Chronic AT1 blockade improves hyperglycemia by decreasing adipocyte inflammation and decreasing hepatic PCK1 and G6PC1 expression in obese rats.

Inappropriate activation of the renin-angiotensin system decreases glucose uptake in peripheral tissues. Chronic angiotensin receptor type 1 (AT1) blockade (ARB) increases glucose uptake in skeletal muscle and decreases the abundance of large adipocytes and macrophage infiltration in adipose. However, the contributions of each tissue to the improvement in hyperglycemia in response to AT1 blockade are not known. Therefore, we determined the static and dynamic responses of soleus muscle, liver, and adipose to an acute glucose challenge following the chronic blockade of AT1. We measured adipocyte morphology along with TNF-α expression, F4/80- and CD11c-positive cells in adipose and measured insulin receptor (IR) phosphorylation and AKT phosphorylation in soleus muscle, liver, and retroperitoneal fat before (T0), 60 (T60) and 120 (T120) min after an acute glucose challenge in the following groups of male rats: 1) Long-Evans Tokushima Otsuka (LETO; lean control; n = 5/time point), 2) obese Otsuka Long Evans Tokushima Fatty (OLETF; n = 7 or 8/time point), and 3) OLETF + ARB (ARB; 10 mg olmesartan/kg/day; n = 7 or 8/time point). AT1 blockade decreased adipocyte TNF-α expression and F4/80- and CD11c-positive cells. In retroperitoneal fat at T60, IR phosphorylation was 155% greater in ARB than in OLETF. Furthermore, in retroperitoneal fat AT1 blockade increased glucose transporter-4 (GLUT4) protein expression in ARB compared with OLETF. IR phosphorylation and AKT phosphorylation were not altered in the liver of OLETF, but AT1 blockade decreased hepatic Pck1 and G6pc1 mRNA expressions. Collectively, these results suggest that chronic AT1 blockade improves obesity-associated hyperglycemia in OLETF rats by improving adipocyte function and by decreasing hepatic glucose production via gluconeogenesis.NEW & NOTEWORTHY Inappropriate activation of the renin-angiotensin system increases adipocyte inflammation contributing to the impairment in adipocyte function and increases hepatic Pck1 and G6pc1 mRNA expression in response to a glucose challenge. Ultimately, these effects may contribute to the development of glucose intolerance.

Non-operative management of biliary complications after Liver Transplantation in pediatric patients: A 30-year experience.

BACKGROUND: To evaluate the efficacy of percutaneous and endoscopic therapeutic interventions for biliary strictures and leaks following LT in children. METHODS: Retrospective analysis of 49 consecutive pediatric liver transplant recipients (27 girls, 22 boys, mean age at transplant 3.9 years) treated at our institution from 1989 to 2019 for biliary leak and/or biliary stricture was performed. Minimally invasive approach was considered clinically successful if it resulted in patency of the narrowed biliary segment and/or correction of the biliary leak. RESULTS: Forty-two patients had a stricture at the biliary anastomosis; seven had a biliary leak. After an average 13.8 years of follow-up, long-term clinical success with minimally invasive treatment (no surgery or re-transplant) was achieved for 24 children (57%) with biliary stricture and 4 (57%) with biliary leaks. Eight patients required re-transplant; however, only one was due to failure of both percutaneous and surgical management. For biliary strictures, failure of non-surgical management was associated with younger age at stricture diagnosis (p < .02). CONCLUSIONS: Percutaneous and endoscopic management of biliary strictures and leaks after LT in children is associated with a durable result in >50% of children.

Simultaneous angiotensin receptor blockade and glucagon-like peptide-1 receptor activation ameliorate albuminuria in obese insulin-resistant rats.

