Sharma's parachute sign a new laparoscopic sign in abdomino pelvic tuberculosis.

AIMS: To demonstrate a new laparoscopic sign "Sharma's Parachute sign" in abdominopelvic tuberculosis in women with infertility. METHODS: A total of 104 women who were diagnosed to have abdominopelvic tuberculosis, on endometrial sampling or on laparoscopy were enrolled in this ongoing study on tuberculosis in infertility. A new laparoscopic "Sharma's parachute sign" was looked for in these cases on laparoscopy. RESULTS: The mean age, pairty and duration of infertility was 27.6 years, 0.58 and 4.1 years respectively. Menstrual dysfuction were common especially hypomenorrhoea (34.61%), oligomenorrhoea (36.53%) along with constitutional symptoms and abdomino pelvic pain or lump. Diagnosis of abdominopelvic tuberculosis was made by identification of acid fast bacilli (AFB) on microscopy or culture of endometrial aspirate or peritoneal biopsy or positive gene Xpert or positive polymerase chain reaction (PCR) or histopathological demonstration of epithelioid granuloma on endometrial or peritoneal biopsy, various laparoscopic findings on pelvic and abdominal organs were tubercles and shaggy areas (white deposits, caseous nodules encysted ascites, abdominal and pelvic adhesions, tubal findings (hydrosalpinx, pyosalpinx, beaded or calcified tubes). A new "Sharma's parachute sign"in which ascending colon was totally adherent to anterior abdominal wall with its mesocolon looking like an open parachute with small caseous nodule was seen in 11 (10.5%) cases. CONCLUSION: Diagnostic laparoscopy is an important investigation for abdominopelvic tuberculosis showing various adhesions including new parachute sign.

MicroRNA-223 modulates the IL-4-medicated macrophage M2-type polarization to control the progress of sepsis.

MicroRNAs play a variety of roles in the progress of inflammation. Herein, we investigated the roles of miR-223 in governing macrophage polarization balance in the progress of sepsis. We firstly observed that miR-223 was down-regulated at the early phase and up-regulated at the late phase of sepsis in macrophages; the levels of miR-223 were positively correlated to the ratio of M2 macrophages during sepsis. In miR-223 knockout mice, we observed that miR-223 was dispensable for efficient pro-inflammatory responses, but was required for efficient M2-associated phenotype and function. miR-223 deletion increased clinical scores of sepsis, leading to increased mortality in septic mice. Furthermore, we found that miR-223 expression in M2-type macrophages was controlled by interleukin (IL)-4, but not IL-10; IL-4 antibodies were able to downregulate the levels of miR-223, increased the expression of targeted genes Nfat5 and Rasa1, reduced the ratio of M2 macrophages, resulting in a decreased survival rate in septic mice. Meanwhile, miR-223 deficient macrophages appeared a markedly decreased M2-type polarization when induced by IL-4, but did not affect macrophages skew to M2 phenotype induced by IL-10. Taken together, our results demonstrate that miR-223 acts as an important regulator to modulate IL-4-meditated M2-type polarization of macrophages via targeting to Nfat5 and Rasa1 to control the progress of sepsis.

A Critical Role of Formyl Peptide Receptors in Host Defense against Escherichia coli.

Formyl peptide receptors (FPRs, mouse Fprs) belong to the G protein-coupled receptor superfamily and mediate phagocyte migration in response to bacteria- and host-derived chemoattractants; however, knowledge about their in vivo roles in bacterial pathogenesis is limited. In this study, we investigated the role of Fpr1 and Fpr2 in host defense against Escherichia coli infection. In vitro, we found that supernatants from E. coli cultures induced chemotaxis of wild-type (WT) mouse bone marrow-derived neutrophils and that the activity was significantly reduced in cells genetically deficient in either Fpr1 or Fpr2 and was almost absent in cells lacking both receptors. Consistent with this, E. coli supernatants induced chemotaxis and MAPK phosphorylation in HEK293 cells expressing either recombinant Fpr1 or Fpr2 but not untransfected parental cells. WT bone marrow -derived neutrophils could actively phagocytose and kill E. coli, whereas both activities were diminished in cells lacking Fpr1 or Fpr2; again, an additive effect was observed in cells lacking both receptors. In vivo, Fpr1 and Fpr2 deficiency resulted in reduced recruitment of neutrophils in the liver and peritoneal cavity of mice infected with inactivated E. coli Moreover, Fpr1-/- and Fpr2-/- mice had significantly increased mortality compared with WT mice after i.p. challenge with a virulent E. coli clinical isolate. These results indicate a critical role of Fprs in host defense against E. coli infection.

