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Objective: To investigate the association between sleep deprivation and vestibular dysfunction by Video Head Impulse Test (vHIT)., Methods: This prospective clinical trial explores the impact of acute sleep deprivation on the vestibular-ocular reflex (VOR) in medical residents. The study involved healthy physicians from diverse medical disciplines. Participants underwent vHIT assessments before and after a 26-h shift. The examinations focused solely on the right lateral semicircular canal. Participants further completed a demographics and fatigue questionnaire, including the Fatigue Severity Scale (FSS) questionnaire and a Visual Analog Fatigue Score (VAFS)., Results: The study involved 30 medical residents. Participants experienced a statistically significant decrease in VOR gain in the right horizontal semicircular canal during a 26-h shift (p < 0.01). While the FSS and VAFS questionnaires showed no significant difference before and after the shift, the analysis of ∆VOR gain indicated a statistically significant increase associated with decreased sleep time during the shift (p = 0.018, 95% Confidence Interval [0.08, 0.68]). The most substantial increase in ∆VOR occurred between 22-26 h of sleep deprivation. No significant differences were observed in ∆VOR between genders, ages, disciplines, department shifts versus emergency room shifts, or years of residency., Conclusion: vHIT can be used as an objective, reliable screening tool for severe sleep deprivation among physicians. The decrease in the VOR gain may indicate that vestibular function is influenced by sleep deprivation. The clinical significance of these findings is still questioned, more studies may help to assess this effect., Level of Evidence: 3 Laryngoscope, 135:1177-1182, 2025., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

To understand whether parental smoking influences adeno/tonsillectomy rates in their offspring. A population-based case-control study using data from Clalit Health Services. Israeli children aged 0-18 years who underwent adeno/tonsillectomy between 2003 and 2022 were 1:3 matched with same-age, sex, and ethnicity controls. Parental smoking habits were linked to their children's files. Conditional logistic regression models estimated odds ratios (ORs) for adeno/tonsillectomy associated with parental smoking, adjusting for socioeconomic status. We identified 11,184 children who underwent surgery and 33,552 controls (mean age ± SD 4.10 ± 2.50 years). The likelihood of undergoing adeno/tonsillectomy was significantly higher for children with either one smoking parent (OR 1.14; 95%CI 1.09-1.19) or both (OR 1.53; 95%CI 1.39-1.68) compared to children of non-smokers. The association was more evident for tonsillectomy alone, with an OR of 3.20 (95%CI 2.06-4.97) when both parents were smokers. These associations remained consistent even after adjusting for socioeconomic status. Parental smoking rates were higher in the surgical group across all categories. Maternal smoking prevalence was 10% versus 7.5%, and paternal smoking prevalence was 36% versus 32%, in the surgical group vs. the control group, accordingly. The proportion of children with only one smoking parent was 34% compared to 31%, and for cases with both parents smoking, the rate was 6.3% versus 4.3%., Conclusion: Parental smoking is associated with higher rates of pediatric adenoidectomy, tonsillectomy, and adenotonsillectomy, especially if both parents smoke. Counseling parents on the negative effects of smoking on their children is crucial in reducing the incidence of these surgeries., What Is Known: • Parental smoking can cause multiple pediatirc diseases., What Is New: • Parental smoking is associated with higher rate of adenotonsillar surgery., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study investigated potential associations between ectropion and various chronic and systemic inflammatory diseases affecting the eyelids and ocular surface. This retrospective case-control study, spanning 2001-2022, used electronic medical records from Clalit Health Services (CHS) in Israel. Patients diagnosed with involutional ectropion served as the case group, while two control groups were used for comparison: one comprising patients diagnosed with senile cataract and the other with various ophthalmic diseases. Matching for the control groups was performed at a 1:3 ratio based on year of birth, sex, and ethnicity. A total of 17,292 patients with involutional ectropion and 51,876 matched controls in each group were included. The average age of the patients with involutional ectropion was 78 ± 10 years and 58% were men. Significant associations were found between involutional ectropion and several local inflammatory eyelid diseases: blepharitis (OR 4.66), chalazion (OR 2.94), hordeolum (OR 2.26), and dermatitis of the eyelid (OR 2.46). Ocular surface diseases associated with ectropion included chronic conjunctivitis (OR2.89 ) and pterygium (OR 2.48). Systemic diseases such as hypertension (OR 1.46), dyslipidemia (OR 1.45), and autoimmune rheumatic diseases (OR 1.43) were also associated with involutional ectropion. This study found that localized chronic inflammatory conditions affecting the periocular tissues and ocular surface are significantly associated with the development of involutional ectropion., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This retrospective, case-control study was approved by the CHS Research Ethics Committee and the Soroka Medical Center Institutional Review Board (approval number: 0335-22-SOR). The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was waived as the data were obtained retrospectively and anonymized., (© 2025. The Author(s).)

