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KEY POINTS: Patients treated with pembrolizumab experience an increase in paranasal sinus inflammationUse of topical triamcinolone in carboxymethylcellulose is a treatment option for such patients [ABSTRACT FROM AUTHOR]

Background  Sinonasal adenocarcinoma (SNAC) is a rare malignancy arising from mucus-secreting glandular tissue. Limited large-scale studies are available due to its rarity. We evaluated SNAC in the National Cancer Database (NCDB), a source that affords multi-institutional, population studies of rare cancers and their outcomes. Methods  The NCDB was queried for adenocarcinoma in the sinonasal tract. Multivariate analyses were performed to evaluate for factors contributing to overall survival (OS). Results  A total of 553 patients were identified. The cohort was composed of 59.3% males. The nasal cavity was the most common primary site, representing 44.1% of cases. About 5.7% of patients presented with nodal disease, while 3.3% had distant metastases. About 40.6% of cases presented with stage IV disease. About 73.5% of patients underwent surgery, 54.2% received radiation therapy, and 27.7% had chemotherapy. Median OS was 71.7 months, while OS at 1, 2, and 5 years was 82, 73.0, and 52%, respectively. On multivariate analysis, advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02–1.05), Charlson–Deyo score of 1 (HR: 1.99; 95% CI: 1.20–3.30), advanced tumor grade (HR: 2.73; 95% CI: 1.39–5.34), and advanced tumor stage (HR: 2.71; 95% CI: 1.33–5.50) were associated with worse OS, whereas surgery (HR: 0.34; 95% CI: 0.20–0.60) and radiation therapy (HR: 0.55; 95% CI: 0.33–0.91), but not chemotherapy (HR: 1.16; 95% CI: 0.66–2.05), predicted improved OS. Conclusions  SNAC is a rare malignancy with 5-year survival approximating 50%. Surgery and radiation therapy, but not chemotherapy, are associated with improved survival, and likely play a critical role in the interdisciplinary management of SNAC. [ABSTRACT FROM AUTHOR]

Background: Inverted papilloma (IP) is a benign sinonasal tumor with a well‐known propensity to recur, especially at its bony attachment site. Anecdotal evidence suggests lower rate of recurrence in primary resection. We also aimed to evaluate the effect of multifocal vs single focus of attachment in disease control. Methods: This work is a retrospective review of 535 IP resections performed during the period from 2006 to 2016 at a tertiary‐care center. Demographic data, tumor location and attachment sites, and follow‐up duration data were obtained. Results: Two hundred ten patients were eligible for analysis. The mean age was 57 years, with an average postoperative surveillance of 36.4 months. Patients who had a previous procedure at an outside institution have a recurrence rate of 22.3%, compared with 12.4% for patients who had primary surgery at our institution. The most common site of attachment was maxillary sinus (47.6%), followed by ethmoid sinus (39%). Individual tumor review showed 50% of the patients to have multifocal attachment disease, of which there is a higher prevalence in secondary cases when compared with primary cases (53.7% vs 44.9%). Multiple tumor attachment sites had a significant effect on recurrence (odds ratio, 3.5; 95% confidence interval, 1.6‐7.6; p = 0.002). Conclusion: Primary resection and single‐focus attachment of inverted papilloma are associated with lower recurrence rates at 3‐year follow‐up. [ABSTRACT FROM AUTHOR]

