Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS.

Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed "original antigenic sin." The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.

Incremental value of copeptin in suspected acute myocardial infarction very early after symptom onset.

BACKGROUND: Patients presenting very early after chest pain onset may provide a diagnostic challenge even when using a high-sensitivity cardiac troponin (hs-cTnT). We hypothesized that in these patients the incremental value of copeptin in the early diagnosis of acute myocardial infarction (AMI) may be substantial. METHODS: We aimed to investigate the incremental value of copeptin in a pre-specified subgroup analysis of patients presenting with suspected AMI to the emergency department within 2 hours of symptom onset in a multicenter study. Copeptin was measured in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis using all available clinical informations, including high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: Overall, 2000 patients were enrolled, of whom 519 (26%) arrived within 2 hours of symptom onset. Of these, 102 patients (20%) had an AMI. The additional use of copeptin did not increase diagnostic accuracy as quantified by the area under the receiver-operating characteristic curve (AUC) of hs-cTnT (0.87 (95% confidence interval (CI): 0.83-0.90) for hs-cTnT alone to 0.86 (95% CI: 0.82-0.90) for the combination; p = NS). Copeptin (using 9 pmol/L as a cut-off) increased the negative predictive value (NPV) of hs-cTnT (using 14 ng/L as a cut-off) alone from 93% (95% CI: 90-95%) to 96% (95% CI: 93-98%). The NPV for the combination of hs-cTnT and copeptin was lower in patients arriving in the first 2 hours than in those arriving after 2 hours: 96% (95% CI: 93-98%) versus 99% (95% CI: 99-100%), respectively. CONCLUSIONS: The additional use of copeptin on top of hs-cTnT seems to lead to a small increase in NPV, but no increase in AUC. Routine use of copeptin in early presenters does not seem warranted.

Incremental value of heart-type fatty acid-binding protein in suspected acute myocardial infarction early after symptom onset.

BACKGROUND: The early diagnosis of acute myocardial infarction (AMI) very soon after symptom onset remains a major clinical challenge, even when using high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS: We investigated the incremental value of heart-type fatty acid-binding protein (hFABP) in a pre-specified subgroup analysis of patients presenting with suspected AMI within 1 h of symptom onset to the emergency department (ED) in a multicentre study. HFABP was measured in a blinded fashion. Two independent cardiologists using all available clinical information, including hs-cTnT, adjudicated the final diagnosis. Overall, 1411 patients were enrolled, of whom 105 patients presented within 1 h of symptom onset. Of these, 34 patients (32.4%) had AMI. The diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) of hFABP was high (0.84 (95% CI 0.74-0.94)). However, the additional use of hFABP only marginally increased the diagnostic accuracy of hs-cTnT (AUC 0.88 (95% CI 0.81-0.94) for hs-cTnT alone to 0.90 (95% CI 0.83-0.98) for the combination; p=ns). After the exclusion of 18 AMI patients with ST-segment elevation, similar results were obtained. Among the 16 AMI patients without ST-segment elevation, six had normal hs-cTnT at presentation. Of these, hFABP was elevated in two (33.3%) patients. CONCLUSIONS: hFABP does not seem to significantly improve the early diagnostic accuracy of hs-cTnT in the important subgroup of patients with suspected AMI presenting to the ED very early after symptom onset.

[Drivers licence for the doctor's lab]. / Der Fähigkeitsausweis Praxislabor (FAPL).

In Switzerland a general practitioner as well as a specialist needs a qualification to be entitled to do laboratory tests in their private offices and take advantage of health insurance funding. This qualification is reached by accomplishing the so called FAPL-course (FAPL = Fähigkeitsausweis Praxislabor). The course was introduced in 2003 and is expanding year by year. Up to 480 practitioners are thus educated per year, mostly in Luzern for the German speaking region, but also in Lausanne for the French speaking and in Locarno for the Italian speaking participants. Managing a laboratory in a medical office requires a wide knowledge concerning preanalytics including the correct sampling of body fluids, analytical techniques, the correct use and the limits of testing procedures. Furthermore postanalytical interpretations imply a good understanding of statistics. In addition legal regulations have to be respected. These topics are partially communicated using an e-learning platform and partially in a two day practical course.

