Paediatric sleep apnea event prediction using nasal air pressure and machine learning.

Sleep-disordered breathing is an important health issue for children. The objective of this study was to develop a machine learning classifier model for the identification of sleep apnea events taken exclusively from nasal air pressure measurements acquired during overnight polysomnography for paediatric patients. A secondary objective of this study was to differentiate site of obstruction exclusively from hypopnea event data using the model. Computer vision classifiers were developed via transfer learning to either normal breathing while asleep, obstructive hypopnea, obstructive apnea or central apnea. A separate model was trained to identify site of obstruction as either adeno-tonsillar or tongue base. In addition, a survey of board-certified and board-eligible sleep physicians was completed to compare clinician versus model classification performance of sleep events, and indicated very good performance of our model relative to human raters. The nasal air pressure sample database available for modelling comprised 417 normal, 266 obstructive hypopnea, 122 obstructive apnea and 131 central apnea events derived from 28 paediatric patients. The four-way classifier achieved a mean prediction accuracy of 70.0% (95% confidence interval [67.1-72.9]). Clinician raters correctly identified sleep events from nasal air pressure tracings 53.8% of the time, whereas the local model was 77.5% accurate. The site of obstruction classifier achieved a mean prediction accuracy of 75.0% (95% confidence interval [68.7-81.3]). Machine learning applied to nasal air pressure tracings is feasible and may exceed the diagnostic performance of expert clinicians. Nasal air pressure tracings of obstructive hypopneas may "encode" information regarding the site of obstruction, which may only be discernable by machine learning.

Utility of dual energy computed tomography in the evaluation of infiltrative skeletal lesions and metastasis: a literature review.

Computed tomography (CT) is routinely used to diagnose and evaluate metastatic lesions in oncology. CT alone suffers from lack of sensitivity, especially for skeletal lesions in the bone marrow and lesions that have similar attenuation profiles to surrounding bone. Magnetic resonance imaging and nuclear medicine imaging remain the gold standard in evaluating skeletal lesions. However, compared to CT, these modalities are not as widely available or suitable for all patients. Dual energy computed tomography (DECT) exploits variations in linear attenuation coefficient of materials at different photon energy levels to reconstruct images based on material composition. DECT in musculoskeletal imaging is used in the imaging of crystal arthropathy and detecting subtle fractures, but it is not broadly utilized in evaluating infiltrative skeletal lesions. Malignant skeletal lesions have different tissue and molecular compositions compared to normal bone. DECT may exploit these physical differences to delineate infiltrative skeletal lesions from surrounding bone better than conventional monoenergetic CT. Studies so far have examined the utility of DECT in evaluating skeletal metastases, multiple myeloma lesions, pathologic fractures, and performing image-guided biopsies with promising results. These studies were mostly retrospective analyses and case reports containing small samples sizes. As DECT becomes more widely used clinically and more scientific studies evaluating the performance of DECT are published, DECT may eventually become an important modality in the work-up of infiltrative skeletal lesions. It may even challenge MRI and nuclear medicine because of relatively faster scanning times and ease of access.

The classification of ATP-binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system.

IMPORTANCE: The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a vital role in surfactant homeostasis. Mutations in the ABCA3 gene lead to the development of interstitial lung disease. In the most severe manifestation, mutations can lead to a fatal respiratory distress syndrome in neonates. ABCA3 belongs to the same ATP-binding cassette transporter superfamily as the cystic fibrosis transmembrane conductance regulator (CFTR), the gene that causes cystic fibrosis. OBJECTIVE: To classify ABCA3 mutations in a manner similar to CFTR mutations in order to take advantage of recent advances in therapeutics. METHODS: Sequence homology between the CFTR protein and the ABCA3 protein was established. The region of CFTR that is a target for the new potentiator class of drugs was of particular interest. We performed a literature search to obtain all published mutations that were thought to be disease causing. We classified these mutations using the established CFTR classification system. When possible, we drew on previous experimental classification of ABCA3 mutations. RESULTS: Although the proteins share the same overall structure, only a 19% identity was established between CFTR and ABCA3. The CFTR therapeutic target region has a 22% homology with the corresponding ABCA3 region. Totally 233 unique protein mutations were identified. All protein mutations were classified and mapped to a schematic diagram of the ABCA3 protein. INTERPRETATION: This new classification system for ABCA3, based on CFTR classification, will likely aid further research of clinical outcomes and identification of mutation-tailored therapeutics, with the aim for improving clinical care for patients with ABCA3 mutations.

