Role of hydrogen peroxide injection for penetrating abdominal injury in creating CT Tractogram.

Penetrating abdominal trauma is responsible for approximately 35% of patients admitted to urban trauma centers, and up to 12% of those admitted in suburban or rural centers in the United States. Current protocol relies heavily on CT imaging as the diagnostic tool in evaluating for peritoneal violation in hemodynamically stable patients, however it is associated with false negative rates. In addition, visualization of the fascia of the rectus abdominis, the transversalis fascia, and the peritoneum cannot be reliably identified with CT. Studies have probed into the use of injecting IV contrast dyes prior to imaging to establish a CT tractography. We present a case of a 31-year-old male presenting to the emergency department for evaluation of stab wounds following an altercation. On exam, a 1 cm penetrating wound to the LUQ of his abdomen was noted. A CT scan of the abdomen and pelvis was performed with 91 mL of Omnipaque-350 intravenous contrast. Prior to imaging, 30 mL of hydrogen peroxide was injected directly into the opening site of the stab wound to amplify the wound tract. The result was a well-visualized intact peritoneum. We propose hydrogen peroxide as an alternative method to liquid contrast in reestablishing the stab wound tract. This method creates a negative contrast level to augment the ability of CT imaging to determine peritoneal penetration. Key Words: Penetrating Abdominal Injury, CT Tractography, Abdominal Trauma, Hydrogen Peroxide, Trauma Management.

Individual specialist physical activity assessment and intervention in advanced cancer patients on a palliative care ward; the 3STEPS-study.

The aim of this prospective study was to evaluate the feasibility and outcome of an activity assessment and intervention on a specialized palliative care ward. All patients admitted between May 2017 and April 2018 were screened for basic assessment (Step 1). Whenever possible the Tinetti-mobility test (TT) was performed by a physiotherapist. A comparison between physician and nurse-led assessment and patient report was performed (Step 2), followed by a low-intensity individually adapted activity intervention (Step 3). Physical function and global quality of life was measured at intervention start and at discharge. Home care training adherence was controlled by phone call. In total, 437 patients were admitted in one year. In 248 patients, a basic assessment was done of which 131 performed a TT. In this group, median age was 63 years. Types of cancer were gastrointestinal (n=39), lung (n=27), urogenital (n=20), non-cancer (n=26) and other (n=26). Median length of stay was 13 days. Correlations between assessment methods were low to moderate, the highest between the TT and the nurse led assessment. Six patients started the intervention. Four patients completed the intervention, of which two continued with the home based training. In all four patients, an improvement in outcomes was measured. In conclusion in around a quarter of patients on a palliative care ward a TT could be performed. The TT correlated to most with nurse led mobility assessment. In the few accrued patients, the activity intervention showed an effect.

Preliminary Studies of the Impact of CXCL12 on the Foreign Body Reaction to Pancreatic Islets Microencapsulated in Alginate in Nonhuman Primates.

BACKGROUND: We previously demonstrated that the incorporation of the chemokine CXCL12 into alginate microbeads supported long-term survival of microencapsulated auto-, allo-, and xenogeneic islets in murine models of diabetes without systemic immune suppression. The purpose of this study was to test whether CXCL12 could abrogate foreign body responses (FBRs) against alginate microbeads which were empty or contained autologous islets in healthy nonhuman primates (NHPs; n = 4). METHODS: Two NHPs received intraperitoneal implants of 400 000 alginate microbeads with or without CXCL12, and postimplantation immunological and histopathological changes were evaluated up to 6 months postimplantation. A similar evaluation of autologous islets in CXCL12-containing alginate microbeads was performed in NHPs (n = 2). RESULTS: CXCL12-containing alginate microbeads were associated with a markedly reduced FBR to microbeads. Host responses to microbead implants were minimal, as assessed by clinical observations, blood counts, and chemistry. Evaluation of encapsulated islets was limited by the development of necrotizing pancreatitis after hemipancreatectomy in 1 NHP. A limited number of functioning islets were detectable at 6 months posttransplantation in the second NHP. In general, empty microbeads or islet-containing beads were found to be evenly distributed through the intraperitoneal cavity and did not accumulate in the Pouch of Douglas. CONCLUSIONS: Inclusion of CXCL12 in alginate microbeads minimized localized FBR. The NHP autologous islet implant model had limited utility for excluding inflammatory/immune responses to implanted islets because of the complexity of pancreatic surgery (hemipancreatectomy) before transplantation and the need to microencapsulate and transplant encapsulated autologous islets immediately after pancreatectomy and islet isolation.

The Impact of the Opioid Antagonist Naloxone on Experimentally Induced Craving in Nicotine-Dependent Individuals.

