Citations

Fusobacterium nucleatum and Prevotella loescheii are anaerobic gram-negative rods that exist in the oral cavity. To our knowledge, pediatric central nervous system complications with these pathogens have not been well described. An 11-year-old previously healthy vaccinated female child presented for 2 weeks of sinusitis that progressed to left arm and leg hemiplegia. Initial neuroimaging demonstrated a superior sagittal sinus thrombosis and a right hemispheric subdural empyema with midline shift, necessitating surgical evacuation. Culture of the subdural accumulation demonstrated coinfection of Fusobacterium nucleatum and Prevotella loescheii . Within 24 hours of evacuation, the patient progressed to have right hemispheric electrographic status epilepticus, with neuroimaging demonstrating reaccumulation of the empyema and a moderate right middle cerebral artery vasospasm. Transcranial doppler ultrasonography of the right middle cerebral artery territory demonstrated mean flow velocities up to 148 cm/s with a Lindengaard ratio of 3.44. The patient underwent repeat subdural evacuation and was managed with intravenous fluids, permissive hypertension, oral nimodipine, and intravenous milrinone. Electrographic status epilepticus was treated with intravenous lacosamide and levetiracetam. Repeat neuroimaging demonstrated improvement in subdural collection size and resolution of vasospasms. She was discharged after 16 days with continued lacosamide and levetiracetam for seizures, and enoxaparin (Lovenox) for the superior sagittal sinus thrombosis. We present a novel pediatric case of Fusobacterium nucleatum and Prevotella loescheii manifesting with rapid subdural empyema reaccumulation after surgical evacuation, status epilepticus, cerebrovascular vasospasms, and cerebral sinus venous thrombosis. Further work is needed to understand the potential neurologic complications of this condition.

ABSTRACTBackgroundHidradenitis suppurativa (HS) is a chronic inflammatory condition. While obesity is linked to increased HS severity in adults, data on its impact in pediatric HS remain limited. This study investigates the relationships between obesity, HS severity, HS‐related comorbidities, and therapeutic management in pediatric patients.MethodsThis is a retrospective cohort analysis on patients diagnosed with HS before 18 years of age. Data were collected on disease severity, comorbidity development, and treatments. Trends were compared between HS patients with and without obesity and with healthy controls for comorbidity development.ResultsThere was no difference in disease severity using Hurley staging between patients with and without obesity (p = 0.679). Patients with obesity were more likely to be prescribed biologics (p = 0.012), but not other treatments. The risk of developing dyslipidemia, anxiety, depression, and thyroid disease was elevated in pediatric HS patients, even after controlling for BMI (p < 0.001).ConclusionsIn this study, obesity was not associated with HS disease severity in children. However, children with obesity were more likely to be prescribed biologics. HS may independently increase the risk of dyslipidemia, anxiety, depression, and thyroid disease.

Abstract Rationale: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a pulmonary condition characterised by neuroendocrine cell proliferation along respiratory bronchioles resulting in tumourlet formation which may progress to pulmonary carcinoid. DIPNECH is a rare and under-recognised condition that predominantly affects females, with an estimated worldwide incidence of 5-6 people per million population. Given it's rarity and the poor understanding around the pathogenesis and treatment of this condition, we undertook the largest international case series to date of DIPNECH patients. We aim to further characterise this patient cohort to better understand the clinical features, identify common pulmonary function test (PFT) patterns and radiographic findings and describe current treatment practices. Methods: We collated data from 17 centres across 8 different countries comprising a total of 258 patients. Data collected included patient demographics, smoking history, symptoms, co-morbidities, pathological diagnosis, imaging findings, PFT pattern and therapies. Results: In total 258 patients were identified. The median age was 65 (SD+/- 10.6). 241 (93%) were female. 39% (n= 94/243) were ex-smokers. 79% (n=186/234) of patients reported pulmonary symptoms with cough being the most common symptom reported in 81% (n=151/186) of patients. Many patients were polysymptomatic, with cough and dyspnoea being the most common combination of symptoms described. (50.54%; n=94/186). Complete spirometry pattern was documented for 180 patients (69.78%) with an obstructive pattern being the most commonly observed (n=76/180; 42%). 27.5% (n=41/139) had clinically significant FEV1 reversibility post bronchodilator administration. Pathology specimens were available in 219 cases. Most common pathological features were neuroendocrine hyperplasia which was observed in 75% (n=165/219) and tumourlets in 74% (n=162/219) of cases. Carcinoid, either typical or atypical, was observed in 64% (n=141/219) of samples. 252 patients had computed tomography (CT) imaging performed. Pulmonary nodules were the most common feature identified in 99.60% of cases (248/250). Mosaic attenuation (69.30%; n=50/173) and airway dilatation (28.90%; n=50/173) were also frequently reported. There was no significant correlation between symptoms (cough, dyspnoea, wheeze) and airway dilatation (p=0.496), mosaic attenuation (p=0.496) and PFT pattern (p=0.837). There was a significant association between presence of symptoms and mosaic attenuation on CT (p=0.003). Conclusions: DIPNECH, while a rare disorder, is understudied. This international case series is the largest performed to date and highlights the complexity in management of these patients.

