The Florida Scoring System for stratifying children with suspected Sjögren's disease: a cross-sectional machine learning study.

BACKGROUND: Childhood Sjögren's disease is a rare, underdiagnosed, and poorly-understood condition. By integrating machine learning models on a paediatric cohort in the USA, we aimed to develop a novel system (the Florida Scoring System) for stratifying symptomatic paediatric patients with suspected Sjögren's disease. METHODS: This cross-sectional study was done in symptomatic patients who visited the Department of Pediatric Rheumatology at the University of Florida, FL, USA. Eligible patients were younger than 18 years or had symptom onset before 18 years of age. Patients with confirmed diagnosis of another autoimmune condition or infection with a clear aetiological microorganism were excluded. Eligible patients underwent comprehensive examinations to rule out or diagnose childhood Sjögren's disease. We used latent class analysis with clinical and laboratory variables to detect heterogeneous patient classes. Machine learning models, including random forest, gradient-boosted decision tree, partial least square discriminatory analysis, least absolute shrinkage and selection operator-penalised ordinal regression, artificial neural network, and super learner were used to predict patient classes and rank the importance of variables. Causal graph learning selected key features to build the final Florida Scoring System. The predictors for all models were the clinical and laboratory variables and the outcome was the definition of patient classes. FINDINGS: Between Jan 16, 2018, and April 28, 2022, we screened 448 patients for inclusion. After excluding 205 patients due to symptom onset later than 18 years of age, we recruited 243 patients into our cohort. 26 patients were excluded because of confirmed diagnosis of a disorder other than Sjögren's disease, and 217 patients were included in the final analysis. Median age at diagnosis was 15 years (IQR 11-17). 155 (72%) of 216 patients were female and 61 (28%) were male, 167 (79%) of 212 were White, and 20 (9%) of 213 were Hispanic, Latino, or Spanish. The latent class analysis identified three distinct patient classes: class I (dryness dominant with positive tests, n=27), class II (high symptoms with negative tests, n=98), and class III (low symptoms with negative tests, n=92). Machine learning models accurately predicted patient class and ranked variable importance consistently. The causal graphical model discovered key features for constructing the Florida Scoring System. INTERPRETATION: The Florida Scoring System is a paediatrician-friendly tool that can be used to assist classification and long-term monitoring of suspected childhood Sjögren's disease. The resulting stratification has important implications for clinical management, trial design, and pathobiological research. We found a highly symptomatic patient group with negative serology and diagnostic profiles, which warrants clinical attention. We further revealed that salivary gland ultrasonography can be a non-invasive alternative to minor salivary gland biopsy in children. The Florida Scoring System requires validation in larger prospective paediatric cohorts. FUNDING: National Institute of Dental and Craniofacial Research, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Heart, Lung, and Blood Institute, and Sjögren's Foundation.

A Rare Case of Ectopic Colonic Mucosa Presenting With Airway Compromise in a Neonate.

This case report documents a rare and unique presentation of an oropharyngeal duplication cyst and subsequent neonatal airway management. A one-day-old premature female presented with postpartum respiratory distress requiring emergent intubation secondary to an oropharyngeal mass of the left tongue. After being stabilized and transferred to an academic center, imaging revealed a cystic lesion that was then marsupialized and drained by the otolaryngology team. Pathology demonstrated mature colonic tissue and was consistent with an enteric duplication cyst. This report highlights the importance of prenatal diagnosis and the potential of a lifesaving ex utero intrapartum treatment (EXIT) procedure.

Postoperative Pain Exacerbation After Adenotonsillectomy Due to Oral Candida Infection?

Post-tonsillectomy complications can include bleeding, dehydration, edema, airway obstruction, and infection. Oral candidiasis or thrush is a rare complication that can occur post-operatively. We describe a case of a 10-year-old female with oral candidiasis as a postoperative complication of bilateral adenotonsillectomy, presenting on postoperative day (POD) 7 for poor oral intake secondary to worsening odynophagia. A physical exam revealed an easily scrapable, white plaque located mainly over her surgical sites, tongue, and hard palate. Microscopic examination of tissue scrapings revealed pseudohyphae confirming the diagnosis of oral candidiasis. She was treated with seven days of topical nystatin therapy, including topical and systemic pain control with significant improvement of symptoms by POD 13 and complete resolution on POD 21.

