Ralph C. Quillin

Interleukin-37 reduces liver inflammatory injury via effects on hepatocytes and non-parenchymal cells.

Background and Aim:  The purpose of the present study was to determine the effects of interleukin‐37 (IL‐37) on liver cells and on liver inflammation induced by hepatic ischemia/reperfusion (I/R).

Laparoscopic cholecystectomy in the cirrhotic patient: Predictors of outcome

BACKGROUND We sought to determine the outcome predictors of 94 cirrhotic patients undergoing laparoscopic cholecystectomy (LC). METHODS We performed a single-center, retrospective review of cirrhotic patients undergoing LC for symptomatic gallbladder disease. Statistical analysis was completed using the Chi-square, Wilcoxon rank-sum, and Student t tests as appropriate. RESULTS Ninety-four procedures were completed. The median Child-Turcotte-Pugh (CTP) score was 6 (range, 5-12), and the average Model for End-Stage Liver Disease (MELD) score was 11 ± 5. Hepatitis C was the most common etiology of liver disease (50%) followed by Laennecs cirrhosis (22%). The average length of stay was 2.6 ± 4.3 days; 21% were outpatient procedures. The conversion rate was 11%. Conversion risk factors were decreased serum albumin, increased MELD score, and blood loss. Morbidity occurred in 32 patients. Predictors of morbidity were decreases in serum albumin, increases in International Normalized Ratio (INR) and CTP score, and the number of intraoperative red blood cell transfusions. Mortality occurred in 4 patients. Increased INR, CTP score, CTP class, the number of intraoperative blood and platelet transfusions were predictors of mortality. CONCLUSION LC can be safely performed in cirrhotic patients with appropriate patient selection. Liver synthetic function, operative blood loss, transfusion requirement, CTP, and MELD scores may be used to predict outcomes in these patients.

How Residents Learn Predicts Success in Surgical Residency

BACKGROUND Predictors of success in surgical residency have been poorly understood. Previous studies have related prior performance to future success without consideration of personal attributes that help an individual succeed. Surgical educators should consider how residents learn to gain insight into early identification of residents at risk of failing to complete their surgical training. METHODS We examined our 14-year database of surgical resident learning-style assessments, Accreditation Council for Graduate Medical Education operative log data of graduating residents from 1999 to 2012, first time pass rates on the American Board of Surgery Qualifying and Certifying examinations, and departmental records to identify those residents who did not complete their surgery training at our institution. Statistical analysis was performed using the chi-square test, Wilcoxon rank-sum, and regression analysis with significance set at p < 0.05. RESULTS We analyzed 441 learning-style assessments from 130 residents. Surgical residents are predominantly action-based learners, with converging (219, 49.7%) and accommodating (112, 25.4%) being the principal learning styles. Assimilating (66, 15%) and diverging (44, 10%) learning styles, where an individual learns by observation, were less common. Regression analysis comparing learning style with case volume revealed that residents who are action-based learners completed more cases at graduation (p < 0.05 for each). Additionally, surgical residents who transferred to a nonsurgical residency or nonphysician field were more likely to learn by observation (p = 0.0467). CONCLUSIONS Surgical residents are predominantly action-based learners. However, a subset of surgical residents learn primarily by observation. These residents are at risk for a less robust operative experience and not completing surgical training. Learning-style analysis may be utilized by surgical educators to identify the potential at-risk residents in general surgery.

Inhibition of acidic sphingomyelinase reduces established hepatic fibrosis in mice

Liver fibrosis occurs as a result of several chronic liver diseases and leads to portal hypertension, cirrhosis and liver failure, often requiring liver transplantation. Activated hepatic stellate cells (HSC) are known to contribute to liver fibrosis, but currently there are no effective therapies for the treatment of established liver fibrosis. Activation of the acidic sphingomyelinase (ASM) has been shown to be involved in HSC activation. In the present study we investigated whether treatment with the ASM inhibitor, amitriptyline (TCA), could prevent and/or reverse fibrosis induced in mice by carbon tetrachloride (CCl4).

