Background
Non-resectional strategies (NRS) have improved outcomes for a sub-group of patients with perforated diverticulitis. NRS are applicable to patients with non-faeculant peritonitis (Hinchey ...II and III). Success is dependent on the initial perforation sealing, which Hinchey estimated occurred ‘most of the time’. An exact percentage remains ill-defined.
Objective
We aimed to define the percentage and clinical significance of a persistent perforation in non-faeculant diverticular peritonitis.
Design
A retrospective review was conducted of all patients admitted with a diagnosis of perforated diverticulitis between January 1999 and July 2010. Patients undergoing an emergency operation were analysed according to Hinchey and physiological and operative severity scores and compared with histological findings.
Results
One hundred fifteen patients were identified. Fifty-three patients underwent a ‘resectional’ procedure. At surgery, 15 patients had faeculent peritonitis, 27 patients had purulent peritonitis and 11 patients had a contained abscess. Of the patients with non-faeculant peritonitis, 2/9 (22.2 %) Hinchey II and 10/27 (37.1 %) Hinchey III patients had persistent perforation on review of histology. Persistent perforation was associated with a significant increase in morbidity, length of stay, physiological and operative severity score (
p
= 0.015, 0.011, 0.049 and 0.002, respectively).
Conclusion
A proportion of patients with non-faeculant peritonitis have a persistent perforation which is associated with a poorer outcome and is likely to result in failure of a non-resectional management strategy. Updated classification systems and tailored peri-operative investigations are required to identify this sub-group of patients and improve patient outcomes.
Taurolidine, a derivative of the amino acid taurine, exhibits antiendotoxin, antibacterial, and antiadherence activity. We hypothesized that Taurolidine may inhibit tumor cell growth, both in an in ...vitro and in vivo setting. Our aim was to examine the effect of Taurolidine on the growth of a rat metastatic colorectal tumor cell line (DHD/K12/TRb) in vitro and in vivo.
In the in vitro experiments, DHD/K12/TRb cells were incubated with 5, 10, 15, 25, microg/ml of Taurolidine. Cells incubated in culture medium alone were used as controls. Cell proliferation, cell viability, cell death, and cell apoptosis were measured using commercially available techniques. In the in vivo experiment, BD IX rats were randomized into two groups (n = 10/group). Group A (control) underwent laparotomy and instillation of DHD/K12/TRb tumor cells intraperitoneally followed by phosphate buffered saline (PBS). Group B received Taurolidine (100 mg/kg) instead of PBS. Animals were killed after 24 days and tumor burden assessed by counting the number of tumor nodules in the peritoneal cavity.
Incubation of the tumor cells with Taurolidine resulted in a 4-fold decrease in proliferation rates (25+/-4% vs. 100+/-28% for controls) and a 4-fold increase in cell necrosis as demonstrated by the increase in LDH release (403+/-28% vs. 100+/-26% for controls), at a Taurolidine concentration of 25 microg/ml. A dose-dependent decrease in cell viability was also observed. In the in vivo study, local Taurolidine administration resulted in significant decreases in tumor burden (3+/-1 nodules in Group B animals vs. 649+/-101 nodules in Group A animals).
Taurolidine inhibits the growth of a rat metastatic colorectal tumor cell line in vitro and in vivo and thus may have potential in the prevention of peritoneal metastases.
Introduction : Aggressive non-operative intervention and evolving surgical strategies have altered the treatment of perforated diverticulitis in the acute setting. These strategies have predominantly ...been implemented over the last decade. The aim of this study was to assess the impact of this on patient outcome during their index admission and subsequently.
Methods : Consecutive patients admitted with acute diverticulitis between 1999 and 2010 were identified. Patient demographics, treatment strategies and outcomes were collected and analysed. Patients who had an episode of perforated diverticulitis during their index admission were followed.