OBJECTIVE: Preclinical and clinical findings suggest a substantial association of the endogenous opioid system in nicotine dependence. The present study investigates the possible dose-dependent influence of naloxone, an unspecific opioid-receptor-antagonist, combined with cue exposure on the physiological state, locomotor activity, craving and the hypothalamic-pituitary-adrenal axis in nicotine-dependent humans. METHODS: Twenty nicotine-dependent, outpatient participants were deprived of nicotine for over 4 h, before receiving challenges with naloxone (1.6 mg or 3.2 mg q70 kg IV) or the placebo. Additionally, following drug administration, either smoking-related cues or neutral images were presented. Nicotine withdrawal was monitored by evaluating the following objective signs - skin conductance, heart rate, temperature, respiration, locomotor activity, cortisol, prolactin and ACTH levels as well as craving. RESULTS: With respect to subjective effects, participants administered a higher dosage of naloxone and those who were shown smoking-related cues were significantly less pleased (p = 0.019), felt more depressed (p = 0.033) and thought smoking would make them feel better (p = 0.028) than participants given naloxone and shown neutral cues. Participants given no naloxone but with smoking-related cues felt a higher urge to smoke than participants given naloxone and shown neutral cues (p = 0.042). Naloxone - in both dosages - also decreased the desire and intention to smoke in comparison to placebo. Compared to the placebo group, significantly higher cortisol, prolactin and ACTH values were observed after administration of lower and higher dosage of naloxone followed by smoking-related cues. CONCLUSION: Naloxone influenced nicotine withdrawal and strengthened significantly by cue exposure, both on objective measurement and on craving scales. These findings suggest an involvement of the endogenous opioid system in the development and maintenance of nicotine dependence.

ß Cell Replacement Therapy: The Next 10 Years.

ß cell replacement with either pancreas or islet transplantation has progressed immensely over the last decades with current 1- and 5-year insulin independence rates of approximately 85% and 50%, respectively. Recent advances are largely attributed to improvements in immunosuppressive regimen, donor selection, and surgical technique. However, both strategies are compromised by a scarce donor source. Xenotransplantation offers a potential solution by providing a theoretically unlimited supply of islets, but clinical application has been limited by concerns for a potent immune response against xenogeneic tissue. ß cell clusters derived from embryonic or induced pluripotent stem cells represent another promising unlimited source of insulin producing cells, but clinical application is pending further advances in the function of the ß cell like clusters. Exciting developments and rapid progress in all areas of ß cell replacement prompted a lively debate by members of the young investigator committee of the International Pancreas and Islet Transplant Association at the 15th International Pancreas and Islet Transplant Association Congress in Melbourne and at the 26th international congress of The Transplant Society in Hong Kong. This international group of young investigators debated which modality of ß cell replacement would predominate the landscape in 10 years, and their arguments are summarized here.

PD-L1 genetic overexpression or pharmacological restoration in hematopoietic stem and progenitor cells reverses autoimmune diabetes.

Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy ß cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model. Notably, the immunoregulatory molecule PD-L1 plays a determinant role in controlling/inhibiting activated T cells and thus maintains immune tolerance. Furthermore, our genome-wide and bioinformatic analysis revealed the existence of a network of microRNAs (miRNAs) controlling PD-L1 expression, and silencing one of key altered miRNAs restored PD-L1 expression in HSPCs. We therefore sought to determine whether restoration of this defect would cure T1D as an alternative to immunosuppression. Genetically engineered or pharmacologically modulated HSPCs overexpressing PD-L1 inhibited the autoimmune response in vitro, reverted diabetes in newly hyperglycemic NOD mice in vivo, and homed to the pancreas of hyperglycemic NOD mice. The PD-L1 expression defect was confirmed in human HSPCs in T1D patients as well, and pharmacologically modulated human HSPCs also inhibited the autoimmune response in vitro. Targeting a specific immune checkpoint defect in HSPCs thus may contribute to establishing a cure for T1D.

Testing of microencapsulated porcine hepatocytes in a new model of fulminant liver failure in baboons.

BACKGROUND: There is no standard therapy for acute liver failure. Hepatocyte transplantation has been proposed for temporary liver function support, while the injured liver regenerates or while waiting for transplantation. We have previously shown such efficacy for microencapsulated porcine hepatocytes in mice with fulminant liver failure. We aimed to establish a large animal model for fulminant liver failure to assess the efficacy of microencapsulated porcine hepatocytes in temporary liver function support. METHODS: The model was developed in baboons; for testing microencapsulated hepatocytes, the best condition was 75% hepatectomy and 60 min warm ischemia time. Fulminant liver failure was characterized by steep increases in liver biochemical parameters, severe steatosis, and massive hepatocyte necrosis during the first 10 days. Hepatocytes from miniature swine were microencapsulated in alginate-poly-l-lysine microspheres, and transplanted intraperitoneally immediately after hepatectomy and warm ischemia (80-120 mL packed hepatocytes in 200-350 mL microspheres, about 30%-50% of the baboon's native liver volume). RESULTS: In the control group, three of five animals were sacrificed after 6-10 days because of fulminant liver failure, and two of five animals recovered normal liver function and survived until elective euthanasia (28 days). In the treatment group of four animals, one animal developed liver failure but survived to 21 days, and three animals recovered completely with normal liver function. CONCLUSIONS: The results indicate that microencapsulated porcine hepatocytes provide temporary liver function support in baboons with fulminant liver failure. These data support development of this cell therapy product toward clinical trials in patients with acute liver failure.

