Severe Abdominal Sepsis Research Articles

Laparostomy in a rural hospital: an African case report for a very important tool to be spread and increased

Laparostomy is a surgical technique enabling the surgeon to leave abdominal fascial edges opened after a laparotomy. This is a useful tool that can be very important in patients with intraabdominal hypertension. Open abdomen indications are: trauma, severe abdominal sepsis, intestinal infarction, vascular surgery and when the surgeon cannot close the abdomen due to high intra abdominal pressure in order to avoid abdominal compartment syndrome or in case of a second look in order to evaluate the conditions of the abdomen (and particularly of the gut). We used this technique in a low income country for a patient with intestinal obstruction where performing a primary anastomosis during the first operation was at high risk of leakage. A middle-aged woman was admitted in Pope John’s Hospital - Aber, Uganda for abdominal pain and intestinal obstruction (IO) symptoms. A laparotomy found a tract of small gut necrotic and twisted under a single adhesion. The small gut above the volvulus was dilated for the obstruction created by the adhesion. We decided to excise the necrotic intestine and leave the abdomen open for a second look and delayed anastomosis and closure. The managing of the IO was conducted by inserting a big Foley catheter in the proximal intestine to drain its enteric content in a similar fashion to a guided external fistula. Open abdomen is a very important technique, relatively new, that can impact positively in treating some surgical patients even in rural hospitals and in the absence of Intensive Care Unit. A simple trick can solve successfully the IO due to the volvulus. Laparostomy should be spread more in African and low-income countries.

FTY720-Induced Lymphopenia Does Not Aggravate Mortality in a Murine Model of Polymicrobial Abdominal Sepsis.

FTY720 is an immunosuppressive molecule licensed for the treatment of chronic relapsing multiple sclerosis (MS). It attenuates the adaptive immune response by sequestering T cells within secondary lymphoid organs via its action as functional antagonist of sphingosine-1-phasphate. To date, it is unknown whether FTY-induced lymphopenia puts MS patients at increased risk for severe forms of postoperative infectious complications such as abdominal sepsis. To determine the effect of FTY720-induced lymphopenia on survival to sepsis secondary to postoperative intraabdominal infections in a murine model of polymicrobial sepsis. Detailed analysis of cellular dynamics in secondary lymphoid organs and of cytokine profiles was performed in FTY720-treated or placebo-treated C57BL/6 mice after induction of colon ascendens stent peritonitis (CASP). Furthermore, survival analysis was performed in FTY720-treated and placebo-treated animals in severe CASP. Fifty percent of each group were treated with broad spectrum antibiotics. FTY720 treatment resulted in remodeling of cell populations present in the peripheral blood, the peritoneal cavity, and the spleen after CASP induction. Both lymphoid and myeloid cell lines were affected. However, survival in lymphopenic FTY720-treated animals was similar to placebo-treated mice following CASP. Antibiotic treatment increases survival in untreated as well as FTY720-treated animals to a similar extent. Our data demonstrate that inhibition of T-cell migration and induction of peripheral lymphopenia did not affect survival in a model of severe murine sepsis. The presence of reduced T- and B-cell numbers in the peripheral blood during a septic challenge did not negatively affect sepsis mortality in our model of severe abdominal sepsis. The absence of increased mortality under FTY720 treatment in the CASP model suggests that FTY720 treatment will probably not result in increased mortality in MS patients suffering from sepsis.

КЛЮЧЕВЫЕ МАРКЕРЫ "КАПИЛЛЯРНОЙ УТЕЧКИ" ПРИ СЕПСИСЕ И СЕПТИЧЕСКОМ ШОКЕ

To identify the most prognostically significant markers of the «increased vascular permeability» syndrome among patients with severe abdominal sepsis and septic shock an open prospective cohort study was carried out. That study involved 70 patients with severe abdominal sepsis and septic shock, the cause of which were generalized peritonitis in acute surgical diseases of abdominal cavity (APACHE II value is 17 marks). All patients were tested on the «capillary leak» presence, colloid «infusion load» and the indicators of Central and peripheral hemodynamics before and after colloid infusion were evaluated. As a result, it turned out that quite simple tests on «capillary leak» are prognostically significant for the severity evaluation of vascular wall damage in severe abdominal sepsis. The tests can be used to select the starting infusion therapy for patients with widespread peritonitis complicated by sepsis, septic shock and multiple organ failure.

