FDG-Avid Focal Liver Reaction From Proton Therapy in a Patient With Primary Esophageal Adenocarcinoma.

A 25-year-old man with IgA deficiency was treated with 2 months of chemotherapy and proton therapy for gastroesophageal junction adenocarcinoma. Restaging PET/CT 18 days posttherapy demonstrated 2 new foci of increased FDG uptake in the left hepatic lobe, which were favored to represent radiation injury as opposed to new metastases. Follow-up MRI with contrast 2 weeks later demonstrated hypoenhancement and T1/T2 hypointensity in the liver, without restricted diffusion, which correlated with the dominant FDG-avid focus. The hepatic lesions resolved on subsequent FDG PET/CT and MRI studies, confirming the diagnosis of acute radiation injury.

Emerging Gene Therapies for Genetic Hearing Loss.

Gene therapy, or the treatment of human disease using genetic material, for inner ear dysfunction is coming of age. Recent progress in developing gene therapy treatments for genetic hearing loss has demonstrated tantalizing proof-of-principle in animal models. While successful translation of this progress into treatments for humans awaits, there is growing interest from patients, scientists, clinicians, and industry. Nonetheless, it is clear that a number of hurdles remain, and expectations for total restoration of auditory function should remain tempered until these challenges have been overcome. Here, we review progress, prospects, and challenges for gene therapy in the inner ear. We focus on technical aspects, including routes of gene delivery to the inner ear, choice of vectors, promoters, inner ear targets, therapeutic strategies, preliminary success stories, and points to consider for translating of these successes to the clinic.

Factors influencing the need for endoscopic sinus surgery in adult patients with cystic fibrosis.

BACKGROUND: Risk factors in adult patients with cystic fibrosis (CF) associated with surgical intervention have not been delineated. OBJECTIVE: To identify characteristics of adult patients with CF and with chronic rhinosinusitis that predict surgical intervention with endoscopic sinus surgery (ESS). METHODS: Patients were identified in a tertiary sinus center by the International Classification of Diseases, Ninth Revision codes 277.00-277.03, which represent CF. Charts were reviewed for the CF transmembrane conductance regulator (CFTR) gene mutation, Lund-Mackay score (LMS), the 22-item Sino-Nasal Outcome Test (SNOT-22) score, previous ESS, and occurrence of ESS after presentation. The Fisher exact test was used to test frequency of events between the groups, and the Mann Whitney U test and the t-test were used to compare means among LMS, SNOT-22, and age. The Cox proportional hazard analysis was used to calculate hazard ratios (HR) for the impact of LMS, SNOT-22 score, previous ESS, and CFTR gene mutation status on the occurrence of ESS after presentation. RESULTS: One hundred and fifteen patients met the inclusion criteria for the study. Patients with a history of surgery more often underwent ESS after presentation (p ≤ 0.01). The LMS and the SNOT-22 score were not significantly different between the groups of previous ESS and no previous ESS (p = 0.23 and p = 0.28, respectively). A severe mutation genotype was predictive of ESS after presentation (p = 0.03). SNOT-22 scores did not differ between the severe and mild groups (36.0 and 32.4, respectively; p = 0.57), but the mean LMS was significantly higher in the severe mutation group (12.5 and 9.7; p ≤ 0.01). Univariate Cox proportional hazard analysis revealed an increased occurrence of ESS for patients with severe mutations (HR, 3.6; p ≤ 0.01) or a history of ESS (HR, 2.3; p ≤ 0.01). CONCLUSION: The occurrence of ESS in adult patients with CF was predicted by previous ESS intervention as well as the severity of CFTR mutation.

Evolution of Movement Disorders Surgery Leading to Contemporary Focused Ultrasound Therapy for Tremor.

Progressively less invasive neurosurgical approaches for the treatment of movement disorders have evolved, beginning with open craniotomy for placement of lesions within pyramidal structures followed by refined stereotactic ablation of extrapyramidal targets that encouraged nondestructive electrode stimulation of deep brain structures. A noninvasive approach using transcranial high-energy focused ultrasound has emerged for the treatment of intractable tremor. The ability to target discreet intracranial sites millimeters in size through the intact skull using focused acoustic energy marks an important milestone in movement disorders surgery. This article describes the evolution of magnetic resonance-guided focused ultrasound for ventrolateral thalamotomy for tremor.

Tmc gene therapy restores auditory function in deaf mice.

Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mouse models of genetic deafness. We focused on DFNB7/11 and DFNA36, which are autosomal recessive and dominant deafnesses, respectively, caused by mutations in transmembrane channel-like 1 (TMC1). Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36. We screened several adeno-associated viral (AAV) serotypes and promoters and identified AAV2/1 and the chicken ß-actin (Cba) promoter as an efficient combination for driving the expression of exogenous Tmc1 in inner hair cells in vivo. Exogenous Tmc1 or its closely related ortholog, Tmc2, were capable of restoring sensory transduction, auditory brainstem responses, and acoustic startle reflexes in otherwise deaf mice, suggesting that gene augmentation with Tmc1 or Tmc2 is well suited for further development as a strategy for restoration of auditory function in deaf patients who carry TMC1 mutations.