Suppression of epithelial signal transducer and activator of transcription 1 activation by extracts of Aspergillus fumigatus.

Aspergillus fumigatus (AF) is often pathogenic in immune-deficient individuals and can cause life-threatening infections such as invasive aspergillosis. The pulmonary epithelial response to AF infection and the signaling pathways associated with it have not been completely studied. BEAS-2B cells or primary human bronchial epithelial cells were exposed to extracts of AF and challenged with IFN-ß or the Toll-like receptor 3 agonist double-stranded RNA (dsRNA). Cytokine release (B-cell activating factor of the TNF family [BAFF], IFN-γ-induced protein-10 [IP-10], etc.) was assessed. AF extract was separated into low-molecular-weight (LMW) and high-molecular-weight (HMW) fractions using ultra 4 centrifugal force filters to characterize the activity. Real-time PCR was performed with a TaqMan method, and protein estimation was performed using ELISA techniques. Western blot was performed to assess phosphorylation of signal transducer and activator of transcription 1 (STAT1). IFN-ß and dsRNA induced messenger RNA (mRNA) expression of BAFF (350- and 452-fold, respectively [n = 3]) and IP-10 (1,081- and 3,044-fold, respectively [n = 3]) in BEAS-2B cells. When cells were pretreated with AF extract for 1 hour and then stimulated with IFN-ß or dsRNA for 6 hours, induction of BAFF and IP-10 mRNA was strongly suppressed relative to levels produced by IFN-ß and dsRNA alone. When compared with control, soluble BAFF and IP-10 protein levels were maximally suppressed in dsRNA-stimulated wells treated with 1:320 wt/vol AF extract (P < 0.005). Upon molecular size fractionation, a LMW fraction of AF extract had no measurable suppressive effect on IP-10 mRNA expression. However, a HMW fraction of the AF extract significantly suppressed IP-10 expression in BEAS-2B cells that were stimulated with dsRNA or IFN-ß. When BEAS-2B cells were pretreated with AF extract and then stimulated with IFN-ß, reduced levels of pSTAT1 were observed, with maximum suppression at 4 and 6 hours. Our results show that AF extracts suppressed expression of inflammatory cytokines in association with inhibition of the IFN-ß signaling pathway and suppression of the formation of pSTAT1.

Preliminary data using computed tomography texture analysis for the classification of hypervascular liver lesions: generation of a predictive model on the basis of quantitative spatial frequency measurements--a work in progress.

OBJECTIVE: Computed tomography texture analysis (CTTA) is a method of quantifying lesion heterogeneity based on distribution of pixel intensities within a region of interest. This study investigates the ability of CTTA to distinguish different hypervascular liver lesions and compares CTTA parameters by creating a proof-of-concept model to distinguish between different lesions. METHODS: Following institutional review board approval, CTTA software (TexRAD Ltd) was used to retrospectively analyze 17 cases of focal nodular hyperplasia, 19 hepatic adenomas, 25 hepatocellular carcinomas, and 19 cases of normal liver parenchyma using arterial phase scans. Two radiologists read the same image series used by the CTTA software and reported their best guess diagnosis. Computed tomography texture analysis parameters were computed from regions of interest using spatial band-pass filters to quantify heterogeneity. Random-forest method was used to construct a predictive model from these parameters, and a separate regression model was created using a subset of parameters. RESULTS: The random-forest model successfully distinguished the 3 lesion types and normal liver with predicted classification performance accuracy for 91.2% for adenoma, 94.4% for focal nodular hyperplasia, and 98.6% for hepatocellular carcinoma. This error prediction was generated using a subset of data points not used in generation of the model, but not on discrete prospective cases. In contrast, the 2 human readers using the same image series data analyzed by the CTTA software had lower accuracies, of 72.2% and 65.6%, respectively. The explicit regression model with a subset of image parameters had intermediate overall accuracy of 84.9%. CONCLUSIONS: Computed tomography texture analysis may prove valuable in lesion characterization. Differentiation between common hypervascular lesion types could be aided by the judicious incorporation of texture parameters into clinical analysis.

Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis.

BACKGROUND: Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. METHODS: We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m(2)) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5-6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. FINDINGS: Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). INTERPRETATION: Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. FUNDING: None.

Clinical indicators that predict the presence of moderate to severe obstructive sleep apnea after adenotonsillectomy in children.

