Gianna Vettore

Copeptin decrease from admission to discharge has favorable prognostic value for 90-day events in patients admitted with dyspnea

Abstract Background: With patients referred to emergency departments (EDs) for acute dyspnea, emergency physicians should consider all possible diagnoses and assess patients’ risk stratification. Copeptin has been shown to have prognostic power for subsequent events, such as death and rehospitalization in patients admitted for dyspnea. The aim of this study was to investigate prognostic role of copeptin variations during hospitalization in patients admitted for dyspnea. Methods: We conducted a prospective, multicentric, observational study in acute dyspneic patients in three ED centers in Italy. Clinical data and copeptin assessments were performed at admission, and at discharge. A 90-day follow-up was performed. Results: A total of 336 patients were enrolled, and on the basis of final diagnosis distinguished into two groups: acute heart failure and no acute heart failure. Compared to a control group, in all studied population copeptin values at admission resulted in a significantly (p<0.001) higher median (maximum–minimum): 31 (0–905) versus 8 (0–13) pmol/L. Median copeptin value at admission was 42 (0–905) pmol/L in acute heart failure patients and 20 (0–887) pmol/L in no acute heart failure, respectively (p<0.001). In all studied patients and in each group copeptin at admission and discharge showed significant predictive value for 90-day events (p<0.001). Furthermore, in all patients population and in both groups Δ copeptin values from admission to discharge also showed significant predictive value for 90-day events (p<0.001). Conclusions: In patients admitted for acute dyspnea, admission, discharge and Δ copeptin variations have significant prognostic value from subsequent 90-day death and rehospitalization.

An Uncommon Cause of Acute Pancreatitis

Question: A 32-year-old woman presented to the emergency department in acute distress; she had a distended abdomen with marked tenderness and poor peristalsis. Nausea, vomiting, and severe abdominal pain radiating to her back was resistant to analgesic and anti-emetic drugs that had been started 6 hours before admission. Her past clinical history was characterized by recurrent episodes of cutaneous swelling unresponsive to antihistamines, steroids, and other anti-allergy drugs. Laboratory tests revealed hemoconcentration (hematocrit, 48%), leukocytosis (white blood cell count, 11.410 10 9 /L; neutrophils, 9.830 10 9 /L), and hyperamylasemia (470 U/L; reference range, 0‐53), with transaminases and bilirubin in the normal range. Computed tomography was performed and showed an enlarged, edematous pancreas with indistinct edges (Figure A, white arrows) and left pararenal fluid collection (Figure A, black arrow), as well as additional pathologic findings (Figures B and C). What is the diagnosis? How should the patient be managed?

An uncommon cause of acute pancreatitis. Hereditary angioedema-induced acute pancreatitis.

Question: A 32-year-old woman presented to the emergency department in acute distress; she had a distended abdomen with marked tenderness and poor peristalsis. Nausea, vomiting, and severe abdominal pain radiating to her back was resistant to analgesic and anti-emetic drugs that had been started 6 hours before admission. Her past clinical history was characterized by recurrent episodes of cutaneous swelling unresponsive to antihistamines, steroids, and other anti-allergy drugs. Laboratory tests revealed hemoconcentration (hematocrit, 48%), leukocytosis (white blood cell count, 11.410 10 9 /L; neutrophils, 9.830 10 9 /L), and hyperamylasemia (470 U/L; reference range, 0‐53), with transaminases and bilirubin in the normal range. Computed tomography was performed and showed an enlarged, edematous pancreas with indistinct edges (Figure A, white arrows) and left pararenal fluid collection (Figure A, black arrow), as well as additional pathologic findings (Figures B and C). What is the diagnosis? How should the patient be managed?

