogen and creatinine could predict in-hospital 28-day mortality. The area under the curve of serum activated partial thromboplastin time combined with fibrinogen and creatinine is 0.875 (0.806-0.944). CONCLUSION: In conclusion, this pilot study demonstrated that these factors can predict the prognosis of septic shock caused by enteric perforation. In order to reduce the mortality, surgeons and intensive care units physician may consider these data in perioperative period.

Outcome of Using Intraventricular Plus Intravenous Polymyxin B in Post-neurosurgical Patients With Multi/Extensively Drug-Resistant Gram-Negative Bacteria-Induced Intracranial Infection.

Introduction: Post-neurosurgical central nervous system (CNS) infection caused by multidrug-resistant (MDR)/extensively drug-resistant (XDR) Gram-negative bacteria remains a major clinical challenge. This study describes our experience of treating such patients with combined intraventricular (IVT) and intravenous (IV) polymyxin B administration. Methods: This retrospective study included six patients with post-neurosurgical CNS infections of carbapenem-resistant Acinetobacter baumannii (CRAB) or carbapenem-resistant Klebsiella pneumoniae (CRKP). All patients were treated in the intensive care unit (ICU) of First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) between November 2020 and November 2021, and all received IVT plus IV polymyxin B. Data including patients' characteristics, therapeutic process, symptoms, cerebrospinal fluid (CSF) examination, laboratory tests, and complications were collected. Results: Six patients with post-neurosurgical CNS infection were enrolled in the study. The patients comprised five males and one female, and the average age was 58 years (range, 38-73 years). Four out of the six cases were CRAB-positive in CSF culture, while two cases were CRKP-positive. The mean duration of polymyxin B administration was 14 ± 5.69 days (range, 6-20 days). The average period of patients reaching CSF sterilization was 10.33 ± 3.67 days (range, 5-14 days). All six cases were cured without acute kidney injury or epilepsy. Conclusion: IVT plus IV polymyxin B is a safe and effective treatment for post-neurosurgical patients with intracranial infection caused by MDR/XDR Gram-negative bacteria.

MicroRNA-449c-5p alleviates lipopolysaccharide-induced HUVECs injury via inhibiting the activation NF-κb signaling pathway by TAK1.

BACKGROUND: Acute kidney injury caused by sepsis has become a hotspot of scientific research in recent years. Since the kidney is the most abundant of all organs with vascular endothelium, activation and injury of vascular endothelial cells is a main reason to renal dysfunction. In our research, we identify that miRNA-449c-5p can alleviate HUVECs injury through inhibiting the NF-κb signaling pathway activation by targeting TAK1 with the method of bioinformatics and in vitro experiment. METHODS: Datasets of GSE28750 and GSE94717 were obtained from the GEO database. Differential analysis was performed on the two data sets using the GEO2R tool of the GEO database, and the miRNA-mRNA network was further constructed. Lipopolysaccharide (LPS) against Human umbilical vein endothelial cells induced an in vitro model of AKI were used for verification. RT-PCR, Western blotting, ELISA, CCK8, EDU and luciferase reporter genes were used to verify whether miR-449c-5p could alleviate the apoptosis of vascular endothelial cells and the release of inflammatory factors during the progression of sepsis by inhibiting the expression of TAK1. RESULTS: TAK1 was identified as a direct target of miR-449c-5p by luciferase reporter gene assay, and TAK1 expression was negatively regulated by miR-449c-5p. Overexpression of miR-449c-5p promoted cell viability, inhibited apoptosis rate and inhibited the expression of inflammatory cytokines in HUVECs after LPS stimulation. Moreover, miR-449c-5p deactivated NF-κB signaling by targeting TAK1. CONCLUSION: In cell model experiments, it was found that miRNA-449c-5p could inhibit the release of LPS induced inflammatory cytokine, inhibit the occurrence of apoptosis and promote cell proliferation by inhibiting the expression of TAK1. Therefore, thus miRNA-449c-5p played a protective role on vascular endothelial cells.

Role of TLR5 in the Translocation and Dissemination of Commensal Bacteria in the Intestine after Traumatic Hemorrhagic Shock.

