Excess BAFF May Impact HIV-1-Specific Antibodies and May Promote Polyclonal Responses Including Those from First-Line Marginal Zone B-Cell Populations.

We have previously shown that blood levels of B-cell Activating Factor (BAFF) rise relatively to disease progression status in the context of HIV-1 infection. Excess BAFF was concomitant with hyperglobulinemia and the deregulation of blood B-cell populations, notably with increased frequencies of a population sharing characteristics of transitional immature and marginal zone (MZ) B-cells, which we defined as marginal zone precursor-like" (MZp). In HIV-uninfected individuals, MZp present a B-cell regulatory (Breg) profile and function, which are lost in classic-progressors. Moreover, RNASeq analyses of blood MZp from classic-progressors depict a hyperactive state and signs of exhaustion, as well as an interferon signature similar to that observed in autoimmune disorders such as Systemic Lupus Erythematosus (SLE) and Sjögren Syndrome (SS), in which excess BAFF and deregulated MZ populations have also been documented. Based on the above, we hypothesize that excess BAFF may preclude the generation of HIV-1-specific IgG responses and drive polyclonal responses, including those from MZ populations, endowed with polyreactivity/autoreactivity. As such, we show that the quantity of HIV-1-specific IgG varies with disease progression status. In vitro, excess BAFF promotes polyclonal IgM and IgG responses, including those from MZp. RNASeq analyses reveal that blood MZp from classic-progressors are prone to Ig production and preferentially make usage of IGHV genes associated with some HIV broadly neutralizing antibodies (bNAbs), but also with autoantibodies, and whose impact in the battle against HIV-1 has yet to be determined.

Excess BAFF Alters NR4As Expression Levels and Breg Function of Human Precursor-like Marginal Zone B-Cells in the Context of HIV-1 Infection.

We have reported excess B-cell activating factor (BAFF) in the blood of HIV-infected progressors, which was concomitant with increased frequencies of precursor-like marginal zone (MZp) B-cells, early on and despite antiretroviral therapy (ART). In controls, MZp possess a strong B-cell regulatory (Breg) potential. They highly express IL-10, the orphan nuclear receptors (NR)4A1, NR4A2 and NR4A3, as well as the ectonucleotidases CD39 and CD73, all of which are associated with the regulation of inflammation. Furthermore, we have shown MZp regulatory function to involve CD83 signaling. To address the impact of HIV infection and excessive BAFF on MZp Breg capacities, we have performed transcriptomic analyses by RNA-seq of sorted MZp B-cells from the blood of HIV-infected progressors. The Breg profile and function of blood MZp B-cells from HIV-infected progressors were assessed by flow-cytometry and light microscopy high-content screening (HCS) analyses, respectively. We report significant downregulation of NR4A1, NR4A2, NR4A3 and CD83 gene transcripts in blood MZp B-cells from HIV-infected progressors when compared to controls. NR4A1, NR4A3 and CD83 protein expression levels and Breg function were also downregulated in blood MZp B-cells from HIV-infected progressors and not restored by ART. Moreover, we observe decreased expression levels of NR4A1, NR4A3, CD83 and IL-10 by blood and tonsillar MZp B-cells from controls following culture with excess BAFF, which significantly diminished their regulatory function. These findings, made on a limited number of individuals, suggest that excess BAFF contributes to the alteration of the Breg potential of MZp B-cells during HIV infection and possibly in other situations where BAFF is found in excess.

Gray Zone Lymphoma Arising in the Neck of a Teenager With a Germline Mutation in TP53.

Gray zone lymphoma is an aggressive disease for which appropriate management is still debated. We report a 15-year-old girl with a cervical mass, an enlarged ipsilateral tonsil, and anemia. Both sites showed hypermetabolism on F18-FG positron emission tomography/CT. Surgical resection was diagnostic of Epstein-Barr virus-negative gray zone lymphoma cervical and tonsillar involvement. No abnormality was found in cytogenetic analysis on tumor cells. However, exome sequencing in peripheral blood DNA revealed a germline mutation in TP53. Complete response was achieved after surgery and 6 cycles of rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin regimen.

Persistent sleep disordered breathing after adenoidectomy and/or tonsillectomy: a long-term survey in a tertiary pediatric hospital.

