The impact of adenotonsillectomy on healthcare utilization in children with obstructive sleep apnea: Experience of an integrated medical model.

BACKGROUND AND OBJECTIVES: Studies suggest that children with obstructive sleep apnea (OSA) have increased healthcare utilization patterns in comparison to matched controls. However, the effect of adenotonsillectomy (AT) on utilization patterns in these children is poorly understood. Additionally, no previous studies have compared the effect of AT on healthcare utilization patterns across different OSA severity groups. The aim of this retrospective cohort study is to assess the effects of surgical treatment on the level of healthcare utilization among children with OSA at a large integrated multicenter healthcare system. METHODS: Retrospective analysis was performed of children aged 3-12 diagnosed with OSA via an attended polysomnogram (PSG) between December 2016 and February 2019. Demographic variables including age (at time of PSG), body mass index (BMI), race, and ethnicity were obtained. Variables for healthcare utilization were assessed for 12 months prior to PSG, and for 12 months after PSG (or after AT, delayed for the first 30 days after surgery to account for surgery-related visits). Healthcare utilization variables assessed included the total number of outpatient visits, inpatient, and emergency department (ED) visits, visits involving diagnostic codes associated with upper respiratory infection (URI), otitis media (OM), and allergic rhinitis (AR), prescription data involving intranasal steroids or leukotriene receptor antagonists (LTRA), and communication data such as secure message load and specialty referrals. Repeated measure linear difference-in-difference (D-I-D) models were used to assess the causal impact of AT on healthcare utilization outcomes. Sensitivity analyses were performed using modeling with a Poisson distribution and as an unadjusted model, with statistical significance set to p < 0.05. RESULTS: Analysis elicited 577 children identified with OSA. Of these, 336 (58.2 %) underwent observation while 241 (41.8 %) underwent AT. The mean age was 6.4 years, with a slight male predominance (60.5 %). Analysis of baseline healthcare utilization patterns revealed that the treatment group had a significantly higher number of baseline inpatient/ED visits and OM visits in comparison to the observation group, but no differences in regards to baseline outpatient visits, or in visits involving URI or AR. Analysis of the entire OSA cohort via D-I-D modelling showed a significantly larger reduction in outpatient visits, secure messages, specialty referrals, and the use of intranasal steroid and LTRA in the treatment group compared to the observation group. Stratification of children based on OSA severity showed that the significant differences in healthcare utilization attributed to surgical treatment were primarily driven by the severe OSA group. Children with severe OSA who underwent AT showed significant reductions in most variables including outpatient visits, inpatient/ED visits, and OM visits. Alternatively, the only significant reductions in healthcare utilization among children with mild OSA treated with AT were in AR visits, intranasal steroid use, and LTRA use. Pattern changes among children with moderate OSA compared similarly to those with mild OSA. CONCLUSION: To the authors' knowledge this study represents the largest available study assessing the impact of AT on healthcare utilization in children with OSA that also considers the effect of OSA severity on utilization patterns. AT appears to decrease healthcare utilization patterns, particularly in children with severe OSA. Alternatively, children with mild or moderate OSA treated with AT had only modest reductions in healthcare utilization patterns.

Oral bacteria accelerate pancreatic cancer development in mice.

OBJECTIVE: Epidemiological studies highlight an association between pancreatic ductal adenocarcinoma (PDAC) and oral carriage of the anaerobic bacterium Porphyromonas gingivalis, a species highly linked to periodontal disease. We analysed the potential for P. gingivalis to promote pancreatic cancer development in an animal model and probed underlying mechanisms. DESIGN: We tracked P. gingivalis bacterial translocation from the oral cavity to the pancreas following administration to mice. To dissect the role of P. gingivalis in PDAC development, we administered bacteria to a genetically engineered mouse PDAC model consisting of inducible acinar cell expression of mutant Kras (Kras +/LSL-G12D; Ptf1a-CreER, iKC mice). These mice were used to study the cooperative effects of Kras mutation and P. gingivalis on the progression of pancreatic intraepithelial neoplasia (PanIN) to PDAC. The direct effects of P. gingivalis on acinar cells and PDAC cell lines were studied in vitro. RESULTS: P. gingivalis migrated from the oral cavity to the pancreas in mice and can be detected in human PanIN lesions. Repetitive P. gingivalis administration to wild-type mice induced pancreatic acinar-to-ductal metaplasia (ADM), and altered the composition of the intrapancreatic microbiome. In iKC mice, P. gingivalis accelerated PanIN to PDAC progression. In vitro, P. gingivalis infection induced acinar cell ADM markers SOX9 and CK19, and intracellular bacteria protected PDAC cells from reactive oxygen species-mediated cell death resulting from nutrient stress. CONCLUSION: Taken together, our findings demonstrate a causal role for P. gingivalis in pancreatic cancer development in mice.

