Temporal bone manifestation of primary extranodal Rosai-Dorfman disease: a case report.

BACKGROUND: Rosai-Dorfman disease is a rare benign histiocytic disorder characterized in most cases by painless cervical adenopathy. Less than 10% of extranodal cases involve bony lesions. Primary bone Rosai-Dorfman disease in the absence of nodal disease is extremely rare. CASE PRESENTATION: A 48 year-old Caucasian male presented with progressive right-sided otalgia, tinnitus, vertigo, and hearing loss. A right temporal bone lytic lesion was detected on diagnostic imaging. Resection of the lesion and histopathological examination revealed Rosai-Dorfman disease. CONCLUSIONS: Rosai-Dorfman disease primary bone lesions are an atypical presentation of a rare disease. This is the second reported case of Rosai-Dorfman disease arising within the temporal bone. This case study reveals that Rosai-Dorfman disease should be considered for patients presenting with inflammatory/lytic lesions of the temporal bone, in cases where infection and malignancy have been excluded.

Side effects and complications of injection laryngoplasty for treatment of congenital type 1 laryngeal clefts.

INTRODUCTION: Injection laryngoplasty (IL) is a brief, minimally invasive procedure involving injection of agents to augment the interarytenoid space. It was initially described as a diagnostic and temporizing measure for management of type one laryngeal clefts (LC1) and associated swallowing dysfunction (SwD), but more gradually it is being proposed as a definitive treatment modality. However, the morbidity of this treatment for LC1 remains under-investigated. This study sought to determine the morbidities associated with IL as a treatment modality for LC1 and associated SwD. METHOD: Single centre retrospective review of a prospective surgical database of one Pediatric Otolaryngologist at a tertiary care center. Participants included pediatric patients with an endoscopic diagnosis of LC1, treated with IL between 2000 and 2018-excluding those with concurrent upper airway anomalies. Patient charts were reviewed for demographic information, immediate post-op complications (within the first 14 days following IL), and subsequent management. RESULTS: Out of 85 consecutive, eligible patients, 12 were excluded (5 subglottic stenosis, 6 laryngomalacia, and one tracheomalacia). Of the 73 included patients, 42 were male and 31 females. The median age at IL was 29 months (range 1-132, interquartile range of 38 months). All IL procedures in this study utilized hyaluronic acid derivatives. From this series, 13 patients experienced post-operative complications. The complications encountered were respiratory distress (N = 5), croup-like cough (N = 6), and stridor (N = 6). These complications were either self-limiting (N=9), managed by systemic or inhaled steroids (N = 4), or admitted to hospital for monitoring (N=3). One case (augmented with dextranomer and hyaluronic acid) required intubation, repeat endoscopy, and drainage of seroma. CONCLUSION: IL was followed by respiratory morbidity in nearly two in ten of this series of consecutive patients. All the morbidities occurred in association with one injection product. Parents should be counselled appropriately about potential morbidities associated with this procedure.

Release and pharmacokinetics of near-infrared labeled albumin from monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) microspheres after subcapsular renal injection.

Subcapsular renal injection is a novel administration method for local delivery of therapeutics for the treatment of kidney related diseases. The aim of this study was to investigate the feasibility of polymeric microspheres for sustained release of protein therapeutics in the kidney and study the subsequent redistribution of the released protein. For this purpose, monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres (40 µm in diameter) loaded with near-infrared dye-labeled bovine serum albumin (NIR-BSA) were prepared by a membrane emulsification method. Rats were injected with either free NIR-BSA or with NIR-BSA loaded microspheres (NIR-BSA-ms) and the pharmacokinetics of the released NIR-BSA was studied for 3 weeks by ex vivo imaging of organs and blood. Quantitative release data were obtained from kidney homogenates and possible metabolism of the protein was investigated by SDS-PAGE analysis of the samples. The ex vivo images showed a rapid decrease of the NIR signal within 24h in kidneys injected with free NIR-BSA, while, importantly, the signal of the labeled protein was still visible at day 21 in kidneys injected with NIR-BSA-ms. SDS-PAGE analysis of the kidney homogenates showed that intact NIR-BSA was released from the microspheres. The locally released NIR-BSA drained to the systemic circulation and subsequently accumulated in the liver, where it was degraded and excreted renally. The in vivo release of NIR-BSA was calculated after extracting the protein from the remaining microspheres in kidney homogenates. The in vivo release rate was faster (89 ± 4% of the loading in 2 weeks) compared to the in vitro release of NIR-BSA (38 ± 1% in 2 weeks). In conclusion, PLHMGA microspheres injected under the kidney capsule provide a local depot from which a formulated protein is released over a prolonged time-period.

Formulation and characterization of microspheres loaded with imatinib for sustained delivery.

The aim of this study was the development of imatinib-loaded poly(d,l-lactide-co-glycolide) (PLGA) microspheres with high loading efficiency which can afford continuous release of imatinib over a prolonged period of time. Imatinib mesylate loaded PLGA microspheres with a size of 6-20 µm were prepared by a double emulsion (W1/O/W2) method using dichloromethane as volatile solvent. It was found that the microspheres were spherical with a non-porous surface; imatinib loading efficiency (LE) was highly dependent on the pH of the external water phase (W2). By increasing the pH of W2 phase above the highest pKa of imatinib (pKa 8.1), at which imatinib is mainly uncharged, the LE increased from 10% to 90% (pH 5.0 versus pH 9.0). Conversely, only 4% of its counter ion, mesylate, was retained in the microspheres at the same condition (pH 9.0). Since mesylate is highly water soluble, it is unlikely that it partitions into the organic phase. We demonstrated, using differential scanning calorimetry (DSC), that imatinib was molecularly dispersed in the polymeric matrix at loadings up to 8.0%. At higher drug loading, imatinib partially crystallized in the matrix. Imatinib microspheres released their cargo during three months by a combination of diffusion through the polymer matrix and polymer erosion. In conclusion, we have formulated imatinib microspheres with high LE and LC. Although we started with a double emulsion of imatinib mesylate, the obtained microspheres contained imatinib base which was mainly molecularly dispersed in the polymer matrix. These microspheres release imatinib over a 3-month period which is of interest for local treatment of cancer.

Sunitinib microspheres based on [PDLLA-PEG-PDLLA]-b-PLLA multi-block copolymers for ocular drug delivery.

Sunitinib is a multi-targeted receptor tyrosine kinase (RTK) inhibitor that blocks several angiogenesis related pathways. The aim of this study was to develop sunitinib-loaded polymeric microspheres that can be used as intravitreal formulation for the treatment of ocular diseases. A series of novel multi-block copolymers composed of amorphous blocks of poly-(D,L-lactide) (PDLLA) and polyethylene glycol (PEG) and of semi-crystalline poly-(L-lactide) (PLLA) blocks were synthesized. Sunitinib-loaded microspheres were prepared by a single emulsion method using dichloromethane as volatile solvent and DMSO as co-solvent. SEM images showed that the prepared microspheres (∼ 30 µm) were spherical with a non-porous surface. Sunitinib-loaded microspheres were studied for their degradation and in-vitro release behavior. It was found that increasing the percentage of amorphous soft blocks from 10% to 30% accelerated the degradation of the multi-block copolymers. Sunitinib microspheres released their cargo for a period of at least 210 days by a combination of diffusion and polymer erosion. The initial burst (release in 24h) and release rate could be tailored by controlling the PEG-content of the multi-block copolymers. Sunitinib-loaded microspheres suppressed angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These microspheres therefore hold promise for long-term suppression of ocular neovascularization.