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.

Delayed admission to ICU does not increase the mortality of patients post neurosurgery.

Increasing shortage of intensive care resources is a worldwide problem. While routine postoperative admission to the intensive care unit (ICU) of patients undergoing neurosurgery is a long established practice for many hospitals. Therefore, some neurosurgical patients have to be cared in post anesthesia care unit (PACU) before ICU admission during high ICU occupancy. The aim of this study was to compare the outcome of neurosurgical patients immediately admitted to the ICU post operation with those who were required to wait for ICU bed in PACU and managed by anesthesiologists before ICU admission. All adult neurosurgical patients admitted to our ICU between January 2010 and July 2013 were retrospectively analyzed. Recorded data included demographic data, surgical categories, end time of operation, operation hours, postoperative complication, hospital/ICU length of stay and cost, Glasgow coma score (GCS) on ICU discharge and ICU mortality. A total of 989 neurosurgical patients were evaluated. Nine hundred thirty-seven (94.7%) patients were immediately admitted and 52 (5.3%) patients had delayed ICU admission. Median PACU waiting hours was 4.3 h (interquartile range: 2.0-10.2 h). Delayed ICU admission post neurosurgery was highly associated with the end time of operation (p = 0.019) and high ICU occupancy (p < 0.0001). Average GCS on ICU discharge was higher in immediately admitted group (13.0 ± 3.5 vs. 11.4 ± 4.5, p = 0.012). However, delayed admission to ICU post neurosurgery was not associated with prolonged ICU length of stay, increased ICU mortality, increased postoperative complication and hospital/ICU cost (all p > 0.05). Thus, an algorithm for appropriate disposition of neurosurgical patients is warranted so as to balance the quality of care and control of scarce intensive resources.

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.

Outcome of Intravenous and Inhaled Polymyxin B treatment in Patients with Multidrug-Resistant Gram-Negative Bacterial Pneumonia.

PURPOSE: The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited. METHODS: This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed. RESULTS: Median PMB concentrations in the ELF were 7.83 (0.72-66.5), 116.72 (17.37-571.26), 41.1 (3.69-133.78), and 33.82 (0.83-126.68) mg/L at 0, 2, 6, and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6, and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were > 2 mg/L in most patients. Of the patients, 57.14 % were cured and 71.43 % showed a favorable microbiological response. The incidence of side effects with PMB was low. CONCLUSIONS: Inhaled plus intravenous PMB can achieve high ELF concentrations and favorable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB.

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This study presents a multi-center clinical data management platform that facilitates unified and structured management of real-world data and serves as an ideal tool to enhance the quality and progress of clinical research related to severe acute pancreatitis (SAP). The use of the platform enables clinical teams to obtain safe, accurate, structurally unified, traceable, scene-clear, and fully functional real-world medical data in the diagnosis, treatment, and research of acute pancreatitis (AP).

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.

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.

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).

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.

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.

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.

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.

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.

cDNA clone, prokaryotic expression and purification of human interleukin-13 receptor [alpha]2 chain.

Despite advances in surgical technology and radiation therapy, the prognosis in the patients with malignant glioma remains poor. Recent studies show that interleukin-13 receptor [alpha]2 chain (IL-13Ra2), a brain tumor-associated receptor for IL-13, may play a role in immunotherapy for glioblastoma. We thus amplified human IL-13Ra2 gene from the human glioblastoma cell line using RT-PCR and cloned the target gene into the pET-28a, a prokaryotic expressing plasmid. After transformation, the recombinant plasmid expressed a soluble protein induced by IPTG. The purified recombinant protein was shown to be a single band on the SDS-PAGE with a predicated molecular weight of human IL-13Ra2 gene, suggesting that the recombinant protein of human IL-13Ra2 was successfully expressed. Recombinant IL-13Ra2 protein can be used as an anti-tumor vaccine, which may provide a promising new strategy for the treatment of brain malignant gliomas.

Familial and genetic researches on three Chinese families with von Hippel-Lindau disease.

OBJECTIVE: Hemangioblastoma of the central nervous system (CNS) occur as sporadic tumors or as a part of von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary tumor syndrome caused by germline mutation of the VHL tumor suppressor gene. This study shows the clinical characteristics of three large Chinese families with VHL disease and evaluates the consequence of the genetic test for the diagnosis of VHL disease and clinical screening of the family members. METHODS: DNA is extracted from peripheral blood in 43 members from three large families with VHL disease and amplified by PCR to three exons of the VHL gene. The PCR products were directly sequenced and the mutations compared with the Human Gene Mutation Database. RESULTS: The ages of the patients who are given the initial diagnosis ranged from 16 to 47 years (mean: 31 years), and the mean time was 17.3 months (2-30 months) from the emergence of the symptom to patients' first visit. Furthermore, the gender distribution was 20% female (4) and 80% male (16). Twenty VHL disease patients in the three families have the most common manifestation of CNS hemangioblastoma. The cytosine replaced the 716th guanine on four patients and three carriers of virulence gene from the first family, which made the 168th serine replaced by threonine. And no mutation was found on the 22 members of the second family. Meanwhile, it was also found that the guanine replaced the 559th cytosine on one patient and two carriers from the third family, which made the 116th leucine replaced by valine. CONCLUSION: The DNA analysis of VHL germline mutations is clearly superior to clinical information to diagnose VHL disease. The CNS hemangioblastoma is the early manifestation in VHL disease. It is recommended that every patient with CNS hemangioblastoma should be screened for VHL gene mutation. The test for the VHL gene plays a key role in the discovery of asymptomatic patients and the carriers of virulence gene.

Incidence of unexplained intra-abdominal free fluid in patients with blunt abdominal trauma.

BACKGROUND: Intra-abdominal free fluid is commonly caused by injuries of solid or hollow organs in patients suffering from blunt abdominal trauma (BAT). However, it presents a diagnostic dilemma for surgeons when free fluid is unexplained, especially in stable BAT patients. This study was to analyze the incidence of such unexplained free fluid in BAT patients and its diagnostic value in abdominal organ injury. METHODS: Altogether 597 patients with BAT who had been treated at our trauma center over a 10-year period were reviewed. Stable patients with free fluid but without free air or definite organ injury on abdominal computed tomography were studied. Clinical management and operative findings were analyzed. RESULTS: Thirty-four (5.70%) of the 597 patients met the inclusion criteria: 24 (4.02%) underwent therapeutic exploratory laparotomy: bowel injuries were found in 13, hepatic rupture in 3, colon rupture in 3, duodenal rupture in 2, spleen rupture in 1, pancreas rupture in 1, and gallbladder perforation in 1. In 2 patients, laparotomy was nontherapeutic. Those with moderate or large amounts of free fluid were more likely to suffer from a hollow viscus injury and have a therapeutic procedure. The mean time of hospital stay for the delayed laparotomy group was longer than that for the emergency group (19+/-5.12 vs. 12+/-2.24 days; t=2.73, P<0.01). CONCLUSIONS: There was a positive correlation between the amount of unexplained free fluid and the determination of intra-abdominal organ injury. The proportion of BAT patients who required surgical intervention was high, particularly those with a moderate or large amount of free fluid, and most of them suffered from a hollow organ injury. Emergency laparotomy is recommended for these patients.

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.