5 research outputs found
Maintenance of Elective Patient Care at Berlin University Children's Hospital During the COVID-19 Pandemic
Background: In Germany, so far the COVID-19 pandemic evolved in two distinct waves, the first beginning in February and the second in July, 2020. The Berlin University Children's Hospital at Charité (BCH) had to ensure treatment for children not infected and infected with SARS-CoV-2. Prevention of nosocomial SARS-CoV-2 infection of patients and staff was a paramount goal. Pediatric hospitals worldwide discontinued elective treatments and established a centralized admission process.
Methods: The response of BCH to the pandemic adapted to emerging evidence. This resulted in centralized admission via one ward exclusively dedicated to children with unclear SARS-CoV-2 status and discontinuation of elective treatment during the first wave, but maintenance of elective care and decentralized admissions during the second wave. We report numbers of patients treated and of nosocomial SARS-CoV-2 infections during the two waves of the pandemic.
Results: During the first wave, weekly numbers of inpatient and outpatient cases declined by 37% (p < 0.001) and 29% (p = 0.003), respectively. During the second wave, however, inpatient case numbers were 7% higher (p = 0.06) and outpatient case numbers only 6% lower (p = 0.25), compared to the previous year. Only a minority of inpatients were tested positive for SARS-CoV-2 by RT-PCR (0.47% during the first, 0.63% during the second wave). No nosocomial infection of pediatric patients by SARS-CoV-2 occurred.
Conclusion: In contrast to centralized admission via a ward exclusively dedicated to children with unclear SARS-CoV-2 status and discontinuation of elective treatments, maintenance of elective care and decentralized admission allowed the almost normal use of hospital resources, yet without increased risk of nosocomial infections with SARS-CoV-2. By this approach unwanted sequelae of withheld specialized pediatric non-emergency treatment to child and adolescent health may be avoided
The relevance of the proteins Bax and Bak to the induction of apoptosis by the BH3-only protein Harakiri
In malignen Zellen ist Apoptose häufig dysreguliert. Entscheidend bei der
Regulierung der Apoptoseinduktion ist die Bcl-2-Proteinfamilie, deren
Vertreter mittels Bcl-2-homologen Domänen (BH 1-4) interagieren. Die
Proteinfamilie umfasst antiapoptotische Proteine wie Mcl-1 und proapoptotische
wie Bax und Bak. Harakiri (Hrk) gehört zur proapoptotischen Untergruppe der
lediglich die BH3-Domäne aufweisenden BH3 only-Proteine, die Bax und Bak durch
Hemmung der antiapoptotischen Proteine aktivieren. Da die Expression von Hrk
in verschiedenen Neoplasien erniedrigt ist, sollte in dieser Arbeit untersucht
werden, welche Expressionsmuster von Bax und Bak Neoplasien einer
Tumortherapie mittels Substitution von Hrk zugänglich machen. Um die durch Hrk
aktivierten Signalwege zu untersuchen, wurde ein rekombinanter adenoviraler
Vektor (Ad-Hrk) zur regulierbaren Ăśberexpression von Hrk hergestellt. Mit dem
Vektor transfizierte Hrk-negative HCT 116-Coloncarcinomzellen zeigen unter
sog. On-Bedingungen eine deutliche Hrk-Expression. Die durchflusszytometrische
Bestimmung der Rate hypodiploider Zellen erwies, dass die ektope Expression
von Hrk in Wildtyp-HCT-116-Zellen Apoptose induziert. Um eine Abhängigkeit
Hrk-induzierter Apoptose von Bax und Bak zu adressieren, wurde Hrk zusätzlich
in HCT-116-Zellen mit spezifischem Verlust von Bax, Bak oder Bax und Bak
ĂĽberexprimiert. Im Gegensatz zu Bax-profizienten Zellen erwiesen sich Bax-
defiziente HCT-116-Zellen unabhängig vom Bak-Expressionsstatus als resistent
gegenĂĽber Hrk. Hrk-Expression fĂĽhrte in Bax-profizienten Zellen, nicht aber in
Bax-defizienten Zellen zum Verlust des mitochondrialen Membranpotentials, zur
Caspase 3-Aktivierung und zur DNA-Fragmentierung. Die Hrk-Resistenz Bax-
negativer/Bak-positiver HCT-116-Zellen konnte interessanterweise durch siRNA-
vermittelte Herunterregulation des Bak-Inhibitors Mcl 1 ĂĽberwunden werden. Die
Ergebnisse zeigen, dass eine erniedrigte Bax-Expression in Kombination mit Mcl
1-Expression ein Resistenzfaktor gegenĂĽber Hrk-induzierter Apoptose ist.