Background: Solitary chemosensory cells (SCCs) are rare epithelial cells enriched in nasal polyps and are the primary source of interleukin‐25 (IL‐25), an innate cytokine eliciting T‐helper 2 (Th2) immune response. Although it is proposed that SCCs are stimulated by antigens released by upper airway pathogens, the exogenous triggers of human SCCs remain elusive. We studied patients with noninvasive fungal rhinosinusitis to determine whether extracts of Aspergillus fumigatus and Alternaria alternata stimulate SCC proliferation as an early event in type 2 inflammation. Methods: Multicolor flow cytometry, immunofluorescence, and enzyme‐linked immunoassay were used to interrogate mucosa from patients with mycetomas and allergic fungal rhinosinusitis (AFRS) for SCCs and IL‐25. Primary sinonasal epithelial cells from AFRS patients and noninflamed inferior turbinates were stimulated with fungal extracts for 72 hours, and SCC population frequency as well as mitotic activity were quantified using flow cytometry. Results: SCCs producing IL‐25 are enriched in inflamed mucosa compared with intrapatient noninflamed control tissue (38.6% vs 6.5%, p = 0.029). In cultured sinonasal epithelial cells from AFRS nasal polyps, Aspergillus fumigatus and Alternaria alternata stimulated higher SCC frequency compared with controls (27.4% vs 10.6%, p = 0.002; 18.1% vs 10.6%, p = 0.046), which led to increased IL‐25 secretion in culture media (75.5 vs 3.3 pg/mL, p < 0.001; 32.3 vs 3.3 pg/mL, p = 0.007). Ki‐67 expression was higher in SCCs grown in fungal stimulation conditions compared with controls. Conclusion: Although fungal antigens are known to potentiate immune response through innate cytokines, including IL‐25, the early expansion of SCCs in the presence of fungus has not been described. This early event in the pathogenesis of noninvasive fungal rhinosinusitis may represent a target for intervention. [ABSTRACT FROM AUTHOR]

Recent evidence has demonstrated an expanding role of respiratory epithelial cells in immune surveillance and modulation. Studies have been focusing on the earliest events that link epithelial injury to downstream inflammatory responses. Cytokines produced by and released from respiratory epithelial cells are among these early trigger signals. Epithelial‐derived cytokines, namely thymic stromal lymphopoietin (TSLP), interleukin (IL)‐25, and IL‐33, have come to the forefront of recent investigations. Each of these 3 cytokines has been implicated in chronic rhinosinusitis (CRS), asthma, and atopy. Herein we review studies elucidating the roles of epithelial‐derived cytokines in the pathobiology of upper airway disease, with particular emphasis on type 2 inflammatory conditions. [ABSTRACT FROM AUTHOR]

Evidence is emerging that shows taste receptors serve functions outside of taste sensation of the tongue. Taste receptors have been found in tissue across the human body, including the gastrointestinal tract, bladder, brain, and airway. These extraoral taste receptors appear to be important in modulating the innate immune response through detection of pathogens. This review discusses taste receptor signaling, focusing on the G-protein–coupled receptors that detect bitter and sweet compounds in the upper airway epithelium. Emphasis is given to recent studies which link the physiology of sinonasal taste receptors to clinical manifestation of upper airway disease. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly characterized by type‐2 inflammation. It is established that group‐2 innate lymphoid cells (ILC2s) are a subset of immune cells important in orchestrating mucosal type‐2 response. IL‐25 is an epithelial‐derived cytokine that is a critical activator of ILC2s. Recent evidence demonstrates that specialized taster epithelial cells, such as solitary chemosensory cells (SCCs), may be producers of IL‐25. To elucidate the relationship between SCCs and ILC2s in CRSwNP, we sought to quantify ILC2s and SCCs to determine if these cell types are enriched in nasal polyps compared to healthy sinonasal mucosa. Methods: We quantified SCCs and ILC2s using multicolor flow cytometry in nasal polyps and non‐inflamed turbinate mucosa from seven patients and investigated the role of IL‐13 and dexamethasone on SCC frequency using tissue explants of nasal polyps and turbinate mucosa. Results: SCCs were found to be the primary source of IL‐25. Nasal polyps demonstrated higher populations of SCCs (33.0% vs 5.6%, p < 0.001) and ILC2s (2.40% vs 0.19%, p = 0.008) compared to patient‐matched nonpolypoid turbinates. In cultured polyp explants, exogenous IL‐13 increased the proportion of epithelial SCCs (40.2% IL‐13 condition vs 28.9% untreated, p = 0.012), and this effect was reversed by addition of dexamethasone (40.2% vs 8.9%, p < 0.0005). Conclusion: These data support SCC and ILC2 expansion as well as increased IL‐25 production in nasal polyps and may represent early events in the pathogenesis of CRSwNP. IL‐13 stimulates proliferation of SCC in a feed‐forward loop, a process that is steroid‐sensitive. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing endoscopic resection of neoplasms with both sinonasal and skull base involvement can develop chronic rhinosinusitis (CRS) after treatment and may occasionally benefit from additional endoscopic sinus surgery (ESS). We investigate risk factors and outcomes associated with revision ESS (rESS) after endoscopic skull‐base surgery (SBS) for neoplasms with combined sinonasal and skull base involvement. Methods: A retrospective review of patients with neoplasms with both sinonasal and skull base involvement who underwent endoscopic resection at a single tertiary care academic institution from 2004 through 2017 was performed. Eighty‐three patients were included. Main outcome measures included incidence and timing of revision surgery, Lund‐Mackay (LM) scores, and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. Results: rESS was performed in 21 (25%) cases, 15 (18%) of which were due to CRS. Time between initial resection and rESS was an average of 42 months (range, 6 to 142 months). Pre‐SBS and post‐SBS LM scores were not significantly different (5.0 vs 4.7, p = 0.640), although pre‐SBS and post‐SBS SNOT‐22 scores showed significant improvement (32.6 vs 24.5, p = 0.030). Malignant pathology correlated with need for rESS (odds ratio [OR] 5.07, p = 0.04), as well as treatment including chemotherapy (OR 5.10, p = 0.003) and radiation (OR 4.15, p = 0.013). Conclusion: A significant proportion of patients develop clinically significant sinusitis after endoscopic SBS for neoplasms with combined sinonasal and skull base involvement and may benefit from rESS. Intervention occurred, on average, 3.5 years after initial tumor resection. Malignant pathology, radiation therapy, and chemotherapy correlate with need for rESS. [ABSTRACT FROM AUTHOR]

