Risk of post-operative pneumocephalus in patients with obstructive sleep apnea undergoing transsphenoidal surgery.

Patients undergoing transsphenoidal surgery (TSS) have an anterior skull base defect that limits the use of positive pressure ventilation post-operatively. Obstructive sleep apnea (OSA) can be seen in these patients and is treated with continuous positive airway pressure (CPAP). In our study we documented the incidence of pre-existing OSA and reported the incidence of diagnosed pneumocephalus and its relationship to OSA. A retrospective review was conducted from a surgical outcomes database. Electronic medical records were reviewed, with an emphasis on diagnosis of OSA and documented symptomatic pneumocephalus. A total of 324 patients underwent 349 TSS for sellar mass resection. The average body mass index of the study cohort was 32.5kg/m(2). Sixty-nine patients (21%) had documented OSA. Only 25 out of 69 (36%) had a documented post-operative CPAP plan. Out of all 349 procedures, there were two incidents of pneumocephalus diagnosed. Neither of the patients had pre-existing OSA. One in five patients in our study had pre-existing OSA. Most patients returned to CPAP use within several weeks of TSS for resection of a sellar mass. Neither of the patients with pneumocephalus had pre-existing OSA and none of the patients with early re-initiation of CPAP developed this complication. This study provides preliminary evidence that resuming CPAP early in the post-operative period might be less dangerous than previously assumed.

Differential effect of omalizumab on pulmonary function in patients with allergic asthma with and without chronic rhinosinusitis.

BACKGROUND: Omalizumab, an anti-immunoglobulin E monoclonal antibody, is approved by the U.S. Food and Drug Administration for the management of patients with allergic asthma and with refractory disease, and has also proven beneficial in the management of selected patients with chronic rhinosinusitis (CRS). The common airway model indicates that patients with both allergic asthma and CRS may be more challenging to manage clinically. This is the first study to evaluate the response of omalizumab in patients with asthma and CRS versus those with asthma alone. OBJECTIVE: To compare pulmonary function test (PFT) responses in omalizumab-treated patients with asthma with CRS with omalizumab-treated patients with asthma without CRS. METHODS: This was a retrospective case-control study at a tertiary university clinic. Between 2007 and 2014, a total of 259 patients with allergic asthma had been prescribed omalizumab for asthma. Outcome measures were absolute, and the percentage changes in PFT results were compared with the baseline. RESULTS: Overall, 81 patients had serial PFT results available for evaluation, among whom 59 (73%) had CRS. Average treatment duration was 27.2, 27.7, and 25.8 months for the entire sample, for patients with asthma and CRS, and for patients with asthma and without CRS, respectively. Overall, PFT metrics improved across all parameters (forced expiratory volume in 1 second, forced vital capacity, forced expiratory volume in 1 second to forced vital capacity ratio, and forced expiratory flow 25-75%). Significant improvement (p < 0.05, paired t-test) was observed for three of four metrics in patients with comorbid CRS but in none of these parameters in patients without CRS. CONCLUSION: Patients with allergic asthma who were treated with omalizumab manifested some improvement in PFT scores. CRS may add to the overall symptom burden experienced by patients with asthma, especially in those with increasing severity, but comorbid CRS did not adversely impact the therapeutic potential of omalizumab. In fact, the benefit of omalizumab was more likely to be observed in patients with asthma and with CRS than in patients with asthma and without CRS.

Impact of omalizumab therapy on medication requirements for chronic rhinosinusitis.

BACKGROUND: Omalizumab is indicated for treatment of patients with moderate to severe allergic asthma. Previous studies have shown 70% of these patients also have chronic rhinosinusitis (CRS). The present series examines the impact of omalizumab on medication use for CRS in a cohort of asthmatic CRS patients who received this therapy. METHODS: The sample included 25 patients with adequate prescription data preinitiation and postinitiation of therapy. Data was available for a full 12 months both preinitiation and postinitiation of therapy in 20 of 25 patients and for 4 to 8 months in the remaining 5 of 25. Average antibiotic use (# of unique prescriptions per month) and systemic steroid dose (mg/month) were tabulated for each patient and compared before and after initiation of therapy. RESULTS: Mean antibiotic prescriptions/month decreased by 37%, and this was statistically significant (p = 0.013). Antibiotic use decreased in 15 of 25 (60%), was the same in 7 of 25 (28%), and increased in 3 of 25 (12%) patients. Chronic steroid administration was required in 19 of 25 patients, and dosing was highly variable. Mean monthly steroid dose decreased substantially in 8 of 19 (42%) patients, with reduction ranging from 40% to 100% from pretreatment levels. A modest decrease of 17% to 30% was observed in 4 of 19 (21%) patients. Steroid use was essentially unchanged in 4 of 19 (21%), but dramatically increased (71% to 366% above pretreatment dose) in 3 of 19 (15%) patients. CONCLUSION: Omalizumab therapy is associated with a decrease in overall antibiotic use for CRS. A subset of patients also experience significant reduction in steroid dependence. Further study is necessary to determine factors predictive of response.

Chronic invasive fungal sinusitis associated with intranasal drug use.

