Publications by authors named "Steven H Yale"

91 Publications

Replacing Bell Palsy with Idiopathic Facial Nerve Paralysis: What Says the Evidence?

Am J Med 2021 May;134(5):e358

Division of General Internal Medicine, University of Florida, Gainesville.

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http://dx.doi.org/10.1016/j.amjmed.2020.07.009DOI Listing
May 2021

The history of observed signs of acute appendicitis and peritoneal inflammation.

Am J Emerg Med 2021 Apr 17. Epub 2021 Apr 17.

University of Florida, Division of General Internal Medicine, 2000 SW Archer Rd., Gainesville, FL 32608, United States.

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http://dx.doi.org/10.1016/j.ajem.2021.04.036DOI Listing
April 2021

Teaching physical examination signs as a novel applied diagnostic skill in medical education.

North Clin Istanb 2021 15;8(1):111-112. Epub 2021 Jan 15.

Marshfield Clinic Research Institute, WI, United States of America.

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http://dx.doi.org/10.14744/nci.2020.53325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881435PMC
January 2021

Letter in response to the article: "Blood glucose levels should be considered as a new vital sign indicative of prognosis during hospitalization" (Kesavdev et al.).

Diabetes Metab Syndr 2021 Jan-Feb;15(1):465. Epub 2021 Feb 6.

University of Central Florida College of Medicine, 6850 Lake Nona Blvd, Orlando, FL, 32827, USA. Electronic address:

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http://dx.doi.org/10.1016/j.dsx.2021.02.005DOI Listing
April 2021

Left hand index finger predominance of Quincke pulse.

North Clin Istanb 2020 28;7(4):415-416. Epub 2020 May 28.

Marshfield Clinic Research Institute, Wisconsin, USA.

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http://dx.doi.org/10.14744/nci.2020.04710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521101PMC
May 2020

Fitz-Hugh-Curtis and Peritonitis: Sorting Through the Features that Define This Syndrome.

Am J Med 2020 10;133(10):e611

University of Florida, Division of General Internal Medicine, Gainesville.

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http://dx.doi.org/10.1016/j.amjmed.2020.04.007DOI Listing
October 2020

Learning about the diagnosis of Bouveret syndrome from Bouveret.

J Microbiol Immunol Infect 2021 Apr 18;54(2):339-340. Epub 2020 Jul 18.

University of Florida, Division of General Internal Medicine, 2000 SW Archer Rd. Gainesville, FL 32608, USA.

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http://dx.doi.org/10.1016/j.jmii.2020.07.005DOI Listing
April 2021

Fothergill and Carnett signs and rectus sheath hematoma.

J Rural Med 2020 Jul 17;15(3):130-131. Epub 2020 Jul 17.

Division of General Internal Medicine, University of Florida, USA.

Fothergill and Carnett signs are used to distinguish intrabdominal from abdominal wall diseases. These bedside techniques may be useful in distinguishing intrabdominal from an abdominal wall cause of disease. Timely and accurate diagnosis of rectus sheath hematoma in at risk patients in the appropriate clinical setting is important because of the associated morbidity and mortality associated with this condition. Diagnosis requires an accurate and thorough history and bedside physical examination and performance of these maneuvers as originally described.
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http://dx.doi.org/10.2185/jrm.2019-019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369406PMC
July 2020

Tomisaku Kawasaki and Kawasaki disease.

Childs Nerv Syst 2020 Jul 11. Epub 2020 Jul 11.

University of Florida, Division of General Internal Medicine, 2000 SW Archer Rd., Gainesville, FL, 32608, USA.

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http://dx.doi.org/10.1007/s00381-020-04784-3DOI Listing
July 2020

A bedside technique and historical aspects of the cutaneous findings in scurvy.

Int J Surg Case Rep 2020 21;71:126-127. Epub 2020 May 21.

University of Florida, Division of General Internal Medicine, 2000 SW Archer Rd., Gainesville, FL 32608, United States. Electronic address:

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http://dx.doi.org/10.1016/j.ijscr.2020.04.105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256203PMC
May 2020

Lemierre Syndrome: An emerging not forgotten disease.

J Microbiol Immunol Infect 2021 Apr 7;54(2):331-332. Epub 2020 May 7.

University of Florida, Division of General Internal Medicine, 2000 SW Archer Rd. Gainesville, FL, 32608, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jmii.2020.04.016DOI Listing
April 2021

Administrative codes inaccurately identify recurrent venous thromboembolism: The CVRN VTE study.