Early Characteristics of Circulation in Patients with Poor Outcome of Abdominal Sepsis (Preliminary Report)

Aim: to study characteristics of the central hemodynamics (CHD) in patients with severe abdominal sepsis with different outcomes of the disease. Materials and Methods. 18 patients with abdominal sepsis, aged 50.2±3, with the APACHE II and SOFA severity scoring of 13.7±0.8 and 8.4±0.5, respectively, were enrolled in the retrospective study. The CHD was studied using the transpulmonary thermodilution. The following groups were identified: Group 1 (deceased, n=9) and Group 2 (survivors, n=9). The groups did not differ (P>0.05) in age, sex, and the severity of the condition at admission to the ICU. The significance of differences was assessed using the t-test and the chi-squared test. The prognostic value of the parameters was studied using the ROC analysis. Results. On Day 1, the intergroup differences included the average blood pressure (BPav) (85.3±3.3 and 101.6±4.6 mmHg, respectively (P 7 (sensitivity: 88.9%, specificity: 88.9%) was the most important predictor of the lethal outcome (areas under ROC curves: 0.957—0.994; P<0.05). Conclusion: during the first five days of the intensive treatment of severe sepsis in patients with unfavorable prognosis, a moderate decrease in the cardiac power index and overall cardiac systolic function was registered. The prognostic significance of such parameters as CPI and GEF may become obvious within the first 3 days of the intensive treatment.

Open abdomen procedure in managing abdominal compartment syndrome in a child with severe fungal peritonitis and sepsis after gastric perforation

Abstract Abdominal compartment syndrome with increased abdominal pressure resulted in multi-organ dysfunctions can be lethal in children. The open abdomen procedure intentionally leaves the abdominal cavity open in patients with severe abdominal sepsis and abdominal compartment syndrome by temporarily relieving the abdominal pressure. We reported our experience of open abdomen procedure in successfully treating a 4-year old boy with abdominal compartment syndrome caused by severe fungal peritonitis and sepsis after gastric perforation.

THE RESULTS OF SURGICAL TREATMENT IN PATIENTS WITH DIFFUSE POSTOPERATIVE PERITONITIS COMPLICATED WITH SEVERE ABDOMINAL SEPSIS

Aim of investigation: improvement the results of treatment in patients with diffuse postoperative peritonitis complicated with severe abdominal sepsis. Materials and methods. The present investigation is performed in 132 patients. According to the way of treatment the patients were divided into 2 groups: the first (control) group included 56 patients with diffuse postoperative peritonitis, severe abdominal sepsis who got complex treatment, sanations and abdominal cavity drainage according to “clinical indications”. The second (main) group included 76 patients with diffuse postoperative peritonitis, severe abdominal sepsis who got complex treatment and a surgical treatment algorithm which we have worked out. The patients were in severe condition with marked multiple organ failure, with equal risk of lethality in both groups. Surgical methods included laparotomy, relaparotomy, sanations, abdominal cavity drainage, mini-laparotomy. Results: application of the elaborated algorithm for surgical treatment of patients with diffuse postoperative peritonitis and severe abdominal sepsis made it possible to improve the results of treatment. Intensive ward stay was 1.4 times less accordingly, 10.0 ± 1.4 days and 14.0 ± 1.9 days (p &lt; 0.1). Hospital stay was 3.3 days less accordingly, 29.0 ± 0.9 days and 32.3 ± 1.2 days (p &lt; 0.05). Lethality was 2.5 times less as compared with abdominal cavity sanations according to “clinical indications”, accordingly 21.1 and 51.8 % (p &lt; 0.01).

The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper.

The open abdomen (OA) procedure is a significant surgical advance, as part of damage control techniques in severe abdominal trauma. Its application can be adapted to the advantage of patients with severe abdominal sepsis, however its precise role in these patients is still not clear.In severe abdominal sepsis the OA may allow early identification and draining of any residual infection, control any persistent source of infection, and remove more effectively infected or cytokine-loaded peritoneal fluid, preventing abdominal compartment syndrome and deferring definitive intervention and anastomosis until the patient is appropriately resuscitated and hemodynamically stable and thus better able to heal.However, the OA may require multiple returns to the operating room and may be associated with significant complications, including enteroatmospheric fistulas, loss of abdominal wall domain and large hernias.Surgeons should be aware of the pathophysiology of severe intra-abdominal sepsis and always keep in mind the option of using open abdomen to be able to use it in the right patient at the right time.