Background: Ketotifen is a second‐generation noncompetitive H1‐antihistamine and mast‐cell stabilizer. It is commonly used to treat or prevent allergic conjunctivitis, asthma, chronic urticaria, anaphylaxis, mast‐cell, and other allergic‐type disorders. However, it has never been studied in aspirin‐exacerbated respiratory disease (AERD), an aggressive phenotype of chronic rhinosinusitis with nasal polyps, where the mast cell plays a prominent role its pathogenesis. Methods: Human sinonasal epithelial cells were grown at an air‐liquid interface (ALI). Ketotifen powder was dissolved in saline to make 4 test solutions at 1.04, 2.08, 10.4, and 20.8 µg/mL. Control (saline) or ketotifen solution was added apically to ALI cultures from tissue of 5 unique patients, and ciliary beat frequency (CBF) changes were recorded. Lactate dehydrogenase was measured at 24 and 48 hours to estimate long‐term cellular toxicity. Results: Apical application of ketotifen at all concentrations was neither ciliotoxic nor ciliostimulatory, with no change in CBF over a period of 15 minutes after application. Cellular toxicity for all concentrations at 24 and 48 hours after application was <3% and <7%, respectively, that of lysed cultures. Conclusion: Topical application of ketotifen to an in vitro model of sinonasal epithelium is safe, as evaluated by CBF and lactate dehydrogenase. Ketotifen is neither ciliotoxic nor ciliostimulatory, and no long‐term cellular toxicity was observed. Ketotifen may have promise as a topical nasal rinse in the treatment of AERD. [ABSTRACT FROM AUTHOR]

Background: Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi‐institutional and multidisciplinary evidence‐based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS. Methods: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non‐sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated. Results: A review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains. Conclusion: Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms. [ABSTRACT FROM AUTHOR]

Background: Broncho‐Vaxom® (OM‐85 BV) is an extract of infectious respiratory bacteria that is used as an immunostimulant outside of the United States for the prevention and treatment of bronchitis and rhinosinusitis. Prior studies have shown that use of OM‐85 BV is associated with reduction in frequency of respiratory infection and decreased duration of antibiotic usage. However, the effects of OM‐85 BV on respiratory mucosal innate immunity are unknown. Methods: Human sinonasal epithelial cells were grown at an air‐liquid interface (ALI). Ciliary beat frequency (CBF) and nitric oxide (NO) production in response to stimulation with OM‐85 BV was measured in vitro. Pharmacologic inhibitors of bitter taste receptor (T2R) signaling were used to determine if this pathway was taste‐receptor–mediated. Results: Apical application of OM‐85 BV resulted in an NO‐mediated increase in CBF (p < 0.05) and increased NO production (p < 0.0001) when compared to saline‐stimulated control cultures. ALI pretreatment with taste receptor pathway inhibitors blocked OM‐85 BV–induced increases in NO. Conclusion: OM‐85 BV has ciliostimulatory and immunogenic properties that may be partially responsible for its observed efficacy as a respiratory therapeutic. These responses were NO‐dependent and consistent with T2R activation. Further work is necessary to elucidate specific component‐receptor signaling relationships. [ABSTRACT FROM AUTHOR]

