Aqueous parenteral nutrition (PN) provides intravenous carbohydrates, electrolytes, amino acids, and minerals to meet nutritional needs when modes of enteral nutrition are compromised. Although caloric requirements can be achieved with carbohydrates and proteins alone, patients may suffer complications ranging from essential fatty acid deficiency to developmental issues, growth restriction, and dermatitis in the absence of fat provision.

Fats are essential macronutrients that play a critical role throughout the body. Fatty acids provide sources of energy as well as structural components of cell membranes, precursors to cellular pathways and immune responses. Over the years, intravenous lipid emulsions (ILEs) have been an essential component of PN, especially in preterm and very low birth infants. Intravenous lipid emulsions have revolutionized the management of infants with gastrointestinal (GI) anomalies and diagnoses such as intestinal failure, allowing nutritional support for intestinal growth and adaptation to occur. In addition, PN and lipids are vital in supporting preterm infants when enteral therapy is contraindicated. However, prolonged PN usage still increases the risk of infection and intestinal failure associated liver disease (IFALD) in both populations which contribute significantly to infant mortality.

 Furthermore, it has been suggested certain intravenous lipid emulsions contribute to the pathogenesis of IFALD, however the pathogenesis of IFALD still remains highly complex.

In the United States, the most common standard-of-care ILE, such as Intralipid, contains 100% soybean oil, rich in omega-6 polyunsaturated fatty acids (PUFA). An alternative lipid formulation that is gaining prevalence in the literature and clinical practice for prevention of cholestasis is SMOF lipid, composed of 30% soybean oil, 30% medium chain triglycerides, 25% olive oil, and 15% fish oil. Another combination ILE that has been investigated, however is not available in the United States, is Lipofundin, composed of equal parts soybean oil and MCT oil. Intralipid and SMOF lipid share a similar dosing strategy, with patients typically receiving 3 grams/kg/day, therefore the same total calories from fat. These alternative lipid emulsions have been trialed to help prevent IFALD as they have been proposed to reduce hepatic inflammation and have also been observed to have positive benefits on other morbidities, such as retinopathy of prematurity and osteopenia. Finally, although not the focus of this review, Omegaven, a 100% fish oil-based ILE, has been studied in the pediatric population and is FDA-approved specifically for reversal of IFALD, however is not indicated for empiric therapy in parenterally fed infants. With countless new studies in the literature, the current standard of care of providing exclusive soybean-based lipid emulsions initially to all patients comes into question.

Whereas the pathogenesis of IFALD seems to be multifactorial and is not fully understood, there has been extensive research reviewing the role of ILEs contributing to inflammation. Traditional soybean oil-based lipids are high in omega-6 PUFA precursors of pro-inflammatory eicosanoids. The high amounts of omega-6 PUFA have a large linoleic acid component which leads to arachidonic acid, a substrate for interleukin-6, platelet activating factor, and tumor necrosis factor-alpha, which are all implicated as pro-inflammatory factors.

 This pro-inflammatory state leads to potentially increased lipid peroxidation, oxidative stress and inflammation, and in turn cholestasis and hepatitis. Alternative lipid emulsions that contain fish oil have rich sources of omega-3 fatty acids which have been shown to have anti-inflammatory properties. Omega-3 fatty acids are precursors for prostaglandins, leukotrienes and factors promoting resolution of inflammation. Low ratios of omega-6 to omega-3 fatty acids, as seen in SMOF lipid compared to soybean lipids, have been shown to be correlate with lower proinflammatory markers, suggesting the potential for less inflammation and cellular damage. Because of this, the opportunity of choosing alternative lipid emulsions for specific clinical scenarios is useful.

First line lipid delection – patients with GI issues

Consequently to the proposed mechanism of action and benefit, use of SMOF lipid in infants has been investigated in patients for the prevention of IFALD with evidence of early liver disease, or who were at high risk of developing liver disease secondary to a known gastrointestinal (GI) or surgical diagnosis. An early randomized evaluation of this was published in 2016 from a population of 26 infants with short bowel disease or known intestinal failure, who had progressed to hepatic dysfunction (conjugated bilirubin >1 mg/dL) requiring ongoing parenteral nutrition.

 Among these patients, the primary outcome of conjugated bilirubin during the final week of trial lipids was found to be significantly lower in the SMOF lipid group. At the endpoint of the trial, fewer patients in the SMOF lipid group had a persistent conjugated bilirubin greater than 2.9 mg/dL compared to Intralipid (27% vs. 69%, 

=0.04). Together, this suggested that SMOF lipid could reduce the risk of progressive IFALD in neonates with intestinal failure, without any significant impact on growth.

In the years following, several other prospective and retrospective analyses of SMOF lipid versus soy- and soy-medium chain triglyceride (MCT)-based comparators were published. Periera-da-Silva and colleagues conducted a trial of infants born at greater than 34 weeks gestation with a history of surgery for a major GI anomaly or another anomaly impacting the function of the GI tract, who were randomized to either SMOF lipid or Lipofundin.

 The study was forced to cease recruitment due to the loss of availability of Lipofundin during the study period, however, no significant difference was detected in the incidence or severity of cholestasis or other labs associated with hepatic dysfunction. Hypertriglyceridemia was notably significantly more frequent in the Lipofundin group compared to the SMOF lipid group, however the authors could not conclude that lipid choice of SMOF versus Lipofundin was significantly beneficial on parenteral nutrition associated cholestasis. Jiang and colleagues also conducted a trial of SMOF lipid versus a Lipofundin control group in 160 infants status-post GI surgery who had received at least 2 weeks of ILEs at the time of enrollment.

 The primary outcome of postoperative weight gain was not found to be different at any of the weekly follow-up timepoints. After two weeks of study lipid, no significant differences existed in the aspartate transaminase (AST), alanine aminotransferase (ALT) or direct bilirubin, however patients who received SMOF lipid exhibited decreased ALT compared to the Lipofundin group at the end of study weeks three and four (

 <0.05 for each). Significantly lower AST and direct bilirubin were also observed in the SMOF lipid group at the end of study week four (

 <0.05). This study indicates that SMOFlipid may be a preferable lipid emulsion in infants who are post-GI surgery and require PN for four or more weeks. Use of a Lipofundin comparator is a complicating factor as the MCT oil component and ratios may have different impacts on IFALD than Intralipid.

