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Background: Hepatocyte transplantation is expected to be an alternative therapy to liver transplantation; however, poor engraftment is a severe obstacle to be overcome. The adipose tissue-derived stem cells (ADSCs) are known to improve engraftment of transplanted pancreatic islets, which have many similarities to the hepatocytes. Therefore, we examined the effects and underlying mechanisms of ADSC cotransplantation on hepatocyte engraftment., Methods: Hepatocytes and ADSCs were cotransplanted into the renal subcapsular space and livers of syngeneic analbuminemic rats, and the serum albumin level was quantified to evaluate engraftment. Immunohistochemical staining and fluorescent staining to trace transplanted cells in the liver were also performed. To investigate the mechanisms, cocultured supernatants were analyzed by a multiplex assay and inhibition test using neutralizing antibodies for target factors., Results: Hepatocyte engraftment at both transplant sites was significantly improved by ADSC cotransplantation ( P < 0.001, P < 0.001). In the renal subcapsular model, close proximity between hepatocytes and ADSCs was necessary to exert this effect. Unexpectedly, ≈50% of transplanted hepatocytes were attached by ADSCs in the liver. In an in vitro study, the hepatocyte function was significantly improved by ADSC coculture supernatant ( P < 0.001). The multiplex assay and inhibition test demonstrated that hepatocyte growth factor, vascular endothelial growth factor, and interleukin-6 may be key factors for the abovementioned effects of ADSCs., Conclusions: The present study revealed that ADSC cotransplantation can improve the engraftment of transplanted hepatocytes. This effect may be based on crucial factors, such as hepatocyte growth factor, vascular endothelial growth factor, and interleukin-6, which are secreted by ADSCs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Context and Objective: The conversion of immunohistochemical (IHC) results from 3-dimensional tissue to a 2-dimensional visual image without considering tissue thickness poses a considerable risk of misleading IHC intensities. The present study aimed to clarify whether tissue thickness interferes with the estimation of IHC staining intensity and to introduce a control system to manage it., Design: We prepared cell lines that are used as controls for human epidermal growth factor receptor 2 (HER2) IHC (MDA-MB-231, MDA-MB-175VII, MDA-MV-453, and SK-BR-3), a polyclonal antibody for HER2, an interferometry to measure the tissue thickness of formalin-fixed paraffin-embedded sections, a microscope with a Halogen or an LED light source, a complementary metal-oxide semiconductor camera in which the output signal can be corrected to γ=1, and a program to estimate color elements (hue, saturation, and luminance). It was examined whether tissue thickness interferes with the experimental scoring systems and practical classification of the routine HER2 scoring system., Results: A noncellular control was shown to be better than a cellular control for managing tissue thickness. The IHC intensity for HER2 was correlated with tissue thickness (R2=0.8094), even under the less-standardized condition, but this correlation was better under the improved standardized condition using corrected γ=1 (R2=0.9282). Discrepancies in practical HER2 scores were increased in sections with thicknesses <2 and >5 μm. A control system to manage tissue thickness was introduced., Conclusions: Tissue thickness interferes with the estimation of the IHC intensity of HER2 in both experimental and practical scoring systems. A control system for managing tissue thickness is essential to increase the benefits of IHC as a standardized assay for clinical applications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In critically injured patients with multiple injuries and unstable pelvic fracture, late mortality almost invariably results from sepsis., Methods: We analyzed the clinical features of 11 patients with sepsis caused by soft tissue infections surrounding the fractured pelvis, of 830 patients with pelvic fracture after blunt trauma treated at our level I trauma center over the past 25 years. Soft tissue infection was defined as abscess formation in subcutaneous tissue or muscle diagnosed by computed tomography or an operation., Results: Mean injury severity score was 48, and mean systolic blood pressure on arrival was 66 mm Hg. All patients had multiple concomitant injuries and prolonged hemorrhagic shock. Open pelvic fracture was present in five patients. Mean blood transfusion volume within 24 hours was 12,611 mL. Intra-aortic balloon occlusion was performed in three patients and transcatheter angiographic embolization in nine patients. Embolic sites of transcatheter angiographic embolization were bilateral internal iliac arteries (n = 9), lumbar artery (n = 5), median sacral artery (n = 2), and circumflex femoral artery (n = 2). Infection sites included the gluteal (n = 11), femoral (n = 6), sacral (n = 4), lumbar (n = 4), anterior iliac (n = 2), inguinal (n = 1), and perineal (n = 1) regions. Necrotic changes of infected soft tissue were found in all patients. They underwent open drainage and daily debridement with pulsatile irrigation followed by intravenous antibiotics. All patients developed severe sepsis, five of whom subsequently died of multiple organ failure., Conclusions: In critically injured patients with multiple injuries and unstable pelvic fracture, peripelvic soft tissue infections occasionally cause sepsis. Peripelvic infections are often accompanied by necrotic changes and easily develop into severe sepsis or multiple organ failure. Identifying high-risk patients and early diagnosis with prompt surgical treatment are indispensable for the patients' survival.