Expression of factor V by resident macrophages boosts host defense in the peritoneal cavity.

Macrophages resident in different organs express distinct genes, but understanding how this diversity fits into tissue-specific features is limited. Here, we show that selective expression of coagulation factor V (FV) by resident peritoneal macrophages in mice promotes bacterial clearance in the peritoneal cavity and serves to facilitate the well-known but poorly understood "macrophage disappearance reaction." Intravital imaging revealed that resident macrophages were nonadherent in peritoneal fluid during homeostasis. Bacterial entry into the peritoneum acutely induced macrophage adherence and associated bacterial phagocytosis. However, optimal control of bacterial expansion in the peritoneum also required expression of FV by the macrophages to form local clots that effectively brought macrophages and bacteria in proximity and out of the fluid phase. Thus, acute cellular adhesion and resident macrophage-induced coagulation operate independently and cooperatively to meet the challenges of a unique, open tissue environment. These events collectively account for the macrophage disappearance reaction in the peritoneal cavity.

Impact of co-amoxicillin-resistant Escherichia coli and Pseudomonas aeruginosa on the rate of infectious complications in paediatric complicated appendicitis.

BACKGROUND: Choice of antibiotics for complicated appendicitis should address local antibiotic resistance patterns. As our local data showed a less than 15% resistance of Escherichia coli to co-amoxicillin (amoxicillin + clavulanic acid), we opted for this antibiotic in 2013. Subsequently, the increasing prevalence of Pseudomonas aeruginosa challenged this choice. AIM OF THE STUDY: The aim of this study was to describe the bacteriology of peritoneal swabs from cases of complicated appendicitis in our paediatric patients, and to determine the risk of infectious complications (wound and/or intra-abdominal abscesses). METHODS: We designed a retrospective cohort study including all children (<18 years old) who had surgery for complicated appendicitis between 1 January 2010 and 31 December 2016 and had a peritoneal swab culture. Microbiological results are presented descriptively. Univariate analyses were performed for potential determinants of infectious complications. All variables with a p-value <0.05 were then included in a multivariable logistic regression model, for which adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: One hundred and thirty-three patients were treated for complicated appendicitis and had cultures of peritoneal fluid. Median age was 9.5 years old (IQR 5.7–12.4), and there were 53 girls (40%). E. coli was isolated in 94 patients (71%) and was resistant to co-amoxicillin in 14% of cases. P. aeruginosa was isolated in 31 patients (23%). The rate of infectious complications was 38% (8/21 patients) when the empiric antibiotic did not cover P. aeruginosa and 0% (0/10 patients) when P. aeruginosa was covered adequately (p = 0.03). In a multivariable analysis, only co-amoxicillin-resistant E. coli significantly predicted infectious complications (OR 4.7; 95% CI 1.4–16.6; p = 0.015). CONCLUSION: Results of the multivariable analysis of this small, retrospective study revealed a statistically significant increase in the risk of postoperative complications in the presence of co-amoxicillin-resistant E. coli. The choice of antibiotic should be adapted accordingly. More data are needed to justify the systematic coverage of P. aeruginosa in children with complicated appendicitis.  .

Connexin-43-dependent ATP release mediates macrophage activation during sepsis.

