Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta-analysis, and meta-regression.

Aims: There have been inconsistent reports regarding the effect of antithrombin on sepsis; furthermore, there are limited reports on how dosage affects therapeutic efficacy. Thus, we aimed to perform a systematic review and meta-analysis of the use of antithrombin for sepsis and a meta-regression analysis of antithrombin dosage. Methods: We included randomized controlled trials (RCTs) and observational studies of adult patients with sepsis who received antithrombin. Outcomes included all-cause mortality and serious bleeding complications. Statistical analyses and data synthesis were performed using a random-effects model; further, meta-regression and funnel plots were used to explore heterogeneity and biases. Results: Seven RCTs and six observational studies were included. Most patients in the RCTs and observational studies had severe sepsis and septic-disseminated intravascular coagulation (DIC), respectively. A meta-analysis using RCTs showed no significant differences in mortality between the antithrombin and control groups. However, the meta-analysis of observational studies indicated a trend of decreasing mortality rates with antithrombin administration (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.68-0.92; p = 0.002). Bleeding complications were significantly higher in the antithrombin group than in the control group in both study types (OR, 1.90; 95% CI, 1.52-2.37; p < 0.01). The meta-regression analysis showed no correlation between antithrombin dosage and mortality. Conclusion: A meta-analysis of RCTs confirmed no survival benefit of antithrombin, whereas that of observational studies, which mostly focused on septic DIC, showed a significant beneficial effect on improving outcomes. Indications of antithrombin should be considered based on its beneficial and harmful effects.

Gastrointestinal Perforation Complicated by Continuous Opioids Administration for Intrahepatic Cystic Hemorrhage Pain Management.

Intracystic hemorrhage is a rare complication of multiple hepatic cysts and can lead to hemorrhagic shock. Hence, measures should be taken to prevent the rupture of cysts. The incidence of intestinal perforation is high in patients undergoing hemodialysis. The diagnosis can be difficult in a patient without typical symptoms. We report the case of a woman in her late 60s with multiple renal and hepatic cysts, which caused chronic renal failure managed with dialysis. She presented with abdominal pain and was diagnosed with intrahepatic cystic bleeding. Continuous intravenous fentanyl was administered for pain management, which temporarily alleviated pain, but abdominal pain recurred with increased intensity when she resumed feeding. Subsequently, a contrast-enhanced computed tomography revealed perforation of the lower gastrointestinal tract. Therefore, in cases of intrahepatic cystic hemorrhage that require administration of analgesics, the complications of other diseases that may also cause acute abdominal pain should also be considered.

Development of a delirium predictive model for adult trauma patients in an emergency and critical care center: a retrospective study.

BACKGROUND: Delirium has been shown to prolong the length of intensive care unit stay, hospitalization, and duration of ventilatory control, in addition to increasing the use of sedatives and increasing the medical costs. Although there have been a number of reports referring to risk factors for the development of delirium, no model has been developed to predict delirium in trauma patients at the time of admission. This study aimed to create a scoring system that predicts delirium in trauma patients. METHODS: In this single-center, retrospective, observational study, trauma patients aged 18 years and older requiring hospitalization more than 48 hours were included and divided into the development and validation cohorts. Univariate analysis was performed in the development cohort to identify factors significantly associated with prediction of delirium. The final scoring system for predicting delirium was developed using multivariate analysis and internal validation was performed. RESULTS: Of the 308 patients in the development cohort, 91 developed delirium. Clinical Frailty Score, fibrin/fibrinogen degradation products, low body mass index, lactate level, and Glasgow Coma Scale score were independently associated with the development of delirium. We developed a scoring system using these factors and calculated the delirium predictive score, which had an area under the curve of 0.85. In the validation cohort, 46 of 206 patients developed delirium. The area under the curve for the validation cohort was 0.86, and the calibration plot analysis revealed the scoring system was well calibrated in the validation cohort. DISCUSSION: This scoring system for predicting delirium in trauma patients consists of only five risk factors. Delirium prediction at the time of admission may be useful in clinical practice. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

Planned Versus On-Demand Relaparotomy Strategy in Initial Surgery for Non-occlusive Mesenteric Ischemia.