OBJECTIVE: To determine if clinical indicators can predict the presence of moderate to severe Obstructive Sleep Apnea (OSA) after Adenotonsillectomy (T&A) in children. STUDY DESIGN: Retrospective study. SETTING: Urban Tertiary Care Pediatric Hospital. METHODS: Parents of children (<18 yrs.) with OSA completed a 55-item questionnaire based on their child's symptoms at the time of preoperative polysomnography and then again at the follow up polysomnography completed 3 to 6 months after T&A. MAIN OUTCOME MEASURES: 55 item questionnaire, polysomnography variables. RESULTS: 97 children were included (59 Male and 38 Female). The mean preoperative apnea hypopnea index (AHI) was 30.5±31.6/h and the mean postoperative AHI was 4.4±6.0/h. After T&A, all 97 children had reduction in AHI, and 35 (36.1%) no longer had OSA (AHI<1/h). The total symptom scores decreased from 15.8±9.4 to 11.3±8.7 after T&A (p<.0001). Fourteen symptoms highly predictive of moderate to severe OSA were identified in the univariate analysis (p<0.1). Using a cut-point of 4, this 14-item subscale illustrated an overall predictability of 72.2% (73.7% sensitivity and 70.0% specificity) for identifying children with moderate to severe OSA. CONCLUSION: A cluster of 14 clinical sleep symptoms are highly predictive of moderate to severe OSA and can serve as clinical predictor for the presence of moderate to severe OSA after T&A.

Effect of a cooling vest on core temperature in athletes with and without spinal cord injury.

BACKGROUND: It is well accepted that persons with spinal cord injury (SCI) have impaired ability to regulate core temperature due to impaired vasomotor and sudomotor activity below their level of injury. Impaired heat dissipation puts SCI athletes at great risk of exercise-induced hyperthermia (EIH) (>37.8°C). There is minimal evidence for efficacy of any specific cooling method in SCI athletes in a thermoneutral sport-specific setting. OBJECTIVE: To evaluate the extent of EIH in persons with and without SCI and subsequently examine the effect of a cooling vest to attenuate rise in core body temperature (Tc). METHODS: SCI (n = 17) and able-bodied (AB; n = 19) athletes participated in a 60-minute intermittent sprinting exercise in a thermoneutral (21.1°C-23.9°C) environment. Participants were separated according to their level of injury: tetraplegia defined as above T1 (TP; n = 6), high paraplegia defined as T5 through T1 (HP; n = 5), low paraplegia defined as T6 and below (LP; n = 6), and AB (n = 19). Tc was recorded at 15-minute intervals using an ingestible thermometer pill. This protocol was completed with a cooling vest (V) and without a cooling vest (NV). RESULTS: All SCI and most AB athletes experienced EIH. After 60 minutes, Tc of TP athletes was significantly increased compared to HP (P = .03) and AB athletes (P = .007). There was no significant effect of the vest on Tc over time for any group. CONCLUSIONS: TP athletes have the highest risk of exercise-induced hyperthermia. The cooling vest does not significantly attenuate rise in Tc in SCI or AB athletes.

International pediatric otolaryngology group (IPOG) consensus on approach to aspiration.

OBJECTIVE: To provide recommendations for a comprehensive management approach for infants and children presenting with symptoms or signs of aspiration. METHODS: Three rounds of surveys were sent to authors from 23 institutions worldwide. The threshold for the critical level of agreement among respondents was set at 80 %. To develop the definition of "intractable aspiration," each author was first asked to define the condition. Second, each author was asked to complete a 5-point Likert scale to specify the level of agreement with the definition derived in the first step. RESULTS: Recommendations by the authors regarding the clinical presentation, diagnostic considerations, and medical and surgical management options for aspiration in children. CONCLUSION: Approach to pediatric aspiration is best achieved by implementing a multidisciplinary approach with a comprehensive investigation strategy and different treatment options.

Fiberoptic Endoscopic Evaluation of Swallowing in the Breastfeeding Infant.