Finally, Casson and colleagues conducted a retrospective review of 44 infants at two intestinal rehabilitation centers, one of which used SMOF lipid and one of which used Intralipid.6 Patients at each center remained on their primary lipid therapy unless their conjugated bilirubin levels rose to beyond 6 mg/dL, at which point they either received a reduced dose, or were initiated on 100% fish oil lipid emulsion as rescue therapy. The authors did not report a difference in the primary outcome of cholestasis (defined as a conjugated bilirubin >2 mg/dL for at least two consecutive weeks), as this outcome was observed in 91% of the Intralipid patients and 76% of the SMOF lipid patients (

=0.18). In the subgroup of infants on full PN without enteral intake (including 9 patients in the SMOF lipid group and 13 patients in the Intralipid group), there was a trend towards a higher incidence of cholestasis in infants receiving Intralipid (92% vs 78%, 

=0.057). There was not a difference in the peak conjugated bilirubin level or rate of patients requiring additional interventions for cholestasis, however the conjugated bilirubin values of infants receiving Intralipid normalized slower compared to those on SMOF lipid (120 vs 83 days, 

=0.04). Overall, in this mixed group of patients on at least partial PN, early SMOF lipid use was not associated with a decreased incidence or severity of cholestasis, but among patients on full PN there may be a benefit of early SMOF lipid initiation.

Together, use of SMOF lipid in patients with GI comorbidities, short bowel disease or intestinal failure may be associated with beneficial effects on prevention and resolution of IFALD. This effect may be most clinically significant in patients on prolonged durations of parenteral nutrition, or in patients who are not receiving any enteral nutrition. Limitations in these studies and others regarding sample size, uniformity of patients and adherence to protocols make interpreting and applying the data in clinical practice challenging.

First line lipid selection – preterm neonates, or before development of GI issues

As the evidence suggests, using SMOF lipid is associated with benefit in infants with GI reasons for prolonged PN use, there is understandably interest in empiric use in another patient population that is highly likely to have prolonged PN requirements: preterm neonates.

Tomsits and colleagues conducted one of the first randomized controlled trial of SMOF lipid versus Intralipid initiated in the first week of life in 60 preterm neonates (born ≤ 34 weeks gestational age).

 The authors investigated the impact of each lipid on triglyceride levels and relative change in weight in the first 8 days of lipid therapy, which were both similar between groups. This study did not address direct bilirubin values, however found no difference in total bilirubin between study entry and conclusion. The authors reported a significant difference between the gamma glutamyl-transferase (GGT) at study entry and end between groups- in the Intralipid group, GGT increased between day zero and study end, whereas in the SMOF lipid group, GGT actually decreased from day zero to the final measurement. Although this study did not directly address measures of IFALD, it demonstrated the tolerability of SMOF lipid in preterm neonates was not significantly worse than Intralipid, which is relevant as lipid intolerance manifested as hypertriglyceridemia is a noteworthy adverse effect requiring monitoring. Following this, Rayaan et al addressed a similar patient population as the prior study in preterm neonates born at <34 weeks who were expected to require a minimum of 7 days of PN.

 The primary outcome focused on triglyceride values, which were not significantly different between groups, though both groups had a significant difference between baseline and post-intervention triglyceride values, endorsing that this is an important monitoring parameter in clinical care. In addition, this study reported the direct bilirubin values following exposure of 8 days of study lipid, and found that the mean direct bilirubin the Intralipid group was significantly higher than that of the SMOF lipid group (mean (SD): 12.83 (7.2) umol/L [0.75 (0.42) mg/dL] vs 10.26 (5.8) umol/L [0.6 (0.34) mg/dL]). Among these patients, the authors similarly concluded that SMOF lipid was well tolerated and had a favorable impact on conjugated bilirubin.

The remaining available literature for use of SMOF lipid empirically in preterm neonates is retrospective, most commonly evaluating outcomes before and after an institutional policy change to utilize SMOF lipid in all preterm neonates. Choudhary, et al retrospectively reviewed 222 patients who were born at <32 weeks gestation who required ILEs for >14 days.

 The authors investigated the impact of the practice change from empiric Intralipid to empiric SMOF lipid on mortality and major neonatal morbidities. There was no significant difference in mortality or the majority of morbidities, including IFALD. The SMOF lipid group did have greater weight at 36 weeks corrected gestational age as well as a greater change in weight from birth to 36 weeks (a mean difference of each of about 125 g) though no differences were observed in length or head circumference measurements at 36 weeks. Different from other studies, the authors found comparable hepatic outcomes with SMOF lipid use. Together though, the favorable growth outcomes may someday associate with long-term benefits in developmental outcomes, but further research is needed.

A large retrospective study of 1297 very low birth weight preterm neonates who had received at least one week of ILE was conducted by Torgalkar and colleagues to evaluate the impact of SMOF lipid versus Intralipid on mortality prior to discharge and major morbidities.10 No significant difference was observed in mortality or morbidity outcomes including chronic lung disease, necrotizing enterocolitis, or infections. Time to regain birth weight was shorter in the SMOF group (median [IQR]: 11 [8, 13] days vs 8 [6, 11] days, 

<0.01), and reduced rates of lipid interruptions, retinopathy of prematurity, and osteopenia of prematurity were also observed in the SMOF group. After adjusting for confounding factors, SMOF lipid was significantly associated with lower odds of lipid interruptions, retinopathy of prematurity, osteopenia of prematurity as well as neonatal cholestasis (OR (95% CI) 0.69 (0.51, 0.95)). Further prospective studies are still necessary, particularly considering the impact on cholestasis in the setting of a shorter PN duration and time to full enteral feeds in the SMOF era, but this large retrospective evaluation indicates that there is benefit of empiric SMOF lipid use in very low birth weight neonates.

An additional large retrospective cohort study including 1332 term and preterm neonates who were on an average of six days of parenteral nutrition found no significant difference in rates of IFALD, however did find significantly fewer patients with direct bilirubin values greater than 1 mg/dL and 1.5 mg/dL after SMOF lipid treatment.

 Even after adjusting for low birth weight and prematurity, the rate of IFALD remained similar between groups. The rate of liver disease was found to be different in subgroups of patients with chronic lung disease, sepsis, or concomitant hepatotoxic medication use, suggesting that there may be an opportunity for future research into the impact of SMOF lipid on cholestasis in patients specifically with those criteria or other hyper-inflammatory conditions. In addition, inclusion of term infants provides value to a more general NICU population but is different than the population included in other empiric SMOF lipid studies, which may have impacted the ultimate outcomes observed.