Complete blood count at the ED: preanalytic variables for hemoglobin and leukocytes

OBJECTIVE The objective of this study is to determine the ways in which preanalytic factors related to physiologic status can affect the complete blood cell count (CBC) in patients referring to an emergency department (ED). METHODS Over a 1-year period, the results of hemoglobin (Hb) level and white blood cell (WBC) counts of the first CBC tests undertaken in consecutive patients (n = 11487) referring to the ED were compared with those obtained in the same patients at a second test undertaken within 24 hours of admission. A prospective evaluation of the same differences was made in another group (group 2) of 1025 consecutive ED patients, several clinical characteristics being taken into consideration. RESULTS Mean Hb concentrations were higher in the first (range, 8.0-15.9 g/dL) than in the second test results (median overestimation, 0.4-0.8 g/dL; P < .0001). At multivariate analysis of results in group 2 patients, fluid administration (>0.5 L) and the presence of edema played a significant role in the initial overestimation of Hb level (P = .001 and P = .045, respectively). The comparison between leukocyte counts (WBC) showed that values from the first were higher than those in the second test (median overestimation ranging from 0.42 to 3.63 × 10(9)/L cells, in the range counts from 4.0 to 30.0 × 10(9)/L). None of the clinical factors studied appeared to have affected this overestimation. CONCLUSIONS On interpreting CBC results in patients admitted to the ED, physicians must consider the effect of physiologic variables on Hb level (mainly hydration status) and WBC count (mental and physical stress).

Determinants of circulating asymmetric and symmetric dimethylarginines in patients evaluated for acute dyspnea.

Abstract Background: The relationship between asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) plasma concentrations and acute heart failure is unknown. We evaluated ADMA and SDMA in patients with acute dyspnea. Methods: We studied 57 dyspneic subjects (50–95 years), with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, presenting to the emergency department. Troponin I, N terminal-proBNP (NT-proBNP), ADMA, and SDMA were measured. Electrocardiogram, chest X-ray and lung ultrasound were performed. Patients were classified into cardiogenic dyspnea and non-cardiogenic dyspnea, and were also classified on the basis of renal function according to their eGFR. Results: Two-way analysis of variance demonstrated that ADMA and SDMA did not differ for type of dyspnea, but increased in renal dysfunction. NT-proBNP significantly increased both in cardiogenic dyspnea and renal dysfunction. Multiple regression analysis demonstrated that after adjustment for troponin and dyspnea, the only variables which significantly correlated with SDMA plasma concentrations were renal function (β=–0.47, p<0.001) and NT-proBNP (β=0.28, p=0.02). Conclusions: Neither type of dimethylarginine showed cardiogenic dyspnea to be a determinant for plasma concentrations. Renal dysfunction was a confounder for both ADMA and SDMA.

Changes in Accident & Emergency Visits and Return Visits in Relation to the Enforcement of Daylight Saving Time and Photoperiod

Daylight saving time (DST) is a source of circadian disruption impinging on millions of people every year. Our aim was to assess modifications, if any, in the number, type, and outcome of Accident & Emergency (A&E) visits/return visits over the DST months. The study included 366,527 visits and 84,380 return visits to the A&E of Padova hospital (Northern Italy) over 3 periods between the years 2007 and 2016: period 1 (2 weeks prior to DST to 19 weeks after), period 2 (2 weeks prior to the return to “winter time” to 4 weeks after), and period 3 (5 consecutive non-DST weeks). For each A&E visit/return visit, information was obtained on triage severity code, main medical complaint, and outcome. Data were aggregated by day, cumulated over the years, and analyzed by generalized Poisson models. Generalized additive models for Poisson data were then used to include photoperiod as an additional covariate. An increase in A&E visits and return visits (mostly white codes, resulting in discharges) was observed a few weeks after the enforcement of DST and was significant over most weeks of period 1 (increase of ≈30 [2.8%] visits and ≈25 [10%] return visits per week per year). After the return to winter time, a decrease in absolute number of return visits was observed (mostly white codes, resulting in discharges), which was significant at weeks 3 and 4 of period 2 (decrease of ≅25 [10%] return visits per week per year). When photoperiod was taken into account, changes in A&E visits (and related white codes/discharges) were no longer significant, while changes in return visits (and related white codes/discharges) were still significant. In conclusion, changes in A&E visits/return visits were observed in relation to both DST and photoperiod, which are worthy of further study and could lead to modifications in A&E organization/staffing.