OBJECTIVE: To demonstrate the importance of utilizing fiberoptic endoscopic evaluation of swallowing (FEES) when evaluating breastfeeding infants with suspected dysphagia. Failure to recognize and account for the fundamentally different physiology of the primarily breastfed infant can lead to false assumptions about the safety of breastfeeding in this understudied patient population. METHODS: Case-series. The medical records of patients referred to an urban, university-based, pediatric hospital for FEES from February 2017 to October 2020 were reviewed. Their presenting symptoms, dysphagia severity, comorbidity, dysphagia workup, and management were analyzed. The standardized Dysphagia Outcome and Severity Scale was used to appraise dysphagia severity. RESULTS: 204 FEES exams were reviewed. 35 were conducted on breastfed infants. 34 of the 35 infants calmed for the FEES exam while breastfeeding. Cohorts were defined by a particular presenting sign (cough, laryngeal congestion, choking, and respiratory illness) and anatomical characteristic (laryngomalacia, vocal cord paralysis, aspiration, penetration, etc.) and then compared to all other exams. The average dysphagia score for all the exams was 2.37. Patients presenting with laryngeal congestion had an average dysphagia score of 2.81. There was no difference in dysphagia score based on comorbidities or anatomy. CONCLUSIONS: FEES is the instrumental exam of choice when evaluating a primarily breastfed infant who has suspected dysphagia. The exam is well tolerated and provides accurate, objective information while accounting for this population's unique swallowing physiology. Primarily breastfed infants presenting with laryngeal congestion are more likely to have clinically worse dysphagia than those presenting with other clinical symptoms. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2803-2807, 2023.

Associations of deep sleep and obstructive sleep apnea with family relationships, life satisfaction, and physical stress experience in children: a caregiver perspective.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and poor quality of sleep negatively impacts health-related quality of life in adults, but few studies have evaluated the association between sleep disturbance (eg, OSA, inadequate sleep) and health-related quality of life domains (eg, family relations, life satisfaction) in children. METHODS: Children ages 8-17 years referred to a sleep center for routine polysomnography from April 2022 to August 2022 were approached to participate in the study, and children visiting the department of pediatrics for their wellness visit were recruited for comparisons. Statistical analysis was conducted using R 3.6.0. RESULTS: Ninety-nine children were recruited from the sleep clinic, and 23 children were recruited from the primary care clinic. Of these children, 62 were diagnosed with obstructive sleep apnea (31 mild, 12 moderate, 19 severe), and 37 did not meet criteria for a diagnosis. Health-related quality of life domains did not differ across OSA severity levels. Children in general had lower life satisfaction and higher physical stress experience compared to children visiting for their wellness examination (well-child visitors, P = .05 and P = .005, respectively). Children with severe OSA had significantly lower life satisfaction and significantly higher physical stress experience when compared with well-child visitors (P = .008 and P = .009, respectively). Correlation analysis showed that N3 (deep) sleep was positively associated with family relations and life satisfaction, while it was negatively associated with anger. CONCLUSIONS: Based on caregiver response, N3 sleep is positively associated with family relations and life satisfaction and negatively associated with anger. Severe OSA is associated with lower life satisfaction and higher physical stress experience. CITATION: Bhushan B, Zee PC, Grandner MA, et al. Associations of deep sleep and obstructive sleep apnea with family relationships, life satisfaction, and physical stress experience in children: a caregiver perspective. J Clin Sleep Med. 2023;19(12):2087-2095.

Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial.

BACKGROUND: Non-randomised studies of haemopoietic stem-cell transplantation (HSCT) in systemic sclerosis have shown improvements in lung function and skin flexibility but high treatment-related mortality. We aimed to assess safety and efficacy of autologous non-myeloablative HSCT in a phase 2 trial compared with the standard of care, cyclophosphamide. METHODS: In our open-label, randomised, controlled phase 2 trial, we consecutively enrolled patients at Northwestern Memorial Hospital (Chicago, IL, USA) who were aged younger than 60 years with diffuse systemic sclerosis, modified Rodnan skin scores (mRSS) of more than 14, and internal organ involvement or restricted skin involvement (mRSS <14) but coexistent pulmonary involvement. We randomly allocated patients 1:1 by use of a computer-generated sequence with a mixed block design (blocks of ten and four) to receive HSCT, 200 mg/kg intravenous cyclophosphamide, and 6·5 mg/kg intravenous rabbit antithymocyte globulin or to receive 1·0 g/m(2) intravenous cyclophosphamide once per month for 6 months. The primary outcome for all enrolled patients was improvement at 12 months' follow-up, defined as a decrease in mRSS (>25% for those with initial mRSS >14) or an increase in forced vital capacity by more than 10%. Patients in the control group with disease progression (>25% increase in mRSS or decrease of >10% in forced vital capacity) despite treatment with cyclophosphamide could switch to HSCT 12 months after enrolment. This study is registered with ClinicalTrials.gov, number NCT00278525. FINDINGS: Between Jan 18, 2006, and Nov 10, 2009 we enrolled 19 patients. All ten patients randomly allocated to receive HSCT improved at or before 12 months' follow-up, compared with none of nine allocated to cyclophosphamide (odds ratio 110, 95% CI 14·04-∞; p=0·00001). Eight of nine controls had disease progression (without interval improvement) compared with no patients treated by HSCT (p=0·0001), and seven patients switched to HSCT. Compared with baseline, data for 11 patients with follow-up to 2 years after HSCT suggested that improvements in mRSS (p<0·0001) and forced vital capacity (p<0·03) persisted. INTERPRETATION: Non-myeloablative autologous HSCT improves skin and pulmonary function in patients with systemic sclerosis for up to 2 years and is preferable to the current standard of care, but longer follow-up is needed. FUNDING: None.

