Early hyperbaric oxygen therapy improves survival in a model of severe sepsis.

Sepsis is a major clinical challenge, with therapy limited to supportive interventions. Therefore, the search for novel remedial approaches is of great importance. We addressed whether hyperbaric oxygen therapy (HBOT) could improve the outcome of sepsis using an acute experimental mouse model. Sepsis was induced in male CD-1 mice by cecal ligation and puncture (CLP) tailored to result in 80-90% mortality within 72 h of the insult. After CLP, mice were randomized into two groups receiving HBOT or not at different times after the initial insult or subjected to multiple HBOT treatments. HBOT conditions were 98% oxygen pressurized to 2.4 atmospheres for 1 h. HBOT within 1 h after CLP resulted in 52% survival in comparison with mice that did not receive the treatment (13% survival). Multiple HBOT at 1 and 6 h or 1, 6, and 21 h displayed an increase in survival of >50%, but they were not significantly different from a single treatment after 1 h of CLP. Treatments at 6 or 21 h after CLP, excluding the 1 h of treatment, did not show any protective effect. Early HBO treatment did not modify bacterial counts after CLP, but it was associated with decreased expression of TNF-α, IL-6, and IL-10 expression in the liver within 3 h after CLP. The decrease of cytokine expression was reproduced in cultured macrophages after exposure to HBOT. Early HBOT could be of benefit in the treatment of sepsis, and the protective mechanism may be related to a reduction in the systemic inflammatory response.

Why Antibiotic Treatment Is Not Enough for Sepsis Resolution: an Evaluation in an Experimental Animal Model.

Sepsis remains a major health problem at the levels of mortality, morbidity, and economic burden to the health care system, a condition that is aggravated by the development of secondary conditions such as septic shock and multiple-organ failure. Our current understanding of the etiology of human sepsis has advanced, at least in part, due to the use of experimental animal models, particularly the model of cecum ligation and puncture (CLP). Antibiotic treatment has been commonly used in this model to closely mirror the treatment of human septic patients. However, whether their use may obscure the elucidation of the cellular and molecular mechanisms involved in the septic response is questionable. The objective of the present study was to determine the effect of antibiotic treatment in the outcome of a fulminant model of CLP. Various dosing strategies were used for the administration of imipenem, which has broad-spectrum coverage of enteric bacteria. No statistically significant differences in the survival of mice were observed between the different antibiotic dosing strategies and no treatment, suggesting that live bacteria may not be the only factor inducing septic shock. To further investigate this hypothesis, mice were challenged with sterilized or unsterilized cecal contents. We found that exposure of mice to sterilized cecal contents also resulted in a high mortality rate. Therefore, it is possible that bacterial debris, apart from bacterial proliferation, triggers a septic response and contributes to mortality in this model, suggesting that additional factors are involved in the development of septic shock.

Elemental, fatty acid, and protein composition of appendicoliths.

Appendicoliths are commonly found obstructing the lumen of the appendix at the time of appendectomy. To identify factors that might contribute to their formation we investigated the composition of appendicoliths using laser ablation inductively coupled plasma mass spectroscopy, gas chromatography, polarized light microscopy, X-ray crystallography and protein mass spectroscopy. Forty-eight elements, 32 fatty acids and 109 human proteins were identified within the appendicoliths. The most common elements found in appendicoliths are calcium and phosphorus, 11.0 ± 6.0 and 8.2 ± 4.2% weight, respectively. Palmitic acid (29.7%) and stearate (21.3%) are the most common fatty acids. Some stearate is found in crystalline form-identifiable by polarized light microscopy and confirmable by X-ray crystallography. Appendicoliths have an increased ratio of omega-6 to omega-3 fatty acids (ratio 22:1). Analysis of 16 proteins common to the appendicoliths analyzed showed antioxidant activity and neutrophil functions (e.g. activation and degranulation) to be the most highly enriched pathways. Considered together, these preliminary findings suggest oxidative stress may have a role in appendicolith formation. Further research is needed to determine how dietary factors such as omega-6 fatty acids and food additives, redox-active metals and the intestinal microbiome interact with genetic factors to predispose to appendicolith formation.