Thromb Res 2020 05 5;189:112-118. Epub 2020 Mar 5.

University of California, San Francisco, 533 Parnassus Ave., Box 0131, room U135, San Francisco, CA 94143, United States of America.. Electronic address:

Background: Studies using administrative data commonly rely on diagnosis codes to identify venous thromboembolism (VTE) events. Our objective was to assess the validity of using International Classification of Disease, 9th Revision (ICD-9) codes in identifying recurrent VTE.

Materials And Methods: Among 5497 adults with confirmed incident VTE from four healthcare delivery systems in the Cardiovascular Research Network (CVRN), we identified all subsequent inpatient, emergency department (ED), and ambulatory clinical encounters associated with an ICD-9 code for VTE (combined with relevant radiology procedure codes for inpatient/ED VTE codes in the secondary discharge position or outpatient codes) during the follow-up period. Medical records were reviewed using standardized diagnostic criteria to assess for the presence of new, recurrent VTE. The positive predictive value (PPV) of codes was calculated as the number of valid events divided by total encounters.

Results: We identified 2397 encounters that were considered potential recurrent VTE by ICD-9 codes. However, only 31.1% (95%CI: 29.3-33.0%) of encounters were verified by reviewers as true recurrent VTE. Hospital or ED encounters with VTE codes in the primary position were more likely to represent valid recurrent VTE (PPV 61.3%, 95%CI: 56.7-66.3%) than codes in secondary positions (PPV 35.4%, 95%CI: 31.9-39.3%), or outpatient codes (PPV 20.3%, 95%CI: 18.3-22.5%). PPV was low for all VTE types (29.9% for pulmonary embolism, 38.3% for lower and 37.7% for upper extremity deep venous thrombosis, and 14.1% for other VTE).

Conclusions: ICD-9 codes do not accurately identify new VTE events in patients with a prior history of VTE.
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http://dx.doi.org/10.1016/j.thromres.2020.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335977PMC
May 2020

Historical terminology and superior mesenteric artery syndrome.

Int J Surg Case Rep 2020 23;67:282-283. Epub 2020 Jan 23.

University of Florida, Division of General Internal Medicine, 2000 SW Archer Rd. Gainesville, FL 32608, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ijscr.2019.12.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076277PMC
January 2020

Abdominal Physical Signs and Medical Eponyms: Part II. Percussion and Auscultation, 1924-1980.

Clin Med Res 2020 08 19;18(2-3):102-108. Epub 2019 Jul 19.

Marshfield Clinic Research Institute, 1000 North Oak Avenue, Marshfield, Wisconsin, USA.

Background: Percussion and auscultation are derived from the Latin words to touch and hear, respectively. Covered are abdominal percussion signs and ausculatory signs discovered from 1924 to 1980. Signs ascribed as medical eponyms pay homage to these physicians who provided new and unique insights into disease.

Data Sources: PubMed, Medline, online Internet word searches, textbooks, and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign.

Conclusion: Many of these signs have been discarded because of modern imaging and diagnostic techniques. When combined with a high clinical suspicion, positive results using percussion combined with palpation is a useful bedside technique in detecting splenic enlargement. Thus, some of these maneuvers remain important bedside techniques that skilled practitioners should master, and along with a meaningful history, provide relevant information to diagnosis. It is through learning about these signs that we gain a sense of humility on the difficulty physicians faced prior to the advent of techniques that now allow us an easier way to visualize and diagnose the underlying disease processes.
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http://dx.doi.org/10.3121/cmr.2018.1429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428204PMC
August 2020

Abdominal Physical Signs and Medical Eponyms: Part I. Percussion, 1871-1900.

Clin Med Res 2020 03 19;18(1):42-47. Epub 2019 Jul 19.

University of Central Florida College of Medicine, Department of Internal Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827. Email:

Background: Percussion is derived from the Latin word to hear and to touch. Percussion of the abdomen is used to detect areas of tenderness, dullness within an area of tenderness suggestive of a mass, shifting dullness representing fluid or blood, splenic, hepatic and bladder enlargement, and free air in the peritoneum. Covered are abdominal signs of percussion attributed as medical eponyms from the time-period beginning in the mid-late nineteenth century. Described is historical information behind the sign, descriptions of the sign, and implication in modern clinical practice.

