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ABSTRACT: Human herpesvirus 6B (HHV-6B) reactivation and disease are increasingly reported after chimeric antigen receptor (CAR) T-cell therapy (CARTx). HHV-6 reactivation in the CAR T-cell product was recently reported, raising questions about product and patient management. Because of overlapping manifestations with immune effector cell-associated neurotoxicity syndrome, diagnosing HHV-6B encephalitis is challenging. We provide 2 lines of evidence assessing the incidence and outcomes of HHV-6B after CARTx. First, in a prospective study with weekly HHV-6B testing for up to 12 weeks after infusion, HHV-6B reactivation occurred in 8 of 89 participants; 3 had chromosomally integrated HHV-6 and were excluded, resulting in a cumulative incidence of HHV-6B reactivation of 6% (95% confidence interval [CI], 2.2-12.5). HHV-6B detection was low level (median peak, 435 copies per mL; interquartile range, 164-979) and did not require therapy. Second, we retrospectively analyzed HHV-6B detection in the blood and/or cerebrospinal fluid (CSF) within 12 weeks after infusion in CARTx recipients. Of 626 patients, 24 had symptom-driven plasma testing, with detection in 1. Among 34 patients with CSF HHV-6 testing, 1 patient had possible HHV-6 encephalitis for a cumulative incidence of 0.17% (95% CI, 0.02-0.94), although symptoms improved without treatment. Our data demonstrate that HHV-6B reactivation and disease are infrequent after CARTx. Routine HHV-6 monitoring is not warranted.
Subject(s)
Herpesvirus 6, Human , Immunotherapy, Adoptive , Receptors, Chimeric Antigen , Roseolovirus Infections , Virus Activation , Humans , Herpesvirus 6, Human/immunology , Male , Female , Middle Aged , Adult , Roseolovirus Infections/immunology , Roseolovirus Infections/virology , Roseolovirus Infections/therapy , Roseolovirus Infections/diagnosis , Receptors, Chimeric Antigen/immunology , Virus Activation/immunology , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Aged , Prospective Studies , Retrospective Studies , Young Adult , IncidenceABSTRACT
BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disorder that is common in children and associated with medical and psychosocial comorbidities. Previous studies have shown that there exist significant racial disparities in healthcare utilization in children with AD; however, literature on disparities in dermatology access is limited. OBJECTIVES: The primary aim of this study was to identify differences in diagnosis of AD and access to dermatologic care by race and ethnicity in infants with AD. METHODS: We conducted a retrospective chart review of infants diagnosed with AD at Boston Children's Hospital from January 1, 2015 - December 31, 2019. Race and ethnicity were categorized as Native American or Alaska Native, Asian, non-Hispanic Black, Hispanic, Native Hawaiian or Other Pacific Islander, non-Hispanic white, and other. Outcomes included time to diagnosis and dermatology visit from rash onset and were analyzed utilizing a Kruskal-Wallis test. Severity of presentation at first dermatology visit, presentation to the emergency department (ED), medications prescribed, and follow up were analyzed using Chi-squared tests. RESULTS: Significantly more non-Hispanic white infants received a prescription by their pediatrician for AD than Hispanic infants (p = 0.002). Non-Hispanic Black and Asian infants waited longer to see a dermatologist after receiving a prescription for AD by their pediatrician compared to non-Hispanic white patients (p < 0.001; p = 0.007). Significantly more non-Hispanic Black and Hispanic infants presented to the ED for AD within the first year of life than non-Hispanic white patients (p < 0.001; p = 0.003). CONCLUSIONS: Our study suggests disparities in diagnosis and access to care for non-Hispanic Black and Hispanic infants with AD, with differences in prescriptions, time to see a dermatologist, and presentation to the ED compared to non-Hispanic white infants.
ABSTRACT
BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.
Subject(s)
Melanoma , Skin Neoplasms , Adult , Humans , Child , Adolescent , Melanoma/pathology , Retrospective Studies , Skin Neoplasms/pathology , Sentinel Lymph Node Biopsy , Risk FactorsABSTRACT
BACKGROUND: MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. PURPOSE: To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. METHODS: We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. RESULTS: Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. CONCLUSION: Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy.
