Laparoscopic ischemic conditioning of the stomach prior to esophagectomy induces gastric neo-angiogenesis.

BACKGROUND: The risk of an anastomotic leakage (AL) following Ivor-Lewis esophagectomy is increased in patients with calcifications of the aorta or a stenosis of the celiac trunc. Ischemic conditioning (ISCON) of the gastric conduit prior to esophagectomy is supposed to improve gastric vascularization at the anastomotic site. The prospective ISCON trial was conducted to proof the safety and feasibility of this strategy with partial gastric devascularization 14 days before esophagectomy in esophageal cancer patients with a compromised vascular status. This work reports the results from a translational project of the ISCON trial aimed to investigate variables of neo-angiogenesis. METHODS: Twenty esophageal cancer patients scheduled for esophagectomy were included in the ISCON trial. Serum samples (n = 11) were collected for measurement of biomarkers and biopsies (n = 12) of the gastric fundus were taken before and after ISCON of the gastric conduit. Serum samples were analyzed including 62 different cytokines. Vascularization of the gastric mucosa was assessed on paraffin-embedded sections stained against CD34 to detect the degree of microvascular density and vessel size. RESULTS: Between November 2019 and January 2022 patients were included in the ISCON Trial. While serum samples showed no differences regarding cytokine levels before and after ISCON biopsies of the gastric mucosa demonstrated a significant increase in microvascular density after ISCON as compared to the corresponding gastric sample before the intervention. CONCLUSION: The data prove that ISCON of the gastric conduit as esophageal substitute induces significant neo-angiogenesis in the gastric fundus which is considered as surrogate of an improved vascularization at the anastomotic site.

HIV DNA reservoir and elevated PD-1 expression of CD4 T-cell subsets particularly persist in the terminal ileum of HIV-positive patients despite cART.

OBJECTIVES: Despite its importance as an HIV anatomic sanctuary, little is known about the characteristics of the HIV reservoir in the terminal ileum (TI). In blood, the immune checkpoint inhibitor programmed-death-1 (PD-1) has been linked to the HIV reservoir and T-cell immune dysfunction. We thus evaluated PD-1 expression and cell-associated HIV DNA in memory CD4 T-cell subsets from TI, peripheral blood (PB) and rectum (RE) of untreated and treated HIV-positive patients to identify associations between PD-1 and HIV reservoir in other sites. METHODS: Using mononuclear cells from PB, TI and RE of untreated HIV-positive (N = 6), treated (n = 18) HIV-positive and uninfected individuals (n = 16), we identified and sorted distinct memory CD4 T-cell subsets by flow cytometry, quantified their cell-associated HIV DNA using quantitative PCR and assessed PD-1 expression levels using geometric mean fluorescence intensity. Combined HIV-1 RNA in situ hybridization and immunohistochemistry was performed on ileal biopsy sections. RESULTS: Combined antiretroviral therapy (cART)-treated patients with undetectable HIV RNA and significantly lower levels of HIV DNA in PB showed particularly high PD-1 expression in PB and TI, and high HIV DNA levels in TI, irrespective of clinical characteristics. By contrast, in treatment-naïve patients HIV DNA levels in memory CD4 T-cell subsets were high in PB and TI. CONCLUSION: Elevated PD-1 expression on memory CD4 T-cells in PB and TI despite treatment points to continuous immune dysfunction and underlines the importance of evaluating immunotherapy in reversing HIV latency and T-cell reconstitution. As HIV DNA particularly persists in TI despite cART, investigating samples from TI is crucial in understanding HIV immunopathogenesis.

Medical students' attitude towards artificial intelligence: a multicentre survey.

OBJECTIVES: To assess undergraduate medical students' attitudes towards artificial intelligence (AI) in radiology and medicine. MATERIALS AND METHODS: A web-based questionnaire was designed using SurveyMonkey, and was sent out to students at three major medical schools. It consisted of various sections aiming to evaluate the students' prior knowledge of AI in radiology and beyond, as well as their attitude towards AI in radiology specifically and in medicine in general. Respondents' anonymity was ensured. RESULTS: A total of 263 students (166 female, 94 male, median age 23 years) responded to the questionnaire. Around 52% were aware of the ongoing discussion about AI in radiology and 68% stated that they were unaware of the technologies involved. Respondents agreed that AI could potentially detect pathologies in radiological examinations (83%) but felt that AI would not be able to establish a definite diagnosis (56%). The majority agreed that AI will revolutionise and improve radiology (77% and 86%), while disagreeing with statements that human radiologists will be replaced (83%). Over two-thirds agreed on the need for AI to be included in medical training (71%). In sub-group analyses male and tech-savvy respondents were more confident on the benefits of AI and less fearful of these technologies. CONCLUSION: Contrary to anecdotes published in the media, undergraduate medical students do not worry that AI will replace human radiologists, and are aware of the potential applications and implications of AI on radiology and medicine. Radiology should take the lead in educating students about these emerging technologies. KEY POINTS: • Medical students are aware of the potential applications and implications of AI in radiology and medicine in general. • Medical students do not worry that the human radiologist or physician will be replaced. • Artificial intelligence should be included in medical training.

