Search

Body packing is the internal concealment of illicit drugs for the purpose of transportation and evasion of law enforcement. It is associated with medical complications such as acute toxicity from ingested drug, bowel obstruction or perforation. It is rare to require surgical intervention with a small amount of ingested drug packet. Here, we present the case of a young adult male who presented with abdominal pain for 3 days. The patient admitted ingesting a condom filled with suboxone several years ago and denied recent ingestion. The patient was found to have small bowel obstruction with ingested foreign body being a transition point on CT scan, requiring exploratory laparotomy and small bowel resection. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post‐hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin‐33 (IL‐33) signaling pathway.Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl4)‐induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity.The Fibrosis‐4 (FIB‐4) index emerged as a salient, non‐invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (n = 385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL‐33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL‐33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence.Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL‐33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL‐33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis. [ABSTRACT FROM AUTHOR]

Interleukin-23 (IL-23) is a proinflammatory cytokine initially studied in autoimmune disease that has been more recently linked to innate immunity. We observed that the expression of IL-23 is upregulated during hypoxia in a hepatocyte and nonparenchymal cell (NPC) coculture system, as well as during ischemia-reperfusion (I/R) injury in the liver. Interferon regulatory factor-1 (IRF-1) is a transcription factor that induces expression of multiple inflammatory cytokines and has been shown to play a critical role in liver I/R injury. We observed that IL-23 signaling induces not only the IL-17/chemokine (C-X-C motif) ligand 2 (CXCL2) pathway but also the IFN-γ/IRF-1 pathway. Quantification of cytokine genes revealed increased liver expression of IL-17a, CXCL2, and IRF-1 messenger RNA during liver transplantation. Recombinant IL-23 treated hepatocytes, and NPC coculture led to IL-17, CXCL2, IFN-γ, and IRF-1 expression. With anti-IL-17 and anti-Ly6G antibody neutralization, neutrophil recruitment and IFN-γ production were decreased during warm I/R injury. Overexpression of IL-23 in vivo through use of an adenovirus vector also led to expression of IL-17, CXCL2, IFN-γ, and IRF-1. The increased expression of IL-23 also led to increased apoptosis in the liver. By neutralization of IL-23 through use of an anti-IL-23p19 antibody, we were able to attenuate liver damage in a wild-type but not a natural killer T (NKT) cell-deficient mouse. This suggests that IL-23 signaling shares a common pathway with NKT cells. In conclusion, IL-23 is induced early by I/R in the liver. Its signaling leads to activation of the IL-17/CXCL2 and IFN-γ/IRF-1 pathways, resulting in increased apoptosis and necrosis. NEW & NOTEWORTHY IL-23 is expressed early during cold ischemia-reperfusion (I/R), and this expression is associated with expression of IL-17 and chemokine (C-X-C motif) ligand 2. Neutralization of IL-23 during cold I/R can significantly reduce liver damage as well as decrease cytokine production and neutrophil infiltration in the liver. IL-23 appears to activate IFN-γ production in natural killer T cells within the liver which, in turn, activates interferon regulatory factor-1, a known inflammatory transcription factor during I/R injury.

Although a key role of cross-dressing has been established in immunity to viral infection and more recently in the instigation of transplant rejection, its role in tolerance is unclear. We investigated the role of intragraft dendritic cells (DCs) and cross-dressing in mouse major histocompatibility complex (MHC)-mismatched liver transplant tolerance that occurs without therapeutic immunosuppression. Although donor interstitial DCs diminished rapidly after transplantation, they were replaced in the liver by host DCs that peaked on postoperative day (POD) 7 and persisted indefinitely. Approximately 60% of these recipient DCs displayed donor MHC class I, indicating cross-dressing. By contrast, only a very minor fraction (0%-2%) of cross-dressed DCs (CD-DCs) was evident in the spleen. CD-DCs sorted from liver grafts expressed much higher levels of T cell inhibitory programed death ligand 1 (PD-L1) and high levels of interleukin-10 compared with non-CD-DCs (nCD-DCs) isolated from the graft. Concomitantly, high incidences of programed death protein 1 (PD-1) hi T cell immunoglobulin and mucin domain containing 3 (TIM-3) + exhausted graft-infiltrating CD8 + T cells were observed. Unlike nCD-DCs, the CD-DCs failed to stimulate proliferation of allogeneic T cells but markedly suppressed antidonor host T cell proliferation. CD-DCs were much less evident in allografts from DNAX-activating protein of 12 kDa (DAP12) -/- donors that were rejected acutely., Conclusion: These findings suggest that graft-infiltrating PD-L1 hi CD-DCs may play a key role in the regulation of alloimmunity and in the induction of liver transplant tolerance. (Hepatology 2018;67:1499-1515)., (© 2017 by the American Association for the Study of Liver Diseases.)