In summary, there is some literature support for the use of empiric SMOF lipid in preterm neonates. This is likely of additional benefit in those who are expected to have prolonged PN use (> 4 weeks), and potentially in those who are receiving hepatotoxic medications or experiencing the impacts of other concomitant inflammatory conditions, which both may contribute to further hepatic inflammation and cholestasis. Finally, it is promising that infants in the SMOF lipid groups across investigations did not experience poorer growth outcomes than those in the standard-of-care groups, supporting that beyond cholestasis, this intervention continues to support the goal of healthy neonatal growth and development.

Lipid emulsions available on the market have evolved over time, and due to new research suggesting added benefits from alternative lipid sources such as SMOF lipid, consideration of empiric use of alternative lipid sources should be addressed. Although SMOF lipid has been approved by the FDA for use in adults, approval has not yet been granted for in infants by the FDA as large randomized trials are awaited. Previous systematic reviews evaluating lipid emulsions for term, late preterm and preterm infants have been inconclusive in determining if there are added benefits, most likely due to the lack of highly powered data and specific patient inclusion criteria.

 The expanding body of literature continues to suggest potential benefits on cholestasis outcomes from alternative lipid emulsions containing fish, MCT, olive and soybean oil, as well as no overall clinical harm, with favorable impacts on triglycerides and growth. Consideration of patient-specific characteristics that were most associated with benefit in the studies is a reasonable starting point when assessing use of SMOF lipid in an off-label manner, particularly patients with GI diagnoses, anomalies, or surgeries that are anticipated to require PN for a prolonged period (> 4 weeks), and those preterm neonates that are anticipated to require prolonged PN, regardless of a GI diagnosis.

1. Goulet OJ, Cai W, Seo JM. Lipid Emulsion Use in Pediatric Patients Requiring Long-Term Parenteral Nutrition. 

. 2020;44 Suppl 1:S55-S67. doi:10.1002/jpen.1762. 

2. Hojsak I, Colomb V, Braegger C, et al. ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children: a Systematic Review and Meta-analysis. 

. 2016;62(5):776-792. doi:10.1097/MPG.000000000000112. 

3. Diamond I, Grant R, Pencharz P et al. Preventing the Progression of Intestinal Failure–Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid. 

Journal of Parenteral and Enteral Nutrition

. 2016;41(5):866-877. doi:10.1177/0148607115626921. 

4. Pereira-da-Silva L, Nóbrega S, Rosa M et al. Parenteral nutrition-associated cholestasis and triglyceridemia in surgical term and near-term neonates: A pilot randomized controlled trial of two mixed intravenous lipid emulsions. 

. 2017;22:7-12. doi:10.1016/j.clnesp.2017.08.007. 

 The effects of two mixed intravenous lipid emulsions on clinical outcomes in infants after gastrointestinal surgery: a prospective, randomized study. 

6. Casson C, Nguyen V, Nayak P et al. A Comparison of Smoflipid® and Intralipid® in the Early Management of Infants with Intestinal Failure. 

. 2020;55(1):153-157. doi:10.1016/j.jpedsurg.2019.09.073. 

7. Tomsits E, Pataki M, Tölgyesi A, Fekete G, Rischak K, Szollár L. Safety and Efficacy of a Lipid Emulsion Containing a Mixture of Soybean Oil, Medium-chain Triglycerides, Olive Oil, and Fish Oil: A Randomised, Double-blind Clinical Trial in Premature Infants Requiring Parenteral Nutrition. 

. 2010;51(4):514-521. doi:10.1097/mpg.0b013e3181de210c. A

8. Rayyan M, Devlieger H, Jochum F, Allegaert K. Short-Term Use of Parenteral Nutrition With a Lipid Emulsion Containing a Mixture of Soybean Oil, Olive Oil, Medium-Chain Triglycerides, and Fish Oil. 

. 2012;36(1_suppl):81S-94S. doi:10.1177/0148607111424411. 

9. Choudhary, N., Tan, K. & Malhotra, A. Inpatient outcomes of preterm infants receiving ω-3 enriched lipid emulsion (SMOFlipid): an observational study. 

 Multi-component lipid emulsion vs soy-based lipid emulsion for very low birth weight preterm neonates: A pre-post comparative study. 

11. Stramara L, Hernandez L, Bloom B, Durham C. Development of Parenteral Nutrition–Associated Liver Disease and Other Adverse Effects in Neonates Receiving SMOFlipid or Intralipid. 

12. Kapoor V, Malviya MN, Soll R. Lipid emulsions for parenterally fed preterm infants. Cochrane Database of Systematic Reviews 2019, Issue 6. Art. No.: CD013163. DOI: 10.1002/14651858.CD013163.pub2. 

13. Kapoor V, Malviya MN, Soll R. Lipid emulsions for parenterally fed term and late preterm infants. 

. 2019;6(6):CD013171. Published 2019 Jun 4. doi:10.1002/14651858.CD013171.pub2. 

Articles

Lipid emulsions available on the market have evolved over time. Here's the latest information.

Empiric selection of lipid emulsion in hospitalized neonates

A 12-year-old previously healthy male was transferred to our institution (Children’s Hospital of New Jersey) from a psychiatric unit for new onset psychosis and an abnormal electroencephalogram (EEG). Less than 2 weeks prior to initial presentation, the patient had upper respiratory tract symptoms and was treated with antibiotics for bilateral acute otitis media. He then developed progressively worsening headaches, auditory and visual hallucinations, behavioral changes, and suicidal ideations. After multiple emergency department visits, the patient was admitted to an inpatient psychiatric unit and started on risperidone and benztropine. Despite psychiatric treatment, his symptoms persisted. A video EEG was done to rule out seizures and was abnormal, prompting transfer.

On admission to our facility, the patient was found to be sleepy and combative with extreme emotional lability. His mental status waxed and waned throughout his first week of admission, with periods of lucidity alternating with periods of slow, slurred speech, agitation, hyper sexuality, visual and auditory hallucinations, insomnia, and paranoia. Physical exam was unremarkable, without any focality on neurologic examination

Due to acute onset neuropsychiatric symptoms of unknown etiology, the patient was initially admitted to the pediatric intensive care unit for close monitoring. Initial differential diagnosis was broad given the patient’s new-onset severe neuropsychiatric symptoms (Table 1). Bacterial or viral meningitis/encephalitis may present similarly, and upper respiratory symptoms may precede presentation, as was the case in our patient. However, these patients also typically present with fever and nuchal rigidity, neither of which were present in our patient. Other infectious etiologies include HIV, syphilis, Bartonella, and Lyme disease. Toxic ingestion, especially of alcohol, ketamine, phencyclidine, or organophosphates can cause new onset agitation; however, symptoms typically do not last as long as they did in our patient. Endocrine and metabolic derangements are also known to cause neuropsychosis. Neoplastic disorder, either primary or secondary, as well as paraneoplastic syndromes can present with focal neurologic signs and/or neuropsychiatric symptoms. Rheumatologic disorders, including lupus, may also present with psychiatric symptoms, though our patient had no other stigmata typical of lupus. Entities that cause inflammation of the central nervous system, such as autoimmune encephalitis (eg, anti-N-methyl-D-asparate receptor [NMDAR] encephalitis and acute disseminated encephalomyelitis) can present with a similar constellation of symptoms as our patient and must also be considered. Primary psychiatric disease should be a diagnosis of exclusion once all organic causes are ruled out or considered sooner if the patient has a known psychiatric history.

