SUMMARY The liver is thought to utilize facultative stem cells, also known as “oval cells” or “atypical ductal cells” (ADCs), for regeneration following various types of injury. However, this notion has been based largely on in vitro studies and transplantation models; where lineage tracing has been used, results have been conflicting and effect sizes have been small. Here, we used genetic and nucleoside analog-based tools to mark and track the origin and contribution of various cell populations to liver regeneration in vivo following several ADC-inducing insults. We report that, contrary to prevailing stem-cell-based models of regeneration, virtually all new hepatocytes come from preexisting hepatocytes.

The receptor for advanced glycation endproducts (RAGE) is a multiligand receptor and member of the immunoglobulin superfamily. RAGE is mainly involved in tissue damage and chronic inflammatory disorders, sustaining the inflammatory response upon engagement with damage-associated molecular pattern molecules (DAMPs) such as S100 proteins and high-mobility group box 1 (HMGB1). Enhanced expression of RAGE and its ligands has been demonstrated in distinct tumors and several studies support its crucial role in tumor progression and metastasis by still unknown mechanisms. Here we show that RAGE supports hepatocellular carcinoma (HCC) formation in the Mdr2 2/2 mouse model, a prototype model of inflammation-driven HCC formation, which mimics the human pathology. Mdr2 2/2 Rage 2/2 (dKO) mice developed smaller and fewer HCCs than Mdr2 2/2 mice. Interestingly, although in preneoplastic Mdr2 2/2 livers RAGE ablation did not affect the onset of inflammation, premalignant dKO livers showed reduced liver damage and fibrosis, in association with decreased oval cell activation. Oval cells expressed high RAGE levels and displayed reduced proliferation upon RAGE silencing. Moreover, stimulation of oval cells with HMGB1 promoted an ERK1/2-Cyclin D1-dependent oval cell proliferation in vitro. Finally, genetic and pharmacologic blockade of RAGE signaling impaired oval cell activation in an independent mouse model of oval cell activation, the choline deficient ethionine-supplemented dietary regime. Conclusion: Our data identified a novel function of RAGE in regulating oval cell activation and tumor development in inflammation-associated liver carcinogenesis. (HEPATOLOGY 2013; 58:363-373)

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(Abstracted from Am J Obstet Gynecol 2020;223:747.e1–747.e13) Maternal hypotension after spinal anesthesia is a common complication. Previous studies have shown that spinal hypotension is associated with neonatal acidosis.

A natomic changes associated with pregnancy may render conduct of neuraxial procedures in parturients more difficult. The standard position for a neuraxial block requires a patient to sit on a bed with the spine flexed and legs supported on a stool, but spinal flexion may be improved by instead sitting cross-legged on the bed. Given the lack of prospective studies on this topic, the aim of this study was ultrasonographic assessment of the paramedian target area's size when a pregnant woman sits in the crosslegged position (CLP) for neuraxial needle placement compared with standard sitting position (SP). The authors hypothesized that a CLP would increase the measured lengths of the posterior longitudinal ligament (PLL) indicating an improved acoustic window between vertebrae.From April to July 2016, 30 pregnant, nonlaboring women at 37 weeks or more gestation were recruited when they arrived at the Obstetric Care Unit during the first stage of labor, for an induction of labor, or for an elective cesarean delivery (all while exhibiting no signs of painful contractions). Exclusion criteria were as follows: language barrier, congenital spine abnormality, a history of spinal trauma or surgery, or women in advanced first stage of labor.Demographic data recorded and patients were first asked to sit with their shoulders relaxed, chin to chest, and back curled outward. Then the patients were asked to sit in both study positions-the standard position and the CLP while hugging a pillow. Ultrasonographic identification of the L3-L4 interspace and the PLL measurement at that level were performed by 2 separate scanners. Patients were asked to record their comfort level in each position (5 = very comfortable, and 1 = very uncomfortable). The primary outcome of the study, increase in length of the PLL, was accompanied by secondary outcomes of evaluated increases in length of the ligamentum flavum and interlaminar distance and subject comfort levels.Records for 28 were included in the analysis. Results demonstrated that the ultrasonographically visualized length of the PLL was significantly greater when measured in the CLP compared with SP. In addition, patients reported comparable comfort levels for both CLP and SP.The study did not assess effectiveness of using CLP during placement of neuraxial anesthesia in obstetric patients. In addition, scanning anesthesiologists were not

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BACKGROUND: Low-dose (≤8 mg) hyperbaric bupivacaine for spinal anesthesia during cesarean delivery results in reduced efficacy, yet as a secondary outcome was associated with reduced frequency of spinal-induced hypotension. Our primary aim was to investigate the relationship between hyperbaric bupivacaine dose and the occurrence of spinal-induced hypotension for cesarean delivery. METHODS: Retrospective study of cesarean delivery under spinal or combined spinal anesthesia with hyperbaric bupivacaine in 1 academic institution (2 centers—tertiary and district) from 2012 to 2018. Data were retrieved from the anesthesia information management systems (Metavision, iMDsoft, Tel Aviv, Israel) and the hospital information system, including potential confounding factors, maternal age and weight, hypertensive disease of pregnancy, single/multiple gestation, gestational age, vasopressor administration, planned/urgent surgery, position during anesthesia placement (sitting/lateral), and anesthesiologist seniority. Spinal-induced hypotension was defined as systolic blood pressure that either dropped >20% from baseline or <100 mm Hg. The primary outcome of interest was the incidence of spinal-induced hypotension according to hyperbaric bupivacaine dose. Logistic regression was used to characterize the association between the dose of hyberbaric bupivacaine and spinal-induced hypotension after adjusting for confounding factors. RESULTS: A total of 8226 women were identified. The hyperbaric bupivacaine dose administered was <9 mg for 2395 (29.1%), 9–9.5 mg for 1031 (12.5%), 10 mg for 4155 (50.5%), and >10 mg for 645 (7.8%). We used a cutoff (<10 vs ≥10 mg) to assess for the primary outcome, using multivariable logistic regression. The incidence of at least 1 spinal-induced hypotension episode was higher in patients who received ≥10 mg hyperbaric bupivacaine, 75.8% vs 62.9% for doses below 10 mg, P < .0001; however, even women with lower doses had hypotension. Hyperbaric bupivacaine dose <10 mg was associated with a lower incidence of spinal hypotension, adjusted odds ratio (OR) of 0.774, 95% confidence interval (CI), 0.669-0.897, and P = .0006, adjusted for confounding factors. Umbilical cord pH was available for 2684 (32.6%) cases. There were significantly more neonates with pH < 7.2, among women who received hyperbaric bupivacaine ≥10 mg (10.1%) versus women who received <10 mg (6.8%), P = .0032; however, in the adjusted model, hyperbaric bupivacaine dose ≥10 mg was not associated with pH < 7.2 and an OR of 0.955 (95% CI, 0.631-1.446, P = .829). CONCLUSIONS: Our major finding was that hypotension occurred at all doses of hyperbaric bupivacaine, yet occurrence of spinal hypotension was significantly associated with doses ≥10 mg after adjustment for potential confounders.

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