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Background & Aims Recently, international experts proposed redefining non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD), based on modified criteria. It is suspected that outcomes such as mortality may differ for these clinical entities. We studied the impact of MAFLD and NAFLD on all-cause and cause-specific mortality in US adults. Methods We analyzed data from 7,761 participants in the Third National Health and Nutrition Examination Survey and their linked mortality through 2015. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other known liver diseases. MAFLD was defined based on the criteria proposed by an international expert panel. The Cox proportional hazard model was used to study all-cause mortality and cause-specific mortality between MAFLD and NAFLD, with adjustments for known risk factors. Results During a median follow-up of 23 years, individuals with MAFLD had a 17% higher risk of all-cause mortality (hazard ratio [HR] 1.17; 95% CI 1.04-1.32). Furthermore, MAFLD was associated with a higher risk of cardiovascular mortality. NAFLD per se did not increase the risk of all-cause mortality. Individuals who met both definitions had a higher risk of all-cause mortality (HR 1.13, 95% CI 1.00-1.26), while individuals who met the definition for MAFLD but not NAFLD had a 1.7-fold higher risk of all-cause mortality (HR 1.66, 95% CI 1.19-2.32). Estimates for all-cause mortality were higher for those with advanced fibrosis and MAFLD than for those with advanced fibrosis and NAFLD. Conclusions In this US population-based study, MAFLD was associated with an increased risk of all-cause mortality, while NAFLD demonstrated no association with all-cause mortality after adjusting for metabolic risk factors. Lay summary Our findings provide further support for the idea that non-alcoholic fatty liver disease (NAFLD) is a part of a broader multi-system disease that also includes obesity, diabetes, high blood pressure, and high cholesterol. Therefore, re-defining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) may help improve our understanding of predictors that increase the risk of death.

Unlabelled: The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. Methods: A modified Delphi process was led by three large pan-national liver associations. Consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. Results: A total of 236 panellists from 56 countries participated in four online surveys and two hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83% and 78%, respectively. 74% of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms 'non-alcoholic' and 'fatty' were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease (SLD) was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least one of five cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic SLD. A new category, outside pure MASLD, termed MetALD was selected to describe those with MASLD who consume greater amounts of alcohol per week (140 to 350g/week and 210 to 420g/week for females and males respectively). Conclusions: The new nomenclature and diagnostic criteria are widely supported, non-stigmatising and can improve awareness and patient identification.

Pulse oximetry is widely used in clinical practice to monitor changes in arterial oxygen saturation (SpO2). However, decreases in SpO2 can be delayed relative to the actual clinical event, and near-infrared spectroscopy (NIRS) may detect alterations in oxygenation earlier than pulse oximetry, as shown in previous cerebral oxygenation monitoring studies.We aim to compare the response of transcutaneous muscle NIRS measures of the tissue saturation index with pulse oximetry SpO2 during hypoxia.Episodes of acute hypoxia were induced in nine anesthetized Yucatan miniature pigs. A standard pulse oximeter was attached to the ear of the animal, and a transcutaneous NIRS sensor was placed on the hind limb muscle. Hypoxia was induced by detaching the ventilator from the animal and reattaching it once the pulse oximeter reported 70% SpO2.Twenty-four episodes of acute hypoxia were analyzed. Upon the start of hypoxia, the transcutaneous NIRS measures changed in 5.3 ± 0.4 s, whereas the pulse oximetry measures changed in 14.9 ± 1.0 s (p0.0001).Transcutaneous muscle NIRS can detect the effects of hypoxia significantly sooner than pulse oximetry in the Yucatan miniature pig. A transcutaneous NIRS sensor may be used as an earlier detector of oxygen saturation changes in the clinical setting than the standard pulse oximeter.