Subject(s)
Protein Kinase Inhibitors , Humans , Protein Kinase Inhibitors/adverse effects , Antineoplastic Agents/adverse effects , Neoplasms/drug therapy , Severity of Illness Index , Drug Eruptions/etiologyABSTRACT
Urticaria in infants can cause significant anxiety in parents, especially if a trigger cannot be identified. In a retrospective study of 246 infants seen for urticaria of unknown etiology at Boston Children's Hospital, 88.2% had resolution of urticaria within 6 weeks. The etiology of urticaria was ultimately established in 62.6% (72/115) of acute urticaria and 12.5% (2/16) of chronic urticaria cases with follow-up data. Pediatric healthcare providers can counsel families that while etiology of urticaria is never determined in over 40% of infants, symptoms are most likely to resolve spontaneously.
Subject(s)
Urticaria , Infant , Child , Humans , Retrospective Studies , Urticaria/diagnosis , Urticaria/epidemiology , Urticaria/etiology , Anxiety , Boston/epidemiology , Chronic DiseaseABSTRACT
Several dermatologic concerns are known to disproportionally affect transgender and gender-diverse (TGD) adults, but little is known about dermatologic conditions in TGD youth. This study assesses the prevalence of acne, androgenic alopecia, scarring from gender-affirming procedures, and eczema in pediatric TGD patients seen at Boston Children's Hospital between April 2021 and April 2022. The results demonstrate that, for TGD youth, the studied dermatologic concerns are common, referral rates to dermatology are low, and acne is significantly associated with testosterone use. Future studies should examine additional dermatologic concerns and barriers to accessing dermatologic care for this historically underserved population.
Subject(s)
Acne Vulgaris , Transgender Persons , Humans , Female , Retrospective Studies , Male , Adolescent , Transgender Persons/statistics & numerical data , Acne Vulgaris/epidemiology , Child , Alopecia/epidemiology , Eczema/epidemiology , Prevalence , Cicatrix , Skin Diseases/epidemiology , Sex Reassignment ProceduresABSTRACT
BACKGROUND: Incidental findings are unrelated to a patient's complaint, found on diagnostic imaging, such as point-of-care ultrasound (POCUS). Incidental findings represent potential harms to patients and may lead to increased patient anxiety and health care costs related to downstream testing and surveillance. STUDY OBJECTIVES: In this study, we aimed to calculate the rate of incidental renal cysts found by POCUS. Further, we hoped to describe how emergency physicians relay the findings to patients. Lastly, we hoped to examine if patients suffered harms in the 12 months following identification of an incidental renal cyst. METHODS: From our single-center, academic emergency department (ED), we reviewed renal POCUS images from 1000 consecutive adult ED patients to determine if there was a renal cyst. Next, we performed manual chart review to determine if patients were informed of the incidental renal cyst or suffered any patient harms. RESULTS: We found the prevalence of renal cysts to be 6.5% (95% confidence interval: 4.9%-8.4%). Those with cysts were more likely to be older compared to those without (63 ± 14 vs. 49 ± 15 years of age). Only 8% of patients had evidence that they were informed of their incidental renal cyst. No patients received a biopsy or were diagnosed with renal cell carcinoma or polycystic kidney disease. CONCLUSION: Incidental renal cysts are common and are more likely to be found in older adults. In our study, physicians infrequently informed patients of their incidental finding.
