Papers by Christoph Kampmann
European Radiology, Nov 2, 2022
Objectives Cardiac involvement in Anderson-Fabry disease (AFD) results in myocardial lipid deposi... more Objectives Cardiac involvement in Anderson-Fabry disease (AFD) results in myocardial lipid depositions. An early diagnosis can maximize therapeutic benefit. Thus, this study aims to investigate the potential of cardiac MRI (CMR) based parameters of left atrial (LA) function and strain to detect early stages of AFD. Methods Patients (n = 58, age 40 (29-51) years, 31 female) with genetically proven AFD had undergone CMR including left ventricular (LV) volumetry, mass index (LVMi), T1, and late gadolinium enhancement, complemented by LA and LV strain measurements and atrial emptying fractions. Patients were stratified into three disease phases and compared to age and sexmatched healthy controls (HC, n = 58, Results A total of 19 early-, 20 intermediate-, and 19 advanced-phase patients were included. LV and LA reservoir strain was significantly impaired in all AFD phases, including early disease (both p < 0.001). In contrast, LA volumetry, T1, and LVMi showed no significant differences between the early phase and HC (p > 0.05). In the intermediate phase, LVMi and T1 demonstrated significant differences. In advanced phase, all parameters except active emptying fractions differed significantly from HC. ROC curve analyses of early disease phases revealed superior diagnostic confidence for the LA reservoir strain (AUC 0.88, sensitivity 89%, specificity 75%) over the LV strain (AUC 0.82). Conclusions LA reservoir strain showed impairment in early AFD and significantly correlated with disease severity. The novel approach performed better in identifying early disease than the established approach using LVMi and T1. Further studies are needed to evaluate whether these results justify earlier initiation of therapy and help minimize cardiac complications. • Parameters of left atrial function and deformation showed impairments in the early stages of Anderson-Fabry disease and correlated significantly with the severity of Anderson-Fabry disease. • Left atrial reservoir strain performed superior to ventricular strain in detecting early myocardial involvement in Anderson-Fabry disease and improved diagnostic accuracies of approaches already using ventricular strain. • Further studies are needed to evaluate whether earlier initiation of enzyme replacement therapy based on these results can help minimize cardiac complications from Anderson-Fabry disease.
European Heart Journal, Mar 29, 2007
Aims Anderson-Fabry disease (AFD) is an uncommon X-linked disorder caused by deficient activity o... more Aims Anderson-Fabry disease (AFD) is an uncommon X-linked disorder caused by deficient activity of the lysosomal enzyme a-galactosidase A. The Fabry Outcome Survey is a European database designed to monitor the long-term efficacy and safety of enzyme replacement therapy (ERT) with agalsidase alfa. The aim of this study was to determine the prevalence and characteristics of cardiac disease in AFD patients. Methods and results Clinical and laboratory data were available in 714 patients from 11 countries (mean age 35+17 years, 369 women, 336 treated). The prevalence of angina was 23 vs. 22%; palpitations and arrhythmias 27 vs. 26%; exertional dyspnoea 23 vs. 23%; and syncope 2 vs. 4%, in women and men, respectively (all P¼NS). The frequency of all cardiac symptoms was significantly higher in treated than in untreated patients. Gender, age, and glomerular filtration rate were independent determinants of echocardiographically assessed left ventricular hypertrophy (LVH). Conclusion This study confirms the high prevalence of cardiac morbidity associated with AFD. The disease burden in treated women exceeds that of untreated men, suggesting that most women selected for ERT have advanced disease. The presence of LVH is associated with higher frequency of cardiac signs and symptoms and relates independently to gender, age, and renal function.