Bacterial spillage into a sterile environment following intestinal hollow-organ perforation leads to peritonitis and fulminant sepsis. Outcome of sepsis critically depends on macrophage activation by extracellular ATP-release and associated autocrine signalling via purinergic receptors. ATP-release mechanisms, however, are poorly understood. Here, we show that TLR-2 and -4 agonists trigger ATP-release via Connexin-43 hemichannels in macrophages leading to poor sepsis survival. In humans, Connexin-43 was upregulated on macrophages isolated from the peritoneal cavity in patients with peritonitis but not in healthy controls. Using a murine peritonitis/sepsis model, we identified increased Connexin-43 expression in peritoneal and hepatic macrophages. Conditional Lyz2cre/creGja1flox/flox mice were developed to specifically assess Connexin-43 impact in macrophages. Both macrophage-specific Connexin-43 deletion and pharmacological Connexin-43 blockade were associated with reduced cytokine secretion by macrophages in response to LPS and CLP, ultimately resulting in increased survival. In conclusion, inhibition of autocrine Connexin-43-dependent ATP signalling on macrophages improves sepsis outcome.

Antimicrobial cathelicidin peptide LL­37 induces NET formation and suppresses the inflammatory response in a mouse septic model.

LL­37 is the only known member of the cathelicidin family of antimicrobial peptides in humans. In addition to its broad spectrum of antimicrobial activities, LL­37 may modulate various inflammatory reactions. The authors previously revealed that LL­37 improves the survival of a murine cecal ligation and puncture (CLP) sepsis model. In the present study, the mechanism for the protective action of LL­37 was elucidated using the CLP model, focusing on the effect of LL­37 on the release of neutrophil extracellular traps (NETs). The results indicated that the intravenous administration of LL­37 suppressed the increase of damage-associated molecular patterns (DAMPs), including histone­DNA complex and high­mobility group protein 1, in addition to interleukin­1ß, tumor necrosis­α and soluble triggering receptor expressed on myeloid cells (TREM)­1 in plasma and peritoneal fluids. Notably, LL­37 significantly suppressed the decrease of mononuclear cell number in blood, and the increase of polymorphonuclear cell (neutrophil) number in the peritoneal cavity during sepsis. Furthermore, LL­37 reduced the bacterial burden in blood and peritoneal fluids. Notably, LL­37 increased the level of NETs (myeloperoxidase­DNA complex) in plasma and peritoneal fluids. In addition, it was verified that LL­37 induces the release of NETs from neutrophils, and NETs possess the bactericidal activity. Overall, these observations suggest that LL­37 improves the survival of CLP septic mice by possibly suppressing the inflammatory responses as evidenced by the inhibition of the increase of cytokines, soluble TREM­1 and DAMPs (host cell death) and the alteration of inflammatory cell numbers, and bacterial growth via the release of NETs with bactericidal activity.

Analysis of early mesothelial cell responses to Staphylococcus epidermidis isolated from patients with peritoneal dialysis-associated peritonitis.

The major complication of peritoneal dialysis (PD) is the development of peritonitis, an infection within the abdominal cavity, primarily caused by bacteria. PD peritonitis is associated with significant morbidity, mortality and health care costs. Staphylococcus epidermidis is the most frequently isolated cause of PD-associated peritonitis. Mesothelial cells are integral to the host response to peritonitis, and subsequent clinical outcomes, yet the effects of infection on mesothelial cells are not well characterised. We systematically investigated the early mesothelial cell response to clinical and reference isolates of S. epidermidis using primary mesothelial cells and the mesothelial cell line Met-5A. Using an unbiased whole genome microarray, followed by a targeted panel of genes known to be involved in the human antibacterial response, we identified 38 differentially regulated genes (adj. p-value < 0.05) representing 35 canonical pathways after 1 hour exposure to S. epidermidis. The top 3 canonical pathways were TNFR2 signaling, IL-17A signaling, and TNFR1 signaling (adj. p-values of 0.0012, 0.0012 and 0.0019, respectively). Subsequent qPCR validation confirmed significant differences in gene expression in a number of genes not previously described in mesothelial cell responses to infection, with heterogeneity observed between clinical isolates of S. epidermidis, and between Met-5A and primary mesothelial cells. Heterogeneity between different S. epidermidis isolates suggests that specific virulence factors may play critical roles in influencing outcomes from peritonitis. This study provides new insights into early mesothelial cell responses to infection with S. epidermidis, and confirms the importance of validating findings in primary mesothelial cells.