Chronic invasive fungal sinusitis (CIFS) is a rare but potentially aggressive form of invasive fungal disease that occurs in immunocompetent patients. We report a case of CIFS in an otherwise healthy young adult associated with intranasal illicit drug abuse. The patient presented with nonhealing nasal septal and palatal perforations. Biopsy demonstrated invasive Aspergillus flavus requiring surgical debridement and extended intravenous antifungal therapy. Tissue necrosis and ulceration related to intranasal drug use should be recognized as a potential risk factor for invasive fungal sinusitis.

Early Practice: External Sinus Surgery and Procedures and Complications.

External approaches to the paranasal sinuses are rarely used in the endoscopic era. However, their indications for use have not changed, and in every surgeon's career those indications may present themselves. For residents training in the endoscopic era, these procedures are also very rarely seen. In this article, the external approaches to the maxillary, ethmoid, and frontal sinuses are described: their original descriptions, modern use, and potential complications. It is hoped that this article will serve to instruct residents and practitioners alike in these techniques.

Pedicled flaps in endoscopic skull base reconstruction: review of current techniques.

PURPOSE OF REVIEW: To discuss the current applications and indications for the use of pedicled flaps in the reconstruction of endoscopic skull base defects. RECENT FINDINGS: Current trends in endoscopic skull base surgery include the use of vascularized pedicled flaps rather than free tissue grafts (autograft or allograft) for the repair of anterior cranial base defects. In particular, recent evidence-based algorithms for skull base reconstruction suggest that use of pedicled flaps for clival defects and high-flow cerebrospinal fluid (CSF) leaks may reduce the incidence of postoperative CSF leaks. The primary workhorse continues to be the nasoseptal flap (NSF); however, other options exist in cases wherein this flap is unavailable because of prior sacrifice or unable to reach the area of interest (e.g., defects adjacent to the frontal recess). SUMMARY: Adoption of vascularized pedicled flaps over the last decade, particularly the recently popularized NSF, has greatly reduced complications associated with endoscopic skull base surgery. The need for vascularized flap reconstruction is governed primarily by defect size and location, and by the presence of a high-flow CSF leak. Additional vascularized flaps can be used in conjunction with the NSF, or as an alternative when the NSF is unfavorable or unavailable.

Metabolic preconditioning of cells with AICAR-riboside: improved cryopreservation and cell-type specific impacts on energetics and proliferation.

In species whose evolutionary history has provided natural tolerance to dehydration and freezing, metabolic depression is often a pre-requisite for survival. We tested the hypothesis that preconditioning of mammalian cells with 5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside (AICAR) to achieve metabolic depression will promote greater survivorship during cryopreservation. AICAR is used extensively to stimulate AMP-activated protein kinase (AMPK), which can result in downregulation of biosynthetic processes. We showed that the metabolic interconversion of AICAR was cell-type dependent. Accumulation of 5-aminoimidazole-4-carboxamide-1b-D-ribofuranosyl-5'-monophosphate (ZMP), as well as other metabolites that possess multiple phosphates (i.e., ZDP, ZTP), varied approximately 3.5-fold across the cell lines tested. AICAR treatment also significantly influenced the concentrations of cellular adenylates (ATP, ADP, and AMP). Depression of cell metabolism and proliferation with AICAR treatment differed among cell lines. Proliferation for a given cell line was negatively correlated with the fold-increase achieved in the 'effective adenylate ratio' ([AMP]+[ZMP])/[ATP]) after AICAR treatment. Metabolic preconditioning with AICAR promoted a significant increase in viability post-freezing in J774.A1 macrophages, HepG2/C3A cells and primary hepatocytes but not in NIH/3T3 fibroblasts or OMK cells. The effect of AICAR on viability after freezing was positively correlated (r(2)=0.94) with the fold-increase in the 'effective adenylate ratio'. Thus for each cell line, the greater the depression of metabolism and proliferation due to preconditioning with AICAR, the greater was the survivorship post-freezing.

Depression of cell metabolism and proliferation by membrane-permeable and -impermeable modulators: role for AMP-to-ATP ratio.

The metabolic and developmental depression commonly observed during natural states of dormancy, such as diapause and quiescence, is typically accompanied by an increase in the intracellular ratio of AMP to ATP. We investigated the impact of artificially increasing the AMP-to-ATP ratio in mouse macrophages. Evidence is presented here that the P2X7 receptor channel can be used as an effective means to load cells with membrane-impermeable compounds. Intracellular loading of adenosine-5'-O-thiomonophosphate (AMPS), a nonhydrolyzable analog of 5'-AMP and potent activator of AMP-activated protein kinase, significantly depresses metabolism and proliferation of macrophages. The intracellular effective AMP-to-ATP ratio obtained (the sum of AMPS plus endogenous 5'-AMP) was 0.073, well above that reported to activate AMP-activated protein kinase in vitro. Optimizing both the conditions under which the P2X7 receptor channel is opened and the duration of opening facilitates high analog uptake and approximately 98% survivorship. An advantage to AMPS is its minimal impact on other components of the nucleotide pool, most notably the unchanged concentration of ADP. An alternative way to shift the effective AMP-to-ATP ratio is by incubation with the membrane-permeable compound 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), which is phosphorylated intracellularly to form the 5'-AMP analog ZMP. Despite a rapid intracellular accumulation of AICAR, conversion to ZMP was slow and inefficient. Furthermore, AICAR incubation increased cellular ADP, and, although cell proliferation was depressed, the overall cellular energy flow was unchanged. The rapid action of AMPS avoids upregulation of compensatory metabolic pathways and may provide a viable approach for promoting cell stasis.