[Small intestinal mucormycosis associated with acute myeloid leukemia: a case report].

The patient was a man in his 70s. During the treatment for acute myeloid leukemia, abdominal pain and bloody stools appeared. A diagnosis of small intestinal ileus was made by computed tomography scan. Treatment with an ileus tube did not improve his condition, and enteroscopy revealed the presence of ileal ulcers. Based on histological examination, small intestinal mucormycosis was suspected, and thus, antifungal drugs were administered. However, the patient developed perforated peritonitis and underwent small intestine resection. He was finally diagnosed with small intestinal mucormycosis with the help of the resected specimen. The gastrointestinal form of mucormycosis rarely occurs, and small intestinal lesions are very rare. Enteroscopy was helpful in its diagnosis and treatment.

Activation of p38 mitogen-activated protein kinase pathway by lipopolysaccharide aggravates postoperative ileus in colorectal cancer patients.

BACKGROUND AND AIM: Patients undergoing abdominal surgery can develop postoperative ileus (POI). Inflammation of the intestinal muscularis following intestinal manipulation may be caused by displaced bacteria or lipopolysaccharide (LPS). The aim of this study was to investigate the relationship between gut microbiota, LPS, and POI in colorectal cancer (CRC) patients and explore underlying mechanisms of LPS-triggered POI. METHODS: Sixty CRC patients undergoing colorectal resection were included. Bacterial communities from fecal samples were characterized by 16S rRNA gene sequencing, and fecal LPS levels were determined by Limulus amebocyte lysate assay. Mice were used to mechanistically investigate the causal relationship between microbiota, LPS, and POI. RESULTS: We discovered that CRC patients who developed prolonged POI (PPOI) had a unique pro-inflammatory gut microbial composition during the perioperative period. The highest proportions of Gram-negative bacteria at the genus level were Escherichia-Shigella and Bacteroides; the abundance of Escherichia-Shigella was higher throughout the perioperative period. Fecal LPS levels were significantly higher in patients with PPOI. In mice treated with an antibiotic cocktail, intestinal muscularis inflammation and intestinal dysfunction were significantly improved. Inflammation and dysfunction were significantly reduced in mice treated with polymyxin B, but were worsened by treatment with LPS. Moreover, LPS upregulated p38 phosphorylation in mice, and treatment with an inhibitor of p38 (SB203580) significantly alleviated intestinal inflammation and dysmotility. CONCLUSION: Lipopolysaccharide increases intestinal muscularis inflammation via activation of p38 signaling, which aggravates POI. Removing bacterial sources of LPS during the perioperative period is promising for the prophylactic treatment of PPOI.

Characterization and origin of heme precursors in amniotic fluid: lessons from normal and pathological pregnancies.

BACKGROUND: Heme is the prosthetic group of numerous proteins involved in vital processes such as oxygen transport, oxidative stress, and energetic mitochondrial metabolism. Free heme also plays a significant role at early stages of development and in cell differentiation processes. The metabolism of heme by the fetal placenta unit is not well-established in humans. METHODS: In a retrospective study, we measured heme precursors in the amniotic fluid (AF) of 51 healthy women, and 10 AF samples from pregnancies with either upper or lower intestinal atresia or ileus were also analyzed. RESULTS: We showed that the porphyrin precursors aminolevulinic acid, porphobilinogen, and protoporphyrin IX are present at the limit of detection in the AF. Total porphyrin levels decreased progressively from week 13 to week 33 (p < 0.01). Interestingly, uroporphyrin, initially detected as traces, increased with maturation, in contrast to coproporphyrin. Uro- and coproporphyrins were type I immature isomers (>90%), suggesting a lack of maturity in the fetal compartment of the heme pathway. Finally, the differential analysis of AF from normal and pathological pregnancies demonstrated the predominant hepatic origin of fetal porphyrins excreted in the AF. CONCLUSION: This study gives the first insight into heme metabolism in the AF during normal and pathological pregnancies.

CCR2-dependent monocyte-derived macrophages resolve inflammation and restore gut motility in postoperative ileus.