Subject(s)
Emergency Service, Hospital , Incidental Findings , Kidney Diseases, Cystic , Point-of-Care Systems , Ultrasonography , Humans , Ultrasonography/methods , Ultrasonography/statistics & numerical data , Male , Middle Aged , Retrospective Studies , Female , Kidney Diseases, Cystic/diagnostic imaging , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Aged , Adult , Point-of-Care Systems/statistics & numerical data , PrevalenceABSTRACT
Planar cell polarity (PCP) proteins localize asymmetrically to instruct cell polarity within the tissue plane, with defects leading to deformities of the limbs, neural tube and inner ear. Wnt proteins are evolutionarily conserved polarity cues, yet Wnt mutants display variable PCP defects; thus, how Wnts regulate PCP remains unresolved. Here, we have used the developing cochlea as a model system to show that secreted Wnts regulate PCP through polarizing a specific subset of PCP proteins. Conditional deletion of Wntless or porcupine, both of which are essential for secretion of Wnts, caused misrotated sensory cells and shortened cochlea - both hallmarks of PCP defects. Wntless-deficient cochleae lacked the polarized PCP components dishevelled 1/2 and frizzled 3/6, while other PCP proteins (Vangl1/2, Celsr1 and dishevelled 3) remained localized. We identified seven Wnt paralogues, including the major PCP regulator Wnt5a, which was, surprisingly, dispensable for planar polarization in the cochlea. Finally, Vangl2 haploinsufficiency markedly accentuated sensory cell polarization defects in Wntless-deficient cochlea. Together, our study indicates that secreted Wnts and Vangl2 coordinate to ensure proper tissue polarization during development.
Subject(s)
Cochlea/embryology , Cochlea/metabolism , Nerve Tissue Proteins/metabolism , Wnt Proteins/metabolism , Animals , Dishevelled Proteins/genetics , Dishevelled Proteins/metabolism , Frizzled Receptors/genetics , Frizzled Receptors/metabolism , Genotype , Immunohistochemistry , In Situ Hybridization , Mice , Microscopy, Electron, Scanning , Nerve Tissue Proteins/genetics , Polymerase Chain Reaction , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Wnt Proteins/geneticsABSTRACT
Macrocephaly, defined as a head circumference greater than 2 standard deviations above the mean, is a relatively common presenting symptom in the pediatric population at routine well-child examinations and a common indication for neuroimaging. Multiple imaging modalities are complementary in evaluating macrocephaly, including US, CT, and MRI. The differential diagnosis for macrocephaly is broad, and many disease processes lead to macrocephaly only when the sutures are open. In patients with closed sutures, these entities instead lead to increased intracranial pressure, according to the Monroe-Kellie hypothesis, which states that there is an equilibrium between intracranial constituents due to the fixed intracranial volume. The authors describe a useful paradigm for classifying macrocephaly by identifying which of the four components of the cranium (ie, cerebrospinal fluid, blood and vasculature, brain parenchyma, or calvarium) has an increased volume. Patient age, additional imaging findings, and clinical symptoms are also useful features. Most cases in the pediatric population are due to increased cerebrospinal fluid spaces, such as benign enlargement of the subarachnoid space, which must be carefully distinguished from subdural fluid collections in patients with accidental or nonaccidental trauma. Other common causes of macrocephaly are discussed, including hydrocephalus secondary to an aqueductal web, hemorrhage, or a neoplasm. The authors also provide information on some of the rarer diseases for which imaging may provide the impetus for genetic testing (eg, overgrowth syndromes and metabolic disorders). ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.
Subject(s)
Megalencephaly , Child , Humans , Infant , Megalencephaly/diagnostic imaging , Megalencephaly/epidemiology , Head , Brain , Subarachnoid Space , Magnetic Resonance ImagingABSTRACT
BACKGROUND: Pediatric oncology patients undergoing cancer treatment can often have numerous and recalcitrant cutaneous warts due to their underlying immunosuppression. There are little published data on the optimal management of warts in pediatric oncology patients undergoing active cancer treatment compared to patients having completed treatment. Our objective was to analyze the clinical course of warts treated within this patient population at Boston Children's Hospital over a 10-year period. METHODS: This was a single-institution retrospective study of 72 pediatric oncology patients from 1 September 2011 to 1 September 2021 who were treated for warts at Boston Children's Hospital. All patients had a diagnosis of cutaneous warts with at least one follow-up visit and were receiving active treatment for cancer either during or after concurrent treatment of their warts. We examined the modality and effectiveness of wart treatments while both on and offactive treatment of their cancer. RESULTS: The median age was 12 years (range 4-18). Fifty-four percent of patients were documented to have plantar warts. Sixty percent of patients with a documented number of warts had more than five warts at presentation. For cases in which outcomes were specified, treatment resulted in complete resolution of warts in only 24.0% of patients undergoing active cancer treatment compared to 63.3% of patients not on active treatment. Warts persisted or worsened in 56.0% of patients undergoing active cancer treatment compared to only 13.4% of patients not on active treatment. CONCLUSION: These data may help guide clinicians in evaluating and treating warts in pediatric oncology patients.
