Antimicrobial resistance of Helicobacter pylori in Germany, 2015 to 2018.

OBJECTIVES: National and international guidelines recommend empiric first-line treatments of individuals infected with Helicobacter pylori without prior antimicrobial susceptibility testing. For this reason, knowledge of primary resistance to first-line antibiotics such as clarithromycin is essential. We assessed the primary resistance of H. pylori in Germany to key antibiotics by molecular genetic methods and evaluated risk factors for the development of resistance. METHODS: Gastric tissue samples of 1851 yet treatment-naïve H. pylori-positive patients were examined with real-time PCR or PCR and Sanger sequencing for mutations conferring resistance to clarithromycin, levofloxacin and tetracycline. Clinical and epidemiological data were documented and univariable and multivariable logistic regression analyses were conducted. RESULTS: Overall primary resistances were 11.3% (210/1851) to clarithromycin, and 13.4% (201/1497) to levofloxacin; resistance to tetracycline (2.5%, 38/1497) was as low as combined resistance to clarithromycin/levofloxacin (2.6%, 39/1497). Female sex and prior antimicrobial therapies owing to unrelated bacterial infections were risk factors for clarithromycin resistance (adjusted OR (aOR) 2.3, 95% CI 1.6-3.4; and 2.6, 95% CI 1.5-4.5, respectively); older age was associated with levofloxacin resistance (aOR for those ≥65 years compared with those 18-35 years: 6.6, 95% CI 3.1-14.2). CONCLUSIONS: Clarithromycin might still be recommended in first-line eradication therapies in yet untreated patients, but as nearly every tenth patient may carry clarithromycin-resistant H. pylori it may be advisable to rule out resistance ahead of treatment by carrying out susceptibility testing or prescribing an alternative therapy.

[Peripartum cardiomyopathy: interdisciplinary challenge]. / Peripartale Kardiomyopathie: Interdisziplinäre Herausforderung.

Peripartum cardiomyopathy (PPCM) is a rare type of heart failure which presents towards the end of pregnancy or in the first 5 months after delivery. Depending on the geographical location the incidence is reported in the literature as 1:300 up to 1:15,000. There are a number of known risk factors, such as multiparity and age of the mother over 30 years. The symptoms of PPCM correspond to those of idiopathic cardiomyopathy. The diagnosis is mainly carried out using echocardiography which shows a clear reduction of systolic left ventricular function. The therapeutic approach is the same as for idiopathic cardiomyopathy and in this context it is absolutely necessary to show caution concerning the state of pregnancy and the resulting contraindications for therapeutic drugs. The prognosis is dependent on recovery from the heart failure during the first 6 months postpartum. The lethality of the disease is high and is given in the literature as up to 28 %. Because of its complexity PPCM is an interdisciplinary challenge. In the peripartum phase a close cooperation between the disciplines of cardiology, cardiac surgery, neonatology, obstetrics and anesthesiology is indispensable. For anesthesiology the most important aspects are the mostly advanced unstable hemodynamic condition of the mother and the planning and implementation of the perioperative management. This article presents the case of a patient in advanced pregnancy with signs of acute severe heart failure and a suspected diagnosis of PPCM. The patient presented as an emergency case and delivery of the child was carried out using peridural anesthesia with a stand-by life support machine.

[Risk stratification in acute coronary syndrome]. / Risikostratifizierung des akuten Koronarsyndroms.

BACKGROUND: The spectrum of symptoms of patients with active ischemic heart disease ranges from silent ischemia to acute myocardial infarction and the extent of myocardial damage from reversible myocardial injury to extensive necrosis. The term "acute coronary syndrome" comprises this continuum. In particular the evaluation of patients without ST-segment elevation is difficult, for clinical symptoms, ECG criteria and CK-MB measurements appear insufficient for appropriate risk stratification. TROPONIN MEASUREMENT: Serial measurements of either troponin T or I reliably detect minor myocardial damage in those patients, who are known to be at a higher risk for adverse cardiac events comparable to the risk of patients with acute myocardial infarction. Hence determination of troponins allow superior risk stratification contributing to early triage and therapeutic decision making. Without elevation of troponins the cardiac risk for death or myocardial infarction will not exceed 1%. CONCLUSION: Patients with elevated troponins should be early hospitalized and further evaluated in order to begin efficacious therapy as soon as possible. These patients represent a high-risk subgroup of patients clinically classified as unstable angina, who might benefit from potential antithrombotic treatment such as low-molecular weight heparin or glycoprotein IIb/IIIa antagonists without or with revascularization strategies.

Analytical and diagnostic performance of troponin assays in patients suspicious for acute coronary syndromes.