Perforated Appendicitis: An Unintended Consequence During the Coronavirus-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had major clinical impact across the globe. Delayed presentation for medical emergencies has been noted by the medical community. There has been limited reporting on the impact for the care for emergent surgical conditions. We sought to describe the effect of the global pandemic on the presentation and outcomes for the most common urgent general surgery disease process, acute appendicitis. METHODS: We performed a retrospective review of patients admitted to the United States Naval Hospital Okinawa during the COVID-19 pandemic, from January 2020 to May 2020 (COVID cohort), and compared them to a historical cohort (pre-COVID cohort) over the prior 2 years. Demographics, clinical presentation data, and interventions were collected. RESULTS: Of the 80 patients with appendicitis, 20% presented perforated. Most patients were male (71%), presented with 1 day of symptoms and had a length of stay of 1 to 2 days. Comparing groups, 13% of the pre-COVID group vs. 31% of the COVID cohort presented perforated (P = .04), with a symptom duration of 1.6 vs. 2.7 days before presentation (P = .075), respectively. CONCLUSIONS: The COVID-19 pandemic and the global systematic response has impacted unrelated medical and surgical conditions. At our overseas military hospital with minimal disease burden, we observed a delay in presentation for acute appendicitis with a higher incidence of perforation. Patients should be empowered to continue to seek care for urgent and emergent medical and surgical conditions so that they are not harmed by fear of COVID-19 rather than by COVID-19 itself.

The Greater Omentum-A Vibrant and Enigmatic Immunologic Organ Involved in Injury and Infection Resolution.

Once thought of as an inert fatty tissue present only to provide insulation for the peritoneal cavity, the omentum is currently recognized as a vibrant immunologic organ with a complex structure uniquely suited for defense against pathogens and injury. The omentum is a source of resident inflammatory and stem cells available to participate in the local control of infection, wound healing, and tissue regeneration. It is intimately connected with the systemic vasculature and communicates with the central nervous system and the hypothalamic pituitary adrenal axis. Furthermore, the omentum has the ability to transit the peritoneal cavity and sequester areas of inflammation and injury. It contains functional, immunologic units commonly referred to as "milky spots" that contribute to the organ's immune response. These milky spots are complex nodules consisting of macrophages and interspersed lymphocytes, which are gateways for the infiltration of inflammatory cells into the peritoneal cavity in response to infection and injury. The omentum contains far greater complexity than is currently conceptualized in clinical practice and investigations directed at unlocking its beneficial potential may reveal new mechanisms underlying its vital functions and the secondary impact of omentectomy for the staging and treatment of a variety of diseases.

The Contribution of the Omentum to the Outcome From Sepsis: An Experimental Animal Study.

The omentum is a large mesenchymal fibro-fatty tissue with remarkable healing capability. It is also rich in immune cells, including macrophages and lymphocytes, within particular structures named milky spots. Clinical observations indicate a high incidence of peritonitis after the removal of the omentum suggesting that it may play a role in sepsis. To test this possibility, male CD-1 mice underwent simultaneous omentectomy and cecal ligation and puncture (CLP), omentectomy-sham operation and CLP alone, and mortality was documented within 72 h post the insults. A significant increase in mortality was observed in mice subjected to omentectomy and CLP in comparison with CLP alone. Mortality was correlated with an increase in cytokine gene expression within the lung after omentectomy and CLP as opposed to CLP alone. However, no differences in bacterial load were observed within the peritoneum or blood between groups. To test the long-term effect of omentectomy, mice were subjected to omentum removal or sham operation, allowed to recover from surgery for 14 or 28 days, and then both were subjected to CLP. In these cases, no differences in mortality were observed between the groups suggesting that the lack of omentum triggers a compensatory mechanism. Finally, omentectomy and sham operation altered the composition of peritoneal immune cells with the disappearance of F4/80 macrophages and the appearance of a new population of F4/80 macrophages within 1 or 14 days post-surgery. The F4/80 positive cells reappeared after 28 days following the procedures. All of these observations suggest that the omentum plays an early role in the outcome from sepsis.

Successful Outcome and Biliary Drainage in an Infant with Concurrent Alpha-1-Antitrypsin Deficiency and Biliary Atresia.

We describe the rare instance of concomitant biliary atresia and alpha-1-antitrypsin deficiency and the first documented successful portoenterostomy in this scenario. The potential for dual pathology must be recognized and underscores that prompt diagnosis of biliary atresia, despite concomitant alpha-1-antitrypsin deficiency, is essential to afford potential longstanding native liver function.