PURPOSE: To determine the long-term prevalence of persistent sleep disordered breathing (SDB) in children, after adenoidectomy, tonsillectomy or adenotonsillectomy, and to assess the relationship between baseline characteristics and persistent nocturnal symptoms. METHODS: The clinical charts of children operated for adenoidectomy and/or tonsillectomy in a tertiary hospital, between January 2000 and March 2016, were retrospectively reviewed. All patients who had signs of SDB prior to surgery received a six-question validated pediatric questionnaire, the Hierarchic Severity Clinical Scale (HSCS). RESULTS: A total of 4000 children showing SDB prior to surgery were selected out of 5809 (68.9%); 1176 parents returned the questionnaire (29.4%), with a mean age at surgery of 4.3 ± 2.2 and age at survey of 9.6 ± 3.6. Complete resolution of SDB was subjectively reported in 798 patients (67.9%), and mild SDB was suspected in 301 children (25.6%, HSCS > 0 with chronic snoring), while 77 (6.5%) had a HSCS > 2.72, suggesting persistent obstructive sleep apnea. In non-syndromic children, male sex, history of sole adenoidectomy, or sole tonsillectomy, and early age of surgery (< 2 years-old) were associated with higher HSCS scores (p < 0.05). Moreover, symptoms had a tendency to decrease from 1 to 6 years, re-occur at age 7-8, and also after 13, with boys reporting more severe symptoms, at a younger age. CONCLUSIONS: Surgical excision of lymphoid tissue to treat SDB in childhood seems to be effective in the long term in two-thirds of subjects, while partial surgeries, specific age groups and early surgery are more likely to have persistent or recurrent symptoms.

The Role of Conservative Management in Pneumosinus Dilatans Frontalis With Minimal Bony Deformity.

The authors describe the conservative management of 2 rare patients of uncomplicated pneumosinus dilatans of the frontal sinus with minimal bossing of the forehead. Regular nasal hygiene in combination with topical corticosteroids was administered with following complete resolution symptoms.

Deleterious impact of Pseudomonas aeruginosa on cystic fibrosis transmembrane conductance regulator function and rescue in airway epithelial cells.

The epithelial response to bacterial airway infection, a common feature of lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis, has been extensively studied. However, its impact on cystic fibrosis transmembrane conductance regulator (CFTR) channel function is not clearly defined. Our aims were, therefore, to evaluate the effect of Pseudomonas aeruginosa on CFTR function and expression in non-cystic fibrosis airway epithelial cells, and to investigate its impact on ΔF508-CFTR rescue by the VRT-325 corrector in cystic fibrosis cells. CFTR expression/maturation was evaluated by immunoblotting and its function by short-circuit current measurements. A 24-h exposure to P. aeruginosa diffusible material (PsaDM) reduced CFTR currents as well as total and membrane protein expression of the wildtype (wt) CFTR protein in CFBE-wt cells. In CFBE-ΔF508 cells, PsaDM severely reduced CFTR maturation and current rescue induced by VRT-325. We also confirmed a deleterious impact of PsaDM on wt-CFTR currents in non-cystic fibrosis primary airway cells as well as on the rescue of ΔF508-CFTR function induced by VRT-325 in primary cystic fibrosis cells. These findings show that CFTR function could be impaired in non-cystic fibrosis patients infected by P. aeruginosa. Our data also suggest that CFTR corrector efficiency may be affected by infectious components, which should be taken into account in screening assays of correctors.

Chronic suppurative otomastoiditis due to nontuberculous mycobacteria: A case series.

INTRODUCTION: Eight new cases of chronic otomastoiditis due to nontuberculous mycobacteria were reported at Center Hospitalier Universitaire Sainte-Justine (CHUSJ) between 2008 and 2018. In the literature, only 89 cases have been described since 1972. This case series aims to define the clinical presentation, infectious pathogens, as well as diagnostic and therapeutic means employed in cases of nontuberculous mycobacteria otitis media encountered in our tertiary pediatric reference center. METHODS: All cases of otitis media caused by nontuberculous mycobacteria diagnosed at Sainte-Justine between 2008 and 2018 were reviewed. Species identification was retrieved from the Laboratoire de Santé Publique du Québec, Quebec's provincial public health and reference laboratory. RESULTS: All 8 cases occurred in immunocompetent children. Clinical features on presentation were chronic tympanostomy tube otorrhea with abundant granulation tissue in 7 cases. CT scan demonstrated coalescent mastoiditis in 3 cases. The median delay between initial presentation and identification of nontuberculous mycobacteria was 81 days. Seven patients had a Mycobacterium (M.) abscessus complex infection. Treatment consisted of weekly microscopic granulation debridement, a combined systemic antibiotic therapy for an average duration of 21 weeks, as well as instillation of boric acid into the middle ear. While 3 cases required at least one mastoidectomy, 2 cases were treated only medically. CONCLUSION: Nontuberculous mycobacteria otitis media is a rare clinical entity, for which high clinical suspicion and specific microbiological analyses could minimize diagnostic delay. The use of boric acid as a desiccating agent may allow for a better local control.