Trends in HbA1c levels and implications for diabetes screening in tuberculosis cases undergoing treatment in India.

SETTING: The optimal timing of screening for diabetes mellitus (DM) among tuberculosis (TB) cases is unclear due to the possibility of stress hyperglycemia. DESIGN: We evaluated adult (18 years) pulmonary TB cases at treatment initiation as well as at 3 months, 6 months and 12 months. DM was identified by self-report (known DM) or glycated hemoglobin (HbA1c)  6.5% (new DM). Trends in HbA1c levels during treatment were assessed using non-parametric tests. RESULTS: Of the 392 participants enrolled, 75 (19%) had DM, 30 (40%) of whom had new DM. Of the 45 participants with known DM, respectively 37 (82%) and 40 (89%) received medication to lower glucose levels at treatment initiation and completion; one participant with new DM initiated glucose-lowering medication during follow-up. The median HbA1c level in participants with known, new and no DM was respectively 10.1% (interquartile range [IQR] 8.3-11.6), 8.5% (IQR 6.7-11.5) and 5.6% (IQR 5.3-5.9) at treatment initiation, and 8.7% (IQR 6.8-11.3), 7.1% (IQR 5.8-9.5) and 5.3% (IQR 5.1-5.6) at treatment completion (P < 0.001). Overall, 5 (12%) with known and 13 (43%) with new DM at treatment initiation had reverted to HbA1c < 6.5% by treatment completion (P = 0.003); the majority of reversions occurred during the first 3 months, with no significant reversions beyond 6 months. CONCLUSION: HbA1c levels declined with anti-tuberculosis treatment. Repeat HbA1c testing at treatment completion could reduce the risk of misdiagnosis of DM.

Impact of the Weekday of Surgery on Outcome in Gastric Cancer Patients who Underwent D2-Gastrectomy.

BACKGROUND: The impact of the weekday of surgery in major elective cases of the upper-GI has been discussed controversially. The objective of this study was to assess whether weekday of surgery influences outcome in patients undergoing D2-gastrectomy. MATERIALS AND METHODS: Patients who underwent D2-gastrectomy for gastric adenocarcinoma between 1996 and 2016 were included. Weekday of surgery was recognized, and subgroups were analyzed regarding clinical and histopathological differences. Survival analysis was performed based on weekday of surgery, and early weekdays (Monday-Tuesday) were compared with late weekdays (Wednesday-Friday). RESULTS: In total, 460 patients, 71% male and 29% female, were included into analysis. The median age was 65 years. Distribution to each weekday was equal and ranged from 86 cases (Wednesday) to 96 cases (Tuesday). The pT, pN and M category and the rate of patients who underwent neoadjuvant treatment did not show significant differences (p = 0.641; p = 0.337; p = 0.752; p = 0.342, respectively). The subgroups did not differ regarding the number of dissected lymph nodes and rate of R-1/2 resections (p = 0.590; p = 0.241, respectively). Survival analysis showed a median survival of 43 months (95% CI 31-55 months), and there was no single weekday or a combination of weekdays (Mon/Tue vs Wed/Thu/Fri) with a significant favorable or worse outcome (p = 0.863; p = 0.30, respectively). The outcome did not differ regarding mortality within the first 90 days after surgery (p = 0.948). CONCLUSIONS: The present study does not show any evidence for a significant impact of weekday of surgery on short- and long-term outcome of patients undergoing gastrectomy for gastric adenocarcinoma.

Prevalence of dysglycemia and clinical presentation of pulmonary tuberculosis in Western India.