OBJECTIVE: Postoperative ileus (POI) is assumed to result from myeloid cells infiltrating the intestinal muscularis externa (ME) in patients undergoing abdominal surgery. In the current study, we investigated the role of infiltrating monocytes in a murine model of intestinal manipulation (IM)-induced POI in order to clarify whether monocytes mediate tissue damage and intestinal dysfunction or they are rather involved in the recovery of gastrointestinal (GI) motility. DESIGN: IM was performed in mice with defective monocyte migration to tissues (C-C motif chemokine receptor 2, Ccr2-/ - mice) and wild-type (WT) mice to study the role of monocytes and monocyte-derived macrophages (MΦs) during onset and resolution of ME inflammation. RESULTS: At early time points, IM-induced GI transit delay and inflammation were equal in WT and Ccr2 -/- mice. However, GI transit recovery after IM was significantly delayed in Ccr2 -/- mice compared with WT mice, associated with increased neutrophil-mediated immunopathology and persistent impaired neuromuscular function. During recovery, monocyte-derived MΦs acquire pro-resolving features that aided in the resolution of inflammation. In line, bone marrow reconstitution and treatment with MΦ colony-stimulating factor 1 enhanced monocyte recruitment and MΦ differentiation and ameliorated GI transit in Ccr2 -/- mice. CONCLUSION: Our study reveals a critical role for monocyte-derived MΦs in restoring intestinal homeostasis after surgical trauma. From a therapeutic point of view, our data indicate that inappropriate targeting of monocytes may increase neutrophil-mediated immunopathology and prolong the clinical outcome of POI, while future therapies should be aimed at enhancing MΦ physiological repair functions.

Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke.

UNLABELLED: Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested a key role of the gut microbiota in autoimmune diseases by modulating immune homeostasis. Therefore, we investigated the mechanistic link among acute brain ischemia, microbiota alterations, and the immune response after brain injury. Using two distinct models of acute middle cerebral artery occlusion, we show by next-generation sequencing that large stroke lesions cause gut microbiota dysbiosis, which in turn affects stroke outcome via immune-mediated mechanisms. Reduced species diversity and bacterial overgrowth of bacteroidetes were identified as hallmarks of poststroke dysbiosis, which was associated with intestinal barrier dysfunction and reduced intestinal motility as determined by in vivo intestinal bolus tracking. Recolonizing germ-free mice with dysbiotic poststroke microbiota exacerbates lesion volume and functional deficits after experimental stroke compared with the recolonization with a normal control microbiota. In addition, recolonization of mice with a dysbiotic microbiome induces a proinflammatory T-cell polarization in the intestinal immune compartment and in the ischemic brain. Using in vivo cell-tracking studies, we demonstrate the migration of intestinal lymphocytes to the ischemic brain. Therapeutic transplantation of fecal microbiota normalizes brain lesion-induced dysbiosis and improves stroke outcome. These results support a novel mechanism in which the gut microbiome is a target of stroke-induced systemic alterations and an effector with substantial impact on stroke outcome. SIGNIFICANCE STATEMENT: We have identified a bidirectional communication along the brain-gut microbiota-immune axis and show that the gut microbiota is a central regulator of immune homeostasis. Acute brain lesions induced dysbiosis of the microbiome and, in turn, changes in the gut microbiota affected neuroinflammatory and functional outcome after brain injury. The microbiota impact on immunity and stroke outcome was transmissible by microbiota transplantation. Our findings support an emerging concept in which the gut microbiota is a key regulator in priming the neuroinflammatory response to brain injury. These findings highlight the key role of microbiota as a potential therapeutic target to protect brain function after injury.

A rare presentation of gallstones: Bouveret´s syndrome, a case report.

CT images and endoscopic findings in a case of Bouveret's syndrome.

Malrotation syndrome resulting in fatal ileus in children.

BACKGROUND: This report deals with two deaths of children involving intestinal volvulus, i. e. a pathological knotting and twisting of the mesenterial root on the basis of congenital malrotation followed by obstruction and extensive ischaenia. CASE REPORTS: (1) A 10-year-old girl (premature, 25th week) with severe disability, amaurosis and epilepsy was admitted to hospital due to general agitation and a bloated abdomen without peristaltic sounds, but died some hours later. Autopsy revealed a volvulus of 2/3 of the small intestine based on congenital malrotation with additional clamping of the intestine underneath adhesions (previous appendectomy). The abdominal cavity showed beginning peritonitis as the cause of death. (2) A 2-month-old premature male baby (surviving twin, 29th week) with a persisting ductus arteriosus was hospitalised for four weeks after failed vascular surgery due to acute general deterioration. Radiological diagnostics using a contrast medium revealed a vascular anomaly (right-sided aortic arch). Around 10 hours later, the infant developed an acute abdomen with ileus symptoms. Emergency surgery showed infarction of the entire small intestine due to an anti-clockwise 180°-volvulus, with death occurring 24h later. Further examination showed a malrotation as anomaly. Apparently, the volvulus had been caused by extensive use of contrast medium resulting in increased intestinal mobility.