Hypoglossal Nerve Stimulation in Adolescents With Down Syndrome and Obstructive Sleep Apnea.

IMPORTANCE: Obstructive sleep apnea (OSA) affects up to 60% of children with Down syndrome (DS) and may persist in half of patients after adenotonsillectomy. Children with DS who have persistent OSA often do not tolerate treatment with positive pressure airway support devices or tracheotomy for their residual moderate to severe OSA. The hypoglossal nerve stimulator is an implantable device that delivers an electrical impulse to anterior branches of the hypoglossal nerve in response to respiratory variation, resulting in tongue base protrusion that alleviates upper airway obstruction in adults. OBJECTIVE: To determine whether hypoglossal nerve stimulation is safe and effective in children with DS. DESIGN, SETTING, AND PARTICIPANTS: Case series of the first 6 adolescents with DS to undergo hypoglossal nerve stimulator implantation. Participants were 6 children and adolescents (12-18 years) with DS and severe OSA (apnea hypopnea index [AHI] > 10 events/h) despite prior adenotonsillectomy. INTERVENTION: Inspire hypoglossal nerve stimulator placement. MAIN OUTCOMES AND MEASURES: Patients were monitored for adverse events. Adherence to therapy was measured by hours of use recorded by the device. Efficacy was evaluated by comparing AHI and OSA-18, a validated quality-of-life instrument, scores at baseline and follow-up. RESULTS: In 6 patients (4 male, 2 female; aged 12-18 years), hypoglossal nerve stimulator therapy was well tolerated (mean use, 5.6-10.0 h/night) and effective, resulting in significant improvement in OSA. At 6- to 12-month follow-up, patients demonstrated a 56% to 85% reduction in AHI, with an overall AHI of less than 5 events/h in 4 children and less than 10 events/h in 2 children. Children also demonstrated a clinically significant improvement (mean [SD] overall change score, 1.5 [0.6]; range, 0.9-2.3) on the OSA-18, a validated quality-of-life instrument. CONCLUSIONS AND RELEVANCE: Hypoglossal nerve stimulation was well tolerated and effective in the study population, representing a potential therapeutic option for patients with DS and refractory OSA after adenotonsillectomy who are unable to tolerate positive pressure airway devices. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT2344108.

Characterisation of artisanal mine waste on Buru Island, Indonesia and toxicity to the brittle star Amphipholis squamata.

Artisanal small-scale gold mining (ASGM) using mercury (Hg) amalgamation commenced on Buru Island, Indonesia, in 2012, but was halted in 2015 due to concerns of widespread Hg contamination. Much of the Hg used in the mining process is lost to trommel waste which is disposed of in settlement ponds that drain into adjacent waterways and into Kayeli Bay. Several thousand unmanaged trommel sites and associated tailing ponds exist on Buru Island. This study shows that waste from the Marloso trommel at the Gogrea site contained 203 mg/kg total Hg (THg), with a negligible proportion present as bioavailable methyl Hg (MeHg) and a low total organic carbon content. There are currently very few tools available for ecotoxicological risk assessment of mine tailings for tropical marine ecosystems, and we support the development of Tailings Toxicity Tests (TTTs) and describe laboratory toxicity test methods using the cosmopolitan benthic echinoderm Amphipholis squamata. Undiluted trommel waste caused 100% mortality of A. squamata within 48 h, and a 96-h LC50 of 6.7% w/w trommel waste (4 mg/kg THg) was estimated. Sub-lethal effects on the water vascular system of the brittle star were assessed by quantification of the Ability to Right Itself (ARI), and a 48-h EC50 of 7.3% w/w trommel waste (14.4 mg/kg THg) was estimated. The results show that trommel waste produced on Buru Island is highly contaminated with THg and is acutely toxic, raising serious concern for receiving ecosystems where Hg methylation to more toxic and bioavailable forms is likely.

Management and outcomes of congenital chylothorax in the neonatal intensive care unit: A case series.

IMPORTANCE: Congenital chylothorax is a rare condition with pulmonary and multiorgan system effects, for which there are no standardized treatment recommendations. Collective review of known cases offers some conclusions and suggestions for treatment. OBJECTIVE: The aim of this study was to present a case series of 5 patients who were treated in the neonatal intensive care unit with chylothorax. METHODS: We describe 5 infants who were diagnosed prenatally with hydrops fetalis and postnatally had clinically significant congenital chylothorax. RESULTS: Treatment guidelines specific to congenital forms of chylothorax have not yet been developed, although there are consistent trends across our cases. Four of the 5 infants in this study have survived to date. Chylothorax was treated with chest tube placement and chylous fluid drainage, scrupulous attention to fluid balance, mechanical ventilation, and nutritional management and, in 3 cases, with octreotide infusions. Some of the infants also required treatment for immunodeficiency and altered coagulation pathways. None of the infants underwent surgical thoracic duct ligation. INTERPRETATION: Aided by the advantage of prenatal diagnosis, many cases of congenital chylothorax can be successfully treated by a combination of nutritional and medical management as well as careful attention to fluid and electrolyte balance and avoidance of infection, thereby avoiding the need for surgical ligation of the thoracic duct.

