Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells.

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies.

Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency.

Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.

A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body.

Process reengineering of preoperative verification, site marking and time-out for patient safety.

In this article, we describe our hospital's journey in implementing the WHO High 5s Project Correct Site Surgery Standard (CSS) protocol. We discuss how we incorporated the protocol into our system by revising the pre-existing checklist, reengineering the existing processes on preoperative verification, site marking and time-out at the Major Operating Theatre (MOT), and performing audit and feedback to ensure effective compliance. We also reflect on the importance of leadership and ministry support, benchmarking and tailoring the practice for each discipline in the pursuit of improving patient safety within the hospital.

Traumatic Cochlear Implant Electrode Extrusion: Considerations, Management, and Outcome.

Cochlear implantation is the mainstay for patients with severe to profound hearing loss that do not benefit from hearing aids. Falls and head trauma can cause direct damage to the implant, of which hard failure is the most common complication. Traumatic electrode migration is an uncommon occurrence. Our patient underwent successful electrode advancement of a partially migrated, normal functioning electrode two months after head injury. We discuss the factors influencing the decision-making process, progress, and outcomes.

Synchronous airway lesions and associated anomalies in children with laryngomalacia evaluated with rigid endoscopy.

OBJECTIVE: To evaluate the prevalence of synchronous airway lesions (SALs) and associated anomalies in children with laryngomalacia requiring rigid endoscopic evaluation, the clinical significance of such lesions, and safety and outcome of selective rigid endoscopy. SETTING: National Children's Hospital. DESIGN AND METHOD: Retrospective analysis. The records of all children diagnosed with laryngomalacia who underwent rigid endoscopy were identified from the surgical database over a 4-year period. OUTCOME MEASURES: Age at presentation, signs and symptoms at time of presentation, presence of associated neurological and/or congenital anomalies (ANCAs), presence of synchronous airway lesions, need for surgical intervention, complications and time to resolution of symptoms were assessed. RESULTS: There were 26 children in the study. The mean age at presentation ranged from 0 to 10 months of age. One child (3.8%) required surgical intervention for severe isolated laryngomalacia. Seven children (26.9%) had at least one SAL identified. Of these, six (85.7%) were previously diagnosed on flexible fibreoptic laryngoscopy (FFL). Two of the seven children with SALs required surgical management of the SAL. Prematurity and ANCAs prolonged hospital stays in these children. However, the presence of SALs did not affect the length of hospital stay or the time to resolution of symptoms. Symptom resolved in all children by 3 years of age, whether or not SALs or ANCAs are present. There was no adverse outcome in the study group. CONCLUSION: Despite having indications for rigid endoscopy, many children with laryngomalacia do not have SALs, which even when present, are rarely clinically significant. SALs and ANCAs do not impact the time to symptom resolution. The current indications for rigid endoscopy in the evaluation of laryngomalacia are appropriate and safe.

Hazardous foreign bodies: complications and management of button batteries in nose.

Miniature batteries are easily available in our domestic environment, powering many electronic devices and toys. Despite improvement in the safety standards, children are able to remove the batteries from these devices. These batteries pose a hazard to children, as they are small and easily inserted into the nose or ears or even swallowed. We describe 6 children who inserted button batteries into their noses. Four of these insertions resulted in septal perforations. The mechanisms and management of button battery injury are discussed. We emphasize the need for urgent removal of a battery from the nose to prevent long-term complications.

Suppurative intracranial complications of sinusitis in children.