Short communication: Subcellular motion compensation for minimally invasive microscopy, in vivo: evidence for oxygen gradients in resting muscle.

RATIONALE: In vivo microscopy seeks to observe dynamic subcellular processes in a physiologically relevant context. A primary limitation of optical microscopy in vivo is tissue motion, which prevents physiological time course observations or image averaging. OBJECTIVE: To develop and demonstrate motion compensation methods that can automatically track image planes within biological tissues, including the tissue displacements associated with large changes in blood flow, and to evaluate the effect of global hypoxia on the regional kinetics and steady state levels of mitochondrial NAD(P)H. METHODS AND RESULTS: A dynamic optical microscope, with real-time prospective tracking and retrospective image processing, was used collect high-resolution images through cellular responses to various perturbations. The subcellular metabolic response to hypoxia was examined in vivo. Mitochondria closest to the capillaries were significantly more oxidized at rest (67+/-3%) than the intrafibrillar mitochondria (83+/-3%; P<0.0001) in the same cell. CONCLUSIONS: These data are consistent with the hypothesis that a significant oxygen gradient from capillary to muscle core exists at rest, thereby reducing the oxidative load on the muscle cell.

Three-dimensional motion tracking for high-resolution optical microscopy, in vivo.

When conducting optical imaging experiments, in vivo, the signal to noise ratio and effective spatial and temporal resolution is fundamentally limited by physiological motion of the tissue. A three-dimensional (3D) motion tracking scheme, using a multiphoton excitation microscope with a resonant galvanometer, (512 × 512 pixels at 33 frames s(-1)) is described to overcome physiological motion, in vivo. The use of commercially available graphical processing units permitted the rapid 3D cross-correlation of sequential volumes to detect displacements and adjust tissue position to track motions in near real-time. Motion phantom tests maintained micron resolution with displacement velocities of up to 200 µm min(-1), well within the drift observed in many biological tissues under physiologically relevant conditions. In vivo experiments on mouse skeletal muscle using the capillary vasculature with luminal dye as a displacement reference revealed an effective and robust method of tracking tissue motion to enable (1) signal averaging over time without compromising resolution, and (2) tracking of cellular regions during a physiological perturbation.

Evaluating dysphagia in infants with congenital heart disease using Fiberoptic Endoscopic Evaluation of Swallowing.

OBJECTIVE: Dysphagia is common in infants with congenital heart disease (CHD). However, there is minimal published data regarding its management outside of the perioperative period. The objective of this study is to describe the role of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in the diagnosis and management of dysphagia in infants with CHD. METHODS: Infants with CHD who underwent FEES exam for evaluation of swallowing dysfunction between February 2015 and February 2021 at a university-based, tertiary care urban pediatric hospital were studied. Demographic data, presenting symptoms, medical history, and dysphagia history were examined. The validated Dysphagia Outcome and Severity Scale (DOSS) was used to standardize and compare dysphagia severity. RESULTS: 62 FEES exams were performed on 48 patients. All 48 patients were diagnosed with dysphagia and had a mean dysphagia severity score (DOSS) of 2.68. Patients with wet laryngeal congestion on presentation had worse mean DOSS score and were more likely to demonstrate aspiration on FEES exam (p < 0.01). There was no significant difference in mean DOSS or presence of aspiration when comparing infants who had cardiothoracic surgery, vocal cord paralysis, or lower respiratory tract illness with those who had not (p > 0.05). CONCLUSION: A FEES exam is an effective and well-tolerated procedure for evaluating swallowing dysfunction in pediatric patients with CHD and its use reduces radiation exposure for this vulnerable population. Wet laryngeal congestion was found to be predictive of more severe dysphagia and aspiration. There is no significant association between severity of dysphagia or aspiration on FEES exam and history of cardiac surgery, vocal cord paralysis, or lower respiratory tract illness.

Diagnosis and management of type I posterior laryngeal clefts.