[Coincidence of colonic lymphoma and gallstone ileus - case report]. / Koincidence lymfomu tracníku a biliárního ileu - kazuistika.

INTRODUCTION: Primary colonic lymphoma is a very rare malignant disease of the gastrointestinal tract, accounting for 14% of all malignant diseases in this location. It is classified in the group of extranodal lymphomas; its long-term asymptomatic progression makes it different from common colorectal carcinomas making its diagnosis very difficult, more often accidental. Gallstone ileus is quite an uncommon complication of cholecystolithiasis diagnosed with difficulty. Up to 50% of cases are diagnosed during surgery. The obturated location depends on the size of the stone, location of the conjunction between the biliary and gastrointestinal tracts, and also on any preexisting stenosis due to another unknown pathology. CASE REPORT: We present a case of an 86-year-old man treated for acute diverticulitis with typical clinical symptoms. Following further examination (colonoscopy, computed tomography) revealed a tumour-like infiltration in the sigmoid colon wall and a voluminous polyp was suspected according to the colonoscopy. Computed tomography described an obstruction by a biliary stone tumbling through the cholecystocolonic fistula. Subsequent biopsy supported the suspected malignant etiology. The patient underwent resection of the sigmoid colon sec. Hartmann; an infiltration was found in the subhepatic space, which corresponded to the described fistulisation between the biliary tract and the colon. A large 40 mm gallstone was found in the resected sigmoid colon over the stenosis and the bowel wall showed diffuse thickening with several polyps; final histopathological assessment confirmed malignant lymphoma of the plasmocytoma type. No serious complications occurred in the postoperative period; after healing, the patient was transferred to hematooncology care. CONCLUSION: The article describes the presence of two rare diseases - colonic lymphoma and gallstone ileus. Clearly, without the biliary stone obstruction in the preexisting tumorous stenosis in the sigmoid colon, the malignant hematooncology disease would not have been diagnosed. KEY WORDS: primary colonic lymphoma - gallstone ileus - complication of the cholecystolithiasis - extranodal lymphoma - acute diverticulitis.

COMPLEX DIAGNOSIS OF AN ACUTE ILEUS.

Results of examination and treatment in 256 patients, suffering an acute ileus (AI), were analyzed. Differentiation­diagnostic program was elaborated, what have permitted to establish a correct diagnosis in 98.4% patients. Higher informativity of ultrasonograph' ic investigation, permitting to verify the diagnosis on early stage of the disease and to estimate conservative treatment efficacy, accordingly, in 94.4 and 87.8% patients, was established while doing comparative analysis of ultrasonographic and radiological diag' nostic methods.

[PECULIARITIES OF SURGICAL TREATMENT OF ADHESIVE DISEASE OF PERITONEUM].

For the adhesive disease of peritoneum (ADP) viscerolysis was performed in 235 patients, of them in 47--a total one, while a great omentum cicatricial-adhesive involvement occurred, so in 33--a partial omental resection was performed. The volume and technique of operative intervention have had depended on the number of operations performed and intestinal changes present. Individualized approach to choice of the surgical method of treatment have permitted to improve its result essentially in ADP, complicated by an acute ileus, in early and remote postoperative period. ; acute adhesive ileus.

[SIGNIFICANCE OF CHANGES OF RENAL FUNCTIONING PROGNOSTICATION IN THE PURULENT­SEPTIC COMPLICATIONS COURSE AFTER AN URGENT INTERVENTIONS, PERFORMED ON INTESTINE].

Rate and severity of the renal function changes in an acute ileus (AI) in dynamics, aiming on determination of early diagnostic criteria for the purulent­septic complications (PSC) occurrence, were studied. Retrospective analysis of clinical and laboratory indices of renal functional state was conducted in 413 patients, and prospective investigations of 174 patients, operated for AI of various origin was done. Concentration index of creatinine, the glomerular filtration reduction, absolute and relative reabsorption of water, the sodium clearance, level of standardized excretion of protein and sodium, as well as of proximal and distal reabsorption of sodium, the middle­molecular mass peptides content in the blood serum and their concentration indices constitutes the most informative early diagnostic criteria of the PSC occurrence.