Background: Major pelvic venous injuries secondary to blunt trauma can be a difficult problem in diagnosis and management. This study aimed to elucidate the clinical significance of iliac vein injuries demonstrated by venography in patients with blunt pelvic injuries who remained unstable even after transcatheter arterial embolization (TAE)., Methods: We reviewed the records of 72 patients with unstable pelvic fracture who presented with shock at our center after blunt trauma from 1999 through 2003. The average Injury Severity Score was 34.3 in this study population., Results: TAE was the first method of choice to control bleeding from pelvic fracture in 61 patients. Thirty-six patients recovered from shock after TAE. Eighteen of 25 who did not recover from shock died. In 11 of these 25, transfemoral venography with a balloon catheter was performed, revealing significant venous extravasation in 9: common iliac vein in 5, internal iliac vein in 3, and external iliac vein in 1. The average Injury Severity Score of patients with iliac vein injury was 45.8. Treatments for venous injuries were laparotomy for hemostasis (n = 1, survivors = 0), retroperitoneal gauze packing (n = 3, survivors = 1), and endovascular stent placement (n = 3, survivors = 3). Two patients suffered from cardiac arrest before treatment for venous injury. External fixations were performed after TAE according to fracture type., Conclusion: The iliac vein injury is the principal cause of hemorrhagic shock in some patients with unstable pelvic fractures after blunt trauma. Venography is useful for identifying iliac vein injuries.

To investigate the efficacy of continuous regional arterial infusion (CRAI) of a protease inhibitor and antibiotic for severe acute pancreatitis (SAP) in patients admitted to an intensive care unit (ICU). A total of 51 patients with SAP requiring admission to an ICU were studied. The patients were divided into two groups: one received the protease inhibitor nafamostat mesylate and the antibiotic imipenem by continuous regional arterial infusion (CRAI group) and the other received protease inhibitors and antibiotics by intravenous infusion (non-CRAI group). To evaluate the therapeutic usefulness of CRAI of a protease inhibitor and antibiotic for SAP, the rate of surgery and the cumulative survival rate were compared between the non-CRAI group and the CRAI group. The rate of surgery was 32% in the non-CRAI group and 9% in the CRAI group (P = 0.08). Cumulative survival rates at 1, 6, and 12 months were 77.9%, 48.9%, and 48.9% in the non-CRAI group compared with 100.0%, 100.0%, and 87.1% in the CRAI group. Outcome was thus significantly better in the CRAI group than in the non-CRAI group (P = 0.002). CRAI of a protease inhibitor and antibiotic may decrease the need for surgical therapy and reduce mortality in patients with SAP.

Increased expression of endothelin-1 (ET-1) immunoreactivity is demonstrated in the active atherosclerotic plaque. Here we show that both ETA and ETB receptors are expressed in rat vascular smooth-muscle cells (VSMCs). ET-1 binding to ETB receptors enhances nitric oxide-induced cell death in VSMCs. These findings suggest that ET-1 may participate in the mechanism of cell death (apoptosis) in the plaque through activation of ETB-mediated pathways and that a selective ETB receptor antagonist could be useful in preventing acute plaque alterations, such as plaque rupture.