Enterogenous infection is a major cause of death during traumatic hemorrhagic shock (THS). It has been reported that Toll-like receptor 5 (TLR5) plays an integral role in regulating mucosal immunity and intestinal homeostasis of the microbiota. However, the roles played by TLR5 on intestinal barrier maintenance and commensal bacterial translocation post-THS are poorly understood. In this research, we established THS models in wild-type (WT) and Tlr5-/- (genetically deficient in TLR5 expression) mice. We found that THS promoted bacterial translocation, while TLR5 deficiency played a protective role in preventing commensal bacteria dissemination after THS. Furthermore, intestinal microbiota analysis uncovered that TLR5 deficiency enhanced the mucosal biological barrier by decreasing RegIIIγ-mediated bactericidal activity against G+ anaerobic bacteria. We then sorted small intestinal TLR5+ lamina propria dendritic cells (LPDCs) and analyzed TH1 differentiation in the intestinal lamina propria and a coculture system consisting of LPDCs and naïve T cells. Although TLR5 deficiency attenuated the regulation of TH1 polarization by LPDCs, it conferred stability to the cells during THS. Moreover, retinoic acid (RA) released from TLR5+ LPDCs could play a key role in modulating TH1 polarization. We also found that gavage administration of RA alleviated bacterial translocation in THS-treated WT mice. In summary, we documented that TLR5 signaling plays a pivotal role in regulating RegIIIγ-induced killing of G+ anaerobic bacteria, and LPDCs mediated TH1 differentiation via RA. These processes prevent intestinal bacterial translocation and enterogenous infection after THS, suggesting that therapeutically targeting LPDCs or gut microbiota can interfere with bacterial translocation after THS.

Hemorrhage and venous thromboembolism in critically ill patients with COVID-19.

OBJECTIVE: The majority of patients with COVID-19 showed mild symptoms. However, approximately 5% of them were critically ill and require intensive care unit admission for advanced life supports. Patients in the intensive care unit were high risk for venous thromboembolism and hemorrhage due to the immobility and anticoagulants used during advanced life supports. The aim of the study was to report the incidence and treatments of the two complications in such patients. METHOD: Patients with COVID-19 (Group 1) and patients with community-acquired pneumonia (Group 2) that required intensive care unit admission were enrolled in this retrospective study. Their demographics, laboratory results, ultrasound findings and complications such as venous thromboembolism and hemorrhage were collected and compared. RESULTS: Thirty-four patients with COVID-19 and 51 patients with community-acquired pneumonia were included. The mean ages were 66 and 63 years in Groups 1 and 2, respectively. Venous thromboembolism was detected in 6 (18%) patients with COVID-19 and 18 (35%) patients with community-acquired pneumonia (P = 0.09). The major type was distal deep venous thrombosis. Twenty-one bleeding events occurred in 12 (35%) patients with COVID-19 and 5 bleeding events occurred in 5 (10%) patients with community-acquired pneumonia, respectively (P = 0.01). Gastrointestinal system was the most common source of bleeding. With the exception of one death due to intracranial bleeding, blood transfusion with or without surgical/endoscopic treatments was able to manage the bleeding in the remaining patients. Multivariable logistic regression showed increasing odds of hemorrhage with extracorporeal membrane oxygenation (odds ratio: 13.9, 95% confidence interval: 4.0-48.1) and COVID-19 (odds ratio: 4.7, 95% confidence interval: 1.2-17.9). CONCLUSION: Venous thromboembolism and hemorrhage were common in both groups. The predominant type of venous thromboembolism was distal deep venous thrombosis, which presented a low risk of progression. COVID-19 and extracorporeal membrane oxygenation were risk factors for hemorrhage. Blood transfusion with or without surgical/endoscopic treatments was able to manage it in most cases.

The "Two-Step" approach for classifying the severity of acute pancreatitis: A retrospective study.

BACKGROUND: The Revised Atlanta Classification (RAC) and Determinant-Based Classification (DBC) are currently two widely adopted systems for evaluating the severity of acute pancreatitis (AP). This study aimed to overcome the inaccuracies and limitations that existed in them. METHODS: We retrospectively analyzed 298 patients with AP. The "Two-Step" approach was divided into an early organ failure (OF) assessment: (I) none, (II) transient, (III) single persistent, and (IV) multiple persistent; and a later local complications assessment: (A) none, (B) sterile, and (C) infectious. Patients with AP who died before the second step were classified into category X. The "Two-Step" approach was then compared to the RAC and DBC. RESULTS: As the patients' grades increased (I to IV), organ support treatment rates, intensive care unit lengths of stay, and mortalities increased. Invasive intervention rates displayed increasing trends with local complications aggravated (A to C). Patients in category X were older and had higher Marshall scores with the highest grades of severity. CONCLUSIONS: By combining the early OF grades and the late local complications, the "Two-Step" approach represents an accurate classification system required for stratified studies of AP, and introduces the category X as the severest forms of AP.