The preliminary clinical results of laparoscopic ileum augmentation cystoplasty for low compliance bladder

To study the effectiveness and safety of the laparoscopic ileal bladder augmentation treatment for low compliance bladder. A retrospective analysis was performed based on 36 cases admitted to the Zhejiang Provincial People's Hospital with highly reflective and low compliance bladder accepted laparoscopic ileal bladder augmentation surgical treatment from June 2011 to December 2013. In accordance with inclusion and exclusion criteria, 22 patients were enrolled in this study, including 13 males, 9 females who aged from 22 to 62 years with an average of 35.8 years. Among the selected sample, there were 15 cases of spinal cord injury, 4 cases of spinal cord dysplasia, and 3 cases of urinary tuberculosis. The duration of disease varied from 1 to 15 years, with an average of 8.5 years. For surgery, intraoperative and perioperative complications were observed, and preoperative serum creatinine in patients with postoperative at 3, 6, 12, 18, 24, 36 months, hydronephrosis, and glomerular filtration rate urodynamic parameters were used for univariate analysis of variance. All patients were successfully completed in laparoscopic surgery, the operative time were (105 ± 17) minutes (90-150 minutes), blood loss was (90 ± 26) ml (60-150 ml), postoperative intestinal function recovery time were (2.5 ± 0.7) d (2-5 d), and postoperative hospital stay was (15.0 ± 4.2) d (11-20 d), while postoperative anastomotic leakage, intestinal blockage, severe abdominal infection or sepsis and other complications did not occur. Patients were followed up for 6 to 36 months, with an average of 16.5 months, among which 17 patients were followed up for over 12 months. The bladder safety capacity increased from (103 ± 38) ml preoperatively to (405 ± 46) ml at the end of the follow-up (F = 381.7, P = 0.000), and bladder compliance increased from (10 ± 3) cmH₂O (1 cmH₂O = 0.098 kPa) preoperatively to (38 ± 4) cmH₂O (F = 678.1, P = 0.000); the average pressure within the bladder filling at the end of the follow-up was (16 ± 6) cmH₂O, which was significantly lower (F = 221.5, P = 0.000) compared to preoperative level of (45 ± 16) cmH₂O, preoperative serum creatinine went down from (184 ± 32) µmol/L to (120 ± 28) µmol/L at the end of the follow-up (F = 189.1, P = 0.000); total glomerular filtration rate rose from (40 ± 26) ml⁻¹ · min⁻¹ · 1.73 m⁻² preoperatively to (66 ± 32) ml⁻¹ · min(-1) · 1.73 m⁻² (F = 137.7, P = 0.000). Qmax of the 3 cases of urinary bladder contracture tuberculosis patients increased significantly, while 4 female patients with residual urine volume decrease had voluntary urination. Laparoscopic ileal bladder augmentation treatment for low compliance bladder is feasible and safe, with less trauma, less bleeding, less post-operative complications, and faster recovery of bowel function. Urinary function improves significantly after surgery, and function of upper urinary tract can also be effectively improved and protected in patients.

Cytokine profile in severe Gram-positive and Gram-negative abdominal sepsis.

Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-β1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors.

All-Thiol HMGB1 Is a Critical Inducer of Anemia in Sepsis Survivors through CXCR4 Signaling