Background Context: Watertight dural repair is crucial for both incidental durotomy and closure after intradural surgery.Purpose: The study aimed to describe a perfusion-based cadaveric simulation model with cerebrospinal fluid (CSF) reconstitution and to compare spine dural repair techniques.Study Design/setting: The study is set in a fresh tissue dissection laboratory.Sample Size: The sample includes eight fresh human cadavers.Outcome Measures: A watertight closure was achieved when pressurized saline up to 40 mm Hg did not cause further CSF leakage beyond the suture lines.Methods: Fresh human cadaveric specimens underwent cannulation of the intradural cervical spine for intrathecal reconstitution of the CSF system. The cervicothoracic dura was then exposed from C7-T12 via laminectomy. The entire dura was then opened in six cadavers (ALLSPINE) and closed with 6-0 Prolene (n=3) or 4-0 Nurolon (n=3), and pressurized with saline via a perfusion system to 60 mm Hg to check for leakage. In two cadavers (INCISION), six separate 2-cm incisions were made and closed with either 6-0 Prolene or 4-0 Nurolon, and then pressurized. A hydrogel sealant was then added and the closure was pressurized again to check for further leakage.Results: Spinal laminectomy with repair of intentional durotomy was successfully performed in eight cadavers. The operative microscope was used in all cases, and the model provided a realistic experience of spinal durotomy repair. For ALLSPINE cadavers (mean: 240 mm dura/cadaver repaired), the mean pressure threshold for CSF leakage was observed at 66.7 (±2.9) mm Hg in the 6-0 Prolene group and at 43.3 (±14.4) mm Hg in the 4-0 Nurolon group (p>.05). For INCISION cadavers, the mean pressure threshold for CSF leakage without hydrogel sealant was significantly higher in 6-0 Prolene group than in the 4-0 Nurolon group (6-0 Prolene: 80.0±4.5 mm Hg vs. 4-0 Nurolon: 32.5±2.7 mm Hg; p<.01). The mean pressure threshold for CSF leakage with the hydrogel sealants was not significantly different (6-0 Prolene: 100.0±0.0 mm Hg vs. 4-0 Nurolon: 70.0±33.1 mm Hg). The use of a hydrogel sealant significantly increased the pressure thresholds for possible CSF leakage in both the 6-0 Prolene group (p=.01) and the 4-0 Nurolon group (p<.01) when compared with mean pressures without the hydrogel sealant.Conclusions: We described the feasibility of using a novel cadaveric model for both the study and training of watertight dural closure techniques. 6-0 Prolene was observed to be superior to 4-0 Nurolon for watertight dural closure without a hydrogel sealant. The use of a hydrogel sealant significantly improved watertight dural closures for both 6-0 Prolene and 4-0 Nurolon groups in the cadaveric model. [ABSTRACT FROM AUTHOR]

Objectives  Pituitary carcinoma is a rare entity with fewer than 200 total cases reported in the English literature. Analysis of the population-level data from the National Cancer Database (NCDB) affords the opportunity to study this poorly understood tumor type. Methods  The NCDB was queried for site, histology, and metastasis codes corresponding to pituitary carcinoma. Statistical analyses were performed to determine factors associated with overall survival (OS). Results  A total of 92 patients with pituitary carcinoma met inclusion criteria. The 1 and 5 years of OS for all patients was 93.3% (95% confidence interval [CI]: 88.2–98.6%) and 80.0% (95% CI: 71.6–89.4%), respectively. Patients with invasive primary tumor behavior had 1 and 5 years of OS of 69.2% (95% CI: 48.2–99.5%) and 52.7% (95% CI: 31.2–89.2%), respectively. Multivariate analysis demonstrated that compared with benign primary behavior, invasive behavior had increased all-cause mortality (hazard ratio [HR], 1,296, 95% CI: 15.1– > 2,000). Surgery without adjuvant radiation or chemotherapy was the most common therapy (48.9%), followed by no treatment (40.2%). Compared with surgery alone, no treatment had worse OS (HR, 11.83, 95% CI: 1.41–99.56). Increasing age and female sex were both associated with increased mortality. Conclusions  The most common treatment for pituitary carcinoma is surgery alone followed by no surgery. Surgery alone has significantly better OS compared with no treatment. The efficacy of radiation, chemotherapy, and neurohormonal treatments needs to be examined with prospective studies. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process. Methods: A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients. Results: Eighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot‐Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high‐power field (44.4% vs 73.6%, p < 0.017). Conclusion: CRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide‐based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management. [ABSTRACT FROM AUTHOR]