Geochemistry and mercury contamination in receiving environments of artisanal mining wastes and identified concerns for food safety.

Artisanal small-scale gold mining (ASGM) using mercury (Hg) amalgamation has been occurring on Buru Island, Indonesia since early 2012, and has caused rapid accumulation of high Hg concentrations in river, estuary and marine sediments. In this study, sediment samples were collected from several sites downstream of the Mount Botak ASGM site, as well as in the vicinity of the more recently established site at Gogrea where no sampling had previously been completed. All sediment samples had total Hg (THg) concentrations exceeding Indonesian sediment quality guidelines and were up to 82 times this limit at one estuary site. The geochemistry of sediments in receiving environments indicates the potential for Hg-methylation to form highly bioavailable Hg species. To assess the current contamination threat from consumption of local seafood, samples of fish, molluscs and crustaceans were collected from the Namlea fish market and analysed for THg concentrations. The majority of edible tissue samples had elevated THg concentrations, which raises concerns for food safety. This study shows that river, estuary and marine ecosystems downstream of ASGM operations on Buru Island are exposed to dangerously high Hg concentrations, which are impacting aquatic food chains, and fisheries resources. Considering the high dietary dependence on marine protein in the associated community and across the Mollucas Province, and the short time period since ASGM operations commenced in this region, the results warrant urgent further investigation, risk mitigation, and community education.

Hypoglossal Nerve Stimulator Implantation in an Adolescent With Down Syndrome and Sleep Apnea.

Obstructive sleep apnea (OSA) is more common in children with Down syndrome, affecting up to 60% of patients, and may persist in up to 50% of patients after adenotonsillectomy. These children with persistent moderate to severe OSA require continuous positive airway pressure, which is often poorly tolerated, or even tracheotomy for severe cases. The hypoglossal nerve stimulator is an implantable device that produces an electrical impulse to the anterior branches of the hypoglossal nerve, resulting in tongue protrusion in response to respiratory variation. It is an effective treatment of sleep apnea in select adult patients because it allows for alleviation of tongue base collapse, improving airway obstruction. Herein we describe the first pediatric hypoglossal nerve stimulator implantation, which was performed in an adolescent with Down syndrome and refractory severe OSA (apnea hypopnea index [AHI]: 48.5 events/hour). The patient would not tolerate continuous positive airway pressure and required a long-standing tracheotomy. Hypoglossal nerve stimulator therapy was well tolerated and effective, resulting in significant improvement in the patient's OSA (overall AHI: 3.4 events/hour; AHI: 2.5-9.7 events/hour at optimal voltage settings depending on sleep stage and body position). Five months after implantation, the patient's tracheotomy was successfully removed and he continues to do well with nightly therapy.

Giant cystic lymphangioma originating from the lesser curvature of the stomach.

Cystic lymphangiomas are rare benign tumors. Most frequently occurring in children and involving the neck or axilla, these tumors are much less common in adults and very rarely involve the abdomen. The known congenital and acquired (traumatic) etiologies result in failure of the lymphatic channels and consequent proliferation of lymphatic spaces. This case report describes a very rare case of a giant mesenteric cystic lymphangioma in an adult male with no clear etiology and successful resolution by standard radical resection. A previously healthy 44-year-old male presented with a 6-wk history of progressive upper abdominal pain, vomiting, anorexia and unintentional weight loss accompanied by rapid abdominal distension. A palpable mass was detected upon physical examination of the distended abdomen and abdominal computed tomography scan showed a giant multilobulated cystic process, measuring 40 cm in diameter. Exploratory laparotomy revealed an enormous cystic mass containing 6 L of serous fluid. The process appeared to originate from the lesser omentum and the lesser curvature of the stomach. Radical resection of the tumor was performed along with a partial gastrectomy to address potential invasion into the adjacent tissues. Histological analysis confirmed the diagnosis of a multicystic lymphangioma. The postoperative recovery was uneventful and the patient was discharged after 6 d. At 3-mo follow-up, the patient was in good health with no signs of recurrence.