Video EEG at our institution did not demonstrate evidence of seizures. Head computed tomography (CT) on admission showed hypoattenuation in bilateral thalami, though more on the right side as compared to the left side. Magnetic resonance imaging (MRI), magnetic resonance angiogram, and magnetic resonance venography were done given concern for vasculitis and significant for hyperintensity flair in the medial thalami/massa intermedia. Urine toxicology screen was negative. A lumbar puncture showed a high opening pressure and cerebrospinal fluid (CSF) pleocytosis with white blood cells of 26, suggesting infectious versus autoimmune processes. Further infectious work-up, including a complete blood count, procalcitonin, meningitis/encephalitis panel, antistreptolysin O (ASO) titer, group A streptococcus direct DNA probe, rapid plasma regain (RPR), Epstein-Barr virus, Lyme disease titers, HIV, quantiferon gold, Bartonella antibodies, and herpes simplex virus (HSV) antibodies were all negative. Rheumatologic workup, including erythrocyte sedimentation rate, c-reactive protein, antinuclear antibody, anti-ds DNA, C3, C4, proteinase-3 antibody, myeloperoxide antibody, and centromere antibody were unrevealing. A comprehensive metabolic panel, lactic acid, ammonia, thyroid stimulating hormone (TSH), free T4, vitamin B1, ceruloplasmin, and copper studies did not demonstrate a toxic or metabolic cause. A CT abdomen and pelvis was done to rule out an oncologic process and was within normal limits. Alpha-fetoprotein was normal. An autoimmune and paraneoplastic panel was sent from the CSF, however results were not available during the patient’s hospital admission.

Laboratory evaluation was largely unrevealing, except for slight CSF pleocytosis. This, along with the CT and MRI findings and the clinical picture of waxing and waning aggression, agitation, and insomnia was concerning for autoimmune encephalitis. One week after discharge, CSF studies returned positive for anti-NMDAR and anti-MOG antibodies.

Given concern for anti-NMDAR encephalitis and known poorer prognosis with delay in treatment, our patient was presumptively treated with high-dose steroids and intravenous immune globulin (IVIG). He did not demonstrate improvement in his neuropsychiatric symptoms with this treatment, and continued to require daily lorazepam for agitation. The patient was subsequently treated with rituximab with clinical improvement.

Our patient was admitted for 16 days and discharged home with mild cognitive delays but no activity restrictions. After discharge, the patient had close follow-up with neurology and hematology/oncology, including a 2nd dose of rituximab and a repeat MRI that showed interval complete resolution of previously identified T2-weighted-fluid-attenuated inversion recovery hyperintensity within pulvinar region of bilateral thalami. He was given a 504 plan for additional time in academic activities, however reports not using it and is earning B’s in school.

In addition, the neuropsychiatric team evaluated the patient in order to delineate sequelae of neurocognitive deficits due to encephalitis. His first evaluation was approximately 3 months after discharge and showed weaknesses in sustained visual attention, auditory memory, and visual memory. There were also concerns regarding impulse control. The neuropsychiatric team conducted a follow up evaluation about 7 months later. Our patient demonstrated significant improvement, specifically in attention, concentration, and memory domains of the evaluation. He also exhibited improved self-control during testing.

The NMDA is a glutamate-gated ion channel critical for multiple central nervous system (CNS) functions

 including processes underlying learning, memory and neuroplasticity.

Anti-NMDAR encephalitis is an autoimmune disorder with IgG antibodies against the NR1 and NR2 subunit of the NMDA receptor. The presenting symptoms of anti-NMDAR encephalitis are quite broad,

 but usually evolve in stages including a prodrome of fever, headaches and viral-like symptoms. Days to weeks after this prodromal phase begins the onset of psychiatric and behavioral problems,

 including personality and behavioral changes, autonomic and cognitive dysfunction, and finally neurologic decompensation leading to insomnia, seizures, altered levels of consciousness, and breathing or autonomic instability.

 In multiple studies, it was shown that the condition, when identified, affects predominantly females (up to 80% of females vs males). Age ranges from 18-35 years, with 40% of patients aged younger than 18 years.

This disorder is a leading cause of encephalitis in young patients, with up to 4% of patients with encephalitis having NMDAR antibodies. In women aged older than 18 years, the majority will have the presence of an underlying tumor, such as teratoma of the ovary, however in children, this is uncommon.

Diagnosis of anti-NMDAR encephalitis is made by identification of NMDAR antibodies in the CSF or serum. First line therapy is typically high dose corticosteroids. Second line therapy includes IVIG and/or plasma exchange. Other attempted therapies include rituximab, azathioprine, and cyclophosphamide. If a neoplasm is found, treatment includes surgical excision of neoplasm, if possible.

Anti-NMDAR encephalitis is the second leading cause of immune-mediated encephalitis, after acute disseminated encephalomyelitis.

 Despite the prevalence of the condition, anti-NMDAR encephalitis is an overlooked diagnosis.

 Timely diagnosis and treatment of anti-NMDAR encephalitis should be considered early on in patients presenting with new onset of altered mental status of unknown etiology. Anti-NMDAR encephalitis is a complex syndrome, with a severe disease course and broad differential diagnosis. Mortality can be up to 25%, whereas many other patients are left with cognitive deficits that may affect education, work, or social life. However, with early recognition and aggressive treatment, prognosis remains good with most cases (up to 75%) making a full recovery or only having mild disability,

1. Miya, Kazushi, Takahaski, Tukitoshi, and Mori, Hisashi. Anti-NMDAR autoimmune encephalitis. 

2. Blanke ML, VanDongen AMJ. Activation Mechanisms of the NMDA Receptor. In: Van Dongen AM, editor. Biology of the NMDA Receptor. Boca Raton (FL): CRC Press/Taylor & Francis; 2009. Chapter 13. Available from: 

https://www.ncbi.nlm.nih.gov/books/NBK5274/

3. Armangue, Thais MD, Petit-Pedrol, Mar, BS, and Dalmau, Josep, MD, PhD. Autoimmune Encephalitis in Children. 

4. Barry, Helen, et al. “Anti-NMDA Receptor Encephalitis: an Important Differential Diagnosis in Psychosis.” 

, vol. 199, no. 6, 2011, pp. 508–509., doi:10.1192/bjp.bp.111.092197.