Roles of hepatocyte and myeloid CXC chemokine receptor‐2 in liver recovery and regeneration after ischemia/reperfusion in mice

Previous studies have demonstrated the significance of signaling through the CXC chemokine receptor‐2 (CXCR2) receptor in the process of recovery and regeneration of functional liver mass after hepatic ischemia/reperfusion (I/R). CXCR2 is constitutively expressed on both neutrophils and hepatocytes; however, the cell‐specific roles of this receptor are unknown. In the present study, chimeric mice were created through bone marrow transplantation (BMT) using wild‐type and CXCR2‐knockout mice, yielding selective expression of CXCR2 on hepatocytes (Hep) and/or myeloid cells (My) in the following combinations: Hep+/My+; Hep−/My+; Hep+/My−; and Hep−/My−. These tools allowed us to assess the contributions of myeloid and hepatocyte CXCR2 in the recovery of the liver after I/R injury. Flow cytometry confirmed the adoption of the donor phenotype in neutrophils. Interestingly, Kupffer cells from all chimeras lacked CXCR2 expression. Recovery/regeneration of hepatic parenchyma was assessed by histologic assessment and measurement of hepatocyte proliferation. CXCR2Hep+/My+ mice showed the least amount of liver recovery and hepatocyte proliferation, whereas CXCR2Hep−/My− mice had the greatest liver recovery and hepatocyte proliferation. CXCR2Hep+/My− mice had enhanced liver recovery, with hepatocyte proliferation similar to CXCR2Hep−/My− mice. Myeloid expression of CXCR2 directly regulated CXC chemokine expression levels after hepatic I/R, such that mice lacking myeloid CXCR2 had markedly increased chemokine expression, compared with mice expressing CXCR2 on myeloid cells. Conclusion: The data suggest that CXCR2 on myeloid cells is the predominant regulator of liver recovery and regeneration after I/R injury, whereas hepatocyte CXCR2 plays a minor, secondary role. These findings suggest that myeloid cell‐directed therapy may significantly affect liver regeneration after liver resection or transplantation. (HEPATOLOGY 2013)

Characterization of microparticles after hepatic ischemia-reperfusion injury.

Background Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs) are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins–platelets, neutrophils, and endolethial cells–following hepatic ischemia-reperfusion injury. Methods A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. Results MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. Conclusion This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver.

Students’ expectations on the surgery clerkship exceed those of residents and faculty

PURPOSE The perceptions and expectations of students on the surgery clerkship were evaluated and compared with those of surgical residents and faculty. METHODS A voluntary and anonymous survey was distributed to third year medical students, general surgery residents, and surgery faculty. Statistical analysis was performed using the χ(2) and Cochran-Mantel-Haenszel tests (P value <0.05 was significant). RESULTS Medical students, surgery residents and faculty largely agreed on student responsibilities during morning rounds. However, more students (96.9%) than residents (86.2%) and faculty (77.3%) believed they should be writing progress notes, and fewer students (85%) than residents (100%) and faculty (95.5%) thought they should be taught during morning rounds (P < 0.01 and P = 0.04, respectively). The expected and actual educational experience on the surgical clerkship was similar. The amount of instruction provided each week by residents and faculty was similar to the amount expected by students; each group believed that surgical residents were good educators. Students, residents, and faculty agreed on many essential skills for a student to learn by the clerkships end; however, more students (85.8%) than residents (58.6%) and faculty (68.2%) viewed identifying surgical complications as an essential skill (P < 0.01). CONCLUSIONS Overall, the expectations of the medical students, surgical residents, and surgical faculty on the surgery clerkship were well matched. However, there were some instances where the students thought they should be more involved in patient care than did the residents and the faculty. It is important for surgical educators to be aware of these discrepancies to fully maximize the educational experience of medical students.