Student nurses' experiences with a digital educational resource supporting learning in nursing home placements: A qualitative study.

BACKGROUND: Nursing education should improve clinical placements in nursing homes to foster and enhance student nurses' learning experiences. Initiatives for digital educational resource used to teach and supervise students to complement learning are increasingly being adopted and considered important in nursing education. However, little is known about how digital educational resources can facilitate learning in placements. Research on the value of such resources from student nurses' perspective is required. AIM: To explore first-year student nurses' experiences with a digital educational resource developed to support learning in nursing home placements. DESIGN: This study has a qualitative explorative design and is part of a larger research project in which a digital educational resource named DigiQUALinPRAX was developed. SETTINGS: This study was conducted at three publicly funded nursing homes affiliated with one Norwegian university. PARTICIPANTS: Twenty-three first-year student nurses. METHODS: Data was generated through pre- and post-placement group interviews and analysed using reflexive thematic analysis. Standards for Reporting Qualitative Research were applied in this stud. FINDINGS: One overreaching theme and three subthemes related to student nurses' experiences with a digital educational resource were identified. The digital educational resource gave a feeling of being acknowledged as a learner by (1) providing a structure and preparation that made the placement feel less overwhelming, (2) supporting professional reflection and assessment practices, and (3) facilitating collaboration when all stakeholders used the resource actively. CONCLUSIONS: This study indicates that student nurses' learning process in nursing home placements can be supported through digital educational resources customised for this learning arena. The findings indicate that the digital educational resource facilitated pre-placement preparedness, provided structure and flexibility, and enhanced reflection and assessment practices during clinical placement. However, encouraging tripartite usage is essential to exploit the full potential of digital educational resources.

First 24-Hour-Long Intensive Care Unit Testing of a Clinical-Scale Microfluidic Oxygenator in Swine: A Safety and Feasibility Study.

Microfluidic membrane oxygenators are designed to mimic branching vasculature of the native lung during extracorporeal lung support. To date, scaling of such devices to achieve clinically relevant blood flow and lung support has been a limitation. We evaluated a novel multilayer microfluidic blood oxygenator (BLOx) capable of supporting 750-800 ml/min blood flow versus a standard hollow fiber membrane oxygenator (HFMO) in vivo during veno-venous extracorporeal life support for 24 hours in anesthetized, mechanically ventilated uninjured swine (n = 3/group). The objective was to assess feasibility, safety, and biocompatibility. Circuits remained patent and operated with stable pressures throughout 24 hours. No group differences in vital signs or evidence of end-organ damage occurred. No change in plasma free hemoglobin and von Willebrand factor multimer size distribution were observed. Platelet count decreased in BLOx at 6 hours (37% dec, P = 0.03), but not in HFMO; however, thrombin generation potential was elevated in HFMO (596 ± 81 nM·min) versus BLOx (323 ± 39 nM·min) at 24 hours ( P = 0.04). Other coagulation and inflammatory mediator results were unremarkable. BLOx required higher mechanical ventilator settings and showed lower gas transfer efficiency versus HFMO, but the stable device performance indicates that this technology is ready for further performance scaling and testing in lung injury models and during longer use conditions.

Weight Loss for Patients With Gout and Concomitant Obesity: A Proof-of-Concept Randomized Trial.

OBJECTIVE: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. METHODS: We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. RESULTS: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. CONCLUSION: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

Human Kidney Proximal Tubule-Microvascular Model Facilitates High-Throughput Analyses of Structural and Functional Effects of Ischemia-Reperfusion Injury.