Insulin resistance increases renal oxidant production by upregulating NADPH oxidase 4 (Nox4) expression contributing to oxidative damage and ultimately albuminuria. Inhibition of the renin-angiotensin system (RAS) and activation of glucagon-like peptide-1 (GLP-1) receptor signalling may reverse this effect. However, whether angiotensin receptor type 1 (AT1) blockade and GLP-1 receptor activation improve oxidative damage and albuminuria through different mechanisms is not known. Using insulin-resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rats, we tested the hypothesis that simultaneous blockade of AT1 and activation of GLP-1r additively decrease oxidative damage and urinary albumin excretion (Ualb V) in the following groups: (a) untreated, lean LETO (n = 7), (b) untreated, obese OLETF (n = 9), (c) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d; n = 9), (d) OLETF + GLP-1 mimetic (EXE; 10 µg exenatide/kg/d; n = 7) and (e) OLETF + ARB +exenatide (Combo; n = 6). Mean kidney Nox4 protein expression and nitrotyrosine (NT) levels were 30% and 46% greater, respectively, in OLETF compared with LETO. Conversely, Nox4 protein expression and NT were reduced to LETO levels in ARB and EXE, and Combo reduced Nox4, NT and 4-hydroxy-2-nonenal levels by 21%, 27% and 27%, respectively. At baseline, Ualb V was nearly double in OLETF compared with LETO and increased to nearly 10-fold greater levels by the end of the study. Whereas ARB (45%) and EXE (55%) individually reduced Ualb V, the combination completely ameliorated the albuminuria. Collectively, these data suggest that AT1 blockade and GLP-1 receptor activation reduce renal oxidative damage similarly during insulin resistance, whereas targeting both signalling pathways provides added benefit in restoring and/or further ameliorating albuminuria in a model of diet-induced obesity.

The use of 3D printing in shared decision making for a juvenile aggressive ossifying fibroma in a pediatric patient.

Juvenile aggressive ossifying fibromas (JAOF) are rare, typically benign pediatric tumors that are locally aggressive and have high recurrence rates. A 7-year old male presented with a palatal mass and a 3D printed model was created and used as a visual aide to highlight the importance of management in terms of functional, cosmetic, and disease-free outcomes with the family. The patient ultimately underwent successful enucleation with final pathology consistent with JAOF. To our knowledge, this is the first description of the use of 3D printing to help in the shared decision-making process for the treatment of this aggressive tumor.

Nonstandardized Terminology to Describe Focal Liver Lesions in Patients at Risk for Hepatocellular Carcinoma: Implications Regarding Clinical Communication.

OBJECTIVE: The purpose of this study is to determine the correlation between malignancy risk of focal liver observations in patients at risk for hepatocellular carcinoma (HCC) implied by phrases used in nonstructured radiology reports with the risk inferred by hepatologists. MATERIALS AND METHODS: We performed a retrospective review of nonstructured radiology reports issued before Liver Imaging and Reporting Data System (LI-RADS) adoption from four-phase liver CT examinations of patients at risk for HCC. The phrase used by the radiologist in the report impression to describe each focal liver observation was recorded. Five hepatologists independently inferred the LI-RADS category from each phrase. Two abdominal radiologists independently reviewed the images and, blinded to all other information, assigned a LI-RADS category to each observation. Discrepancies were resolved by consensus. RESULTS: One hundred five observations in 77 patients were reported by 23 radiologists using 29 phrases. The most common phrase, "consistent with HCC" (n = 20), was applied to radiologist-assigned LR-3 (n = 1), LR-4 (n = 5), LR-5 (n = 11), and LR-5V (n = 3) observations. Eleven phrases were used more than once. Sixteen phrases were associated with LR-4 or higher observations; among these, hepatologists misinterpreted 37% of LR-4 or lower observations as definitely HCC and 46% of LR-5 and LR-5V observations as not definitely HCC. Overall, there was modest correlation (r = 0.69) between radiologist-assigned and hepatologist-inferred categories. CONCLUSION: Nonstandardized terminology results in inaccurate communication of HCC risk. Structured reporting systems such as LI-RADS may improve communication by conveying unambiguous estimates of malignancy risk.

A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver.

