XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions that underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single-cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NAFLD/NASH spectrum showed that type 1 cDCs (cDC1) were more abundant and activated in disease. Sequencing of physically interacting cDC-T cell pairs from liver-draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1DTA mice or using anti-XCL1-blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1+ cDC1 as an important driver of liver pathology.

The impact of bariatric surgery on nonalcoholic fatty liver disease as measured using non-invasive tests.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common in bariatric surgery candidates. We evaluated the effect of sleeve gastrectomy (SG) on NAFLD using validated non-invasive measures. METHODS: Patients with morbid obesity and NAFLD, planned for SG, were evaluated before and after surgery. Data collected included anthropometrics, biochemistry, adiponectin, SteatoTest™, NashTest™, FibroTest™, OWLiver® test and real-time ShearWave™ elastography (SWE). RESULTS: Twenty-six subjects were included in the study, mean age 44.1 ± 4.8 years, 69.2% males. One year following SG, body mass index decreased significantly from 41.7 ± 4.8 kg/m2 to 29.6 ± 4.5 kg/m2. Concomitantly, significant improvements in triglycerides, ALT, diabetes markers and adiponectin were observed. Mean steatosis, as measured by SteatoTest™, was significantly improved. Steatohepatitis score measured by NashTest™ and OWLiver® significantly decreased. Mean fibrosis, as measured by SWE liver stiffness and FibroTest™, did not change over time. CONCLUSION: Steatosis and steatohepatitis are significantly improved by SG as measured by non-invasive measures.

From Mount Sinai to Mount Scopus: differences in the role and value of fine needle aspiration for evaluating thyroid nodules.

BACKGROUND: Fine needle aspiration is the main diagnostic tool used to assess thyroid nodules. OBJECTIVES: To correlate FNA cytology results with surgical pathological findings in two teaching medical centers across the Atlantic. METHODS: We retrospectively identified 484 patients at Hadassah Hebrew University Medical Center, Jerusalem and Mount Sinai Hospital, New York, by means of both preoperative FNA cytology and a final histopathological report. Results compared FNA diagnosis, histological findings and frozen section results (Mt. Sinai only). RESULTS: The sensitivity value of FNA at Hadassah was 83.0% compared with 79.1% at Mt. Sinai (NS). Specificity values were 86.6 vs. 98.5% (P < 0.05), negative predictive value 78.7 vs. 77.6% (NS) and positive predictive value 89.7 vs. 98.6% (P < 0.05), respectively. "Follicular lesion" was diagnosed on FNA in 33.1% of the patients at Hadassah and in 21.5% at Mt Sinai (P < 0.005) with a malignancy rate of 42.5 vs. 23.1% (P < 0.05), respectively. Frozen section was used in 190 patients at Mt. Sinai (78.5%) with sensitivity and specificity values of 72.3% and 100%. Frozen section results altered the planned operative course in only 6 patients (2.5%). Follicular carcinoma was diagnosed in 12 patients at Hadassah vs. 2 patients at Mt. Sinai (P < 0.05). CONCLUSION: The sensitivity of FNA at the two institutions was comparable. While malignancy on frozen section is highly specific, it should be used selectively for suspicious FNA results. Follicular lesions and the rate of malignancy in such lesions were more common at Hadassah, favoring a more aggressive surgical approach.

Learning curve in laparoscopic colorectal surgery: our first 100 patients.

BACKGROUND: Recent data confirming the oncologic safety of laparoscopic colectomy for cancer as well as its potential benefits will likely motivate more surgeons to perform laparoscopic colorectal surgery. OBJECTIVES: To assess factors related to the learning curve of laparoscopic colorectal surgery, such as the number of operations performed, the type of procedures, major complications, and oncologic resections. METHODS: We evaluated the data of our first 100 elective laparoscopic colorectal operations performed during a 2 year period and compared the first 50 cases with the following 50. RESULTS: The mean age of the study population was 66 years and 49% were males. Indications included cancer, polyps, diverticular disease, Crohn's disease, and others, in 50%, 23%, 13%, 7% and 7% respectively. Mean operative time was 170 minutes. One patient died (massive pulmonary embolism). Significant surgical complications occurred in 10 patients (10%). Hospital stay averaged 8 days. Comparison of the first 50 procedures with the next 50 revealed a significant decrease in major surgical complications (20% vs. 0%). Mean operative time decreased from 180 to 160 minutes and hospital stay from 8.6 to 7.2 days. There was no difference in conversion rate and mean number of harvested nodes in both groups. Residents performed 8% of the operations in the first 50 cases compared with 20% in the second 50 cases. Right colectomies had shorter operative times and fewer conversions. CONCLUSIONS: There was a significant decrease in major complications after the first 50 laparoscopic colorectal procedures. Adequate oncologic resections may be achieved early in the learning curve. Right colectomies are less difficult to perform and are recommended as initial procedures.