Background: Children with Down syndrome (DS) often experience recurrent and prolonged hospitalizations from respiratory infections. While Azithromycin has been increasingly used for lower-respiratory tract infections (LRTIs) in children, its potential benefits for DS patients are unexplored. This study evaluates the effect of chronic azithromycin treatment on respiratory morbidity in children with DS., Methods: In this retrospective cohort study, we analyzed data from children with DS aged 0-6 years treated with Azithromycin for at least 6 weeks (10 mg/kg, thrice weekly). Respiratory morbidity indicators, such as primary care visits, medication consumption, emergency department visits, hospitalizations, and hospital length of stay (LOS), were assessed and compared six months before and after the Azithromycin treatment., Results: Twenty-three episodes of Azithromycin treatment (≥ 6 weeks) in eighteen children with DS (mean age of 2.3 years, 78% males) during 2016-2023 were included. A significant reduction in mean respiratory LOS was observed (13.6 vs. 4.7 days, p = 0.05) when comparing pre to post-Azithromycin treatment. Other secondary respiratory outcomes showed no significant differences., Conclusion: The significant reduction in respiratory LOS suggests the potential benefits of Azithromycin in children with DS, and emphasizes the need for larger clinical trials to determine optimal use and long-term effects in this vulnerable population., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the “institutional review board of Soroka University Medical Center”, in accordance with the Helsinki Declaration (approval No. 052 − 21 SOR). Informed consent was deemed unnecessary according to the retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background : Prone positioning is a standard intervention in managing patients with severe acute respiratory distress syndrome (ARDS) and is known to improve oxygenation. However, its effects on other organs, particularly the kidneys, are less well understood. This study aimed to assess the association between prone positioning and the development of acute kidney injury (AKI), specifically in overweight and obese patients. Methods : A retrospective pre-post study was conducted on a cohort of 60 critically ill ARDS patients who were placed in the prone position during hospitalization. The development of AKI was assessed using the Acute Kidney Injury Network (AKIN) criteria, with AKI measured by both creatinine levels (AKIN Cr ) and urine output (AKIN UO ). Patients were divided into two groups based on body mass index (BMI): overweight/obese (BMI ≥ 25) and non-obese (BMI < 25). Data were collected before and after prone positioning. Results : In overweight/obese patients (n = 39, 57 cases), both the median AKIN Cr and AKIN UO scores increased significantly following prone positioning (from 0 to 1, median p < 0.01, and from 0 to 2, median p < 0.01, respectively). No statistically significant changes in AKIN scores were observed in non-obese patients nor were significant differences found in either group after repositioning to supine. Conclusions : Prone positioning is associated with an increased risk of acute kidney injury in overweight and obese ARDS patients. This may be due to the kidneys' susceptibility to intra-abdominal hypertension in these patients. Further research is needed to explore optimal proning strategies for overweight and obese populations.

Purpose: The purpose of this study was to examine the incidence of ocular, periocular, and systemic inflammatory conditions among patients with pterygium and assess if these conditions are risk factors of pterygium development., Methods: A case-control study was conducted using electronic medical records from Clalit Health Services in Israel between 2001 and 2022. Patients diagnosed with pterygium were included; for each case, 3 controls were matched based on birth year, sex, and ethnicity. Mixed models were used to assess differences in the groups' demographic characteristics of ocular and systemic diseases. Generalized estimating equation logistic regression was used to estimate the odds ratios (ORs) and adjust for confounders., Results: A total of 94,652 patients diagnosed with pterygium and 378,608 matched controls were included in the study. The average age of patients with pterygium was 53 ± 16 years; 54% were male. A significant association was found between pterygium and vernal keratoconjunctivitis (OR 2.12, 95% confidence interval [CI], 1.90-2.36), chronic allergic conjunctivitis (OR 1.69, 95% CI 1.58-1.82), blepharitis (OR 1.66, 95% CI 1.61-1.70), and chalazion (OR 1.27, 95% CI 1.23-1.33). A significant association was also found between pterygium and systemic conditions as unspecified systemic allergy (OR 1.08, 95% CI 1.04-1.13), asthma (OR 1.08, 95% CI 1.04-1.11), and atopic dermatitis (OR 1.14, 95% CI 1.08-1.19)., Conclusions: Various inflammatory and allergic diseases-ocular, periocular, and systemic-increase the risk of pterygium. Further research is needed to investigate the role of inflammation in pterygium development., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study investigated the association between involutional ectropion and chronic inflammatory diseases of the eyelid and ocular surface, and other systemic diseases., Methods: This case-control study was conducted using electronic medical records from Clalit Health Services in Israel, 2001-2022. Patients diagnosed with involutional ectropion were compared to two control groups: one with senile cataracts and another with other ophthalmic diseases. The groups were matched 1:3 by birth year, sex, and ethnicity. Mixed models were used to assess differences in