Improving Pneumococcal Vaccination Rates in Immunosuppressed Pediatric Patients with Rheumatic Disease.

Background: Patients with rheumatic diseases are at a high risk of invasive pneumococcal disease due to immunosuppression. We conducted a quality improvement project, and the first aim was to increase the percentage of patients with systemic lupus erythematosus and mixed connective tissue disease that is up to date on pneumococcal vaccinations from 9.6% to 80% within one year. Subsequently, the second aim was to increase the percentage of patients on immunosuppression with systemic lupus erythematosus, mixed connective tissue disease, juvenile dermatomyositis and systemic vasculitis that is up to date on pneumococcal vaccinations from 62.6% to 80% within one year. Methods: Two process measures were up-to-date vaccination status on (1) 13-valent pneumococcal conjugated vaccine (PCV13) and (2) 23-valent pneumococcal polysaccharide vaccine (PPSV23). Our outcome measure was being fully up to date on both pneumococcal vaccinations. Interventions included an immunization algorithm, reporting of eligible patients, education, reminders, and pre-visit planning. Results: There were shifts in the centerline for all quality measures in both phases of this project. The combined pneumococcal vaccination rate for Phase 1 increased from 9.6% to 91.1%, and this centerline was sustained. Pneumococcal vaccination rates also significantly increased for Phase 2: 68.8% to 93.4% for PCV13, 65.2% to 88.5% for PPSV23, and 62.6% to 86.5% for the combined pneumococcal vaccination rate. Conclusions: Quality improvement methodology significantly increased and sustained pneumococcal vaccination rates in our high-risk, immunosuppressed patients. We continue to prioritize this important initiative to mitigate the risk of invasive pneumococcal disease.

Predicting the onset of myopia in children by age, sex, and ethnicity: Results from the CLEERE Study.

SIGNIFICANCE: Clinicians and researchers would benefit from being able to predict the onset of myopia for an individual child. This report provides a model for calculating the probability of myopia onset, year-by-year and cumulatively, based on results from the largest, most ethnically diverse study of myopia onset in the United States. PURPOSE: This study aimed to model the probability of the onset of myopia in previously nonmyopic school-aged children. METHODS: Children aged 6 years to less than 14 years of age at baseline participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study who were nonmyopic and less hyperopic than +3.00 D (spherical equivalent) were followed up for 1 to 7 years through eighth grade. Annual measurements included cycloplegic autorefraction, keratometry, ultrasound axial dimensions, and parental report of children's near work and time spent in outdoor and/or sports activities. The onset of myopia was defined as the first visit with at least -0.75 D of myopia in each principal meridian. The predictive model was built using discrete time survival analysis and evaluated with C statistics. RESULTS: The model of the probability of the onset of myopia included cycloplegic spherical equivalent refractive error, the horizontal/vertical component of astigmatism (J0), age, sex, and race/ethnicity. Onset of myopia was more likely with lower amounts of hyperopia and less positive/more negative values of J0. Younger Asian American females had the highest eventual probability of onset, whereas older White males had the lowest. Model performance increased with older baseline age, with C statistics ranging from 0.83 at 6 years of age to 0.92 at 13 years. CONCLUSIONS: The probability of the onset of myopia can be estimated for children in the major racial/ethnic groups within the United States on a year-by-year and cumulative basis up to age 14 years based on a simple set of refractive error and demographic variables.

Plasma ctDNA enables early detection of temozolomide resistance mutations in glioma.