Kidney ischemia reperfusion injury (IRI) poses a major global healthcare burden, but effective treatments remain elusive. IRI involves a complex interplay of tissue-level structural and functional changes caused by interruptions in blood and filtrate flow and reduced oxygenation. Existing in vitro models poorly replicate the in vivo injury environment and lack means of monitoring tissue function during the injury process. Here, a high-throughput human primary kidney proximal tubule (PT)-microvascular model is described, which facilitates in-depth structural and rapid functional characterization of IRI-induced changes in the tissue barrier. The PREDICT96 (P96) microfluidic platform's user-controlled fluid flow can mimic the conditions of IR to induce pronounced changes in cell structure that resemble clinical and in vivo phenotypes. High-throughput trans-epi/endo-thelial electrical resistance (TEER) sensing is applied to non-invasively track functional changes in the PT-microvascular barrier during the two-stage injury process and over repeated episodes of injury. Notably, ischemia causes an initial increase in tissue TEER followed by a sudden increase in permeability upon reperfusion, and this biphasic response occurs only with the loss of both fluid flow and oxygenation. This study demonstrates the potential of the P96 kidney IRI model to enhance understanding of IRI and fuel therapeutic development.

Malaria and tuberculosis co-infection-a review.

Malaria and tuberculosis remain highly prevalent infectious diseases and continue to cause significant burden worldwide. Endemic regions largely overlap, and co-infections are expected to occur frequently. Surprisingly, malaria-tuberculosis co-infection is relatively understudied. Malaria has long been known to have immunomodulatory effects, for example resulting in reduced vaccination responses against some pathogens, and it is conceivable that this also plays a role if co-infection occurs. Data from animal studies indeed suggest clinically important effects of malaria-tuberculosis co-infection on the immune responses with potential consequences for the pathophysiology and clinical course of both infections. Specifically, rodent studies consistently show reduced control of mycobacteria during malaria infection. Although the underlying immunological mechanisms largely remain unclear, an altered balance between pro- and anti-inflammatory responses may play a role. Some observations in humans also support the hypothesis that malaria infection skews the immune responses against tuberculosis, but data are limited. Further research is needed to unravel the underlying immunological mechanisms and delineate possible implications of malaria-tuberculosis co-infection for clinical practice.

Intracranial Empyema in Children: A Single-center Retrospective Case Series.

We conducted a retrospective, observational study of 42 children with intracranial empyema admitted to a pediatric neurosurgical center over a 9-year period. Intracranial empyema is rare, but causes significant morbidity and mortality. Twenty-eight cases had neurosurgical source control, more commonly for subdural collections. Streptococcus anginosus group bacteria are important pathogens in subdural empyema, whose isolation predicts more complicated postoperative courses.

Toward microfluidic integration of respiratory and renal organ support in a single cartridge.

BACKGROUND: Extracorporeal organ assist devices provide lifesaving functions for acutely and chronically ill patients suffering from respiratory and renal failure, but their availability and use is severely limited by an extremely high level of operational complexity. While current hollow fiber-based devices provide high-efficiency blood gas transfer and waste removal in extracorporeal membrane oxygenation (ECMO) and hemodialysis, respectively, their impact on blood health is often highly deleterious and difficult to control. Further challenges are encountered when integrating multiple organ support functions, as is often required when ECMO and ultrafiltration (UF) are combined to deal with fluid overload in critically ill patients, necessitating an unwieldy circuit containing two separate cartridges. METHODS: We report the first laboratory demonstration of simultaneous blood gas oxygenation and fluid removal in single microfluidic circuit, an achievement enabled by the microchannel-based blood flow configuration of the device. Porcine blood is flowed through a stack of two microfluidic layers, one with a non-porous, gas-permeable silicone membrane separating blood and oxygen chambers, and the other containing a porous dialysis membrane separating blood and filtrate compartments. RESULTS: High levels of oxygen transfer are measured across the oxygenator, while tunable rates of fluid removal, governed by the transmembrane pressure (TMP), are achieved across the UF layer. Key parameters including the blood flow rate, TMP and hematocrit are monitored and compared with computationally predicted performance metrics. CONCLUSIONS: These results represent a model demonstration of a potential future clinical therapy where respiratory support and fluid removal are both realized through a single monolithic cartridge.

Steady-state monitoring of oxygen in a high-throughput organ-on-chip platform enables rapid and non-invasive assessment of drug-induced nephrotoxicity.