demographics, periocular, ocular, and systemic diseases between the groups. Conditional logistic regression was used to estimate the odds ratios (OR) and adjust for confounders., Results: A total of 1786 patients with involutional ectropion and 5358 matched individuals in each control group were included. The average age of the patients with involutional ectropion was 77 ± 10 years, and 60% were men. Significant associations were found between involutional ectropion and several inflammatory diseases: blepharitis (OR 4.25, 95% confidence interval [CI]: 3.68-4.91), chalazion (OR 3.01, 95% CI: 2.3-3.94), hordeolum (OR 2.27, 95% CI: 1.8-2.86), dermatitis of the eyelid (OR 1.69, 95% CI: 1.16-2.47), chronic conjunctivitis (OR 3.49, 95% CI: 2.86-4.26), pterygium (OR 2.21, 95% CI: 1.71-2.86), hypertension (OR 1.5, 95% CI: 1.31-1.72), dyslipidaemia (OR 1.46, 95% CI: 1.3-1.64), and rheumatic disease (OR 1.9, 95% CI: 1.5-2.4)., Conclusions: Periocular, ocular surface, and systemic inflammatory diseases are independent risk factors for involutional ectropion. Further research is necessary to fully understand these associations., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of acute optic nerve damage. While cardiovascular risk factors such as hypertension, diabetes mellitus, and obstructive sleep apnea are well-established, the association between NAION and states of hypoperfusion is underexplored. This study investigated this potential association., Methods: This retrospective case-control study analyzed all electronic medical records of Clalit Health Services' patients from 2001 to 2022. Patients diagnosed with NAION were matched in a 1:4 ratio by year of birth and sex, using propensity score analysis to adjust for various comorbidities. Events of hypoperfusion occurring in the month prior to the diagnosis of NAION were categorized into two physiological mechanisms: a decrease in SVR and a decrease in cardiac output due to cardiac dysfunction or diminished preload (attributed to hypovolemia). Conditional logistic regression was used to explore differences between the groups., Results: A total of 1,374 patients diagnosed with NAION and 5,496 matched controls were included in the study. We found a nearly 6.5-fold increase in the likelihood of NAION in association with events of hypoperfusion that occurred in the month period preceding the diagnosis of NAION (odds ratio [OR] 6.48; 95% confidence interval [CI]: 5.05-8.32). In particular, the group of patients with cardiac dysfunction (OR 6.47; 95% CI: 4.63-9.04) and the group with hypovolemia (OR 6.1; 95% CI: 4.08-9.13) emerged as having the most substantial risk factors. The group with decreased Systemic Vascular Resistance (SVR) (OR 4.64; 95% CI: 2.84-7.59) was also strongly related with NAION. Cerebrovascular accident emerged as an independent significant risk factor for NAION (OR 16.1; 95% CI: 10.8-24)., Conclusion: Hypoperfusion states are significant, independent risk factors for NAION., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gabbay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma outcomes remains unclear. This study compares asthma-related healthcare utilization in preschool children born prematurely between those who received Palivizumab (the Prophylaxis (+) group) and those who did not (the Prophylaxis (-) group)., Methods: This nationwide, population-based retrospective cohort study utilized data from Clalit Healthcare Services in Israel. The study included children born between 32 + 6 and 34 + 6 weeks of gestational age from 2011 to 2018. Descriptive analysis, univariate analysis, and multivariate logistic regression were performed to compare the Prophylaxis (+) and the Prophylaxis (-) groups., Results: In total, 4503 children were included, with 3287 in the Prophylaxis (+) group and 1216 in the Prophylaxis (-) group. Palivizumab administration was associated with reduced hospitalizations for RSV bronchiolitis (1.8% vs. 3.3%, p = 0.003). However, no significant differences were observed in multivariate analysis for long-term asthma outcomes, including asthma diagnosis (OR = 1.04, CI = 0.84-1.30, p = 0.7) or emergency department visits for asthma (OR = 0.79, CI = 0.54-1.17, p = 0.2). Similarly, Palivizumab administration was not associated with the purchase of short-acting beta-agonists (OR = 1.14, 95% CI 0.98-1.32, p = 0.084), inhaled corticosteroids (OR = 1.1, CI = 0.93-1.32, p = 0.3), or oral corticosteroids (OR = 1.09, CI = 0.94-1.26, p = 0.3)., Conclusions: While Palivizumab effectively reduces RSV acute bronchiolitis in preterm infants, it does not significantly impact long-term preschool asthma-related healthcare utilization.

Dendritic cells (DC) are specialized mononuclear phagocytes that link innate and adaptive immunity. They comprise two principal subsets: plasmacytoid DC (pDC) and conventional DC (cDC). Understanding the generation, differentiation, and migration of cDC is critical for immune homeostasis. Through human in vivo deuterium-glucose labeling, we observed the rapid appearance of AXL+ Siglec6+ DC (ASDC) in the bloodstream. ASDC circulate for ∼2.16 days, while cDC1 and DC2 circulate for ∼1.32 and ∼2.20 days, respectively, upon release from the bone marrow. Interestingly, DC3, a cDC subset that shares several similarities with monocytes, exhibits a labeling profile closely resembling that of DC2. In a human in vivo model of cutaneous inflammation, ASDC were recruited to the inflammatory site, displaying a distinctive effector signature. Taken together, these results quantify the ephemeral circulating lifespan of human cDC and propose functions of cDC and their precursors that are rapidly recruited to sites of inflammation., (© 2024 Lubin et al.)

