An Acquired and Endogenous Glycocalyx Forms a Bidirectional "Don't Eat" and "Don't Eat Me" Barrier to Phagocytosis.

Macrophages continuously survey their environment in search of pathogens or apoptotic corpses or debris. Targets intended for clearance expose ligands that initiate their phagocytosis ("eat me" signals), while others avoid phagocytosis by displaying inhibitory ligands ("don't eat me" signals). We report that such ligands can be obscured by the glycosaminoglycans and glycoproteins that coat pathogenic as well as malignant phagocytic targets. In addition, a reciprocal barrier of self-synthesized or acquired glycocalyx components on the macrophage surface shrouds phagocytic receptors, curtailing their ability to engage particles. The coating layers of macrophages and their targets hinder phagocytosis by both steric and electrostatic means. Their removal by enzymatic means is shown to markedly enhance phagocytic efficiency. In particular, we show that the removal of mucins, which are overexpressed in cancer cells, facilitates their clearance. These results shed light on the physical barriers that modulate phagocytosis, which have been heretofore underappreciated. VIDEO ABSTRACT.

[Tuberculous abdominal cocoon as a rare variant of peritonitis]. / Osumkovyvayushchii tuberkuleznyi perivistserit kak redkii variant peritonita.

OBJECTIVE: To study and systematize clinical symptoms of tuberculous perivisceritis, to clarify diagnostic value of laboratory and instrumental survey in these patients and to identify the features of surgical treatment. MATERIAL AND METHODS: There were 8 patients with tuberculous perivisceritis. Examination included computed tomography of the abdominal cavity and chest, ultrasound, laparoscopy. All patients underwent surgical treatment with histological, cytological, microbiological and molecular genetic analysis of peritoneal exudate and biopsy of peritoneal specimens. RESULTS: Clinical picture of tuberculous perivisceritis is variable and non-specific. Periods of exacerbation are replaced by periods of prolonged remission. The complex of radiological survey used in verification of perivisceritis does not allow accurate determining the nature of disease. However, peritoneal tuberculosis may be suspected as a rule considering signs of thickening of the peritoneum. Objective confirmation of perivisceritis is possible only during surgical intervention. In this case, etiological factor can be established only after a thorough histological examination of resected fibrous capsule. CONCLUSION: Clinical picture of tuberculous perivisceritis does not have specific symptoms. The disease is characterized by prolonged and undulating course. Acute peritonitis and acute intestinal obstruction may be suspected during exacerbation of the pathological process. Laparotomy followed by complete excision of fibrous capsule and adhesiolysis is preferred.

Use of adenosine deaminase (ADA) to diagnose suspected peritoneal tuberculosis in Rwanda: a cross-sectional study.

BACKGROUND: Peritoneal tuberculosis is the most common cause of low albumin gradient ascites in developing countries, but it can be easily confused with other causes of ascites. Peritoneal tuberculosis requires early recognition of symptoms and signs in order to make a quick diagnosis for appropriate treatment. Measurement of adenosine deaminase (ADA) level > 39 in ascites fluid is an established test to diagnose peritoneal tuberculosis. Many low-income countries do not currently test for adenosine deaminase in ascites fluid, including Rwanda. METHOD: Cross-sectional, descriptive study conducted through the Internal Medicine Department of three university teaching hospitals in Rwanda. Participants were patients older than 16 years presenting to tertiary referral hospitals with ascites of unknown cause. RESULTS: Of 103 ascites fluid samples collected, 52 of them (50.5%) had an elevated ADA, consistent with a presumptive diagnosis of peritoneal TB. Among those 52 subjects diagnosed with peritoneal TB, 39 out of 52 (75%) did not receive anti-TB medications. Among the 17 subjects who were treated with anti-TB medications, 4 of 17 (23.6%) did not have peritoneal TB based on ADA level. Samples with low-albumin gradient ascites were more likely to have high ADA ≥39 IU/L (p = 0.039). CONCLUSION: Our findings suggest that 3out of 4 patients with PTB in Rwanda are not getting TB treatment and 1 in 4 patients who are taking TB medications do not need it. Even if the true number of Rwandans who are being undertreated and overtreated is less than our study suggests, these results should prompt a larger study of peritoneal tuberculosis. Adding adenosine deaminase (ADA) to the diagnostic tools available to clinicians could help achieve the goal of correctly putting every Rwandan with tuberculosis on treatment, while avoiding unnecessary tuberculosis medications in those who do not have the disease.

Impact of colibacillosis on production in laying hens associated with interference of the phosphotransfer network and oxidative stress.