Folglich kommen nur Bax exprimierende oder Mcl-1-negative Neoplasien fĂĽr eine
Hrk substituierende Tumortherapie in Frage. Da der Verlust von Bax und die
Expression von Mcl-1 in Tumorzellen jedoch häufig vorkommen, ist vermutlich
selbst in solchen Neoplasien ein Teil der Zellen resistent gegenĂĽber Hrk-
Substitution. Daher sollten entsprechende klinische Studien
Kombinationstherapien mit einem Pharmakon nutzen, das diese Zellen mittels
Inhibition von Mcl-1 sensibilisieren kann.Apoptosis is frequently dysregulated in malignant neoplasia. A crucial role in
the regulation of apoptosis induction is played by the Bcl-2 family of
proteins, which interact via Bcl-2 homology domains (BH1-4). The protein
family comprises antiapoptotic proteins, such as Mcl-1, as well as
proapoptotic proteins, such as Bax and Bak. Harakiri (Hrk) belongs to the
subgroup of proapoptotic proteins which exhibit only the BH3 domain and are
therefore called BH3-only proteins. These proteins activate Bax and Bak by
inhibiting the antiapoptotic Bcl-2 family members. As the expression of hrk is
suppressed in different types of neoplasia, Hrk is a potential target of a
therapy that focusses on inducing apoptosis in tumour cells. The aim of this
study is to determine which expression patterns of Bax and Bak in tumours are
suitable for Hrk functionally substituting tumour therapies. To investigate
the signaling pathways downstream of Hrk, a recombinant adenoviral vector
system (Ad-Hrk) for controlled overexpression of the protein was established.
HCT 116 colon carcinoma cells transfected with Ad-Hrk show a distinct
expression of Hrk if incubated under so-called On-conditions. Flow cytometric
analysis of the rate of hypodiploid cells revealed induction of apoptosis in
wild type HCT 116 cells after ectopic expression of Hrk. To address a
potential dependency of Hrk-induced apoptosis from Bax and Bak, Hrk was
overexpressed also in HCT 116 cells with specific loss of Bax, Bak or both. In
contrast to Bax-proficient cells, Bax-deficient HCT 116 cells turned out to be
resistant to Hrk. This was irrespective of the expression status of Bak. In
Bax proficient, but not in Bax deficient cells, expression of Hrk lead to loss
of the mitochondrial membrane potential, activation of Caspase 3 and DNA
fragmentation. Interestingly, the resistance of Bax negative/Bak positive HCT
116 cells towards Hrk was overcome by siRNA-mediated downregulation of the Bak
inhibitor Mcl-1. The results demonstrate that a reduced expression of Bax in
combination with the expression of Mcl 1 is a resistance factor against Hrk
induced apoptosis. Hence only Bax expressing or Mcl-1 negative neoplasms are
suitable for an Hrk substituting tumour therapy. As the loss of Bax and the
expression of Mcl 1 are frequently found in tumour cells, presumably even in
such neoplasms a part of the cells is resistant towards substitution of Hrk.
Therefore accordant clinical studies ought to be based on combination
therapies with drugs which can sensitize these cells by inhibition of Mcl 1
Geographical Accessibility of Pediatric Inpatient, Nephrology, and Urology Services in Europe
Background: Although many children with diseases of the kidneys and the urinary tract may not tolerate long journeys, the number of facilities that provide specialized care for these patients is limited. Therefore, the geographical accessibility of the required health services is critical especially in this patient group. We have analyzed the geographical accessibility of pediatric inpatient and nephro-urology services in Germany, Ireland, and the United Kingdom (UK).
Methods: This study introduces a model to compare countries or regions regarding the geographical accessibility of their health services. We calculated the geodesic distances, travel distances, and travel time by car from evenly distributed random points to the nearest facilities that provide pediatric inpatient or nephro-urology outpatient services (pediatric inpatient ward, urology clinic, nephrology clinic, hemodialysis unit). The results were weighted by population density. We compared the three countries with regard to the accessibility of the named services.
Results: Weighted median travel times from the random points to the nearest pediatric inpatient ward are < 30 min in all countries. Weighted travel times to the nearest point of pediatric service are shortest in the UK (median <50 min) and longest in Ireland (median <90 min), regardless of the type of service (p < 0.0001). Non-weighted travel times to the nearest pediatric inpatient ward and hemodialysis unit, however, are shorter in Germany than in the UK (p < 0.0001).
Conclusions: There is a surprising disparity between the travel times to the nearest facility with pediatric nephro-urology service in these three industrialized European countries. Reasons may be differences in the geographical distribution of the population, the focus of the health care system, and a different degree of clinical networking
A Case Report: First Long-Term Treatment With Burosumab in a Patient With Cutaneous-Skeletal Hypophosphatemia Syndrome
Epidermal nevus syndromes encompass a highly heterogeneous group of systemic
disorders, characterized by epidermal nevi, and a spectrum of neuromuscular, ocular,
and bone abnormalities. Cutaneous-skeletal hypophosphatemia syndrome (CSHS)
constitutes a specific sub-entity in which elevated levels of fibroblast growth factor-23
cause hypophosphatemic rickets that are, to date, not amenable to causal therapy. Here,
we report the first long-term follow-up of causal treatment with burosumab in a 3-year-old
female patient with CSHS. 4 weeks after initiation of burosumab treatment, serum
phosphate normalized to age-appropriate levels. Furthermore, long-term follow-up of
42 months revealed significant improvement of linear growth and gross physical functions,
including respiratory insufficiency. Radiographic rickets severity as well as subjective bone
pain were strongly reduced, and no side effects were observed over the course of
treatment. In summary, we, here, report about a successful treatment of
hypophosphatemic rickets in CSHS with burosumab over the time course of 42
months. In our patient, burosumab showed convincing efficacy and safety profile,
without any loss of effect or increase of dose