Bronchopulmonary dysplasia (BPD) poses a significant challenge as the most common late morbidity of preterm infants. This study aimed to evaluate airway abnormalities in infants with BPD who underwent flexible bronchoscopy (FB) to gain insights into the prevalence of upper airway obstruction and associated complications. A retrospective case-control study was conducted on BPD patients who underwent FB at a tertiary center between 2013 and 2023. BPD patients were matched (1:3) with a reference group based on age, gender, and ethnicity, who also had undergone FB. Demographic data, comorbidities, indications for FB, findings, and complications during and after FB were collected. The study included 50 BPD patients (mean age 1.26 ± 0.9 years, 58% males), and 150 controls. As expected, BPD patients had a lower gestational age, lower birth weight, and longer hospitalizations and were treated with more medications. Abnormal bronchoscopy findings were significantly more common in the BPD group compared to the reference group, with an increased rate of turbinate hypertrophy (OR [95% CI]: 3.44 [1.27-9.37], P = 0.014), adenoid hypertrophy (OR: 2.7 [1.38-5.29], P = 0.004), lingual tonsils (OR: 5.44 [1.29-27.4], P = 0.0024), subglottic stenosis (OR: 6.95 [2.08-27.1], P = 0.002), and tracheomalacia (OR: 2.98 [1.06-8.19], P = 0.034). Complications including desaturation (OR: 3.89 [1.32-11.7], P = 0.013) and PICU admission (OR: 16.6 [2.58-322], P = 0.011) were more frequent in the BPD than in the reference group., Conclusion: The study revealed a high prevalence of structural anomalies leading to upper airway obstruction and complications in infants with BPD undergoing FB. These findings emphasize the importance of careful consideration and preparation for bronchoscopic procedures in this vulnerable population., What Is Known: • Bronchopulmonary dysplasia (BPD) represents the most prevalent late morbidity among preterm infants. • Preterm infants diagnosed with BPD frequently undergo diagnostic procedures, including flexible and rigid bronchoscopies, to identify structural pathologies within the respiratory tract., What Is New: • A significantly higher prevalence of structural anomalies leading to upper airway obstruction was observed in the BPD group compared to controls. • The incidence of complications during flexible bronchoscopy was higher in the BPD group than in controls., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Multisystemic inflammatory syndrome in children (MIS-C) is a rare, severe, post-infectious hyperinflammatory condition that occurs after COVID-19 infection. In this study, we aimed to demonstrate the risk reduction of MIS-C and severe MIS-C after Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccination. This nationwide cohort study included 526,685 PCR-confirmed COVID-19 cases (age < 19 years), of whom 14,118 were fully vaccinated prior to COVID-19 infection. MIS-C cases were collected from all hospitals in Israel from April 2020 through November 2021. The MIS-C rates were calculated among two COVID-19 populations: positive PCR confirmed cases and estimated COVID-19 cases (PCR confirmed and presumed). Vaccination status was determined from Ministry of Health (MoH) records. The MIS-C risk difference (RD) and 95% confidence intervals (95%CI) between vaccinated and unvaccinated patients are presented. Overall, 233 MIS-C cases under the age of 19 years were diagnosed and hospitalized in Israel during the study period. Among the estimated COVID-19 cases, MIS-C RD realistically ranged between 2.1 [95%CI 0.7-3.4] and 1.0 [95%CI 0.4-1.7] per 10,000 COVID-19 cases. For severe MIS-C, RD realistically ranged between 1.6 [95%CI 1.3-1.9] and 0.8 [95%CI 0.7-1.0], per 10,000 COVID-19 cases. Sensitivity analysis was performed on a wide range of presumed COVID-19 rates, demonstrating significant RD for each of these rates., Conclusion: This research demonstrates that vaccinating children and adolescents against COVID-19 has reduced the risk of MIS-C during the study period., What Is Known: • Most of the published literature regarding vaccine effectiveness is based on case-control studies, which are limited due to small sample sizes and the inability to fully estimate the risk of MIS-C among vaccinated and unvaccinated children and adolescents. • The known underestimation of COVID-19 diagnosis among children and adolescents is challenging, as they often have few to no symptoms., What Is New: • Significant risk difference was found in favor of the vaccinated group, even after including extreme assumptions regarding the underdiagnosed COVID-19 rate. • During this nationwide study period, it was found that vaccinating children and adolescents reduced the risk of MIS-C and its complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To evaluate the impact of the pneumococcal conjugate vaccines (PCVs) introduction on the orbital complications of acute rhino-sinusitis (OC-ARS)., Methods: A retrospective cohort study of all pediatric patients with OC-ARS during the period 2002-2019. Data included clinical, demographic, laboratory, and microbiology findings. Patients were divided into three groups: before PCV7 introduction (group 1), after PCV7 and before PCV13 (group 2), and after PCV13 (group 3)., Results: Of 265 enrolled patients, 117, 39, and 109 were assigned to groups 1, 2, and 3. During the study period, a significant decrease was recorded in the percentages of patients in Chandler classification severity category 1, with an increase in patients in category 3 (P = 0.011). The yearly incidence of OC-ARS decreased from 12.64 cases per 100,000 population in 2002 to 5.56 per 100,000 in 2008, and 2.99 per 100,000 in 2019 (P < 0.001). Patients aged 0-4 years showed a dramatic decrease from 29 cases per 100,000 population in 2002 to 4.27 per 100,000 in 2019 (P < 0.001). The pathogens retrieved from all cultures performed were Streptococcus pneumoniae (32.5%), non-typeable Haemophilus influenzae (27.5%), Streptococcus Species, (12.5%), and Staphylococcus aureus (20%), with no changes in distribution during the study periods. Surgery was performed in 28 (10.6%) patients., Conclusions: A significant decrease was seen in the overall incidence of OC-ARS, mainly attributable to the decrease in patients aged 0-4 years. An increase was recorded in the severity of the disease following PCVs introduction., Competing Interests: Declaration of competing interest No competing interests to declare., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the incidence and risk factors for inflammatory conditions among patients with primary acquired nasolacrimal duct obstruction (PANDO)., Methods: A retrospective case-control study was conducted among patients of Clalit Health Services (CHS) in Israel from 2001 to 2022. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Differences in demographic characteristics, ocular surface, eyelid, upper airway, and systemic diseases were assessed between the groups, and odds ratios (OR) were calculated., Results: A total of 60,726 patients diagnosed with PANDO were included. The average age of PANDO patients was 63 ± 18 years, 63% were female. Significant associations were found between PANDO and various ocular surface and eyelid conditions, including chronic conjunctivitis (OR 2.96, 95% CI [2.73-3.20]), vernal keratoconjunctivitis (OR 2.89, 95% CI [2.45-3.29]), and blepharitis (OR 2.75, 95% CI [2.68-2.83]). There was a significant association with various upper airway conditions, including rhinitis (OR 1.62, 95% CI [1.58-1.66]), chronic sinusitis (OR 1.71, 95% CI [1.62-1.80]), and deviated nasal septum (OR 1.76, 95% CI [1.69-1.84]). Association was also observed with systemic conditions, including asthma (OR 1.34, 95% CI [1.27-1.41]) and atopic dermatitis (OR 1.36, 95% CI [1.32-1.41])., Conclusion: Ocular surface, eyelid, upper airway, and systemic inflammatory-related diseases were found to be associated with PANDO, supporting the theory that inflammation has a prominent role in the pathophysiology of PANDO., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus (RSV) bronchiolitis remain unclear. The aim of this study was to evaluate this association. A single-center, retrospective cohort study of infants aged under 24 months, who were hospitalized between 2018 and 2022 for RSV bronchiolitis. Data from computerized medical records were extracted using the MDclone platform. Participants were divided into three groups according to weight percentiles: underweight (below 5th percentile), normal-weight, and overweight (above 85th percentile). A total of 1936 infants (mean age 6.3 months, 55% males) were included, comprising 274 infants who were underweight, 1470 with normal weight, and 192 with overweight. Underweight infants had a higher rate of admission to the pediatric intensive care unit (PICU) (9.1% vs. 3.5%, P < 0.005) and prolonged length of stay (LOS) in the hospital (3.13 vs. 2.79 days P < 0.001) compared to those with normal weight. Hyponatremia was also more common in the underweight group (23% vs. 15%, P < 0.001). A multivariable model accounting for prematurity and birthweight predicted a relative risk of 2.01 (95% CI 1.13-3.48, P = 0.015) for PICU admission and 1.42 (95% CI 1.17-1.7, P < 0.001) for a prolonged LOS. Being overweight was not associated with a more severe disease.  Conclusion: Underweight infants, hospitalized for RSV bronchiolitis, had a more severe disease course with a higher complication rate, including PICU admission and prolonged LOS. Thus, careful attention and supervision should be given to this subgroup of infants. What is Known: • Established risk factors for severe bronchiolitis include prematurity, BPD, CHD, and compromised immunity. • Abnormal weight status has been associated with an increased risk for morbidity and mortality from infectious diseases, proposedly due to the effects on endocrine and immunologic systems. What is New: • Underweight infants hospitalized with RSV bronchiolitis face an independent risk of PICU admission and prolonged hospital stay. • Conversely, overweight infants did not display associations with severity measures in our study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: As the role of sinonasal anatomical variants as predisposing factors in determining the lateralization of acute rhinosinusitis-related orbital complications (ARS-OC) in pediatrics remains a topic of debate, this study further explores the potential association between anatomical variations and ARS-OC., Methods: A retrospective study was conducted on children who had been admitted with ARS-OC using medical records and sinus CT scans to compare anatomical differences between the affected and contralateral sides. This study aimed to identify bony anatomical disparities that may impact OC laterality secondary to ARS. The anatomical features examined included septal deviation, concha bullosa, lamina papyracea dehiscence (LPD), and uncinate process abnormalities., Results: The CT scans of 57 pediatric patients (114 sides) were reviewed. Our results indicated that bony anatomical variations were associated with ARS-OC laterality (63 % vs. 37 %, P = 0.006), yielding an odds ratio of 2.91. Additionally, our study revealed a significant association between ipsilateral LPD with the increased risk of ARS-OC (39 % vs. 1.8 %, P < 0.05), with an odds ratio of 34.3 compared to the opposite side., Conclusions: LPD might play a role in the pathophysiology of pediatric ARS-OC, as it is associated with a significantly higher risk of affecting the ipsilateral side. Further research is necessary to determine whether LPD is a causative factor or a result of ARS., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Summary: Total testosterone, which is peripherally converted to its biologically active form dihydrotestosterone (DHT), is the first-line hormone investigation in hyperandrogenic states and infertility in premenopausal women. Polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism and infertility in young women, is often associated with mild elevations of total testosterone. Whereas very high levels of total testosterone (>2-3 SD of normal reference), are most often associated with hyperandrogenic signs, menstrual irregularity, rapid onset of virilization, and demand a prompt investigation. Herein, we report a case of a 32-year-old woman who was referred to the endocrinology outpatient clinic due to secondary amenorrhea and extremely high testosterone levels without any virilization signs. We initially suspected pitfalls in the testosterone laboratory test. Total serum testosterone decreased after a diethyl-ether extraction procedure was done prior to the immunoassay, but testosterone levels were still elevated. An ovarian steroid-cell tumor (SCT) was then revealed, which was thereby resected. Twenty-four hours post surgery, the total testosterone level returned to normal, and a month later menstruation resumed. This case emphasizes that any discrepancy between laboratory tests and the clinical scenario deserves a rigorous evaluation to minimize misinterpretation and errors in diagnosis and therapeutic approach. Additionally, we describe a possible mechanism of disease: a selective peripheral target-tissue response to high testosterone levels that did not cause virilization but did suppress ovulation and menstruation., Learning Points: Total testosterone is the most clinically relevant hormone in investigating hyperandrogenic states and infertility in premenopausal women. Very high total testosterone levels in women (>2-3 SD of normal reference) are most often associated with hyperandrogenic signs, menstrual irregularities, and a rapid onset of virilization. In women with very elevated testosterone levels and the absence of clinical manifestations, laboratory interference should be suspected, and diethyl ether extraction is a useful technique when other methods fail to detect it. Ovarian steroid cell tumors (SCT) encompass a rare subgroup of sex cord-stromal tumors and usually secrete androgen hormones. SCTs are clinically malignant in 25-43% of cases. A selective response of peripheral target tissues to testosterone levels, with clinical manifestations in some tissues and no expression in others, may reflect differences in the conformation of tumor-produced testosterone molecules.

