An unusual case of metastatic trophoblastic neoplasm presenting with diffuse cystic lung disease and pulmonary artery pseudoaneurysms in a teenager.

Diffuse cystic lung diseases (DCLDs) are a diverse group of lung disorders characterized by the presence of multiple air filled cysts within the lung tissue. These cysts are thin walled and surrounded by normal lung tissue. In adults, DCLD can be associated with various conditions such as lymphangioleiomyomatosis (LAM), Langerhans cell histiocytosis, cancers, and more. In children, DCLD is often linked to lung developmental abnormalities, with bronchopulmonary dysplasia being a common cause. Patients with pulmonary cysts are typically asymptomatic, but some may experience mild symptoms or pneumothorax. While DCLD in children is rarely due to malignancy, metastatic lung disease can be a cause. It is important for clinicians to be aware of the possibility of metastatic lung disease when encountering DCLD.

A pediatric cystic fibrosis arthropathy case who responded to Elexacaftor/Tezacaftor/Ivacaftor therapy.

Cystic fibrosis arthropathy (CFA) is a transient, intermittent form of arthritis that cannot be associated with any other disease other than CF thus making CFA a diagnosis of exclusion. NSAIDs, short-term intermittent splinting, glucocorticoids, and disease-modifying anti-rheumatic drugs are treatment options for CFA. Currently, there is no consensus on how to best treat CFA. Diagnosis and treatment of CFA remain a challenge for physicians and people with CF. The newest CFTR modulator therapy, elexacaftor/tezacaftor/ivacaftor (ETI), was approved by the FDA recently for children over the age of 6 with at least one Phe508del allele in the CFTR gene. Multiple clinical benefits of ETI in pulmonary functions and overall disease burden have been reported since its approval, however, the data on the musculoskeletal therapeutic benefits of ETI has been limited. In this report, we present a 7-year-old female with CF whose CFA symptoms resolved after starting ETI therapy.

Oral Glucose Tolerance Testing Using Candy: A Sweet Solution to Improve Screening in Children with Cystic Fibrosis?

INTRODUCTION: Oral glucose tolerance testing is recommended for all children with CF older than 9 years, yet compliance remains poor across centers. METHODS: We performed a small pilot study assessing the glycemic curves and participant satisfaction in seven children and adolescents. RESULTS: We chose a dextrose-based candy (Nerds®) free of any fat, fiber, gelatin, or corn syrup and performed the candy OGTT 1-4 days following the standard oral dextrose solution OGTT. Glucose values at 120 min were similar between the candy and oral dextrose solution (p = 0.8986). CONCLUSIONS: Our small pilot suggests that a carefully selected candy alternative may result in similar glycemic OGTT when compared to the standard oral dextrose solution. However, some participants preferred the oral dextrose solution to candy due to having to consume a large volume in a short period of time. This may have significant implications as centers consider candy alternatives to increase OGTT adherence rates.

Influence of Chirality of Benzimidazole Amine Hybrids on Inhibition of Human Erythrocytes Carbonic Anhydrase I, II and Acetylcholinesterase.

Novel chiral benzimidazole amine hybrids (4a-4d) were synthesized from commercially available amine [(R)- (+)-phenylethylamine, (-) (S)-(-)-phenylethylamine, (-) (R)-(-)-cyclohexylethylamine, (S)-(+)-cyclohexylethylamine] and 2-(chloromethyl)-N-tosyl-1H-benzimidazole. The synthesized compounds (4a-4d) were characterized by IR, NMR, and LC/MS analysis. The inhibitory effect of 4a-4d on human erythrocytes carbonic anhydrase I (hCA-I), II (hCA-II), and acetylcholinesterase (AChE) activity was investigated. For hCA-I, the IC50 values of 4a-4d were found to be 4.895 µM, 1.750 µM, 0.173 µM, and 0.620 µM, respectively, and for hCA-II, the IC50 values of 4a-4d were found to be 0.469 µM, 0.380 µM, 0.233 µM, 0.635 µM, respectively. Furthermore, IC50 values of 4a-4d on AChE were found as 87.5 nM, 100 nM, 26.92 nM, and 100 nM, respectively. In addition, molecular docking analysis was performed to evaluate the affinity of 4a-4d against hCA-I, hCA-II, and AChE and explain their binding interactions.