One of the only currently available treatment options to potentially improve neurological recovery after acute spinal cord injury (SCI) is augmentation of mean arterial blood pressure (MAP) to promote blood flow and oxygen delivery to the injured cord. However, to optimize such hemodynamic management, clinicians require a method to monitor the physiological effects of these MAP alterations within the injured cord. Therefore, we investigated the feasibility and effectiveness of using a novel optical sensor, based on near-infrared spectroscopy (NIRS), to monitor real-time spinal cord oxygenation and hemodynamics during the first 7 days post-injury in a porcine model of acute SCI. Six Yucatan miniature pigs underwent a T10 vertebral level contusion-compression injury. Spinal cord oxygenation and hemodynamics were continuously monitored by a minimally invasive custom-made NIRS sensor, and by invasive intraparenchymal (IP) probes to validate the NIRS measures. Episodes of MAP alteration and hypoxia were performed acutely after injury, and at 2 and 7 days post-injury to simulate the types of hemodynamic changes SCI patients experience after injury. The NIRS sensor demonstrated the ability to provide oxygenation and hemodynamic measurements over the 7-day post-SCI period. NIRS measures showed statistically significant correlations with each of the invasive IP measures and MAP changes during episodes of MAP alteration and hypoxia throughout the first week post-injury (

Viral hepatitis can cause a wide spectrum of clinical presentations from a benign form with minimal or no symptoms to acute liver failure or death. Hepatitis D coinfection and superinfection have distinct clinical courses, with the latter more likely leading to chronic infection. Management of chronic hepatitis D virus is individualized because of the paucity of treatment options and significant side effect profile of currently available treatments. Sporadic cases of hepatitis E caused by contaminated meats are becoming increasingly prevalent in immunocompromised hosts. Human herpesviruses are an important cause of disease also in immunocompromised individuals.

KEY POINTS We have developed a novel porcine model of high-thoracic midline contusion spinal cord injury (SCI) at the T2 spinal level. We describe this model and the ensuing cardiovascular and neurohormonal responses, and demonstrate the model is efficacious for studying clinically relevant cardiovascular dysfunction post-SCI. We demonstrate that the high-thoracic SCI model, but not a low-thoracic SCI model, induces persistent hypotension along with a gradual reduction in plasma noradrenaline and increases in plasma aldosterone and angiotensin II. We additionally conducted a proof-of-concept long-term (12 weeks) survival study in animals with T2 contusion SCI demonstrating the potential utility of this model for not only acute experimentation but also long-term drug studies prior to translation to the clinic. ABSTRACT Cardiovascular disease is a leading cause of morbidity and mortality in the spinal cord injury (SCI) population, especially in those with high-thoracic or cervical SCI. With this in mind, we aimed to develop a large animal (porcine) model of high-thoracic (T2 level) contusion SCI and compare the haemodynamic and neurohormonal responses of this injury against a low-thoracic (T10 level) model. Ten Yorkshire pigs were randomly subjected to 20 cm weight drop contusion SCI at either the T2 or the T10 spinal level. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were continuously monitored until 4 h post-SCI. Plasma noradrenaline (NA), aldosterone and angiotensin II (ANGII) were measured pre-SCI and at 30, 60, 120 and 240 min post-SCI. Additionally, two Yucatan pigs were subjected to T2-SCI and survived up to 12 weeks post-injury to demonstrate the efficacy of this model for long-term survival studies. Immediately after T2-SCI, SBP, MAP and HR increased (P

Review. Clinical studies have shown that the hemodynamic management of patients following acute spinal cord injury (SCI) is an important aspect of their treatment for maintaining spinal cord (SC) perfusion and minimizing ischemic secondary injury to the SC. While this highlights the importance of ensuring adequate perfusion and oxygenation to the injured cord, a method for the real-time monitoring of these hemodynamic measures within the SC is lacking. The purpose of this review is to discuss current and potential methods for SC hemodynamic monitoring with special focus on applications using near-infrared spectroscopy (NIRS). A literature search using the PubMed database. All peer-reviewed articles on NIRS monitoring of SC published from inception to May 2019 were reviewed. Among 125 papers related to SC hemodynamics monitoring, 26 focused on direct/indirect NIRS monitoring of the SC. Current options for continuous, non-invasive, and real-time monitoring of SC hemodynamics are challenging and limited in scope. As a relatively new technique, NIRS has been successfully used for monitoring human cerebral hemodynamics, and has shown promising results in intraoperative assessment of SC hemodynamics in both human and animal models. Although utilizing NIRS to monitor the SC has been validated, applying NIRS clinically following SCI requires further development and investigation. NIRS is a promising non-invasive technique with the potential to provide real-time monitoring of relevant parameters in the SC. Currently, in its first developmental stages, further clinical and experimental studies are mandatory to ensure the validity and safety of NIRS techniques.