Introduction: Each year, at least 500,000 patients will survive acute sepsis. Anemia is extremely common in sepsis survivors, further interfering with quality of life and activities of daily living. The pathogenesis of anemia of sepsis is unclear. High mobility group box 1 (HMGB1) is a necessary and sufficient inductor of persistent inflammation in sepsis survivors. After translocation form the nucleus to the cytoplasm, HMGB1 undergoes epigenetic changes in response to environmental queues. Redox state is the best well understood inducer of those modifications. In experimental sepsis, the reduced all-thiol form is the predominant form throughout the first four weeks of sepsis. We recently found that HMGB1 is crucial for the development and maintenance of anemia in sepsis in part by inducing a block in differentiation of late erythropoiesis. Here we present evidence indicating a critical role of the all-thiol HMGB1 in anemia of sepsis survivors through a CXCR4-dependent mechanism.Methods and results: In order to investigate the kinetics of anemia of sepsis survivors, we first induced severe polymicrobial abdominal sepsis by surgical cecal ligation and puncture (CLP) in BALB/c mice. Sham-operated mice were used as controls. Within three days after CLP, hematocrit decreased significantly in CLP survivors three days after CLP (p≤0.001), and hemoglobin (Hb) decreased significantly within 5-7 days. Initially normocytic and normochromic, mean corpuscular hemoglobin (MCH) level was reduced significantly 15 days after CLP, while MCV dropped significantly 20 days after CLP. Sepsis-induced anemia persisted for at least 30 days. Administration of an anti-HMGB1 neutralizing monoclonal antibody (nmAb) reversed anemia. Daily administration of recombinant HMGB1 for one week was sufficient to significantly reduce Hb(p≤0.05), and MCH (p≤0.01).To better understand the role of HMGB1 during erythropoiesis, we isolated CD34+ cells from cord blood and derived them in a methylcellulose-based culture, as well as in three phase liquid culture systems. In methylcellulose, all-thiol HMGB1 (the inflammatory form secreted during necrosis) significantly reduced BFU-E formation (P≤0.0001) in a concentration-dependent way, while sulphonyl-HMGB1 (the fully oxidized form released during apoptosis) had no effect. Moreover, all-thiol HMGB1 disrupted the architecture of BFU-E colonies. In liquid culture, HMGB1 significantly reduced CD34+ cell proliferation (Fig. 1A), and reduced the proportion of GPA+ cells by flow cytometry. In the liquid culture system, all-thiol HMGB1 reduced the proportion of GPA+, CD71+ cells by D16. Recently, CXCR4 was recognized as the receptor needed for all-thiol HMGB1 signaling, after forming a heterodimer with CXCL12. In the three-phase culture system, all-thiol HMGB1 significantly reduced the proportion of GPA+, CD71+ cells, and a similar level of inhibition was found when interfering with an anti-CXCR4 nmAb, CXCR4 by adding CXCL14 (a competitive inhibitor of CXCL12), or a small molecule (AMD3100) (Fig. 1B). In the presence of HMGB1, adding CXCL12 failed to rescue erythropoiesis.Conclusions: Our findings suggest that all-thiol HMGB1, the redox form present during the first weeks after sepsis onset, has a critical role in initiating and sustaining anemia in sepsis survivors. Further, all-thiol HMGB1 interferes with late erythropoiesis through a CXCR4-dependent mechanism. This has potential therapeutic implications for a persistent disorder for which the usual support –including erythropoietin and transfusions- fails to improve outcome, survival, or both. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The role of macrophage 1 antigen in polymicrobial sepsis.

Macrophage 1 antigen (Mac-1, CD11bCD18) is a leukocyte adhesion molecule that is involved in many functions including leukocyte recruitment, phagocytosis, and neutrophil apoptosis. The previous report of mild polymicrobial, abdominal sepsis showed that the administration of anti-CD11b-blocking antibody administration attenuated lung injury without any survival benefit. Here we tested the impact of Mac-1 deficiency in severe polymicrobial abdominal sepsis model. Polymicrobial sepsis was studied using cecal ligation and puncture model in wild-type (WT) or Mac-1-deficient (CD11b knockout [KO]) mice, and their outcomes were examined. Bacterial tissue load and the recruitment of neutrophils to the abdominal cavity were assessed. In vitro bacterial killing assay was performed. Serum cytokine levels were measured using multiarray. Apoptosis of spleen tissues was assessed using Western blot analysis and immunohistochemistry (cleaved caspase 3 and TUNEL staining). In addition, in vitro apoptosis assay was performed using primary splenocytes from both WT and KO mice. The recruitment of neutrophils to lung was assessed by measuring myeloperoxidase activity. Macrophage 1 antigen deficiency significantly decreased survival (survival percentage WT 43.5% vs. KO 13.0%; P = 0.0038) with higher bacterial load in blood and more severe systemic inflammation. Knockout mice demonstrated higher apoptosis both in vivo and in vitro. The recruitment of neutrophils to lung was not different between WT and KO mice. Macrophage 1 antigen deficiency was associated with poorer outcomes, more bacterial load, systemic inflammation, and splenic apoptosis. However, Mac-1 deficiency did not attenuate neutrophil recruitment to lung.