Subject(s)
Warts , Child , Humans , Child, Preschool , Adolescent , Retrospective Studies , Warts/drug therapy , Administration, Cutaneous , Immunosuppression Therapy , Boston/epidemiology , Treatment OutcomeABSTRACT
Individuals with bicuspid aortic valve (BAV) have historically been advised to avoid contact sports and isometric exercise for risk of increasing aortic dilation and valve disease. There is mounting evidence that current sports participation guidelines qualify children for a high rate of sports exclusion, and that this population is at increased risk of obesity. The primary aim of this study was to evaluate relationship between sports participation and aortic dilation in children with bicuspid aortic valve and secondarily the relationship between competitive sports participation and obesity. We performed a review of children between the ages of 8 and 17 years with isolated BAV followed at Oregon Health & Science University. We excluded those with other congenital heart diseases, genetic conditions, prior cardiac intervention, and inability to ambulate independently. Parents completed a phone survey detailing their child's level of daily activity and participation in competitive sports. Demographic information and most recent echo findings were collected from the electronic medical record. We found no difference between the aortic diameters of athletes vs non-athletes. We also found that sports participation and daily activity were both associated with a decreased likelihood of obesity (OR 0.24, 95% CI 0.078-0.73 and OR 0.24, 95% CI 0.081-0.71 respectively). In summary, in our sample population, competitive sports participation was associated with a decreased risk of obesity. Competitive sports participation does not appear to be associated with an increased risk of aortic dilation in our population.
ABSTRACT
Although the rates of disease gene discovery have steadily increased with the expanding use of genome and exome sequencing by clinical and research laboratories, only ~16% of genes in the genome have confirmed disease associations. Here we describe our clinical laboratory's experience utilizing GeneMatcher, an online portal designed to promote disease gene discovery and data sharing. Since 2016, we submitted 246 candidates from 243 unique genes to GeneMatcher, of which 111 (45%) are now clinically characterized. Submissions meeting our candidate gene-reporting criteria based on a scoring system using patient and molecular-weighted evidence were significantly more likely to be characterized as of October 2021 versus genes that did not meet our clinical-reporting criteria (p = 0.025). We reported relevant findings related to these newly characterized gene-disease associations in 477 probands. In 218 (46%) instances, we issued reclassifications after an initial negative or candidate gene (uncertain) report. We coauthored 104 publications delineating gene-disease relationships, including descriptions of new associations (60%), additional supportive evidence (13%), subsequent descriptive cohorts (23%), and phenotypic expansions (4%). Clinical laboratories are pivotal for disease gene discovery efforts and can screen phenotypes based on genotype matches, contact clinicians of relevant cases, and issue proactive reclassification reports.
Subject(s)
Diagnostic Techniques and Procedures , Laboratories , Genetic Association Studies , Humans , Phenotype , Exome SequencingABSTRACT
Assessing residents and clinical fellows is a high-stakes activity. Effective assessment is important throughout training so that identified areas of strength and weakness can guide educational planning to optimize outcomes. Assessment has historically been underemphasized although medical education oversight organizations have strengthened requirements in recent years. Growing acceptance of competency-based medical education and its logical extension to competency-based time-variable (CB-TV) graduate medical education (GME) further highlights the importance of implementing effective evidence-based approaches to assessment. The Clinical Competency Committee (CCC) has emerged as a key programmatic structure in graduate medical education. In the context of launching a multi-specialty pilot of CB-TV GME in our health system, we have examined several program's CCC processes and reviewed the relevant literature to propose enhancements to CCCs. We recommend that all CCCs fulfill three core goals, regularly applied to every GME trainee: (1) discern and describe the resident's developmental status to individualize education, (2) determine readiness for unsupervised practice, and (3) foster self-assessment ability. We integrate the literature and observations from GME program CCCs in our institutions to evaluate how current CCC processes support or undermine these goals. Obstacles and key enablers are identified. Finally, we recommend ways to achieve the stated goals, including the following: (1) assess and promote the development of competency in all trainees, not just outliers, through a shared model of assessment and competency-based advancement; (2) strengthen CCC assessment processes to determine trainee readiness for independent practice; and (3) promote trainee reflection and informed self-assessment. The importance of coaching for competency, robust workplace-based assessments, feedback, and co-production of individualized learning plans are emphasized. Individual programs and their CCCs must strengthen assessment tools and frameworks to realize the potential of competency-oriented education.