[INSTRUMENTAL DIAGNOSIS OF ADHESIVE ILEUS].

Results of diagnosis and treatment of 48 patients, suffering an acute adhesiv eileus of small intestine, were analyzed. In 22 (45.8%) patients conservative therapy have appeared effective, in 26 (54.2%) ­ operative interventions were performed. Тransabdominal ultrasonographic investigation ­ noninvasive, available, highly informative diagnostic method ­ permits to differentiate various forms of an acute ileus precisely, and, comparing with roentgenological method, it is more secure and simple, which may be used even in a severely ill patients. The method permits to diagnose an acute adhesive small intestinal ileus in a shorter terms, and to determine severity of changes not in intestine only, but in adjacent abdominal organs as well.

ADHESION ILEUS IN CHILDREN IN THE CONNECTIVE TISSUES DYSPLASIA.

The investigation objective was to estimate the peritoneal adhesions formation risk in children with phenotypic signs of the connective tissues dysplasia (CTD­syndrome). On the first stage the formalized phenotypic clinical signs were estimated in accor' dance to χ2 Pearson criteria (p<0.05). On the second stage a prognostic value of genet' ic polymorphism of N­Ð°rylacetyltransferase­2 (NAT2) gene for determination of risk for the occurrence of postoperative adhesive process in abdominal cavity, using the method of allele­specific amplification of NAT2 аllele with the help of polymerase chain reaction (PCR), was determined. In accordance to results of investigation, obtained in children with CTD­syndrome a genetic polymorphism NAT2 was revealed rather more frequently, responsible for "rapid аcetylation", they constitute the risk group for the adhesion ileus occurrence, in them complex prophylactic measure must be undertak' en, beginning from intraoperative stage.

Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus.

Myocytes are nonhemopoietic in origin and functionally essential in generating gastrointestinal motility. In endotoxemia, a rapid-onset nonhemopoietic mechanism potently triggers early ileus in a Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88)-dependent manner. Moreover, synergistically with hemopoietic cells, nonhemopoietic cells escalate late ileus via an IL-6 receptor-dependent inflammation-driven pathway. We therefore specifically investigated the role of myocytes in TLR4-triggered inflammation and ileus. TLR4(+/+), TLR4(-/-), bmTLR4(+/+)/TLR4(-/-) chimera, SM22-Cre(-/-)TLR4(flox/flox), and selective myocyte TLR4-deficient (SM22-Cre(+/-)TLR4(flox/flox)) mice were injected intraperitoneally with purified lipopolysaccharide. SM22-driven Cre recombinase activity was selectively detected in cardiac, gastrointestinal, skeletal, and vascular myocytes, of small-sized vessels in a two-color fluorescent Cre reporter mouse. In contrast to nonhemopoietic TLR4 deficiency, deletion of myocyte TLR4 signaling prevented neither endotoxin-induced suppression of spontaneous jejunal contractility in vitro nor early ileus in vivo at 6 h. Circulating plasma colony-stimulating factor 3 was greatly elevated during endotoxemia, independent of myocyte TLR4 signaling or time. TLR4 activation of myocytes contributed significantly to an early enteric IL-6 mRNA induction and systemic IL-6 release, as well as to a late increase in circulating chemokine (C-X-C motif) ligand 1 (CXCL1) and IL-17. Consequently, inhibition of myocyte TLR4 signaling allowed functional recovery of motility by preventing inflammation-driven late ileus at 24 h. Direct TLR4 activation of myocytes is not responsible for nonhemopoietic-mediated early ileus. However, myocytes are proinflammatory cells that potently drive enteric and systemic inflammation, subsequently fueling late mediator-triggered ileus. Specifically, the myocyte TLR4-dependent inflammatory signature of elevated plasma IL-6, CXCL1, and IL-17 is strongly associated with late rodent ileus.

Effects of nerve growth factor antagonist K252a on peritoneal mast cell degranulation: implications for rat postoperative ileus.