Archives of Disease in Childhood, May 18, 2023
dosing devices. Vomiting after administration suggested poor palatability. Bottle antisepsis was ... more dosing devices. Vomiting after administration suggested poor palatability. Bottle antisepsis was endangered by use of the cap for administration. Treatment compliance suffered from nonaffordability.Insufficient availability of age-appropriate antibiotic formulations is a biohazard and driver of inappropriate antibiotic use, fuelling antimicrobial resistance. WHO should integrate antibiotics in pediatric drug optimization and medicine prequalification. National regulatory authorities should adopt stringent specifications for formulations and dosing devices when granting marketing authorizations. To enable safe and effective oral switch in low-resource settings, solid flexible dosing formulations based on age/weight bands of Watch antibiotics are needed
Archives of Disease in Childhood, May 18, 2023
Prescribing and medication administration errors are common themes in Paediatrics. We observed an... more Prescribing and medication administration errors are common themes in Paediatrics. We observed an increasing trend of errors in our ward and assessment area. We undertook an audit to quantify errors within our department as per the EQUIP criteria suggested by the General medical council. A zero-tolerance approach was undertaken, and all errors from minor to severe were recorded. An alarming 90% of admissions within the audit period had minor to significant errors recorded in the initial audit. With the zero-tolerance approach, minor errors with no harm to life were also recorded. Previous research has suggested that good quality care depends upon different professions working together. We created a tripartite alliance involving nursing, pharmacy and medical teams. Our primary aim was to reduce medication prescription and administration errors by at least 10%. The small incremental change target was made in line with the quality improvement principles. We placed education at the heart of the change process, and the programme involved no costs apart from the time invested by the team. As a result, medication errors have been substantially reduced over the last five years, and education has been at the heart of the change process. The group has achieved change that is sustainable and prudent in design. We aligned staff, method and delivery to minimise avoidable harm and promoted co-production with patient involvement in educating staff about the impact of such errors. Working together as a team involving all three disciplines has helped us understand and modify practices that have led to an overall reduction in medication errors. We would like to share our change model that has influenced consistent and reliable results over several audit cycles.
Korrelationen zwischen Kardio-MRT und Spiroergometrie bei Patienten mit Pectus excavatum
RöFo, Aug 19, 2021
Frontiers in Pharmacology, May 13, 2022
Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases (LSDs), characterized by th... more Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases (LSDs), characterized by the accumulation of glycosaminoglycans (GAGs). GAG storageinduced inflammatory processes are a driver of cytopathology in MPS and pharmacological immunomodulation can bring improvements in brain, cartilage and bone pathology in rodent models. This manuscript reviews current knowledge with regard to inflammation in MPS patients and provides hypotheses for the therapeutic use of immunomodulators in MPS. Thus, we aim to set the foundation for a rational repurposing of the discussed molecules to minimize the clinical unmet needs still remaining despite enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT).
Archives of Disease in Childhood, Oct 1, 2012
were 4.2% (n=18). Congenital heart abnormalities (85.9%), craniofascial abnormalities (44.6%) and... more were 4.2% (n=18). Congenital heart abnormalities (85.9%), craniofascial abnormalities (44.6%) and genito-urinary anomalies (16.9%) were most common concomittant malformations. Cardiovascular abnormalities were most common malformations in newborns with trisomy 21. Conclusion Frequency and distribution of the chromosomal abnormalities in our NICU were similar compering with other populational studies. Trisomy 21 was most common chromosomal abnormality. Newborns with malformations in more than two organ system should be investigated chromosomally as well. LYSOSOMAL STORAGE DISORDERS IN NON-IMMUNOLOGICAL HYDROPS FETALIS-MORE COMMON THAN ASSUMED?
Drug Design Development and Therapy, Oct 1, 2019
Purpose: Following the publication of 5-year agalsidase alfa enzyme replacement therapy (ERT) out... more Purpose: Following the publication of 5-year agalsidase alfa enzyme replacement therapy (ERT) outcomes data from the Fabry Outcome Survey (FOS), 10-year data were analyzed. Patients and methods: FOS (ClinicalTrials.gov identifier: NCT03289065) data (April 2001 to August 2018) were retrospectively analyzed. Estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) were analyzed after treatment start (baseline) for patients with ≥3 measurements, including baseline and year 10. Results: Median (range) age (years) of the evaluable treated renal cohort at treatment start was 48.8 (17.9-67.3) for females (n=62), 34.4 (18.0-66.8) for males (n=90). With eGFR ≥60 mL/min/1.73 m 2 at baseline, mean (95% CI) rate of eGFR change (eGFR/year) over 10 years was relatively stable in females (n=52; −0.55 [−1.12, +0.01]) and slightly declined in males (n=79; −1.99 [−2.45, −1.54]). With impaired kidney function (eGFR <60 mL/min/1.73 m 2) at baseline, mean (95% CI) eGFR/year was stable in females (n=10; −0.14 [−1.43, +1.15]) and slightly declined in males (n=11; −2.79 [−4.01, −1.56]) over 10 years. Median (range) age (years) of the evaluable treated cardiac cohort at treatment start was 46.7 (3.7-67.3) for females (n=34), 28.2 (4.0-54.2) for males (n=35). With left ventricular hypertrophy (LVH; LVMI >48 g/m 2.7 in females, >50 g/m 2.7 in males) at baseline, mean (95% CI) LVMI/year slightly increased over 10 years in females (n=18; +1.51 [+0.91, +2.12]) and males (n=14; +0.87 (+0.19, +1.55). Without LVH at baseline, mean (95% CI) LVMI/year was stable in females (n=16; +0.52 [−0.13, +1.17]) and males (n=21; +0.57 [+0.02, +1.13]) over 10 years. Conclusion: Agalsidase alfa-treated patients with 10-year FOS data and preserved kidney function and/or normal LVMI at baseline remained largely stable; those with decreased kidney function or LVH at baseline experienced modest declines in renal function and/or increases in LVMI.