The objective of this study was to evaluate the productive impact of colibacillosis on laying hens and to investigate whether energetic metabolism and oxidative stress were involved in the pathogenesis of the disease. An experimental shed containing 270 laying hens of the Hy-Line lineage (32 weeks old) presented approximately 40% daily laying, and many birds presented with diarrhea and apathy followed by death. Necropsy revealed macroscopic lesions compatible with colibacillosis and infectious agent Escherichia coli was isolated from fecal samples of all birds in the infected group, as well as from tissue (ovary, liver and peritoneum). Sixteen chickens were selected for this study, divided into two groups: Control (animals without clinical alterations) and infected (with diarrhea and apathetic). E. coli isolates were subjected to the antimicrobial susceptibility testing according to the methodology approved by CLSI, 2018. This testing showed sensitivity to gentamicin, amoxicillin, norfloxacin and colistin. It was then determined that laying hens would be treated with norfloxacin (15 mg/kg) diluted in water offered at will to the birds for three days. Blood collections were performed via brachial vein after the diagnosis of E. coli (before starting treatment) and seven days after treatment. Three debilitated chickens died on the second day after initiating therapy. Before treatment, birds with clinical signs had higher levels of lipoperoxidation (LPO) and activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) than in the control group (asymptomatic animals). After treatment, LPO levels remained higher in birds that had clinical disease (infected group), whereas the activity of SOD and GPx enzymes did not differ between groups. Activity levels of creatine kinase (CK) and pyruvate kinase (PK) were higher in the group of chickens with clinical disease before treatment. Post-treatment, no differences were observed between groups in terms of CK; however, PK activity remained high in these animals. In the hens that died, there were lesions characteristic of avian colibacillosis, with ovary involvement, explaining the low laying activity of the birds at their peak of production. For 10 days after starting treatment, the percentage of laying increased to 90%. Therefore, we conclude that colibacillosis interferes with the phosphotransfer network by stimulating ATP production, in addition to causing oxidative stress of the birds during laying, that negatively affects health and productive efficiency.

Clinical features and outcomes of abdominal tuberculosis in southeastern Korea: 12 years of experience.

BACKGROUND: Abdominal tuberculosis (TB) is an uncommon form of infection with Mycobacterium tuberculosis in Korea. In this study, we aimed to highlight the clinical features, diagnostic methods, and outcomes of abdominal TB over 12 years in Southeastern Korea. METHODS: A total of 139 patients diagnosed as having abdominal TB who received anti-TB medication from January 2005 to June 2016 were reviewed. Among them, 69 patients (49.6%) had luminal TB, 28 (20.1%) had peritoneal TB, 7 (5.0%) had nodal TB, 23 (16.5%) had visceral TB, and 12 (8.6%) had mixed TB. RESULTS: The most frequent symptoms were abdominal pain (34.5%) and abdominal distension (21.0%). Diagnosis of abdominal TB was confirmed using microbiologic and/or histologic methods in 76 patients (confirmed diagnosis), while the remaining 63 patients were diagnosed based on clinical presentation and radiologic imaging (clinical diagnosis). According to diagnostic method, frequency of clinical diagnosis was highest in patients with luminal (50.7%) or peritoneal (64.3%) TB, while frequency of microscopic diagnosis was highest in patients with visceral TB (68.2%), and frequency of histologic diagnosis was highest in patients with nodal TB (85.2%). Interestingly, most patients, except those with nodal TB, showed a good response to anti-TB agents, with 84.2% showing a complete response. The mortality rate was only 1.4% in the present study. CONCLUSIONS: Most patients responded very well to anti-TB therapy, and surgery was required in only a minority of cases of suspected abdominal TB.

[Tuberculous peritonitis. 'Forgotten' disease]. / Tuberkuleznyi peritonit. 'Zabytaia' bolezn'.