Background Bacterial translocation plays a pivotal role in the natural course of cirrhosis and its complications. Serum-derived bovine immunoglobulin (SBI) is an oral medical food that has been shown to both reduce inflammation in the intestines and neutralize bacteria. It represents a unique intervention that has not been studied in this population. Methodology We conducted a prospective open-label trial with an eight-week treatment phase of SBI. Individuals were assessed using lactulose breath testing, serum markers for enterocyte damage and bacterial translocation, and the Chronic Liver Disease Questionnaire (CLDQ) prior to and after completion of the treatment phase. Results We evaluated nine patients with a diagnosis of decompensated cirrhosis with ascites. Subjects had a mean Model for End-Stage Liver Disease (MELD) score of 11.6 ± 3.0 and were not taking lactulose or antibiotics. All subjects tolerated SBI well with no significant adverse events or changes to any of the six domains of the CLDQ. Laboratory tests including liver tests and MELD score remained stable over the course of treatment. There were no significant changes in the rates of small intestinal bacterial overgrowth (55.6% vs 55.6%, p = 1.00) or serum levels of lipopolysaccharide-binding protein, intestinal fatty acid-binding protein, or soluble CD14 (p-values 0.883, 0.765, and 0.748, respectively) when comparing values prior to and immediately after treatment. Conclusions No adverse events or significant changes to the quality of life were detected while on treatment. There were no statistically significant differences in our outcomes when comparing individuals before and after treatment in this small prospective proof-of-concept pilot study. Further prospective randomized studies could be beneficial.

Nonalcoholic fatty liver disease and chronic kidney disease are both chronic conditions with rapidly increasing prevalence and incidence worldwide that have led to a significant burden on health-care systems. The association between these two disease entities is partly attributed to shared cardiometabolic comorbidities including diabetes, hypertension, obesity, and metabolic syndrome. However, independent of these overlapping risks, there are increased rates and more severe CKD in NAFLD patients. Conversely, more progressive NAFLD is seen with advanced stages of kidney injury. In addition to overlapping risk factors, shared pathogenic mechanisms suggest these two disease entities may resemble different manifestations of a single underlying disease process.

Background: A customized sensor, based on near-infrared spectroscopy (NIRS), was developed to non-invasively monitor spinal cord hemodynamics after acute spinal cord injury (SCI). However, the effect of direct contact and emission of the NIRS signals on the spinal cord tissue structure was not clear. This information is essential because even minimal heating or contact pressure from the NIRS sensor placed over the injured spinal cord may lead to further damage to the spinal cord tissue. Here, we evaluate the safety of the custom-made NIRS sensor as it is essential prior to its clinical translation. Methods: A custom-made multi-wavelength miniaturized NIRS sensor was placed extradurally on the spinal cord of six Yucatan mini-pigs who received a T10 SCI. After seven days of continuous data collection at 100 Hz, the sensor was removed and the spinal cord tissue was examined. Histological assessment of the spinal cord revealed evidence of cellular damage at the NIRS sensor placement in two animals. An in-vitro experiment was performed to evaluate the possibility of heat damage caused by the NIRS sensor. Using a digital thermometer with two probes, one directly touching the NIRS emitter and the other one at a control site one centimeter away from the emitter. The amount of heat generation of the NIRS emitter after seven days of continuous operation at 100 Hz was measured and compared with the control site. Results: In-vitro heat tests showed no heat generation by the NIRS sensor. The temperature measured from the emitter site of the NIRS sensor and control temperature probe was identical during the seven days. Conclusion: The custom-made NIRS sensor does not generate heat at the emitter site and physical damage observed with regards to histology is due to the compression applied from the sensor. By refining the sensor to be smaller and more flexible with an even surface, we will improve the safety of the NIRS sensor before translating this technology to human patients. The new sensor will be further examined.