Does Intraoperative Systematic Bacterial Sampling During Complete Cytoreductive Surgery (CRS) with Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) Influence Postoperative Treatment? A New Predictive Factor for Postoperative Abdominal Infectious Complications.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an emerging curative treatment option for patients with peritoneal carcinomatosis. It has a long-term survival benefit but is associated with high rates of morbidity, ranging from 12 % to 65 %, mainly due to infectious complications. We sought to evaluate the clinical relevance of routine intraoperative bacteriological sampling following CRS/HIPEC. STUDY DESIGN: Between November 2010 and December 2014, every patients receiving CRS/HIPEC were included. Three samples were routinely collected from standardized locations for intraperitoneal rinsing liquid bacteriological analysis (RLBA) after completion of HIPEC. The clinical and surgical features, bacteriological results, and short-term outcomes were retrospectively reviewed. RESULTS: The overall mortality and morbidity rates were 5 and 45 %, respectively. Among the 75 included patients, 40 % (n = 30) had at least one positive bacterial culture. Risk factors for a positive culture were colorectal resection (adjusted hazard ratio [HR] = 3.072, 95 % CI 1.843-8.004; p = 0.009) and blood loss >1000 mL (HR = 4.272, 95 % CI 1.080-18.141; p = 0.031). Among 26 (35 %) patients with abdominal infectious complications, 13 (17 %) experienced isolated complications. A positive RLBA result was independently associated with abdominal infectious complications (HR = 5.108, 95 % CI 1.220-16.336; p = 0.024) and isolated abdominal infectious complications (HR = 4.199, 95 % CI 1.064-15.961; p = 0.04). CONCLUSIONS: Forty percent of the RLBA samples obtained following CRS/HIPEC tested positive for bacteria. Bacterial sampling of rinsing liquid should be systematically performed. An aggressive and immediate antibiotic strategy needs to be evaluated.

Polylactic acid nanosheets in prevention of postoperative intestinal adhesion and their effects on bacterial propagation in an experimental model.

BACKGROUND: Ultrathin films (nanosheets) adhere tightly to organ surfaces but prevent adhesion to other organs. The antiadhesive effect of nanosheets and their effect on bacterial propagation were investigated in a murine intestinal adhesion model. METHODS: Polylactic acid nanosheets (approximately 80 nm thick) were produced. Serosal defects were created by peeling off the intestinal serosa; these were left open or covered with nanosheets or Seprafilm® and the formation of intestinal adhesions was analysed. To examine bacterial propagation, a nanosheet or Seprafilm® was placed on intact murine jejunum followed by Escherichia coli inoculation at the site. RESULTS: Treatment both with nanosheets and with Seprafilm® reduced postoperative intestinal adhesion (mean adhesion score 0·67 for nanosheets, 0·43 for Seprafilm® and 2·87 for no antiadhesive treatment; P < 0·001 for nanosheets or Seprafilm® versus no adhesive treatment). Nanosheet treatment did not affect bacterial propagation in the peritoneal cavity, whereas Seprafilm®-treated mice showed bacterial propagation, leading to increased mortality. CONCLUSION: Nanosheets may be effective novel antiadhesive agents even in the presence of bacterial contamination. Surgical relevance Intra-abdominal adhesions following surgical contamination can trigger postoperative complications and lead to deterioration in long-term quality of life. However, currently there are no effective antiadhesion materials to prevent the formation of adhesions. Treatment with ultrathin nanosheets effectively reduced postoperative intestinal adhesion in an experimental mouse model, and did not affect bacterial propagation in the peritoneal cavity. These nanosheets are potent novel antiadhesive materials that potentially can be applied even in contaminated conditions.

All Three TonB Systems Are Required for Vibrio vulnificus CMCP6 Tissue Invasiveness by Controlling Flagellum Expression.