Abstract Morphogenesis and cell state transitions must be coordinated in time and space to produce a functional tissue. In this study, we reveal that lung mesenchymal Yap levels and fitness antagonize epithelial Yap levels and stemness during lung development and repair following bleomycin injury. Elevated mesenchymal Yap signaling and fitness antagonize epithelial Yap levels and stemness, accelerating alveolar epithelial differentiation while impairing branching during lung development or bronchiolization after bleomycin injury. Conversely, mesenchymal Snail/Slug sequesters Yap/Taz to direct an adipogenic differentiation program towards alveolar fibroblast 1 (AF1) during both lung development and the resolution of pulmonary fibrosis. On the other hand, Yap/Myc-Tead binding instructs a myogenic differentiation program. Through our experiments and modeling, we identify tissue-scale mechanical cooperation as a pivotal factor in orchestrating organ formation and regeneration.

Background: Collaborative methods are necessary to meet patient palliative care (PC) needs because of the inadequate supply of PC specialists. Objective: This study aimed to conduct a needs assessment and determine primary care, emergency, and hospital physicians’ general attitudes about primary PCs, confidence in managing common PC scenarios, and preferences for interaction with specialty PCs. Design: A sequential mixed-methods study design was used, whereby individual qualitative interviews informed the content of a quantitative survey. Semistructured telephone interviews were conducted by a member of the study team with expertise in qualitative research methods. Setting/Subjects: The quantitative survey, delivered to primary care, emergency, and hospital physicians across four distinct geographic locations of a large health system, solicited impressions on common clinical PC scenarios that might pose challenges. Measurements: Survey data included demographic information, clinician confidence levels, preferences for support in managing PC scenarios, and likelihood to refer to PC. Results: The quantitative survey was completed by 126 physicians (response rate, 13.9%). Overall mean (standard deviation) confidence levels were lowest for a scenario about handling pain (5.57 [2.35] out of 10) and highest for goals-of-care conversations with the patient (7.80 [2.02]). Spearman correlations between mean confidence and likelihood to refer to PC demonstrated weak to moderate inverse correlations. Respondents with previous training in PC had higher mean confidence in managing symptoms and goals-of-care conversations. Conclusions: Continuing efforts are needed to help improve physicians’ confidence in primary PC skills and develop innovative methods to provide collaborative support of specialty PCs across various specialties and PC needs.

ABSTRACTItraconazole and posaconazole are frequently prescribed following transplantation to prevent and treat fungal infections. Navigating drug interactions is challenging due to these agents’ potent CYP3A4 inhibition, and literature describing concurrent apixaban, a CYP3A4 substrate, is limited. This retrospective study of cardiothoracic transplant recipients evaluates the impact of itraconazole and posaconazole on apixaban exposure and reports clinical outcomes from routine apixaban dose reduction. Institutional practice reduces apixaban to 2.5 mg twice daily with itraconazole or posaconazole and obtains apixaban therapeutic drug monitoring (TDM), expected range 34–230 ng/mL. Eighteen levels collected in 15 patients on itraconazole displayed a median [IQR] apixaban trough of 143 ng/mL [95–195]. Fifteen levels collected in 13 patients on posaconazole displayed a median [IQR] apixaban trough of 124 ng/mL [93–174]. Two major bleed events, three VTE, two stroke, and eight instances of clot resolution were identified. Reduced‐dose apixaban resulted in apixaban exposure similar to normal dosing in the general population. Apixaban TDM is encouraged for individualized dosing when administered with itraconazole and posaconazole.

This cohort study examines the validity of an electronic health record data model for organ transplantation.