SETTING: Pune, India. OBJECTIVES: To estimate the prevalence and risk factors of pre-diabetes mellitus (DM) and DM, and its associations with the clinical presentation of tuberculosis (TB). DESIGN: Screening for DM was conducted among adults (age  18 years) with confirmed TB between December 2013 and January 2017. We used multinomial regression to evaluate the risk factors for pre-DM (glycated hemoglobin [HbA1c]  5.7-6.5% or fasting glucose 100-125 mg/dl) and DM (HbA1c  6.5% or fasting glucose  126 mg/dl or random blood glucose > 200 mg/dl or self-reported DM history/treatment) and the association of dysglycemia with the severity of TB disease. RESULTS: Among 1793 participants screened, 890 (50%) had microbiologically confirmed TB. Of these, 33% had pre-DM and 18% had DM; 41% were newly diagnosed. The median HbA1c level among newly diagnosed DM was 7.0% vs. 10.3% among known DM (P < 0.001). DM (adjusted OR [aOR] 4.94, 95%CI 2.33-10.48) and each per cent increase in HbA1c (aOR 1.42, 95%CI 1.01-2.01) was associated with >1+ smear grade or 9 days to TB detection. CONCLUSION: Over half of newly diagnosed TB patients had DM or pre-DM. DM and increasing dysglycemia was associated with higher bacterial burden at TB diagnosis, potentially indicating a higher risk of TB transmission to close contacts.

Associations of dietary calcium intake with metabolic syndrome and bone mineral density among the Korean population: KNHANES 2008-2011.

Excessive amount of calcium intake increased risk for metabolic syndrome in men. However, modest amount decreased the risk of metabolic syndrome and osteoporosis in postmenopausal women. Modest amount of calcium also increased bone mineral density (BMD) in both men and postmenopausal women. INTRODUCTION: The present study aimed to evaluate the associations of dietary calcium intake with metabolic syndrome and bone mineral density (BMD) in Korean men and women, especially postmenopausal women. METHODS: The study was performed using data from the Korean National Health and Nutrition Examination Survey (2008-2011) and included 14,705 participants (5953 men, 4258 premenopausal women, and 4494 postmenopausal women). Clinical and other objective characteristics, presence of metabolic syndrome, and the BMD of the femur neck and lumbar spine were evaluated according to dietary calcium intake. RESULTS: There was a higher tendency for metabolic syndrome in men with a dietary calcium intake of >1200 mg/day than with ≤400 mg of calcium intake; >400 and ≤800 mg of calcium intake was helpful for postmenopausal women to decrease risk for metabolic syndrome. Overall, the group with calcium intake >400 and ≤800 mg daily had significantly increased BMD in both femoral neck and lumbar spine from both men and postmenopausal women. From both femoral neck and lumbar spine, the prevalence of osteoporosis in postmenopausal women significantly decreased in the group whose calcium intake was >400 and ≤800 mg daily. CONCLUSION: Excessive dietary calcium may increase the prevalence of metabolic syndrome in men. For postmenopausal women, calcium intake does not increase the risk of metabolic syndrome, but modest amount decreases the risk. It may increase the BMD in men and postmenopausal women, and also reduce the prevalence of both osteoporosis and metabolic syndrome in postmenopausal women.

The effect of prolonged breast-feeding on the development of postmenopausal osteoporosis in population with insufficient calcium intake and vitamin D level.

UNLABELLED: Breast-feeding affects bone metabolism and calcium homeostasis, and prolonged breast-feeding may influence the development of postmenopausal osteoporosis, particularly in highly susceptible populations. The study determined that breast-feeding may be a risk factor for postmenopausal osteoporosis, especially in people with low calcium intakes and vitamin D deficiencies. INTRODUCTION: The purpose of this study was to determine whether breast-feeding is a risk factor in the development of postmenopausal osteoporosis, especially in highly susceptible population. METHODS: The study was performed using data from the 2010 to 2011 Korea National Health and Nutrition Examination Survey, and it included 1231 postmenopausal women who were aged between 45 and 70 years. Osteoporosis was defined using the World Health Organization's T-score criteria, namely, a T-score of ≤-2.5 at the femoral neck or the lumbar spine. The patients' ages, body mass indexes, daily calcium intakes, serum vitamin D levels, exercise levels, smoking histories, and reproductive factors relating to menarche, menopause, delivery, breast-feeding, hormone treatment, and oral contraceptive use were evaluated. Comparisons between the osteoporosis and non-osteoporosis groups were undertaken using Student's t test and the chi-square test, and logistic regression models were built. RESULTS: A significant increase in the risk of osteoporosis was apparent in postmenopausal women with prolonged breast-feeding histories (≥24 months) (model 1: odds ratio [OR] = 2.489; 95 % confidence interval [CI] = 1.111 to 5.578, p = 0.027; model 2: OR = 2.503; 95 % CI = 1.118 to 5.602, p = 0.026; model 3: OR = 2.825; 95 % CI = 1.056 to 7.56, p = 0.039), particularly in those with inadequate serum vitamin D levels and calcium intakes (<800 mg/day). CONCLUSIONS: Breast-feeding seems to increase the risk of postmenopausal osteoporosis; however, its impact may not be definitive in women with sufficient vitamin D levels and calcium intakes. Therefore, sufficient calcium intakes and adequate vitamin D levels may be important to prevent osteoporosis in postmenopausal women that is derived from breast-feeding.