BACKGROUND: The controversy whether there is a clinically significant difference between troponin T (cTnT) and troponin I (cTnI) in regard to predictive value and cardiac specificity is still ongoing. METHODS: We evaluated enzyme-linked immunosorbent assay systems for cTnI and cTnT in patients with acute coronary syndromes and multiple control groups to define threshold values for risk stratification and compare their predictive value. RESULTS: In 312 patients with noncardiac chest pain, cTnI levels were below the detection limit of 0.2 microg/L and cTnT levels were 0.011 [0.010-0. 013] microg/L. In patients with end-stage renal failure (n = 26) and acute (n = 38) or chronic (n = 16) skeletal muscle damage, median concentrations were 0.20 [0.20-0.35], below the detection limit, and 0.20 [0.20-0.25] for cTnI, and 0.04 [0.01-0.10], 0.011 [0.005-0.025], and 0.032 [0.009-0.054] microg/L for cTnT. In patients with acute coronary syndromes (n = 1130), maximized prognostic value for 30-day outcome (death, infarction) was observed at a threshold level of 1.0 microg/L for cTnI (29.0% positive) and at 0.06 microg/L for cTnT (35. 0% positive). Significant differences in the area-under-the-curve values were observed between cTnI and cTnT (0.685 vs. 0.802; p = 0. 005). For both markers, the area-under-the-curve values did not increase with the second (within 24 h after enrollment) or third (48 h) blood draw. CTnI showed a less strong association with 30-day outcome than cTnT. When cTnI was put in a logistic multiple-regression model first, cTnT did add significant information. CONCLUSION: By using the defined threshold values and the employed test systems, single testing for cTnI and cTnT within 12 h after symptom onset was appropriate for risk stratification. Despite the lower cardiac specificity for cTnT, it appears to have a stronger association with the patients' outcome, whereas, as previously shown, the ability to identify patients who benefit from treatment with a GP IIb/IIIa receptor antagonist is similar.

Cardiovascular risk and therapeutic benefit of coronary interventions for patients with unstable angina according to the troponin T status.

AIMS: Elevation of troponin T in patients with unstable angina is predictive of adverse outcomes. Since no advanced therapeutic concept for such high-risk patients has been established, we investigated cardiac risk prior to, during, and after coronary revascularization in patients with unstable angina stratified according to the troponin T status. METHODS AND RESULTS: Out of 351 patients with unstable angina, troponin was elevated for 36% of the patients as determined by qualitative bedside tests. The patients were followed during hospitalization and 30 days after discharge for incidence of death and myocardial infarction. In troponin-positive patients, clinical symptoms were more refractory to medical treatment than in troponin-negative patients (78% vs 44%;P=0.002). Although these patients were catheterized earlier (1.6 vs 3.4 days;P=0.005) and more frequently (95% vs 69%;P<0.001), troponin-positive patients suffered a higher incidence of cardiac events prior to scheduled revascularization (death, myocardial infarction; 6.4% vs 0.4%;P<0.001). The angiogram for troponin-positive patients confirmed a more severe coronary artery disease requiring revascularization (69% vs 50%;P=0.001). Also the following coronary intervention was more complicated (death, myocardial infarction; 15.3% vs 4.8%;P=0.02). During the 30-day follow-up period, cardiac risk remained elevated for troponin-positive patients. CONCLUSIONS: Troponin T rapid testing reliably identified high-risk patients with unstable angina. A higher event rate was observed prior to and particularly in association with the coronary intervention. Coronary revascularization did not abrogate the increased risk of troponin-positive patients during the 30-day follow-up.

Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban. PRISM Study Investigators. Platelet Receptor Inhibition in Ischemic Syndrome Management.

BACKGROUND: A major challenge for physicians is to identify patients with acute coronary syndromes who may benefit from treatment with glycoprotein-IIb/IIIa-receptor antagonists. We investigated whether troponin concentrations can be used to stratify patients for benefit from treatment with tirofiban. METHODS: We enrolled 2222 patients of the Platelet Receptor Inhibition in Ischemic Syndrome Management study with coronary artery disease and who had had chest pain in the previous 24 h. All patients received aspirin and were randomly assigned treatment with tirofiban or heparin. We took baseline measurements of troponin I and troponin T. We recorded death, myocardial infarction, or recurrent ischaemia after 48 h infusion treatment and at 7 days and 30 days. FINDINGS: 629 (28.3%) patients had troponin I concentrations higher than the diagnostic threshold of 1.0 microg/L and 644 (29.0%) troponin T concentrations higher than 0.1 microg/L. 30-day event rates (death, myocardial infarction) were 13.0% for troponin-I-positive patients compared with 4.9% for troponin-I-negative patients (p<0.0001), and 13.7% compared wth 3.5% for troponin T (p<0.001). At 30 days, in troponin-I-positive patients, tirofiban had lowered the risk of death (adjusted hazard ratio 0.25 [95% CI 0.09-0.68], p=0.004) and myocardial infarction (0.37 [0.16-0.84], p=0.01). This benefit was seen in medically managed patients (0.30 [0.10-0.84], p=0.004) and those undergoing revascularisation (0.37 [0.15-0.93] p=0.02) after 48 h infusion treatment. By contrast, no treatment effect was seen for troponin-I-negative patients. Similar benefits were seen for troponin-T-positive patients. INTERPRETATION: Troponin I and troponin T reliably identified high-risk patients with acute coronary syndromes, managed medically and by revascularisation, who would benefit from tirofiban.

