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Introduction An increasing number of case reports have associated vaccinations against coronavirus disease 2019 (COVID-19) with immune-mediated thrombotic thrombocytopenic purpura (iTTP), a very rare but potentially life-threatening thrombotic microangiopathy, which leads to ischemic organ dysfunction. Thrombus formation in iTTP is related to a severe deficiency of the specific von Willebrand-factor-cleaving protease ADAMTS13 due to ADAMTS13 autoantibodies. Methods We present a case of iTTP following exposure to the mRNA-based COVID-19 vaccine BNT162b2 (Comirnaty®, Pfizer-BioNTech). In addition, we review previously reported cases in the literature and assess current evidence. Results Apart from our case, twenty cases of iTTP occurring after COVID-19 vaccination had been published until the end of November 2021. There were 11 male and 10 female cases; their median age at diagnosis was 50 years (range 14-84 years). Five patients (24%) had a preexisting history of iTTP. Recombinant adenoviral vector-based vaccines were involved in 19%, mRNA-based vaccines in 81%. The median onset of symptoms after vaccination was 12 days (range 5-37), with 20 cases presenting within 30 days. Treatment included therapeutic plasma exchange in all patients. Additional rituximab, caplacizumab, or both these treatments were given in 43% (9/21), 14% (3/21), and 24% (5/21) of cases, respectively. One patient died, despite a prolonged clinical course in one patient, all surviving patients were in clinical remission at the end of the observational period. Conclusion Clinical features of iTTP following COVID-19 vaccination were in line with those of pre-pandemic iTTP. When timely initiated, an excellent response to standard treatment was seen in all cases. ADAMTS13 activity should be determined pre-vaccination in patients with a history of a previous iTTP episode. None of the reported cases met the WHO criteria for assessing an adverse event following immunization (AEFI) as a consistent causal association to immunization. Further surveillance of safety data and additional case-based assessment are needed.

Hintergrund und Ziele: Bei Kindern mit klassischem adrenogenitalen Syndrom mit 21-Hydroxylase Defekt (AGS) und Salzverlust sind adrenale Krisen im Rahmen von Stress-Situationen besonders gefürchtet. Das Ziel der Arbeit war die Untersuchung der Häufigkeit und Ursachen von adrenalen Krisen bei Patienten mit klassischem AGS mit Salzverlust, die in der Kinderklinik des Universitätsklinikums Erlangen ambulant betreut werden. Methoden (Patienten, Material und Untersuchungsmethoden): In einem Zeitraum von 1981 bis 2016 wurden 100 Kinder mit klassischem AGS (42 m, 58 w) im Alter von 0.1 bis 18 Jahren in die Untersuchung eingeschlossen (Stichtag: 18.2.2016). Die Daten wurden retrospektiv anhand der Patientenakten und Arztbriefe erhoben. Erfasst wurden mit einem standardisierten Bogen neben den Basisdaten der Patienten, die Zahl der ambulanten Vorstellungen sowie die Zahl der stationären Aufnahmen und der adrenalen Krisen im Untersuchungszeitraum, sowie die jeweiligen Auslöser der adrenalen Krise. Eine Addison-Krise wurde durch das Vorliegen von mindestens 2 der folgenden Kriterien definiert: Hypotonie, Übelkeit/Erbrechen, Abgeschlagenheit, Somnolenz, Hyponatriämie, Hyperkaliämie, Hypoglykämie. Die Auswertung der Daten erfolgte nach 4 Altersgruppen: Säuglingsalter (< 1 Jahr), Kleinkindalter (2.-6.Lebensjahr), Grundschulalter (7.-10. Lebensjahr) und Adoleszenz (11.-18. Lebensjahr). Ergebnisse und Beobachtungen (MW ± SD): Von den Patienten wurden 50 im Säuglingsalter und 50 erstmals im Alter von über einem Jahr ambulant vorgestellt. Ambulante Verlaufsuntersuchungen erfolgten im Säuglingsalter mit 2.42 ± 1.60 pro Jahr signifikant häufiger als in den anderen Altersgruppen (Kleinkindalter 1.60 ± 0.66, Grundschulalter 1.70 ± 0.60, Adoleszenz 1.33 ± 0.6). Insgesamt wurden 118 stationäre Aufnahmen dokumentiert, d.h. 9.9 stationäre Aufnahmen pro 100 Patientenjahre. Kleinkinder wurden mit 13.8 stationären Aufnahmen/Jahr signifikant häufiger hospitalisiert als Säuglinge (6/Jahr), Kinder im Grundschulalter (4.5/Jahr) und Adoleszenten (3.1/Jahr). Ursächlich waren am häufigsten fieberhafte Infekte (43 %), virale Infektionen (42 %) und Gastroenteritiden (31 %). Insgesamt wurden 14 Addisonkrisen dokumentiert. Dies entspricht 1.1 Krisen pro 100 Patientenjahre bzw. 10.2 % der stationären Aufnahmen. Bei der Addison-Krise wurde ein Serum-Natriumwert im Median von 128 mmol/l (Min – Max: 109 - 135), ein Serum-Kaliumwert von 5.7 mmol/l (3.8 – 7.5) und ein pH-Wert von 7.26 (7.19 - 7.41) gefunden. Schlussfolgerungen: Die Ergebnisse der vorliegenden Untersuchung haben einige Einschränkungen und müssen daher kritisch bewertet werden. Die ambulante Betreuung der Kinder erfolgte zwar in Erlangen, aber die stationären Aufnahmen erfolgten überwiegend in externen Kinderkliniken. Die klinischen und laborchemischen Daten wurden aus den Arztberichten entnommen und waren nicht immer vollständig. Die häufigsten stationären Aufnahmen fanden im Kleinkindalter statt und dienten der Verhinderung einer Addison-Krise. Pro 100 Patientenjahre fanden sich 9.9 stationäre Aufnahmen, eine Zahl die mit der Literatur gut übereinstimmt. Insgesamt wurden 14 