Single Nucleotide Polymorphism of Interleukin-18 and Interleukin-18 Receptor and the Risk of Papillary Thyroid Cancer.

PURPOSE: Growing evidence suggests that interleukin-18 (IL-18) levels may affect neoplasia and that single nucleotide polymorphisms (SNPs) within IL-18 gene may influence its production. In this study, we evaluated whether IL-18 and IL-18 receptor (IL-18R) polymorphisms are associated with the development and clinicopathological features of papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: Using direct sequencing, we investigated the association between functional polymorphisms of IL-18 and IL-18R genes and susceptibility to PTC in 94 PTC patients and 260 healthy controls. Genetic data were analyzed using commercially available software. Multiple logistic regression models were used to calculate odds ratios, 95% confidence intervals, and P-values for the association between the genotypes and risk of PTC. The PTC patients were further subgrouped and compared with respect to their clinicopathological characteristics. RESULTS: 3 SNPs of IL-18 (rs549908, rs360717, and rs187238) and one of IL-18R (rs1420106) examined in this study were significantly associated with the development of PTC. The allelic frequencies of the 3 SNPs of IL-18 also showed significant association with lymph node metastasis. CONCLUSION: IL-18 and IL-18R polymorphisms may contribute to the development and lymph node metastasis of PTC.

Association of metabolic syndrome with coronary atherosclerosis in non-diabetic postmenopausal women.

OBJECTIVE: We investigated the possible association of metabolic syndrome with arterial stiffness and coronary atherosclerosis in non-diabetic, postmenopausal women. METHODS: A total of 293 non-diabetic, postmenopausal women who visited the health promotion center for a routine health check-up were included in a cross-sectional study. Arterial stiffness was measured by brachial-ankle pulse wave velocity, and coronary atherosclerosis was detected using 64-row multi-detector computed tomography. RESULTS: Women with coronary atherosclerosis had a significantly higher proportion of metabolic syndrome than those without coronary atherosclerosis. The brachial-ankle pulse wave velocity was significantly higher in women who had metabolic syndrome compared to those who had no metabolic syndrome (1567.71 ± 211.81 vs. 1336.75 ± 159.62 cm/s, p < 0.001). In addition, the brachial-ankle pulse wave velocity was shown to increase with increasing number of metabolic syndrome components (p for trend < 0.001). Metabolic syndrome was associated with increased risk of coronary atherosclerosis (adjusted odds ratio 2.38; 95% confidence interval 1.01-5.06), after adjusting for confounding factors. CONCLUSIONS: Metabolic syndrome increases the risk of coronary atherosclerosis in postmenopausal women. Increased arterial stiffness may partly explain an increased risk of coronary atherosclerosis in postmenopausal women with metabolic syndrome.

Incretin-based therapy and pancreatic beta cells.

Type 2 diabetes (T2D) is a complex, progressive disease with life-threatening complications and one of the most serious public-health problems worldwide. The two main mechanisms of T2D pathogenesis are pancreatic beta cell dysfunction and insulin resistance. It is now recognized that pancreatic beta cell dysfunction is a necessary factor for T2D development. Traditional therapies for controlling blood glucose are suboptimal as they fail to meet target goals for many patients. Glucagon-like peptide-1 receptor agonists (GLP1RA) and dipeptidyl peptidase-4 inhibitors (DPP4I) are an attractive class of therapy because they reduce blood glucose by targeting the incretin hormone system and, in particular, have the potential to positively affect pancreatic beta cell biology. This review outlines our current understanding of pancreatic beta cell incretin system dysfunction in T2D and summarizes recent evidence of the effect of incretin-based therapies on beta cell function and mass. Incretin-based therapies have shown strong evidence for beneficial effects on beta cell function and mass in animal studies. In humans, incretin-based therapies are effective glucose-lowering agents, but further study is still required to evaluate their long-term effects on beta cell function and safety as well as beta cell mass expansion.