Data Sources: PubMed, Medline, online Internet word searches, textbooks, and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign.

Conclusion: Percussion signs defined as medical eponyms were important discoveries adopted by physicians prior to the advent of radiographs and other imaging and diagnostic techniques. The signs perfected during this time-period provided important clinical cues as to the presence of air within the peritoneum or rupture of the spleen.
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http://dx.doi.org/10.3121/cmr.2018.1428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153795PMC
March 2020

Abdominal Physical Signs and Medical Eponyms: Part III. Physical Examination of Palpation, 1926-1976.

Clin Med Res 2019 12 15;17(3-4):107-114. Epub 2019 Jul 15.

University of Central Florida College of Medicine, Department of Internal Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827

Background: This paper describes medical eponyms associated with abdominal palpation from the period 1926-1976. Despite opposition by some, eponyms are a long standing tradition and widely used in medicine. The techniques may still be useful in some cases, assisting in the selection of an appropriate and cost-effective approach to patient care. In this piece, we cover signs named in honor of physicians who contributed to medicine by developing new palpatory techniques in an attempt to better diagnose disease of the abdominal wall, umbilicus, gallbladder, pancreas, and appendix.

Data Sources: PubMed, Medline, online Internet word searches, textbooks, and references from other source texts. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign.

Conclusion: We describe brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication into today's medical practice.
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http://dx.doi.org/10.3121/cmr.2018.1427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886893PMC
December 2019

Abdominal Physical Signs of Inspection and Medical Eponyms.

Clin Med Res 2019 12 15;17(3-4):115-126. Epub 2019 Jul 15.

University of Central Florida College of Medicine, Department of Internal Medicine, 6850 Lake Nona Blvd, Orlando, Florida

Background: An eponym in clinical medicine is an honorific term ascribed to a person(s) who may have initially discovered or described a device, procedure, anatomical part, treatment, disease, symptom, syndrome, or sign found on physical examination. Signs, although often lacking sufficient sensitivity and specificity, assist in some cases to differentiate and diagnose disease. With the advent of advanced technological tools in radiological imaging and diagnostic testing, the importance of inspection, the initial steps taught during the physical examination, is often overlooked or given only cursory attention. Nevertheless, in the era of evidence-based and cost-effective medicine, it becomes compelling, and we contend that a meticulously performed history and physical examination, applying the basic tenets of inspection, remains paramount prior to obtaining appropriate diagnostic tests.

Data Sources: PubMed, Medline, online Internet word searches and bibliographies from source text and textbooks. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign.

Conclusions: We describe the historical aspect, clinical application, and performance of medical eponymous signs of inspection found on physical examination during the 18th to 20th centuries.
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http://dx.doi.org/10.3121/cmr.2019.1420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886890PMC
December 2019

Venothromboembolic signs and medical eponyms: Part I.

Thromb Res 2019 Oct 21;182:194-204. Epub 2019 Jun 21.

University of Central Florida College of Medicine, Department of Internal Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827, United States of America. Electronic address:

Eponyms are honorific terms ascribed to individuals who discovered a sign, test, syndrome, technique, or instrument. Despite some contentions, eponyms continue to be widely ingrained and incorporated into the medical literature and contemporary language. Physical signs are considered unreliable methods alone for detecting deep venous thrombosis (DVT). The accuracy of the majority of these signs is unknown. For those signs that have been studied, there are a number of methodological limitations hindering the ability to draw meaningful conclusions about their accuracy and validity in clinical practice. Nevertheless, some findings when present and used in conjunction with other key signs, symptoms, and aspects of the patients history may be useful in further supporting the clinical suspicion and likelihood of DVT and/or pulmonary embolism (PE) or venothromboembolism (VTE). These signs also provide the means to better recognize the relationship between clinical findings and VTE. The acquisition of historical knowledge about these signs is important as it further enhances our understanding and appreciation of the diagnostic acumen that physicians were required to employ and to diagnose VTE prior to the advent of advanced imaging methods. Described in this paper is a brief overview of thrombosis as enumerated by Rudolf Virchow, and eponymous signs described in the late eighteenth and nineteenth centuries.
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http://dx.doi.org/10.1016/j.thromres.2019.06.012DOI Listing
October 2019

Venothromboembolic signs and medical eponyms: Part II.

Thromb Res 2019 Oct 21;182:205-213. Epub 2019 Jun 21.