OBJECTIVES: We review the diagnosis and management of type I posterior laryngeal clefts (PLCs). METHODS: We performed a retrospective study at a tertiary-care children's hospital of children who were diagnosed with a PLC between January 2003 and August 2008. We studied concurrent airway anomalies, comorbidities, presenting symptoms, age at the time of aspiration resolution, and rate of aspiration resolution. RESULTS: Sixty-seven children with PLCs were identified (41 boys and 26 girls). Fifty-nine had type I clefts, 6 had type II, and 2 had type III. Of the 59 type I cases, 15 (25.4%) were surgically repaired by endoscopy. Eleven of these 15 children (73.3%) have had symptomatic improvement since the surgery, and 7 of those 11 (63.6%) are tolerating thin liquids by mouth. Two of the 15 (13.3%) displayed no improvement with surgery, and 2 of the 15 (13.3%) were lost to follow-up. Forty-four of the 59 type I clefts (74.6%) were managed nonsurgically. Twenty of these 44 children (45.5%) did not present with aspiration. Twenty-four of the 44 (54.5%) presented with aspiration, and 16 of the 24 (66.7%) are now tolerating thin liquids by mouth. Seven of these 24 patients (29.2%) are still aspirating, and 1 has died. The average time to resolution of aspiration was 7.8 months for the surgical group and 13.6 months for the nonsurgical group (p = 0.19). In the surgical group, the average age at resolution of aspiration for patients who received their diagnosis at 0 to 6 months of age was 21.5 months; that for those with a diagnosis at 6 to 12 months was 27.3 months; and that for those with a diagnosis at older than 12 months was 27.3 months (p = 0.31). In the nonsurgical group, the average age at resolution of aspiration for patients who received their diagnosis at 0 to 12 months of age was 15.8 months; that for those with a diagnosis at 12 to 24 months was 27.3 months; and that for those with a diagnosis at older than 24 months was 77.3 months (p = 0.0015). CONCLUSIONS: We found that (1) the reported incidence of type I PLCs is increasing; (2) type I PLCs can often present without clinical aspiration; (3) aspiration caused by type I PLCs can be managed medically or surgically; and (4) operative intervention is advantageous for patients who have severe symptoms or who have persistent aspiration after 2 years of age.

Fiberoptic Endoscopic Evaluation of Swallowing Across the Age Spectrum.

Purpose Fiberoptic endoscopic evaluation of swallowing (FEES) is a widely used instrumental procedure used to assess swallowing function in persons of all ages, from infants to older adults. In this article, the history of FEES in adults, the protocol, the scoring system, and the interpretation of abnormal findings are summarized. The use of FEES to guide treatment in adults is also covered briefly. Following this review in adults, the use of FEES in infants and children is presented, including the anatomical-physiological assessment and the assessment of swallowing of food and liquid. Interpretation of findings and therapeutic applications are discussed. Conclusion FEES is a valuable part of the clinical protocol for evaluation and management of dysphagia across the life span. It provides a mechanism for in-depth analysis of swallowing structures and function during intake of liquid and food boluses. Future developments include standardized training content to ensure clinical competency and the development of standardized examination and interpretation protocols.

Polysomnography Outcomes after Supraglottoplasty in Children with Obstructive Sleep Apnea.

OBJECTIVE: Laryngomalacia has been reported to contribute to the severity of obstructive sleep apnea (OSA) in children. It is unclear if surgical treatment of laryngomalacia improves polysomnography (PSG) outcomes in these patients. The objective of this study is to report the impact of supraglottoplasty on PSG parameters in children with laryngomalacia-related OSA. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: Historical cohort study of consecutive children with laryngomalacia who underwent supraglottoplasty and who had undergone overnight PSG before and after surgery. RESULTS: Forty-one patients were included in the final analysis: 22 (53.6%) were male, and 19 (46.3%) were female. The mean ± SEM age of patients at preoperative PSG was 1.3 ± 0.89 years (range, 0.003-2.9). In entire cohort, the mean obstructive apnea-hypopnea index score was reduced from 26.6 events/h before supraglottoplasty to 7.3 events/h after surgery (P = .003). Respiratory disturbance index was reduced from 27.3 events/h before supraglottoplasty to 7.8 events/h after surgery (P = .003). The percentage of REM sleep decreased from 30.1% ± 2.4 to 24.8% ± 1.3 (P = .04). Sleep efficiency was improved (P = .05). CONCLUSION: Overall, supraglottoplasty significantly improved several PSG outcomes in children with laryngomalacia. However, mild to moderate OSA was still present postoperatively in most children. This suggested a multifactorial cause for OSA in this population.