AIM: To analyze diagnosis and treatment of patients with tuberculous peritonitis, to develop the algorithms for instrumental examination and differential diagnosis. MATERIAL AND METHODS: There were 48 patients with tuberculous peritonitis. The examination included radiography, abdominal and thoracic computed tomography, ultrasound, and laparoscopy. All patients underwent histological, cytological, microbiological and molecular-genetic analysis of abdominal exudate and peritoneal biopsy. Exclusion criterion was signs of secondary peritonitis. RESULTS: Clinical picture of tuberculous peritonitis was accompanied by nonspecific symptoms. Previously identified pulmonary tuberculosis and HIV-infection were present in 93.8 and 70.8% of patients. Diagnostic laparoscopy of abdominal cavity as the main method of instrumental diagnosis together with cytological, molecular-genetic and microbiological research of peritoneal exudate and tissue specimens were useful to determine diagnosis in 87.2-95.8% of cases. CONCLUSION: Tuberculous peritonitis may be assumed in patients with previous tuberculosis of lungs or other localizations, HIV-infection. Computed tomography is the most informative method to diagnose tuberculous peritonitis. Diagnostic laparoscopy is indicated for suspected tuberculous peritonitis. This procedure is supplemented by peritoneal biopsy, cytological, molecular-genetic and microbiological examination of peritoneal exudate and tissue specimens.

Tissue macrophages as mediators of a healthy relationship with gut commensal microbiota.

Mammals and microorganisms have evolved a complex and tightly controlled mutual relationship. This interaction grants protection and energy source for the microorganisms, and on the other hand, provides several immunologic, metabolic and physiological advantages for the host. The gastrointestinal tract (GI) harbors the largest bacteria diversity within the body and complex mechanisms control microbiota community under homeostasis. However, once disrupted, microbiota imbalance can lead to overt growth of resident and invasive populations, with potential risk for lethal diseases. In these cases, bacteria might also escape from the intestines and reach different organs through the blood and lymphatic circulation. To control these unwanted conditions, all body tissues are populated with resident macrophages that have the ability to capture and eliminate pathogens, avoiding their dissemination. Here we discuss the different routes for bacterial translocation from the intestinal tract, and how macrophages act in the removal of these microorganisms to prevent systemic infections and restore the homeostasis.

Inflammatory response and peritoneal contamination after transrectal natural orifice specimen extraction (NOSE) versus mini-laparotomy: a porcine in vivo study.

BACKGROUND: Transrectal natural orifice specimen extraction (NOSE) avoids abdominal organ retrieval during laparoscopic procedures and may reduce surgical trauma. However, this has not been proven clinically and transrectal peritoneal contamination is feared to cause infectious complications. This experimental study was designed to evaluate inflammatory response and peritoneal contamination after transrectal NOSE versus mini-laparotomy. METHODS: 24 German Landrace pigs underwent transrectal NOSE (N = 12) or mini-laparotomy (N = 12) for standardized extraction of water-instilled balloon. Blood samples were taken for analysis of leucocytes, CRP, IL-6, IL-10, and TNFα at 6, 12, 24, 48, 72 h as well as 7 and 14 days postoperatively. After 14 days laparoscopy was performed to inspect the abdomen and for microbiological swab sampling. RESULTS: Leucocytes were higher in the NOSE group at 72 h (19.3 ± 3.9/nl vs. 15.8 ± 4.2/nl, p = 0.046). IL-6 was lower in the NOSE group at day 7 (165 ± 100/nl vs. 306 ± 70/nl, p = 0.030). No difference was found comparing inflammatory parameters at all other time points. No difference was found regarding peritoneal contamination, which was 58.3% (7/12) in the NOSE group and 41.7% (5/12) in the MiniLap group (p = 0.414). CONCLUSIONS: The results suggest a pronounced acute inflammatory response after transrectal NOSE compared to mini-laparotomy, while late cytokine response seems to be less after transrectal NOSE, which may reflect less intense wound healing process. Using standardized rectal decontamination and endolumenal colon occlusion transrectal NOSE seems to be safe and comparable to mini-laparotomy with regard to peritoneal contamination. Clinical evidence is needed now to weight transrectal NOSE against mini-laparotomy during laparoscopic surgery.

A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.

The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.

Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study.

Alterations of the innate immunity contribute to the development of spontaneous bacterial peritonitis (SBP) in liver cirrhosis. Given its role in immune signaling, antimicrobial function, and macrophage differentiation, we hypothesized that genetic polymorphisms of TRAF6 modulate the risk of SBP. Thus, we determined theTRAF6 haplotype in 432 patients with cirrhosis and ascites using the haplotype-tagging single nucleotide polymorphisms rs331457 and rs5030419. In addition, peritoneal macrophages were immunomagnetically isolated and characterized. Overall, 122 (28%) patients had an episode of SBP. In the combined prospective-retrospective analysis the frequency of SBP differed between the four haplotypes (P = 0.014) and was the highest in 102 patients carrying the rs331457 but not the rs5030419 variant, when compared to other haplotypes (odds ratio 1.95 [1.22-3.12]) or to the wild-type (odds ratio 1.71 [1.04-2.82]). This association was confirmed in multivariate logistic regression (adjusted odds ratio 2.00 [1.24-3.22]) and in prospective sensitivity analysis (hazard ratio 2.09 [1.08-4.07]; P = 0.03). The risk haplotype was associated with lower concentrations of the immune activation marker soluble CD87 in ascitic fluid and with a decreased expression of IL-6 and CXCL8 in isolated peritoneal macrophages. In conclusion, genetic polymorphisms of TRAF6 are associated with decreased peritoneal immune activation and an increased risk of SBP.

