A location-based anatomic classification system for acute pancreatic fluid collections: Roadmap for optimal intervention in the step-up era.

Walled-off pancreatic necrosis (WOPN) is a local complication of acute necrotizing pancreatitis frequently requiring intervention. Treatment is typically through the coordinated efforts of a multidisciplinary team. Current management guidelines recommend a step-up approach beginning with minimally invasive techniques (percutaneous or transmural endoscopic drainage) followed by escalation to more invasive procedures if needed. Although the step-up approach is an evidence-based treatment paradigm for management of pancreatic fluid collections, it lacks guidance regarding optimal invasive technique selection based on the anatomic characteristics of pancreatic fluid collections. Similarly, existing cross-sectional imaging-based classification systems of pancreatic fluid collections have been used to predict disease severity and prognosis; however, none of these systems are designed to guide intervention. We propose a novel classification system which incorporates anatomic characteristics of pancreatic fluid collections (location and presence of disconnected pancreatic duct) to guide intervention selection and clinical decision making. We believe adoption of this simple classification system will help streamline treatment algorithms and facilitate cross-study comparisons for pancreatic fluid collections.

Spotlight on Givosiran as a Treatment Option for Adults with Acute Hepatic Porphyria: Design, Development, and Place in Therapy.

Small interfering ribonucleic acids [siRNAs] are short ribonucleic acid (RNA) fragments cleaved from double-stranded RNA molecules that target and bind to specific sequences on messenger RNA (mRNA), leading to their destruction. Therefore, the siRNA down-regulates the formation of selected mRNAs and their protein products. Givosiran is one such siRNA that uses this mechanism to treat acute hepatic porphyrias. Acute hepatic porphyrias are a group of rare, inherited metabolic disorders, characterized by acute potentially life-threatening attacks as well as chronic symptoms with a negative impact on quality of life. It has four types, each associated with distinct enzyme defects in the heme biosynthesis pathway in the liver. By targeting the expression of hepatic 5-aminolevulinic acid [ALA] synthase-1 [ALAS1], givosiran can down-regulate levels of toxic metabolites, leading to biochemical and clinical improvement. Givosiran selectively targets hepatocytes due to its linkage to N-acetylgalactosamine (GalNac) leading to its selective uptake via asialoglycoprotein receptors (ASGPR). We provide an up-to-date literature review regarding givosiran in the context of a clinical overview of the porphyrias, an overview of siRNAs for therapy of human disorders, the design and development of givosiran, key clinical trial results of givosiran for prevention of acute porphyric attacks, emerging concerns regarding chronic use of givosiran, and the overall management of acute hepatic porphyrias. These insights are important not only for the management of acute hepatic porphyrias but also for the emerging field of siRNAs and their role in novel therapies for various diseases.

Clinical characteristics associated with idiopathic rapid gastric emptying in patients referred for gastric emptying studies.

OBJECTIVES: Rapid gastric emptying (RGE) is diagnosed using nuclear medicine gastric emptying scintigraphy (GES). The clinical symptoms are non-specific and its pathophysiology in the absence of gastric surgery is poorly understood. We aimed to evaluate the clinical characteristics associated with idiopathic RGE. METHODS: GES studies were reviewed from a database of 1958 4-hour solid-phase GES performed over an 8-year period. RGE was defined as <30% of the test meal remaining in the stomach at 1 hour. Patients who had had any gastric operation were excluded. A chart review was conducted to extract patients' baseline data and clinical characteristics. RESULTS: Of the 1958 GES studies reviewed, 156 (8.0%) patients had RGE, and 534 (27.3%) had delayed gastric emptying (>10% retained food at 4 h), respectively. Idiopathic RGE constituted 22.6% (156/690) of all abnormal GES studies. The patients' average age at diagnosis was 54.0 years and 53.8% of patients with RGE were female. Most (69.2%) of these studies were ordered with an initial clinical suspicion of gastroparesis, compared with only 12.2% with a suspicion of RGE. Among this idiopathic RGE cohort, 71.2% presented with symptoms of nausea, 42.9% with vomiting, 32.1% with abdominal pain, 21.2% with bloating and 17.9% with early satiety. Only 7.7% presented with diarrhea, 0.6% with palpitations and 0.6% with hypoglycemia. CONCLUSIONS: Idiopathic RGE is an important differential diagnosis in patients with symptoms classically associated with gastroparesis. Few have postprandial diarrhea or palpitations as their presenting symptom. Further studies of idiopathic RGE syndrome are warranted.

Are There Gender Differences Among Leaders of Regional Orthopaedic Societies of the United States?