University of Central Florida College of Medicine, Department of Internal Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827, United States of America. Electronic address:

Eponyms were established to serve the purpose of honoring individuals who have made important observations and discoveries. The use of eponyms remains controversial, and important questions have been raised regarding their appropriateness. Although there have been instances where eponyms were abandoned, the remainder are largely embedded within the established literature making their disappearance unlikely. Physicians used a variety of techniques to describe signs of medical eponyms as a method for diagnosing deep venous thrombosis (DVT), pulmonary embolism (PE) or venothromboembolism (VTE). These methods (observation, palpation, pressure, or maneuvers), were detected during the physical examination and using bedside sphygmomanometer or radiographic imaging. Reviewed are both common and less frequently encountered VTE eponyms identified during the physical examination and radiologic imaging. Most of these signs have not been further studied and, therefore, there is a lack of information regarding their accuracy and reliability in clinical practice.
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http://dx.doi.org/10.1016/j.thromres.2019.06.011DOI Listing
October 2019

Treatment and Outcomes of Acute Pulmonary Embolism and Deep Venous Thrombosis: The CVRN VTE Study.

Am J Med 2019 12 25;132(12):1450-1457.e1. Epub 2019 Jun 25.

Division of Research, Kaiser Permanente Northern California, Oakland; Departments of Epidemiology, Biostatistics and Medicine, University of California, San Francisco; Departments of Medicine, Health Research and Policy, Stanford University School of Medicine, Palo Alto, Calif.

Background: Few studies describe both inpatient and outpatient treatment and outcomes of patients with acute venous thromboembolism in the United States.

Methods: A multi-institutional cohort of patients diagnosed with confirmed pulmonary embolism or deep venous thrombosis during the years 2004 through 2010 was established from 4 large, US-based integrated health care delivery systems. Computerized databases were accessed and medical records reviewed to collect information on patient demographics, clinical risk factors, initial antithrombotic treatment, and vital status. Multivariable Cox regression models were used to estimate the risk of death at 90 days.

Results: The cohort comprised 5497 adults with acute venous thromboembolism. Pulmonary embolism was predominantly managed in the hospital setting (95.0%), while 54.5% of patients with lower extremity thrombosis were treated as outpatients. Anticoagulant treatment differed according to thromboembolism type: 2688 patients (92.8%) with pulmonary embolism and 1625 patients (86.9%) with lower extremity thrombosis were discharged on anticoagulants, compared with 286 patients (80.1%) with upper extremity thrombosis and 69 (54.8%) patients with other thrombosis. While 4.5% of patients died during the index episode, 15.4% died within 90 days. Pulmonary embolism was associated with a higher 90-day death risk than lower extremity thrombosis (adjusted hazard ratio 1.23; 95% confidence interval, 1.04-1.47), as was not being discharged on anticoagulants (adjusted hazard ratio 5.56; 95% confidence interval, 4.76-6.67).

Conclusions: In this multicenter, community-based study of patients with acute venous thromboembolism, anticoagulant treatment and outcomes varied by thromboembolism type. Although case fatality during the acute episode was relatively low, 15.4% of people with thromboembolism died within 90 days of the index diagnosis.
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http://dx.doi.org/10.1016/j.amjmed.2019.05.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917856PMC
December 2019

Abdominal Physical Signs and Medical Eponyms: Part II. Physical Examination of Palpation, 1907-1926.

Clin Med Res 2019 06;17(1-2):47-54

University of Central Florida College of Medicine, Department of Internal Medicine, Orlando, Florida, USA

Background: Abdominal palpation is an important clinical skill used by physicians to detect the cause of the underlying disease. Abdominal physical signs reported as medical eponyms are sometimes helpful in supporting or confirming clinical suspicion of a diagnosis. With the advent of advanced and rapid imaging techniques physicians often know the diagnosis prior to setting their hands on patients. Nevertheless, knowledge of these signs may still remain important in settings where imaging may not be readily available and importantly provide deeper insights into the mechanism of disease. In this paper, described are medical eponyms associated with abdominal palpation from the period 1907-1926.

Data Sources: PubMed, Medline, on-line Internet word searches, textbooks, and references from other source text were used as the data source. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign.

Conclusion: We describe brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication into today's medical practice.
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http://dx.doi.org/10.3121/cmr.2018.1426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546280PMC
June 2019

Abdominal Physical Signs and Medical Eponyms: Movements and Compression.