5. Day, Gregory S., et al. “Anti-NMDA-Receptor Encephalitis: Case Report and Literature Review of an Under-Recognized Condition.” 

, vol. 26, no. 7, 2011, pp. 811–816., doi:10.1007/s11606-011-1641-9.

6. Armangue, Thaís, et al. “Pediatric Anti-N-Methyl-D-Aspartate Receptor Encephalitis—Clinical Analysis and Novel Findings in a Series of 20 Patients.” 

, vol. 162, no. 4, 2013, doi:10.1016/j.jpeds.2012.10.011.

7. Finke, Carsten, et al. “Cognitive Deficits Following Anti-NMDA Receptor Encephalitis.” 

Journal of Neurology, Neurosurgery & Psychiatry

, vol. 83, no. 2, 2011, pp. 195–198., doi:10.1136/jnnp-2011-300411.

8. Kelley, Patel, Marin, Corrigan, Mitsias, Griffith. Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis. 

A 12-year-old previously healthy male was transferred to a children's hospital from a psychiatric unit for new onset psychosis and an abnormal electroencephalogram. What's the diagnosis?

A case of acute psychosis that will make your head spin

Every physician has likely committed a medical error at some time.

 Fortunately, most medical errors are minor, and many do not reach the patient. However, one recent study suggested that medical errors are the third leading cause of death in the United States.

 In a study of internal medicine trainees, 45% reported being involved in a serious medical error.

 In a survey of practicing physicians, 10.5% reported they were involved in a major medical error during the prior 3 months.

 Provider burnout has been linked to medical errors. Medical errors often lead to burnout, and the reverse is also probable.

The Emergency Department (ED) is a high-risk area where medical errors are likely. This is, in part, because the ED is often extremely busy with multiple ill or complicated patients. Emergency clinicians often must make rapid decisions in a chaotic environment, so the chance for error is high. (This is not entirely unique to the ED. Pediatricians in office practice may find their office fits this mold on many days!) Many errors in pediatric emergency medicine relate to physician fatigue. Others relate to frequent distractions that are prevalent in the ED setting. In one study,

 attending physicians and nurses were followed in a level 1 trauma center. It was noted that physicians were interrupted 10 times within an hour, and nurses were interrupted 12 times in an hour. These providers performed between

 other activities before returning to the original task. They were interrupted by phones, pagers, other staff members. It is easy to see how errors can result from these frequent disruptions. In some cases, ED providers commit cognitive errors, perhaps because of “premature closure.” That is, the clinician fixes on a diagnosis early on and ignores other findings that could lead to a different diagnosis.

In many cases, errors result from poor communication. In the ED it is obviously crucial for staff to work as a cohesive team. Certainly, ED providers must communicate well with nursing staff, and consultants. Numerous errors result when there is a breakdown in this communication. In fact, the Joint Commission notes that communication issues are the third leading cause of sentinel events.

 Likewise, ED providers must communicate well with patients and families to obtain an accurate history and develop a management plan together.

Although this seems obvious, it is not guaranteed. In one interesting study

involving 2 teaching hospitals in Michigan, patients were asked about 4 domains soon after their ED visit:

2. ­Do you understand what was done for you in the ED?

3. ­Do you know what you are supposed to do after your ED visit (discharge instructions).

4. ­Do you understand what symptoms should prompt you to return to the ED?

Surprisingly, 78% of those surveyed were deficient in recalling one of these domains and 51% were deficient in 2 or more domains. One could interpret this as a failure to communicate! Clearly, there is room for improvement.

In the ED, procedures can also go badly due to clinician error or failure to monitor the patient carefully. Even more common are ED diagnostic errors.

 summarizes common causes of medical errors in the ED; again, office practices are not immune to these. Whether you practice in a pediatric emergency department or an office setting, the following examples (all real cases) offer good teaching points. It is hoped these cases will help clinicians avoid similar errors in the future.

A 15-year-old boy presented to the ED with the complaint of chest pain for 1 week. He reported that he was hit over his ribs on the right side of his chest when playing football a week ago. His pain, described as achy and stabbing, worsened in the past few days. It was worse with walking and for one day, he had difficulty climbing the stairs. He was short of breath at times and had mild dizziness with standing. He had no fever, no vomiting or diarrhea, no cough or rhinorrhea. Physical examination revealed temperature 100.9° F, heart rate 78 beats per minute (up to 106 beats per minute when standing), respiration 24/minute, blood pressure 128/84 (124/92 standing). He was alert and talkative and in no distress. He had mild tenderness over his sternum. Cardiac exam was normal. Lungs were clear. Abdomen was benign. His exam was otherwise unremarkable.

A chest x-ray showed clear lungs; the heart was noted to be “top normal” in size. (see radiograph Figure 1). An electrocardiogram had ‘non-specific’ findings such as ST elevation in some leads and borderline prolonged QT interval.

The patient received ibuprofen for his pain, and intravenous saline because it was thought he may be dehydrated. His vital signs remained unchanged after the fluids. A cardiologist was consulted by phone. The cardiologist believed the patient had musculoskeletal pain, and he did not need immediate cardiology evaluation. The patient was discharged to home. About 8 hours later, he collapsed and died. Myocarditis was found on autopsy.

 In retrospect, the diagnosis of myocarditis is obvious. The patient had classic findings: chest pain for several days, worsening with exertion and leading to shortness of breath. He also had a low-grade fever in the ED, that seems to have been ignored by the cardiologist who was consulted. Myocarditis can be a difficult diagnosis, and in many cases the patient is evaluated multiple times before myocarditis is considered.

Chest pain associated with fever is concerning. If pneumonia is ruled out, consider myocarditis as the etiology for pain. Chest pain with exertion is concerning for a cardiac etiology rather than musculoskeletal pain, which should improve over time, not worsen. Pay attention to the vital signs! If the patient continues to have tachycardia (or dizziness) with standing, after intravenous fluids, perhaps there is cardiac insufficiency rather than dehydration.