Journal of Inherited Metabolic Disease, Jun 5, 2012
Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untrea... more Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine 4-sulfatase, galsulfase, Naglazyme®). Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg/kg during phase 1/2, phase 2, and phase 3 trials of rhASB. At baseline, mitral and aortic valve obstruction was present and was significantly greater in those ≥12 years of age. Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those <12 years. Left ventricular hypertrophy, with averaged z-scores ranging from 1.6-1.9 SD greater than normal, was present for ages both <12 and Communicated by: Gregory M. Pastores *The MPS VI Study Group co-investigators (see Acknowledgment section)
Early initiation of agalsidase alfa treatment improves clinical outcomes in male patients with classical Fabry disease: A Fabry Outcome Survey (FOS) analysis
Molecular Genetics and Metabolism, Feb 1, 2023
A precision medicine tool for high utilization and quality of individual treatment trials with immunomodulatory drugs in mucopolysaccharidosis
Molecular Genetics and Metabolism, Feb 1, 2023
Pediatric Cardiology, Feb 19, 2016
Atrial septal defect, while rare in dogs, can result in severe clinical signs. ' Surgical correct... more Atrial septal defect, while rare in dogs, can result in severe clinical signs. ' Surgical correction of atrial septal defect requires open-heart surgery. ' Transcatheter closure techniques provide minimally invasive surgical alternatives.
Orphanet Journal of Rare Diseases, Jun 20, 2022
Background: Patient registries provide long-term, real-world evidence that aids the understanding... more Background: Patient registries provide long-term, real-world evidence that aids the understanding of the natural history and progression of disease, and the effects of treatment on large patient populations with rare diseases. The year 2021 marks the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The primary aims of FOS are to broaden the understanding of Fabry disease (FD), an X-linked lysosomal storage disorder, and to improve the clinical management of affected patients. Here, we review the history of FOS and the analyses and publications disseminated from the registry, and we discuss the contributions FOS studies have made in understanding FD. Results: FOS was initiated in April 2001 and, as of January 2021, 4484 patients with a confirmed diagnosis and patient informed consent have been enrolled from 144 centers across 26 countries. Data from FOS have been published in nearly 60 manuscripts on a wide variety of topics relevant to FD. Analyses of FOS data have investigated the long-term effectiveness and safety of enzyme replacement therapy (ERT) with agalsidase alfa and its effects on morbidity and mortality, as well as the benefits of prompt and early treatment with agalsidase alfa on the progression of cardiomyopathy and the decline in renal function associated with FD. Based on analyses of FOS data, ERT with agalsidase alfa has also been shown to improve additional signs and symptoms of FD experienced by patients. FOS data analyses have provided a better understanding of the natural history of FD and the specific populations of women, children, and the elderly, and have provided practical tools for the study of FD. FOS has also provided methodology and criteria for assessing disease severity which contributed to the continuous development of medical practice in FD and has largely improved our understanding of the challenges and needs of long-term data collection in rare diseases, aiding in future rare disease real-world evidence studies. Conclusion: FOS over the last 20 years has substantially increased the scientific knowledge around improved patient management of FD and continues to expand our understanding of this rare disease.