Systematic Review and Meta-Analysis of the Efficacy of Appropriate Empiric Anti-Enterococcal Therapy for Intra-Abdominal Infection.

Background: Delayed treatment of seriously infected patients results in increased mortality. However, antimicrobial therapy for the initial 24 to 48 hours is mostly empirically provided, without evidence regarding the causative pathogen. Whether empiric anti-enterococcal therapy should be administered to treat intra-abdominal infection (IAI) before obtaining culture results remains unknown. We performed a meta-analysis to explore the effects of empiric enterococci covered antibiotic therapy in IAI and the risk factors for enterococcal infection in IAI. Methods: We searched multiple databases systematically and included 23 randomized controlled trials (RCTs) and 13 observational studies. The quality of included studies was assessed, and the reporting bias was evaluated. Meta-analysis was performed using random effects or fixed effects models according to the heterogeneity. The risk ratio (RR), odds ratio (OR), and 95% confidence interval (CI) were calculated. Results: Enterococci-covered antibiotic regimens provided no improvement in treatment success compared with control regimens (RR, 0.99; 95% CI, 0.97-1.00; p = 0.15), with similar mortality and adverse effects in both arms. Basic characteristic analysis revealed that most of the enrolled patients with IAI in RCTs were young, lower risk community-acquired intra-abdominal infection (CA-IAI) patients with a relatively low APACHE II score. Interestingly, risk factor screening revealed that malignancy, corticosteroid use, operation, any antibiotic treatment, admission to intensive care unit (ICU), and indwelling urinary catheter could predispose the patients with IAI to a substantially higher risk of enterococcal infection. "Hospital acquired" itself was a risk factor (OR, 2.81; 95% CI, 2.34-3.39; p < 0.001). Conclusion: It is unnecessary to use additional agents empirically to specifically provide anti-enterococcal coverage for the management of CA-IAI in lower risk patients without evidence of causative pathogen, and risk factors can increase the risk of enterococcal infection. Thus, there is a rationale for providing empiric anti-enterococcal coverage for severely ill patients with CA-IAI with high risk factors and patients with hospital-acquired intra-abdominal infection (HA-IAI).

Efficacy of Early Percutaneous Catheter Drainage in Acute Pancreatitis of Varying Severity Associated With Sterile Acute Inflammatory Pancreatic Fluid Collection.

OBJECTIVE: The aim of the study was to evaluate the efficacy of early percutaneous catheter drainage (PCD) for sterile acute inflammatory pancreatic fluid collection (AIPFC) in acute pancreatitis (AP) of varying severity. METHODS: Retrospective analyses were performed based on the presence of sterile AIPFC and different AP severities according to 2012 Revised Atlanta Classification. RESULTS: Early PCD contributed to obvious decreases in operation rate (OR, P = 0.006), infection rate (IR, P = 0.020), and mortality (P = 0.009) in severe AP (SAP). In moderate SAP with sterile AIPFCs, however, early PCD was associated with increased OR (P = 0.009) and IR (P = 0.040). Subgroup analysis revealed that early PCD led to remarkable decreases in OR for patients with persistent organ failure (OF) within 3 days (P = 0.024 for single OF, P = 0.039 for multiple OF) and in mortality for patients with multiple OF (P = 0.041 for OF within 3 days and P = 0.055 for 3-14 days). Moreover, lower mortality was found in SAP patients with early PCD-induced infections than with spontaneous infections (P = 0.027). CONCLUSIONS: Early PCD may improve the prognosis of SAP with drainable sterile AIPFCs by reducing the OR, IR, and mortality.

Screening and identification of key gene in sepsis development: Evidence from bioinformatics analysis.