[Spectrum of laparoscopic surgery for gastric tumors]. / Spektrum der laparoskopischen Chirurgie bei Magentumoren.

Minimally invasive operative procedures are increasingly being used for treating tumors of the upper gastrointestinal tract. While minimally invasive surgery (MIS) has become established as a standard procedure for benign tumors and gastrointestinal stromal tumors (GIST) based on current studies, the significance of MIS in the field of gastric cancer is the topic of heated debate. Until now the majority of studies and meta-analyses on gastric cancer have come from Asia and these indicate the advantages of MIS in terms of intraoperative blood loss, minor surgical complications and swifter convalescence although without any benefits in terms of long-term oncological results and quality of life. Unlike in Germany, gastric cancer in Asia with its unchanged high incidence rate, 50 % frequency of early carcinoma and predominantly distal tumor localization is treated at high-volume centres. Due to the proven marginal advantages of MIS over open resection described in the published studies no general recommendation for laparoscopic surgery of gastric cancer can currently be given.

Pulmonary tuberculosis among patients hospitalised with community-acquired pneumonia in a tuberculosis-prevalent area.

SETTING: A suburban teaching hospital in a tuberculosis (TB) prevalent area. OBJECTIVES: To evaluate the proportion of pulmonary TB among patients hospitalised with suspected community-acquired pneumonia (CAP), and to develop a diagnostic index for identifying TB among these patients. DESIGN: TB cases confirmed using 1) sputum culture, or 2) both sputum acid-fast bacilli smear and polymerase chain reaction for Mycobacterium tuberculosis, were compared with non-tuberculous CAP by demographic, clinical, laboratory and radiographic information. Using multiple logistic regression analysis, risk factors for TB were identified. A diagnostic index was developed by summing up their simplified regression coefficients. Its performance was checked using c-statistic. RESULTS: TB was the second leading cause of CAP (37/528, 7.0%). Risk factors were initial symptoms >7 days, serum albumin <3.5 g/dl, cavitary/nodular infiltrates and upper lobe involvement (1 point for each). The c-statistic of the index was 0.856 (95%CI 0.789-0.923), and for bootstrapping samples of 1000 repetitions it was 0.856 (95%CI 0.791-0.921). For scores ≥2, sensitivity and specificity were respectively 81.1% and 75.8%. CONCLUSION: TB is one of the leading causes of CAP in TB-prevalent areas. Our diagnostic index may help clinicians identify TB immediately from CAP and initiate appropriate isolation and optimal treatment.

Thickness of superficial basal cell carcinoma (sBCC) predicts imiquimod efficacy: a proposal for a thickness-based definition of sBCC.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in the white population. It is an important driver of healthcare costs and causes significant morbidity. Topical imiquimod is a good noninvasive treatment alternative for surgical excision in superficial BCC (sBCC). However, there are currently no uniform histological definitions of sBCC. A definition based on tumour thickness might be a good alternative. OBJECTIVES: To determine whether tumour thickness in sBCC is a predictor of treatment failure. METHODS: We retrospectively examined 127 histological biopsy specimens of sBCC treated primarily with imiquimod five times a week for 6 weeks. Mean follow-up was 34 months (range 3-91). Recurrence was evaluated clinically with histological verification. RESULTS: Among nonrecurrent cases the median tumour thickness was 0·26 mm (range 0·09-0·61), while for recurrent cases the median tumour thickness was 0·57 mm (range 0·41-1·41, P < 0·0001). Among lesions ≤ 0·40 mm in thickness, none recurred, whereas for lesions > 0·40 mm the recurrence rate was 58% (P < 0·0001). CONCLUSIONS: We recommend the use of tumour thickness to define the superficial pattern in pathology reports for BCC as this can help to determine treatment response of sBCC to imiquimod.

Infiltrating Foxp3+ regulatory T cells and histopathological features in canine classical and spermatocytic seminomas.