Background: Liquid biopsy based on circulating tumor DNA (ctDNA) is a novel tool in clinical oncology, however, its use has been limited in glioma to date, due to low levels of ctDNA. In this study, we aimed to demonstrate that sequencing techniques optimized for liquid biopsy in glioma patients can detect ctDNA in plasma with high sensitivity and with potential clinical utility. Methods: We investigated 10 glioma patients with tumor tissue available from at least 2 surgical operations, who had 49 longitudinally collected plasma samples available for analysis. Plasma samples were sequenced with CAPP-seq (AVENIO) and tissue samples with TSO500. Results: Glioma-derived ctDNA mutations were detected in 93.8% of plasma samples. 25% of all mutations detected were observed in plasma only. Mutations of the mismatch repair (MMR) genes MSH2 and MSH6 were the most frequent circulating gene alterations seen after temozolomide treatment and were frequently observed to appear in plasma prior to their appearance in tumor tissue at the time of surgery for recurrence. Conclusions: This pilot study suggests that plasma ctDNA in glioma is feasible and may provide sensitive and complementary information to tissue biopsy. Furthermore, plasma ctDNA detection of new MMR gene mutations not present in the initial tissue biopsy may provide an early indication of the development of chemotherapy resistance. Additional clinical validation in larger cohorts is needed.

Plasma ctDNA liquid biopsy of IDH1, TERTp, and EGFRvIII mutations in glioma.

Background: Circulating tumor DNA has emerging clinical applications in several cancers; however, previous studies have shown low sensitivity in glioma. We investigated if 3 key glioma gene mutations IDH1, TERTp, and EGFRvIII could be reliably detected in plasma by droplet digital polymerase chain reaction (ddPCR) thereby demonstrating the potential of this technique for glioma liquid biopsy. Methods: We analyzed 110 glioma patients from our biobank with a total of 359 plasma samples (median 4 samples per patient). DNA was isolated from plasma and analyzed for IDH1, TERTp, and EGFRvIII mutations using ddPCR. Results: Total cfDNA was significantly associated with tumor grade, tumor volume, and both overall and progression-free survival for all gliomas as well as the grade 4 glioblastoma subgroup, but was not reliably associated with changes in tumor volume/progression during the patients' postoperative time course. IDH1 mutation was detected with 84% overall sensitivity across all plasma samples and 77% in the preoperative samples alone; however, IDH1 mutation plasma levels were not associated with tumor progression or survival. IDH1m plasma levels were not associated with pre- or postsurgery progression or survival. The TERTp C228T mutation was detected in the plasma ctDNA in 88% but the C250T variant in only 49% of samples. The EGFRvIII mutation was detected in plasma in 5 out of 7 patients (71%) with tissue EGFRvIII mutations in tumor tissue. Conclusions: Plasma ctDNA mutations detected with ddPCR provide excellent diagnostic sensitivity for IDH1, TERTp-C228T, and EGFRvIII mutations in glioma patients. Total cfDNA may also assist with prognostic information. Further studies are needed to validate these findings and the clinical role of ctDNA in glioma.

Cardiovascular Symptoms, Dysautonomia, and Quality of Life in Adult and Pediatric Patients with Hypermobile Ehlers-Danlos Syndrome: A Brief Review.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder characterized by joint hypermobility and other systemic manifestations, such as cardiovascular symptoms, musculoskeletal pain, and joint instability. Cardiovascular symptoms, such as lightheadedness and palpitations, and types of dysautonomia, including postural orthostatic tachycardia syndrome (POTS), are frequently reported in adults with hEDS and have been shown to negatively impact quality of life (QoL). OBJECTIVE: This brief review will be an overview of co-occurring symptoms in POTS and hEDS to inform potential cardiovascular screening procedures. RESULTS: While many patients with hEDS report cardiovascular symptoms, few have structural abnormalities, suggesting that dysautonomia is likely responsible for these symptoms. One validated screening measure for dysautonomia symptom burden is the Composite Autonomic Symptom Scale (COMPASS-31). Studies have found that adults with POTS, hEDS, and both POTS and hEDS have higher COMPASS-31 scores than the general population, suggesting a high symptom burden due to dysautonomia, which leads to impaired QoL. CONCLUSION: While studies have examined cardiovascular symptoms and the impact of dysautonomia in adults with and without hEDS, there is scant literature on dysautonomia in pediatric patients with hEDS. Therefore, more studies on cardiovascular symptoms and dysautonomia, as they relate to the quality of life in pediatric patients with hEDS, are needed. This brief review summarizes the current literature on dysautonomia and cardiovascular symptoms in pediatric and adult populations with hEDS.