Sepsis is one of the leading causes of mortality in intensive care units (ICU). The growing incidence rate of sepsis and its high mortality rate result are very important sociosanitary problems. Sepsis is a result of infection which can cause systemic inflammatory and organ failure. But the pathogenesis and the molecular mechanisms of sepsis is still not well understood. The aim of the present study was to identify the candidate key genes in the progression of sepsis.Microarray datasets GSE28750, GSE64457, and GSE95233 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. Furthermore, to verify the results of the bioinformatics analyses, the expression levels of selected DEGs were quantified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in libobolysaccharide (LPS)-induced Human Umbilical Vein Endothelial Cells (HUVECs) to support the result of bioinformatics analysis.Thirteen hub genes were identified and biological process analysis revealed that these genes were mainly enriched in apoptotic process, inflammatory response, innate immune response. Hub genes with high degrees, including MAPK14, SLC2A3, STOM, and MMP8, were demonstrated to have an association with sepsis. Furthermore, RT-PCR results showed that SLC2A3 and MAPK14 were significantly upregulated in the HUVECs induced by LPS compared with controls.In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms of sepsis, and provide candidate targets for diagnosis and treatment of sepsis.

Effects of Short-Peptide-Based Enteral Nutrition on the Intestinal Microcirculation and Mucosal Barrier in Mice with Severe Acute Pancreatitis.

SCOPE: Short-peptide-based enteral nutrition (SPEN) is absorbed more efficiently in patients with severe acute pancreatitis (SAP). More importantly, SPEN decreases SAP-induced enterogenous infection risk. This study aims to investigate whether SPEN alleviates intestinal bacterial translocation in mice with SAP, and the underlying mechanisms. METHODS AND RESULTS: The SAP model is established after pre-treatment with SPEN or intact-protein-based enteral nutrition. Although there is no improvement in pancreas injury, as evaluated through Hematoxylin-Eosin staining or serum amylase, SPEN obviously attenuates intestinal bacterial translocation after SAP. To unveil the mechanisms, it is found that the intestinal mechanical barrier destroyed by SAP is significantly relieved by SPEN, which presents with recovered ZO-1 expression, mucus layer, and goblet cell function. Additionally, SPEN alleviates local CCR6/CCL20 induced CD11c+ dendritic cell infiltration, systemic immunosuppression, and inhibits the secretion of luminal secretory immunoglobulin A. Possibly responsible for SAP-induced mucosal dysfunctions, destroyed intestinal mucosal microcirculation and local hypoxia are largely improved in SAP+SPEN group. CONCLUSION: SPEN can improve downregulated intestinal mucosal microcirculation secondary to SAP, which may be responsible for mucosal inflammation relief, maintenance of the mechanical barrier and mucosal immunity, the correction of systemic immunosuppression, and play a protective role in defending commensal bacterial translocation after SAP.

Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice.

Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice.Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1ß, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05).Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.

Dexamethasone protects the glycocalyx on the kidney microvascular endothelium during severe acute pancreatitis.

OBJECTIVE: This study demonstrated that dexamethasone (DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α (TNF-α) during severe acute pancreatitis (SAP), and improves the renal microcirculation. METHODS: Ninety mice were evenly divided into 3 groups (Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology (hematoxylin and eosin (H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). The protective effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. RESULTS: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. CONCLUSIONS: Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.

Severe traumatic hemorrhagic shock induces compromised immune barrier function of the mesenteric lymph node leading to an increase in intestinal bacterial translocation.

Critically ill patients have increased susceptibility to translocation of gut bacteria. However, the mechanisms are complicated and remain unclear, and the aim of this study was to explore these mechanisms. Rats exposed to different levels of shock were orally administrated with bioluminescent Citrobacter. We found that severe shock caused an increase in bacterial translocation to the visceral organs, such as liver, spleen and blood, compared with mild shock. Surprisingly, bacterial translocation to mesenteric lymph node (MLN) was unchanged between the two shock groups. Various methods, including flow cytometry, a co-culture model and western blots, were used to evaluate MLN-associated immune function. Specifically, we focused on mesenteric lymph node dendritic cells (MLN-DCs), the critical antigen presenting cells involved in the construction of the immune barrier in MLN. We also found that severe shock impaired the phenotypic maturation of MLN-DCs and induced a tolerogenic phenotype. Furthermore, co-culture assays of DCs with naive CD4+ T cells showed that DCs subject to severe shock were more inclined to polarize native CD4+ T cells into Th2 and Treg cells. This study successfully reproduced the clinical phenomenon of severe shock resulting in increased bacterial translocation to extraintestinal tissues, and this may be related to the compromised immune barrier function of MLN, as maturation and function of MLN-DC's were badly impaired.

Clinical characteristics and treatment of thyroid cancer in children and adolescents: a retrospective analysis of 83 patients.