Copeptin as a diagnostic and prognostic biomarker in patients admitted to Emergency Department with syncope, presyncope and vertiginous syndrome

Syncope is a transient loss of consciousness (T-LOC) due to global cerebral hypoperfusion characterised by rapid onset, short duration and spontaneous complete recovery. It may be preceded by prodromal symptoms (lightheadedness, nausea, sweating, weakness and visual disturbances). Some patients report signs and symptoms similar to the prodrome of syncope, but without an LOC, a condition called presyncope. However, it is not clear whether the pathophysiological mechanisms involved are the same as in syncope [1]. In other patients, similar symptoms are due to a vertiginous syndrome. Finally, it is often not clear whether an LOC actually occurred. Currently, no biomarker is included in the guidelines for the diagnosis and management of syncope [1]. Copeptin, a 39-amino acid glycopeptide of unknown function, is the C-terminal portion of provasopressin and is released in an equimolar ratio to vasopressin. Unlike vasopressin, copeptin is very stable in plasma and can be measured with an automated sandwich immunoassay without complex preanalytical requirements [2]. Copeptin may be a suitable biomarker for syncope for two reasons: first, the global cerebral hypoperfusion that causes LOC in syncope is due to arterial hypotension – a stimulus that induces vasopressin secretion; second, syncope constitutes a stress condition, and vasopressin is a stress hormone. Copeptin levels were indeed claimed to correlate with the global stress level of an individual and to be associated to an unfavourable prognosis in several acute conditions [3, 4]. The aim of this study was to evaluate the usefulness of copeptin in a cohort of patients admitted to the emergency department (ED) with a T-LOC or its alleged prodromal symptoms: (a) as a diagnostic biomarker, to distinguish syncope from presyncope or vertiginous syndrome; (b) as a prognostic biomarker, to recognize patients at higher risk of short-term rehospitalisation. The study included 54 subjects admitted to the ED of the University-Hospital of Padua (Italy) reporting a T-LOC or symptoms of a likely imminent T-LOC (blurred vision, dizziness, feeling of faintness) from October to December 2014. Only subjects whose symptoms were of obvious non-syncopal origin (e.g. presentation and medical history strongly suggesting epilepsy) were excluded. Blood samples were obtained soon after admission to ED; after performing the routine blood tests, an aliquot of K2-EDTA plasma was stored at −80 °C. Copeptin was determined in these samples after thawing and centrifuging 5 min at 3500g. The measurement was performed using the BRAHMS Copeptin-us assay on the platform Kryptor Compact Plus (ThermoFisher Scientific, Milan, Italy). The diagnosis of syncope or other conditions was made by clinical criteria. Patients were followed for 45 days after the first ED admission: during this period, all-cause rehospitalisations were registered, excluding only those due to accidents. Data collection was carried out by consulting the patients’ clinical records. The study was conducted in accordance with the Declaration of Helsinki and with the hospital’s ethical guidelines. Quantitative variables were expressed as median and range, and qualitative variables as count and percentage. Two-group comparisons were performed by *Corresponding author: Luca Schiavon, University-Hospital of Padova, Department of Laboratory Medicine, via N. Giustiniani 2, 35128 Padova, Italy, Phone: +39 3400510080, E-mail: lucasch83@gmail.com Alessandra Casarotti, Monica M. Mion, Martina Zaninotto and Mario Plebani: University-Hospital of Padova, Department of Laboratory Medicine, Padova, Italy. http://orcid.org/0000-00020270-1711 (M. Plebani) Stefania Vigolo and Gianna Vettore: University-Hospital of Padova, Emergency Department, Padova, Italy

Clinical Challenges and Images in GIAn Uncommon Cause of Acute Pancreatitis

Question: A 32-year-old woman presented to the emergency department in acute distress; she had a distended abdomen with marked tenderness and poor peristalsis. Nausea, vomiting, and severe abdominal pain radiating to her back was resistant to analgesic and anti-emetic drugs that had been started 6 hours before admission. Her past clinical history was characterized by recurrent episodes of cutaneous swelling unresponsive to antihistamines, steroids, and other anti-allergy drugs. Laboratory tests revealed hemoconcentration (hematocrit, 48%), leukocytosis (white blood cell count, 11.410 10 9 /L; neutrophils, 9.830 10 9 /L), and hyperamylasemia (470 U/L; reference range, 0‐53), with transaminases and bilirubin in the normal range. Computed tomography was performed and showed an enlarged, edematous pancreas with indistinct edges (Figure A, white arrows) and left pararenal fluid collection (Figure A, black arrow), as well as additional pathologic findings (Figures B and C). What is the diagnosis? How should the patient be managed?