Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK).

Systemic forms of amyloidosis affecting the heart are mostly light-chain (AL) and transthyretin (ATTR) amyloidoses. The latter is caused by deposition of misfolded transthyretin, either in wild-type (ATTRwt) or mutant (ATTRv) conformation. For diagnostics, specific serum biomarkers and modern non-invasive imaging techniques, such as cardiovascular magnetic resonance imaging (CMR) and scintigraphic methods, are available today. These imaging techniques do not only complement conventional echocardiography, but also allow for accurate assessment of the extent of cardiac involvement, in addition to diagnosing cardiac amyloidosis. Endomyocardial biopsy still plays a major role in the histopathological diagnosis and subtyping of cardiac amyloidosis. The main objective of the diagnostic algorithm outlined in this position statement is to detect cardiac amyloidosis as reliably and early as possible, to accurately determine its extent, and to reliably identify the underlying subtype of amyloidosis, thereby enabling subsequent targeted treatment.

[52 year-old patient with severe heart failure due to multiple myeloma]. / 52-jähriger Patient mit schwerer Herzinsuffizienz bei multiplem Myelom.

Cardiac amyloidosis represents a prognostically relevant comorbidity in multiple myeloma. We report the case of a patient in whom severe heart failure symptoms as a consequence of cardiac AL-amyloidosis resolved after tandem high-dose melphalan therapy followed by autologous blood-stem cell transplantation. Partial regression of cardiac amyloid deposits and improvement of cardiac function were objectified.

Reverse epidemiology in different stages of heart failure.

BACKGROUND: In heart failure (HF), traditional cardiovascular risk factors (RF) as body mass index (BMI), total cholesterol (TC) and systolic blood pressure (SBP) are associated with better survival. It is unknown at which time point along the disease continuum the adverse impact of these RF ceases and may 'start to reverse'. We analyzed the distribution of RF and their association with survival across HF stages. METHODS: We pooled data from four cohort studies from the German Competence Network HF. Employing ACC/AHA-criteria, patients were allocated to stage A (n=218), B (n=1324), C1 (i.e., New York Heart Association [NYHA] classes I & II; n=1134), and C2+D (NYHA III & IV; n=639). RESULTS: With increasing HF severity median age increased (63/67/67/70 years), whereas the proportion of females (56/52/37/35%), median BMI (26.1/28.8/27.7/26.6 kg/m(2)), TC (212/204/191/172 mg/dl), and SBP (140/148/130/120 mmHg) decreased (P<0.001 for trend for all). In the total cohort, higher levels of all RF were associated with better survival, even after extensive adjustment for multiple confounders. If analyses were stratified, however, a higher RF burden predicted better survival only in clinically symptomatic patients: hazard ratio (HR) per +2 kg/m(2) BMI 0.91 (95% confidence interval 0.88; 0.95); per +10 mg/dl TC 0.93 (0.92; 0.95); per +5 mmHg SBP 0.94 (0.92; 0.95). CONCLUSION: In this well-characterized sample of patients representing the entire HF continuum, reverse associations were only consistently observed in symptomatic HF stages. Our data indicate that the phenomenon of a "reverse epidemiology" in HF is subject to significant selection bias in less advanced disease.

Comparative effects of prenatal cocaine, alcohol, and undernutrition on maternal/fetal toxicity and fetal body composition in the Sprague-Dawley rat with observations on strain-dependent differences.

Pregnant rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7 through 19. Pair-fed and untreated control groups and a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups. Females were sacrificed on gestation day 20 and the fetuses examined. Maternal weight gain and food consumption showed dose-dependent decreases. Maternal water consumption, by contrast, was significantly increased in the cocaine-treated animals and may reflect a diuretic effect. The maternal mortality rates in Sprague-Dawley rats were less than in two strains of Long-Evans rats, suggesting important strain-dependent differences in susceptibility to cocaine toxicity. Cocaine caused a significant dose-dependent decrease in fetal weights. Physical anomalies in the cocaine-exposed and alcohol-exposed fetuses included occasional hemorrhaging, edema, anophthalmia, and limb reduction. Despite increased maternal water consumption by cocaine-treated dams, there were no increases in fetal body water content. There were, however, significant decreases in fetal body fat content in the pair-fed, alcohol-treated, and two highest cocaine-treated groups.

Autospec: computerized processing of the data output from a spectrophotometer in a biochemical laboratory.