Results : 739 patients were admitted with acute diverticulitis. Of these, 115 (15.7%) had perforated diverticulitis. 53 (47.8%) underwent an intervention. There was a reduction in the mean age of patients admitted with acute diverticulitis of 8.9% over the study period (p = 0.002). There was a significant increase in the use of CT scanning pre-operatively (p < 0.001). 'Non-resectional' interventions have emerged in the form of laparoscopic lavage (n = 5) and percutaneous abscess drainage (n = 14). There was associated improved length of stay (p < 0.001).
Conclusion : Outcomes for patients with perforated diverticulitis have improved, contributed to in part by an increased use of non-resectional management strategies.
Background: Neonates are susceptible to a wide range of microbial infection and at a high risk to develop severe sepsis and septic shock. Emerged evidence has shown that induction of trained immunity ...triggers a much stronger inflammatory response in adult monocytes/macrophages, thereby conferring protection against microbial infection. Methods: This study was carried out to examine whether trained immunity is inducible and exerts its protection against microbial sepsis in neonates. Results: Induction of trained immunity by Bacillus Calmette-Guerin (BCG) plus bacterial lipoprotein (BLP) protected neonatal mice against cecal slurry peritonitis-induced polymicrobial sepsis, and this protection is associated with elevated circulating inflammatory cytokines, increased neutrophil recruitment, and accelerated bacterial clearance. In vitro stimulation of neonatal murine macrophages with BCG+BLP augmented both inflammatory response and antimicrobial activity. Notably, BCG+BLP stimulation resulted in epigenetic remodeling characterized by histone modifications with enhanced H3K4me3, H3K27Ac, and suppressed H3K9me3 at the promoters of the targeted inflammatory and antimicrobial genes. Critically, BCG+BLP stimulation led to a shift in cellular metabolism with increased glycolysis, which is the prerequisite for subsequent BCG+BLP-triggered epigenetic reprogramming and augmented inflammatory response and antimicrobial capacity. Conclusion: These results illustrate that BCG+BLP induces trained immunity in neonates, thereby protecting against microbial infection by boosting both inflammatory and antimicrobial responses. Keywords: trained immunity, inflammatory response, antimicrobial activity, epigenetic reprogramming, intracellular metabolic rewiring, neonatal sepsis
Breast tumors contain high numbers of infiltrating macrophages. The role and function of these cells within the tumor remain unclear, but a number of studies have found an association between poor ...prognosis and macrophage content in human breast cancer. Both hypoxia and TGFbeta-1 have been shown to regulate VEGF in other cell types. We hypothesized that breast tumor-associated macrophages produce VEGF and that macrophage production of this factor is regulated by both hypoxia and TGFbeta-1.
Paraffin-embedded breast tumor sections were stained immunohistochemically with anti-VEGF, anti-CD68, and anti-cytokeratin. Monocytes were matured for 3 days in 20% autologous plasma and activated with 1000 U/mL interferon-gamma for 24 hours. Supernatants were assayed for VEGF protein by ELISA. Total RNA was isolated from cells and reverse transcribed to cDNA, which was used as a template in PCR reactions for VEGF and beta-actin.
Both tumor cells and tumor macrophages produce VEGF in human breast tumors. Hypoxia increases VEGF protein and mRNA levels in monocyte-derived macrophages, whereas TGFbeta-1 increases VEGF protein but not mRNA under hypoxic growth conditions.
Breast tumor-associated macrophages may contribute to the angiogenic activity of human breast tumors by producing VEGF. Macrophage production of VEGF is upregulated by hypoxia and TGFbeta-1, both of which occur in the tumor environment. Macrophage production of VEGF is regulated at both the mRNA and protein levels.
Background
Many vascular events, such as myocardial infarction and cerebrovascular accident, demonstrate a circadian pattern of presentation. Blood pressure is intimately related to these pathologies ...and is the one physiological variable consistently associated with abdominal aortic aneurysm rupture. It also demonstrates a diurnal variation. The purpose of this study was to determine if rupture of an abdominal aortic aneurysm (RAAA) exhibits a diurnal variation.