Purpose: Point-of-care ultrasound (POCUS) is a sensitive, safe, and efficient tool used in many clinical settings and is an essential part of medical education in the United States. Numerous studies present improved diagnostic performances and positive clinical outcomes among POCUS users. However, others stress the degree to which the modality is user-dependent, rendering high-quality POCUS training necessary in medical education. In this study, the authors aimed to investigate the potential of an artificial intelligence (AI) based quality indicator tool as a teaching device for cardiac POCUS performance., Methods: The authors integrated the quality indicator tool into the pre-clinical cardiac ultrasound course for 4th-year medical students and analyzed their performances. The analysis included 60 students who were assigned to one of two groups as follows: the intervention group using the AI-based quality indicator tool and the control group. Quality indicator users utilized the tool during both the course and the final test. At the end of the course, the authors tested the standard echocardiographic views, and an experienced clinician blindly graded the recorded clips. Results were analyzed and compared between the groups., Results: The results showed an advantage in quality indictor users' median overall scores (P = 0.002) with a relative risk of 2.3 (95% CI: 1.10, 4.93, P = 0.03) for obtaining correct cardiac views. In addition, quality indicator users also had a statistically significant advantage in the overall image quality in various cardiac views., Conclusions: The AI-based quality indicator improved cardiac ultrasound performances among medical students who were trained with it compared to the control group, even in cardiac views in which the indicator was inactive. Performance scores, as well as image quality, were better in the AI-based group. Such tools can potentially enhance ultrasound training, warranting the expansion of the application to more views and prompting further studies on long-term learning effects., Competing Interests: I have reviewed the journal’s policy, and the authors of this manuscript have the following competing interests: GE Healthcare© provided the POCUS devices used in this study. Lior Fuchs declares that he is a consultant for GE Healthcare. However, it’s important to note that the company had no access to the idea, to the study’s primary objective, nor to its design, data analysis, or writing. This affiliation does not affect our adherence to PLOS ONE policies regarding data and material sharing. The remaining authors declare that they have no competing interests., (Copyright: © 2024 Aronovitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To compare seizure burden between newborn infants treated with therapeutic hypothermia (TH) and those that were not and to compare the need for antiseizure medications (ASM) in a cohort of infants who were diagnosed with neonatal hypoxic-ischemic encephalopathy (HIE)., Methods: This was a retrospective cohort study on infants born after 35 weeks' gestation, diagnosed with moderate to severe HIE, monitored with amplitude-integrated electroencephalography (aEEG) and eligible for TH. Infants born before the implementation of TH in 2008 were compared with infants born thereafter who received TH. Seizure burden was assessed from aEEG as total time in minutes of seizures activity per hour of recording. Other clinical and demographic data were retrieved from a prospective local database of infants with HIE., Results: Overall, 149 of 207 infants were included in the study: 112 exposed to TH and 37 not exposed. Cooled infants had a lower seizure burden overall (0.4 vs 2.3 min/h, P < 0.001) and were also less likely to be treated with ASM (74% vs 100%, P < 0.001). In multivariable regression models, not exposed to TH, having a depressed aEEG background, and having higher Apgar scores were associated with higher seizure burden (incidence rate ratio: 4.78 for noncooled infants, P < 0.001); also, not exposed to TH was associated with a higher likelihood of multidrug ASM (odds ratio: 4.83, P < 0.001)., Conclusions: TH in infants with moderate to severe HIE is associated with significant reduction of seizure burden and ASM therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The prevalence of nontuberculous mycobacteria (NTM) infections is rising in people with cystic fibrosis (pwCF). NTM infection, especially infection with Mycobacterium abscessus complex (MABC), is commonly associated with severe lung deterioration. The current treatment modalities, including multiple intravenous antibiotics, frequently fail to achieve airway eradication. Although treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to modulate the lung microbiome, data regarding its role in eradicating NTM in pwCF is lacking. Our aim was to evaluate the impact of ETI on the rate of NTM eradication in pwCF., Methods: This retrospective multicenter cohort study included pwCF from five CF centers in Israel. PwCF aged older than 6 who had at least one positive NTM airway culture in the past two years and were treated with ETI for at least one year were included. The annual NTM and bacterial isolations, pulmonary function tests, and body mass index were analyzed before and after ETI treatment., Results: Fifteen pwCF were included (median age 20.9 years, 73.3% females, 80% pancreatic