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Background: Pediatric laryngotracheal stenosis often requires open airway reconstruction. While these surgeries establish an airway for adequate ventilation, many patients develop subsequent dysphonia. Numerous studies have reported outcomes related to voice. Objective: This study aims to evaluate dysphonia in pediatric patients following open airway reconstruction, focusing on acoustic parameters, perceptual voice quality, and voice-related quality of life. Methods: A comprehensive search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across 6 databases identified articles involving pediatric patients who underwent open airway reconstruction and reported postoperative vocal acoustic parameters, perceptual voice quality, voice-related quality of life, or vocal mechanics. Articles were assessed for bias risk, and common outcomes were synthesized qualitatively and quantitatively using meta-analyses. Results: Among 4089 articles, 21 were included, involving 497 pediatric patients. Laryngotracheoplasty was the most common procedure followed by cricotracheal resection. The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) scale was frequently used to assess voice quality, with a mean score of 55.6 [95% confidence intervals (CIs): 47.9-63.3]. Voice-related quality of life was measured using the pediatric Voice Handicap Index (pVHI) and Pediatric Voice-Related Quality of Life Survey, with mean scores of 35.6 (95% CI: 21.4-49.7) and 83.7 (95% CI: 74.1-93.2), respectively. The fundamental frequency was 210.5 (95% CI: 174.6-246.3). Other common findings included supraglottic phonation, anterior commissure blunting, posterior glottic diastasis, and abnormal vocal cord mobility. Conclusion: Pediatric patients experiencing dysphonia after open airway reconstruction exhibited moderately decreased voice quality and reduced voice-related quality of life. However, there was inconsistency in study protocols and outcome measures used. Preserving voice quality during airway reconstruction is crucial to avoid negative impacts on quality of life. [ABSTRACT FROM AUTHOR]

Objective: The first pediatric tracheostomy tube change often occurs within 7 days after placement; however, the optimal timing is not known. The primary objective was to determine the rate of adverse events of an early tube change. Secondary objectives compared rates of significant peristomal wounds, sedation requirements, and expedited intensive care discharges.Study Design: Prospective randomized controlled trial.Setting: Tertiary children's hospital between October 2018 and April 2020.Methods: A randomized controlled trial enrolled children under 24 months to early (day 4) or late (day 7) first tracheostomy tube changes.Results: Sixteen children were enrolled with 10 randomized to an early change. Median age was 5.9 months (interquartile range, 5.4-8.3), and 86.7% required tracheostomy for respiratory failure. All tracheostomy tube changes were performed without adverse events. There were no accidental decannulations. Significant wounds developed in 10% of children with early tracheostomy tube changes and 83.3% of children with late tracheostomy tube changes (odds ratio [OR], 45.0; 95% CI, 2.3-885.6; P = .01). This significant reduction in wound complications justified concluding trial enrollment. Hours of dexmedetomidine sedation (P = .11) and boluses of midazolam during the first 7 days (P = .08) were no different between groups. After the first change, 90% of the early group were discharged from intensive care within 5 weeks compared to 33.3% of patients in the late group (OR, 18.0; 95% CI, 1.2-260.9; P = .03).Conclusion: The first tracheostomy tube change in children can occur without adverse events on day 4, resulting in fewer significant peristomal wounds and earlier intensive care discharge. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is an iron-binding glycoprotein present in secretory fluids from human and bovine sources. Sequence alignment was employed to identify a region on the C-lobe of Lf capable of binding to bacterial cell surfaces, followed by all-atom explicit solvent molecular dynamics simulations to study the conformational changes of Lf after exposure to three processing temperatures: pasteurisation (72°C), spray drying (90°C) and ultra-high temperature (UHT) (127°C). Below 90°C, the simulations indicate relatively minor changes in overall protein structure. At UHT conditions (127°C), however, marked disruptions to protein structure were found as demonstrated by a substantial decrease in protein dimensions due to collapse in the inter-lobe region. There was also a marked increase in residue fluctuations in several regions of known functional importance, including antibacterial, iron-binding, and putative membrane binding regions, the latter of which is stabilised by a triplet of hydrophobic residues comprised of Leu446, Trp448 and Leu451 at low temperature, but which are disrupted under UHT conditions. A unique network analysis confirmed these results as demonstrated by large clusters of residues with increased dynamical correlation in the N-terminal lobe. [ABSTRACT FROM AUTHOR]