A 5-year-old girl presented to the ED with persistent vomiting. She was seen by her pediatrician who obtained a rapid throat swab that was positive for Group A 

. She also had an abdominal radiograph that showed constipation. She was referred to the ED because her emesis had a foul odor. It smelled of ‘fecal material.’ In the ED, it was noted that she had been vomiting intermittently for about 3 months, but had 8-9 episodes today. Her emesis was ‘greenish-brown’ and there was no blood in her stool. She had crampy abdominal pain. Physical exam revealed temperature 98.9° F, heart rate 96 beats per minute, respiratory rate 20/minute, blood pressure 106/66. She was alert, well-nourished, with an injected pharynx. Her chest was clear; abdomen was soft and unremarkable.

The patient was given an enema and was able to tolerate oral fluids. She was discharged to home with a diagnosis of constipation, and strep throat. The next day, she had a generalized seizure and was brought back to the hospital. A computed tomography (CT) scan of her brain was promptly obtained and showed a large brain tumor. The child expired the next day.

 Vomiting has many etiologies. Viral gastroenteritis is perhaps the most common etiology. However, when a child has vomiting without diarrhea, other conditions must be considered. Vomiting is sometimes associated with strep pharyngitis, and perhaps the clinicians in this case were misled by the rapid test of the pharynx. Constipation is unlikely to cause persistent vomiting-it is wise to look for another etiology before concluding that constipation is the culprit. Diabetic ketoacidosis and pneumonia are other possibilities, but unlikely in the case above. A viral infection, gastritis without diarrhea, is possible. However, clinicians must also consider an intracranial cause for vomiting, such as a brain tumor. In this case, a neurologic exam was not even documented in the medical record. Her history of prolonged vomiting over several months was apparently ignored.

A 2-year-old girl was bitten by a dog. She presented to the ED with extensive facial wounds. A plastic surgeon was consulted, and the face lacerations were meticulously repaired. She was discharged to home. She returned to the ED a few days later because of frequent vomiting and low-grade fever. A head CT scan was obtained and showed a brain abscess. With careful inspection, it was noted there was a defect in the patient’s skull. The dog’s tooth had apparently penetrated the child’s skull, leading to intracranial infection. The skull defect was not noted under the toddler’s extensive hair and thus it was not cleaned or addressed at the initial visit.

 When an injured child arrives, clinicians often focus on the most obvious injury, or perhaps the most impressive. It is wise to examine the rest of the child first. No one will miss the dramatic wound, so a careful look elsewhere is advised before devoting attention to the noticeable face laceration. Also, consider that when a big dog attacks a little child, the jaws of the animal can likely encompass a large area of the child. Look for a second wound!

A 2-year-old boy presented to the ED with the complaint of “something in his nose.”

 Despite multiple attempts, the physician’s assistant and the physician were unable to remove a foreign body. In fact, they were not able to clearly visualize the foreign body, believing it was deeply embedded in the nostril. The providers recommended that the child see a specialist in the next few days. When the child was evaluated by an otolaryngologist, a radiograph was obtained. (Figure 2) The rim of the metallic foreign body is evidence that it is a ‘button battery’. This child had a complicated course with perforation of the nasal septum, and he required extensive surgery.

 Button batteries in the nose, ears, or esophagus can cause extensive burns and tissue necrosis in a short period of time.

 It is important to visualize a foreign body in these locations. A plastic bead can likely wait for the specialist appointment; a button battery cannot. It is wise to consider a radiograph to identify the presumed foreign body if it cannot be seen on physical examination.

On a warm summer day, a 15-year-old girl fell when playing baseball and hit her head on the turf.

 She was briefly unresponsive with “twitching” movements. She was brought to the ED, was noted to have a scalp laceration, but her exam was otherwise unremarkable. Routine blood tests were obtained, and her scalp laceration was repaired. Her syncope was thought to be related to heat exhaustion. The patient did well until about a year later. She then had a brief syncopal episode when she was doing laundry. She dropped to her knees, was briefly unresponsive and recovered quickly. She was brought to the ED where her exam was unremarkable. Routine blood studies were again unremarkable. She was diagnosed with vasovagal syncope and discharged to home.

One year later, the patient again collapsed during baseball. She was brought to the ED and found to have Long QT syndrome. Unfortunately, she suffered a cardiac arrest and after resuscitation, had a severe brain injury.

 Exercise related syncope is concerning. Consider a cardiac etiology, like Long QT syndrome.

 Routine blood tests are not often helpful with a syncopal episode, but many recommend obtaining an electrocardiogram in most cases of syncope, and for all those related to exercise. Some syncopal episodes can resemble a seizure. This patient had brief ‘twitching’ movements. But unlike a seizure, the patient with cardiac related syncope often recovers quickly, without a post-ictal state. Also, a syncopal episode that results in an injury should raise a red flag. Most children with vasovagal syncope have some warning of the event and fall slowly to the ground. Significant injury is less likely in such cases. With a cardiac arrhythmia, the patient has no warning and may fall to the ground with more force.

A 7-year-old boy developed abdominal pain at school. After being sent home, his parents brought him to his pediatrician for evaluation. The physician noted right lower quadrant pain, but no other concerning findings. The family was instructed to take the patient home and give supportive care. The next day, his parents called the pediatrician to inform him that their son’s pain had worsened. The pediatrician recommended an over-the-counter analgesic and follow up if he did not improve. As the pain continued to worsen, the boy was brought to the ED, where a testicular exam revealed a swollen, tender testicle. He was found to have testicular torsion. The testicle was noted to be necrotic in the operating room and it was surgically removed. After review of the initial evaluation by the pediatrician, it was noted that a testicular exam was not performed.

 This child did not initially present to the ED; however, the case provides an important lesson for ED clinicians and pediatricians in office practice – always perform a testicular exam for males with abdominal pain! Many pathologies can manifest or be interpreted as abdominal pain by a young child. In fact, several studies show that abdominal pain can be the presenting symptom of testicular torsion. One study

 found that 9/76 (12%) patients with testicular torsion presented with acute abdominal pain as their only symptom. Of those 9 patients, 7 did not have a testicular exam initially and the diagnosis of torsion was delayed. Similarly, the child in our case had referred pain to the abdomen from his testicular pathology, therefore, the diagnosis was initially missed, which likely led to his poor outcome. Also keep in mind, even if pain is not referred, a young boy may have difficulty articulating where the pain is originating from or may be embarrassed to discuss this. Therefore, it is very important to consider testicular torsion for any boy with vague complaints, especially abdominal pain.