Spatial architecture of high-grade glioma reveals tumor heterogeneity within distinct domains.

Background: High-grade gliomas (HGGs) are aggressive primary brain cancers with poor response to standard regimens, driven by immense heterogeneity. In isocitrate dehydrogenase (IDH) wild-type HGG (glioblastoma, GBM), increased intratumoral heterogeneity is associated with more aggressive disease. Methods: Spatial technologies can dissect complex heterogeneity within the tumor ecosystem by preserving cellular organization in situ. We employed GeoMx digital spatial profiling, CosMx spatial molecular imaging, Xenium in situ mapping and Visium spatial gene expression in experimental and validation patient cohorts to interrogate the transcriptional landscape in HGG. Results: Here, we construct a high-resolution molecular map of heterogeneity in GBM and IDH-mutant patient samples to investigate the cellular communities that compose HGG. We uncovered striking diversity in the tumor landscape and degree of spatial heterogeneity within the cellular composition of the tumors. The immune distribution was diverse between samples, however, consistently correlated spatially with distinct tumor cell phenotypes, validated across tumor cohorts. Reconstructing the tumor architecture revealed two distinct niches, one composed of tumor cells that most closely resemble normal glial cells, associated with microglia, and the other niche populated by monocytes and mesenchymal tumor cells. Conclusions: This primary study reveals high levels of intratumoral heterogeneity in HGGs, associated with a diverse immune landscape within spatially localized regions.

Barriers to the Diagnosis, Care, and Management of Pediatric Patients With Ehlers-Danlos Syndrome in the United States: A Qualitative Analysis.

Objectives: Ehlers-Danlos Syndromes (EDS) are a family of heritable connective tissue diseases. Primary practitioners are capable of diagnosing and managing EDS; however, few are knowledgeable and comfortable enough to see patients with EDS, resulting in delays in diagnosis and care. This study explores the barriers physicians experience with diagnosing, managing, and caring for patients with EDS, and potential resolutions to those barriers. Methods: As part of a larger online study, providers (n = 107) in the United States were asked to specify "What information would improve (their) comfort" in diagnosing, caring for, and managing EDS via open-ended questions. Results: Providers reported wanting clinical practice guidelines, in formats that were easily accessible and usable, information on their roles in the management of EDS, the best ways to coordinate with specialty care, and available specialty consultation. Conclusions: Providers overall are willing to diagnose and treat EDS; however, additional supports and training are needed.

Peripheral Defocus, Pupil Size, and Axial Eye Growth in Children Wearing Soft Multifocal Contact Lenses in the BLINK Study.

Purpose: The purpose of this study was to evaluate the relationship between peripheral defocus and pupil size on axial growth in children randomly assigned to wear either single vision contact lenses, +1.50 diopter (D), or +2.50 D addition multifocal contact lenses (MFCLs). Methods: Children 7 to 11 years old with myopia (-0.75 to -5.00 D; spherical component) and ≤1.00 D astigmatism were enrolled. Autorefraction (horizontal meridian; right eye) was measured annually wearing contact lenses centrally and ±20 degrees, ±30 degrees, and ±40 degrees from the line of sight at near and distance. Photopic and mesopic pupil size were measured. The effects of peripheral defocus, treatment group, and pupil size on the 3-year change in axial length were modeled using multiple variables that evaluated defocus across the retina. Results: Although several peripheral defocus variables were associated with slower axial growth with MFCLs, they were either no longer significant or not meaningfully associated with eye growth after the treatment group was included in the model. The treatment group assignment better explained the slower eye growth with +2.50 MFCLs than peripheral defocus. Photopic and mesopic pupil size did not modify eye growth with the +2.50 MFCL (all P ≥ 0.37). Conclusions: The optical signal causing slower axial elongation with +2.50 MFCLs is better explained by the lens type worn than by peripheral defocus. The signal might be something other than peripheral defocus, or there is not a linear dose-response relationship within treatment groups. We found no evidence to support pupil size as a criterion when deciding which myopic children to treat with MFCLs.

