Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

Implementation of a PCR-based strategy to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit.

OBJECTIVES: To evaluate the clinical and epidemiological impact of a new molecular surveillance strategy based on qPCR to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit (NICU). METHODS: We design a specific qPCR for the detection of S. marcescens in rectal swabs of patients admitted to a NICU. We divided the surveillance study into two periods: (a) the pre-PCR, from the outbreak declaration to the qPCR introduction, and (b) the PCR period, from the introduction of the qPCR until the outbreak was solved. In all cases, S. marcescens isolates were recovered and their clonal relationship was analysed by PFGE. Control measures were implemented during the outbreak. Finally, the number of bloodstream infections (BSI) was investigated in order to evaluate the clinical impact of this molecular strategy. RESULTS: Nineteen patients colonized/infected by S. marcescens were detected in the pre-PCR period (October 2020-April 2021). On the contrary, after the PCR implementation, 16 new patients were detected. The PFGE revealed 24 different pulsotypes belonging to 7 different clonal groups, that were not overlapping at the same time. Regarding the clinical impact, 18 months after the qPCR implementation, no more outbreaks by S. marcescens have been declared in the NICU of our hospital, and only 1 episode of BSI has occurred, compared with 11 BSI episodes declared previously to the outbreak control. CONCLUSIONS: The implementation of this qPCR strategy has proved to be a useful tool to control the nosocomial spread of S. marcescens in the NICU.

Examining the immune signatures of SARS-CoV-2 infection in pregnancy and the impact on neurodevelopment: Protocol of the SIGNATURE longitudinal study.

The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders. Based on the hypothesis that neuroinflammation during early stages of life is associated with neurodevelopmental disorders and confers a greater risk of developing neuropsychiatric disorders, we propose a cohort study of SARS-CoV-2-infected pregnant women and their newborns. The main objective of SIGNATURE project is to explore how the presence of prenatal SARS-CoV-2 infection and other non-infectious stressors generates an abnormal inflammatory activity in the newborn. The cohort of women during the COVID-19 pandemic will be psychological and biological monitored during their pregnancy, delivery, childbirth and postpartum. The biological information of the umbilical cord (foetus blood) and peripheral blood from the mother will be obtained after childbirth. These samples and the clinical characterisation of the cohort of mothers and newborns, are tremendously valuable at this time. This is a protocol report and no analyses have been conducted yet, being currently at, our study is in the recruitment process step. At the time of this publication, we have identified 1,060 SARS-CoV-2 infected mothers and all have already given birth. From the total of identified mothers, we have recruited 537 SARS-COV-2 infected women and all of them have completed the mental health assessment during pregnancy. We have collected biological samples from 119 mothers and babies. Additionally, we have recruited 390 non-infected pregnant women.

[Langerhans cell histiocytosis with atypical and early neonatal debut]. / Histiocitosis de células de Langerhans con debut neonatal atipico y precoz.

Langerhans cell histiocytosis is a systemic disease associated with the proliferation of this type of cells in tissues. Its prevalence is estimated at 1-9/100 000. Bone is the most frequently affected organ, followed by the skin, lymph nodes, haematopoietic system, pituitary gland, lungs and liver. In the majority of cases, onset occurs during childhood, with peak between one and three years of age, and poor prognosis before two years of age. The haematological forms (pancytopenia) are usually aggressive in infants. We report a case of Langerhans cell histiocytosis with neonatal onset and complex diagnosis: maintained and significant leukocytosis was the predominant data for the first two months of life, so some type of leukemia was considered. However, the most common blood disorder in Langerhans cell histiocytosis is pancytopenia rather than leukocytosis, so that the diagnosis was delayed.

La histiocitosis de células de Langerhans es una enfermedad sistemica asociada con la proliferación de este tipo de células en distintos tejidos. La prevalencia estimada es de 1-9/100 000. El órgano más frecuentemente afectado es el hueso, seguido por la piel, ganglios linfáticos, sistema hematopoyético, hipófisis, pulmones e hígado. En la mayoría de los casos, la enfermedad debuta en la infancia, con pico entre uno y tres años de edad, y tiene mal pronóstico cuando ocurre antes de los dos años. La afectación del sistema hematopoyético, manifestada en forma de pancitopenia, suele ser agresiva en los lactantes. Se presenta un caso de histiocitosis de células de Langerhans con debut neonatal y complejo diagnóstico, ya que, los dos primeros meses de vida, el dato predominante era una leucocitosis importante mantenida que obligaba a descartar alguna forma de leucemia, mientras que la alteración hematológica más frecuente en la histiocitosis de células de Langerhans, como se ha comentado, es la pancitopenia, lo que motivó un retraso en el diagnóstico.