A 23-day old baby presented to the ED with excessive crying. A brief history was notable for premature birth at 36 weeks and the birth weight was 2778 grams Examination of the baby was documented as grossly normal, except the baby’s weight in the ED was 2268 grams. The infant fed in the ED and his crying improved. He was discharged to home and the parents were instructed to follow-up with his pediatrician if there were any concerns. After arriving home, the baby continued crying. His parents brought him to a different ED where the baby was diagnosed with severe dehydration. When receiving an intravenous fluid bolus, the infant developed cardiovascular collapse. Cardiopulmonary resuscitation was initiated, and he was stabilized. However, the baby suffered severe brain damage and subsequent developmental delay. Close review of the infant’s record revealed multiple factors that likely contributed to his poor outcome, including the mother’s perinatal drug use and child neglect, leading to malnourishment.

 This case reminds us to carefully consider an infant’s social situation before discharge from the ED. In addition, it is essential to always review and interpret the infant’s weight and growth curve. In this case, it is unclear if any of the original ED providers took note that this infant’s documented weight was 20% below his birth weight. If that association were made, perhaps the physician would have recognized a bigger issue, such as severe dehydration due to neglect and poor feeding. This may have prompted more aggressive care, hospital admission, as well as support and education for the family. Taking a few extra moments to review the weight and growth curve can clue the provider into the whole picture and help make more informed decisions.

A 14-year-old male presented to the ED after suffering a left knee injury when he was playing basketball. He was evaluated, radiographs were obtained, and no fracture was identified. He was discharged to home with a knee immobilizer, crutches, and pain medication. The following day, he had significant, worsening pain and he was brought to a different ED. At that time, he was found to have absent distal pulses in left lower extremity. It was discovered that his left popliteal artery was transected, and he required emergent fasciotomy due to compartment syndrome. He subsequently needed multiple surgeries for debridement of necrotic tissue and ultimately underwent left lower extremity amputation. Upon review of the case, it was found that the initial triage notes by nursing staff documented “+3 swelling of left leg and pedal pulses not discernable by palpation.” Based upon documentation, it was apparent that the nurse’s concerning findings were not read by nor discussed with the ED physician.

 This is a very sad, unfortunate case that exemplifies how important communication is in the ED, as well as the importance of a thorough musculoskeletal exam following an extremity injury. Had there been good communication regarding lack of pulses noted by the nurse, one of the cardinal “5-Ps” of compartment syndrome (pain, pulse, pallor, paresthesia, paralysis), the poor outcome could have potentially been prevented. Although there is clinical variation in the diagnosis and management of compartment syndrome, early diagnosis is crucial to avoid morbidity. When clinical examination is concerning (or discrepant in this case), prompt orthopedic consultation for measurement of intramuscular pressure is warranted.

 Admission to the hospital for close monitoring should be considered. Perhaps these measures would have been taken if the nurse’s findings were communicated to the physician. This is a great reminder to read all nursing notes and keep open, strong communication with the medical team.

The above cases highlight just a small sample of errors that can haunt medical providers. Hopefully, these stories shed light on how even the most well intentioned, thoughtful providers can miss something. To prevent errors, it is crucial to maintain good communication, pay attention to detail, listen closely to patients and families, form a broad differential and avoid premature closure before making a diagnosis. It is most important to be in the moment with our patients.

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Durani Y, Egan M, Baffa G, Selbst SM, Nager A: Pediatric myocarditis: Presenting clinical characteristics. 

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A medical error is not an unusual event, although most are minor. The emergency department is one place where medical errors are more likely because of the chaotic nature. Here's a look at common mistakes and some cases where mistakes were made.

Medical errors in the pediatric emergency department: Don't make these mistakes!

What a difference a year makes. Last year, when 

s put out its annual issues and attitudes survey, 57% of respondents said they were feeling less optimistic about their ability to provide adequate care for patients (which was, by the way a 13% jump from 2013). This year, that percentage rose even more, to 60%, a notable majority. But although the reasons around the pessimism remained the same in both 2013 and 2019 (insufficient time with patients, inadequate reimbursement, and health care reform), this year—no surprise—the top reason was concerns about adequately treating patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). That was followed by inadequate insurance reimbursement and not enough time with patients. Interesting too, is that those who answered they were more optimistic (only 9%), felt that way because of new tech tools (38%), good relationships with local specialists that they refer patients to (34%), and having more treatment options for COVID-19/MIS-C (24%). 

(Editor’s note: this survey went out in September, when treatments like remdesivir and convalescent plasma had been approved by the US Food and Drug Administration for use of COVID-19)

In 2019, when asked what the top 2 challenges to their practice were, 45% of health care providers said transitioning to electronic health records (EHRs) and dealing with insurance (42%) were the greatest obstacles. This year, EHRs were not even mentioned in the top 5 reasons, taking a back seat to lack of patients due to issues around COVID-19/MIS-C, which 60% of respondents gave as the biggest challenge, followed by compensation (36 %), dealing with insurance (28%), not having effective treatments for COVID-19 and MIS-C (20%), and vaccine hesitancy (20%). Also not surprising was that more than 40% of respondents reported that their work level had decreased over the year, (compared to only 10% claiming that the year prior), another sober indication of how the pandemic has affected patient traffic in pediatric offices around the United States.

In regards to vaccine hesitancy, 70% of respondents said that they believe that some of their patients would be hesitant to get a COVID-19/MIS-C vaccine, even one that had been judged safe and effective; 28% thought most would be hesitant, and only 2% thought that none would be wary of a vaccine on the market. Considering the recent news about 3 vaccines that might soon be available to the public, this hesitancy is worrisome indeed.

The good news here: The pediatric medical community continues to stand behind its scientists. A whopping 74% of you would encourage your patients to get a vaccine, if a reliable and safe one came on the market to combat the pandemic. Only 23% of respondents were unsure, and 3% would advise not getting a vaccine at all.

On another encouraging note, pediatric providers are riding the tech tidal wave in ways they never have before. The fact that EHRs didn’t even make the list of challenges this year suggests that they are now a way of life. Furthermore, more than 70% of respondents said they were doing more telehealth than previous years.

Once we can see our way out of the pandemic, what changes will be permanent as a result of living and working under the COVID-19 cloud? We can’t wait to hear from you to tell us.

With the United States still in the throes of a pandemic, nearly 400 pediatric health care providers share their struggles in getting patients back to the office, advocating for a COVID-19 vaccine, and working their way toward optimism in the face of the biggest health care challenge of their lives.

