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OBJECTIVE: This study examined radiation exposure and the possible risk of radiation-induced cancer in a large sample of newborn and premature patients. MATERIAL AND METHODS: In this retrospective study, we included all hospitalised neonates treated at our university hospital who received at least one X-ray examination from 1 January 2013 to 31 December 2018. We evaluated the dose area product (DAP), effective dose (ED), and estimated risk. The International Commission on Radiological Protection Publication 60 defines values (2.8-13 × 10-2 Sv-1) to calculate the estimated risk in relation to the ED. RESULTS: Of the 3843 patients (aged 241.1 ± 35.45 days) treated in the neonatal care unit, 1307 (34%) received at least one X-ray. The mean number of X-ray examinations per patient was 3.19 and correlated negatively with birth weight. The mean cumulative DAP was 5.9 mGy*cm2, and the cumulative ED was 23.7 µSv per hospital stay. Patients with a birth weight of < 1000 g showed the highest cumulative ED and DAP (p < 0.001). Patients with a birth weight of < 2500 g had the highest ED and DAP per image (p < 0.001). The highest radiation exposure (ED/DAP) occurred for thoracic/abdominal examinations, especially for neonates < 500 g (p < 0.001). CONCLUSION: There is a strong correlation between immaturity, the number of X-ray examinations, and radiation exposure. The total exposure was minimal, and the number of X-rays per patient has been decreasing in recent years. CLINICAL RELEVANCE: Possible risks to newborns and premature infants caused by ionising X-rays are often the subject of scientific and clinical discussion. Nevertheless, conventional X-ray imaging remains a frequently used tool, and total exposure remains at a very low level. KEY POINTS: The number of X-rays per patient has been decreasing in a large university hospital. Half of all patients received only one X-ray; most had a birth weight over 1500 g. This radiation risk can be classified as 'minimal' for patients with a birth weight of < 500 g and as 'negligible' for others.
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BackgroundSince the beginning of the war in Ukraine in February 2022, Ukrainians have been seeking shelter in other European countries.AimWe aimed to investigate the prevalence and the molecular epidemiology of multidrug-resistant Gram-negative (MDRGN) bacteria and meticillin-resistant Staphylococcus aureus (MRSA) in Ukrainian patients at admittance to the University Hospital Frankfurt, Germany.MethodsWe performed screening and observational analysis of all patients from March until June 2022. Genomes of MDRGN isolates were analysed for antimicrobial resistance, virulence genes and phylogenetic relatedness.ResultsWe included 103 patients (median age: 39⯱â¯23.7 years), 57 of whom were female (55.3%; 95% confidence interval (CI): 45.2-5.1). Patients were most frequently admitted to the Department of Paediatrics (29/103; 28.2%; 95%â¯CI: 19.7-37.9). We found 34 MDRGN isolates in 17 of 103 patients (16.5%; 95%â¯CI: 9.9-25.1). Ten patients carried 21 carbapenem-resistant (CR) bacteria, five of them more than one CR isolate. Four of six patients with war-related injuries carried eight CR isolates. In six of 10 patients, CR isolates caused infections. Genomic characterisation revealed that the CR isolates harboured at least one carbapenemase gene, bla NDM-1 being the most frequent (nâ¯=â¯10). Core genome and plasmid analysis revealed no epidemiological connection between most of these isolates. Hypervirulence marker genes were found in five of six Klebsiella pneumoniae CR isolates. No MRSA was found.ConclusionHospitals should consider infection control strategies to cover the elevated prevalence of MDRGN bacteria in Ukrainian patients with war-related injuries and/or hospital pre-treatment and to prevent the spread of hypervirulent CR isolates.