Introduction: Pulse oximetry is commonly used in critical care to monitor changes in arterial oxygen saturation (SpO2). However, studies have reported that decreases in SpO2 may lag behind the actual clinical event. Previous studies have demonstrated that cerebral oxygenation monitoring using near-infrared spectroscopy (NIRS) can detect alterations in oxygenation earlier than pulse oximetry. Here, we compare responses of NIRS monitoring of spinal cord tissue oxygenation (TOI) to pulse oximetry SpO2 during hypoxia. Methods: During a study on optical monitoring of spinal cord hemodynamics in an animal model of spinal cord injury (SCI), episodes of acute (70-80% SpO2) hypoxia were induced. Six anesthetized Yucatan miniature pigs were studied. A standard pulse oximeter was attached to the ear of the animal and a custom-made NIRS sensor was placed extradurally on the spinal cord. Hypoxia was induced by removing the ventilator from the animal and reattaching it once SpO2 reached 70% or 80% as reported by the pulse oximeter. Results: 21 episodes of acute hypoxia were analyzed. Upon the start of hypoxia, NIRS TOI responded in 1.8 ± 0.5 seconds, while pulse oximetry SpO2 responded in 11.4 ± 0.6 seconds (p > 0.0001). Conclusion: NIRS can detect the effects of hypoxia on spinal cord tissue earlier than pulse oximetry can detect arterial oxygenation changes in the periphery. The NIRS sensor may be used as an earlier detector of oxygen saturation changes in the clinical setting than the standard pulse oximeter.

Liver transplantation (LT) is definitive treatment for end‐stage liver disease. This study evaluated factors predicting successful evaluation in patients transferred for urgent inpatient LT evaluation. Eighty‐two patients with cirrhosis were transferred for urgent LT evaluation from January 2016 to December 2018. Alcohol‐associated liver disease was the common etiology of liver disease (42/82). Of these 82 patients, 35 (43%) were declined for LT, 27 (33%) were wait‐listed for LT, 5 (6%) improved, and 15 (18%) died. Psychosocial factors were the most common reasons for being declined for LT (49%). Predictors for listing and receiving LT on multivariate analysis included Hispanic race (odds ratio [OR], 1.89; P = 0.003), Asian race (OR, 1.52; P = 0.02), non‐Hispanic ethnicity (OR, 1.49; P = 0.04), hyponatremia (OR, 1.38; P = 0.04), serum albumin (OR, 1.13; P = 0.01), and Model for End‐Stage Liver Disease (MELD)‐Na (OR, 1.02; P = 0.003). Public insurance (i.e., Medicaid) was a predictor of not being listed for LT on multivariate analysis (OR, 0.77; P = 0.02). Excluding patients declined for psychosocial reasons, predictors of being declined for LT on multivariate analysis included Chronic Liver Failure Consortium (CLIF‐C) score >51.5 (OR, 1.26; P = 0.03), acute‐on‐chronic liver failure (ACLF) grade 3 (OR, 1.41; P = 0.01), hepatorenal syndrome (HRS) (OR, 1.38; P = 0.01), and respiratory failure (OR, 1.51; P = 0.01). Predictors of 3‐month mortality included CLIF‐C score >51.5 (hazard ratio [HR], 2.52; P = 0.04) and intensive care unit (HR, 8.25; P

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-4-reading-cheung a video presentation of this article - http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-4-interview-cheung an interview with the author https://www.wileyhealthlearning.com/Activity/7088571/disclaimerspopup.aspx questions and earn CME.

