Etiologies of hearing loss in Fanconi Anemia.

OBJECTIVES: We aim to describe types of hearing loss associated with Fanconi anemia patients who underwent a bone marrow transplant (BMT) to identify possible etiologies of hearing loss. Additionally, we hope to investigate hearing loss early in life as a potential predictor of needing a BMT surgery. Fanconi anemia is a rare autosomal recessive disease that is the most common inherited bone marrow failure syndrome, characterized by bone marrow failure and multiple congenital anomalies, including hearing loss. This is the largest study to date reviewing types of hearing loss in patients with Fanconi anemia, specifically in those who have undergone BMTs. METHODS: A retrospective chart review of patients diagnosed with Fanconi anemia at a single institution, tertiary, referral-based children's hospital with a bone marrow transplant team specializing in Fanconi anemia was conducted from 4/19/1976 to 10/19/2015. History, physical examination, audiometry, and imaging findings were reviewed in patients with and without history of bone marrow transplant. Patient hearing levels, as measured by pure tone audiometry at 500 Hz, 1, 2, and 4 kHz, were evaluated. Patients were grouped by transplant status and results and were assessed to determine type and degree of hearing loss. Statistical analysis was performed to compare the likelihood of bone marrow transplant procedures in Fanconi anemia patients with normal and abnormal hearing. RESULTS: There were 252 patients with Fanconi anemia identified via diagnosis search in institutional electronic medical records using CPT codes and cross referencing with the Fanconi Anemia database, 58 of whom had available audiometric data. Of the 58 Fanconi anemia patients with available audiograms, 21 (36%) had abnormal audiograms; 37 patients had normal audiograms. Twenty out of 21 (95%) patients who had abnormal audiograms had undergone bone marrow transplants. Thirty-one of 37 (84%) patients with normal audiograms had received bone marrow transplants. Statistical analysis showed that patients with hearing loss were more likely to require a BMT in the future (OR = 3.87, p = 0.05). Of the patients with abnormal audiograms and a bone marrow transplant (n = 20), 14 (70%) had conductive hearing loss, 5 (25%) had mixed hearing loss, and 1 patient (5%) had sensorineural hearing loss. 13 of 20 patients (65%) had bilateral hearing loss and eight of 20 (40%) had unilateral hearing loss. Of those patients with conductive hearing loss (n = 15), the most common etiologies were Eustachian tube dysfunction (47%), external auditory canal stenosis (33%), and abnormal middle ear anatomy (13%). CONCLUSIONS: Hearing loss is a common finding in Fanconi anemia patients who have undergone BMTs with conductive hearing loss being the most common audiologic manifestation in our cohort of patients. This demonstrates the necessity of frequent hearing screenings in this population and close collaboration with audiology throughout patient care. Our study indicates that hearing status early in life may be a predictor of needing a bone marrow transplant in the future. Further studies should explore the long-term impact of BMT surgery on hearing status.

Associated syndromes in patients with Pierre Robin Sequence.

OBJECTIVES: Classically, Pierre Robin Sequence (PRS) is a triad of micrognathia, glossoptosis, and airway obstruction, although frequently associated with cleft palate. Current literature reports that Stickler syndrome is the most common syndrome associated with PRS, and 22q11 deletion syndrome (22q11 DS) as the second most common. This study identifies associations between PRS and genetic syndromes. METHODS: A retrospective chart review was performed to identify patients diagnosed with PRS over a 10-year period from 4/1/2007 to 4/1/2017 at a tertiary children's hospital. RESULTS: 4,052 consecutive charts were reviewed and 234 patients had a diagnosis of PRS confirmed with the triad of micrognathia, glossoptosis, and airway obstruction. Of note, all of these patients had cleft palate. Of the 234 patients with PRS, 65 patients had syndromic diagnoses (28%). One patient had 22q11 DS (0.43%), and 31 patients had Stickler syndrome (13.2%). Additionally, 3 patients had central hypoventilation syndrome, 3 patients had Duane syndrome, 2 patients had Cornelia de Lange syndrome, 2 patients had Emanuel syndrome, 2 patients had Gordon syndrome, 2 patients had Mobius syndrome, 2 patients had Nager syndrome. Multiple other syndromes were identified, but occurred in isolated cases. CONCLUSION: This study supports literature that PRS is most commonly associated with Stickler Syndrome but rarely associated with 22q11 DS given that only 1 patient had both PRS and 22q11 DS.

Risk factors for neo-osteogenesis in cystic fibrosis and non-cystic fibrosis chronic rhinosinusitis.

