Airway and Blood Monocyte Transcriptomic Profiling Reveals an Antiviral Phenotype in Infants With Severe Respiratory Syncytial Virus Infection.

BACKGROUND: Respiratory syncytial virus (RSV) infection is the primary cause of lower respiratory tract infections in children <5 years of age. Monocytes, especially in the respiratory tract, are suggested to contribute to RSV pathology, but their role is incompletely understood. With transcriptomic profiling of blood and airway monocytes, we describe the role of monocytes in severe RSV infection. METHODS: Tracheobronchial aspirates and blood samples were collected from control patients (n = 9) and those infected with RSV (n = 14) who were admitted to the pediatric intensive care unit. Monocytes (CD14+) were sorted and analyzed by RNA sequencing for transcriptomic profiling. RESULTS: Peripheral blood and airway monocytes of patients with RSV demonstrated increased expression of antiviral and interferon-responsive genes as compared with controls. Cytokine signaling showed a shared response between blood and airway monocytes while displaying responses that were more pronounced according to the tissue of origin. Airway monocytes upregulated additional genes related to migration and inflammation. CONCLUSIONS: We found that the RSV-induced interferon response extends from the airways to the peripheral blood. Moreover, RSV induces a migration-promoting transcriptional program in monocytes. Unraveling the monocytic response and its role in the immune response to RSV infection could help the development of therapeutics to prevent severe disease.

[Child psychiatric learning goals for general psychiatric training: a Delphi study]. / Leerdoelen over kinder- en jeugdpsychiatrie in de opleiding psychiatrie: een delphistudie.

BACKGROUND: The new Dutch training plan for psychiatrists puts more emphasis on life course psychiatry. Subsequently, adjustments in the educational program regarding child and adolescent psychiatric knowledge, skills and attitudes are needed. AIM: A broadly supported agreement and consensus on Dutch national learning objectives of education in child and adolescent psychiatry. METHOD: With a modified Delphi method, a set of preliminary learning objectives formulated by a working group of experts was presented to trainees (n = 9), adult psychiatrists (n = 12), child and adolescent psychiatrists (n = 17) and adult patients and their relatives (n = 15). In two rounds, the learning objectives were commented on, supplemented, scored for relevance and prioritized. RESULTS: Out of 27 original learning objectives, 20 were assessed as important or necessary by over 80% of the respondents (knowledge 7/9, skills 8/10, attitudes 5/8). Two learning objectives were rejected (less than 60% considered these to be important or necessary). Seven learning objectives were re-assessed in a second round as these were modified (5) or added (2). Four of them were rated as important or necessary by over 80% of participants. The following goals were most often prioritized: knowledge about healthy development and intergenerational issues; ability to make contact with children and families and to integrate protective and risk factors of the child and environment; and knowing one’s own limitations of child psychiatric themes. CONCLUSION: A Delphi study helped gain support from stakeholders for adjustments in training and education by creating consensus about child psychiatric learning goals for general psychiatric training.

Liposome-encapsulated dexamethasone attenuates ventilator-induced lung inflammation.

BACKGROUND AND PURPOSE: Systemic glucocorticoid therapy may effectively attenuate lung inflammation but also induce severe side-effects. Delivery of glucocorticoids by liposomes could therefore be beneficial. We investigated if liposome-encapsulated dexamethasone inhibited ventilator-induced lung inflammation. Furthermore, we evaluated whether targeting of cellular Fcγ-receptors (FcγRs) by conjugating immunoglobulin G (IgG) to liposomes, would improve the efficacy of dexamethasone-liposomes in attenuating granulocyte infiltration, one of the hallmarks of lung inflammation. EXPERIMENTAL APPROACH: Mice were anaesthetized, tracheotomized and mechanically ventilated for 5 h with either 'low' tidal volumes ∼7.5 mL·kg(-1) (LV(T) ) or 'high' tidal volumes ∼15 mL·kg(-1) (HV(T) ). At initiation of ventilation, we intravenously administered dexamethasone encapsulated in liposomes (Dex-liposomes), dexamethasone encapsulated in IgG-modified liposomes (IgG-Dex-liposomes) or free dexamethasone. Non-ventilated mice served as controls. KEY RESULTS: Dex-liposomes attenuated granulocyte infiltration and IL-6 mRNA expression after LV(T) -ventilation, but not after HV(T) -ventilation. Dex-liposomes also down-regulated mRNA expression of IL-1ß and KC, but not of CCL2 (MCP-1) in lungs of LV(T) and HV(T) -ventilated mice. Importantly, IgG-Dex-liposomes inhibited granulocyte influx caused by either LV(T) or HV(T) -ventilation. IgG-Dex-liposomes diminished IL-1ß and KC mRNA expression in both ventilation groups, and IL-6 and CCL2 mRNA expression in the LV(T) -ventilated group. Free dexamethasone prevented granulocyte influx and inflammatory mediator expression induced by LV(T) or HV(T) -ventilation. CONCLUSIONS AND IMPLICATIONS: FcγR-targeted IgG-Dex-liposomes are pharmacologically more effective than Dex-liposomes particularly in inhibiting pulmonary granulocyte infiltration. IgG-Dex-liposomes inhibited most parameters of ventilator-induced lung inflammation as effectively as free dexamethasone, with the advantage that liposome-encapsulated dexamethasone will be released locally in the lung thereby preventing systemic side-effects.

Internal maxillary artery pseudoaneurysm: a near fatal complication of seemingly innocuous pharyngeal trauma.

A 2-year-old boy presented with persistent pain and oral blood loss after falling with a toothbrush in his mouth. Initial routine inspection of the oropharynx showed no abnormalities. Recurrent blood loss instigated a reinspection under general anesthesia revealing the head of the toothbrush embedded in the nasopharynx. The toothbrush was removed without problems but several hours later a near fatal rebleeding occurred, requiring aggressive fluid resuscitation. Subsequently, the patient was transferred to our pediatric intensive care unit for further evaluation and treatment. CT angiography (CTA) showed a pseudoaneurysm of the internal maxillary artery which was successfully coiled, and further recovery was uneventful. Pediatric pharyngeal trauma is a common entity with rare, but potentially life-threatening, complications. In case of pharynx lesions, bleeding, and persistent pain, flexible endoscopy by an otolaryngologist is mandatory. In case of persistent bleeding vascular imaging is essential with CTA being a reliable alternative for the more invasive angiography.