Subject(s)
Clinical Competence , Internship and Residency , Competency-Based Education , Education, Medical, Graduate , Humans , Self-AssessmentABSTRACT
PURPOSE OF REVIEW: Children with systemic malignancies can present with concomitant dermatological manifestations. Cutaneous findings can occur before, during or after diagnosis. Recognizing these features can aid in diagnosis, inform prognosis, and help determine appropriate treatment. Following a review of the literature published over the past two years, we provide an update on cutaneous signs of pediatric systemic malignancies, concentrating on; leukemia cutis, lymphoma cutis, neuroblastoma, sarcomas, Langerhans cell histiocytosis and paraneoplastic syndromes. RECENT FINDINGS: Authors highlight the persistently heterogeneous features of cutaneous manifestations of systemic malignancy. Findings are often nonspecific, and a definitive diagnosis requires skin biopsy with immunophenotyping. Several studies describe dermoscopy features, demonstrating this as a useful tool in clinical evaluation. Genetic mutations underlying the pathogenesis of disease continue to be elucidated. Further, advances in medical treatment led to improved prognosis in many systemic malignancies, with early and aggressive treatment heralding better outcomes. SUMMARY: Comprehensive cutaneous evaluation alongside thorough clinical history and review of systems remains of paramount importance as dermatological manifestations of systemic malignancy are notoriously variable with a shared feature of often appearing benign but persisting despite usual treatment. Urgent referral to dermatology is recommended when suspicion for any cutaneous presentation of malignancy arises.
Subject(s)
Leukemia , Sarcoma , Skin Neoplasms , Child , Humans , Immunotherapy , Skin/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/therapyABSTRACT
PURPOSE: The physician voice is crucial to shaping health policy and public health guidelines, particularly during COVID-19. However, there are gaps in health policy and advocacy education within graduate medical education. This study sought to characterise the impact of a virtual COVID-19 focused advocacy day among medical trainees in Massachusetts. STUDY DESIGN: The half-day event featured speakers drawn from government relations experts, physician advocates, and state and federal legislators as well as breakout discussions among attendees. A 25-question Redcap survey and list of resources/opportunities for continued advocacy was administered to all participants at event's conclusion on 19 May 2020. RESULTS: There were 60 responses from 141 participants (43% response rate). One-third reported no prior formal health policy instruction, and over half reported getting information from news publications, social media and peers. 58% believed physician involvement in advocacy to be 'extremely important' prior to COVID-19; 83% believed the same after onset of COVID-19 (p<0.0001). The most common barriers to advocacy engagement were lack of time and knowledge. Most attendees felt participation increased their knowledge and likelihood to engage in the COVID-19 response, imparted useful skills/knowledge for continued advocacy, increased their interest in future similar events, and that such events should be available to all trainees. CONCLUSIONS: Trainees recognise the importance of health policy and advocacy and value opportunities to gain the necessary skills/knowledge to effect tangible change. Virtual advocacy days can be replicated nationwide to help trainees learn about advocacy efforts and find their legislative voices during COVID-19 and beyond.
Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Education, Medical, Graduate , Health Policy , Humans , Surveys and QuestionnairesABSTRACT
Melanocyte stem cells (McSCs) are the undifferentiated melanocytic cells of the mammalian hair follicle (HF) responsible for recurrent generation of a large number of differentiated melanocytes during each HF cycle. HF McSCs reside in both the CD34+ bulge/lower permanent portion (LPP) and the CD34- secondary hair germ (SHG) regions of the HF during telogen. Using Dct-H2BGFP mice, we separate bulge/LPP and SHG McSCs using FACS with GFP and anti-CD34 to show that these two subsets of McSCs are functionally distinct. Genome-wide expression profiling results support the distinct nature of these populations, with CD34- McSCs exhibiting higher expression of melanocyte differentiation genes and with CD34+ McSCs demonstrating a profile more consistent with a neural crest stem cell. In culture and in vivo, CD34- McSCs regenerate pigmentation more efficiently whereas CD34+ McSCs selectively exhibit the ability to myelinate neurons. CD34+ McSCs, and their counterparts in human skin, may be useful for myelinating neurons in vivo, leading to new therapeutic opportunities for demyelinating diseases and traumatic nerve injury.
Subject(s)
Antigens, CD34/metabolism , Melanocytes/immunology , Melanocytes/physiology , Stem Cells/immunology , Stem Cells/physiology , Animals , Cell Differentiation , Cells, Cultured , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Hair Color/physiology , Hair Follicle/cytology , Hair Follicle/physiology , Melanocytes/classification , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Mice, Nude , Mice, Transgenic , Myelin Basic Protein/deficiency , Myelin Basic Protein/genetics , Neural Crest/cytology , Neural Crest/immunology , Neural Crest/physiology , Pigmentation/physiology , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Regeneration/physiology , Stem Cells/classificationABSTRACT
BACKGROUND/OBJECTIVES: Complications of hematopoietic stem cell transplant (HSCT) include acute graft-versus-host disease (aGVHD). Severe cutaneous aGVHD can present with generalized erythroderma, desquamation, and bullae which can mimic toxic epidermal necrolysis (TEN). TEN occurs in response to a culprit medication. Transplant patients are often on many medications, making it difficult to distinguish between the two conditions. Given that TEN-like aGVHD is rare, we describe a case series of pediatric patients and review the literature. METHODS: This is a multi-institutional case series of children who developed TEN-like aGVHD following bone marrow transplantation. Demographic, clinical, and treatment information was collected. RESULTS: Ten patients were identified. Median age at transplantation was 8.5 years (range 0.12-17 years). Median time from transplant to first skin symptoms was 35 days (range 6-110 days) and to first TEN-like symptoms was 40 days (range 16-116 days). 7/10 had other organ GVHD involvement. All patients were on concurrent medications at time of first skin symptoms including immunosuppression for GVHD prophylaxis, infection prophylaxis or treatment, and pain medication. Treatments for TEN-like aGVHD included immunosuppression. CONCLUSIONS: We observe that patients with > or equal to 50% BSA involvement of their skin with TEN-like aGVHD, extracutaneous GVHD, and lack of reepithelization tend to have poor outcomes. Given the rarity of this condition, multidisciplinary care of these patients is important for accurate and timely diagnosis and treatment.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Stevens-Johnson Syndrome , Humans , Child , Infant , Child, Preschool , Adolescent , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/drug therapy , Bone Marrow Transplantation/adverse effects , Stevens-Johnson Syndrome/diagnosis , Stevens-Johnson Syndrome/etiology , Stevens-Johnson Syndrome/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Bone Marrow , Acute DiseaseABSTRACT
BACKGROUND: Children with CHD are at risk for obesity and low levels of activity. These factors are associated with an increased risk of poor outcome. Participation in organised sports is an important avenue for children to maintain physical activity, though the relationship between sports participation and obesity has not been examined in the Fontan population. METHODS: We performed a cross-sectional study of children aged 8-18 who had been evaluated between January 1, 2015 and October 1, 2019 at the Doernbecher Children's Hospital outpatient paediatric cardiology clinic and had previously undergone a Fontan. Patients were excluded if they were unable to ambulate independently or if they had undergone a heart transplant. Patient characteristics were recorded from the electronic medical record. Parents were interviewed via a telephone survey and asked to describe their child's activity levels and sports participation. RESULTS: Our final cohort included 40 individuals, 74% were male. The overall prevalence of obesity (CDC BMI >95% for sex/age) in the cohort (23%) was significantly higher in non-athletes (33%) than athletes (0) (p = 0.02). There was no difference in cardiac complications or comorbidities between athletes and non-athletes. Athletes were more likely to meet daily activity recommendations (p = 0.05). CONCLUSION: Fontan patients who do not participate in sports are significantly more likely to be obese and less likely to be active than those who do. This is the first study to demonstrate the association between competitive sports participation and decreased likelihood of obesity in the Fontan population.