Evaluation of a rapid whole blood ELISA for quantification of troponin I in patients with acute chest pain.

BACKGROUND: Troponin I (cTnI) provides important prognostic information in patients with chest pain. We wished to evaluate a rapid, whole-blood analyzer for quantitative point-of-care testing. METHODS: A quantitative point-of-care test system (Stratus CS((R)); Dade-Behring) for cTnI with an incorporated centrifuge was evaluated in 412 patients with chest pain less than 12 h. RESULTS: Results were available within 15 min. CVs were 4.5% at 0.1 microgram/L, 4.2% at 0.25 microgram/L, and 6.5% at 0.82 microgram/L. The detection limit was 0. 01 microgram/L. The 97.5% percentile in a healthy population was 0.08 microgram/L. Based on ROC curve analysis, a threshold of 0.15 microgram/L was calculated for the detection of acute myocardial infarction (AMI). With it, sensitivity for the detection of patients with AMI (n = 62) was 63% at arrival and 98% after 4 h (Stratus II((R)), 48% and 85%, respectively; P <0.01). In 42% of patients with unstable angina (n = 121), cTnI was >/=0.08 microgram/L (Stratus II, 28%; P <0. 01). During 30 days, death or AMI occurred in 25.5% of these cTnI-positive vs 2.9% of cTnI-negative patients (Stratus II, 29.4% vs 5.8%). CONCLUSION: The Stratus CS provided better analytical performance and comparable or better prognostic information than the Stratus II.

Prehospital testing for troponin T in patients with suspected acute myocardial infarction.

BACKGROUND: Cardiac troponin T (TnT) is a highly sensitive and specific marker for myocardial damage and can be detected early after myocardial injury. Our hypothesis was to use TnT as an objective marker to verify acute myocardial infarction before hospital admission. METHODS AND RESULTS: We evaluated the sensitivity of a rapid qualitative assay for serum TnT for the detection of acute myocardial infarction in the ambulance and assessed the predictive value of a positive prehospital TnT test for death and myocardial infarction during 6-months of follow-up. The study, conducted in an urban area, included 158 consecutive patients with suspected acute myocardial infarction (93 men aged 69 +/- 13 years). A myocardial infarction was confirmed in 40 and excluded in 118 patients. The prehospital TnT test was positive in 11 patients, of whom 7 had acute myocardial infarction. Fifty-three patients had a positive test result at hospital admission, with evidence of myocardial infarction in 39 of them. The sensitivity to acute myocardial infarction was 18% for the prehospital and 98% for the in-hospital test with 78% and 88% specificity, respectively. During follow-up, patients with a positive prehospital TnT test result had cardiac events more often (9 of 11) than patients with a negative result (26 of 147; P <.0001). CONCLUSIONS: In areas with short transport times to the patient the rapid TnT test performed at the point of care identified only a minority of the patients with acute myocardial infarction. A positive prehospital TnT test result seems to be an objective marker for a worse outcome in patients presenting with suspected acute myocardial infarction.

Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators.