BACKGROUND: There has been insufficient evidence regarding a treatment strategy for patients with non-occlusive mesenteric ischemia (NOMI) due to the lack of large-scale studies. We aimed to evaluate the clinical benefit of strategic planned relaparotomy in patients with NOMI using detailed perioperative information. METHODS: We conducted a multicenter retrospective cohort study that included NOMI patients who underwent laparotomy. In-hospital mortality, 28-day mortality, incidence of total adverse events, ventilator-free days, and intensive care unit (ICU)-free days were compared between groups experiencing the planned and on-demand relaparotomy strategies. Analyses were performed using a multivariate mixed effects model and a propensity score matching model after adjusting for pre-operative, intra-operative, and hospital-related confounders. RESULTS: A total of 181 patients from 17 hospitals were included, of whom 107 (59.1%) were treated using the planned relaparotomy strategy. The multivariate mixed effects regression model indicated no significant differences for in-hospital mortality (61 patients [57.0%] in the planned relaparotomy group vs. 28 patients [37.8%] in the on-demand relaparotomy group; adjusted odds ratio [95% confidence interval] = 1.94 [0.78-4.80]), as well as in 28-day mortality, adverse events, and ICU-free days. Significant reduction in ventilator-free days was observed in the planned relaparotomy group. Propensity score matching analysis of 61 matched pairs with comparable patient severity did not show superiority of the planned relaparotomy strategy. CONCLUSIONS: The planned relaparotomy strategy, compared with on-demand relaparotomy strategy, did not show clinical benefits after the initial surgery of patients with NOMI. Further studies estimating potential subpopulations who may benefit from this strategy are required.

High-dose Factor XIII administration induces effective hemostasis for trauma-associated coagulopathy (TAC) both in vitro and in rat hemorrhagic shock in vivo models.

BACKGROUND: Trauma-associated coagulopathy (TAC) is an early and primary complication in severe trauma patients. Factor XIII (FXIII) is reported to stabilize a clot in the late phase of the coagulation cascade. The goal of this study was to investigate whether the administration of FXIII improves the condition of TAC both in vitro and in vivo. METHODS: We evaluated the effects of different doses, including a very high dose of FXIII (3.6-32.4 IU/mL) on tissue-plasminogen activator-induced hyperfibrinolysis and the combined condition of dilutional coagulopathy and tissue-plasminogen activator-induced hyperfibrinolysis in vitro. The coagulation status was analyzed by rotational thromboelastometry (ROTEM) and Sonoclot. Then, we evaluated the effect of high-dose FXIII (300 IU/kg) for severe coagulopathy in vivo using a rat liver trauma model in which coagulopathy similar to TAC was observed. Survival time and the amount of intra-abdominal bleeding of rats were measured, and a coagulation test was also performed. Histologic evaluations of rats' lung and kidney after FXIII administration were completed. RESULTS: High-dose FXIII significantly improved clot strength as well as increased resistance to hyperfibrinolysis in vitro which was confirmed by ROTEM. Platelet function on Sonoclot was significantly increased by FXIII in a dose-dependent manner. Factor XIII significantly decreased the total amount of bleeding and prolonged the survival time compared to control (control vs FXIII: 108.9 ± 11.4 vs 32.6 ± 5.5 mL/kg; p < 0.001; 26.0 ± 8.8 vs 120 minutes, p < 0.001) in a rat model. Rotational thromboelastometry parameters and platelet function on Sonoclot were significantly improved in the FXIII (+) group compared to control. No adverse effects of FXIII were detected histologically. CONCLUSION: Factor XIII not only generated stable clot resistance to hyperfibrinolysis but also enhanced platelet function by facilitating clot retraction. High-dose FXIII administration therapy has significant clinical impact for severe trauma accompanied with TAC. STUDY TYPE: Human in vitro and rat in vivo experimental study.

Utility of rotational thromboelastometry for the diagnosis of asymptomatic hyperfibrinolysis secondary to anaphylaxis.

We present a case of hyperfibrinolysis induced by oxaliplatin-derived anaphylactic shock, which was diagnosed with rotational thromboelastometry (ROTEM). A 57-year-old male patient underwent a second course of oxaliplatin (126 mg/m/course)-based chemotherapy for stage IV metastatic rectal cancer. Two minutes after the infusion of oxaliplatin, the patient lost consciousness and developed generalized urticarial lesions, followed by hemodynamic instability and respiratory insufficiency. He was diagnosed anaphylactic shock and transported to emergency department (ED) after intramuscular injection of 0.2 mg of adrenaline, an intravenous injection of 100 mg of hydrocortisone, and 500 mg of methylprednisolone. After arriving in the ED, the patient remained in shock and early resuscitation with administration of 5 mg of D-chlorpheniramine maleate and 20 mg of famotidine was performed. He recovered from his state of shock 30 min after the resuscitation. ROTEM findings showed fulminant hyperfibrinolysis with minimal changes in standard coagulation tests (SCTs) and no remarkable coagulopathy. Seven hours after the attack, he became asymptomatic and follow-up ROTEM revealed values within normal limits with the exception of sustained slight abnormalities of SCTs. He was discharged the next day without any signs of spontaneous bleeding and has continued his outpatient chemotherapy uneventfully. A review of the literature on anaphylaxis-induced hyperfibrinolysis and a discussion of the mechanism between anaphylactic shock and hyperfibrinolysis were performed. Although administration of tissue-type plasminogen activator can play a vital role in anaphylactic shock-induced hyperfibrinolysis, early effective resuscitation is imperative to prevent severe hemorrhagic complications. Therefore, ROTEM is a useful tool that can detect these dynamic changes faster and more accurately than SCTs.