The minor protein in milk, lactoferrin (Lf), is known for a variety of biological functions, and has been investigated as a protective encapsulant for probiotic bacteria in health-promoting food products. Lf is likely to be exposed to extreme pH conditions which are known to have disruptive influences on its functionality. The molecular mechanisms underlying these pH-dependent changes are not wellunderstood. To explore the potential of Lf as an encapsulant, molecular dynamics (MD) simulations were applied to study its conformational changes under extreme acidic (pH 1.0) or basic (pH 14.0) conditions, relative to neutral pH. Simulations indicate that the structure of apo-Lf is relatively stable at neutral pH, while acidic and basic pH result in substantially greater flexibility, partly induced by the loss of contacts between the N- and C-terminal lobes, causing them to undergo extensive relative bending and twisting motions. Basic pH causes greater structural disruption compared to acidic exposure. The latter has greater influence on the N-terminus, with increased fluctuations and disruptions of interresidue contacts compared to those at neutral pH; while basic pH was found to more prominently disrupt contacts at the C-terminus. These results help elucidate possible functional consequences on Lf of exposure to extreme pH conditions. [ABSTRACT FROM AUTHOR]

Background: In otologic surgery good visualization is paramount, and patients with bleeding diatheses or who need to be anti-coagulated can present a significant challenge. Here, we determine whether Floseal™, a hemostatic matrix, is ototoxic in a validated animal model. Methods: Nine chinchillas housed in the animal care facilities of the Montreal Children's Hospital Research Institute were used for the study. After a myringotomy incision was made in each tympanic membrane, baseline auditory brainstem response measurements were performed at 8, 20, and 25 kHz. In each animal one ear was randomized to receive Floseal™ to the middle ear cavity, whereas the other ear served as the control and received 0.9% sodium chloride. Outcome measures included early (day 7) and late (day 30) auditory brainstem response, clinical evidence of facial nerve or vestibular disturbance and histological evidence of ototoxity. Results: There was no significant hearing threshold shift on auditory brainstem response across all tested frequencies for both experimental and control ear. No animals receiving Floseal™ developed facial or vestibular nerve dysfunction and there was no histological evidence of ototoxicity. Conclusion: Based on the preliminary ototoxicity assessment on nine chinchillas, transtympanic Floseal™ does not appear to be ototoxic. More studies are warranted to assess the safety and applicability of the product in humans. [ABSTRACT FROM AUTHOR]

Objective: Hypocalcemia following thyroidectomy often prolongs hospital stay and is potentially life-threatening. The objective of this study is to determine whether the season when thyroidectomy is performed is associated with postoperative hypocalcemia.Study Design: Retrospective case series of patients undergoing thyroid surgery from 2009 to 2015.Setting: Tertiary care academic institution in Montreal, Canada.Subjects and Methods: A consecutive sample of 823 patients undergoing thyroidectomy by a single high-volume otolaryngologist for a suspected or confirmed thyroid malignancy. Patient demographics, procedure type, calcium and vitamin D supplementation, and seasonal rate of hypocalcemia postthyroidectomy were calculated and compared.Results: Average seasonal rates of postthyroidectomy hypocalcemia in the winter, spring, summer, and autumn were, respectively, 8.3% (8 of 216), 7.3% (12 of 165), 1.5% (3 of 201), and 3.5% (8 of 228; P < .005). Patients operated in the winter were 5.6 times more likely to develop hypocalcemia as compared with those in the summer (P < .01; 95% confidence interval: 1.7-18.7). In a multiple regression analysis factoring in season when surgery was performed, procedure type, and preoperative vitamin D/calcium supplementation, surgery occurring in the winter predicted a hypocalcemia event (correlation coefficient [SE]: 0.72 [0.024], P = .026; 0.006 [0.025], P = .81; 0.004 [0.019], P = .82, respectively).Conclusion: In this study, patients undergoing thyroidectomy in the winter months were more likely to develop postoperative hypocalcemia when compared with those operated in the summer. Further studies are needed to understand the role of vitamin D in the observed seasonal difference in hypocalcemia rates. [ABSTRACT FROM AUTHOR]