Screening for genital tuberculosis in a limited resource country: case report.

BACKGROUND: Screening for benign or malignant process of pelvis in young females is a challenge for a physician in a limited resource country. Tuberculosis should be always considered in the differential diagnosis of a pelvic mass in countries with high prevalence of tuberculosis. Negative results of analysis of peritoneal fluid for acid-fast staining, late cultures, and unavailability of new diagnostics methods such as polymerase chain reaction and adenosine deaminase of the aspirated fluid from peritoneal cavity can often result in invasive diagnostic procedures such as laparotomy. CASE PRESENTATION: We report a case of a 24 year old Albanian unemployed female living in urban place in Kosovo who presented with abdominal pain, loss of appetite, fever, headache, a weight loss, nonproductive cough and menstrual irregularity for three weeks. In this example case, the patient with cystic mass in tubo-ovarial complex and elevated serum cancer antigen 125 levels was diagnosed for genital tuberculosis after performing laparotomy. Caseose mass found in left tubo-ovarial complex and histopathological examination of biopsied tissue were the fastest diagnostic tools for confirming pelvis TB. The Lowenstein-Jensen cultures were positive after six weeks and her family history was positive for tuberculosis. CONCLUSION: Young females with abdominopelvic mass, ascites, a positive family history for tuberculosis and high serum cancer antigen 125, should always raise suspicion of tuberculosis especially in a limited resource country. A laparoscopy combined with peritoneal biopsy should be performed to confirm the diagnosis as this could lead to a prevention of unnecessary laparotomies.

Protective effects of oridonin on the sepsis in mice.

This study aimed to investigate the protective effects of oridonin (ORI) on cecal ligation and puncture (CLP)-induced sepsis in mice. Male C57BL/6 mice weighing 22-30 g and aged 8-10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 µg/kg) was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin-eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6), and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05). Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05). The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05). Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.

Endolumenal colon occlusion reduces peritoneal contamination during a transrectal NOTES procedure: a controlled porcine survival study.

BACKGROUND: To enable an efficient and enduring decontamination of the rectal mucosa during transanal endosocopic procedures, we developed a device for reversible endolumenal colon occlusion (ColoShield). The aim of this study was to assess the value of ColoShield in reducing peritoneal contamination during a transrectal procedure. METHODS: Sixteen pigs underwent transrectal hybrid NOTES cholecystectomy after standardized disinfective rectal washout either with endolumenal colon occlusion using ColoShield (N = 8) or without colon occlusion (N = 8). Rectal swab samples were taken before and after rectal washout and at the end of the procedure. Peritoneal biopsies for microbiological evaluation were obtained at the end of the procedure and at necropsy 7 days after surgery. RESULTS: Peritoneal contamination at the end of surgery was significantly lower using ColoShield compared to not using colon occlusion [13 (1/8) vs. 75 % (6/8); P = 0.012]. No significant differences were found regarding contamination of rectal swabs and peritoneal contamination at necropsy. CONCLUSION: The application of ColoShield may increase the safety of transrectal NOTES and transanal endoscopic procedures by reducing peritoneal contamination and consecutive infectious complications.

Peritoneal Coccidioidomycosis: a Rare Case Report and Review of the Literature.

Coccidioidomycosis is a fungal infection endemic to the southwestern United States that typically causes a self-limited pulmonary illness. Extrapulmonary dissemination is extremely rare and typically localized to the skin, bone, and meninges. The gastrointestinal system has generally been thought to be spared from this disease. This report describes a patient who was initially diagnosed with pulmonary coccidioidomycosis with mediastinal lymphadenopathy and skin dissemination. Ten months after completion of treatment, he presented with nonspecific abdominal pain and diffuse musculoskeletal and constitutional symptoms. Radiographic imaging revealed near resolution of previously noted thoracic findings but new peritoneal thickening and enhancement suggestive of peritoneal carcinomatosis. Laparoscopic biopsies confirmed Coccidioides immitis by culture and histology without evidence of other abnormalities. This case is unique for several reasons. It is one of a relatively small number of cases that describes a diagnosis of peritoneal coccidioidomycosis and the first case identified in which a healthy patient developed extensive peritoneal disease in spite of near-complete resolution of pulmonary and skin manifestations after appropriate treatment. This case underscores the complexity of this disease and motivates more investigation into pathophysiology and treatment considerations of coccidioidomycosis in the gastrointestinal system. We will review the risk factors associated with dissemination, the interpretation of serologies, the characteristics of patients with peritoneal involvement, and finally, the current treatment guidelines.