Prevalence of malocclusions and oral dysfunctions in children with persistent sleep-disordered breathing after adenotonsillectomy in the long term.

STUDY OBJECTIVES: To evaluate the prevalence of craniofacial/orthodontic abnormalities and oral dysfunctions in a population of children with persistent sleep-disordered breathing despite adenotonsillectomy. METHODS: Medical charts of 4,000 children with sleep-disordered breathing operated on in a tertiary hospital were retrospectively reviewed. Patients reporting persistent sleep-disordered breathing symptoms were invited to an orthodontic/myofunctional evaluation following the Sleep Clinical Score), followed by a 1-night ambulatory type III sleep study. RESULTS: One hundred nonsyndromic symptomatic patients were examined (mean age 8.8 ± 3.5 years), from 1 to 12 years after surgery (mean 4.6 ± 3.1 years); 24% were overweight/obese; 69 had a sleep study. Although prevalent, oronasal abnormalities and malocclusions were not specifically associated with pathological sleep parameters (cartilage hypotonia 18%, septal deviation 5%, short lingual frenulum 40%). Malocclusions were associated with a higher respiratory event index in children under 8 years only, whereas an impaired nasal dilator reflex and tongue immaturity were associated with an increased obstructive respiratory event index in all patients (1.72 ± 2.29 vs 0.72 ± 1.22 events/h, P = .011) and Respiratory Event Index, respectively (3.63 ± 3.63 vs 1.19 ± 1.19 events/h). Male sex, phenotype, nasal obstruction, oral breathing, and young age at surgery (< 3 years) were significantly related to higher respiratory event index. Using the Sleep Clinical Score > 6.5 cut-off, patients with persistent sleep apnea were significantly distinct from chronic snoring (2.72 ± 2.67 vs 0.58 ± 0.55, P < .01). CONCLUSIONS: Oronasal anatomical and functional abnormalities were quite prevalent and various in persistent sleep-disordered breathing after adenotonsillectomy. Nasal disuse and tongue motor immaturity were associated with a higher obstructive respiratory event index in the long term, whereas craniofacial risk factors might have a more pronounced impact at younger age.

Characteristics of children with refractory acute otitis media treated at the pediatric emergency department.

INTRODUCTION: Refractory acute otitis media (rAOM) is defined as the persistence of signs and symptoms of AOM for more than 48 to 72 hours after the initiation of antibiotic treatment. These patients are often referred to the pediatric emergency department (PED). We sought to study rAOM cases referred to our PED, and to evaluate their clinical characteristics and response to our local management guidelines. METHODS: A retrospective chart review of all children treated for rAOM between 1/2012-3/2014 was performed. Data recorded included demographics, clinical presentation, antibiotic treatments, need for surgery, and culture results. RESULTS: A total of 255 patients were included with a mean age of 19 months. Prior to admission, all the children had received at least one course of antibiotics. Amoxicillin was the most common first-line antibiotic prescribed while amoxicillin-clavulanic acid was the most common second and third-line antibiotic given. Intravenous ceftriaxone was the treatment administered at the PED. Myringotomy and pressure equalizing tube (PET) insertion were required in 60% of cases. Middle ear cultures (55 ears) were positive for Streptococcus pneumoniae in two, and Moraxella catarrhalis in only one culture. There were no differences between the mean age of children who had PET insertion and those who did not with regards to fever, rhinorrhea, and preschool or school attendance. Children presenting with otorrhea were less likely to undergo surgery (P = 0.013). CONCLUSIONS: This is the first study evaluating the established local practice guideline with regards to clinical characteristics and need for surgical management. We showed that myringotomy and PET insertion due to antibiotic failure is commonly performed for cases of rAOM. The majority of the middle ear cultures were sterile.

Treatment of bilateral choanal atresia in the premature infant.

An innovative technique for choanal atresia repair was used for a unique case of bilateral choanal atresia in a 28-week premature newborn. Endoscopic transnasal KTP laser was employed as an alternative to standard instrumentation to reach the very small atretic plate of a premature nose, providing good visualization of the operative field, thereby avoiding damage to the adjacent structures. The successful repair allowed for early extubation and avoidance of a tracheotomy. The clinical and surgical aspects of the case are discussed. With the likelihood of encountering more premature infants with choanal atresia given the improving neonatal intensive care, we propose that KTP laser repair be considered as an alternative to conventional procedures for this particular population.

Restricting indications for sinonasal computed tomography in children with cystic fibrosis.