Objective: To determine whether patients with vitamin D deficiency (VDD) are at increased risk for hypocalcemia following total thyroidectomy. Methods: A retrospective study of 246 consecutive patients undergoing thyroidectomy at a McGill University teaching hospital was conducted. Patients who had subtotal thyroidectomy or concomitant parathyroidectomy or whose laboratory tests were incomplete for analysis were excluded, as were pediatric patients. The remaining 139 patients had preoperative 25-hydroxyvitamin D [25(OH)D], corrected calcium, and parathyroid hormone (PTH) measured. Postoperatively, PTH and serum calcium were measured to assess for hypocalcemia. Low vitamin D (LVD) was defined as 25(OH)D ≤ 70 nmol/L (≤ 28 ng/mL), which includes vitamin D insufficiency, 25(OH)D > 35 nmol/L (>14 ng/mL) but ≤70nmol/L (≤28 ng/mL), and VDD, 25(OH)D ≤35nmol/L (≤14 ng/mL). Adequate vitamin D (AVD) corresponded to levels > 35 nmol/L (> 14 ng/mL), whereas optimal vitamin D (OVD) levels corresponded to levels > 70 nmol/L (> 28 ng/mL). Results: The rate of postthyroidectomy hypocalcemia in OVD patients was 10.4% (8 of 77) compared to 3.2% (2 of 62) in LVD patients (odds ratio = 0.29, p = .10). There was no hypocalcemia in the 9 VDD patients, meaning that all hypocalcemic episodes occurred in patients with AVD (7.7%; 10 of 130). The mean preoperative PTH levels for LVD patients was 4.65 pmol/L (43 ng/L) compared to 4.18 pmol/L (38.9 ng/L) for OVD patients (p = .073). Conclusions: In this series, preoperative LVD did not predict early postthyroidectomy hypocalcemia. On the contrary, it showed a trend toward protective effect. Adaptive changes in the parathyroid glands, such as hypertrophy, hyperplasia, or the ability to secrete more hormone secondary to prolonged VDD, may contribute to this phenomenon. A large prospective study is needed to better understand the relationship between preoperative vitamin D levels and postoperative hypocalcemia. [ABSTRACT FROM AUTHOR]

Recently, we have identified proinsulin (P-Ins)73-90 as an immunodominant T cell epitope of HLA-DRB1*0401 (DR4) subjects with β-islet cell autoimmunity and of HLA-DR4/CD4 double-transgenic mice immunized with human P-Ins. We have compared the fine specificities of one human CD4 T cell clone and two mouse T cell hybridoma clones recognizing this epitope, and, although these three clones all recognized the same core region (LALEGSLQK), there were major differences in how they interacted with the peptide (p)/HLA complex, reflecting the fact that human P-Ins is a foreign antigen in the mouse and an autoantigen in the type 1 diabetes patient. The human T cell clone was forkhead transcription factor 3 (Foxp3)-positive, a marker for regulatory T cell lineages, and secreted predominantly IL-5, IL-10, and low levels of IFNγ in response to P-Ins73-90. This finding is compatible with the previously detected regulatory cytokine pattern in subjects with β-cell autoimmunity. However, added N- or C-terminal amino acids drastically changed HLA and tetramer binding capacity as well as T cell reactivity and the cytokine phenotype of the P-Ins73-90-specific human CD4T-cell clone, suggesting a potential for this P-Ins epitope as a target for therapeutic intervention in HLA-DR4-positive humans with β-islet cell autoimmunity or recent-onset type 1 diabetes. [ABSTRACT FROM AUTHOR]