High-throughput, rapid and non-invasive readouts of tissue health in microfluidic kidney co-culture models would expand their capabilities for pre-clinical assessment of drug-induced nephrotoxicity. Here, we demonstrate a technique for monitoring steady state oxygen levels in PREDICT96-O2, a high-throughput organ-on-chip platform with integrated optical-based oxygen sensors, for evaluation of drug-induced nephrotoxicity in a human microfluidic co-culture model of the kidney proximal tubule (PT). Oxygen consumption measurements in PREDICT96-O2 detected dose and time-dependent injury responses of human PT cells to cisplatin, a drug with known toxic effects in the PT. The injury concentration threshold of cisplatin decreased exponentially from 19.8 µM after 1 day to 2.3 µM following a clinically relevant exposure duration of 5 days. Additionally, oxygen consumption measurements resulted in a more robust and expected dose-dependent injury response over multiple days of cisplatin exposure compared to colorimetric-based cytotoxicity readouts. The results of this study demonstrate the utility of steady state oxygen measurements as a rapid, non-invasive, and kinetic readout of drug-induced injury in high-throughput microfluidic kidney co-culture models.

A Clinical-Scale Microfluidic Respiratory Assist Device with 3D Branching Vascular Networks.

Recent global events such as COVID-19 pandemic amid rising rates of chronic lung diseases highlight the need for safer, simpler, and more available treatments for respiratory failure, with increasing interest in extracorporeal membrane oxygenation (ECMO). A key factor limiting use of this technology is the complexity of the blood circuit, resulting in clotting and bleeding and necessitating treatment in specialized care centers. Microfluidic oxygenators represent a promising potential solution, but have not reached the scale or performance required for comparison with conventional hollow fiber membrane oxygenators (HFMOs). Here the development and demonstration of the first microfluidic respiratory assist device at a clinical scale is reported, demonstrating efficient oxygen transfer at blood flow rates of 750 mL min⁻1 , the highest ever reported for a microfluidic device. The central innovation of this technology is a fully 3D branching network of blood channels mimicking key features of the physiological microcirculation by avoiding anomalous blood flows that lead to thrombus formation and blood damage in conventional oxygenators. Low, stable blood pressure drop, low hemolysis, and consistent oxygen transfer, in 24-hour pilot large animal experiments are demonstrated - a key step toward translation of this technology to the clinic for treatment of a range of lung diseases.

Restraint stress during neonatal hypoxia-ischemia alters brain injury following normothermia and hypothermia.

Rodent models of neonatal hypoxic-ischemic (HI) injury require a subset of animals to be immobilized for continuous temperature monitoring during the insult and subsequent treatment. Restrained animals are discarded from the analysis due to the effect of restraint on the brain injury as first demonstrated by Thoresen et al 1996. However, the effects of restraint on responses to hypothermic (HT) post-insult therapy are not well described. We examine the effects of restraint associated with different probe placements on HI brain injury. We have conducted a meta-analysis of 23 experiments comparing probe rats (skin n = 42, rectal n = 35) and free-moving matched non-probe controls (n = 80) that underwent HI injury (left common carotid artery ligation and 90 min 8% O2 ) at postnatal day 7 (P7), followed by 5 h of NT (37°C) or HT (32°C). On P14, brain regions were analyzed for injury (by neuropathology and area loss), microglial reactivity and brain-derived neurotrophic factor (BDNF). HI injury was mitigated in NT skin and rectal probe rats, with greater neuroprotection among the rectal probe rats. Following HT, the skin probe rats maintained the restraint-associated neuroprotection, while brain injury was significantly exacerbated among the rectal probe rats. Microglial reactivity strongly correlated with the acquired injury, with no detectable difference between the groups. Likewise, we observed no differences in BDNF signal intensity. Our findings suggest a biphasic neuroprotection from restraint stress, which becomes detrimental in combination with HT and the presumed discomfort from the rectal probe. This finding is useful in highlighting unforeseen effects of common experimental designs or routine clinical management.

A high-throughput, 28-day, microfluidic model of gingival tissue inflammation and recovery.