TonB systems actively transport iron-bound substrates across the outer membranes of Gram-negative bacteria. Vibrio vulnificus CMCP6, which causes fatal septicemia and necrotizing wound infections, possesses three active TonB systems. It is not known why V. vulnificus CMCP6 has maintained three TonB systems throughout its evolution. The TonB1 and TonB2 systems are relatively well characterized, while the pathophysiological function of the TonB3 system is still elusive. A reverse transcription-PCR (RT-PCR) study showed that the tonB1 and tonB2 genes are preferentially induced in vivo, whereas tonB3 is persistently transcribed, albeit at low expression levels, under both in vitro and in vivo conditions. The goal of the present study was to elucidate the raison d'être of these three TonB systems. In contrast to previous studies, we constructed in-frame single-, double-, and triple-deletion mutants of the entire structural genes in TonB loci, and the changes in various virulence-related phenotypes were evaluated. Surprisingly, only the tonB123 mutant exhibited a significant delay in killing eukaryotic cells, which was complemented in trans with any TonB operon. Very interestingly, we discovered that flagellum biogenesis was defective in the tonB123 mutant. The loss of flagellation contributed to severe defects in motility and adhesion of the mutant. Because of the difficulty of making contact with host cells, the mutant manifested defective RtxA1 toxin production, which resulted in impaired invasiveness, delayed cytotoxicity, and decreased lethality for mice. Taken together, these results indicate that a series of virulence defects in all three TonB systems of V. vulnificus CMCP6 coordinately complement each other for iron assimilation and full virulence expression by ensuring flagellar biogenesis.

Risk of infection after iatrogenic perforation of the gut wall? Evaluation of preventive strategies in a randomized controlled animal trial.

BACKGROUND: Interventional endoscopies entail a risk of infection secondary to perforation of the luminal wall. Thereby, bacteria may be introduced into the sterile environment of the peritoneal cavity (PC). Limited data are available regarding the efficacy of prophylactic anti-infective treatments. The aim of the study was to examine the efficacy/safety of anti-infective means in the prevention of infection by interventional endoscopies in a randomized controlled animal trial. METHODS: Forty pigs were randomized to: 1: control; 2: oral lavage; 3: gastric lavage; 4: oral/gastric lavage; 5: i.m. antibiotics. Lavage was performed with Octenisept prior to the operation. After gastric wall perforation, peritoneoscopy was performed. Before the procedure, after closure and prior to autopsy, intraabdominal lavage for bacterial culture was taken using mini-laparoscopy. At autopsy, macroscopic appearance of the PC was scored. Lavage fluids were grown to identify/quantify bacterial load. Concentration of intraperitoneal bacteria at autopsy was defined as main outcome parameter. RESULTS: No major complications occurred in any of the procedures. Bacterial load of the PC at autopsy was significantly reduced with antibiotics compared to all other groups, whereas it did not differ between the lavage groups and control. Macroscopic scoring of the PC showed significant lower rate of intraabdominal abscesses in the antibiotic group compared to the lavage groups and control (p < 0.01). CONCLUSION: Only antibiotic prophylaxis is effective for the prevention of infection after iatrogenic perforation of the gastrointestinal wall. There was no difference between any form of lavage and the control group. Further studies in humans are required to prove these animal data.

Endogenous Acetylcholine Controls the Severity of Polymicrobial Sepsisassociated Inflammatory Response in Mice.

Acetylcholine (ACh) is the main mediator associated with the anti-inflammatory cholinergic pathway. ACh plays an inhibitory role in several inflammatory conditions. Sepsis is a severe clinical syndrome characterized by bacterial dissemination and overproduction of inflammatory mediators. The aim of the current study was to investigate the participation of endogenous ACh in the modulation of inflammatory response induced by a model of polymicrobial sepsis. Wild type (WT) and vesicular acetylcholine transporter knockdown (VAChT(KD)) mice were exposed to cecal ligation and perforation- induced sepsis. Levels of Tumor Necrosis Factor Alpha (TNF-α) and bacterial growth in peritoneal cavity and serum, and neutrophil recruitment into peritoneal cavity were assessed. The concentration of TNF-α in both compartments was higher in VAChT(KD) in comparison with WT mice. VAChT(KD) mice presented elevated burden of bacteria in peritoneum and blood, and impairment of neutrophil migration to peritoneal cavity. This phenotype was reversed by treatment with nicotine salt. These findings suggest that endogenous ACh plays a major role in the control of sepsis-associated inflammatory response.