Immunogenicity of ß-cells for autologous transplantation in type 1 diabetes.

The success of clinical islet transplantation calls for a broader application of this curative treatment for type 1 diabetes mellitus. The toxicity of immunosuppression, limited organ donor supply and high procedural costs are deterrents to expand this therapy to patients with uncomplicated diabetes. The use of pancreatic ß-cell like cells derived from the patient's own induced pluripotent cells (iPSC) holds potential to overcome these barriers. In this review, we discuss the practicality of this regenerative medicine approach and existing evidence regarding the true immunogenicity of iPSC derived cells.

Mechanisms of xenogeneic baboon platelet aggregation and phagocytosis by porcine liver sinusoidal endothelial cells.

BACKGROUND: Baboons receiving xenogeneic livers from wild type and transgenic pigs survive less than 10 days. One of the major issues is the early development of profound thrombocytopenia that results in fatal hemorrhage. Histological examination of xenotransplanted livers has shown baboon platelet activation, phagocytosis and sequestration within the sinusoids. In order to study the mechanisms of platelet consumption in liver xenotransplantation, we have developed an in vitro system to examine the interaction between pig endothelial cells with baboon platelets and to thereby identify molecular mechanisms and therapies. METHODS: Fresh pig hepatocytes, liver sinusoidal and aortic endothelial cells were isolated by collagenase digestion of livers and processing of aortae from GTKO and Gal+ MGH-miniature swine. These primary cell cultures were then tested for the differential ability to induce baboon or pig platelet aggregation. Phagocytosis was evaluated by direct observation of CFSE labeled-platelets, which are incubated with endothelial cells under confocal light microscopy. Aurintricarboxylic acid (GpIb antagonist blocking interactions with von Willebrand factor/vWF), eptifibatide (Gp IIb/IIIa antagonist), and anti-Mac-1 Ab (anti-α(M)ß(2) integrin Ab) were tested for the ability to inhibit phagocytosis. RESULTS: None of the pig cells induced aggregation or phagocytosis of porcine platelets. However, pig hepatocytes, liver sinusoidal and aortic endothelial cells (GTKO and Gal+) all induced moderate aggregation of baboon platelets. Importantly, pig liver sinusoidal endothelial cells efficiently phagocytosed baboon platelets, while pig aortic endothelial cells and hepatocytes had minimal effects on platelet numbers. Anti-MAC-1 Ab, aurintricarboxylic acid or eptifibatide, significantly decreased baboon platelet phagocytosis by pig liver endothelial cells (P<0.01). CONCLUSIONS: Although pig hepatocytes and aortic endothelial cells directly caused aggregation of baboon platelets, only pig liver endothelial cells efficiently phagocytosed baboon platelets. Blocking vWF and integrin adhesion pathways prevented both aggregation and phagocytosis.

Smoking and predictors of nicotine dependence in a homeless population.

OBJECTIVE: To assess prevalence rates of tobacco use and dependence in a sample of homeless individuals and to investigate trends for demographic and clinical characteristics across different levels of nicotine dependence (nonsmokers vs. lowly dependent smokers vs. highly dependent smokers). METHODS: A cross-sectional study of 489 homeless men and women in 3 Canadian cities. Each subject was assessed using structured clinical interviews and the Fagerström Test for Nicotine Dependence (FTND). Cochran-Armitage trend tests were applied to determine unadjusted trends in sociodemographic and clinical variables across levels of nicotine dependence. A generalized logit model was computed to adjust for potential confounding. RESULTS: The mean age was 37.9 years; 39.2% of the participants were women. About 80.8% were current smokers; the mean FTND score was 5.0. Although no significant differences were found between nonsmokers and smokers with low nicotine dependence, smokers with high nicotine dependence were only half as likely as nonsmokers to be Aboriginal, were 2.39 times more likely to have ever been incarcerated, and 2.44 times more likely to have current drug dependence. There were significant trends for the use of cocaine, opioids, and alcohol, with nonsmokers having the lowest and highly dependent smokers having the highest rates of using these substances. CONCLUSIONS: Available public health smoking cessation treatment opportunities should be made available within health care services for the homeless. There is also a need for developing and implementing tobacco dependence treatment programs, which are accessible and tailored to meet the needs of this specific population, accounting for polysubstance use and concurrent substance dependence and mental health disorders.