insufficient). In nine patients (66%) NTM isolations were eradicated following treatment with ETI. Seven of them had MABC. The median time between the first NTM isolation and treatment with ETI was 2.71 years (0.27-10.35 years). Eradication of NTM was associated with improved pulmonary function tests (p<0.05)., Conclusions: For the first time, we report successful eradication of NTM, including MABC, following treatment with ETI in pwCF. Additional studies are needed to assess whether treatment with ETI can result in the long-term eradication of NTM., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Objective: We sought to study adenoidectomy rates in children with adenoid hypertrophy (AH) who were either treated with medical therapy or not during a 2-year follow-up period in a longitudinal population-based study., Methods: We retrospectively identified healthy children aged 1-18 years between 2014 and 2020 with AH diagnosis from the Clalit Health Services database, the largest healthcare maintenance organization in Israel. The main outcome was adenoidectomy alone or in combination with other procedures performed within 2 years after diagnosis. The treatment group consisted of children who received medical therapy, defined as a pharmacy purchase of montelukast, nasal steroid sprays and/or antihistamines (medical therapy aimed to reduce AH) for ≥2 consecutive months, while the control group consisted of untreated children., Results: We identified 68,356 unique children with AH, of them 56 % were boys, with a mean age of 4.9 ± 3.3 years. Of them, 5310 (7.7 %) received medical therapy. Overall, 6633 (9.7 %) underwent adenoidectomy within 2 years following diagnosis. There was no significant difference in surgery referral rates between the treatment and the control groups, 10 % vs. 9.7 %, respectively (p = 0.3). When adjusted for age and sex, the likelihood of undergoing adenoidectomy was similar in both groups (HR = 0.98, 95 % CI = 0.90-1.07, p = 0.6). Among operated children, the average time from diagnosis to surgery was statistically significantly longer in the treatment group than in the control group, 346 ± 180 vs 311 ± 175 days (p < 0.001)., Conclusion: Prescribing montelukast, nasal steroids and/or oral antihistamines was not associated with a reduction in adenoidectomy rates and was associated with an average surgery delay of 35 days., Competing Interests: Declaration of competing interest There are no conflict of interests to be disclosed by any of the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Acute bronchiolitis is the most common cause of hospitalization in young children. Data on monocyte-to-lymphocyte-ratio (MLR) and neutrophil-to-lymphocyte-ratio (NLR) as biomarkers are limited. We aim to evaluate these ratios in children hospitalized with respiratory syncytial virus (RSV) bronchiolitis and their value as biomarkers for severe clinical outcomes., Study Design: A single-center retrospective cohort study of children aged <2 years hospitalized due to RSV bronchiolitis, between January 2018 and March 2022, with a complete blood count upon admission. We divided the cohort into quartiles based on MLR and NLR values. We examined associations between quartiles and four clinical severity outcomes., Results: A total of 2038 children (median age: 4.4 months, IQR: 1.9-9.8) were included in the study. The median MLR and NLR values for quartiles 1-4 were 0.14, 0.22, 0.30, 0.47, and 0.37, 0.70, 1.16, 2.29, respectively. Children with higher MLR had higher hospitalization rates to the pediatric intensive care unit (PICU) (Q1 2.4%, Q4 9.4%, p < .001), extended hospital stays (Q1 19.4%, Q4 32%, p < .001), and lower minimal oxygen saturation (Q1 90%, Q4 87%, p < .001). Cut-off values of 0.34 for MLR and 0.67 for NLR optimally identified PICU admissions. In a model accounting for age and sex, the fourth MLR quartile had an RR of 3.4 (95% CI: 1.76-7.22) and successfully predicted PICU admissions (area under the curve = 0.73; 95% CI: 0.681-0.789)., Conclusions: MLR and NLR are potential biomarkers for identifying children with RSV bronchiolitis at a higher risk for severe outcomes, specifically PICU admission., (© 2023 Wiley Periodicals LLC.)

Histiocytoses are inflammatory myeloid neoplasms often driven by somatic activating mutations in mitogen-activated protein kinase (MAPK) cascade genes. H syndrome is an inflammatory genetic disorder caused by germ line loss-of-function mutations in SLC29A3, encoding the lysosomal equilibrative nucleoside transporter 3 (ENT3). Patients with H syndrome are predisposed to develop histiocytosis, yet the mechanism is unclear. Here, through phenotypic, molecular, and functional analysis of primary cells from a cohort of patients with H syndrome, we reveal the molecular pathway leading to histiocytosis and inflammation in this genetic disorder. We show that loss of function of ENT3 activates nucleoside-sensing toll-like receptors (TLR) and downstream MAPK signaling, inducing cytokine secretion and inflammation. Importantly, MEK inhibitor therapy led to resolution of histiocytosis and inflammation in a patient with H syndrome. These results demonstrate a yet-unrecognized link between a defect in a lysosomal transporter and pathological activation of MAPK signaling, establishing a novel pathway leading to histiocytosis and inflammation., (© 2023 by The American Society of Hematology.)