In humans, regulatory T (T reg) cells are known to play a critical role in both the regulation of immune homoeostasis and the progression of cancer. However, there is little information about the identification, characterization and the function of T reg cells in canine tumours. We identified T reg cells in 28 canine seminoma samples using a Forkhead box P3 (Foxp3) antibody and investigated the relationship between T reg cell infiltration and histopathological features of classical and spermatocytic seminomas (SE and SS, respectively). The Foxp3 protein showed nuclear immunostaining in infiltrating lymphocytes, and Foxp3+ cells were diffused or focally distributed in seminoma tissues. Foxp3+ cells were frequently present in the SS histotype, in seminomas that showed no evidence of tumour cell invasion into the vessels and in seminomas showing a diffuse growth pattern with three cell types. Neither the SE/SS histotype nor the histopathological features of the tumour correlated with Foxp3+ cell counts. These results indicate that Foxp3+ T reg cells may be associated with a less malignant histological phenotype or may not play a critical role in the immune response of canine seminomas. Moreover, Foxp3+ T reg cells may be associated with SS seminoma, but further studies, involving a larger number of samples, are required to better understand whether these cells play a critical role in the immune response in canine seminomas. This is the first report to demonstrate the characteristics of T reg cell infiltration in canine seminoma.

P-glycoprotein expression in canine mammary gland tumours related with myoepithelial cells.

P-glycoprotein is influential in chemotherapy-resistance in numerous cancers and has been widely studied in human breast cancer research, but is less studied in canine mammary gland tumour (MGT). The study was to evaluate P-glycoprotein expression and its localisations related with prognostic factors with monoclonal antibody C219, by immunohistochemistry (IHC) of 68 cases of canine malignant (n=54) and benign (n=14) MGT. Additional immunofluorescence (IF) and reverse transcriptase-polymerase chain reaction (RT-PCR) were also performed. There was a novel finding that P-glycoprotein expression with C219 localised at two different cell types: epithelial and myoepithelial cells. Myoepithelial localised tumours were 5 benign (35.5%) and 21 malignant (63.6%), while epithelial localised tumours were 12 cases, all malignant (36.5%). Unlike conventional belief, semi-quantitative evaluation of IHC intensity scores of C219 expression in malignant MGT was related with favourable histopathological parameters.

A novel PRKAR1A mutation in Korean Carney complex family.

Carney complex (CNC) is an autosomal dominant hereditary or sporadic multiple neoplastic syndrome that shows variable clinical symptoms. Generally, CNC appears as skin pigmentation, cardiac or cutaneous myxomas, and multiple endocrine tumours. We performed an extensive evaluation of 9 individuals within 1 family in whom CNC was suspected. Among them, 5 had CNC with various clinical manifestations. We also performed mutational analysis of suspected genes in these patients. Although all patients were members of the same family, variable CNC-related manifestations were observed in each patient. An analysis showed a novel deletion mutation (c.537delA) in exon 6 of the PRKAR1A gene in the patients. Based on our results, the patients were determined to have CNC type I. This is the first such mutational report in Korea.

Effect of necrosis modulator necrox-7 on hepatic ischemia-reperfusion injury in beagle dogs.

OBJECTIVE: The liver is susceptible to ischemia-reperfusion (IR) injury during inflow occlusion for hepatectomy. There is no effective pharmacologic agent available to prevent the release of high-mobility-group box 1 (HMGB1) or to ameliorate IR injury. This pilot study sought to develop a model in beagle dogs for the purpose of testing the efficacy of a necrosis modulator, necrox-7, to prevent hepatic IR injury in beagle dogs. METHODS: Six male beagle dogs were randomly assigned to the control group (group A; n = 3) or the treatment group (group B; n = 3). Under general anesthesia, group B received intravenous infusion of necrox-7 (13 mg/kg over 20 minutes) followed by 60 minutes of left hepatic inflow occlusion and 60 minutes of reperfusion. Both groups were tested for serum biochemicals, hematology values, liver biopsies, and plasma HMGB1 levels over a 48-hour period. RESULTS: The maximum alanine transferase (ALT), aspartate transferase (AST), and lactate dehydrogenase (LDH) levels among group A versus group B were: ALT 868.3 ± 337.4 IU/L vs 274.3 ± 72.6 IU/L (P = .041); AST 1,024.7 ± 246.5 IU/L vs 505.3 ± 66.7 IU/L (P = .024); and LDH 962.7 ± 226.2 IU/L vs 552.7 ± 62.4 IU/L (P = .039). Liver biopsy demonstrated marked necrosis and inflammatory infiltrates in group A, whereas group B showed little evidence of IR injury. The plasma HMGB1 concentration was significantly lower among group B versus A. CONCLUSION: This pilot study developed a hepatic IR injury model, demonstrating that necrox-7 reduced hepatic necrosis secondary to IR injury in a large animal setting.