Coexistence of tuberculosis with histiocytic sarcoma: A rare association.

Histiocytic sarcoma (HS) is an exceedingly rare hematolymphoid neoplasm of histiocytic lineage. We report a case of 25-year-old Woman who presented with generalized lymphadenopathy and ascites. There was no personal or family history of tuberculosis (TB). Histopathological examination of omental and peritoneal biopsy revealed TB while mesenteric lymph node showed HS. This case highlights the fact that a patient may be harboring coexistent malignancy/lymphoma along with TB. Therefore, the clinician should have a high index of suspicion, especially when there is therapeutic failure to antitubercular drugs (ATT) and persistence of fever or generalized lymphadenopathy. Sometimes, there may be surprising presence of uncommon malignancies, like in our case, where we found HS with TB. Since both diseases share similar clinical and radiological features, it is highly possible that one may not look further, once one of these is diagnosed.

Population Pharmacokinetics and Target Attainment of Meropenem in Plasma and Tissue of Morbidly Obese Patients after Laparoscopic Intraperitoneal Surgery.

Meropenem serves as a clinically important, broad-spectrum antibiotic. While meropenem is commonly used in obese patients, its pharmacokinetics in this patient group is not well known. Our aim was to characterize the population pharmacokinetics and target attainment in plasma, subcutaneous tissue, and peritoneal fluid for meropenem in morbidly obese patients. Four doses of 1g meropenem were given as 15-min infusions every 8 h to five morbidly obese patients (body mass index [BMI], 47.6 to 62.3 kg/m(2)). After the fourth dose, serial meropenem concentrations were determined in plasma and, via microdialysis, in subcutaneous tissue and peritoneal fluid. All concentrations were analyzed simultaneously via population modeling, and target attainment probabilities predicted via Monte Carlo simulations using the target of unbound meropenem concentrations above the MIC for at least 40% of the dosing interval. For patients with 53 kg fat-free mass, total clearance was 18.7 liters/h and volume of distribution at steady state was 27.6 liters. The concentrations in subcutaneous tissue and peritoneal fluid largely paralleled those in plasma (equilibration half-life, <30 min). The area under the curve (AUC) in subcutaneous tissue divided by the plasma AUC had a mean of 0.721. For peritoneal fluid, this AUC ratio had a mean of 0.943. Target attainment probabilities were >90% after 1 g meropenem every 8 h as a 15-min infusion for MICs of up to 2 mg/liter in plasma and peritoneal fluid and 0.5 mg/liter in subcutaneous tissue. Meropenem pharmacokinetics in plasma and peritoneal fluid of obese patients was predictable, but subcutaneous tissue penetration varied greatly. (This study has been registered at ClinicalTrials.gov under registration no. NCT01407965.).

Interferon-gamma and nitric oxide synthase 2 mediate the aggregation of resident adherent peritoneal exudate cells: implications for the host response to pathogens.