Will the COVID-19 cloud change pediatric medicine forever?

A healthy 16-year-old girl presented with asymptomatic lesions she had at birth. Examination revealed a 15 cm well-demarcated light brown hyperpigmented background patch localized to the right inguinal skin-fold and, within it, café-au-lait macules and patches, greater than 1.5 cm, with diffuse freckling (Figure 1).

Diagnosis: Classic segmental form of mosaic neurofibromatosis (MNF1)

NF1 is the most common form of neurofibromatosis, with an estimated prevalence of 1 in 4500, although the mosaic form has a prevalence of 1 in 36,000-40,000, but is likely to be underreported.

 The skin condition MNF1 occurs after microdeletion mutations in the NF1 gene during embryonic development. Skin involvement can range from a narrow segment to half of the body in either symmetrical or asymmetrical distribution, depending on the timing of the mutation and the cell lines affected.

Patients with MNF1 may meet the diagnostic criteria for NF1, but their findings occur in more localized areas as in our patient. Diagnosis is made using the National Institutes of Health criteria based on the presence of at least 2 clinical findings, of which our patient has 6 or more café-au-lait macules or patches (greater than 0.5 cm in children or 1.5 cm in adults) and freckling in the inguinal crease.

 However, children with only 3-5 café-au-lait lesions could also be affected by MNF1, though these cases are often underreported. For this presentation, the natural progression of MNF1 is similar to that of NF1, with patients first presenting with café-au-lait lesions, followed by freckling. A classic sign seen in our patient is a subtle hyperpigmented background patch in the affected area. Other diagnostic criteria include 2 or more neurofibromas or one plexiform neurofibroma, two or more Lisch nodules, optic glioma, bony dysplasia, or a first-degree relative with NF1. When they arise, neurofibromas are usually seen in adulthood.

Complications seen in NF1 include hypertelorism, macrocephaly, short stature, and thorax abnormalities, as well as learning disabilities, ophthalmologic and orthopedic issues, and increased risk of certain malignancies.

 However, among MNF1 with localized skin involvement, complications are more rare, but have been reported to occur, especially with larger involvement of the skin, though not necessarily in the same location as skin involvement.

About 10% of the general population has 1 to 2 café-au-lait lesions, which can be normal.

 Other important differential diagnoses include syndromes associated with café-au-lait macules (NF2, legius syndrome, McCune Albright syndrome, and multiple familial café-au-lait), conditions associated with pigmented macules (Peutz-Jeghers syndrome, LEOPARD syndrome, neurocutaneous melanosis), and other conditions causing tumor or localized overgrowth (lipomatosis, fibromatoses, speckled lentiginous segmental eruption)

There are no specific guidelines for management of patients with MNF1 as there are for NF1.

 It is important for pediatricians to recognize MNF1 as it is likely underdiagnosed. Patients should be advised of lower risk of complications compared to NF1, but be aware that complications and gonadal involvement are possible.

 It has thus been recommended that MFN1 patients undergo a complete physical exam and global assessment as well as consider genetic counseling as well.

 Patients with MNF1 can be reassured that, although the involved area can evolve in appearance during childhood, new lesions or spreading of the lesions would not be expected to occur on other areas in adulthood.

Our patient is growing and developing normally, has a normal eye exam, and has no signs of systemic NF1.

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2. García-Romero MT, Parkin P, Lara-Corrales I. Mosaic neurofibromatosis type 1: a systematic review. 

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. 2017;21(5):379-382. doi:10.1177/1203475417708163

A healthy 16-year-old girl presented with asymptomatic lesions she had at birth. Examination revealed a 15 cm well-demarcated light brown hyperpigmented background patch localized to the right inguinal skin-fold and, within it, café-au-lait macules and patches, greater than 1.5 cm, with diffuse freckling.

Segmental form of mosaic neurofibromatosis 1

I first want to extend an official welcome to the latest additions to the Editorial Advisory Board: Dr Candice Jones—a general pediatrician practicing in Orlando, Florida and Dr Amin Barakat—a professor of Clinical Pediatrics and Pediatric Nephrology at Georgetown University Medical Center in Washington, DC. Both these individuals bring incredible passion and diverse talent to the editorial board.

As the COVID­-19 pandemic surges again across the country and new restrictions, travel bans, and stay­-at­-home orders are implemented‑ the specter of “COVID­-19 fatigue” becomes increasingly apparent. As we all continue to work to provide the most comprehensive and compassionate care to our patients, it is important to remember to care for ourselves. As cliché as it sounds, self-­care and wellness are now more important than ever. I was recently reminded of this while attending a very busy inpatient infectious diseases service with a number of severely ill patients, including those with COVID­-19 associated multisystem inflammatory syndrome in children. Working long hours with very sick patients day in and day out‑ getting little sleep, not taking time to eat, putting everyone else’s needs before your own personal needs, in addition to juggling other responsibilities is not sustainable or healthy. In the midst of the chaos, a friend reminded me that I cannot provide the level of care to my patients that I am accustomed to if I don’t take care of myself. Incorporating moments during the day to recharge helps to build resilience and allows one to work through challenges. As Mary Holloway said, “Resilience is knowing that you are the only one that has the power and the responsibility to pick yourself up.”

As we move deep into the winter season‑ please stay safe and well. And as always‑ I welcome your suggestions‑ comments‑ and questions.

Dr. Tina Q. Tan mulls over the need for self-care and the very real specter of COVID-19 fatigue.

Reflecting on the pandemic

Celiac disease (CD) is an autoimmune disease in which a reaction to gluten consumption damages the small intestine. With a steadily increasing global prevalence of close to 1%

, public awareness of CD and gluten-related disorders has grown considerably over the last few decades.

Celiac disease is more common in children with the following risk factors:

Since the middle of the 20th century and into the 21st century, the incidence of celiac disease has been rising significantly throughout the Western world. Here is what you need to know about this autoimmune condition.

Vol 37 No 12

Empiric selection of lipid emulsion in hospitalized neonates

A case of acute psychosis that will make your head spin

Medical errors in the pediatric emergency department: Don't make these mistakes!

Will the COVID-19 cloud change pediatric medicine forever?

Segmental form of mosaic neurofibromatosis 1

Reflecting on the pandemic

A new diagnostic paradigm for celiac disease

When it comes to infant distress, acid reflux often gets a bum rap!

Acetaminophen is not the best choice for fever in asthmatics

Prefilled pen may be a better way to deliver methotrexate to children with JIA