Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study.

OBJECTIVE: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not. DESIGN: Secondary analysis of multicenter retrospective cohort study. SETTING: Ten PICUs in the United States between 2009 and 2021. PATIENTS: Nine hundred thirteen patients 0-21 years old who died after WLST. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality). CONCLUSIONS: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

Extracorporeal Life Support for Respiratory Failure in Patients With Electronic Cigarette or Vaping Product Use-Associated Lung Injury.

OBJECTIVES: Electronic cigarette or vaping product use-associated lung injury is a clinical entity that can lead to respiratory failure and death. Despite the severity of electronic cigarette or vaping product use-associated lung injury, the role of extracorporeal life support in its management remains unclear. Our objective was to describe the clinical characteristics and outcomes of patients with electronic cigarette or vaping product use-associated lung injury who received extracorporeal life support. DESIGN: We performed a retrospective review of records of electronic cigarette or vaping product use-associated lung injury patients who received extracorporeal life support. Standardized data were collected via direct contact with extracorporeal life support centers. Data regarding presentation, ventilatory management, extracorporeal life support details, and outcome were analyzed. SETTING: This was a multi-institutional, international case series with patients from 10 different institutions in three different countries. PATIENTS: Patients who met criteria for confirmed electronic cigarette or vaping product use-associated lung injury (based on previously reported diagnostic criteria) and were placed on extracorporeal life support were included. Patients were identified via literature review and by direct contact with extracorporeal life support centers. MEASUREMENTS AND MAIN RESULTS: Data were collected for 14 patients ranging from 16 to 45 years old. All had confirmed vape use within 3 months of presentation. Nicotine was the most commonly used vaping product. All patients had respiratory symptoms and radiographic evidence of bilateral pulmonary opacities. IV antibiotics and corticosteroids were universally initiated. Patients were intubated for 1.9 days (range, 0-6) prior to extracorporeal life support initiation. Poor oxygenation and ventilation were the most common indications for extracorporeal life support. Five patients showed evidence of ventricular dysfunction on echocardiography. Thirteen patients (93%) were placed on venovenous extracorporeal life support, and one patient required multiple rounds of extracorporeal life support. Total extracorporeal life support duration ranged from 2 to 37 days. Thirteen patients survived to hospital discharge; one patient died of septic shock. CONCLUSIONS: Electronic cigarette or vaping product use-associated lung injury can cause refractory respiratory failure and hypoxemia. These data suggest that venovenous extracorporeal life support can be an effective treatment option for profound, refractory respiratory failure secondary to electronic cigarette or vaping product use-associated lung injury.

Growth failure in focal dermal hypoplasia.

Focal dermal hypoplasia (FDH) is a rare genetic disorder caused by mutations in the PORCN gene located on the X chromosome. Short stature was previously noted to be a common finding in FDH, however the etiology of this is unclear. The present study sought to elucidate specific causes for short stature by assessing growth charts, determining bone ages and auxologic measurements, examining laboratory data for the common causes of growth failure, assessing dietary intake, and performing a growth hormone stimulation test. Sixteen patients with FDH between the ages of 3 and 18 years of age consented to the study. While 11 out of 16 patients had short stature based on height less than 2 standard deviations below mid-parental target height percentile and bone age not suggestive of likely catch-up growth, only four had a BMI less than the 5th percentile for age. Laboratory studies did not support a gastrointestinal, allergy or autoimmune cause of growth failure. Three patients had results suggestive of possible growth hormone deficiency. Although short stature is a common feature in FDH, our data suggests that severe undernutrition is not common in this group and that there may be underlying treatable causes for this short stature in some patients.

Patients with mutations in Gsalpha have reduced activation of a downstream target in epithelial tissues due to haploinsufficiency.