BACKGROUND: In patients with refractory unstable angina, the platelet glycoprotein IIb/IIIa-receptor antibody abciximab reduces the incidence of cardiac events before and during coronary angioplasty. We investigated whether serum troponin T levels identify patients most likely to benefit from therapy with this drug. METHODS: Among 1265 patients with unstable angina who were enrolled in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) trial, serum samples drawn at the time of randomization to abciximab or placebo were available from 890 patients; we used these samples for the determination of troponin T and creatine kinase MB levels. Patients with postinfarction angina were not included. RESULTS: Serum troponin T levels at the time of study entry were elevated (above 0.1 ng per milliliter) in 275 patients (30.9 percent). Among patients receiving placebo, the risk of death or nonfatal myocardial infarction was related to troponin T levels. The six-month cumulative event rate was 23.9 percent among patients with elevated troponin T levels, as compared with 7.5 percent among patients without elevated troponin T levels (P<0.001). Among patients treated with abciximab, the respective six-month event rates were 9.5 percent for patients with elevated troponin T levels and 9.4 percent for those without elevated levels. As compared with placebo, the relative risk of death or nonfatal myocardial infarction associated with treatment with abciximab in patients with elevated troponin T levels was 0.32 (95 percent confidence interval, 0.14 to 0.62; P=0.002). The lower event rates in patients receiving abciximab were attributable to a reduction in the rate of myocardial infarction (odds ratio, 0.23; 95 percent confidence interval, 0.12 to 0.49; P<0.001). In patients without elevated troponin T levels, there was no benefit of treatment with respect to the relative risk of death or myocardial infarction at six months (odds ratio, 1.26; 95 percent confidence interval, 0.74 to 2.31; P=0.47). CONCLUSIONS: The serum troponin T level, which is considered to be a surrogate marker for thrombus formation, identifies a high-risk subgroup of patients with refractory unstable angina suitable for coronary angioplasty who will particularly benefit from antiplatelet treatment with abciximab.

[Cost-effectiveness of a rapid test for troponin in emergency admissions]. / Kosteneffektivität eines Troponin-Schnelltests in der Notaufnahme.

BACKGROUND AND OBJECTIVE: The assessment of patients with acute chest pain according to the risk of cardiac involvement takes time and expensive tests. This study was undertaken to evaluate whether the measurement of troponin 1 (Tnl) would reliably recognize those patients with an increased risk of cardiac disease so that unnecessary hospital stay could be avoided or at least reduced. PATIENTS AND METHODS: A qualitative rapid test for Tnl was performed, at emergency admission and 4 hours later, on the blood of 812 consecutive patients with acute left-chest pain of < or = 12 hours' duration. Admission was decided on the basis of clinical symptoms, ECG findings and CK-MB results. All cardiac events (death, myocardial infarction) within the next 30 days were recorded for all patients. RESULTS: Of the 812 patients (56% males; average age 62 +/- 12 years) 65% were admitted. At a daily cost of DM 635 and a mean duration of stay of 4.2 days, the total costs were DM 173,000 per 100 evaluated patients. None of the patients with a negative Tnl test and normal or ECGs that were not interpretable regarding ischaemic signs had cardiac events during the follow-up period of 30 days. By restricting hospitalization to patients with positive Tnl test and/or ST-T changes in the ECG a cost reduction of up to 14% could be achieved (P < 0.01). The cost of the Tnl test (DM 18) would be covered by reducing the number of admitted patients by about 2.1%. CONCLUSION: Performance of two Tnl tests is a cost-effective way of assessing the risk of cardiac events in patients with acute left-chest pain.

Analytical performance and clinical application of a new rapid bedside assay for the detection of serum cardiac troponin I.

Detection of cardiac troponin I (cTnI) in patients suspected of having an acute coronary syndrome is highly predictive for an adverse outcome. We evaluated a bedside test for cTnI that uses a polyclonal capture antibody and two monoclonal indicator antibodies. Clinical studies were performed in patients with acute coronary syndrome and patients with chest pain but no evidence of acute myocardial injury. The whole-blood, 15-minute assay had a concordance of 98.9% with an ELISA for cTnI and a detection limit of 0.14 microg/L, and the device tolerated temperatures between 4 degrees C and 37 degrees C. Diagnostic sensitivity for myocardial infarction at arrival (3.5 +/- 2.7 h after onset of symptoms) was 60% [creatine kinase isoenzyme MB (CK-MB) mass, 48%; CK activity, 36%; P < 0.01], and 4 h later, diagnostic sensitivity was 98% (CK-MB mass, 91%; CK activity, 61%; P < 0.01). In 38% of the patients with unstable angina, at least one positive cTnI test was found (CK-MB mass, 4%; CK activity, 2%). No false-positive test results were found in renal failure or injury of skeletal muscle. We conclude that the diagnostic efficacy of the cTnI rapid test was comparable with the cTnI ELISA and superior to CK-MB determination. Therefore, this device could facilitate decision-making in patients with chest pain at the point of care.

Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I.