Background: Primary sinonasal mucoepidermoid carcinoma (SN‐MEC) is a malignancy arising from seromucinous glands of the nasal cavity and paranasal sinuses. Given its rarity, few large‐scale studies have been performed. In this study we describe the incidence and determinants of survival of patients with SN‐MEC leveraging the National Cancer Database (NCDB). Methods: This was a retrospective, population‐based cohort study of patients diagnosed with SN‐MEC between 2004 and 2012 within the NCDB. The main outcome measure was overall survival (OS). Results: A total of 164 patients were identified. The cohort was composed of 47.6% males. Mean age at diagnosis was 59.7 years. The maxillary sinus was the most common primary site, accounting for 45.7% of cases. Eleven percent of patients presented with nodal disease, whereas 2.1% had distant metastases. Stage IV disease was seen in 30.4% of cases. A total of 79.8% of the patients underwent surgery, 61.0% received radiation therapy, and 15.1% had chemotherapy. OS at 1, 2, and 5 years was 83%, 77.0%, and 57%, respectively. On multivariate analysis, Medicaid insurance status (hazard ratio [HR], 7.29; 95% confidence interval [CI], 1.74‐30.57), advanced tumor size (HR, 4.94; 95% CI, 1.19‐20.5), and advanced nodal disease (N1: HR, 9.48; 95% CI, 1.66‐54.23; N2B: HR, 19.3; 95% CI, 1.07‐350.64) were associated with worse OS. Conclusion: Mucoepidermoid carcinoma is the most common salivary gland malignancy but a rare sinonasal malignancy, with 5‐year survival for SN‐MEC approximating 50%. A significant proportion of patients present with advanced disease. Both socioeconomic factors and tumor characteristics are associated with survival. [ABSTRACT FROM AUTHOR]

H1N1 influenza virus infection induces dramatic and permanent alveolar remodeling mediated by p63 progenitor cell expansion in both mice and some patients with acute respiratory distress syndrome. This persistent lung epithelial dysplasia is accompanied by chronic inflammation, but the driver(s) of this pathology are unknown. This work identified de novo appearance of solitary chemosensory cells (SCCs), as defined by the tuft cell marker doublecortin-like kinase 1, in post-influenza lungs, arising in close proximity with the dysplastic epithelium, whereas uninjured lungs are devoid of SCCs. Interestingly, fate mapping demonstrated that these cells are derived from p63-expressing lineage-negative progenitors, the same cell of origin as the dysplastic epithelium. Direct activation of SCCs with denatonium succinate increased plasma extravasation specifically in post-influenza virus-injured lungs. Thus we demonstrate the previously unrecognized development and activity of SCCs in the lung following influenza virus infection, implicating SCCs as a central feature of dysplastic remodeling. [ABSTRACT FROM AUTHOR]

Background: Sinonasal adenoid cystic carcinoma (SNACC) is a rare malignancy with a propensity for distant metastasis. In this study we describe the incidence and determinants of survival among patients with SNACC between the years 2004 and 2012 using the National Cancer Database (NCDB). Methods: This was a retrospective, population‐based cohort study performed at a tertiary academic medical center. All participants were diagnosed with SNACC between 2004 and 2012 within the NCDB. The main outcome was overall survival (OS). Results: A total of 793 patients were identified. The cohort was composed of 46.9% males. Mean age at diagnosis was 59.6 years. The maxillary sinus was the most common primary site (49.7%). Nodal disease was seen in 3.6% of the patients, whereas 3.7% had distant metastases. Stage IV disease was seen in 49.1% of cases. In total, 77.4% of patients underwent surgery, 68.2% received radiation therapy, and 16.4% had chemotherapy. Median OS was 78.5 months; OS at 1, 2, and 5 years was 91%, 83%, and 61%, respectively. On multivariate analysis, advanced age (p = 0.001), frontal sinus primary site (p < 0.001), positive margins (p < 0.001), Charlson comorbidity index >0 (p = 0.01), residing in an urban setting (p = 0.04), poorly differentiated or undifferentiated tumor grade (p = 0.003), and advanced tumor stage (p = 0.01) were associated with worse OS, whereas surgery (p < 0.001), but not radiation therapy (p = 0.52) or chemotherapy (p = 0.57), predicted improved OS. Conclusion: Predictors of survival in SNACC include age, comorbidity status, grade, and stage. Surgery is associated with improved survival and remains the mainstay of therapy, whereas the roles of radiation therapy and chemotherapy require future investigation. [ABSTRACT FROM AUTHOR]