Management of pancreatic ductal leaks and fistulae

Pancreatic duct leaks can occur as a result of both acute and chronic pancreatitis or in the setting of pancreatic trauma. Manifestations of leaks include pseudocysts, pancreatic ascites, high amylase pleural effusions, disconnected duct syndrome, and internal and external pancreatic fistulas. Patient presentations are highly variable and range from asymptomatic pancreatic cysts to patients with severe abdominal pain and sepsis from infected fluid collections. The diagnosis can often be made by high-quality cross-sectional imaging or during endoscopic retrograde cholangiopancreatography (ERCP). Because of their complexity, pancreatic leak patients are best managed by a multidisciplinary team comprised of therapeutic endoscopists, interventional radiologists, and surgeons in the field of pancreatic interventions. Minor leaks will often resolve with conservative management while severe leaks will frequently require interventions. Endoscopic treatments for pancreatic duct leaks have replaced surgical interventions in many situations. Interventional radiologists also have the ability to offer therapeutic interventions for many leak patients. The mainstay of endotherapy for pancreatic leaks is transpapillary pancreatic duct stenting with a stent that bridges the leak if possible, but varies based on the manifestation and clinical presentation. Fluid collections that result from leaks, such as pseudocysts, can often be treated by endoscopic transluminal drainage with or without endoscopic ultrasound or by percutaneous drainage. Endoscopic interventions have been shown to be effective and have an acceptable complication rate.

New Methods of Treatment of the Diffused Peritonitis

Despite the achievements of the modern medicine, diffused peritonitis until the present time remains the urgent problem in the emergent abdominal surgery. According to the data of the leading Russian and foreign clinics, mortality rate in this pathology in the last decades has not showed any reduction tendency and varied in the range of minimum 20-30%, achieving at maximum 50-70%. The article presents analytical review of new approaches to the treatment of the diffused peritonitis. The authors describe in detail their own developed three methods of treatment of peritonitis and indications for their application. In traditional (semi-closed method of treatment) sanitation of the abdominal cavity was conducted with the use of immobilized forms of sodium hypochlorite in the gel of carboxymetilcellulose. Deponent of the antiseptic prolongs its bactericidal action, while the gel of carboxymetilcellulose prevents the gluing of the organs’ surfaces , by which reduces the severity of adhesive process. In surgical-laporoscopic method of treatment video-endoscopic sanitations of the abdominal cavity were done by pulsating irrigation of antiseptic. To close the defects of the abdominal cavity in semi-open method of treatment there was used large-net endoprothesis made from polypropylene. Between the edges of the wound there was left diastases, at which intra-abdominal pressure was below 15 mm. of mercury column. For selection of the appropriate method of treatment there was used the original scale of quantitative evaluation of factors, influencing lethality rate of patients. It was proved that semi-closed method of treatment is reasonable to use in patients without signs of the abdominal sepsis, while programmed video-laparoscopic sanitations should be used in cases of abdominal sepsis without poly-organic dysfunction and intra-abdominal pressure below 20 mm. of mercury column, programmed surgical sanitations are indicated for patients with severe abdominal sepsis with poly-organic insufficiency and abdominal hypertension above 20 mm of mercury column. Introduction of new methods of treatment to practice enabled to decrease the number of post???operative complications by 10% and lethality – by 8,2%

Complement C3 depletion links to the expansion of regulatory T cells and compromises T-cell immunity in human abdominal sepsis: A prospective pilot study

PurposeComplement depletion commonly occurred in septic patients, but this problem was often underestimated during the treatment process. This study was designed to determine the association between complement depletion and T-cell immunosuppression. MethodsFrom November 2011 to March 2012, patients with severe abdominal sepsis were prospectively enrolled in a single center. The baseline levels of complement C3 were used to stratify subjects into 2 groups. Plasma levels of complement components, percentage of regulatory T cells (Tregs), and T-cell immunity indexes were monitored at times after admission. The relationship between C3 depletion and T-cell response was investigated, with clinical outcomes explored meanwhile. ResultsA total of 60 patients aged 43.9 ± 11.3 years were included within the period. C3 depletion, occurring in 65% of enrolled subjects, was strongly correlated with Treg expansion (P = .001) and decreased CD4+/CD8+ ratio (P = .008). This depletion was also related to prolonged hospital stay (P = .001), delayed time to operation (P < .001), increased postoperative complications (P = .036), and hospital expenditure (P < .001). ConclusionsComplement C3 depletion was found to be linked to the expansion of Tregs during abdominal sepsis. Such depletion and associated immunosuppression should be paid close attention in the critical care.

Steroid inhibition with RU486 in a human glucocorticoid receptor isoform that lacks a ligand binding domain

METHODS: This was a prospective cohort study in a single center, patients with severe abdominal sepsis enrolled. Currently recommended treatments, such as early goal directed resuscitation, source control, nutritional support and antibiotics therapy, were implemented in all patients. The baseline levels of complement C3 were used to stratify subjects into two groups. Plasma levels of complement C3/C4, percentage of regulatory T cells (Tregs), and other immunity indexes were monitored at times after admission. The 28-day mortality, length of stay, postoperative complications and other outcomes were compared between two groups.