Suicide attempts in adolescents with cystic fibrosis on Elexacaftor/Tezacaftor/Ivacaftor therapy.

Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a recently approved cystic fibrosis (CF) transmembrane conductance regulator modulator therapy that has shown promising clinical and laboratory improvements on multiple organ systems in people with CF (pwCF). While original clinical trials found little to no effect on depression and anxiety, many post-marketing reports have suggested that ETI may be associated with adverse mental health effects. Here we report on two pwCF with adverse mental health effects shortly after starting ETI. Although many factors such as the burden of living with a chronic disease or widespread effects of the Covid-19 pandemic may have contributed to these events, similar reports have led to mounting concern that ETI may be the cause of such events. Regular mental health screening before the initiation of ETI and monitoring for signs and symptoms of mental diseases afterward should be a routine part of care, given the gravity of possible outcomes.

Pilot study to determine whether reduced-dose photon-counting detector chest computed tomography can reliably display Brody II score imaging findings for children with cystic fibrosis at radiation doses that approximate radiographs.

BACKGROUND: The Brody II score uses chest CT to guide therapeutic changes in children with cystic fibrosis; however, patients and providers are often reticent to undergo chest CT given concerns about radiation. OBJECTIVE: We sought to determine the ability of a reduced-dose photon-counting detector (PCD) chest CT protocol to reproducibly display pulmonary disease severity using the Brody II score for children with cystic fibrosis (CF) scanned at radiation doses similar to those of a chest radiograph. MATERIALS AND METHODS: Pediatric patients with CF underwent non-contrast reduced-dose chest PCD-CT. Volumetric inspiratory and expiratory scans were obtained without sedation or anesthesia. Three pediatric radiologists with Certificates of Added Qualification scored each scan on an ordinal scale and assigned a Brody II score to grade bronchiectasis, peribronchial thickening, parenchymal opacity, air trapping and mucus plugging. We report image-quality metrics using descriptive statistics. To calculate inter-rater agreement for Brody II scoring, we used the Krippendorff alpha and intraclass correlation coefficient (ICC). RESULTS: Fifteen children with CF underwent reduced-dose PCD chest CT in both inspiration and expiration (mean age 8.9 years, range, 2.5-17.5 years; 4 girls). Mean volumetric CT dose index (CTDIvol) was 0.07 ± 0.03 mGy per scan. Mean effective dose was 0.12 ± 0.04 mSv for the total examination. All three readers graded spatial resolution and noise as interpretable on lung windows. The average Brody II score was 12.5 (range 4-19), with moderate inter-reader reliability (ICC of 0.61 [95% CI=0.27, 0.84]). Inter-rater reliability was moderate to substantial for bronchiectasis (0.52), peribronchial thickening (0.55), presence of opacity (0.62) and air trapping (0.70) and poor for mucus plugging (0.09). CONCLUSION: Reduced-dose PCD-CT permits diagnostic image quality and reproducible identification of Brody II scoring imaging findings at radiation doses similar to those for chest radiography.

Aminoglycoside induced ototoxicity risk in the cystic fibrosis population: The utility of large-scale screening.