The COVID-19 pandemic notably influenced the transmission of infectious diseases across various age groups. In this study, we assessed its impact on pediatric acute conjunctivitis trends in southern Israel. We analyzed acute conjunctivitis diagnoses from 2017 to 2022, categorizing them into pre-lockdown, lockdown, and post-lockdown intervals. A control group of non-infectious dermatologic conditions was included. Time-series analysis, adjusted for seasonality, was employed. Pre-lockdown data indicated steady conjunctivitis diagnoses, primarily in winter. Post-lockdown interval exhibited an added summer peak before the regular winter surge. The lockdown saw a 56% decline in diagnoses, most pronounced in younger ages. Post-lockdown observed a 7% overall drop with age-specific variations. The acute conjunctivitis IRR was 0.44 (95% CI 0.39-0.49) during lockdowns and 0.93 (95% CI 0.86-1.02) post-lockdowns. Control group IRRs were 0.84 (95% CI 0.78-0.89) and 0.90 (95% CI 0.84-0.96), respectively, with the 0-5 age range demonstrating significant disparities. Pediatric acute conjunctivitis in southern Israel decreased significantly during the pandemic. Post-lockdown patterns varied by age group. An unusual summer peak in cases was observed post-lockdown; this peak may be influenced by a combination of altered behaviors in the summer and possibly increased susceptibility to infection., (© 2023. The Author(s).)

Purpose: To evaluate risk factors for pterygium and prevalence of periocular and systemic diseases among patients with pterygium., Methods: A retrospective case-control study was conducted among members of Clalit Health Services (CHS) in Israel, from 2001 to 2022. A total of 13,944 patients diagnosed with pterygium were included. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Mixed models were used to assess differences in demographic characteristics, ocular and systemic diseases between the groups. Generalized estimating equation (GEE) logistic regression was used to estimate the odds ratios (OR) and adjust for confounders., Results: The average age of pterygium patients was 49 ± 17 years; 51% were male. The results showed significant associations between pterygium and risk factors of vernal kerato-conjunctivitis (OR 2.52, 95% confidence interval [CI]: [1.96-3.24]), chronic allergic conjunctivitis (OR 1.98, 95% CI: [1.65-2.39]), blepharitis (OR 1.91, 95% CI: [1.78-2.04]), chalazion (OR 1.47, 95% CI: [1.30-1.67]) and unspecified systemic allergy (OR 1.21, 95% CI [1.09-1.34]), after adjusting for rural residency status. Glaucoma (OR 0.74, 95% CI [0.64-0.85]) and smoking (OR 0.70, 95% CI [0.66-0.75]) were protective factors against pterygium., Conclusion: Systemic and periocular inflammatory and allergic diseases are risk factors for pterygium.

Objective: To investigate the rates of delayed postoperative cochlear implantation pain (DPCIP) in the pediatric population, using a "reach-out" proactive approach. Secondary aims included the possible impact of surgery extent or the patient ethnicity on DPCIP rates., Materials and Methods: A cross-sectional study was conducted at Soroka University Medical Center in Israel. Demographics and data regarding the surgery and surgical complications were collected from the medical records of the patients. A telephone questionnaire was conducted for parents of all children who underwent cochlear implantation (CI) between 2007 and 2020. The questions addressed pain at four time periods: during hospitalization after surgery, 3 months, 2 years, and 5 years after surgery., Results: Out of 213 patients, 129 (60%) were included in this study. The mean age was 41 months (±40). Unilateral CI was performed in 72 (56%) patients. At 3 months and 2 years after surgery, 8.5% of patients reported pain (visual analog scale [VAS] ≥ 1). Five years after surgery, a slight increase in the number of patients who reported pain (12%) was observed. Of those experiencing pain 2 years and 5 years after surgery, 10/12 (83%) and 11/16 (69%), respectively, reported a new onset of the pain. Surgery extent and cultural background were not significantly associated with DPCIP rates. No correlations were found between patients complaining of pain and any surgical complications., Conclusions: DPCIP rates may be underrecognized and higher than previously reported, reaching up to 12%. This long-term effect should be acknowledged and discussed with parents upon informed consent., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Dendritic cells (DCs) enable the immune system to mount and modulate precisely targeted responses to various threats across the organism by bridging innate and adaptive immunity. Historically, DCs have been classified as conventional (cDC) and plasmacytoid (pDC). More recently, cDCs were acknowledged as a heterogenous population composed of several subsets. Examining the functional diversity of cDCs in healthy homeostasis and pathology requires a robust experimental pipeline, beginning with an efficient enrichment protocol in preparation for cell sorting. Unfortunately, several commercial DC enrichment kits were developed before the discovery of the more recently described DC populations. Here, we detail two approaches to enrich human blood DCs or certain DC subsets and an in vitro protocol to examine DC stimulation of naïve T cells. The methods employed here overcome many hurdles encountered while enriching human DC subsets. Basic Protocol 1 describes a method that will enrich pDC, Axl Siglec6-DC (AS-DC), cDC1, DC2, DC3, monocytes, and human HLA + cells by crosslinking unwanted cells to erythrocytes. Basic Protocol 2 describes the enrichment of pDC, AS-DC, cDC1, and DC2 but not DC3 via a highly efficient negative magnetic selection that is valuable in circumstances where DC3 is not required. Finally, Basic Protocol 3 describes a conventional protocol to perform a Mixed leucocyte Reaction (MLR) following the isolation of these DC subsets. These methods detail the advantages and pitfalls when isolating a heterogeneous population of cells. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Human peripheral mononuclear phagocyte enrichment Basic Protocol 2: DC enrichment of pDC, cDC1, AS-DC, and DC2 but not DC3 Basic Protocol 3: Basic mixed lymphocyte reaction protocol with sorted human DC subsets., (© 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.)