Nearly half of American adults suffer from gum disease, including mild inflammation of gingival tissue, known as gingivitis. Currently, advances in therapeutic treatments are hampered by a lack of mechanistic understanding of disease progression in physiologically relevant vascularized tissues. To address this, we present a high-throughput microfluidic organ-on-chip model of human gingival tissue containing keratinocytes, fibroblast and endothelial cells. We show the triculture model exhibits physiological tissue structure, mucosal barrier formation, and protein biomarker expression and secretion over several weeks. Through inflammatory cytokine administration, we demonstrate the induction of inflammation measured by changes in barrier function and cytokine secretion. These states of inflammation are induced at various time points within a stable culture window, providing a robust platform for evaluation of therapeutic agents. These data reveal that the administration of specific small molecule inhibitors mitigates the inflammatory response and enables tissue recovery, providing an opportunity for identification of new therapeutic targets for gum disease with the potential to facilitate relevant preclinical drug efficacy and toxicity testing.

Rheumatic disease and fatigue: Participants' experiences of an activity-pacing group.

BACKGROUND: Fatigue is a common symptom of inflammatory rheumatic disease and has a great impact on everyday life. Activity-pacing is proposed as an intervention to increase participation in meaningful activities. AIMS: To explore participants' experiences with an activity-pacing group, how participants perceived self-managing everyday life after group attendance, and their reflections on unmet needs that could enhance self-management of everyday life with fatigue. MATERIALS AND METHODS: Semi-structured interviews were conducted with 10 participants who had attended an activity-pacing group. Thematic analyses were conducted. FINDINGS: Prior to group attendance, the participants expressed an awareness of their lack of knowledge of fatigue. Through group attendance, they increased their understanding of fatigue and their ability to apply strategies to better manage everyday life. Participants found it difficult to balance their energy use and realised that implementing activity-pacing strategies takes time. Therefore, they requested follow-up sessions with the activity-pacing group. They also desire that rheumatologists pay more attention to and acknowledge fatigue. CONCLUSIONS AND SIGNIFICANCE: Enhancing the understanding of fatigue and how to manage everyday life with fatigue, appears to be important. Group interventions led by occupational therapists and with a focus on activity-pacing may be a suitable approach. Follow-up sessions are recommended.

Multilayer Scaling of a Biomimetic Microfluidic Oxygenator.

Extracorporeal membrane oxygenation (ECMO) has been advancing rapidly due to a combination of rising rates of acute and chronic lung diseases as well as significant improvements in the safety and efficacy of this therapeutic modality. However, the complexity of the ECMO blood circuit, and challenges with regard to clotting and bleeding, remain as barriers to further expansion of the technology. Recent advances in microfluidic fabrication techniques, devices, and systems present an opportunity to develop new solutions stemming from the ability to precisely maintain critical dimensions such as gas transfer membrane thickness and blood channel geometries, and to control levels of fluid shear within narrow ranges throughout the cartridge. Here, we present a physiologically inspired multilayer microfluidic oxygenator device that mimics physiologic blood flow patterns not only within individual layers but throughout a stacked device. Multiple layers of this microchannel device are integrated with a three-dimensional physiologically inspired distribution manifold that ensures smooth flow throughout the entire stacked device, including the critical entry and exit regions. We then demonstrate blood flows up to 200 ml/min in a multilayer device, with oxygen transfer rates capable of saturating venous blood, the highest of any microfluidic oxygenator, and a maximum blood flow rate of 480 ml/min in an eight-layer device, higher than any yet reported in a microfluidic device. Hemocompatibility and large animal studies utilizing these prototype devices are planned. Supplemental Visual Abstract, http://links.lww.com/ASAIO/A769.

Measurement of oxygen consumption rates of human renal proximal tubule cells in an array of organ-on-chip devices to monitor drug-induced metabolic shifts.