Histiocitosis de células de Langerhans con debut neonatal atipico y precoz / Langerhans cell histiocytosis with atypical and early neonatal debut

La histiocitosis de células de Langerhans es una enfermedad sistemica asociada con la proliferación de este tipo de células en distintos tejidos. La prevalencia estimada es de 1-9/100 000. El órgano más frecuentemente afectado es el hueso, seguido por la piel, ganglios linfáticos, sistema hematopoyético, hipófisis, pulmones e hígado. En la mayoría de los casos, la enfermedad debuta en la infancia, con pico entre uno y tres años de edad, y tiene mal pronóstico cuando ocurre antes de los dos años. La afectación del sistema hematopoyético, manifestada en forma de pancitopenia, suele ser agresiva en los lactantes. Se presenta un caso de histiocitosis de células de Langerhans con debut neonatal y complejo diagnóstico, ya que, los dos primeros meses de vida, el dato predominante era una leucocitosis importante mantenida que obligaba a descartar alguna forma de leucemia, mientras que la alteración hematológica más frecuente en la histiocitosis de células de Langerhans, como se ha comentado, es la pancitopenia, lo que motivó un retraso en el diagnóstico.

Langerhans cell histiocytosis is a systemic disease associated with the proliferation of this type of cells in tissues. Its prevalence is estimated at 1-9/100 000. Bone is the most frequently affected organ, followed by the skin, lymph nodes, haematopoietic system, pituitary gland, lungs and liver. In the majority of cases, onset occurs during childhood, with peak between one and three years of age, and poor prognosis before two years of age. The haematological forms (pancytopenia) are usually aggressive in infants. We report a case of Langerhans cell histiocytosis with neonatal onset and complex diagnosis: maintained and significant leukocytosis was the predominant data for the first two months of life, so some type of leukemia was considered. However, the most common blood disorder in Langerhans cell histiocytosis is pancytopenia rather than leukocytosis, so that the diagnosis was delayed.

Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville.

BACKGROUND: Early diagnosis of primary immunodeficiency such as severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) improves outcome of affected children. T-cell-receptor-excision circles (TRECs) and kappa-deleting-recombination-excision circles (KRECs) determination from dried blood spots (DBS) identify neonates with severe T- and/or B-lymphopenia. No prospective data exist of the impact of gestational age (GA) and birth weight (BW) on TRECs and KRECs values. METHODS: TRECs and KRECs determination using triplex RT-PCR (TRECS-KRECS-ß-actin-Assay) from prospectively collected DBS between 02/2014 and 02/2015 in three hospitals in Seville, Spain. Cut-off levels were TRECs < 6/punch, KRECs < 4/punch and -ß-actin>700/punch. Internal (SCID, XLA, ataxia telangiectasia) and external controls (NBS quality assurance program, CDC) were included. RESULTS: A total of 5160 DBS were tested. Re-punch was needed in 77 samples (1.5%) due to insufficient ß-actin (<700 copies/punch). Pre-term neonates (GA<37 weeks) and neonates with a BW<2500 g showed significantly lower TRECs and KRECs levels (p < 0.001). Due to repeat positive results five neonates were re-called (<0.1%): Fatal chromosomopathy (n = 1; TRECs 1/KRECs 4); extreme pre-maturity (n = 2; TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch); neonates born to mothers receiving azathioprine during pregnancy (n = 2; TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch). All internal and external controls were correctly identified. CONCLUSIONS: TRECS-KRECS-ß-actin-Assay correctly identifies T- and B-cell lymphopenias. Pre-maturity and low BW is associated with lower TREC and KREC levels. Extreme pre-maturity and maternal immune suppressive therapy may be a cause for false positive results of TRECs and KRECs values, respectively. To reduce the rate of insufficient samples, DBS extraction and storage need to be improved.

Neonatal fulminant type 2 infantile hepatic hemangioendothelioma involving skin, viscera and soft tissue.

We present the fulminant case of a neonate whose symptoms, lesions, imaging, and laboratory tests perfectly simulated a neonatal neuroblastoma and the definitive diagnosis was finally given by necropsy as follows: Infantile hepatic hemangioendothelioma type 2 with extrahepatic extension affecting skin, lung, intestine, suprarenal, and soft tissue.

Rabdomiomatosis cardíaca asociada a esclerosis tuberosa / Cardiac rhabdomyomatosis associated with tuberous sclerosis

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