Diagnostics
Background: The severity of pectus excavatum is classified by the Haller Index (HI) and/or Correc... more Background: The severity of pectus excavatum is classified by the Haller Index (HI) and/or Correction Index (CI). These indices measure only the depth of the defect and, therefore, impede a precise estimation of the actual cardiopulmonary impairment. We aimed to evaluate the MRI-derived cardiac lateralization to improve the estimation of cardiopulmonary impairment in Pectus excavatum in connection with the Haller and Correction Indices. Methods: This retrospective cohort study included a total of 113 patients (mean age = 19.03 ± 7.8) with pectus excavatum, whose diagnosis was verified on cross-sectional MRI images using the HI and CI. For the development of an improved HI and CI index, the patients underwent cardiopulmonary exercise testing to assess the influence of the right ventricle’s position on cardiopulmonary impairment. The indexed lateral position of the pulmonary valve was utilized as a surrogate parameter for right ventricle localization. Results: In patients with PE, the...
Fabry Outcome Survey (FOS): Highlights from a 20-year patient registry of Fabry disease
Molecular Genetics and Metabolism, 2021
How complete is our clinical assessment of patients with mucopolysaccharidosis type II in real life? A question from the Hunter Outcome Survey (HOS)
Molecular Genetics and Metabolism, 2022
BackgroundPatients are the most important stakeholders in the care of any disease and have an edu... more BackgroundPatients are the most important stakeholders in the care of any disease and have an educational need to learn about their condition and the treatment they should receive. Considering this need for patient-focused materials, we present a directed approach for mucopolysaccharidosis (MPS) VI and MPS IVA, a pair of rare, inherited diseases that affects multiple organs and parts of the body. Independent guidelines on the treatment of these diseases were recently published, providing evidence- and expertise-driven recommendations to optimize patient management. However, while healthcare providers may have the training and knowledge to understand these guidelines, patients and their caregivers can find the technical content challenging. Hence, we aimed to develop plain language summaries (PLS) of the MPS VI and MPS IVA guidelines with patients as the primary audience.ResultsA review of the guidelines by an expert team identified six domains of information relevant to patients: Th...
Treatment of Fabry's Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS)
Clinical Pharmacology & Therapeutics, 2020
Fabry's disease (FD) is an X‐linked lysosomal storage disorder caused by the deficient activi... more Fabry's disease (FD) is an X‐linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α‐galactosidase A (α‐Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous α‐Gal A activity. We assessed safety along with cardiovascular, renal, and patient‐reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under “real‐world” conditions. Fifty‐nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) with amenable mutations were recruited. Migalastat was generally safe and well tolerated. Females and males presented with a reduction of left ventricular mass index (primary end point) (−7.2 and −13.7 g/m2, P = 0.0050 and P = 0.0061). FD‐specific manifestations and symptoms remained stable (all P > 0...
Pferdeheilkunde Equine Medicine, 2001
Ein 11-jähriger Warmblutwallach zeigte über zwei Tage zunächst milde, dann akute hochgradige Koli... more Ein 11-jähriger Warmblutwallach zeigte über zwei Tage zunächst milde, dann akute hochgradige Koliksymptome, ohne dass bei der rektalen Untersuchung ein von der Norm abweichender Befund erhoben werden konnte. Zusätzlich zeigte das Pferd eine hochgradige Kardiopathie mit Kardiomegalie, Vorhofflimmern und Trikuspidalklappeninsuffizienz. Aufgrund fehlender Operationserlaubnis wurde das Pferd wegen der schlechten Prognose euthanasiert. Pathomorphologisch wurde als Kolikursache eine venöse Thrombose mit Nekrose eines Blinddarmsegmentes festgestellt. Mögliche Ursachen venöser Thrombosen und ein möglicher Zusammenhang mit der hochgradigen Kardiopathie werden diskutiert.
Diagnosis and Care of Infants and Children with Pompe Disease
Klinische Pädiatrie, 2020
Pompe disease is a rare metabolic myopathy caused by deficiency of lysosomal α-glucosidase. Reduc... more Pompe disease is a rare metabolic myopathy caused by deficiency of lysosomal α-glucosidase. Reduced enzyme activity results in abnormal intra- and extralysosomal glycogen deposition as well as impaired cellular function and autophagy. Age at manifestation and severity of disease depend on residual enzyme activity. Enzyme replacement therapy (ERT) is available since 2006. In infantile onset Pompe disease, the most severe form, markedly prolonged survival has resulted in a new phenotype with symptoms and problems not encountered previously. In addition, it became apparent that antibody formation against the recombinant human enzyme may adversely affect the response to ERT. This review summarizes new knowledge gained in the last years concerning care of pediatric patients with Pompe disease and gives recommendations for diagnostics, treatment, and follow-up.
Uploads
Papers by Christoph Kampmann