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Infecções por Klebsiella , Staphylococcus aureus Resistente à Meticilina , Lesões Relacionadas à Guerra , Humanos , Criança , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Filogenia , Lesões Relacionadas à Guerra/tratamento farmacológico , beta-Lactamases/genética , Bactérias , Hospitais Universitários , Alemanha/epidemiologia , Bactérias Gram-Negativas/genética , Klebsiella pneumoniae/genética , Infecções por Klebsiella/tratamento farmacológicoRESUMO
BACKGROUND: Congenital toxoplasmosis can be associated with serious clinical consequences from fetus to adulthood. Hence, early detection is required to minimize severe sequelae through appropriate therapy. We describe the first case of a congenital toxoplasmosis after maternal coinfection with Toxoplasma gondii and severe acute respiratory syndrome coronavirus 2 and the challenging serological diagnosis of the disease in this context. CASE PRESENTATION: A Caucasian boy was born at 27 weeks 2 days of gestation by cesarean section due to maternal COVID-19-related respiratory failure. Postpartum serological screening of the mother revealed a previously unrecognized active Toxoplasma gondii infection. The premature child initially tested negative for anti- Toxoplasma gondii immunoglobulin A and M antibodies 1, 2 and 4 weeks after birth, whereas immunoglobulin G antibodies were only weakly positive with no evidence of child-specific production. Neither neurological nor ophthalmological abnormalities were detected. Approximately 3 months after birth, serological testing indicated a congenital toxoplasmosis by presence of immunoglobulin A and M, in combination with a child-specific immunoglobulin G synthesis. Additionally, cerebrospinal fluid was tested positive for Toxoplasma gondii DNA. Although no clinical manifestations of congenital toxoplasmosis were detected, an antiparasitic therapy was initiated to minimize the risk of late sequelae. There were no hints for a transplacental transmission of severe acute respiratory syndrome coronavirus 2. CONCLUSION: This case raises the awareness of possible coinfections with the risk of transplacental transmission in cases of maternal coronavirus disease 2019. The report emphasizes the need for screening vulnerable patients for toxoplasmosis in general and especially in the context of pregnancy. It becomes evident that prematurity can complicate the serological diagnosis of congenital toxoplasmosis due to a delayed antibody response. Repeated testing is recommended to carefully monitor children at risk and especially those with a history of preterm birth.
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COVID-19 , Coinfecção , Nascimento Prematuro , Toxoplasma , Toxoplasmose Congênita , Toxoplasmose , Masculino , Gravidez , Recém-Nascido , Humanos , Feminino , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/prevenção & controle , SARS-CoV-2 , Cesárea , Imunoglobulina G , Imunoglobulina A , Imunoglobulina MRESUMO
Background: After enterostomy creation, the distal bowel to the ostomy is excluded from the physiologic passage of stool, nutrient uptake, and growth of this intestinal section. Those infants frequently require long-term parenteral nutrition, continued after enterostomy reversal due to the notable diameter discrepancy of the proximal and distal bowel. Previous studies have shown that mucous fistula refeeding (MFR) results in faster weight gain in infants. The aim of the randomized multicenter open-label controlled MUCous FIstula REfeeding ("MUC-FIRE") trial is to demonstrate that MFR between enterostomy creation and reversal reduces the time to full enteral feeds after enterostomy closure compared to controls, resulting in shorter hospital stay and less adverse effects of parenteral nutrition. Methods/Design: A total of 120 infants will be included in the MUC-FIRE trial. Following enterostomy creation, infants will be randomized to either an intervention or a non-intervention group.In the intervention group, perioperative MFR between enterostomy creation and reversal will be performed. The control group receives standard care without MFR.The primary efficacy endpoint of the study is the time to full enteral feeds. Secondary endpoints include first postoperative bowel movement after stoma reversal, postoperative weight gain, and days of postoperative parenteral nutrition. In addition adverse events will be analyzed. Discussion: The MUC-FIRE trial will be the first prospective randomized trial to investigate the benefits and disadvantages of MFR in infants. The results of the trial are expected to provide an evidence-based foundation for guidelines in pediatric surgical centers worldwide. Trial registration: The trial has been registered at clinicaltrials.gov (number: NCT03469609, date of registration: March 19, 2018; last update: January 20, 2023, https://clinicaltrials.gov/ct2/show/NCT03469609?term=NCT03469609&draw=2&rank=1).
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UNLABELLED: Allergic bronchopulmonary aspergillosis (ABPA) is a rare pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. The prevalence is estimated to be about 1-2% in adult patients with asthma and 2-15% in patients with cystic fibrosis. In paediatric patients with asthma, only single case reports on ABPA exist. We report on a 13-year-old boy with allergic asthma complicated by ABPA. Despite the presentation of typical clinical symptoms, it took 6 years before he was diagnosed. The clinical course improved rapidly after ABPA therapy was started, and 12 months after diagnosis, the boy is still free of symptoms. Clinical symptoms of ABPA may be unspecific making a rapid diagnosis difficult in some cases. CONCLUSION: A delay in diagnosis and treatment increases the risk for irreversible lung damage. Once bronchiectasis has developed, the outcome is unfavourable. Thus, ABPA has to be considered in patients whose asthma remains uncontrolled despite adequate therapy.