UNLABELLED: Identification of microRNAs (miRNAs) that regulate lipid metabolism is important to advance the understanding and treatment of some of the most common human diseases. In the liver, a few key miRNAs have been reported that regulate lipid metabolism, but since many genes contribute to hepatic lipid metabolism, we hypothesized that other such miRNAs exist. To identify genes repressed by miRNAs in mature hepatocytes in vivo, we injected adult mice carrying floxed Dicer1 alleles with an adenoassociated viral vector expressing Cre recombinase specifically in hepatocytes. By inactivating Dicer in adult quiescent hepatocytes we avoided the hepatocyte injury and regeneration observed in previous mouse models of global miRNA deficiency in hepatocytes. Next, we combined gene and miRNA expression profiling to identify candidate gene/miRNA interactions involved in hepatic lipid metabolism and validated their function in vivo using antisense oligonucleotides. A candidate gene that emerged from our screen was lipoprotein lipase (Lpl), which encodes an enzyme that facilitates cellular uptake of lipids from the circulation. Unlike in energy-dependent cells like myocytes, LPL is normally repressed in adult hepatocytes. We identified miR-29a as the miRNA responsible for repressing LPL in hepatocytes, and found that decreasing hepatic miR-29a levels causes lipids to accumulate in mouse livers. CONCLUSION: Our screen suggests several new miRNAs are regulators of hepatic lipid metabolism. We show that one of these, miR-29a, contributes to physiological lipid distribution away from the liver and protects hepatocytes from steatosis. Our results, together with miR-29a's known antifibrotic effect, suggest miR-29a is a therapeutic target in fatty liver disease.

Plasma FGF21 concentrations, adipose fibroblast growth factor receptor-1 and ß-klotho expression decrease with fasting in northern elephant seals.

Fibroblast growth factor (FGF)-21 is secreted from the liver, pancreas, and adipose in response to prolonged fasting/starvation to facilitate lipid and glucose metabolism. Northern elephant seals naturally fast for several months, maintaining a relatively elevated metabolic rate to satisfy their energetic requirements. Thus, to better understand the impact of prolonged food deprivation on FGF21-associated changes, we analyzed the expression of FGF21, FGF receptor-1 (FGFR1), ß-klotho (KLB; a co-activator of FGFR) in adipose, and plasma FGF21, glucose and 3-hydroxybutyrate in fasted elephant seal pups. Expression of FGFR1 and KLB mRNA decreased 98% and 43%, respectively, with fasting duration. While the 80% decrease in mean adipose FGF21 mRNA expression with fasting did not reach statistical significance, it paralleled the 39% decrease in plasma FGF21 concentrations suggesting that FGF21 is suppressed with fasting in elephant seals. Data demonstrate an atypical response of FGF21 to prolonged fasting in a mammal suggesting that FGF21-mediated mechanisms have evolved differentially in elephant seals. Furthermore, the typical fasting-induced, FGF21-mediated actions such as the inhibition of lipolysis in adipose may not be required in elephant seals as part of a naturally adapted mechanism to support their unique metabolic demands during prolonged fasting.

Preoperative Imaging in Cochlear Implants.

OBJECTIVE: To determine the utility of computed tomography (CT) and magnetic resonance imaging (MRI) in cochlear implant candidates. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: A total of 207 cochlear implanted patients with CT and/or MRI. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Age versus abnormal radiologic findings, imaging abnormality versus postoperative outcomes, postoperative outcomes versus electrode design, Cambridge Cochlear Implant Protocol (CCIP) status for imaging abnormalities, sensitivity and specificity of CT and MRI for round-window/cochlear occlusion, and MRI for incomplete partitions. RESULTS: A total of 207 patients with CT, MRI, or both were reviewed retrospectively. Less than half (15.5%) of CT scans had findings that might affect surgical intervention compared with 5.9% of MRI. No significant difference was found between children and adults for relevant imaging abnormalities (grade 4 or higher) with either CT (p = 0.931) or MRI (p = 0.606). CCIP status correlated with cochlear abnormalities (p = 0.040); however, only 46.2% of radiographic abnormalities on CT would be identified by these criteria. For detecting cochlear occlusion requiring surgical intervention, the sensitivity and specificity for CT were 40% (4 of 10; 95% confidence interval [CI], 12.16-73.76) and 95.73% (95% CI, 91.40-98.27), respectively. For MRI, the sensitivity and specificity were 33.33% (1 of 3; 95% CI, 0.84-90.57) and 96.97% (63 of 65; 95% CI, 89.32-99.63), respectively. There was no difference for postoperative AzBio scores for higher-grade imaging abnormalities (p = 0.6012) or for electrode designs (p = 0.3699). CONCLUSIONS: Significant radiographic abnormalities were relatively uncommon in cochlear implant patients on either CT or MRI at our single-center institution. If present, abnormal imaging findings rarely translated to management changes. CCIP status does not reliably predict which patients are likely to have abnormalities. Both MRI and CT have low sensitivity for round-window or cochlear occlusion, but detection likely leads to changes in surgical management.