Current practice guidelines for acute spinal cord injury (SCI) recommend augmenting mean arterial blood pressure (MAP) for the first 7 days post-injury. After SCI, the cord may be compressed by the bone/ligaments of the spinal column, limiting regional spinal cord blood flow. Following surgical decompression, blood flow may be restored, and can potentially promote a "reperfusion" injury. The effects of MAP augmentation on the injured cord during the compressed and decompressed conditions have not been previously characterized. Here, we used our porcine model of SCI to examine the impact of MAP augmentation on blood flow, oxygenation, hydrostatic pressure, metabolism, and intraparenchymal (IP) hemorrhage within the compressed and then subsequently decompressed spinal cord. Yucatan mini-pigs underwent a T10 contusion injury followed by 2 h of sustained compression. MAP augmentation of ∼20 mm Hg was achieved with norepinephrine (NE). Animals received MAP augmentation either during the period of cord compression (CP), after decompression (DCP), or during both periods (CP-DCP). Probes to monitor spinal cord blood flow (SCBF), oxygenation, pressure, and metabolic responses were inserted into the cord parenchyma adjacent to the injury site to measure these responses. The cord was harvested for histological evaluation. MAP augmentation increased SCBF and oxygenation in all groups. In the CP-DCP group, spinal cord pressure steadily increased and histological analysis showed significantly increased hemorrhage in the spinal cord at and near the injury site. MAP augmentation with vasopressors may improve blood flow and reduce ischemia in the injured cord but may also induce undesirable increases in IP pressure and hemorrhage.

Infections remain a leading cause of morbidity and mortality among patients with liver failure. A number of factors, including relative immune dysfunction and systemic inflammation, bacterial translocation, gut dysbiosis, small intestine bacterial overgrowth, altered bile acid pools, and changes in pH due to acid suppression, contribute to the high rates of infection in this population. Though a range of infections can complicate the course of cirrhotic patients, spontaneous bacterial peritonitis (SBP), cholangitis, and cholecystitis in addition to other infections (i.e. pneumonia, urinary tract infection, bacteremia, and Clostridioides difficile colitis) are more common in this population and will be reviewed in this article. Preventative strategies are directed at minimizing the risk of SBP through the use of targeted antimicrobial prophylaxis. Lastly, the critically ill cirrhotic patient may present with an acute need for liver transplantation. Thus, careful assessment for ongoing infection should be performed and treated to optimize outcomes of transplant, if needed.

During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis. Using siRNA-mediated knockdown in mature adipocytes, we explored the effect of glucose transporters and glycolytic enzymes on brown adipocyte functions such as consumption of glucose and oxygen. Basal oxygen consumption in brown adipocytes was equally dependent on glucose and fatty acid oxidation, whereas isoproterenol (ISO)-stimulated respiration was fueled mainly by fatty acids, with a significant contribution from glucose oxidation. Knockdown of glucose transporters in brown adipocytes not only impaired ISO-stimulated glycolytic flux but also oxygen consumption. Diminishing glycolytic flux by knockdown of the first and final enzyme of glycolysis, i.e., hexokinase 2 (HK2) and pyruvate kinase M (PKM), respectively, decreased glucose uptake and ISO-stimulated oxygen consumption. HK2 knockdown had a more severe effect, which, in contrast to PKM knockdown, could not be rescued by supplementation with pyruvate. Hence, brown adipocytes rely on glucose consumption and glycolytic flux to achieve maximum thermogenic output, with glycolysis likely supporting thermogenesis not only by pyruvate formation but also by supplying intermediates for efferent metabolic pathways.

The focus in liver transplantation in the next 10 years will likely change from preventing viral disease recurrence to minimizing the toll of rejection and fatty liver disease, minimizing the complications from immunosuppression with withdrawal strategies, and more optimal management of long-term risks, such as malignancy, cardiovascular disease, and renal failure. In addition, now that short-term results (

Painful or threatening experiences trigger escape responses that are guided by nociceptive neuronal circuitry. Although some components of this circuitry are known and conserved across animals, how this circuitry is regulated at the genetic and developmental levels is mostly unknown. To escape noxious stimuli, such as parasitoid wasp attacks, Drosophila melanogaster larvae generate a curling and rolling response. Rover and sitter allelic variants of the Drosophila foraging (for) gene differ in parasitoid wasp susceptibility, suggesting a link between for and nociception. By optogenetically activating cells associated with each of for’s promoters (pr1–pr4), we show that pr1 cells regulate larval escape behavior. In accordance with rover and sitter differences in parasitoid wasp susceptibility, we found that rovers have higher pr1 expression and increased sensitivity to nociception relative to sitters. The for null mutants display impaired responses to thermal nociception, which are rescued by restoring for expression in pr1 cells. Conversely, knockdown of for in pr1 cells phenocopies the for null mutant. To gain insight into the circuitry underlying this response, we used an intersectional approach and activity-dependent GFP reconstitution across synaptic partners (GRASP) to show that pr1 cells in the ventral nerve cord (VNC) are required for the nociceptive response, and that multidendritic sensory nociceptive neurons synapse onto pr1 neurons in the VNC. Finally, we show that activation of the pr1 circuit during development suppresses the escape response. Our data demonstrate a role of for in larval nociceptive behavior. This function is specific to for pr1 neurons in the VNC, guiding a developmentally plastic escape response circuit.