OBJECTIVES To evaluate whether a low rate of exposure to sinonasal computed tomographic (CT) scans can be achieved when strict criteria are applied for their use in children with cystic fibrosis (CF) and to emphasize the importance of limiting radiation exposure in the context of the current longer life expectancy in this group of patients. DESIGN Retrospective chart review. SETTING Tertiary care children's hospital. PATIENTS The study included 277 children who were regularly followed up in the CF clinic in the last 11 years (mean duration of follow up, 7.87 years), 33 of whom underwent sinonasal CT. MAIN OUTCOME MEASURES Indications used for scanning, health professional (ear, nose, and throat specialist or pulmonologist) ordering the test, eventual modifications of ongoing treatment according to CT results, and time lapse between CT scanning and surgery. RESULTS Of 277 children with CF, 33 (12%) underwent a total of 39 sinonasal CT scans during the follow-up period (0.018 scans per patient per year of follow-up). Twenty-nine of the CT scans (74% of all cases, 90% of CT scans ordered by the ear, nose, and throat surgeon) were performed in the preoperative context and demonstrated the extent of the polypoid disease whenever present (26 cases [90%]) and the cause of nasal obstruction (20 cases [69%]). The mean period between the scanning and the surgery was 57 days (range, 0.10-173 days). Computed tomographic scans that were not meant for preoperative planning were performed in 10 cases (26%). The indications were disease evaluation (10%), ruling out a mucocele (5%); pre-lung transplantation status (5%), ruling out an intraorbital complication (3%); and headache investigation (3%). The results of the scans did not modify the management of the disease in those patients. CONCLUSIONS With the use of stringent criteria, it is possible to achieve a low rate of exposure to sinonasal CT scans in the population of children with CF. The main indication should be the preoperative planning regarding anatomy, extent of disease, and sites of nasal obstruction. The use of CT scans for disease evaluation does not seem to appreciably modify the treatment course and could be avoided.

Propranolol as first-line treatment of head and neck hemangiomas.

OBJECTIVES: To report the efficacy of propranolol as first-line treatment of head and neck hemangiomas in children and to present an optimized protocol for treating hemangiomas. DESIGN: Multi-institutional retrospective study. SETTING: Two tertiary care referral pediatric centers. PATIENTS: Thirty-nine children with head and neck infantile hemangiomas were treated. MAIN OUTCOME MEASURES: Review of clinical records. RESULTS: Propranolol was the sole treatment in 60% of patients and was started at a mean age of 4.1 months (age range, 1-11 months) for early interventions among 33 of 39 patients. Propranolol therapy resulted in lightening and reduction of hemangiomas at 37 of 39 locations within 2 days to 2 weeks. One subglottic hemangioma and 1 nasal tip hemangioma did not respond or showed only a partial response; in these patients, propranolol therapy was delayed and followed other treatment failures. After successful therapeutic regression, 6 recurrences occurred; when reintroduced, propranolol was again effective. Recurrences were avoided by prolonged treatment. Twenty-six hemangiomas occurring at locations for which corticosteroid treatment previously would not have been initiated (nose, lips, and parotid area) unless a complication had occurred were treated with propranolol and were rapidly controlled. The mean duration of propranolol therapy was 8.5 months. No instances of ß-blocker discontinuation because of complications occurred, but propranolol was substituted by acebutolol in 5 patients because of trouble sleeping. CONCLUSIONS: Propranolol is an effective treatment of head and neck infantile hemangiomas, especially when started early within the rapid growth phase, and is first-line treatment of orbit and larynx hemangiomas. The efficacy and tolerability of propranolol led us to treat some hemangiomas in patients whom we previously would have observed rather than subject to corticosteroid therapy. Relapse was avoided if treatment was prolonged after theoretical involution (age 12 months). Questions remain about optimal dosing and age at treatment cessation.

Nontuberculous mycobacterial cervicofacial adenitis in children: epidemiologic study.

OBJECTIVES: To determine whether there is an increase in the incidence of nontuberculous mycobacteria (NTM) adenitis at our tertiary care pediatric hospital and to determine whether there is an association between geographic location and prevalence of cases. Also, to investigate the role of nongeographic risk factors such as bacille Calmette-Guérin (BCG) vaccination in the incidence of NTM adenitis. METHOD: We conducted a retrospective chart review of 153 pediatric patients with NTM adenitis diagnosed between 1994 and 2004 and a prospective telephone survey of geographic and nongeographic risk factors for 82 patients. RESULTS: The annual incidence, calculated with the number of hospitalizations for that year as the denominator, was 25.1 in 100,000 during the 1994-1998 period and 107.4 in 100,000 for 1999-2004. A statistically significant increase in the incidence of NTM adenitis was observed after 1999, with an incidence ratio of 4.28 (95% confidence interval 2.84-6.65; p < .0000). We found a nonsignificant increase in incidence for cases in the suburbs compared with the city. The survey did not reveal any significant risk factors for NTM adenitis in our population. However, none of the affected children had had the BCG vaccination. CONCLUSION: There has been a significant increase in the incidence of NTM adenitis at our tertiary care centre, particularly since 1999. No clear risk factors could be identified to account for this increase, even though geographic location and discontinuation of BCG vaccination could be implicated. More studies are needed to confirm those hypotheses.