Measurement of cell metabolism in moderate-throughput to high-throughput organ-on-chip (OOC) systems would expand the range of data collected for studying drug effects or disease in physiologically relevant tissue models. However, current measurement approaches rely on fluorescent imaging or colorimetric assays that are focused on endpoints, require labels or added substrates, and lack real-time data. Here, we integrated optical-based oxygen sensors in a high-throughput OOC platform and developed an approach for monitoring cell metabolic activity in an array of membrane bilayer devices. Each membrane bilayer device supported a culture of human renal proximal tubule epithelial cells on a porous membrane suspended between two microchannels and exposed to controlled, unidirectional perfusion and physiologically relevant shear stress for several days. For the first time, we measured changes in oxygen in a membrane bilayer format and used a finite element analysis model to estimate cell oxygen consumption rates (OCRs), allowing comparison with OCRs from other cell culture systems. Finally, we demonstrated label-free detection of metabolic shifts in human renal proximal tubule cells following exposure to FCCP, a drug known for increasing cell oxygen consumption, as well as oligomycin and antimycin A, drugs known for decreasing cell oxygen consumption. The capability to measure cell OCRs and detect metabolic shifts in an array of membrane bilayer devices contained within an industry standard microtiter plate format will be valuable for analyzing flow-responsive and physiologically complex tissues during drug development and disease research.

Evaluation of rapid transepithelial electrical resistance (TEER) measurement as a metric of kidney toxicity in a high-throughput microfluidic culture system.

Rapid non-invasive kidney-specific readouts are essential to maximizing the potential of microfluidic tissue culture platforms for drug-induced nephrotoxicity screening. Transepithelial electrical resistance (TEER) is a well-established technique, but it has yet to be evaluated as a metric of toxicity in a kidney proximal tubule (PT) model that recapitulates the high permeability of the native tissue and is also suitable for high-throughput screening. We utilized the PREDICT96 high-throughput microfluidic platform, which has rapid TEER measurement capability and multi-flow control, to evaluate the utility of TEER sensing for detecting cisplatin-induced toxicity in a human primary PT model under both mono- and co-culture conditions as well as two levels of fluid shear stress (FSS). Changes in TEER of PT-microvascular co-cultures followed a dose-dependent trend similar to that demonstrated by lactate dehydrogenase (LDH) cytotoxicity assays and were well-correlated with tight junction coverage after cisplatin exposure. Additionally, cisplatin-induced changes in TEER were detectable prior to increases in cell death in co-cultures. PT mono-cultures had a less differentiated phenotype and were not conducive to toxicity monitoring with TEER. The results of this study demonstrate that TEER has potential as a rapid, early, and label-free indicator of toxicity in microfluidic PT-microvascular co-culture models.

Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children's Hospital.

BACKGROUND: A previous study showed that investigation of children with invasive pneumococcal disease (IPD) revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children with IPD, to assess the proportion with an immunodeficiency in our setting. METHODS: We retrospectively identified patients who presented with IPD from January 2015 to November 2020 and collected data from medical records. Immunological investigations included complement C3 and C4 levels, classical and alternative pathway complement function, IgG, IgA and IgM levels, specific IgG levels (H. influenza B, tetanus and pneumococcal serotypes), peripheral blood film, lymphocyte subsets, and CD62L-shedding upon activation with Toll-like receptor-agonists in selected cases. RESULTS: We identified a total of 68 children with IPD, with a mortality of 6%. Immunological investigations were performed in 51 children. Four children (8%) had abnormal findings that were deemed of clinical significance. Two children had complement deficiencies (Factor I and C2 deficiency), one child had specific antibody deficiency, and another child had low IgM, low NK-cells and poor persistence of serotype-specific anti-pneumococcal IgG concentrations. Of the 17 children with IPD who were not tested for immunodeficiencies, 4 died and four had possible explanations for the infection. CONCLUSIONS: We identified clinically relevant abnormal immunological findings in 4/51 (8%) of children with IPD. Our results support the recommendation to perform immunological investigations in children with IPD, since this might reveal underlying immunodeficiencies, allowing for necessary preventive measures and close follow-up.

T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases.