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Aspergilose Broncopulmonar Alérgica/complicações , Aspergilose Broncopulmonar Alérgica/diagnóstico , Asma/complicações , Sons Respiratórios/etiologia , Adolescente , Humanos , MasculinoRESUMO
BACKGROUND: Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. METHODS: In this randomized multicenter trial, 216 preterm infants born at 26 + 0-29 + 6 gestational weeks will be allocated to receive a higher (6-8 cmH2O) or a lower (3-5 cmH2O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO2 > 0.5 for > 1 h or pCO2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). DISCUSSION: Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4-8 cmH2O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. TRIAL REGISTRATION: drks.de DRKS00019940 . Registered on March 13, 2020.
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Síndrome do Desconforto Respiratório do Recém-Nascido , Síndrome do Desconforto Respiratório , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Pulmão , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , RessuscitaçãoRESUMO
OBJECTIVE: Sphingosine-1-phosphate (S1P) is a bioactive lipid, which influences migration and proliferation of endothelial cells through activation of S1P receptors and has been shown to support SDF-1 induced migration and bone marrow homing of CD34+ progenitors. METHODS AND RESULTS: Here, we show that incubation of patient-derived endothelial progenitor cells (EPCs) with S1P or its synthetic analog FTY720 improved blood flow recovery in ischemic hind limbs. Likewise, recovery of blood flow was dramatically reduced after induction of hindlimb ischemia in mice deficient for the S1P receptor 3 (S1P3). S1P3-/- bone marrow-derived mononuclear cells (BMCs) failed to augment neovascularization after hind limb ischemia. Of note, treatment of BMCs derived from S1P3-/- mice with S1P did not rescue blood flow recovery. Mechanistically, S1P and FTY720 induced phosphorylation of CXCR4, activated the Src kinase, and stimulated phosphorylation of JAK2. The contribution of CXCR4 for S1P-mediated effects was further supported by the findings that S1P preincubation failed to stimulate invasion capacity and in vivo blood flow recovery of BMCs from CXCR4+/- mice. The activation of CXCR4 was dependent on the Src kinase family as demonstrated by preincubation with the Src inhibitor PP2. The activation of the CXCR4 signaling by S1P is mediated via the S1P3 receptor, since S1P-induced Src phosphorylation was abrogated in EPC from S1P3-/- mice. CONCLUSIONS: S1P agonists might serve as sensitizers of CXCR4-mediated signaling and may be applied in clinical progenitor cell therapy to improve EPC or BMC function in patients with coronary artery disease.
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Lisofosfolipídeos/farmacologia , Receptores CXCR4/fisiologia , Receptores de Lisoesfingolipídeo/fisiologia , Transdução de Sinais/fisiologia , Esfingosina/análogos & derivados , Células-Tronco/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Ativação Enzimática/efeitos dos fármacos , Cloridrato de Fingolimode , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lisofosfolipídeos/genética , Camundongos , Camundongos Transgênicos , Propilenoglicóis/farmacologia , Receptores CXCR4/genética , Receptores de Lisoesfingolipídeo/genética , Transdução de Sinais/efeitos dos fármacos , Esfingosina/genética , Esfingosina/farmacologia , Células-Tronco/efeitos dos fármacos , Quinases da Família src/genética , Quinases da Família src/fisiologiaRESUMO
Transplantation of bone marrow cells as well as circulating endothelial progenitor cells (EPC) enhances neovascularization after ischemia. The chemokine receptor CXCR4 is essential for migration and homing of hematopoietic stem cells. Therefore, we investigated the role of CXCR4 and its downstream signaling cascade for the angiogenic capacity of cultured human EPC. Ex vivo, differentiated EPC derived from peripheral blood abundantly expressed CXCR4. Incubation of EPC from healthy volunteers with neutralizing antibodies against CXCR4 profoundly inhibited vascular endothelial growth factor- and stromal-derived factor-1-induced migration as well as EPC-induced angiogenesis