BACKGROUND: Evaluation of patients with acute chest pain in emergency rooms is time-consuming and expensive, and it often results in uncertain diagnoses. We prospectively investigated the usefulness of bedside tests for the detection of cardiac troponin T and troponin I in the evaluation of patients with acute chest pain. METHODS: In 773 consecutive patients who had had acute chest pain for less than 12 hours without ST-segment elevation on their electrocardiograms, troponin T and troponin I status (positive or negative) was determined at least twice by sensitive, qualitative bedside tests based on the use of specific monoclonal antibodies. Testing was performed on arrival and four or more hours later so that one sample was taken at least six hours after the onset of pain. The troponin T results were made available to the treating physicians. RESULTS: Troponin T tests were positive in 123 patients (16 percent), and troponin I tests were positive in 171 patients (22 percent). Among 47 patients with evolving myocardial infarction, troponin T tests were positive in 44 (94 percent) and troponin I tests were positive in all 47. Among 315 patients with unstable angina, troponin T tests were positive in 70 patients (22 percent), and troponin I tests were positive in 114 patients (36 percent). During 30 days of follow-up, there were 20 deaths and 14 nonfatal myocardial infarctions. Troponin T and troponin I proved to be strong, independent predictors of cardiac events. The event rates in patients with negative tests were only 1.1 percent for troponin T and 0.3 percent for troponin I. CONCLUSIONS: Bedside tests for cardiac-specific troponins are highly sensitive for the early detection of myocardial-cell injury in acute coronary syndromes. Negative test results are associated with low risk and allow rapid and safe discharge of patients with an episode of acute chest pain from the emergency room.

The prognostic value of serum troponin T in unstable angina.

BACKGROUND: Cardiac troponin T is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. We used a newly developed enzyme immunoassay for troponin T to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator. METHODS: We screened 109 patients with unstable angina (25 with accelerated or subacute angina and 84 with acute angina at rest) for serum creatine kinase activity, creatine kinase isoenzyme MB activity, and troponin T every eight hours for two days after admission to the hospital. The outcomes of interest during the hospitalization were death and myocardial infarction. RESULTS: Troponin T was detected (range, 0.20 to 3.64 micrograms per liter; mean, 0.78; median, 0.50) in the serum of 33 of the 84 patients (39 percent) with acute angina at rest. Only three of these patients had elevated creatine kinase MB activity (two were positive for troponin T, and one was negative). Of the 33 patients who were positive for troponin T, 10 (30 percent) had myocardial infarction (3 after coronary-artery bypass surgery), and 5 of these died during hospitalization. In contrast, only 1 of the 51 patients with angina at rest who were negative for troponin T had an acute myocardial infarction (P less than 0.001), and this patient died (P = 0.03). Thus, 10 of the 11 patients with myocardial infarctions had detectable levels of troponin T; only 1 had elevated creatine kinase MB activity. Troponin T was not detected in any of the 25 patients with accelerated or subacute angina, and none of these patients died. CONCLUSIONS: Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial-cell injury than serum creatine kinase MB activity, and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina.

[Carrier detection and prenatal diagnosis in phenylketonuria, cystic fibrosis and adrenal hyperplasia use of molecular biology techniques].

With the advent of molecular biology techniques the prenatal diagnosis of many inherited diseases is now possible. In our Division of Transplantation Immunology we provide prenatal diagnosis for phenylketonuria (PKU), cystic fibrosis (CF) and congenital adrenal hyperplasia (CAH). In CF and PKU the chromosome carrying the disease gene is identified by the molecular probe, while in CAH it can also be determined by HLA phenotyping. Accurate diagnosis of a disease is dependent on the physical distance on the chromosome between the probe and the disease gene. Chorionic villous sampling allows evaluation of embryos at 9-10 weeks of gestation and also identification of carriers. DNA prepared from white blood cells of members of 4 families with CAH was digested with restriction endonucleases. Southern transfers were hybridized with the probe for 21-hydroxylase, and with 3 HLA probes mapped to both sides of the gene for 21-OH. In 2 families the embryo was found to be normal and in 2 diseased. Using the same techniques, but with probe and endonucleases specific for PKU, prenatal diagnosis was provided for 11 families with that condition. An embryo with PKU was found in each of 2 families, normal ones in 7, and in the remaining 2 families the testing was not informative. As of the present, 6 normal and 2 diseased children have been born, all as predicted. In 8 families with CF, DNA was examined with 5 probes mapped to both sides of the CF gene. Carriers and healthy sibs were identified, and in 1 family prenatal diagnosis was provided.

Rabies.

Medical science has evolved tremendously from the days when local cauterization was used to treat victims of rabies exposure. Indeed, with appropriate wound care and vaccination procedures, human rabies is a preventable disease. Despite these advances, physicians treating the uncommon but very dramatic cases of human rabies have not been so successful. As research in this field continues, our hope must be that not only will rabies be preventable and curable but that other mystifying central nervous system disorders will become better understood as well.