Normal joint range of motion in children with Down syndrome.

Down syndrome (DS) is one of the most common chromosomal conditions that results in intellectual disability. Children with DS have many different inflammatory and noninflammatory conditions that can affect joint mobility leading to arthralgia and altered joint range of motion (ROM), and it is important to have normal reference values for comparison to determine the degree of impairment. The objective of this study was to establish normative joint ROM values, using a standardized measurement approach, for upper and lower joints of healthy children of both genders with DS. This study evaluated joint ROM in healthy males and females with DS who had no previous musculoskeletal pathology. Younger males have more ROM than females at the same age and both genders lose ROM with age but continue to have increased ROM in the ankles compared to children without DS. This study establishes optimal estimates of joint ROM in children with DS, and this information should be helpful to clinicians when assessment requires evaluation of joint ROM to know if evaluation falls within the normal ROM. This reference should be helpful to track joint disease progression over time or as part of a musculoskeletal screen for abnormal joint ROM in children with DS.

Quality of life after wearing multifocal contact lenses for myopia control for 2 weeks in the BLINK Study.

PURPOSE: To validate Pediatric Refractive Error Profile 2 (PREP2) subscales that can be used to evaluate contact lens wearers and compare vision-specific quality of life measurements between children wearing multifocal and single vision contact lenses for 2 weeks. METHODS: Two hundred and ninety-four myopic children aged 7-11 years (inclusive) were enrolled in the 3-year, double-masked Bifocal Lenses In Nearsighted Kids (BLINK) Study. Participants completed the PREP2 survey after having worn contact lenses for 2 weeks. The Vision, Symptoms, Activities and Overall PREP2 subscales were used to compare participants' subjective assessment while wearing +1.50 or +2.50 D add multifocal or single vision contact lenses. Rasch analysis was used to validate each subscale and to compare participants' subjective assessment of contact lens wear. RESULTS: Item fit to the Rasch model was good for all scales, with no individual items having infit mean square statistics outside the recommended range (0.7-1.3). Response category function was acceptable for all subscales, with ordered category thresholds. Measurement precision, assessed by the Rasch person reliability statistic, was less than ideal (≥0.8) for three of the subscales, but met the minimum acceptable standard of 0.5. Scores for the Vision subscale differed by treatment assignment (p = 0.03), indicating that participants with the highest add power reported statistically worse quality of vision, although the difference was only 3.9 units on a scale of 1-100. Girls reported fewer symptoms than boys (p = 0.006), but there were no other differences between boys and girls. CONCLUSIONS: Rasch analysis demonstrates that the PREP2 survey is a valid instrument for assessing refractive error-specific quality of life. These results suggest that vision-related quality of life is not meaningfully affected by 2 weeks of soft multifocal contact lens wear for myopia control.

Decellularization: Leveraging a Tissue Engineering Technique for Food Production.

The edible nature of many plants makes leaves particularly useful as scaffolds for the development of cultured meat, where animal tissue is grown in the laboratory setting. Recently, we demonstrated that decellularized spinach leaves can serve as scaffolds to grow and differentiate cells for cultured meat products. However, conventional decellularization methods use solutions that are not considered safe for use in food, such as organic solvents (hexanes) and detergents (triton X-100 (TX100)). This study modified decellularization protocols to incorporate detergents that are regulated (REG) by the United States Food and Drug Administration (FDA) for use in food, such as Polysorbate 20 (PS20), and eliminates the use of hexanes for cuticle removal. Spinach leaves were decellularized with sodium dodecyl sulfate and then with either TX100 (control) or PS20. The average DNA content for TX100 samples and PS20 samples was similar (1.3 ± 0.07 vs 1.3 ± 0.05 ng/mg; TX100 vs PS20, p = ns). The importance of cuticle removal was tested by removing hexanes from the protocol. Groups that included the cuticle removal step exhibited an average reduction in DNA content of approximately 91.7%, and groups that omitted the cuticle removal step exhibited an average reduction of approximately 90.3% (p = ns), suggesting that the omission of the cuticle removal step did not impede decellularization. Lastly, primary bovine satellite cells (PBSCs) were cultured for 7 days (d) on the surface of spinach leaves decellularized using the REG protocol. After the 7 d incubation period, PBSCs grown on the surface of REG scaffolds had an average viability of approximately 97.4%. These observations suggest that the REG protocol described in this study is an effective decellularization method, more closely adhering to food safety guidelines, that could be implemented in lab grown meat and alternative protein products.