Critically ill patients frequently present with the systemic inflammatory response syndrome, which is largely a reflection of the liver's response to injury. Underlying hepatic congestion is a major risk factor for hypoxic liver injury, the most common cause for hepatocellular injury. Cholestatic liver injury often occurs in critically ill patients due to inhibition of farnesoid X receptor (FXR), the main regulator of bile acid handling, particularly in the liver and intestines. Additional injury to the liver occurs due to alterations in the bile acid pool with increased cytotoxic forms and disturbance in the typical processing of xenobiotics in the liver.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly dominant cause of liver disease worldwide. The progressive subtype, nonalcoholic steatohepatitis, is a leading indication for liver transplantation and a noteworthy cause of hepatocellular carcinoma. The overall prevalence of NAFLD is on the rise, and even more concerning data modeling predicts that an increasing percentage of those with NAFLD will develop advanced disease. This increased volume of patients with advanced liver disease will impose a significant health care burden in terms of resources and cost. Thus, the identification of patients with established fibrosis or at high risk of developing advanced liver disease is critical to effectively intervene and prevent overall and liver-related morbidity and mortality. Herein, we provide a framework to consider for the identification of patients with NAFLD at high risk of nonalcoholic steatohepatitis with advanced fibrosis and provide a critical assessment of currently accessible diagnostic and treatment modalities.

Renal cell carcinoma can present with a variety of paraneoplastic syndromes. Reversible hepatic dysfunction in the setting of non-metastatic renal cell carcinoma is a rare paraneoplastic phenomenon that was first described by Stauffer in 1961. This clinical entity is characterized by reversal of liver chemistry abnormalities after resection of the primary tumor. Here we present an unusual case of non-metastatic hepatic dysfunction secondary to renal cell carcinoma, also known as Stauffer’s syndrome, in a 55-year old patient who presented with liver synthetic dysfunction and notable hyperbilirubinemia. Unlike earlier reports, the icteric variant of Staffer’s syndrome has been emerging as the predominantly reported variant in the recent literature. Moreover, poor correlation between the severity of hepatic dysfunction and the liver biopsy findings was noted. The variable and non-specific presenting symptoms and signs as well as the need for extensive evaluation for abnormal liver chemistry usually results in a delay in the diagnosis of the primary tumor. Therefore, physicians need to be familiar with this clinical entity as a possible reversible etiology of liver chemistry abnormalities in patients with renal and other solid tumors as this may guide further investigations, lead to earlier diagnosis and treatment of the primary tumor, and ultimately improve outcomes.

General purpose To provide information from a review of literature about economic evaluations of preventive strategies for pressure injuries (PIs). Target audience This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. Learning objectives/outcomes After participating in this educational activity, the participant should be better able to:1. Identify the purpose and methods used for this study.2. Compare costs and effectiveness related to preventative strategies for PIs. Abstract BACKGROUND: Pressure injuries (PIs) are a common and resource-intensive challenge for acute care hospitals worldwide. While a number of preventive strategies have the potential to reduce the cost of hospital-acquired PIs, it is unclear what approach is the most effective. Objective The authors performed a narrative review of the literature on economic evaluations of preventive strategies to survey current findings and identify important factors in economic assessments. Data sources Ovid, MEDLINE, NHS Economic Evaluation Databases, and the Cochrane Database of Systematic ReviewsSELECTION CRITERIA: Potentially relevant original research articles and systematic reviews were considered. Data extraction Selection criteria included articles that were written in English, provided data on cost or economic evaluations of preventive strategies of PIs in acute care, and published between January 2004 and September 2015. Data were abstracted from the articles using a standardized approach to evaluate how the items on the Consolidated Health Economic Evaluation Reporting Standards checklist were addressed. Data synthesis The searches identified 192 references. Thirty-three original articles were chosen for full-text reviews. Nineteen of these articles provided clear descriptions of interventions, study methods, and outcomes considered. Conclusions Limitations in the available literature prevent firm conclusions from being reached about the relative economic merits of the various approaches to the prevention of PIs. The authors' review revealed a need for additional high-quality studies that adhere to commonly used standards of both currently utilized and emerging ways to prevent hospital-acquired PIs.