CONTEXT: Patients with Albright hereditary osteodystrophy (AHO) have defects in stimulatory G protein signaling due to loss of function mutations in GNAS. The mechanism by which these mutations lead to the AHO phenotype has been difficult to establish due to the inaccessibility of the affected tissues. OBJECTIVE: The objective of the study was to gain insight into the downstream consequences of abnormal stimulatory G protein signaling in human epithelial tissues. PATIENTS AND DESIGN: We assessed transcription of GNAS and Gsalpha-stimulated activation of the cystic fibrosis transmembrane conductance regulator (CFTR) in AHO patients, compared with normal controls and patients with cystic fibrosis. MAIN OUTCOME MEASURES: Relative expression of Gsalpha transcripts from each parental GNAS allele and cAMP measurements from nasal epithelial cells were compared among normal controls and AHO patients. In vivo measurements of CFTR function, pulmonary function, and pancreatic function were assessed in AHO patients. RESULTS: GNAS was expressed equally from each allele in normals and two of five AHO patients. cAMP generation was significantly reduced in nasal respiratory epithelial cells from AHO patients, compared with normal controls (0.4 vs. 0.6, P = 0.0008). Activation of CFTR in vivo in nasal (P = 0.0065) and sweat gland epithelia (P = 0.01) of AHO patients was significantly reduced from normal. In three patients, the reduction in activity was comparable with patients with cystic fibrosis due to mutations in CFTR. Yet no AHO patients had pulmonary or pancreatic disease consistent with cystic fibrosis. CONCLUSIONS: In humans, haploinsufficiency of GNAS causes a significant reduction in the activation of the downstream target, CFTR, in vivo.

Perinatal calcium metabolism: physiology and pathophysiology.

Disturbances in mineral homeostasis are common in the neonatal period, especially in premature infants and infants who are hospitalised in an intensive care unit. In many cases these disturbances are thought to be exaggerated responses to the normal physiological transition from the intrauterine environment to neonatal independence. By contrast, some disturbances in calcium homeostasis are the result of genetic defects, which in many instances can now be identified at the molecular level. In other cases hypocalcaemia or hypercalcaemia may result from pathological intrauterine conditions, birth trauma or stress, or fetal immaturity. Diagnosis and management of hypocalcaemia and hypercalcaemia in the neonate and infant requires specific knowledge of perinatal mineral physiology and the unique clinical and biochemical features of newborn mineral metabolism. In this chapter we will provide a brief overview of calcium metabolism with an emphasis on the neonatal transition, followed by discussion of the common causes of hypercalcaemia and hypocalcaemia.

Primary hyperparathyroidism in children and adolescents: the Johns Hopkins Children's Center experience 1984-2001.

Primary hyperparathyroidism (PHPT) generally affects older adults, yet it also occurs in a small number of children, adolescents, and young adults. The early presentation of PHPT in children and adolescents suggests that these parathyroid tumors may differ in pathobiology from more typical tumors that occur in older adults. We performed a retrospective analysis of cases of PHPT treated surgically at the Johns Hopkins Children's Center between 1984 and 2001. Patients were ascertained by review of surgical pathology records, which confirmed the diagnosis of PHPT, and clinical and biochemical characteristics were extracted from medical records. We retrieved data on 16 of 17 patients; these patients (9 male, 7 female) were aged 10.5-20 years (16.3 +/- 2.9 years, median 16.8 years) at the time of diagnosis. Five patients had known metabolic risk factors for development of hyperparathyroidism, whereas 11 patients had spontaneous PHPT. The preoperative serum calcium level was markedly elevated (2.98 +/- 0.25 mM) in all 13 patients with normal renal function. Nearly all (77%) of these patients were found to have at least one symptom or sign of PHPT, most commonly hypercalciuria (83%) or nephrolithiasis (54%). Of these patients, 11 (85%) had single adenomas (mean weight, 597 mg; median, 600 mg; range, 170-1550 mg) while 2 had multiple gland disease, including 1 patient with multiple endocrine neoplasia type 2 (MEN2). In all cases, surgery was curative. These data suggest that PHPT in children is a more severe disease than in older adults, which may reflect a bias of ascertainment or a difference in fundamental parathyroid pathobiology.