BACKGROUND: Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite-stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumor-infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T-cell infiltration in CLM using T-cell receptor (TCR) repertoire sequencing. Eighty-five resected CLMs from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T-cell fractions were calculated, repertoire clonality was analyzed based on Hill evenness curves, and TCR sequence convergence was assessed using network analysis. RESULTS: Increased T-cell fractions (10.6% vs. 6.3%) were detected in CLMs exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT-exposed tumors independently of the timing of NACT administration and surgery. While private clones made up >90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence. CONCLUSIONS: TCR repertoire sequencing can be used to quantify T-cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T-cell clonal expansion in CLM in a clinical context.

Long-term first-in-man Phase I/II study of an adjuvant dendritic cell vaccine in patients with high-risk prostate cancer after radical prostatectomy.

BACKGROUND: Patients with high-risk prostate cancer (PC) can experience biochemical relapse (BCR), despite surgery, and develop noncurative disease. The present study aimed to reduce the risk of BCR with a personalized dendritic cell (DC) vaccine, given as adjuvant therapy, after robot-assisted laparoscopic prostatectomy (RALP). METHODS: Twelve weeks after RALP, 20 patients with high-risk PC and undetectable PSA received DC vaccinations for 3 years or until BCR. The primary endpoint was the time to BCR. The immune response was assessed 7 weeks after surgery (baseline) and at one-time point during the vaccination period. RESULTS: Among 20 patients, 11 were BCR-free over a median of 96 months (range: 84-99). The median time from the end of vaccinations to the last follow-up was 57 months (range: 45-60). Nine patients developed BCR, either during (n = 4) or after (n = 5) the vaccination period. Among five patients diagnosed with intraductal carcinoma, three experienced early BCR during the vaccination period. All patients that developed BCR remained in stable disease within a median of 99 months (range: 74-99). The baseline immune response was significantly associated with the immune response during the vaccination period (p = 0.015). For patients diagnosed with extraprostatic extension (EPE), time to BCR was longer in vaccine responders than in non-responders (p = 0.09). Among 12 patients with the International Society of Urological Pathology (ISUP) grade 5 PC, five achieved remission after 84 months, and all mounted immune responses. CONCLUSION: Patients diagnosed with EPE and ISUP grade 5 PC were at particularly high risk of developing postsurgical BCR. In this subgroup, the vaccine response was related to a reduced BCR incidence. The vaccine was safe, without side effects. This adjuvant first-in-man Phase I/II DC vaccine study showed promising results. DC vaccines after curative surgery should be investigated further in a larger cohort of patients with high-risk PC.

Kikuchi Disease in Children: Case Report and Review of the Literature.

BACKGROUND: Kikuchi disease (KD) is a rare and generally benign condition of uncertain etiology that presents with nonspecific symptoms including fever and cervical lymphadenopathy. Clinical presentations can vary. Here, we present an atypical case of KD in a 10-year-old girl, as well as an updated literature review of the clinical presentation, laboratory features and management of KD in children. METHODS: Studies (published up until February 2020) were identified through searches of PubMed using the following search items: Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis or Kikuchi disease. Our primary search resulted in 1117 publications. A total of 34 publications with a total of 670 patients were included in the final analysis. RESULTS: All children present with lymphadenopathy. Almost all (96.3%) have cervical lymphadenopathy. Fever is recorded in the majority of children (77.1%). Analysis of laboratory features found that the majority of children have leukopenia (56.0%) and a raised erythrocyte sedimentation rate (56.0%). Over 30% have a raised C-reactive protein and anemia. Other features such as leukocytosis, thrombocytopenia and antinuclear antibodies positivity are less common. KD is mostly self-limiting, but steroids, hydroxychloroquine and intravenous immunoglobulin are used in protracted courses. Their efficacy has yet to be established in clinical trials. CONCLUSIONS: The presentation of KD is variable, and there is no specific set of symptoms or laboratory features that reliably establishes the diagnosis. Thus, histopathology is crucial. Definitive evaluation and establishment of effective treatments will require future prospective research studies for a more comprehensive description of the clinical course and effects of treatment. Given the rarity of the disease, this will have to be performed in collaborative consortia.