Spontaneous retropharyngeal and mediastinal thoracic duct cyst in an infant with respiratory distress.

Thoracic duct cysts (TDC) within the retropharyngeal space and mediastinum are exceedingly rare lesions, with the majority related to trauma or neoplasm. We describe a case of an otherwise healthy 8-month-old boy who presented with severe respiratory distress, which was found to be caused by a large, spontaneous TDC occupying most the retropharyngeal and mediastinal space. To our knowledge, this is the youngest patient to date presenting with TDC. Ultimately, his TDC was completely resolved with sclerotherapy, however the patient's age and size presented unique challenges to his medical management, which we describe below.

Structural basis for selective targeting of leishmanial ribosomes: aminoglycoside derivatives as promising therapeutics.

Leishmaniasis comprises an array of diseases caused by pathogenic species of Leishmania, resulting in a spectrum of mild to life-threatening pathologies. Currently available therapies for leishmaniasis include a limited selection of drugs. This coupled with the rather fast emergence of parasite resistance, presents a dire public health concern. Paromomycin (PAR), a broad-spectrum aminoglycoside antibiotic, has been shown in recent years to be highly efficient in treating visceral leishmaniasis (VL)-the life-threatening form of the disease. While much focus has been given to exploration of PAR activities in bacteria, its mechanism of action in Leishmania has received relatively little scrutiny and has yet to be fully deciphered. In the present study we present an X-ray structure of PAR bound to rRNA model mimicking its leishmanial binding target, the ribosomal A-site. We also evaluate PAR inhibitory actions on leishmanial growth and ribosome function, as well as effects on auditory sensory cells, by comparing several structurally related natural and synthetic aminoglycoside derivatives. The results provide insights into the structural elements important for aminoglycoside inhibitory activities and selectivity for leishmanial cytosolic ribosomes, highlighting a novel synthetic derivative, compound 3: , as a prospective therapeutic candidate for the treatment of VL.

Clinical evaluation of the NiTiBOND stapes prosthesis, an optimized shape memory alloy design.

OBJECTIVE: To prospectively analyze short-term (3 mo) results in patients with otosclerosis who underwent stapedotomy with the newly designed NiTiBOND prosthesis and compare them with patients that underwent SMart piston stapedotomy. We aimed to assess "noninferiority" for the new prosthesis. STUDY DESIGN: Prospective controlled trial. SETTING: Tertiary referral center. PATIENTS: Thirty-eight patients were included in the NiTiBOND group (41 ears), and 74 patients were included in the SMart Piston group (75 ears). INTERVENTION(S): Stapedotomy. MAIN OUTCOME MEASURE(S): Pure-tone audiometry 3 months after surgery, intraoperative prosthesis handling as assessed using a questionnaire, and complications were analyzed. RESULTS: Pure-tone audiometry showed postoperative air-bone gap means (standard deviation) of 8.1 (8.3) and 9.9 (5.4) dB; air-bone gap closure within 10 dB was achieved in 71% and 72% and within 20 dB in 93% and 96% for the NiTiBOND and the SMart piston prosthesis, respectively. Noninferiority was shown at all frequencies and in the pure-tone average. The NiTiBOND prosthesis provides excellent intraoperative handling, and no adverse reactions were reported. CONCLUSION: Preliminary short-term results suggest safety and reliability for the new NiTiBOND stapes prosthesis.

Blood markers of alcohol use in epistaxis patients.

Epistaxis and alcohol overconsumption are frequently encountered in patients admitted to emergency wards. The aim of the study was to analyze indirect markers of alcohol overconsumption in epistaxis patients and evaluate its role as a risk factor. In a cohort of 510 epistaxis patients indirect markers of alcohol overuse were measured including the mean corpuscular volume (MCV), gamma glutamyltransferase (GGT), aspartate aminotransferase and alanine aminotransferase. The results were compared to the normal findings in literature. Pathologic mean levels of GGT were found in epistaxis patients. Almost 5% had macrocytosis and MCV correlated positively with liver enzyme levels. Platelet counts were negatively correlated with both corpuscular volumes and liver enzymes. Indirect markers of alcohol overconsumption were found to be elevated in epistaxis patients. These results suggest that a subgroup of epistaxis patients overconsumes alcoholic beverages supporting the idea of alcohol abuse being a risk factor in epistaxis. Questioning about drinking habits should be employed and help offered to affected patients.

