Somatostatin Regulates the Extracellular Regulated Kinase Cascade of Human Rheumatoid Arthritis Synoviocytes

Somatostatin (SRIF, somatotropin release inhibitory factor) is a ubiquitously expressed neuropeptide, interacting with cells via five SRIF receptor subtypes (sst.-sst.), belonging to the guanine nucleotide binding protein-coupled receptor (GPCR) superfamily. SRIF receptors have been well documented for their ability to inhibit cell proliferation and secretion in a variety of animal tissues. Over the past l S years, pre-clinical and clinical studies implicate that SRIF and SRIF analog therapy improve symptoms in patients suffering from rheumatoid arthritis (RA). In this study, we investigate SRIF\u27s effects on intracellular signaling in the synovium, the cellular layer that lines synovial joints, using in vitro cultures of human synovial fibroblasts. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis of synovial isolated mRNA established the presence of sst, in these cells. The sst, receptor links somatostatin action to control of synovial intracellular signaling. We have examined SRIF effects on the synoviocyte extracellular regulated kinase pathway (ERK). Using phospho-specific antisera, we demonstrate that SRIF and SRIF analogs decrease phospho-ERK.1/2 levels, suggesting basal ERK.1/2 is upregulated in RA synoviocytes. SRIF also suppressed basal levels of activated Raf and MEKl/2, two upstream regulatory kinases ofERKl/2. Furthermore, SRIF suppressed 1NFa­ stimulated activation ofERK.112 in RA synoviocytes. We also observed that SRIF increases a sodium vanadate-sensitive intracellular protein phosphatase activity in RA synoviocytes, indicating a possible intracellular mechanism by which SRIF controls the phosphorylation status of the ERK.112 kinases. Fluorescent confocal scanning microscopy reveals that TNF-o. stimulated the localization of phospho-ERK.112 in the nuclei of RA synoviocytes, which was inhibited upon co-treatment with SRIF. Taken together our results demonstrate that SRIF regulates intracellular signaling in rheumatoid synoviocytes

Somatostatin Regulates the Extracellular Regulated Kinase Cascade of Human Rheumatoid Arthritis Synoviocytes

Somatostatin (SRIF, somatotropin release inhibitory factor) is a ubiquitously expressed neuropeptide, interacting with cells via five SRIF receptor subtypes (sst.-sst.), belonging to the guanine nucleotide binding protein-coupled receptor (GPCR) superfamily. SRIF receptors have been well documented for their ability to inhibit cell proliferation and secretion in a variety of animal tissues. Over the past l S years, pre-clinical and clinical studies implicate that SRIF and SRIF analog therapy improve symptoms in patients suffering from rheumatoid arthritis (RA). In this study, we investigate SRIF\u27s effects on intracellular signaling in the synovium, the cellular layer that lines synovial joints, using in vitro cultures of human synovial fibroblasts. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis of synovial isolated mRNA established the presence of sst, in these cells. The sst, receptor links somatostatin action to control of synovial intracellular signaling. We have examined SRIF effects on the synoviocyte extracellular regulated kinase pathway (ERK). Using phospho-specific antisera, we demonstrate that SRIF and SRIF analogs decrease phospho-ERK.1/2 levels, suggesting basal ERK.1/2 is upregulated in RA synoviocytes. SRIF also suppressed basal levels of activated Raf and MEKl/2, two upstream regulatory kinases ofERKl/2. Furthermore, SRIF suppressed 1NFa­ stimulated activation ofERK.112 in RA synoviocytes. We also observed that SRIF increases a sodium vanadate-sensitive intracellular protein phosphatase activity in RA synoviocytes, indicating a possible intracellular mechanism by which SRIF controls the phosphorylation status of the ERK.112 kinases. Fluorescent confocal scanning microscopy reveals that TNF-o. stimulated the localization of phospho-ERK.112 in the nuclei of RA synoviocytes, which was inhibited upon co-treatment with SRIF. Taken together our results demonstrate that SRIF regulates intracellular signaling in rheumatoid synoviocytes

Improving Proficiency in Central Venous Catheter Insertion: Standardized Simulation Based Training for Internal Medicine House Staff

Objectives: The objectives of this study are to assess residents\u27 pre-workshop ability and comfort with CVC placement, undergo a standardized online didactic and hands-on clinical training simulation workshop, and subsequently undergo a proficiency test using simulation models to assess competency. The goal of a standardized training module is to create a universal approach to CVC placement in our institution and improve comfort and technical ability of house staff. We hypothesize that this will reduce complications and improve patient care and safety.https://jdc.jefferson.edu/patientsafetyposters/1063/thumbnail.jp

A Guide to Point of Care Ultrasound Evaluation of Pneumonia

A patient presenting with fever, hypoxia, productive cough, and leukocytosis can be diagnosed with pneumonia without any imaging findings. However, we often rely on X-ray and computed tomography (CT) imaging to support the clinical diagnosis. Ultrasound is an effective imaging modality for identifying pneumonia without delay and radiation risks.1,2 A meta-analysis by Ye et al. in 2015 found that ultrasound diagnosis of pneumonia had a pooled sensitivity of 0.95 and a pooled specificity of 0.9, which is superior to X-ray imaging which had a pooled sensitivity of 0.77 and a similar pooled specificity of 0.9.3 This study used CT imaging as a gold standard for comparison

A Guide to Point of Care Ultrasound Lung and IVC Examination of a Volume Overloaded Patient

A patient presents with dyspnea, hypoxia, and lower extremity edema. Their history is notable for recent high salt intake and non-compliance with diuretics, and their lungs have rales bilaterally. Clinically, we can diagnose a heart failure exacerbation with pulmonary edema. However, we often rely on X-ray and computed tomography (CT) imaging to support the clinical diagnosis and explore the etiology of the hypoxia and dyspnea to narrow the differential. Ultrasound is an effective modality for identifying pulmonary edema and pleural effusions while at the same time ruling out other etiologies such as pneumonia and pneumothorax. With bedside point of care ultrasound (POCUS), there is no radiation risk and no delay in obtaining imaging. A systematic review and meta-analysis study by Maw et al. published in 2019 found that lung ultrasound diagnosis of pulmonary edema in the setting of clinical suspicion for acute decompensated heart failure had a pooled sensitivity of 0.88 and specificity of 0.9, which is superior to X-ray imaging which demonstrated a pooled sensitivity of 0.73 and a pooled specificity of 0.9.