Subject(s)
Fontan Procedure , Heart Diseases , Pediatric Obesity , Sports , Child , Cross-Sectional Studies , Female , Fontan Procedure/adverse effects , Heart Diseases/etiology , Humans , MaleABSTRACT
Sirtuin-3 (Sirt3) is a major mitochondrial deacetylase enzyme that regulates multiple metabolic pathways, and its expression is decreased in diabetes type 1 and type 2 diabetes. This study aimed to elucidate Sirt3's molecular mechanism in regulating insulin sensitivity in adipocytes that can contribute to the effort of targeting Sirt3 for the treatment of obesity and type 2 diabetes. We found that the Sirt3 activator honokiol (HNK) induced adipogenesis compared to the control, in contrast to Sirt3 inhibitor, 3-TYP. Accordingly, HNK increased expression of adipocyte gene markers, gene-involved lipolysis and glucose transport (GLUT4), while 3-TYP reduced expression of those genes. Interestingly, 3-TYP caused an increase in gene expression of adipocyte-specific cytokines including IL6, resistin, and TNF-α. However, changes in adipocyte-specific cytokines in HNK treated cells were not significant. In addition, HNK stimulated insulin pathway by promoting insulin receptor beta (IRß) and PI3K/AKT/mTOR pathways, resulting in an increase in phosphorylation of the forkhead family FoxO1/FoxO3a/FoxO4 and glycogen synthase kinase-3 (GSK-3ß), opposing 3-TYP. In line with these findings, HNK increased free fatty acid and glucose uptake, contrary to 3-TYP. In conclusion, Sirt3 activator-HNK induced adipogenesis and lipolysis reduced adipocytes specific cytokines. Intriguingly, HNK activated insulin signaling pathway and increased free fatty acid as well as glucose uptake and transport, in sharp contrast to 3-TYP. These results indicate that, via insulin signaling regulation, Sirt3 activation by HNK improves insulin resistance, while Sirt3 inhibition by 3-TYP might precipitate insulin resistance.
Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Sirtuin 3 , Adipocytes/metabolism , Cytokines/metabolism , Diabetes Mellitus, Type 2/metabolism , Fatty Acids, Nonesterified/metabolism , Glucose/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Insulin/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Sirtuin 3/genetics , Sirtuin 3/metabolism , TOR Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing remains essential for early identification and clinical management of cases. We compared the diagnostic performance of 3 specimen types for characterizing SARS-CoV-2 in infected nursing home residents. METHODS: A convenience sample of 17 residents were enrolled within 15 days of first positive SARS-CoV-2 result by real-time reverse transcription polymerase chain reaction (RT-PCR) and prospectively followed for 42 days. Anterior nasal swabs (AN), oropharyngeal swabs (OP), and saliva specimens (SA) were collected on the day of enrollment, every 3 days for the first 21 days, and then weekly for 21 days. Specimens were tested for presence of SARS-CoV-2 RNA using RT-PCR and replication-competent virus by viral culture. RESULTS: Comparing the 3 specimen types collected from each participant at each time point, the concordance of paired RT-PCR results ranged from 80% to 88%. After the first positive result, SA and OP were RT-PCR-positive for ≤48 days; AN were RT-PCR-positive for ≤33 days. AN had the highest percentage of RT-PCR-positive results (21/26 [81%]) when collected ≤10 days of participants' first positive result. Eleven specimens were positive by viral culture: 9 AN collected ≤19 days following first positive result and 2 OP collected ≤5 days following first positive result. CONCLUSIONS: AN, OP, and SA were effective methods for repeated testing in this population. More AN than OP were positive by viral culture. SA and OP remained RT-PCR-positive longer than AN, which could lead to unnecessary interventions if RT-PCR detection occurred after viral shedding has likely ceased.