in an ex vivo assay. Preincubation of transplanted EPC with CXCR4 antibody reduced EPC incorporation and impaired blood-flow recovery in ischemic hindlimbs of nude mice (57+/-4% of normal perfusion versus untreated EPC: 80+/-11%, P<0.001). Bone marrow mononuclear cells (BM-MNC) or EPC of heterozygous CXCR4(+/-) mice displayed reduced CXCR4 expression and disclosed impaired in vivo capacity to enhance recovery of ischemic blood flow in nude mice (blood flow 27+/-11% versus 66+/-25% using wild-type cells, P<0.01). Importantly, impaired blood flow in ischemic CXCR4(+/-) mice was rescued by injection of wild-type BM-MNC. Next, we investigated the role of CXCR4 for functional capacities of EPC from patients with coronary artery disease (CAD). Surface expression of CXCR4 was similar in EPC from patients with CAD compared with healthy controls. However, basal Janus kinase (JAK)-2 phosphorylation was significantly reduced and less responsive to stromal-derived factor-1 in EPC from patients with CAD compared with healthy volunteers, indicating that CXCR4-mediated JAK-2 signaling is dysregulated in EPC from patients with CAD. The CXCR4 receptor signaling profoundly modulates the angiogenic activity and homing capacity of cultured human EPC. Disturbance of CXCR4 signaling, as demonstrated by reduced JAK-2 phosphorylation, may contribute to functional impairment of EPC from patients with CAD. Stimulating CXCR4 signaling might improve functional properties of EPC and may rescue impaired neovascularization capacity of EPC derived from patients with CAD.
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Doença das Coronárias/fisiopatologia , Células Endoteliais/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Neovascularização Fisiológica , Receptores CXCR4/fisiologia , Transdução de Sinais/fisiologia , Animais , Movimento Celular , Células Cultivadas , Quimiocina CXCL12 , Quimiocinas CXC/fisiologia , Humanos , Interleucina-3/farmacologia , Janus Quinase 2 , Camundongos , Proteínas Tirosina Quinases/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Transplante de Células-TroncoRESUMO
BACKGROUND: Transplantation of endothelial progenitor cells (EPCs) improves neovascularization after ischemia, but patients with coronary artery disease (CAD) or diabetes mellitus show a reduced number of EPCs and impaired functional activity. Therefore, we investigated the effects of risk factors, such as glucose and TNF-alpha, on the number of EPCs in vitro to elucidate the underlying mechanisms. METHODS AND RESULTS: EPCs of patients or healthy subjects were isolated from peripheral blood. Incubation with glucose or TNF-alpha dose-dependently reduced the number of EPCs (79.9+/-1.3% and 74.3+/-8.1% of control; P<0.05, respectively). This reduction was not caused by apoptosis. TNF-alpha and glucose induced a dose- and time-dependent activation of the p38 MAP kinase, the downstream kinase mitogen- and stress-activated kinase 1, and the transcription factor cAMP-responsive element-binding protein (CREB), in EPCs. Moreover, EPCs from CAD patients had significantly higher basal p38-phosphorylation levels (1.83+/-0.2-fold increase; P<0.05) compared with healthy subjects. The inhibition of the p38-kinase by SB203580 or infection with a dominant negative p38 kinase adenovirus significantly increased basal number of EPCs (136.7+/-6.3% and 142.9+/-18% versus control, respectively). Likewise, ex vivo cultivation of EPCs from patients with CAD with SB203580 significantly increased the number of EPCs and partially reversed the impaired capacity for neovascularization of EPCs in vivo (relative blood flow: 0.40+/-0.03 versus 0.64+/-0.08, P<0.05). The increased numbers of EPCs by SB203580 were associated with an augmentation of EPC proliferation and a reduction of cells expressing the monocytic marker proteins CD14 and CD64, suggesting that p38 regulates proliferation and differentiation events. CONCLUSIONS: These results demonstrate that p38 MAP kinase plays a pivotal role in the signal transduction pathways regulating the number of EPCs ex vivo. SB203580 can prevent the negative effects of TNF-alpha and glucose on the number of EPCs and may be useful to improve the number of EPCs for potential cell therapy.