Introduction The goal of this study was to compare the incidence of biliary strictures in orthotopic liver transplant (OLT) patients treated with previous transarterial chemoembolization (TACE) versus those with no TACE history. Patients and Methods A single-center retrospective review was performed on 248 patients who underwent OLT from 2006 to 2012. Patient demographic characteristics, history of TACE for treatment of hepatocellular carcinoma, OLT data, and biliary stricture data were obtained. TACE was generally performed in a segmental manner using chemotherapy to ethiodized oil mixture (1:1). Clinically significant biliary strictures resulting in cholestasis or obstructive jaundice were diagnosed by using endoscopic retrograde cholangiopancreatography. Group characteristics were compared by using the Wilcoxon rank sum test, χ 2 analysis, and Kaplan-Meier statistics with log-rank comparison. Results Forty-six patients (35 men, 11 women; median age, 58 years) with a history of pre-OLT TACE were compared with 185 patients (111 men, 74 women; median age, 54 years) with no history of TACE. TACE and non-TACE patients had 30% and 31% cumulative incidence of biliary stricture, respectively. The median time to stricture was not reached in either group. There was no statistically significant difference in biliary stricture incidence ( P = .928) or time to biliary stricture development ( P = .803). Biliary strictures were primarily anastomotic in location in both groups: 79% in TACE patients and 84% in non-TACE patients ( P = .233). Conclusions Selective TACE treatment of hepatocellular carcinoma in pretransplant patients does not increase the rate of posttransplant biliary strictures. These findings corroborate the safety of TACE in the treatment of hepatocellular carcinoma in potential OLT patients as a bridge to transplantation.

Research regarding the reliability of the Braden Scale and nurses' perspectives on the instrument for predicting pressure ulcer (PU) risk in acute care settings is limited. A mixed-methods study was conducted in a tertiary acute care facility to examine interrater reliability (IRR) of the Braden Scale and its subscales, and a qualitative survey using semi-structured interviews was conducted among nurses caring for patients in acute care units to gain nurse perspective regarding scale usability. Data were extracted from a previous retrospective, randomized, controlled trial involving adult patients with compromised mobility receiving care in a tertiary acute care hospital in Canada. One-way, intraclass correlation coefficients (ICCs) were calculated on item and total scores, and kappa statistics were used to determine reliability of categorizing patients on their risk. Interview results were categorized by common themes. Reliability was assessed on 64 patients, where nurses and research staff independently assessed enrolled participants at baseline and after 72 hours using the Braden Scale as it appeared on an electronic medical record. IRR for the total score was high (ICC = 0.807). The friction and shear item had the lowest reliability (ICC = 0.266). Reliability of categorizing patients' level of risk had moderate agreement (κ = 0.408). Three (3) major and 12 subthemes emerged from the 14 nurse interviews; nurses were aware of the scale's purpose but were uncertain of its effectiveness, some items were difficult to rate, and questions were raised as to whether using the scale enhanced patient care. Aspects identified by nurses to enhance usability included: 1) changes to the electronic version (incorporating the scale into daily assessment documents with readily available item descriptions), 2) additional training, and 3) easily available resource material to improve reliability and usability of scale. These findings need to be considered when using the Braden Scale in clinical practice. Further study of the value of the total Braden Scale and its subscales is warranted.