Plastic orbital foreign body: the rise of plastic and its unintended consequences.

Intraorbital foreign bodies (IOrFBs) are a significant cause of ocular morbidity. Although plastic IOrFBs are rare, the increasing use of plastic and polymer composites in motor vehicles will increase their prevalence. Although challenging to identify, plastic IOrFBs have unique radiographic characteristics. The authors describe a case of an 18-year-old man with a history of a motor vehicle accident and a left upper eyelid laceration. In retrospect, imaging suggested a plastic IOrFB, which was initially overlooked. A follow-up examination demonstrated persistent left upper lid ptosis with an underlying mass. Further work-up revealed a retained IOrFB, which was removed via anterior orbitotomy. Scanning electron microscopy of the material was consistent with a plastic polymer. This case demonstrates the importance of maintaining a high suspicion for IOrFBs in the correct clinical context, the need for increased awareness of plastic and polymer composite IOrFBs, and the use of diagnostic imaging for identification.

History matters: Thermal environment before but not during wasp attack determines the efficiency of symbiont-mediated protection.

The outcome of natural enemy attack in insects is commonly impacted by the presence of defensive microbial symbionts residing within the host. The thermal environment is a factor known to affect symbiont-mediated traits in insects. Lower temperatures, for instance, have been shown to reduce Spiroplasma-mediated protection in Drosophila. Our understanding of protective symbiosis requires a deeper understanding of environment-symbiont-protection links. Here, we dissect the effect of the thermal environment on Spiroplasma-mediated protection against Leptopilina boulardi in Drosophila melanogaster by examining the effect of temperature before, during and after wasp attack on fly survival and wasp success. We observed that the developmental temperature of the mothers of attacked larvae, but not the temperature of the attacked larvae themselves during or after wasp attack, strongly determines the protective influence of Spiroplasma. Cooler maternal environments were associated with weaker Spiroplasma protection of their progeny. The effect of developmental temperature on Spiroplasma-mediated protection is probably mediated by a reduction in Spiroplasma titre. These results indicate that historical thermal environment is a stronger determinant of protection than current environment. Furthermore, protection is a character with transgenerational nongenetic variation probably to produce complex short-term responses to selection. In addition, the cool sensitivity of the Spiroplasma-Drosophila symbioses contrasts with the more common failure of symbioses at elevated temperatures, indicating a need to understand the mechanistic basis of low temperature sensitivity on this symbiosis.

The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis.

Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma survival, proliferation and invasion when cells are starved of glucose. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients. Glioblastoma cell lines over-expressing IL-11Rα displayed greater survival, proliferation, migration and invasion in glucose-free conditions compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα reversed these pro-tumorigenic characteristics. In addition, these IL-11Rα-over-expressing cells displayed enhanced glutamine oxidation and glutamate production compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα or the pharmacological inhibition of several members of the glutaminolysis pathway resulted in reduced survival (enhanced apoptosis) and reduced migration and invasion. Furthermore, IL-11Rα expression in glioblastoma patient samples correlated with enhanced gene expression of the glutaminolysis pathway genes GLUD1, GSS and c-Myc. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell survival and enhances cell migration and invasion in environments of glucose starvation via glutaminolysis.

Development of a Multidisciplinary Clinic for Patients with Ehlers Danlos Syndromes: Considerations and Strategies.