OBJECTIVE: To study the clinical characteristics, treatment, and prognosis of thyroid cancer in children and adolescents. METHODS: We performed a retrospective analysis of clinical data from 83 cases of thyroid cancer in children and adolescents from January 1990 to December 2010. We compared extra-thyroid extension, lymph node metastasis, distant metastasis, and prognosis between pediatric patients ≤12 years of age (27 cases) and those >12 years of age (56 cases). All the patients agreed to undergo thyroidectomy and endocrine therapy, and the consent was obtained from parents or guardians. RESULTS: Histopathology included papillary carcinoma in 67 cases, papillary carcinoma with partial follicular growth pattern in 1 case, papillary carcinoma with squamous metaplasia in 4 cases, follicular carcinoma in 7 cases, medullary carcinoma in 3 cases, and poorly differentiated carcinoma in 1 case. The total lymph node metastasis rate was 78.31%. Patients ≤12 years of age showed a higher rate of lymph node metastasis than the older group (92.59% vs. 71.43%, P=0.028). The incidence rate in females in the older group was higher than that in the younger group (80.36% vs. 59.26%, P=0.041). There were no significant differences in extra-thyroid extension, distant metastasis, survival rate, or recurrent disease between the two groups. CONCLUSIONS: The lymph node metastasis of thyroid cancer is higher in patients ≤12 years of age than in those >12 years of age; the incidence rate is higher in females than in males. Childhood thyroid cancer has a good prognosis, surgery being the most effective treatment. Choosing a reasonable surgery method and comprehensive postoperative treatment can achieve a cure and satisfactory survival rate.

Protective effects of neurotensins on lipopolysaccaride-induced acute lung injury by blocking tachykinin mediated pathway.

Neurotensin, a bioactive tridecapeptide, has been shown to regulate inflammatory process in lung tissues. However, the effect of neurotensin on LPS-induced lung injury and underlying detailed molecular mechanisms has not been studied. The aim of present study is to investigate the effect of neurotensin on LPS-induced acute lung injury in mice. Mice were treated with LPS intratracheally to induce acute lung injury. 1 hour after ALI induction, and then mice were treated with neurotensins (NTs) (20 mg/kg, 40 mg/kg, and 80 mg/kg) via tail vein injection. Next, the severity of lung injury, MPO activity, neutrophils infiltration, lung edema, protein and pro-inflammatory cytokines concentration in BALF were determined to evaluate the effect of Nts on ALI. Additionally, the expression of tachykinins receptors, including NK1, NK2, and NK3 and the production of IL-8, COX-2, and PGE2 mediated by tachykinins-tachykinins receptors pathway were determined to investigate the blocking effect of Nts on tachykinins and its receptors pathway. Neurotensins treatment significantly decreased the lung edema and the infiltration of inflammatory cells into lung tissue caused by LPS induction. Meanwhile, the elevation of pro-inflammatory cytokines and chemokine in BALF was dramatically reduced by neurotensins treatment. Furthermore, neurotensins could interact with tachykinins receptors and block the inflammatory responses activated by tachykinins pathways. In summary, neurotensins has a potentially protective effect on LPS-induced acute lung injury through the interaction with tachykinins receptors and subsequently blocking the inflammatory responses induced by activation of tachykinins pathway.

Allicin ameliorates intraintestinal bacterial translocation after trauma/hemorrhagic shock in rats: The role of mesenteric lymph node dendritic cell.