Incidence of Blepharoptosis Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To determine the incidence of blepharoptosis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and compare the rates of blepharoptosis between patients injected with an eyelid speculum and those injected without a speculum. DESIGN: Retrospective cohort study. METHODS: International Classification of Diseases, Tenth Revision (ICD-10), codes were used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis after intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as controls. The outcomes were the incidence of ptosis in the injection group compared to the noninjection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without a speculum. RESULTS: We recruited 1100 exudative AMD patients who received at least 1 intravitreal anti-VEGF injection and 2258 nonexudative AMD patients who had not received an injection. In the injection group, 18 of 1100 patients (1.6%) developed ptosis, compared with 52 of 2258 patients (2.3%) in the noninjection group (P = .25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months after the initial injection, and after more than a 1-year injection-free period. Eleven of 537 patients (2.0%) injected without a speculum developed ptosis, compared with 8 of 444 patients (1.8%) injected with a speculum (P = .82). CONCLUSIONS: No statistically significant differences in incidence rates of ptosis were observed. In this analysis, neither intravitreal anti-VEGF injections nor speculum use during injections appears to increase the risk of ptosis.

Impact of time of day on outcomes after stereotactic radiosurgery for non-small cell lung cancer brain metastases.

BACKGROUND: This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non-small cell lung cancer (NSCLC) brain metastases. METHODS: At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables. RESULTS: Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS. CONCLUSIONS: Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables.

Outcomes of metallic biliary stent insertion in patients with malignant bilobar obstruction.

PURPOSE: To assess clinical outcomes of metal stent insertion in patients with bilobar bile duct obstruction by malignant tumors. MATERIALS AND METHODS: Records of 120 consecutive patients who underwent placement of metallic stents for palliation of malignant bilobar biliary obstruction between 1995 and 2010 were retrospectively reviewed. Single-duct stent insertion was performed in 44 patients with one liver lobe that accounted for more than 70% of total liver volume or only one patent lobar portal vein (group 1). Bilobar stent insertion was performed in 60 patients with approximately equal lobe sizes, patent lobar portal veins, or cholangitis at presentation (group 2). In 16 patients with discontiguous right anterior and posterior segmental ducts (group 3), three stents were deployed in the left lobar and right anterior and posterior segmental ducts. Overall survival, primary patency, and patient morbidity rates following stent insertion were assessed. RESULTS: No significant differences in mean overall survival (group 1, 7.3 mo; group 2, 10.3 mo; group 3, 6.5 mo; P = .21) or mean primary stent patency (group 1, 4.2 mo; group 2, 5.9 mo; group 3, 3.5 mo; P = .17) were demonstrated. However, patients in group 3 were significantly more likely to require hospitalizations for cholangitis and additional invasive procedures for recurrent biliary obstruction than patients in groups 1 and 2. CONCLUSIONS: Unilobar and bilobar metal stent insertion led to similar outcomes when treatment decision was based on relative liver lobe volumes, lobar portal vein patency, and presence of cholangitis on presentation.

Quantitative Evaluation of Aerosol Generation During In-Office Flexible Laryngoscopy.