BACKGROUND: MT-RNR1 variants are a well-known cause of aminoglycoside-induced hearing loss (AIHL). Individuals with cystic fibrosis (CF) routinely receive aminoglycosides and are at high risk of AIHL. However, genetic testing before treatment is not routinely performed due to perceived rarity of risk, and cost ineffectiveness with traditional technologies. AIM: Assess the utility of large-scale screening for AIHL risk in the CF population, using digital droplet polymerase chain reaction (ddPCR), a novel and scalable low-cost molecular technique. METHODS: Using a clinically validated ddPCR assay, we performed retrospective testing on 122 and prospective testing on 32 individuals with CF for the two most common pathogenic variants associated with AIHL, MT-RNR1 m.1555 A > G and m.1494 C > T. Our study screened the largest known cohort of pediatric cases of CF (94/154) for these specific alterations. RESULTS: We identified two individuals positive for MT-RNR1 m.1555 A > G and no positives for m.1494 C > T. Of 32 prospective cases, 17 had aminoglycoside exposure. The positive case in our prospective group recently began inhaled tobramycin and denied hearing issues. The clinician adjusted to care for both the patient and sibling with CF (not included in cohort) who is presumed positive for m.1555 A > G due to the nature of mitochondrial inheritance. CONCLUSION: Our findings demonstrate the utility of pretreatment screening in the cystic fibrosis population for AIHL risk using ddPCR, a scalable and robust testing methodology at a fraction of the cost as compared to other sequencing-based methods. Therefore, the use of large-scale screening for AIHL risk in the cystic fibrosis community should be re-visited.

A Rare Case Report of NEHI in a Preterm Infant with Review of the Literature.

Background: Neuroendocrine cell hyperplasia of infancy (NEHI) is a rare respiratory disorder. During infancy, it typically presents with hypoxemia, tachypnea, and respiratory distress, and is commonly misdiagnosed as common childhood illnesses such as pneumonia, reactive airway disease, or bronchiolitis. Lack of awareness about this relatively new and rare disorder in primary care and acute care settings lead to delayed diagnosis and unnecessary use of antibiotics. Case Presentation. We present a case of a 7-month-old girl, born prematurely at 32 weeks with tachypnea and respiratory distress who was initially diagnosed with viral pneumonia, then upper respiratory infection, and finally with community-acquired bacterial pneumonia, while the child never had any fever or upper respiratory symptoms. Failure of outpatient treatment with oral antibiotic and bronchodilator, with the persistence of respiratory symptoms such as retractions, bilateral crackles, and hypoxemia led to hospitalization for intravenous antibiotics. Given persistent symptoms, further evaluation was performed, and she was diagnosed with NEHI based on characteristic chest CT findings. Conclusions: Viral respiratory infections are the most frequent cause of respiratory illnesses in the first years of life. Primary care providers should be aware of less frequent causes of persistent respiratory symptoms in infancy like NEHI and other interstitial lung diseases in children. This may prevent unnecessary use of antibiotics and delayed diagnosis.

Acute thrombosis of a giant perimedullary arteriovenous fistula in a pediatric HHT patient.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant hereditary disorder that results in arteriovenous malformations (AVMs) in the nose, mucocutaneous surfaces and visceral organs, including lung, brain, liver, bowel and rarely spinal cord. We describe a case of a young child with HHT who presented with acute paraparesis due to acute thrombosis of a spinal perimedullary arteriovenous fistula. Patient underwent coil embolization of spinal arteriovenous shunt with resolution of clinical symptoms. This case highlights the possibility of catastrophic complications in young children with HHT, the potential preventive role of screening for spinal AVMs in HHT and the importance of timely intervention.

Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection.

Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/ß-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs). Activation of ß-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, ß-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted ß-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This ß-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by ß-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases.

Healthcare Utilization and Costs associated with Hereditary Hemorrhagic Telangiectasia Patients in a Large US Claims Database.