Risk factors for bowel necrosis in patients with hepatic portal venous gas.

PURPOSE: To evaluate the risk factors for bowel necrosis in adult patients with hepatic portal venous gas (HPVG). METHODS: This retrospective study comprised 33 adult patients treated for HPVG between August, 2008 and December, 2011. The patients were divided into a necrotic group (n = 14) and a non-necrotic group (n = 19). We analyzed the clinical demographics, laboratory data, multi-detector computed tomography findings, treatments, and outcomes in each group. RESULTS: Abdominal pain, peritoneal signs, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH), small intestinal dilatation, poor enhancement of the bowel wall, and intestinal pneumatosis were all significantly associated with bowel necrosis. Moreover, there were significantly more operative cases and deaths in the necrotic group. Multivariate analysis revealed that systolic BP (p = 0.048), LDH (p = 0.022), and intestinal pneumatosis (p = 0.038) were independent risk factors for bowel necrosis. Thus, we created new diagnostic criteria for bowel necrosis based on these three factors, the sensitivity, specificity, and accuracy of which were 100, 78.9, and 87.9 %, respectively. CONCLUSIONS: This study demonstrates new and important findings to evaluate the risk factors for bowel necrosis. Using our diagnostic criteria, the indications for emergency laparotomy can be established more accurately.

Usefulness of the endotoxin activity assay to evaluate the degree of lung injury.

PURPOSE: It has been reported that the Pulse Contour Cardiac Output (PiCCO) is very useful mainly in the field of intensive care and treatment to grasp the pathophysiological conditions of pulmonary edema because of its capability of obtaining data such as Pulmonary Vascular Permeability Index (PVPI) and Extra Vascular Lung Water (EVLW). Furthermore, a high degree of usability of various markers has been reported for better understanding of the pathological conditions in cases with septicemia. MATERIALS AND METHODS: The correlation between the cardiorespiratory status based upon the PiCCO monitor (EVLW and PVPI) and inflammatory markers including C reactive protein, procalcitonin (PC), and Endotoxin Activity Assay (EAA) were evaluated in 11 severe cases that required treatment with a respirator in an intensive care unit. RESULTS: The EAA values were significantly higher in patients with abnormal EVLW at 0.46±0.20 compared to the normal EVLW group at 0.21±0.19 (p=0.0064). In a similar fashion, patients with abnormal PVPI values tended to have higher PC levels at 18.9±21.8 compared to normal PVPI cases at 2.4±2.2 (p=0.0676). On the other hand, PVPI was significantly higher in the abnormal EAA group at 3.55±0.48 in comparison with the normal EAA group at 1.99±0.68 (p=0.0029). The abnormal EAA group tended to have higher PVPI values than the normal EAA group. CONCLUSION: The EAA is a measurement method designed to estimate the activity of endotoxins in the whole blood. Our results suggest that the EAA value, which had the greatest correlation with lung disorders diagnosed by the PiCCO monitoring, reflects inflammatory reactions predominantly in the lungs.

Expression and functional characterization of the adhesion molecule spermatogenic immunoglobulin superfamily in the mouse testis.

Spermatogenic immunoglobulin superfamily (SgIGSF) is a mouse protein belonging to the immunoglobulin superfamily expressed in the spermatogenic cells of seminiferous tubules. We produced a specific polyclonal antibody against SgIGSF. Western blot analysis of the testes from postnatal developing mice using this antibody demonstrated multiple immunopositive bands of 80-130 kDa, which increased in number and size with the postnatal age. Enzymatic N-glycolysis caused reduction in the size of these bands to 70 kDa, indicating that SgIGSF is a glycoprotein and its glycosylation pattern and extent are developmentally regulated. Immunohistochemical analysis of the adult testis demonstrated that SgIGSF was present in the spermatogenic cells in the earlier steps of spermatogenesis and increased in amount from intermediate spermatogonia through zygotene spermatocytes but was diminished in the steps from early pachytene spermatocytes through round spermatids. After meiosis, SgIGSF reappeared in step 7 spermatids and was present in the elongating spermatids until spermiation. The immunoreactivity was localized primarily on the cell membrane. Consistent with the findings in adult testes, the analysis of the developing testes revealed that SgIGSF was expressed separately in the spermatogenic cells in earlier and later phases. Sertoli cells had no expression of SgIGSF, whereas both SgIGSF immunoprecipitated from the testis lysate and produced in COS-7 cells was shown to bind to the surface of Sertoli cells in primary culture. These results suggested that SgIGSF on the surface of spermatogenic cells binds to some membrane molecules on Sertoli cells in a heterophilic manner and thereby may play diverse roles in the spermatogenesis.