Importance: Despite growing scientific knowledge and research, it is still unknown if office flexible laryngoscopy (FL) is aerosol generating and thereby potentially increases the risk of SARS-CoV-2 transmission. The limited literature that exists is conflicting, precluding formal conclusions. Objective: To determine whether FL is aerosol generating. Design, Setting, and Participants: This prospective cohort study included 134 patients seen in the otolaryngology clinic at a single tertiary care academic institution between February and May 2021. Two optical particle sizer instruments were used, quantifying particles ranging from 0.02 µm to 5 µm. Measurements were taken every 30 seconds, with sample periods of 15 seconds throughout the patient encounter. Instruments were located 12 inches from the patient's nares. Timing of events was recorded, including the start and end of physical examination, topical spray administration, start and end of laryngoscopy, and other potential aerosol-generating events (eg, coughing, sneezing). Data analysis was performed from February to May 2021. Exposures: Office examination and office FL. Main Outcomes and Measures: Bayesian online change point detection (OCPD) algorithm was used to detect significant change points (CPs) in this time-series data. The primary outcome was significant CP after FL compared with baseline physiologic variations, such as breathing and phonation. Results: Data were collected from 134 patients between February and May 2021. Ninety-one encounters involved FL. Of this group, 51 patients (56%) wore no mask over their mouth during FL. There was no statistically significant CP in either visits involving FL or visits where FL was not performed. Use of nasal spray did not result in CP in aerosol levels. Overall, neither the number of people present in the examination room, masks over patients' mouth, the duration of the visit, nor the duration of FL were associated with mean aerosol counts, regardless of the exposure. For larger aerosol sizes (≥1 µm), however, rooms with higher air exchange rates had significantly higher reductions in mean aerosol counts for visits involving FL. Conclusions and Relevance: The findings of this cohort study support that FL, including topical spray administration, is not a significant aerosol-generating procedure. The Bayesian OCPD model has a promising application for future aerosol studies in otolaryngology.

Prophylactic Unfractionated Subcutaneous Heparin Does Not Increase Postoperative Hemorrhage in Elderly Patients Undergoing Emergency Neurosurgical Procedures.

Purpose The purpose of this study is to evaluate the impact in the development of intracerebral hemorrhage in elderly critically ill patients who received prophylactic subcutaneous unfractionated heparin (SCUFH) less than 24 hours after undergoing emergency neurosurgery.  Methods A retrospective analysis was performed on patients who underwent emergency neurosurgery and were admitted to the surgical intensive care unit (SICU) at a tertiary care center over a 10-year period. Administration of prophylactic SCUFH within 24 hours of neurosurgery was required for inclusion. Demographic and clinical characteristics were recorded. The primary outcome was a rate of postoperative hemorrhagic complications with respect to age. Results We identified 223 emergency neurosurgical patients: 100 (45%) patients did not receive prophylactic SCUFH and were excluded. The remaining 123 (55%) patients met all inclusion criteria, of whom 73 (59%) patients were under 65 years old, and 50 (41%) patients were over 65 years old. Patients under 65 years old had significantly lower body mass index (BMI), lower Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, and Simplified Acute Physiology Score (SAPS) scores, and shorter median SICU length of stay compared to patients over 65 years old. No statistically significant difference in the rate of postoperative hemorrhagic or non-hemorrhagic neurological complications was observed between patients in either age group.  Conclusion Age over 65 years was not associated with a higher risk of postoperative hemorrhage in patients who received SCUFH after emergency neurosurgery. SCUFH can be safely used as a chemoprophylactic agent against venous thromboembolism for elderly patients when used within 24 hours after emergency neurosurgery.

Deep sleep and beeps II: Sleep quality improvement project in general surgery patients.