Interferon-gamma (Ifnγ), a key macrophage activating cytokine, plays pleiotropic roles in host immunity. In this study, the ability of Ifnγ to induce the aggregation of resident mouse adherent peritoneal exudate cells (APECs), consisting primarily of macrophages, was investigated. Cell-cell interactions involve adhesion molecules and, upon addition of Ifnγ, CD11b re-localizes preferentially to the sites of interaction on APECs. A functional role of CD11b in enhancing aggregation is demonstrated using Reopro, a blocking reagent, and siRNA to Cd11b. Studies with NG-methyl-L-arginine (LNMA), an inhibitor of Nitric oxide synthase (Nos), NO donors, e.g., S-nitroso-N-acetyl-DL-penicillamine (SNAP) or Diethylenetriamine/nitric oxide adduct (DETA/NO), and Nos2-/- mice identified Nitric oxide (NO) induced by Ifnγ as a key regulator of aggregation of APECs. Further studies with Nos2-/- APECs revealed that some Ifnγ responses are independent of NO: induction of MHC class II and CD80. On the other hand, Nos2 derived NO is important for other functions: motility, phagocytosis, morphology and aggregation. Studies with cytoskeleton depolymerizing agents revealed that Ifnγ and NO mediate the cortical stabilization of Actin and Tubulin which contribute to aggregation of APECs. The biological relevance of aggregation of APECs was delineated using infection experiments with Salmonella Typhimurium (S. Typhimurium). APECs from orally infected, but not uninfected, mice produce high amounts of NO and aggregate upon ex vivo culture in a Nos2-dependent manner. Importantly, aggregated APECs induced by Ifnγ contain fewer intracellular S. Typhimurium compared to their single counterparts post infection. Further experiments with LNMA or Reopro revealed that both NO and CD11b are important for aggregation; in addition, NO is bactericidal. Overall, this study elucidates novel roles for Ifnγ and Nos2 in regulating Actin, Tubulin, CD11b, motility and morphology during the aggregation response of APECs. The implications of aggregation or "group behavior" of APECs are discussed in the context of host resistance to infectious organisms.

Nosocomial rapidly growing mycobacterial infections following laparoscopic surgery: CT imaging findings.

OBJECTIVE: To identify the distribution and frequency of computed tomography (CT) findings in patients with nosocomial rapidly growing mycobacterial (RGM) infection after laparoscopic surgery. METHOD: A descriptive retrospective study in patients with RGM infection after laparoscopic surgery who underwent CT imaging prior to initiation of therapy. The images were analyzed by two radiologists in consensus, who evaluated the skin/subcutaneous tissues, the abdominal wall, and intraperitoneal region separately. The patterns of involvement were tabulated as: densification, collections, nodules (≥1.0 cm), small nodules (<1.0 cm), pseudocavitated nodules, and small pseudocavitated nodules. RESULTS: Twenty-six patients met the established criteria. The subcutaneous findings were: densification (88.5%), small nodules (61.5%), small pseudocavitated nodules (23.1 %), nodules (38.5%), pseudocavitated nodules (15.4%), and collections (26.9%). The findings in the abdominal wall were: densification (61.5%), pseudocavitated nodules (3.8%), and collections (15.4%). The intraperitoneal findings were: densification (46.1%), small nodules (42.3%), nodules (15.4%), and collections (11.5%). CONCLUSION: Subcutaneous CT findings in descending order of frequency were: densification, small nodules, nodules, small pseudocavitated nodules, pseudocavitated nodules, and collections. The musculo-fascial plane CT findings were: densification, collections, and pseudocavitated nodules. The intraperitoneal CT findings were: densification, small nodules, nodules, and collections. KEY POINTS: • Rapidly growing mycobacterial infection may occur following laparoscopy. • Post-laparoscopy mycobacterial infection CT findings are densification, collection, and nodules. • Rapidly growing mycobacterial infection following laparoscopy may involve the peritoneal cavity. • Post-laparoscopy rapidly growing mycobacterial intraperitoneal infection is not associated with ascites or lymphadenopathy.

Impact of antibiotic treatment intensity on long-term sepsis-associated kidney injury in a polymicrobial peritoneal contamination and infection model.