BACKGROUND: Great efforts are currently being made toward improving gender and racial equity in orthopaedic surgery in the United States. Nonetheless, no research has reported on whether these efforts have increased representation of women and underrepresented minorities in leadership roles in orthopaedic surgery societies. QUESTIONS/PURPOSES: Are women proportionally represented in the leadership of regional orthopaedic societies in the United States? METHODS: The latest version of the American Association of Orthopaedic Surgeons census data was evaluated to determine the numbers (and percentages) of women and men practicing orthopaedic surgery in the United States. We also queried data for regional orthopaedic societies members who held a position of leadership (four societies; n = 53) between 2012 and 2017. Collected data included gender, years of experience, and practice setting. A chi-square analysis was conducted to compare the percentage of women in leadership with the percentage of women in practice in each of four geographic regions (Western Orthopaedic Association [WOA]; Southern Orthopaedic Association [SOA]; Eastern Orthopaedic Association [EOA]; Mid-America Orthopaedic Association [MAOA]) to see if the representation of women was proportional to that of men. RESULTS: With the numbers available, there was no difference in the observed-to-expected proportions between men and women in leadership in any of the regional societies we studied For the eastern region, there were 6% (392 of 6514) versus 0% (0 of 12; p = 0.591) of practicing women orthopaedic surgeons versus women orthopaedic surgeons holding positions in EOA leadership. For the Western region, there were 5% (304 of 5744) versus 7% (1 of 14; p = 0.836) practicing women orthopaedic surgeons versus women orthopaedic surgeons holding positions in WOA leadership. For the Midwest United States region, there were 6% (443 of 6937) versus 0% (0 of 15; p = 0.509) of practicing women orthopaedic surgeons versus women orthopaedic surgeons holding positions in MAOA leadership. For the Southern United States region, there were 4% (443 of 9601) versus 0% (0 of 13; p = 0.662) of practicing women orthopaedic surgeons versus women orthopaedic surgeons holding positions in SOA leadership. CONCLUSIONS: We found that women were represented in leadership roles in the regional societies in the United States in proportion to their overall numbers. However, that overall number was small, and so the percentages of regional society leaders who were women were correspondingly small. CLINICAL RELEVANCE: The low number of women orthopaedic surgeons holding leadership positions in regional societies are most likely a function of the low overall number of women orthopaedic surgeons, but focused efforts to change the status quo may increase the diversity of leadership in these societies.

Ultrasound in the Evaluation of Radial Neuropathies at the Elbow.

There are five sites at which radial nerve entrapment at the elbow has been commonly reported. These include the level of the fibrous bands within the extensor carpi radialis brevis, the thickened fascial tissue at the radiocapitellar joint, the leash of Henry, the arcade of Frohse, and the distal border of the supinator muscle. This review describes the anatomy of the radial nerve at the elbow and the surrounding structures, and then provides an overview of the literature supporting the use of ultrasound to assist in the evaluation of suspected radial neuropathy at the elbow. This review concludes with a suggested ultrasonographic approach for the systematic evaluation of suspected radial neuropathy at the elbow.

Assessing the accuracy of neuromuscular ultrasound for inclusion body myositis.

INTRODUCTION: Inclusion body myositis (IBM) can have clinical and electrodiagnostic features similar to other neuromuscular diseases, making it a diagnostic challenge. This prospective study was designed to determine the accuracy of forearm ultrasound for IBM. METHODS: Sixty adults were recruited (15 with IBM, 15 with amyotrophic lateral sclerosis [ALS], 15 with other myopathies, and 15 healthy controls), and each underwent ultrasound of the bilateral forearms (imaging the flexor digitorum profundus and flexor carpi ulnaris muscles). Three clinicians with varying ultrasound expertise assigned a diagnosis of IBM, ALS, other myopathy, or control, based on images alone. RESULTS: Intrarater reliability was moderately strong. Interrater reliability varied based on clinician experience. Sensitivity was 73.33% and 66.67% for the expert raters. Specificity was strong for all 3 clinicians (93.33%, 84.44%, and 91.11%). DISCUSSION: Neuromuscular ultrasound of the forearm is reliable and accurate for the diagnosis of IBM, although sensitivity was higher among experienced clinicians. Muscle Nerve 59:478-481, 2019.

Applying dynamic contrast enhanced MSOT imaging to intratumoral pharmacokinetic modeling.

Examining the dynamics of an agent in the tumor microenvironment can offer critical insights to the influx rate and accumulation of the agent. Intratumoral kinetic characterization in the in vivo setting can further elicudate distribution patterns and tumor microenvironment. Dynamic contrast-enhanced Multispectral Optoacoustic Tomographic imaging (DCE-MSOT) acquires serial MSOT images with the administration of an exogenous contrast agent over time. We tracked the dynamics of a tumor-targeted contrast agent, HypoxiSense 680 (HS680), in breast xenograft mouse models using MSOT. Arterial input function (AIF) approach with MSOT imaging allowed for tracking HS680 dynamics within the mouse. The optoacoustic signal for HS680 was quantified using the ROI function in the ViewMSOT software. A two-compartment pharmacokinetics (PK) model constructed in MATLAB to fit rate parameters. The contrast influx (kin) and outflux (kout) rate constants predicted are kin = 1.96 × 10-2 s-1 and kout = 9.5 × 10-3 s-1 (R = 0.9945).