Obstructive neonatal respiratory distress: infected pyriform sinus cyst.

Infected lateral cervical cysts in newborn are rare. We present the case of a baby born at 41 weeks of gestation. At day 3, persistent cyanosis was noted, and a mass appeared in the left cervical region next to the sternocleidomastoid muscle. No cutaneous sinus was visible. Ultrasound imaging showed no sign of blood flow within the mass and no septae. The mass extended down to the aortic arch and pushed the trachea to the right. A cervical lymphangioma was first suspected. Puncture of the mass evacuated 80 mL of pus, and a drain was put in place. Opacification through the drain showed a tract originating from the left pyriform fossa. Preoperative laryngoscopy and catheterization of the fistula tract confirmed the diagnosis. The cyst was totally excised up to the sinus with the assistance of a guidewire inserted orally through a rigid laryngoscope. This is a rare case of an infected pyriform sinus cyst in the neonatal period.

3-year impact of a provincial choking prevention program.

OBJECTIVE: To determine the impact of a provincial choking prevention program (CPP) on the incidence of aerodigestive foreign body cases among children. METHODS: The CPP, including posters, pamphlets, an informative video, and annual participation in the Parents & Kids Fair, was launched throughout Quebec in October 1999. The incidence rates of aerodigestive foreign body cases prior to implementation (during 1997-1998) and subsequently (2000-2002) within the province and our tertiary care centre (Sainte-Justine Hospital) were compared by estimating incidence rate ratios (IRRs) and associated 95% confidence intervals (95% CIs). RESULTS: No significant changes in the incidence of aerodigestive foreign body cases after program implementation were observed in our hospital (age-adjusted IRR 0.92, 95% CI 0.79-1.07). The provincial rates were higher after program implementation (age-adjusted IRR 1.15, 95% CI 1.05-1.25). CONCLUSIONS: To influence choking prevention habits, modifications to the campaign are required. Strategies are discussed.

Subannular ventilation tubes: retrospective study.

OBJECTIVE: To evaluate the efficiency of a subannular tube insertion technique in a group of pediatric patients with adhesive otitis or severe atelectasis of the tympanic membrane. DESIGN: Retrospective nonrandomized case series. SETTING: Tertiary referral centre. MAIN OUTCOME MEASURES: The main outcomes of this study are tube duration according to the type of tube used, the complication rate, and the audiometric gain associated with this procedure. RESULTS: The study group consisted of 190 patients (316 tubes) aged between 3 and 19 years (average 9 years old) and operated on between 1993 and 1999 by four pediatric otolaryngologists. The average follow-up was 53 months. The tubes remained in place for an average of 21.8 months, with fluoroplastic tubes lasting 17.8 months and Goode T tubes lasting 23.8 months. When used in children between 5 and 9 years of age and in cases of adhesive otitis, Goode T tubes showed statistically significantly better results than fluoroplastic tubes. The complications of this technique were otorrhea (17.7%), perforation (7.9%), a plugged tube (7.0%), and cholesteatoma (1.6%). The 5- to 9-year-old group and the reintervention group of patients showed statistically higher complication rates compared with all other groups. Sixty-four patients (128 tubes) were eligible for audiogram analysis, which showed a gain of 13.4 dB (speech reception threshold). CONCLUSIONS: The technique of subannular tube insertion is a safe and effective method for long-term middle ear ventilation in cases of adhesive otitis or severely atelectatic tympanic membrane or for patients with pathology related to dysfunction of the eustachian tube. It offers an alternative to repeated short-term tube insertions for otitis media with effusion or recurrent acute otitis media.

Complications of ENT infections: pseudoaneurysm of the internal carotid artery.

Ear, nose and throat infections are common, especially in children and young adults. Since the advent of antibiotics, complications from tonsillitis and pharyngeal abscess are rare, but potentially lethal. Vascular complications can be imaged with Doppler ultrasound and CT scan. The treatment of infectious vascular complications represents a significant challenge. We describe the case of a young girl presenting with a pseudoaneurysm of the internal carotid and thrombosis of the internal jugular vein. Endovascular therapy was utilized to treat the patient.