OBJECTIVE: To assess the health care costs and utilization in patients with hereditary hemorrhagic telangiectasia (HHT) in the United States. PATIENTS AND METHODS: Retrospective analysis of patients with HHT diagnosed between 2007 and 2017 was performed using deidentified administrative claims data from the OptumLabs Data Warehouse. Adult patients with new (incident) diagnosis of HHT between January 1, 2007, and December 31, 2017, were included. Comparisons were made using the Wilcoxon rank sum test. RESULTS: Three thousand nine hundred seventy-seven patients with a first diagnosis of HHT between 2007 and 2017 were identified, of which 3590 were matched 1:1 to non-HHT patients with similar baseline characteristics and comorbidities. These 3590 patients with HHT were 63.1% female and 83.9% white with a mean age of 51.1 ± 18.5 years, and a mean follow-up period of 3.2 ± 2.2 years (range, 1.0-11.7 years). Compared with the control group, the cumulative 5-year median total health care cost for patients with HHT was 41.4% higher ($21,118 vs $14,929; P < .001) in those with private commercial insurance and 31.7% higher ($35,462 vs $26,925; P < .001) in those with Medicare Advantage coverage. The median annual health care costs were significantly higher in patients with HHT with commercial insurance and Medicare Advantage in the first year after diagnosis ($4,333 vs $1,804; P < .001), and ($7,322 vs $5,245; P < .001), respectively, and remained higher throughout the duration of follow-up. Further analysis showed that outpatient clinic visits, hospital admission, imaging rates, invasive procedures, iron infusions, and blood transfusions were all significantly higher in the HHT group. CONCLUSION: Patients with HHT have significantly higher health care costs compared with a matched control group. A better understanding of the reasons underlying these cost differences will provide opportunities for patients, providers, and other stakeholders to better manage this rare condition.

Sleep and Breathing After Nusinersen Therapy in a Child With Spinal Muscular Atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) type 3 is an autosomal recessive neurological disorder associated with a deletion/mutation in the survival motor neuron gene, with gradually progressive degeneration of the motor neurons of the spinal cord and brainstem, which causes muscle weakness responsible for impairment of swallowing, breathing, and mobility. REPORT OF CASE: We report an 11-year-old girl with SMA type 3 with moderate to severe obstructive sleep apnea (OSA) syndrome refractory to adenotonsillectomy and noninvasive ventilatory support. She was started on nusinersen, which is a novel disease modifying therapy for SMA. This new treatment led to improvement of the OSA in a short period, likely from better respiratory muscle function. CONCLUSIONS: The improvement in OSA supports the role of nusinersen in sleep-related upper respiratory muscle function in SMA type 3.

Institutional Factors Associated With Burnout Among Assistant Professors.

Phenomenon: Factors related to individual circumstance and organizational climate are contributing to a worsening burnout problem among providers in healthcare settings. In the academic health center, junior faculty may be at particular risk for burnout given intersecting responsibilities of clinical expertise, research rigor, teaching commitments, and service expectations. To date, much of the focus on preventing and mitigating burnout has been located at the individual level, addressing lifestyle modification and self-regulation skills. We sought to examine relationships between institutional context and burnout qualities as a means to identify opportunities for organizational leadership to address faculty burnout. Approach: Data are from a baseline survey of assistant professors (faculty with diverse ratios for clinical, research, and teaching responsibilities) located within a pediatrics department in an academic medical center. Pearson correlation coefficients and logistic regression models were used to examine relationships between institutional factors (mentorship, collaboration opportunities, feelings of empowerment, value, and support of well-being) and experiences of burnout as measured by the original 22-item Maslach Burnout Inventory (subscales: Emotional Exhaustion, Depersonalization, and Low Personal Accomplishment). Findings: Three perceived institutional characteristics were significantly associated with all three dimensions of burnout, particularly emotional exhaustion, which decreased with increasing perception of (a) empowerment to communicate professional needs, (b) feeling valued for contributions to the department, and (c) department commitment to support faculty well-being. In multivariate logistic regression models, adjusted for gender identity and years since training, increased positive perceptions of these three institutional characteristics were associated with significantly lower odds of burnout. For example, for each unit increase along a 5-point rating scale in feeling empowered to communicate needs and feeling valued for contributions to the department, the odds of meeting cutoff scores for burnout were reduced by 78% (p = .002) to 84% (p = .002), respectively. Insights: Although much of the focus on addressing burnout in healthcare settings has been on promoting coping skills and building resilience at the individual level, our findings add to a growing literature documenting a significant role for institutional leadership in identifying and facilitating strategies to promote faculty well-being. Findings also support leadership's role for improving institutional climate via creating opportunities to increase faculty perceptions of empowerment and value in the department.