BACKGROUND: Poor sleep leads to poor health outcomes. Phase I of our sleep quality improvement project showed severe sleep disturbance in the ward setting. We implemented a novel PostOp Pack to improve sleep quality. METHODS: Patients underwent elective, general surgery procedures. Fitbit trackers measured total sleep time. Patients completed the inpatient Richards-Campbell Sleep Questionnaire, which combines 5 domains into a cumulative score (0-100). Patients completed the outpatient Pittsburgh Sleep Quality Index preoperatively and postoperatively. Patients received the PostOp Pack, which included physical items and a sleep-protective order set to reduce nighttime awakenings. Patients from phase I served as the historical control. The primary outcome was the percentage of patients with Richards-Campbell Sleep Questionnaire total sleep score ≥50. The secondary outcomes included the mean Richards-Campbell Sleep Questionnaire domain scores and Fitbit total sleep time. RESULTS: A total of 49 patients were compared with 64 historical controls. The percentage of patients with a total sleep score ≥50 was significantly higher in patients receiving a PostOp Pack versus historical control (69% vs. 44%, difference 26%, 95% confidence interval 6.1-45%, P = .01). The mean Richards-Campbell Sleep Questionnaire Total Sleep Score was significantly higher in patients with a PostOp Pack (62 vs 49, mean difference 13, 95% confidence interval 6-21, P ≤ .01). The PostOp Pack Richards-Campbell Sleep Questionnaire domain scores were significantly higher in various areas: Sleep Latency (68 vs 49, P ≤ .01), Awakenings (56 vs 40, P = .01), Sleep Quality (61 vs 49, P = .02), and Noise Disturbance (70 vs 59, P = .04). Of all patients, 92% would use PostOp Pack again in a future hospitalization. No patients had a failure to rescue event with PostOp Pack. The mean total sleep time was significantly improved with PostOp Pack on night 1 (6.4 vs 4.7 hours, P = .03). CONCLUSION: The PostOp Pack improves inpatient sleep quality and is safe.

Therapeutic liver reconstitution with murine cells isolated long after death.

BACKGROUND & AIMS: Due to the shortage of donor organs, many patients needing liver transplantation cannot receive one. For some liver diseases, hepatocyte transplantation could be a viable alternative, but donor cells currently are procured from the same sources as whole organs, and thus the supply is severely limited. METHODS: Here, we investigated the possibility of isolating viable hepatocytes for liver cell therapy from the plentiful source of morgue cadavers. To determine the utility of this approach, cells were isolated from the livers of non-heart-beating cadaveric mice long after death and transplanted into fumarylacetoacetate hydrolase-deficient mice, a model for the human metabolic liver disease hereditary tyrosinemia type I and a stringent in vivo model for hepatic cell transplantation. RESULTS: Surprisingly, complete and therapeutic liver repopulation could be achieved with hepatocytes derived up to 27 hours post mortem. CONCLUSIONS: Competitive repopulation experiments showed that cadaveric liver cells had a repopulation capacity similar to freshly isolated hepatocytes. Importantly, viable hepatocytes also could be isolated from cadaveric primate liver (monkey and human) efficiently. These data provide evidence that non-heart-beating donors could be a suitable source of hepatocytes for much longer time periods than previously thought possible.

MicroRNAs control hepatocyte proliferation during liver regeneration.

UNLABELLED: MicroRNAs (miRNAs) constitute a new class of regulators of gene expression. Among other actions, miRNAs have been shown to control cell proliferation in development and cancer. However, whether miRNAs regulate hepatocyte proliferation during liver regeneration is unknown. We addressed this question by performing 2/3 partial hepatectomy (2/3 PH) on mice with hepatocyte-specific inactivation of DiGeorge syndrome critical region gene 8 (DGCR8), an essential component of the miRNA processing pathway. Hepatocytes of these mice were miRNA-deficient and exhibited a delay in cell cycle progression involving the G(1) to S phase transition. Examination of livers of wildtype mice after 2/3 PH revealed differential expression of a subset of miRNAs, notably an induction of miR-21 and repression of miR-378. We further discovered that miR-21 directly inhibits Btg2, a cell cycle inhibitor that prevents activation of forkhead box M1 (FoxM1), which is essential for DNA synthesis in hepatocytes after 2/3 PH. In addition, we found that miR-378 directly inhibits ornithine decarboxylase (Odc1), which is known to promote DNA synthesis in hepatocytes after 2/3 PH. CONCLUSION: Our results show that miRNAs are critical regulators of hepatocyte proliferation during liver regeneration. Because these miRNAs and target gene interactions are conserved, our findings may also be relevant to human liver regeneration.