Clin Med Res 2018 12;16(3-4):76-82

Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida, USA

Background: Prior to the advent of modern imaging techniques, maneuvers were performed as part of the physical examination to further assess pathological findings or an acute abdomen and to further improve clinicians' diagnostic acumen to identify the site and cause of disease. Maneuvers such as changing the position of the patient, extremity, or displacing through pressure a particular organ or structure from its original position are typically used to exacerbate or elicit pain. Some of these techniques, also referred to as special tests, are ascribed as medical eponym signs.

Data Sources: PubMed, Medline, online Internet word searches, textbooks and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign.

Conclusion: These active and passive maneuvers of the abdomen, reported as medical signs, have variable performance in medical practice. The lack of diagnostic accuracy may be attributed to confounders such as the position of the organ, modification of the original technique, or lack of performance of the maneuver as originally intended.
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http://dx.doi.org/10.3121/cmr.2018.1422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306146PMC
December 2018

Factors associated with participation and completion of a survey-based study.

Int J Health Care Qual Assur 2018 Oct;31(8):888-895

Minneapolis Medical Research Foundation, Minneapolis, Minnesota, USA.

Purpose: The Healthy Work Place (HWP) study investigated methods to improve clinicians' dissatisfaction and burnout. The purpose of this paper is to identify factors that influenced study enrollment and completion and assess effects of initial clinic site enrollment rates on clinician outcomes, including satisfaction, burnout, stress and intent to leave practice.

Design/methodology/approach: In total, 144 primary care clinicians (general internists, family physicians, nurse practitioners and physician assistants) at 14 primary care clinics were analyzed.

Findings: In total, 72 clinicians enrolled in the study and completed the first survey (50 percent enrollment rate). Of these, 10 did not complete the second survey (86 percent completion rate). Gender, type, burnout, stress and intervention did not significantly affect survey completion. Hence, widespread agreement about most moral/ethical issues (72 percent vs 22 percent; p=0.0060) and general agreement on treatment methods (81 percent vs 50 percent; p=0.0490) were reported by providers that completed both surveys as opposed to just the initial survey. Providers with high initial clinic site enrollment rates (=50 percent providers) obtained better outcomes, including improvements in or no worsening of satisfaction (odds ratio (OR)=19.16; p=0.0217) and burnout (OR=6.24; p=0.0418).

Social Implications: More providers experiencing workplace agreement completed the initial and final surveys, and providers at sites with higher initial enrollment rates obtained better outcomes including a higher rate of improvement or no worsening of job satisfaction and burnout.

Originality/value: There is limited research on clinicians' workplace and other factors that influence their participation in survey-based studies. The findings help us to understand how these factors may affect quality of data collecting and outcome. Thus, the study provides us insight for improvement of quality in primary care.
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http://dx.doi.org/10.1108/IJHCQA-02-2017-0029DOI Listing
October 2018

Abdominal Physical Signs and Medical Eponyms: Physical Examination of Palpation Part 1, 1876-1907.

Clin Med Res 2018 12 30;16(3-4):83-91. Epub 2018 Aug 30.

Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida, USA

Background: Abdominal palpation is a difficult skill to master in the physical examination. It is through the tactile sensation of touch that abdominal tenderness is detected and expressed through pain. Its findings can be used to detect peritonitis and other acute and subtle abnormalities of the abdomen. Some techniques, recognized as signs or medical eponyms, assist clinicians in detecting disease and differentiating other conditions based on location and response to palpation. Described in this paper are medical eponyms associated with abdominal palpation from the period 1876 to 1907.

Data Sources: PubMed, Medline, on-line Internet word searches, textbooks and references from other source text were used as the data source. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign.

Conclusion: We present brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication in today's medical practice.
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http://dx.doi.org/10.3121/cmr.2018.1423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306141PMC
December 2018

Flushing Disorders Associated with Gastrointestinal Symptoms: Part 2, Systemic Miscellaneous Conditions.

Clin Med Res 2018 06 12;16(1-2):29-36. Epub 2018 Apr 12.

University of Central Florida College of Medicine/HCA, Consortium Graduate Medical Education, North Florida, Regional Medical Center, 6500 W Newberry Rd, Gainesville, FL 32605.