Ehlers-Danlos Syndromes (EDS) is a group of connective tissue disorders often encountered within rheumatology clinics and is associated with several overlapping symptoms, which may require attention from other medical subspecialities. Barriers exist to implementing multidisciplinary care for EDS, including a lack of knowledge, comfort, and time managing EDS. In the absence of multidisciplinary care, patients are often forced to self-coordinate care. This can lead to gaps in care and a lack of clarity of medical ownership over the patient's care. Integrated multidisciplinary clinics are sorely needed, but the development and implementation of such clinics is limited by resources and personnel. As such, the development of a multidisciplinary clinic can be daunting and may serve to discourage providers with competencies in EDS from attempting to develop this service. In this editorial, we share our experiences in developing a multidisciplinary clinic for EDS at a moderately-sized children's hospital, relying on several core disciplines with established EDS clinical loads (ie, rheumatology, cardiology, genetics, and psychology). We discuss considerations for the expansion of this service, pitfalls, and barriers throughout the development of the clinic, and our rationale underlying our process-related decisions. Development of a greater number of multidisciplinary EDS clinics, even in the potential absence of larger institutional support, is both possible and imperative for improving EDS care globally.

Vergence/accommodative therapy for symptomatic convergence insufficiency in children: Time course of improvements in convergence function.

PURPOSE: To evaluate the time course of improvements in clinical convergence measures for children with symptomatic convergence insufficiency treated with office-based vergence/accommodative therapy. METHODS: We evaluated convergence measures from 205, 9- to 14-year-old children with symptomatic convergence insufficiency randomised to office-based vergence/accommodative therapy in the Convergence Insufficiency Treatment Trial - Attention and Reading Trial (CITT-ART). Near-point of convergence (NPC) and near-positive fusional vergence (PFV) were measured at baseline and after 4, 8, 12 and 16 weeks of therapy; mean change in NPC and PFV between these time points were compared using repeated measures analysis of variance. Rates of change in NPC and PFV from: (1) baseline to 4 weeks and (2) 4-16 weeks were calculated. For each time point, the proportion of participants to first meet the normal criterion for NPC (<6 cm), PFV blur (break if no blur; >15Δ and >2 times the exodeviation) and convergence composite (NPC and PFV both normal) were calculated. RESULTS: The greatest change in NPC and PFV (7.6 cm and 12.7 Δ) and the fastest rate of improvement in NPC and PFV (1.9 cm/week and 3.2 Δ/week, respectively) were both found during the first 4 weeks of therapy, with both slowing over the subsequent 12 weeks. After 12 weeks of therapy, the NPC, PFV and convergence composite were normal in 93.2%, 91.7% and 87.8% of participants, respectively, and normalised with another 4 weeks of therapy in 4.4%, 2.0% and 4.4% of participants, respectively. CONCLUSION: Although the greatest improvements in NPC and PFV occurred in the first 4 weeks of therapy, most participants had weekly improvements over the subsequent 12 weeks of treatment. While most children with convergence insufficiency obtained normal convergence following 12 weeks of therapy, an additional 4 weeks of vergence/accommodative therapy may be beneficial for some participants.

Multicenter Study of Utility and Acceptability of Depression and Anxiety Screening in Adolescents and Young Adults With Childhood-Onset Systemic Lupus.

OBJECTIVE: To determine the utility and acceptability for depression and anxiety screening of adolescents and young adults (AYA) with childhood-onset systemic lupus erythematosus (cSLE) in the pediatric rheumatology setting. METHODS: AYA with cSLE, ages 12-21 years, from 8 collaborating sites, were consecutively screened for depression and anxiety with the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic and disease characteristics were collected, as well as patient-reported outcome measures using the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric profile-25. Acceptability of screening was assessed with postscreening surveys completed by AYA and parents. Chi-square and Wilcoxon rank sum tests examined the relationship between patient characteristics and history of previous screening. Spearman correlations examined relationships between screening scores, PROMIS domains, and other disease factors. RESULTS: Among 106 AYA screened, 64 (60%) had been previously screened, 25 (24%) by general pediatricians. Thirty-two (30%) AYA screened positive, including 24% for depression, 17% for anxiety, and 14% for suicidal ideation. Depression and anxiety symptom severity were highly correlated with increased PROMIS domain scores for fatigue and pain interference and moderately correlated with increased pain severity, decreased mobility, and decreased peer relationships. Eighty-six percent of AYA and 95% of parents expressed comfort with screening in the pediatric rheumatology setting. CONCLUSION: Depression, anxiety, and suicidal ideation are common among AYA with cSLE, and symptoms are correlated with important patient-reported outcomes. Mental health screening in the pediatric rheumatology setting was highly acceptable among AYA with cSLE and their parents.