Primary mucinous adenocarcinoma of the appendix is a rare gastrointestinal malignancy. Fistulous tract formation is a complication that is cited in literature. An 85-year-old man with multiple comorbidities presented with several weeks of persistent non-bloody diarrhea. Laboratory work-up was non-diagnostic. Abdominal imaging with barium contrast showed an enterocolonic fistulous tract extending from the duodenum to the cecum involving an enlarged appendiceal mass. Subsequent biopsy confirmed mucinous appendiceal neoplasm with peritoneal spread to the liver and mesentery. This is the first report describing an enterocolonic fistula formation resulting from this malignancy.

Idiopathic hypereosinophilic syndrome (HES) is a rare diagnosis defined by the World Health Organization as a persistent eosinophilia for 6 months and resulting in end-organ dysfunction. While many patients present with nonspecific symptoms, others will present with symptoms of the affected organs, most commonly those involving the heart, skin, or nervous system. Gastrointestinal or liver involvement is estimated to affect up to one-third of patients with HES, although patients with clinically significant disease are limited to case reports. This is the first report of a patient presenting with hepatitis and achalasia related to idiopathic HES.

SummaryCell polarity plays a key role in the development of the central nervous system (CNS). Interestingly, disruption of cell polarity is seen in many cancers. ASPP2 is a haplo-insufficient tumor suppressor and an activator of the p53 family. In this study, we show that ASPP2 controls the polarity and proliferation of neural progenitors in vivo, leading to the formation of neuroblastic rosettes that resemble primitive neuroepithelial tumors. Consistent with its role in cell polarity, ASPP2 influences interkinetic nuclear migration and lamination during CNS development. Mechanistically, ASPP2 maintains the integrity of tight/adherens junctions. ASPP2 binds Par-3 and controls its apical/junctional localization without affecting its expression or Par-3/aPKCλ binding. The junctional localization of ASPP2 and Par-3 is interdependent, suggesting that they are prime targets for each other. These results identify ASPP2 as a regulator of Par-3, which plays a key role in controlling cell proliferation, polarity, and tissue organization during CNS development.

Objective: Missing medical equipment in health care settings decrease productivity, increase spending to replace losses, and potentially endanger patient safety. By documenting and investigating the causes of these incidents, strategies to prevent future occurrences can be developed.Methods: As an example of this approach, we describe the inadvertent disposal of an expensive medical device during a randomized controlled trial (RCT) conducted within a medical facility. The incident was carefully documented and investigated shortly after it occurred. This information was used to develop targeted interventions to prevent further occurrences.Results: The device was a mattress overlay connected to a computer monitor that generated a continuous pressure image for use by nursing staff in the prevention of pressure injuries. An Environmental Services staff member disposed of one of these devices when the room of an enrolled patient was cleaned following their transfer to another unit. Miscommunication (or a misunderstanding of communicated information) and lack of awareness were identified as the main causes of this error.Discussion: By using the loss as a learning opportunity, the investigation of the incident led to strategies for preventing future occurrences. These included frequent training sessions for staff and improvements in signage. A detailed, factual and timely investigation of the events around the loss of armamentarium coupled with analysis on how to prevent future occurrences should be considered for all incidents involving high cost equipment.Conclusions: A standardized, non-judgmental approach to documenting and investigating the causes of costly equipment loss can lead to strategies for improved asset management and the prevention of further incidents of this nature.

SummaryPyramidal neurons of the neocortex can be subdivided into two major groups: deep- (DL) and upper-layer (UL) neurons. Here we report that the expression of the AT-rich DNA-binding protein Satb2 defines two subclasses of UL neurons: UL1 (Satb2 positive) and UL2 (Satb2 negative). In the absence of Satb2, UL1 neurons lose their identity and activate DL- and UL2-specific genetic programs. UL1 neurons in Satb2 mutants fail to migrate to superficial layers and do not contribute to the corpus callosum but to the corticospinal tract, which is normally populated by DL axons. Ctip2, a gene required for the formation of the corticospinal tract, is ectopically expressed in all UL1 neurons in the absence of Satb2. Satb2 protein interacts with the Ctip2 genomic region and controls chromatin remodeling at this locus. Satb2 therefore is required for the initiation of the UL1-specific genetic program and for the inactivation of DL- and UL2-specific genes.