BACKGROUND/AIMS: Long-term kidney affections after sepsis are poorly understood. Animal models for investigating kidney damage in the late phase of disease progression are limited. The aim of this study was to investigate the impact of two antibiotic regimes on persistence of kidney injury after peritonitis. METHODS: Kidney damage was investigated 65 days after polymicrobial peritoneal contamination and infection (PCI) sepsis induction in C57BL/6 mice. Short-term antibiotic therapy (STA, 4 days) was compared to long-term (LTA, 10 days) treatment using plasma creatinine, plasma and urine neutrophil gelatinase-associated lipocalin (NGAL), urine albumin/creatinine ratio and renal histology. RESULTS: Sepsis resulted in mortality rates of 68.2% (STA) and 61.0% (LTA). Surviving STA animals showed the most pronounced kidney damage indicated by significantly elevated levels of creatinine and acute tubular damage (ATD), whereas NGAL was significantly increased in LTA survivors only. A creatinine level above 0.3 mg/dl was used to define kidney injury, found in 21.4% of STA animals and 7.8% of LTA animals. While animals with kidney injury demonstrated significantly higher ATD scores and persistent tubular damage, no significant differences were found for plasma or urine NGAL levels or urine albumin/creatinine ratios. CONCLUSION: Prolonged antibiotic treatment reduced the rate of ongoing peritonitis-induced kidney injury in a C57BL/6 mouse model. Plasma or urine NGAL levels were not able to identify animals with or without persistent kidney injury. The kidney injury after the PCI mouse model represents prototypic clinical findings and should be used for further studies investigating disease mechanisms.

Peritoneal cavity is a route for gut-derived microbial signals to promote autoimmunity in non-obese diabetic mice.

Macrophages play a crucial role in innate immune reactions, and peritoneal macrophages (PMs) guard the sterility of this compartment mainly against microbial threat from the gut. Type 1 diabetes (T1D) is an autoimmune disease in which gut microbiota and gut immune system appear to contribute to disease pathogenesis. We have recently reported elevated free radical production and increased permeability of gut epithelium in non-obese diabetic (NOD) mice. Impaired barrier function could lead to bacterial leakage to the peritoneal cavity. To explore the consequences of impaired gut barrier function on extra-intestinal immune regulation, we characterized peritoneal lavage cells from young newly weaned NOD mice. We detected a rapid increase in the number of macrophages 1-2 weeks after weaning in NOD mice compared to C57BL/6 and BALB/c mice. Interestingly, this increase in macrophages was abrogated in NOD mice that were fed an antidiabetogenic diet (ProSobee), which improves gut barrier function. Macrophages in young (5-week-old) NOD mice displayed a poor TNF-α cytokine response to LPS stimulation and high expression of interleukin-1receptor-associated kinase-M (IRAK-M), indicating prior in vivo exposure to TLR-4 ligand(s). Furthermore, injection of LPS intraperitoneally increased T cell CD69 expression in pancreatic lymph node (PaLN), suggestive of T cell activation. Leakage of bacterial components such as endotoxins into the peritoneal cavity may contribute to auto-reactive T cell activation in the PaLN.

Low-dose cisplatin administration to septic mice improves bacterial clearance and programs peritoneal macrophage polarization to M1 phenotype.

Sepsis is a systemic inflammatory response to infection, and early responses of macrophages are vital in controlling the infected microorganisms. We used a cecal ligation and puncture (CLP) model of sepsis to determine the role of cisplatin (0.1, 0.5 and 1 mg kg(-1)) with respect to peritoneal macrophages, controlling peritoneal/blood bacterial infection, and systemic inflammation. We found that mice which received low-dose (0.1 and 0.5 mg kg(-1)) i.p. cisplatin had lower mortality rate and improved clinical scores compared with mice in normal saline-treated group, and the level of IL-6 and TNF-α was significantly reduced after cisplatin administration in peritoneal fluid of mice underwent CLP. Although cisplatin had no directly bactericidal ability, the numbers of bacteria in peritoneal and blood were significantly reduced at 24 and 72 h after the onset of CLP. Besides, in vivo phagocytosis and killing assay showed that the ability of macrophage derived from peritoneum was significantly increased with cisplatin treatment (5, 10, and 15 µM) for both gram-positive (Enterococcus faecalis) and gram-negative (Escherichia coli) bacteria. This was associated with the macrophage phenotype polarization from CD11b(+) F4/80(high) CD206(-) to CD11b(+) F4/80(low) CD206(-) M1 group. These findings underscore the importance of low-dose cisplatin in the treatment of sepsis.