Candida parapsilosis bloodstream infection in an immunocompromised host with discordant multiplex polymerase chain reaction and conventional blood culture results: a case report.

Prompt treatment of candidemia, especially in immunocompromised hosts, is known to improve outcomes. We present a case of discordance among results of Gram stain, multiplex polymerase chain reaction (PCR)-based rapid diagnostic technology, and conventional cultures that subsequently resulted in delayed therapy and hospitalization. An immunocompromised patient presented to the outpatient oncology clinic with signs and symptoms of systemic infection. Blood cultures were obtained, and Gram stain showed gram-negative rods, while multiplex PCR results (BioFire® FilmArray® BCID 1) returned positive for both Enterobacter cloacae and Candida parapsilosis. Conventional cultures only grew E. cloacae. Because of the discordant results, the primary team elected to give ertapenem monotherapy and defer antifungal therapy. The patient's symptoms progressed, and 11 days later, the patient was admitted with subsequent positive blood cultures for C. parapsilosis. The patient required a 9-day hospitalization due to complications associated with candidemia. This case highlights the value of understanding and interpretation of rapid diagnostics, shared decision-making in antimicrobial management of high-risk patients, and the important responsibility of antimicrobial stewardship teams across the continuum of care.

Is Three Company or a Crowd? Comparing and Contrasting U.S. and European Clostridioidesdifficile Clinical Practice Guidelines.

In 2021, the American College of Gastroenterology (ACG), the Infectious Diseases Society of America in conjunction with the Society for Healthcare Epidemiology of America (IDSA/SHEA), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published updated clinical practice guidelines (CPGs) for the management of Clostridioides difficile infections. The differences, sometimes subtle, between these guideline recommendations have caused some debate among clinicians. This paper delves into select key recommendations from each respective CPG and analyzes the differences and evidence associated with each. One primary difference between the CPGs is the preference given to fidaxomicin over vancomycin for initial treatment in non-severe and severe disease endorsed by IDSA/SHEA and ESCMID guidelines, while the ACG-sponsored CPGs do not offer a preference. The emphasis on cost effective data was also a noticeable difference between the CPGs and thus interpretation of the available evidence. When using guidelines to help support local practice or institutional treatment pathways, clinicians should carefully balance CPG recommendations with local patient populations and feasibility of implementation, especially when multiple guidelines for the same disease state exist.

Resource utilization and multidisciplinary care needs for patients with Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos syndrome (EDS) represents a family of heritable connective tissue disorders with overlapping phenotypic features, frequently including joint hypermobility, tissue fragility, and skin hyperextensibility. Comorbid symptoms are common for patients with EDS and include multiple body systems marked by neurologic, cardiovascular, gastrointestinal, musculoskeletal issues, chronic pain, headaches, and anxiety and depression. The many comorbidities lead to high disease burden, which requires greater healthcare utilization. METHODS: This survey of families examines healthcare utilization, of adults and minors, through evaluation of subspecialty care appointments across many healthcare systems in one region. RESULTS: There were 155 adults and 83 minors with a diagnosis of EDS with a total of 693 unique visits across 27 different specialties at over 20 different hospitals or clinics in the surveyed area. Cardiology, neurology, and gastroenterology were the most utilized subspecialties for adults, while rheumatology, cardiology, and neurology were most utilized by minors. Many respondents (67%) reported their medical care needs are not being met, and 87% reported interest in a multidisciplinary clinic for EDS with the most interest in pain management, physical and occupational therapy, and rheumatology. CONCLUSION: Understanding healthcare utilization and needs of those with EDS can provide the foundation for improved care for those with EDS through a coordinated multidisciplinary care model.