There has been a conscious effort to address osteoporosis in the aging population. As bisphosphonate and intermittent parathyroid hormone (PTH) therapy become more widely prescribed to treat osteoporosis, it is important to understand their effects on other physiologic processes, particularly the impact on spinal fusion. Despite early animal model studies and more recent clinical studies, the impact of these medications on spinal fusion is not fully understood. Previous animal studies suggest that bisphosphonate therapy resulted in inhibition of fusion mass with impeded maturity and an unknown effect on biomechanical strength. Prior animal studies demonstrate an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. The purpose of this study was to determine if bisphosphonates and intermittent PTH treatment have impact on human spinal fusion. A systematic review of the literature published between 1980 and 2015 was conducted using major electronic databases. Studies reporting outcomes of human subjects undergoing 1, 2, or 3-level spinal fusion while receiving bisphosphonates and/or intermittent PTH treatment were included. The results of relevant human studies were analyzed for consensus on the effects of these medications in regards to spinal fusion. There were nine human studies evaluating the impact of these medications on spinal fusion. Improved fusion rates were noted in patients receiving bisphosphonates compared to control groups, and greater fusion rates in patients receiving PTH compared to control groups. Prior studies involving animal models found an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. No significant complications were demonstrated in any study included in the analysis. Bisphosphonate use in humans may not be a deterrent to spinal fusion. Intermittent parathyroid use has shown early promise to increase fusion mass in both animal and human studies but further studies are needed to support routine use. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective analysis of a nationwide private insurance database. Chi-square analysis and linear regression models were utilized for outcome measures. Purpose: The purpose of this study was to investigate any relationship between lumbar degenerative disc disease, diabetes, obesity and smoking tobacco. Overview of Literature: Diabetes, obesity, and smoking tobacco are comorbid conditions known to individually have effect on degenerative disc disease. Most studies have only been on a small populous scale. No study has yet to investigate the combination of these conditions within a large patient cohort nor have they reviewed the combination of these conditions on degenerative disc disease. Methods: A retrospective analysis of insurance billing codes within the nationwide Humana insurance database was performed, using PearlDiver software (PearlDiver, Inc., Fort Wayne, IN, USA), to identify trends among patients diagnosed with lumbar disc degenerative disease with and without the associated comorbidities of obesity, diabetes, and/or smoking tobacco. Patients billed for a comorbidity diagnosis on the same patient record as the lumbar disc degenerative disease diagnosis were compared over time to patients billed for lumbar disc degenerative disease without a comorbidity. There were no sources of funding for this manuscript and no conflicts of interest. Results: The total number and prevalence of patients (per 10,000) within the database diagnosed with lumbar disc degenerative disease increased by 241.4% and 130.3%, respectively. The subsets of patients within this population who were concurrently diagnosed with either obesity, diabetes, tobacco use, or a combination thereof, was significantly higher than patients diagnosed with lumbar disc degenerative disease alone (p <0.05 for all). The number of patients diagnosed with lumbar disc degenerative disease and smoking rose significantly more than patients diagnosed with lumbar disc degenerative disease and either diabetes or obesity (p <0.05). The number of patients diagnosed with lumbar disc degenerative disease, smoking and obesity rose significantly more than the number of patients diagnosed with lumbar disc degenerative disease and any other comorbidity alone or combination of comorbidities (p <0.05). Conclusions: Diabetes, obesity and cigarette smoking each are significantly associated with an increased diagnosis of lumbar degenerative disc disease. The combination of smoking and obesity had a synergistic effect on increased rates of lumbar degenerative disc disease. Patient education and preventative care is a vital goal in prevention of degenerative disc disease within the general population. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective analysis of national insurance billing database.Objective: To examine trends in reoperation after single-level lumbar discectomy.Summary Of Background Data: Lumbar discectomy is the most commonly performed procedure for treatment of radiculopathy caused by disc herniation. Randomized clinical trials have demonstrated the advantage of discectomy over nonsurgical treatment options, allowing for a more rapid reduction in symptoms. However, population-level data regarding reoperation after single level discectomy is limited.Methods: Data were collected using the commercially available PearlDiver software for patients billed with the Current Procedural Terminology code for our index procedure, hemilaminotomy and removal of disc material, between January 2007 and September 2014. The index group was then followed for up to 4 years for recurrent lumbar surgery, including spinal fusion, laminectomy, and additional discectomy.Results: Analysis of data obtained from 13,654 patient records revealed a rate of additional lumbar surgeries after single-level discectomy of 3.95% (539/13654) within 3 months and 12.2% (766/6274) within 4 years of the index procedure. Lumbar spinal fusion was performed on 5.9% (370/6274) of patients within 4 years. Patients who received a re-exploration discectomy within 2 years of the index procedure went on to receive lumbar fusion at a rate of 38.4% (48/125) within the 4 years after the re-exploration discectomy. The average additional cost of lumbar reoperation, as measured by insurance reimbursement, was approximately $11,161 per-patient per year.Conclusion: We report an overall 4-year reoperation rate of 12.2% after single-level discectomy. In addition, we report a rate of progression to lumbar fusion following re-exploration discectomy of 38.4% within 4 years of reoperation. Further studies are needed regarding the best treatment algorithm in patients with reherniation or iatrogenic instability after lumbar discectomy. This study should enhance the shared decision making process by providing surgeons and patients with valuable data regarding the frequency and nature of reoperations after discectomy.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Background Context: Minimally invasive sacroiliac (SI) joint fusion has become increasingly relevant in recent years as a treatment for SI joint pathology. Previous studies have found minimally invasive SI fusion to be an effective and safe treatment option for chronic SI joint pain. However, these studies have been primarily single-center, case-based, or manufacturer-sponsored investigations, and as such their findings are limited to their sample populations.Purpose: The aim of this study was to investigate the safety of minimally invasive SI fusion using a large nationwide sample group to more accurately identify complication rates of this increasingly popular procedure.Study Design/setting: This is a retrospective database study.Patient Sample: The sample includes patients within the orthopedic subset of Humana database who underwent minimally invasive SI fusion between 2007 and 2014.Outcome Measures: Complications and novel lumbar and nerve pathology were the outcome measures.Methods: Patients undergoing minimally invasive SI fusion from 2007 to 2014 were identified using the Pearl Diver patient record database (Pearl Diver Technologies, West Conshohocken, PA, USA) from the nationwide private insurance provider Humana Inc. This approach provided access to records of over 18 million patients in every major geographic region of the country. Using the ICD-9 diagnosis codes (International Classification of Diseases 9th edition), data from patient records were analyzed to reveal incidence of postoperative infection, pain, osteomyelitis, joint derangement, urinary tract infection, and novel lumbar and nervous system pathology.Results: Four hundred sixty-nine patients (305 female; 164 male) within the Humana insurance database received minimally invasive SI fusion between 2007 and 2014. Data from these patients showed a substantial increase in the use of the procedure over this 7-year period. Among these patients, an overall complication rate of 13.2% (n=62) was seen at 90 days postoperatively and 16.4% (n=77) at 6 months. The number of patients receiving a first time diagnosis of lumbar pathology following minimally invasive SI fusion in the sample population was also analyzed. The incidence of novel lumbar pathology in this population was 3.6% (n=17) at 90 days postoperatively and 5.3% (n=25) at 6 months. Men experienced diagnoses of novel lumbar pathology at higher rates than women within both 90 days (men=6.7%; women≤3.3%) and 6 months (men=9.1%; women≤3.3%) of the procedure (p<.01).Conclusions: The results of this study show that minimally invasive SI joint fusion could possibly carry higher risks of complications than previously stated. These findings are useful for physicians and patients when considering treatment for chronic SI joint pain. [ABSTRACT FROM AUTHOR]