Management of the Open Abdomen

To determine clinical outcome of open abdomen therapy and assess the influence of negative pressure wound therapy on outcome. Leaving the abdomen open (laparostomy) is an option following laparotomy for severe abdominal sepsis or trauma. Negative pressure wound therapy (NPWT) has become a popular means of managing laparostomy wounds. It may facilitate nursing care and delayed primary wound closure but the evidence to support its use is poor and concern has arisen about the risk of intestinal fistulation from exposed bowel, leading to an increased risk of death. Prospective observational study of 578 patients treated with an open abdomen in 105 hospitals in the United Kingdom between January 1, 2010, and June 30, 2011. Propensity analysis was used to compare adverse outcomes (fistulation, death, intestinal failure, bleeding requiring intervention) and delayed primary closure rates in patients who did and did not receive NPWT. The most common indication for an open abdomen (n = 398, 68.9%) was abdominal sepsis. Overall hospital mortality was 28.2%. The majority of patients (n = 355, 61.4%) were treated with NPWT. Intestinal fistulation [relative risk (RR) = 0.83, 95% confidence interval (CI): 0.44-1.58], death (RR = 0.87, 95% CI: 0.64-1.20), bleeding (RR = 0.74, 95% CI: 0.45-1.23), and intestinal failure (RR = 1.00, 95% CI: 0.64-1.57) were no more common in patients receiving NPWT, but the rate of delayed primary closure was significantly lower (RR = 0.74, 95% CI: 0.60-0.90, P = 0.002) when NPWT was used. The indications for an open abdomen in the United Kingdom appear to be significantly different to those described in N. America, where its use in the management of trauma predominates. NPWT in patients with an open abdomen is not associated with an increase in mortality or intestinal fistulation. It is, however, associated with a reduced rate of delayed primary closure. Although this may be related to patient selection, NPWT may leave patients with abdominal wall defects that require further treatment.

HMGB1 impairs erythropoiesis during sepsis (P3163)

Abstract Severe sepsis is one of the leading causes of mortality and disability. Anemia is common in acute sepsis and related to decreased quality of life and increased mortality in sepsis survivors. Serum levels of HMGB1, a critical mediator of sepsis pathophysiology, remain elevated for weeks after onset of sepsis. We used a murine model of severe abdominal sepsis to study effect of HMGB1 on erythropoesis. Mice subjected to sepsis have significant decrease in hemoglobin (p=0.03 by day 3) and hematocrit (p=0.05 by day 7). Reticulocytosis, an indicator of bone marrow proliferation, was only transiently found on day 10. Administration of neutralizing anti-HMGB1 antibody to survivors beginning 9 days post- sepsis significantly improved hemoglobin and hematocrit levels. Exposure of erythropoetic stem cells, generated by culturing cord blood CD34+ cells with erythropoietin, stem cell factor and IL-3, to recombinant HMGB1 (rHMGB1) induced a decrease in hemoglobinization, and expression of GPA (CD235a) and transferrin receptor (CD71), indicating suppression of erythroid differentiation. rHMGB1 induced suppression of erythropoesis when added before day 8 and not later indicating that HMGB1 inhibits initial phases of differentiation. Together, these findings indicate that HMGB1 impairs erythropoiesis by altering differentiation of erythropoetic stem cells, and suggest that it may be possible to prevent or reverse anemia in sepsis survivors by administration of anti-HMGB1 antibodies.

Correction: Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime?

Correction: Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime?

Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime?

BackgroundThe complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction.ObjectiveThis study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored.MethodsForty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups.ResultsWithin the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845–0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications.ConclusionsComplement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care.Trial RegistrationClinicalTrials.gov NCT01568853

Successful treatment of a life-threatening air leakage, complicating severe abdominal sepsis, with a one-way endobronchial valve

A 41-year-old woman had a jeopardizing air leak from an alveolar-pleural and transdiaphragmatic fistula with pulmonary cavitation, secondary to a severe postoperative abdominal sepsis. Her condition dramatically improved by introduction, in the lower bronchus, of a one-way endobronchial valve, leading to immediate cessation of air leakage and removal of extracorporeal membrane oxygenation, and thus avoiding a lower left lobectomy with myoplasty. Furthermore, removal of the valve nine weeks later led to near-complete recovery of the left lower lobe.