BACKGROUND: Intestinal dendritic cells play important roles in regulating the function of the intestinal immune barrier and the intestinal bacterial translocation. In this study, we aim to investigate the effects of allicin on the function of mesenteric lymph node-dendritic cells after trauma/hemorrhagic shock. METHODS: One hundred and eight-four Sprague-Dawley rats were randomly assigned into a sham group (n = 46), sham + allicin group (n = 46), trauma/hemorrhagic shock group (n = 46), and trauma/hemorrhagic shock + allicin group (n = 46). Studies were performed on an in vivo model of spontaneously breathing rats with induced trauma/hemorrhagic shock. Allicin was diluted in resuscitation fluid and was administered through the right jugular vein. Flow cytometry was used to determine the expression of CD80, CD86, and major histocompatibility complex II (MHC II) on the surface of mesenteric lymph node-dendritic cells, as well as apoptosis. Intraintestinal bacterial translocation was monitored by using bioluminescent citrobacter. Intestinal permeability tests were conducted by using both FITC-Dextran and Ussing-Chember assay. RESULT: CD80 and MHC-II expression levels were downregulated in the trauma/hemorrhagic shock group compared with the sham and sham + allicin groups; however, the expression was upregulated after allicin treatment. Also, allicin could ameliorate the trauma/hemorrhagic shock-induced increase in early apoptosis of mesenteric lymph node-dendritic cells. A significant increase was observed in the permeability of the intestinal barrier after severe traumatic shock, along with an obvious intraintestinal bacterial translocation to mesenteric lymph node. No difference was noticed in the bacterial translocation in mesenteric lymph node in the trauma/hemorrhagic shock group compared with trauma/hemorrhagic shock + allicin group (P = .589), which indicated allicin could not block bacterial translocation into mesenteric lymph node after trauma/hemorrhagic shock. However, it may increase the capacity of mesenteric lymph node to block intraintestinal bacterial translocation to extraintestinal organs as a statistical difference was noticed in the bacterial translocation in liver, blood, and spleen between trauma/hemorrhagic shock and trauma/hemorrhagic shock + allicin groups (P < .05). CONCLUSION: Trauma/hemorrhagic shock resulted in a decrease of mature mesenteric lymph node-dendritic cells. Allicin treatment could block intraintestinal bacterial translocation through increasing the immunologic barrier function of mesenteric lymph node by modulating dendritic cells maturation.

Impact of misplaced subclavian vein catheter into jugular vein on transpulmonary thermodilution measurement variables.

OBJECTIVE: The subclavian vein (SCV) is usually used to inject the indicator of cold saline for a transpulmonary thermodilution (TPTD) measurement. The SCV catheter being misplaced into the internal jugular (IJV) vein is a common occurrence. The present study explores the influence of a misplaced SCV catheter on TPTD variables. METHODS: Thirteen severe acute pancreatitis (SAP) patients with malposition of the SCV catheter were enrolled in this study. TPTD variables including cardiac index (CI), global end-diastolic volume index (GEDVI), intrathoracic blood volume index (ITBVI), and extravascular lung water index (EVLWI) were obtained after injection of cold saline via the misplaced SCV catheter. Then, the misplaced SCV catheter was removed and IJV access was constructed for a further set of TPTD variables. Comparisons were made between the TPTD results measured through the IJV and misplaced SCV accesses. RESULTS: A total of 104 measurements were made from TPTD curves after injection of cold saline via the IJV and misplaced SCV accesses. Bland-Altman analysis demonstrated an overestimation of +111.40 ml/m(2) (limits of agreement: 6.13 and 216.70 ml/m(2)) for GEDVI and ITBVI after a misplaced SCV injection. There were no significant influences on CI and EVLWI. The biases of +0.17 L/(min·m(2)) for CI and +0.17 ml/kg for EVLWI were revealed by Bland-Altman analysis. CONCLUSIONS: The malposition of an SCV catheter does influence the accuracy of TPTD variables, especially GEDVI and ITBVI. The position of the SCV catheter should be confirmed by chest X-ray in order to make good use of the TPTD measurements.

Successful Resolution of Gastric Outlet Obstruction Caused by Pancreatic Pseudocyst or Walled-Off Necrosis After Acute Pancreatitis: The Role of Percutaneous Catheter Drainage.

OBJECTIVE: Delayed gastric emptying (DGE) in patients with acute pancreatitis (AP) can be caused by gastroparesis or gastric outlet obstruction, which may occur when pancreatic pseudocyst (PP) or walled-off necrosis (WON) compresses the stomach. The aim of the study was to explore a proper surgical treatment. METHODS: From June 2010 to June 2013, 25 of 148 patients with AP suffered DGE. Among them, 12 were caused by gastroparesis, 1 was a result of obstruction from a Candida albicans plug, and 12 were gastric outlet obstruction (GOO) compressed by PP (n = 8) or WON (n = 4), which were treated by percutaneous catheter drainage (PCD). RESULTS: All 12 cases of compressing GOO achieved resolution by PCD after 6 [1.86] and 37.25 [12.02] days for PP and WON, respectively. Five cases developed intracystic infection, 3 cases had pancreatic fistulae whereas 2 achieved resolution and 1 underwent a pseudocyst jejunostomy. CONCLUSIONS: Gastric outlet obstruction caused by a PP or WON is a major cause of DGE in patients with AP. Percutaneous catheter drainage with multiple sites, large-bore tubing, and lavage may be a good therapy due to high safety and minimal invasiveness.