Flushing disorders with involvement of the gastrointestinal tract represent a heterogeneous group of conditions. In part 1 of this review series, neuroendocrine tumors (NET), mast cell activation disorders (MCAD), and hyperbasophilia were discussed. In this section we discuss the remaining flushing disorders which primarily or secondarily involve the gastrointestinal tract. This includes dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications. With the exception of paroxysmal pain disorders, panic disorders and some medications, these disorders presents with dry flushing. A detailed and comprehensive family, social, medical and surgical history, as well as recognizing the presence of other systemic symptoms are important in distinguishing the different disease that cause flushing with gastrointestinal symptoms.
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http://dx.doi.org/10.3121/cmr.2017.1379bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108508PMC
June 2018

Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila.

Clin Med Res 2018 06 12;16(1-2):16-28. Epub 2018 Apr 12.

University of Central Florida College of Medicine/HCA Consortium Graduate Medical Education, North Florida Regional Medical Center, 6500 W Newberry Rd, Gainesville, FL 32605.

Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins, respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.
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http://dx.doi.org/10.3121/cmr.2017.1379aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108509PMC
June 2018

The effect of solifenacin on postvoid dribbling in women: results of a randomized, double-blind placebo-controlled trial.

Int Urogynecol J 2018 07 24;29(7):1051-1060. Epub 2018 Mar 24.

University of Central Florida College of Medicine, Orlando, FL, USA.

Introduction And Hypothesis: To determine the effectiveness of the muscarinic receptor antagonist solifenacin (VESIcare®) in the treatment of postvoid dribbling (PVD).

Methods: We carried out a multicenter, 12-week, double-blind, randomized, placebo-controlled, parallel design study. Between 2012 and 2015, a total of 118 women (age 18-89 years) with PVD at least twice/weekly, were randomized to receive solifenacin (5 mg; n = 58) or placebo (n = 60) once daily. The primary outcome was the percentage reduction in PVD episodes. Secondary outcomes included the percentage of patients with ≥50% reduction in PVD episodes and changes in quality of life.

Results: There were no differences in either the primary or secondary outcome variables. Subgroup analysis, based on those with more severe disease (>10 PVD episodes/week), showed a greater and significant percentage reduction in the frequency of PVD episodes per day (60.3% vs 32.1%; p = 0.035) and a higher percentage of patients showing ≥50% reduction in the frequency of PVD episodes with solifenacin (68.1% vs 45.8%; p = 0.0476). A significant solifenacin effect occurred at week 2 and continued through week 12 for the subgroup. For solifenacin, PVD reduction was the same for the entire cohort and subgroup, whereas for placebo, it was 10% lower in the subgroup, declining from 42% to 32%.

Conclusion: There were no differences in PVD outcomes between the solifenacin and placebo groups. Solifenacin may play a role in treating women with the most severe symptoms. Because of the powerful placebo response seen in this study, behavior-based interventions may be useful for treating PVD.
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http://dx.doi.org/10.1007/s00192-018-3594-6DOI Listing
July 2018

Gene Expression Profiling and Assessment of Vitamin D and Serotonin Pathway Variations in Patients With Irritable Bowel Syndrome.

J Neurogastroenterol Motil 2018 Jan;24(1):96-106

School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, USA.

Background/aims: Irritable bowel syndrome (IBS) is a multifaceted disorder that afflicts millions of individuals worldwide. IBS is currently diagnosed based on the presence/duration of symptoms and systematic exclusion of other conditions. A more direct manner to identify IBS is needed to reduce healthcare costs and the time required for accurate diagnosis. The overarching objective of this work is to identify gene expression-based biological signatures and biomarkers of IBS.

Methods: Gene transcripts from 24 tissue biopsy samples were hybridized to microarrays for gene expression profiling. A combination of multiple statistical analyses was utilized to narrow the raw microarray data to the top 200 differentially expressed genes between IBS versus control subjects. In addition, quantitative polymerase chain reaction was employed for validation of the DNA microarray data. Gene ontology/pathway enrichment analysis was performed to investigate gene expression patterns in biochemical pathways. Finally, since vitamin D has been shown to modulate serotonin production in some models, the relationship between serum vitamin D and IBS was investigated via 25-hydroxyvitamin D (25[OH]D) chemiluminescence immunoassay.