Pulmonary Hemorrhage: An Unusual Life-Threatening Presentation of Factor IX Deficiency in a Monochorionic-Diamniotic Twin Neonate.

Pulmonary hemorrhage is a rare, life-threatening condition affecting premature infants. There is no single etiological explanation for it but some common denominators include the presence of extreme prematurity, respiratory distress syndrome, surfactant use, birth asphyxia, etc. Although the incidence of pulmonary hemorrhage in neonates may be small, it is associated with a high risk of mortality. Congenital bleeding disorders such as hemophilia are rare coagulation disorders that have been known to present in the early neonatal period with an increased tendency for bleeding after blood draws, circumcision, surgical interventions, intracranial hemorrhage, oral or mucosal bleeding, and very rarely as gastrointestinal hemorrhage. There are no reports so far in the published literature of hemophilia presenting as pulmonary hemorrhage in early life. We report an unusual primary presentation of hemophilia B in a premature, monochorionic-diamniotic twin with acute life-threatening pulmonary hemorrhage with no family history of bleeding disorders.

Outcomes of balloon occlusion in the University of California Morbidly Adherent Placenta Registry.

BACKGROUND: Morbidly adherent placenta, also known as placenta accreta spectrum, is associated with severe maternal morbidity and mortality. Multiple adjunctive procedures have been proposed to improve outcomes, and at many institutions, interventional radiologists will play a role in assisting obstetricians in these cases. OBJECTIVE: The objective of the study was to evaluate the outcomes of women with morbidly adherent placenta who underwent cesarean hysterectomy with aortic balloon occlusion or internal iliac artery balloon occlusion catheters, compared with cesarean hysterectomy with surgical ligation of the iliac arteries, or cesarean hysterectomy without adjunctive procedures. STUDY DESIGN: A retrospective review of women with morbidly adherent placenta treated with cesarean hysterectomy was performed at 5 institutions from May 2014 to April 2018. The balloon occlusion group had either prophylactic aortic or iliac balloons placed prior to cesarean hysterectomy. Comparison groups included those who underwent internal iliac artery ligation prior to hysterectomy or a control group if they underwent cesarean hysterectomy without adjuvant procedures. Evaluated outcomes include estimated blood loss, transfusion requirements, intensive care unit admission, and adverse event rates. RESULTS: There were 171 women with morbidly adherent placenta included in the study. Twenty-eight had balloon placement prior to cesarean hysterectomy, 18 had intraoperative internal iliac artery ligation, and there were 125 control women who underwent cesarean hysterectomy without any adjunctive procedures. Compared with the women who underwent cesarean hysterectomy without adjunctive procedures, women who underwent aortic or iliac artery balloon occlusion prior to hysterectomy had significantly lower estimated blood loss (30.9% decrease, P < .001), transfusion requirements (76.8% decrease, P < .001), intensive care unit admission rates (0% vs 15.2%, P < .001), and intensive care unit stay lengths (0.0 vs 3.1 days, P < .001). Compared with women who underwent surgical ligation of the internal iliac arteries prior to hysterectomy, women who underwent aortic or iliac artery balloon occlusion prior to cesarean hysterectomy had lower estimated blood loss (54.2% decrease, P < .01), transfusion requirements (90.5% decrease, P < .001), operating room times (40.0% decrease, P < .01), intensive care unit admissions rates (0% vs 77.8%, P < .001), intensive care unit stay lengths (0.0 vs 1.4 days, P < .001), and adverse events (3.6% vs 44.4%, P < .01). CONCLUSION: Aortic and iliac artery balloon occlusion are associated with lower estimated blood loss, transfusion requirements, intensive care unit admission rates, and adverse event rates compared with women who underwent internal iliac artery ligation prior to cesarean hysterectomy or women who had no adjunctive interventions prior to cesarean hysterectomy for morbidly adherent placenta.