BACKGROUND: The purpose of this retrospective review was to determine how patient-related factors and culture data affect neo-osteogenesis in patients with chronic rhinosinusitis (CRS) and patients with cystic fibrosis (CF) with CRS. METHODS: Information from a database associated with a large tertiary medical center was used to assess adult patients with CF CRS and non-CF CRS (total, n = 102; CF CRS, n = 31; non-CF CRS, n = 71). Radiologic evidence of neo-osteogenesis was measured using the Global Osteitis Scoring Scale (GOSS), and mucosal disease was assessed using the Lund-Mackay score (LMS) by 2 independent reviewers who were blinded to the patient's disease state. Bacterial cultures were obtained endoscopically. Multiple logistic regression models were used to evaluate the effect of age, sex, number of previous surgeries, CF, and culture species on the odds of neo-osteogenesis. RESULTS: Fifty-one of the 102 patients (50%) met radiologic criteria for neo-osteogenesis. Sixty-nine patients (67.6%) with CF CRS and non-CF CRS had culture data. In the multiple logistic regression model, male gender was significantly associated with neo-osteogenesis (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.68-17.86; p = 0.006). Pseudomonas aeruginosa was not associated with neo-osteogenesis (OR, 3.12; 95% CI, 0.84-12.80; p = 0.097). Age, number of surgeries, CF, Staphylococcus aureus, and coagulase-negative Staphylococcus were not statistically significant. CONCLUSION: To our knowledge, this is the first study to assess risk factors associated with neo-osteogenesis and patients with CF CRS. Interestingly, male gender was the only significant predictor of neo-osteogenesis.

Hypoglossal nerve stimulator generator migration: INSPIRE device reimplantation with parallels to cardiac implantable electronic devices.

Implantation rates of hypoglossal nerve stimulators, such as INSPIRE, are increasing. The device is still in its early stages of complication reporting, which to date includes implant related infection requiring device removal, and stimulation lead cuff dislodgement requiring replacement. Here we present a 48-year-old female who experienced generator migration and stimulator lead tension requiring an additional operation in order to resecure the generator device. This proved unsuccessful and a second surgery was performed with complete relocation of the device generator to inhibit device migration. This is the first documented case of INSPIRE migration to date, though the implant generator has comparable likeness to cardiovascular implantable electronic devices (CIEDs) where migration risk factors are better studied. Given our patient's case, we identify obesity and abundant breast tissue as potential risk factors for device migration. We believe such factors can be identified prior to initial device implantation to avoid migration and the need for surgical revision. Superior positioning of the generator proved successful, and can be a solution in those with similar body habitus as TYRX pouching and additional security sutures were ineffective. Also, for revisions requiring tunneling of the stimulation lead as in this case we recommend the use of zero degree endoscope for ease of adhesion lysis.

Pulmonary aspiration of sinus secretions in patients with cystic fibrosis.

BACKGROUND: Indirect evidence suggests that sinonasal secretions are aspirated into the lungs of patients with cystic fibrosis (CF), contributing to infection, subsequent tissue damage, and decreased lung function. Our objective is to determine whether sinonasal secretions are transferred to the lungs in patients with CF-related sinus disease and healthy subjects, particularly in the recumbent position and during sleep. METHODS: We performed a prospective, controlled trial to detect pulmonary aspiration of radiolabeled albumin applied to the nasal mucosa of study subjects with chronic sinusitis related to CF and control subjects without sinus disease. Radioactive counts were measured in the lungs and compared to background counts in both groups after 8 hours of rest/sleep. RESULTS: Complete data was collected on 12 CF patients and 6 controls. Eleven patients with CF demonstrated higher lung counts than background counts. The average counts of radiolabeled albumin in the lungs of CF patients were significantly greater than background counts (p = 0.03). Controls did not demonstrate this finding (p > 0.90), with only one-half demonstrating lung counts greater than background counts. CONCLUSION: This study provides direct evidence of aspiration of sinonasal secretions into the lungs of patients with CF and healthy adults in the recumbent position. The fact that both patients and controls aspirated secretions suggests that aspiration alone does not account for the pathogenesis of lung disease in CF patients.

The antipsoriatic agent monomethylfumarate has antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes.

Monomethylfumarate (MMF) is thought to be the bioactive ingredient of the drug Fumaderm (Biogen Idec, Cambridge, MA), licensed in Germany since 1994 for the treatment of moderate-to-severe psoriasis. Psoriasis is a common inflammatory hyperproliferative skin disorder that involves cross-talk between different cell types, including immune cells and keratinocytes. Psoriatic lesions are characterized by hyperproliferation, aberrant differentiation, and inflammation, with the psoriatic cytokine network maintained by communication between immune cells and keratinocytes. Recently, there is increasing evidence regarding the pivotal role of keratinocytes in mediating the disease process, and these cells can be regarded as safe therapeutic targets. From the data available on human subjects treated with Fumaderm, MMF is an effective antipsoriatic agent with known effects on immune cells. However, little is known about its direct effects on keratinocytes. We hypothesized that MMF has direct antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes. Indeed, MMF dose-dependently inhibited [(3)H]thymidine incorporation into DNA, indicating a direct antiproliferative action on keratinocytes. MMF significantly increased the protein level of keratin 10, the early keratinocyte differentiation marker, and the activity of transglutaminase, a late differentiation marker. These results are consistent with an ability of MMF to promote keratinocyte differentiation and inhibit proliferation, thereby improving psoriatic lesions. In 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced keratinocytes, MMF significantly inhibited the expression of the proinflammatory cytokines, tumor necrosis factor-α (TNFα), interleukin-6, and interleukin-1α as well as the production of TNFα. Our results support the notion that MMF has direct antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes, highlighting its potential use as a multifactorial antipsoriatic agent.