[The concept of reference change values (RCV). Will it supersede reference intervals?]. / Der Referenzbereich ist tot - es lebe der Reference Change Value.

Reference values are generally used to allow a decision on whether a laboratory value is in the normal range or if it mirrors a pathological process. This decision is especially difficult to take, when the pathological process is just starting and the values are relatively close to the normal range. Particularly in this phase, the decision is extremely important. Harris and later on Fraser have realized that there are two variables that contribute to the credibility and significance of a measured analyte. 1. The imprecision of the measurement itself. These values have become relatively low in recent years: they amount to values between 1 and 5 %. 2. The within person biological variability, which can be 100 % or more. Both variables combined yield the "reference change value" (RCV) to define the minimal significant difference between two measurements at different time points. When using this concept, differences between two measurements can be detected before the normal range is exceeded. For any given patient the reference values of a population is actually not of primary concern. It is important to know that his personal data exceed his personal normal range, which is dependent on RCV. For many analytes in clinical chemistry and hematology the use of RCV rather than the normal range as reference improves the decision making process in a clinical setting.

Comparisons of home and daytime ambulatory blood pressure measurements.

BACKGROUND: Home (HBPM) and ambulatory (ABPM) blood pressure measurements have their advantages and disadvantages in diagnosing and managing hypertension. We studied HBPMs and ABPMs in volunteers taking part in a survey. METHODS: Of 366 respondents, 270 provided a total of 5997 triplicate HBPMs (Part 1); 175 also provided data on ABPMs, of which the measurements obtained between 6 am and 10 pm were used in this study (Part 2). RESULTS: Part 1, When all 5997 triplicate HPPMs were considered, 1st readings tended to be significantly higher than those of the 2nd and 3rd for both, systolic and diastolic pressures, but when the consideration was restricted to the very first triplicate of each of the 270 subjects, this was true only for systolic HBPM. Part 2, The ABPMs tended to have a wider range than the corresponding HBPMs, and to be distributed towards higher values. Of the non-parametric indices of (ABPM - corresponding HBPM), (First Quartile, Median, Third Quartile and Maximim) all but the minima had positive values. CONCLUSIONS: In triplicate HBPMs, the first measurement is usually but not always the highest. Increasing the number of triplicates provided by each subject increases the chance of discriminating between measurements in the triplicates. ABPMs tended to be higher than the corresponding HBPMs.

Impact of a proprietary concentrate of Sambucus nigra L. on urinary pH.

A proprietary concentrate from Sambucus nigra L.--in its diluted preparation as part of a hypocaloric diet available in Switzerland--had no impact on urinary pH, urinary hydrogen ion concentrations or 24 h excretion and thus did not influence the solubility of stone-inducing ions.

Clinical correlates of very high brain natriuretic peptide levels in hospitalized patients.

While low brain natriuretic peptide (BNP) values have been shown to improve diagnostic accuracy by excluding congestive heart failure in acute dyspnea, the meaning of excessively elevated BNP is not clear. This is a retrospective analysis of clinical, echocardiographic, and laboratory data in patients with BNP values >2500 ng/L. Sixty-seven patients (36 men) with a median age of 79 years were included. The median BNP level was 3118 ng/L (2506-5000 ng/L). Forty-six percent of the patients had no dyspnea or New York Heart Association class II dyspnea. Most patients had impaired renal function. BNP value did not correlate with ejection fraction (r=0.2; P=.15) and weakly correlated with left ventricular end-diastolic diameter index (r=0.26; P=.02). Very high BNP values only poorly correlated with dyspnea and traditional echocardiographic markers of congestive heart failure. The clinical usefulness of very high BNP values is questionable and needs evaluation in a prospective trial.