Autospec was designed to acquire data output from a Beckman DU series 60 spectrophotometer and to process these data with an IBM or IBM-compatible computer. It functions in conjunction with the Beckman DU Data Capture and Lotus 1-2-3 softwares. Autospec automatically stores data produced by the spectrophotometer, determines standard curves and calculates unknown concentrations of the substance being assayed. The principal features of Autospec are simplicity of use, adaptability and flexibility, minimal intervention from the operator, standardized print-outs of all data in tabular and graphic forms, accuracy of computations, speed of operation, and ease of storage and back-up of data files.

Determination of body composition in growing rats by total body electrical conductivity.

Total body electrical conductivity (TOBEC), measured with an Em-Scan SA-1 analyzer, was evaluated as a means of estimating fat-free mass and total body water content noninvasively in small laboratory animals. Ninety-four rats whose weight ranged from 5.53 to 170.84 g at 0-50 days of age were studied. The animals were killed by intraperitoneal injection of a pentobarbital overdose. After weight, crown-rump length (CRL) and TOBEC were measured, and the animals were minced with scissors and desiccated to constant weight in a convection oven. Fat was extracted by multiple bathings in petroleum ether followed by Soxhlet extraction. Fifty-four rats were used to determine the relation between fat-free mass (FFM), total body water (TBW), and TOBEC# (E) by regression analysis. The best correlations were observed between FFM and (E x CRL)1/2 (r = 0.995, p less than 0.0001). Forty rats were used to determine the predictive value of TOBEC estimates. With this instrument, TOBEC tended to underestimate FFM by an average of 3.9% and TBW by 5.3%. Accuracy was questionable for animals smaller than 13 g and TOBEC did not provide useful estimates of total body fat. Subject to these limitations, TOBEC instruments should prove to be useful for sequential in vivo estimations of body composition during growth and development of small animals.

Effects of thiazide diuretics on the lipid profile of infants with bronchopulmonary dysplasia.

Hyperlipidemia has been reported in some infants with bronchopulmonary dysplasia (BPD) who received thiazides for extended periods. In this prospective, controlled trial, we studied 17 infants with BPD who received diuretic therapy and 26 control infants who did not receive diuretics. Plasma triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol were measured enzymatically prior to onset of diuretic therapy in the study group of infants and on the day of recruitment into the study in control infants, and every 2 weeks thereafter. Plasma low-density lipoprotein cholesterol concentrations were calculated. At the end of 4 weeks, plasma lipid concentrations were comparable in both groups of infants except for significantly higher plasma HDL cholesterol concentrations observed in infants who received chlorothiazide (39 +/- 15 vs. 30 +/- 6 mg/dl, p less than 0.05). Short-term administration of chlorothiazide to infants with BPD is not associated with clinically significant changes in plasma lipid concentrations.

A prospective randomized trial comparing continuous versus intermittent feeding methods in very low birth weight neonates.

OBJECTIVE: To compare the effects of continuous versus intermittent feedings on physical growth, gastrointestinal tolerance, and macronutrient retention in very low birth weight infants ( < 1500 gm). STUDY DESIGN: Very low birth weight neonates stratified by birth weight were randomly assigned to either continuous (24-hour) or intermittent (every 3 hours) nasogastric feedings. Feedings with half-strength Similac Special Care formula were initiated between day 2 and 3 and were advanced isoenergetically to goal. Daily weights, volume/caloric intakes, weekly anthropometric and dynamic skin-fold thickness measurements, and data on feeding milestones and clinical complications were collected. Nitrogen, carbohydrate, and fat balance studies were performed on a subset of male subjects. RESULTS: Eighty-two neonates with birth weights between 750 and 1500 gm who were born between 27 and 34 weeks of gestation were randomly assigned to continuous (n = 42) and intermittent (n = 40) feeding groups. There were no significant differences in baseline demographics and severity of respiratory distress between groups. There were no significant differences in days to regain birth weight, days to full enteral feedings, days to discharge, and discharge anthropometric measurements between continuously fed and intermittently fed infants, both when evaluated together and according to 250 gm weight intervals. Retention rates of nitrogen, fat, total carbohydrate, and lactose were comparable in the continuously fed (n = 17) and intermittently fed (n = 13) male neonates. Very low birth weight neonates who were fed continuously did not have feeding-related complications. CONCLUSION: Very low birth weight infants achieve similar growth and macronutrient retention rates and have comparable lengths of hospital stay whether they are fed with continuous or intermittent feedings.