Results: A total of 858 genetic features were identified with differential expression levels between IBS and asymptomatic populations. Gene ontology enrichment analysis revealed the serotonergic pathway as most prevalent among the differentially expressed genes. Further analysis via real-time polymerase chain reaction suggested that IBS patient-derived RNA exhibited lower levels of tryptophan hydroxylase-1 expression, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis. Finally, mean values for 25(OH)D were lower in IBS patients relative to non-IBS controls.

Conclusions: Values for serum 25(OH)D concentrations exhibited a trend towards lower vitamin D levels within the IBS cohort. In addition, the expression of select IBS genetic biomarkers, including tryptophan hydroxylase 1, was modulated by vitamin D. Strikingly, the direction of gene regulation elicited by vitamin D in colonic cells is "opposite" to the gene expression profile observed in IBS patients, suggesting that vitamin D may help "reverse" the pathological direction of biomarker gene expression in IBS. Thus, our results intimate that IBS pathogenesis and pathophysiology may involve dysregulated serotonin production and/or vitamin D insufficiency.
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http://dx.doi.org/10.5056/jnm17021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753908PMC
January 2018

Validity of Using Inpatient and Outpatient Administrative Codes to Identify Acute Venous Thromboembolism: The CVRN VTE Study.

Med Care 2017 12;55(12):e137-e143

*Division of Hospital Medicine, University of California, San Francisco †Division of Research, Kaiser Permanente Northern California, Oakland, CA ‡Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT §Office for Health Services, Marshfield Clinic Research Foundation, Marshfield, WI ∥Geisinger Health System, Center for Health Research, Danville, PA ¶Scripps Translational Science Institute, La Jolla, CA #Departments of Epidemiology, Biostatistics and Medicine, University of California, San Francisco **Department of Health Research and Policy, Stanford University School of Medicine, Palo Alto, CA.

Background: Administrative data are frequently used to identify venous thromboembolism (VTE) for research and quality reporting. However, the validity of these codes, particularly in outpatients, has not been well-established.

Objective: To determine how well International Classification of Diseases, Ninth Revision (ICD-9) codes for VTE predict chart-confirmed acute VTE in inpatient and outpatients.

Patients And Methods: We selected 4642 adults with an incident ICD-9 diagnosis of VTE between years 2004 and 2010 from the Cardiovascular Research Network Venous Thromboembolism cohort study. Medical charts were reviewed to determine validity of events. Positive predictive values (PPVs) of ICD-9 codes were calculated as the number of chart-validated VTE events divided by the number with specific VTE codes. Analyses were stratified by VTE type [pulmonary embolism (PE), deep venous thrombosis (DVT)], code position (primary, secondary), and setting [hospital/emergency department (ED), outpatient].

Results: The PPV for any diagnosis of VTE was 64.6% for hospital/ED patients and 30.9% for outpatients. Primary diagnosis codes from hospital/ED patients were more likely to represent acute VTE than secondary diagnosis codes (78.9% vs. 44.4%, P<0.001). Primary hospital/ED codes for PE and lower extremity DVT had higher PPV than for upper extremity DVT (89.1%, 74.9%, and 58.1%, respectively). Outpatient codes were poorly predictive of acute VTE: 28.0% for PE and 53.6% for lower extremity DVT.

Conclusions: ICD-9 codes for VTE obtained from outpatient encounters or from secondary diagnosis codes do not reliably reflect acute VTE. More accurate ways of identifying VTE in outpatients are needed before these codes can be adopted for research or policy purposes.
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http://dx.doi.org/10.1097/MLR.0000000000000524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125903PMC
December 2017

Colorectal Cancer Screening.

WMJ 2017 02;116(1):27-33

Colorectal cancer (CRC) continues to be one of the most commonly diagnosed cancers and contributes significantly to many cancer-related deaths despite sustained progress in diagnostic and treatment options. Many forms of CRC can be prevented through early and routine screening, when precancerous lesions may be detected and removed before they undergo malignant transformation or metastasis. Despite widespread efforts to improve CRC screening rates, at least 40% of age-eligible adults do not adhere to screening guidelines. A new generation of noninvasive, molecular-based diagnostic tests with high sensitivities and specificities has the potential to improve screening rates through optimal risk stratification of patients who may benefit from more invasive screening techniques. This review presents various guidelines and methods that are currently available for CRC screening, summarizes the rationale behind utilization of novel molecular-based diagnostic tests for CRC screening and prevention, and discusses appropriate screening techniques and intervals in populations of varying risk.
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February 2017