[Role of laparoscopy in the diagnosis of peritoneal tuberculosis in endemic areas]. / Intérêt de la laparoscopie dans le diagnostic de la tuberculose péritonéale en zones endémiques.

The aim of our study is to demonstrate the difficulties of diagnosis of peritoneal tuberculosis in endemic areas and the value of laparoscopy for diagnostic confirmation. We report a retrospective study of 60 cases of peritoneal tuberculosis, collected from January 2004 to December 2009. The patients' median age was 41 years, and the sex ratio 0.4. The dominant reasons for consultation were pain and abdominal distension. Abdominal ultrasound found ascites in all patients. Computed tomography (CT) was performed in 30 patients and confirmed the ultrasound data. Paracentesis of the ascites took place in all patients, collecting exudative fluid in all cases; lymphocytes predominance in 83%. Screening for Mycobacterium tuberculosis in the ascites on direct examination and after culture was performed in 43 cases and negative in all of them. Surgical biopsy was performed laparoscopically in 29 patients and by laparotomy in 31 patients. Histological examination of the peritoneal biopsies confirmed the diagnosis of peritoneal tuberculosis in all cases.

Intra-abdominal bacterial contamination in TAMIS total mesorectal excision for rectal carcinoma: a prospective study.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is currently gaining a lot of attention. NOTES is expected to further reduce surgical trauma and improve patient care due to eliminating abdominal incisions. The interest in transrectal NOTES has grown slowly, because of concerns of bacterial contamination due to transection of the rectum at the start of the procedure. However, different studies already demonstrated that transanal TME (TaTME) can be performed without major complications. This prospective study focuses on the presence and clinical significance of peritoneal bacterial contamination after TaTME for rectal cancer. METHODS: Three bacterial cultures were taken at standardized locations from the pelvic area after completion of the TaTME procedure and before closure of the incisional wounds. The cultures were evaluated for bacterial count and species identification. Furthermore, C-reactive protein and white blood cell count were measured perioperatively, and postoperative complications were recorded. RESULTS: Twenty-three consecutive patients were included between July 2013 and December 2014. Thirty-nine percent (9/23) of the cultures showed gastrointestinal flora. Four of these patients (44 %) developed presacral abscesses. The remaining 61 % (14/23) of the cultures were negative. None of these patients developed infectious complications. CONCLUSION: Transanal TME procedures are associated with positive cultures in more than one-third of the patients. In these patients, postoperative locoregional infectious complications are more common.

Is the use of prosthetic mesh recommended in severely obese patients undergoing concomitant abdominal wall hernia repair and sleeve gastrectomy?

BACKGROUND: The concomitant use of nonabsorbable mesh during stapled bariatric surgery has been discouraged due to potential contamination. The aim of our study was to compare and quantify the extent of bacterial load and gross contamination of the peritoneal cavity in patients undergoing laparoscopic sleeve gastrectomy (LSG) vs those undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB). STUDY DESIGN: We prospectively enrolled all patients undergoing LSG and LRYGB. Peritoneal fluid aspirate samples were collected from each subject. Sample A was obtained at the beginning of the procedure, and sample B was obtained at the end of the procedure either from the staple line wash of the LSG or the gastrojejunostomy in the LRYGB. RESULTS: A total of 77 patients (51 LSG and 26 LRYGB) and 154 samples (102 from LSG and 52 from LRYGB) were included in this study. All samples obtained at the beginning of each procedure (sample A) were culture negative. Samples of peritoneal fluid obtained at the end of the procedure (sample B) in sleeve gastrectomy procedures were all negative (0%) after a minimum of 72 hours for aerobic and anaerobic cultures. Those obtained for LRYGB (sample B) were culture positive in 4 of 26 (15%). The latter results are statistically significant (p < 0.05). CONCLUSIONS: Intraperitoneal bacterial cultures in patients undergoing LSG are negative, contrary to those in patients undergoing LRYGB. The concomitant use of prosthetic material to repair ventral hernias in patients undergoing an LSG procedure should be safe and feasible.