Addisonkrisen (9 im Kleinkindalter, 5 in der Adoleszenz) dokumentiert, wobei 2 Kinder in der Krise verstarben. Die Zahl der manifesten adrenalen Krisen von 1.17 pro 100 Patientenjahre ist im Vergleich zu anderen Untersuchungen niedrig. Background and objectives: Adrenal crises are particularly feared in stress situations in children with classic congenital adrenal syndrome with 21 Hydroxylase defect (CAH) and salt loss. The goal was to examine the frequency and causes of adrenal crises in patients with classic CAH with salt loss who are treated in the outpatients‘ department of the University Children‘s Hospital in Erlangen. Patients and methods: 100 children with classic CAH (42 m, 58 f) aged between 0.1 and 18 years between 1981 and 2016 were included in the study (cut-off date: 18.2.2016). The data were compiled retrospectively from the patient files and physicians‘ letters. In addition to the basic patient data, a standardised form was used to collect data on the number of out-patient presentations and in-patient admissions, on the adrenal crises during the investigation period and the trigger event of the adrenal crisis. An adrenal crisis was defined as the presence of at least 2 of the following criteria: hypotension, nausea/vomiting, lassitude, drowsiness, hyponatraemia, hyperkalaemia, hypoglycaemia. The data were evaluated in four age groups: infancy (< 1 year), early childhood (2nd-6th year of life), primary school age (7th-10th year of life) and adolescence (11th-18th year of life). Results (Mean ± SD): 50 of the patients presented in our outpatients‘ department in the first year of life and 50 presented for the first time over the age of one year. Outpatient follow-up examinations in infancy (2.42 ± 1.60 per year) were significantly more frequent than in the other age groups (early childhood 1.60 ± 0.66, primary school age 1.70 ± 0.60, adolescence 1.33 ± 0.6). 118 in-patient admissions were recorded in total, i.e. 9.9 in-patient admissions per 100 patient years. Small children were significantly more frequently hospitalised with 13.8 admissions/year than infants (6/year), children of primary school age (4.5/year) and adolescents (3.1/year). The most common causes were febrile infections (43 %), viral infections (42 %) and gastro-enteritis (31 %). 14 Addison crises were documented in total. This equates to 1.17 crises per 100 patient years or 10.2 % of the in-patient admissions. On admission, the Addison crisis was found to have a median serum-sodium of 124 mmol/l (min – max: 109 - 135), a serum-potassium of 5.7 mmol/l (3.8 – 7.5) and a pH value of 7.26 (7.19 - 7.41). Conclusions: The results of the present study have some limitations and must therefore be evaluated critically. Although the outpatient care of the children was carried out in Erlangen, in-patient admissions predominantly occurred in external children’s hospitals. The clinical and lab data were gathered from the doctors‘ reports and were not always complete. In-patient admissions occurred most frequently in early childhood in order to avoid an Addisonian crisis. There were 9.9 in-patient admissions per 100 patient years, a number which tallies with the literature. A total of 14 adrenal crises was documented (9 in early childhood, 5 during adolescence), whereby 2 children died during the crisis. The number of adrenal crises of 1.17 per 100 patient years is low in comparison with other studies.

Methane (CH4) production within the oceanic mixed layer is a widespread phenomenon, but the underlying mechanisms are still under debate. Marine algae might contribute to the observed CH4 oversaturation in oxic waters, but so far direct evidence for CH4 production by marine algae has only been provided for the coccolithophore Emiliania huxleyi. In the present study we investigated, next to E. huxleyi, other widespread haptophytes, i.e., Phaeocystis globosa and Chrysochromulina sp. We performed CH4 production and stable carbon isotope measurements and provide unambiguous evidence that all three investigated marine algae are involved in the production of CH4 under oxic conditions. Rates ranged from 1.9±0.6 to 3.1±0.4 µg of CH4 per gram of POC (particulate organic carbon) per day, with Chrysochromulina sp. and E. huxleyi showing the lowest and highest rates, respectively. Cellular CH4 production rates ranged from 16.8±6.5 (P. globosa) to 62.3±6.4 ag CH4 cell−1 d−1 (E. huxleyi; ag = 10−18 g). In cultures that were treated with 13C-labeled hydrogen carbonate, δ13CH4 values increased with incubation time, resulting from the conversion of 13C–hydrogen carbonate to 13CH4. The addition of 13C-labeled dimethyl sulfide, dimethyl sulfoxide, and methionine sulfoxide – known algal metabolites that are ubiquitous in marine surface layers – resulted in the occurrence of 13C-enriched CH4 in cultures of E. huxleyi, clearly indicating that methylated sulfur compounds are also precursors of CH4. By comparing the algal CH4 production rates from our laboratory experiments with results previously reported in two field studies of the Pacific Ocean and the Baltic Sea, we might conclude that algae-mediated CH4 release is contributing to CH4 oversaturation in oxic waters. Therefore, we propose that haptophyte mediated CH4 production could be a common and important process in marine surface waters.