Congenital laryngeal stenosis.

Congenital subglottic stenosis is rare and as a consequence may not be considered in children experiencing respiratory difficulty at birth. Diagnosis after a child already is intubated complicates the recognition and blurs the boundary between congenital and acquired lesions. This article discusses the anatomy of the larynx, its common anatomic variations, and its response to trauma, a thorough understanding of which is required for the accurate diagnosis and treatment of this complicated problem. The authors discuss evaluation and assessment options to guide treatment.

Aspiration following CO(2) laser-assisted supraglottoplasty.

OBJECTIVE: To review the incidence, risk factors, and treatment of aspiration following CO(2) laser-assisted supraglottoplasty for severe laryngomalacia (LM). DESIGN: IRB approved retrospective study of pediatric patients with severe LM treated with CO(2) laser supraglottoplasty over a 5-year period. SETTING: Tertiary pediatric hospital. PATIENTS: Fifty-two patients met inclusion criteria. Indication for supraglottoplasty was respiratory distress in 90% of patients and/or failure to thrive in 19%. INTERVENTIONS: All children underwent bilateral CO(2) laser supraglottoplasty and were assessed postoperatively with swallow evaluation by a speech pathologist. Videoflouroscopic evaluation was utilized to confirm aspiration and guide management. MAIN OUTCOME MEASURES: Aspiration, treatment required to manage aspiration, duration of treatment required. RESULTS: Thirty-seven percent (20/52) of patients had postoperative aspiration. Aspiration was demonstrated on videoflouroscopic swallow study (VFSS) after supraglottoplasty is 28% (12/43). All patients with newly diagnosed aspiration had treatment with thickened and/or nasogastric feedings with mean resolution time of 6 months. In nine children with preoperative aspiration, eight (89%) had postoperative aspiration and seven required gastrostomy tube placement for feeding management. All individuals requiring gastrostomy for aspiration management had neurological conditions. In the absence of preoperative clinically evident aspiration, children with neurological conditions have an equivalent rate of postoperative aspiration as healthy children. The only risk factor for postoperative aspiration was preoperative aspiration. CONCLUSION: Aspiration is more common after CO(2) laser-assisted supraglottoplasty than previously recognized. In otherwise healthy children, postoperative aspiration is of short duration and can be treated with conservative measures. Optimal treatment after supraglottoplasty includes screening for and management of aspiration in conjunction with a speech pathologist.

A Chronic Glottic Foreign Body Diagnosed by Radiograph after 9 Months of Symptoms.

A six-year-old girl presented to an emergency room after describing choking on a rubber band. She was in no distress and was discharged. Over the course of the next 9 months, she had numerous outpatient and emergency room visits due to intermittent stridor, difficulty breathing, and hoarseness. Eventually, dedicated airway films revealed a laryngeal foreign body. During rigid bronchoscopy, a two-centimeter rubber band was discovered in the larynx. It extended from the supraglottis, through the glottis, and into the subglottis. It was successfully removed. The patient was asymptomatic 24 hours later. This case highlights the appropriate evaluation and management of a child with stridor.

Five year follow-up after autologous peripheral blood hematopoietic stem cell transplantation for refractory, chronic, corticosteroid-dependent systemic lupus erythematosus: effect of conditioning regimen on outcome.

Some patients with systemic lupus erythematosus (SLE) are refractory to traditional therapies, dependent on chronic corticosteroids, have organ damage, and are at high risk of mortality. In this group of patients, we report outcome at a median of five years after autologous hematopoietic stem cell transplant (HSCT) using two different non-myeloablative regimens. Four patients received a conditioning regimen of cyclophosphamide (200 mg/kg) and alemtuzumab (60 mg), while 26 patients underwent conditioning with cyclophosphamide (200 mg/kg), rATG (Thymoglobulin) (5.5 mg/kg), and rituximab 1000 mg. Unselected peripheral blood stem cells were infused on day 0. There were no treatment related deaths. Of the four patients treated with cyclophosphamide and alemtuzumab, none entered remission. For the 26 patients treated with cyclophosphamide, rATG, and rituximab, disease remission defined as no immune suppressive drugs except hydroxychloroquine and/or 10 mg or less of prednisone a day was 92% at 6 months, 92% at one year, 81% at 2 years, 71% at 3 years, and 62% at 4 and 5 years post-HSCT. Autologous HSCT outcome is dependent on the conditioning regimen but prior organ damage may cause lingering symptoms.