A Guide to Point of Care Ultrasound Examination of Acute Decompensated Heart Failure

A patient presents with dyspnea on exertion, orthopnea, and lower extremity edema. They have a prior history of coronary artery disease and reported episodes of chest pain three months ago. They did not seek medical evaluation at the time and have had no chest pain recently. In this setting, there is a high clinical suspicion of heart failure with concern for ischemic heart disease. The gold standard for diagnosis of heart failure is a formal transthoracic echocardiogram. Bedside point of care ultrasound (POCUS) is a tool that can provide essential information without delay in diagnosis

Preventing Iatrogenic Pneumothorax “Just-In-Time”

In 2020 a high incidence of iatrogenic pneumothorax was noticed at TJUH after internal jugular central line insertion - Accepted rate is 0.1% With long periods of time between ICU rotations, residents suffer from significant procedural skill decay The COVID-19 pandemic brought with it an increase in the number of central lines placed During the COVID-19 pandemic, there has been a lack of large group training opportunities due to social distancing constraints By December 31st 2021, our intervention will improve rates of iatrogenic pneumothorax after US-guided internal jugular central line insertion by 50% of baseline, as measured by chart review via Epic EMR

A Guide to Point of Care Ultrasound Examination of a Pericardial Effusion

A patient presents with pleuritic chest pain, dyspnea, and a recent viral illness. They have no prior cardiac or pulmonary history. Their X-ray on admission demonstrates no pulmonary findings and an enlarged cardiac silhouette, and their EKG is low voltage with electrical alternans. Ultrasound is an effective modality for identifying pericardial effusion and cardiac tamponade while at the same time evaluating for other causes, such as heart failure. Often patients with symptomatic pericardial ef fusion present with non-specific symptoms. While a “formal” transthoracic echocardiogram remains the gold standard for diagnosis, a bedside point of care ultrasound (POCUS) cardiac evaluation can significantly decrease the time to diagnosis and trigger an order for an urgent “formal” echocardiogram.1 A retrospective study by Hanson and Chan in 2021 found that POCUS led to an expedited average time to diagnosis of 5.9 hours compared to \u3e12 hours with other imaging. Those with a symptomatic pericardial effusion identified by POCUS had a significantly decreased time to treatment; time to pericardiocentesis of 28.1 hours compared to \u3e 48 hours with other diagnostic modalities.

Point-of-care versus central testing of hemoglobin during large volume blood transfusion.

BACKGROUND: Point-of-care (POC) hemoglobin testing has the potential to revolutionize massive transfusion strategies. No prior studies have compared POC and central laboratory testing of hemoglobin in patients undergoing massive transfusions. METHODS: We retrospectively compared the results of our point-of-care hemoglobin test (EPOC®) to our core laboratory complete blood count (CBC) hemoglobin test (Sysmex XE-5000™) in patients undergoing massive transfusion protocols (MTP) for hemorrhage. One hundred seventy paired samples from 90 patients for whom MTP was activated were collected at a single, tertiary care hospital between 10/2011 and 10/2017. Patients had both an EPOC® and CBC hemoglobin performed within 30 min of each other during the MTP. We assessed the accuracy of EPOC® hemoglobin testing using two variables: interchangeability and clinically significant differences from the CBC. The Clinical Laboratory Improvement Amendments (CLIA) proficiency testing criteria defined interchangeability for measurements. Clinically significant differences between the tests were defined by an expert panel. We examined whether these relationships changed as a function of the hemoglobin measured by the EPOC® and specific patient characteristics. RESULTS: Fifty one percent (86 of 170) of paired samples\u27 hemoglobin results had an absolute difference of ≤7 and 73% (124 of 170) fell within ±1 g/dL of each other. The mean difference between EPOC® and CBC hemoglobin had a bias of - 0.268 g/dL (p = 0.002). When the EPOC® hemoglobin was \u3c 7 g/dL, 30% of the hemoglobin values were within ±7, and 57% were within ±1 g/dL. When the measured EPOC® hemoglobin was ≥7 g/dL, 55% of the EPOC® and CBC hemoglobin values were within ±7, and 76% were within ±1 g/dL. EPOC® and CBC hemoglobin values that were within ±1 g/dL varied by patient population: 77% for cardiac surgery, 58% for general surgery, and 72% for non-surgical patients. CONCLUSIONS: The EPOC® device had minor negative bias, was not interchangeable with the CBC hemoglobin, and was less reliable when the EPOC® value was \u3c 7 g/dL. Clinicians must consider speed versus accuracy, and should check a CBC within 30 min as confirmation when the EPOC® hemoglobin is \u3c 7 g/dL until further prospective trials are performed in this population

Improving Time to Defibrillation at Thomas Jefferson University Hospital

Aims for Improvement Increase in timely defibrillation by 30% over 1 year Decrease in the amount of Vfib/VTach cardiac arrests that are not defibrillated to \u3c1% within a 1 year time fram