OBJECTIVE: A review of suppurative intracranial complications of sinusitis in children. METHODS: Case series review over a two-year period from 1998 to 1999 in a children's hospital, Singapore. RESULTS: There were seven cases, all male, and age range 9 to 14. Six had subdural empyemas and one had meningitis. The most common presenting symptoms included fever, headache and vomiting. Sinusitis was suspected as the cause in only one patient initially. The intracranial infections were not apparent from the initial brain CT of two patients and were only confirmed later on repeated imaging. Four patients had lumbar punctures without any adverse effects. All seven children had infections involving the frontal, ethmoid and maxillary sinuses and two also had sphenoid involvements. All were treated with high-dose intravenous antibiotics together with drainage of both the intracranial (n=six) and sinus (n=seven) suppurations. Five needed repeated intracranial drainages. Streptococcus species were isolated in five cases. Three patients developed seizures post-operatively which resolved on follow-up. One patient needed a ventriculo-peritoneal shunt for hydrocephalus. All patients had a good Glasgow Outcome Score. The hospital stay ranged from 30 to 89 days with a median of 43 days. CONCLUSIONS: Only males were identified in this review, collaborating the feeling that teenage males are at greatest risk of developing intracranial infections from sinusitis. We recommend that radiologic imaging of the brain for suspected intracranial infection should always include the sinuses as this aids early identification of actual cause. Initial CT imaging may be negative and hence repeated scans are warranted if the index of suspicion is high. The successful outcome of the children in this series supports the opinion that combined aggressive surgical and medical treatment is preferable in this patient population.

Mass newborn screening for hearing impairment.

Significant hearing impairment is common and impairs communication potential if not detected early. Babies born at the National University Hospital from March 1999 to February 2001 were screened at birth using the strategy of measuring Transient Evoked Oto Acoustic Emissions with the ILO 88 Otodynamics Echoport. The screening was conducted within 24 hours of birth in the majority of patients. Those testing positive were re-screened at about 2 weeks and at 6 weeks if still testing positive. Those who tested positive at 6 weeks were referred to Otolaryngology for formal evaluation of hearing. A total screening rate of 97.2% (4,387 out of 4,514 livebirths) was achieved. Of the 312 testing positive at 6 weeks, 8 were subsequently proven to have significant hearing impairment. Four of them required binaural amplification, giving a 1 in 1,096 incidence of severe hearing impairment. A specificity, positive predictive value and sensitivity of 93%, 26% and 100% respectively were obtained. In all but one, the diagnosis was made by 7 months of age and interventions set in place within 2 months of diagnosis. The screening strategy was reliable and sensitive. A strategy to reduce the high false positive rate needs to be developed.

Preauricular sinuses in the pediatric population: techniques and recurrence rates.

AIM: To review the outcomes of two surgical techniques in the management of preauricular sinus in the pediatric population. METHODS: The clinical records of pediatric patients who underwent surgical excision of preauricular sinus in the Department of Otolaryngology of KK Children's and Women's Hospital between January 1997 and March 2009 were retrospectively reviewed. Patients were categorized into two groups, based on the method used for sinus tract visualization or delineation: (1) Microscope group and (2) methylene blue dye and probe group. The latest information on recurrence of preauricular sinus and complications after surgery were updated by phone interview. RESULTS: 208 out of 305 preauricular sinuses were included in this study (n=114 in microscope group; n=94 in methylene blue dye and probe group). 97 cases were excluded as these patients were not contactable by phone or had inadequate data from the clinical records. The mean age of the patients is 6.5 years old. The overall recurrence rate was 2.4% (95% confidence interval (CI) 0.010-0.055) and the overall complication rate was 6.3% (CI 0.037-0.104). Surgical excision with microscope guidance had significantly lower recurrence rate (0.9%) compared to surgical excision with methylene blue dye and probe guidance (4.3%), with an odds ratio of 28.4 (CI 1.22-659.99, P=0.037). The complication rates were not statistically significant between the two groups. The recurrence and complication rates were not significantly affected by race, gender, sex, location of sinus, indication for surgery, history of previous sinus excision, presence of infection during surgery and duration of surgery. CONCLUSION: Surgical excision of preauricular sinus under microscope guidance and under methylene blue and probe guidance in our series had very low overall recurrence and complication rates compared to that reported in the literature. The microscope group had a lower recurrence rate in comparison to that of the methylene blue and probe group.