Ossiculoplasty with total ossicular replacement prosthesis and Omega Connector: early clinical results and functional measurements.

OBJECTIVE: Among other difficulties, achieving a stable position of a total ossicular replacement prosthesis (TORP) is demanding because of a limited view on the TORP-footplate interface and individual angles between the footplate and tympanic membrane. The Kurz Omega Connector aims at a simplified insertion of the TORP. The performance of total ossicular reconstruction using the Omega Connector was evaluated. STUDY DESIGN: Prospective cohort study and experimental measurements with a fresh human temporal bone. SETTING: Tertiary referral center. PATIENTS: Seventeen consecutive patients receiving total ossicular reconstruction were included. Historical control group composed of 36 patients. INTERVENTIONS: Total ossicular reconstruction using the Omega Connector. MAIN OUTCOME MEASURES: (a) Handling of the TORP and Omega Connector intraoperatively, (b) functional short-term results compared with a historical control group, (c) sound transmission properties with 3 different connective positions between the TORP and the Omega Connector. RESULTS: Placing the Omega Connector on the footplate and coupling the Omega Connector to the TORP was straightforward in 65% of cases. A stable final position of the TORP was obtained in 88% of cases. Mean (SD) preoperative and postoperative air-bone gaps were 36.00 (11.05) and 25.29 (12.25) dB and were almost identical with those in the historical control group (p = 0.9). In the experimental measurements, functional outcomes with "partial connection" showed almost the same results as those with "full connection." CONCLUSION: The Omega Connector provides easy handling of the TORP. The short-term functional results were comparable to those achieved previously without the Omega Connector. The temporal bone measurement supports tolerance in connective position between the TORP and the Omega Connector.

The value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography for staging of primary extranodal head and neck lymphomas.

OBJECTIVES/HYPOTHESIS: Using a retrospective approach, the aim of this study was to confirm the previously described value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in patients with primary extranodal lymphoma of the head and neck region. Additionally, the clinical significance of the semiquantitative analysis of the standardized uptake value (SUV), its predictive role in the follow-up setting, and its value in detection of synchronous primaries were studied. STUDY DESIGN: Retrospective chart review. METHODS: Twenty-six patients with a primary extranodal head and neck lymphoma (22 diffuse large B-cell lymphoma, one Hodgkin's lymphoma, three malignant T-cell lymphomas) were included. We retrospectively evaluated the clinical outcomes according to the maximum standardized uptake values of the primary lesion (SUV(max)) and whether a positron emission tomography/computed tomography (PET/CT) was performed or not in the follow-up studies. The median SUV(max) was chosen as the cutoff value. The patients were then grouped as those with either low or high SUV(max), respective to the cutoff value. Event-free survival and cumulative survival were endpoints of interest. RESULTS: Nineteen patients (73%) were above the age of 60 years; the median age was 70 years (range, 28-87 years). Most primary sites were in the Waldeyer's ring (15 patients, 60%), whereas in four patients (27%) only the palatine tonsil was affected. The SUV(max) ranged from 5.8 to 33.9. In one patient, relevant fluorodeoxyglucose (FDG) uptake within the intestine revealed a cecal adenocarcinoma as a secondary primary. Twenty of the 25 clinically followed patients (80%) achieved complete remission after treatment. Patients with high SUV(max) showed favorable survival (log-rank test, P = .044). A tendency for longer survival within the group with follow-up PET/CT studies could be noted but with no significant statistical difference (P = .349). CONCLUSIONS: (18)F-FDG-PET/CT imaging is a potent primary staging tool. It also has application as an instrument for evaluation of follow-up and response to therapy in patients suffering from primary extranodal lymphoma and for detection of secondary malignancies. Furthermore, (18)F-FDG uptake by the primary lesion may be related to better survival.