Methods
A retrospective cohort‐based study was performed to determine the timing of presentation of RAAA to the vascular unit of Cork University Hospital over a 15‐year period. Time of admission, symptom onset, and co‐morbidities such as hypertension were noted. Fournier’s analysis and chi‐squared analysis were performed. To ameliorate possible confounding factors, patients admitted with perforated peptic ulcers were examined in the same manner.
Results
A total of 148 cases of RAAA were identified, with a male preponderance (71.7% 124 male versus 29.3% 44 female patients) and a mean age of 74.4 ± 7.2 years at presentation. 70.9% (105) were known to have hypertension, 52.2% (77) were current smokers, and 46.8% (69) were being treated for chronic obstructive airway disease (COAD). Time of symptom onset was recorded in 88.5% (131) of patients. There was a marked early morning peak in RAAA admissions, with the highest number of RAAA being admitted between 08.00 and 09.59. A second, smaller peak was observed at 14.00‐15.59. These findings were suggestive of diurnal variation. χ2 =16.75, p < 0.003. Some 40% (59) of patients were admitted between 00.00 and 06.00, an incidence significantly higher than for other time periods (06.00‐12.00, 12.00‐18.00, and 18.00‐24.00) χ2 = 18.72; df = 3; p < 0.0003. A significantly higher number of patients admitted between 00.00 and 06.00 were known hypertensives (χ2 = 7.94; p < 0.05).
Conclusions
The findings of this study suggest a distinct circadian pattern of presentation for RAAA. Systolic blood pressure has a circadian rhythm that mirrors this pattern of presentation. Our results further support the association between RAAA and hypertension, and they may also indicate that chronotropic blood pressure control combating the early‐morning peak in systolic blood pressure may assist in the management of abdominal aortic aneurysms.
Angiogenesis is essential for normal bone formation and repair. Avascularity characterizes aberrant fracture union in the elderly, while angiogenic mechanisms during cutaneous wound repair are ...attenuated in aged humans. We hypothesized that skeletal injury results in local (circulating) and systemic (fracture site) `angiogenic' responses and that these reparative mechanisms are attenuated with advanced patient age. This prospective study examined peripheral blood and fracture hematoma from 32 patients, 16 under 40 years and 16 over the age of 75, undergoing emergent surgery for isolated fracture. The angiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were assayed. Endothelial cell cultures were supplemented with patient plasma and fracture hematoma and angiogenesis determined in vitro by measuring cell proliferation and blood vessel tube formation. Angiogenesis was determined in vivo using a murine dorsal wound pocket model and quantification of new blood vessel formation after 7 days. We found that all injured patients, irrespective of age, have elevated plasma and fracture hematoma levels of VEGF and PDGF. These elevated cytokine concentrations translate into biologically significant angiogenic effects, in vitro and in vivo. These effects are primarily VEGF mediated and are not dependent on patient age. The biological activity of these growth factors does not diminish with advanced age. Thus skeletal injury does result in local and systemic angiogenic responses whereby angiogenic cytokine availability and activity is preserved in the aged suggesting alternative mechanisms for the development of avascularity in delayed and fracture non-union in the elderly.
Acetaminophen overdose causes acute liver injury in both humans and animals. This study was designed to investigate the potential role of the conditionally essential amino acid taurine in preventing ...acetaminophen-induced hepatotoxicity. Male Sprague-Dawley rats were administered acetaminophen (800 mg/kg) intraperitoneally. Taurine (200 mg/kg) was given 12 h before, at the time of, and 1 or 2 h after acetaminophen injection. Acetaminophen treatment increased the plasma levels of aspartate transaminase, alanine aminotransferase, and alkaline phosphatase and caused hepatic DNA fragmentation and hepatocyte necrosis. Taurine administered before, simultaneously with, or 1 h after acetaminophen resulted in significant improvement in hepatic injury as represented by decrease of hepatocellular enzyme release and attenuation of hepatocyte apoptosis and necrosis, and this correlated with taurine-mediated attenuation of hepatic lipid peroxidation. These results indicate that taurine possesses prophylactic and therapeutic effects in acetaminophen-induced hepatic injury.
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