Stabilization of mast cell (MC) degranulation has been proposed to prevent postoperative ileus (POI). Nerve growth factor (NGF) mediates MC degranulation. The aim of the study was to evaluate whether NGF receptor antagonist K252a acts as a MC stabilizer in vitro and in vivo model of POI. Peritoneal mast cells (PMCs) were obtained from Sprague-Dawley rats and were incubated with K252a and exposed to NGF or Compound 48/80 (C48/80). MC degranulation was assessed by ß-hexosaminidase assay. POI was induced in rats by intestinal manipulation (IM). Rats were pretreated with K252a (100 µg/kg sc) 20 min prior to POI induction. At 20 min after IM, release of rat mast cell protease 6 (RMCP-6) was evaluated in peritoneal lavage. At 24 h, intestinal transit (IT) and gastric emptying (GE) were evaluated. Ileal inflammation was assessed by myeloperoxidase (MPO) activity, expression of IL-6, NGF, TrkA, RMCP-2 and 6, and MC density within the full-thickness ileum. C48/80 and NGF evoked degranulation of PMCs in a dose-dependent manner. K252a prevented NGF-evoked, but not C48/80-evoked, MC degranulation. IM evoked the release of peritoneal RMCP-6 and subsequently delayed IT and GE. IM increased MPO activity and expression of IL-6. In IM rats, K252a prevented upregulation of IL-6 expression and reduced TrkA. IT, GE, and inflammation were not affected by K252a. K252a inhibited NGF-evoked degranulation of PMCs in vitro. In vivo, K252a decreased IL-6 and PMC degranulation. This may be of relevance for the development of new therapeutic targets for POI.

[Dynamics of reparative processes in wall of a small bowel loop after elimination of its acute mechanical ileus, depending on duration of incarceration].

The results of experimental investigation of regenerative process peculiarities in the intestinal wall after its mechanical lower impassability (ileus) in terms of 1, 3, 7 and 14 days without medicinal correction and together with using the solutions of sorbitol and L-arginine (tivortin) in combination with application of the intratissue electrophoresis with a constant current density 0.05 MA/cm2 are adduced. Optimal regenerative changes in the wall of a changed intestine was observed while application of a medicinal correction in combination with a halvanic current. Application of the method proposed is permitted to restoration of wall damade intestine stucture elements on strangulation region after ileus during up to 72 h.

[Experimental substantiation of possibility of sanation for purulent enteritis in mechanical acute ileus].

In experiment on the model of mechanical acute ileus (AI) in accordance to morphological and microbiological investigations data there was established, that in intestinal wall, situated above the obstacle place, purulent enteritis occurs, what may constitute the origin of purulent-septic complications after elimination of the Al cause. Application of antibacterial preparations permits to slow down the progression of destructive processes in the affected intestinal wall.

[Prophylaxis of purulent complications in mechanical ileus].

In experiment, while simulating an acute ileus, the possibility of antibacterial preparations for prophylaxis of purulent--septic complications was studied. There was established, that while progressing purulent intestinal inflammation its wall already in 12 h losses a capacity to cumulate penicillines and aminoglycosides. In a phlegmon-like changed intestine during 48 h cephalosporins and fluorochinolons are accumulated in bactericidal concentration, making a destruction of intestinal wall and occurrence of purulent peritonitis by 6-12 h slower.

[Prognostication and prophylaxis of the adhesions recurrence postoperatively in patients suffering acute adhesive peritoneal disease complicated by ileus].

The results of treatment of 92 patients, suffering an acute ileus, were analyzed. After urgent operative interventions for an acute ileus the recurrence have occurred in 19.6% patients. To reduce the operative intervention traumaticity the preference was given to local viscerolysis conduction. For the adhesions occurrence prophylaxis a barrier medicines were used, what have promoted the reduction of contents of a connective tissue metabolites, excluding oxyprolin, concentration of which have exceeded such in a control, what have guaranteed the risk lowering for postoperative adhesions occurrence.

[PROPHYLAXIS OF AN ACUTE ADHESIVE ILEUS RECURRENCE].

The results of treatment of 56 patients were studied, in whom for adhesive abdominal disease, complicated by an acute adhesive ileus (AAI), the adhesiolysis with intraabdominal introduction of antiadhesive measures, named Mezogel, Defensal were conducted, as well as in 42 patients, operated on in emergency for AAI, using a routine method. Application of videolaparoscopy gives a possibility to control the adhesive process in the early postoperative period, what is necessary for prophylaxis of the adhesive disease occurence. Application of the apparatus, we have elaborated, permitted to conduct a precisional viscerolysis due to good visualization of organs, pathologically changed and healthy tissues. Application of the procedures elaborated for prophylaxis of the AAI recurrence have promoted the reduction of risk for the AAI occurence down to 1.8%, and of disorders of the gut contents transit in terms up to 1 yr - to 3.6%.