Decreased Pseudomonas aeruginosa detection in children after separation of pediatric from adult cystic fibrosis clinics: A single center experience.

BACKGROUND: The impact of separating the adult from pediatric patients on Pseudomonas aeruginosa (P. aeriginosa) detection in the respiratory cultures of patients was examined at the University of Minnesota CF Center. METHODS: This study was a retrospective review using data recorded in the University of Minnesota CF Database between 1995 and 2010. Respiratory culture results obtained during routine University of Minnesota Cystic Fibrosis (CF) Center. CF clinic encounters of two cohorts of pediatric and adult CF patients (pre- and post-separation) were analyzed for presence of P. aeruginosa. RESULTS: The odds of a pediatric patient having P. aeruginosa were significantly less if the first culture was obtained after separation of pediatric and adult clinics. Being diagnosed by newborn screening or introduction of inhaled tobramycin did not affect this outcome. This reduction in P. aeruginosa was not detected in the adult cohort. CONCLUSIONS: Separation of pediatric and adult CF clinics has contributed to decrease in P. aeruginosa detection in pediatric patients.

Respiratory distress in a 2-month-old infant: Is the primary cause cardiac, pulmonary or both?

A 2-month-old female with worsening cough, respiratory distress and an abnormal chest X-ray was referred to our institution for further evaluation of suspected scimitar syndrome. She was found to have normal pulmonary venous drainage with a large patent ductus arteriosus and severe pulmonary arterial hypertension. Chest CT was suggestive of interstitial lung disease. Wedge lung biopsy revealed alveolar simplification and patchy pulmonary interstitial glycogenosis. A definitive diagnosis of Filamin A deficiency was made with genetic studies. The patient is currently showing clinical improvement on systemic glucocorticoid therapy.

Pulmonary Mycobacterium Avium-Intracellulare Complex Infection in an Infant: A Silent and Coincidental Finding.

An 11-month-old healthy infant girl was noted to have left lower lobe (LLL) opacities on chest X-ray (CXR) after developing desaturations during an elective cochlear implant surgery. Repeat CXR 10 days later revealed hyperexpansion of the left lung and persistent LLL opacity. Chest computerized tomography revealed enlarged mediastinal lymph nodes, left mainstem bronchial obstruction, and nodular opacities. Bronchoscopic biopsy of the endobronchial tissue revealed multiple necrotizing granulomas and grew Mycobacterium avium-intracellulare, Streptococcus viridans, and Actinomyces odontolyticus. This case illustrates the potential for significant mediastinal lymphadenopathy, and endobronchial and parenchymal lesions caused by nontuberculous mycobacteria, which can present insidiously and without respiratory symptoms in otherwise healthy infants, despite advanced pulmonary disease.

Bilateral diaphragmatic paresis following pediatric liver transplantation.

BACKGROUND: Although diaphragm paresis or paralysis is fairly common following cardiac procedures; it is a less common complication following liver transplantation. Unilateral diaphragm paresis, usually right sided, has been described following liver transplantation in adults and has been rarely described in children. PURPOSE: Diaphragmatic injury following LT is often unrecognized and is typically unilateral, involving the right hemidiaphragm. Bilateral diaphragm dysfunction following liver transplantation in children is a rare complication. METHODS: This is a case report of bilateral diaphragm paresis in a young child following a repeat liver transplantation. CONCLUSION: Bilateral diaphragm paresis following liver transplantation in children is rare and spontaneous resolution is possible. A conservative approach with noninvasive ventilation as a first line treatment to allow the diaphragm to regain function should be considered.