Microdebrider complications in sinus surgery: Analysis of the openFDA database.

Objective: Functional endoscopic sinus surgery is a commonly performed otolaryngologic procedure that often uses the microdebrider device for tissue removal. Given the ubiquitous nature of the instrument, we sought to better define the patterns of device failure using the postmarket surveillance openFDA database. Methods: The openFDA database was queried for all microdebrider-related adverse events from January 1, 2000 to November 1, 2020. Descriptive information on the nature of device failure and any associated patient injury was compiled. Reports not directly related to device failure were excluded from the analysis. Results: A total of 641 events were included in the analysis. The most common device failure was overheating (n = 348, 54.3%), followed by material separation (n = 173, 27%), and inconsistent device activation (n = 52, 8.1%). Of the reported events, the vast majority did not result in patient harm (n = 579, 90.3%). On review of the remaining cases, only 24 events (3.7%) resulted in true harm to the patient, defined as a temporary or permanent injury or >30 min of additional anesthesia time. Of these cases, the need to reschedule surgical cases (n = 5, 0.8%), retained foreign body (n = 5, 0.8%), and thermal tissue injury (n = 3,0.5%) were the most common. Five patients suffered an injury due to surgeon error unrelated to device malfunction (n = 5, 0.8%). Conclusions: Microdebrider device failures are extremely rare. When they do occur, less than 10% result in patient harm. In cases of patient harm related to microdebrider failure, preoperative testing of the device before use could prevent many of the reported malfunctions.

Steroid Efficacy on Audiologic Recovery in Patients With Sudden Sensorineural Hearing Loss and Vestibular Schwannoma: A Retrospective Review.

OBJECTIVES: The objectives of this study are to (i) estimate the incidence of vestibular schwannoma (VS) among patients in an integrated healthcare system who present for evaluation of sudden sensorineural hearing loss (SSNHL) and (ii) evaluate the efficacy of empiric steroid therapy on audiologic recovery among SSNHL patients ultimately diagnosed with VS. METHODS: A retrospective chart review was performed on patients presenting with SSNHL in 2021 at a multicenter integrated healthcare system serving over 4 million members. Patient demographics, audiometric data, VS diagnosis, therapeutic steroid intervention, and data regarding treatment response were recorded. A clinically significant audiometric improvement was defined as (i) an increase of 15% in word recognition score, (ii) a decrease of 15 dB in four-frequency pure-tone average (PTA) using frequencies of 500, 1000, 2000, and 4000 Hz, or (iii) a PTA of <20 dB on follow-up audiogram. RESULTS: Six hundred fifty-eight patients were reviewed, of which 309 (56.0% male; mean, 57.5 years) met the inclusion criteria with audiometric data and magnetic resonance imaging data. Ten patients (70.0% male; mean, 51.3 years) were found to have VS. Of these, five patients received oral steroid therapy alone, and five had combination therapy (oral + intratympanic steroid injections). No patients received intratympanic steroid therapy alone. Median PTA improvement with steroid therapy was 3.1-dB hearing loss, and median word recognition score improvement was 16.5%. Six of 10 patients demonstrated clinically significant audiometric improvement with steroid therapy. CONCLUSION: This study represents the largest US-based study showcasing the prevalence of VS in patients originally presenting with SSNHL. It also reinforces previous findings that VS does not preclude trials of steroid therapy.

Pediatric vagal nerve stimulator explantation: A comprehensive literature review and tertiary care experience.

OBJECTIVE: Patients with medically-refractory epilepsy who undergo vagal nerve stimulator (VNS) implantation to reduce seizure burden sometimes require device removal. Complete explantation refers to the removal of both the generator and vagal nerve leads, and is uncommonly performed by otolaryngologists due to the perceived risk associated with lead removal. This comprehensive literature review and case series studies safety outcomes among pediatric patients undergoing complete VNS explantation. STUDY DESIGN/SETTING: Literature review and tertiary care case series. METHODS: PubMed, Embase, Web of Science, and Google Scholar were searched to identify all articles involving VNS explantation prior to January 2023. A retrospective review of pediatric patients undergoing complete VNS explantation from 2009 to 2023 at our tertiary center was also conducted. RESULTS: After screening, 36 articles were retained involving 399 patients (139 confirmed children) who underwent complete VNS explantation. 26 patients (6.5%) experienced 1+ peri/post-operative complications. These included temporary VF paresis or dysphonia (n = 14; 3.6%), permanent vocal fold (VF) paralysis/paresis (n = 6; 1.5%), internal jugular vein injury (n = 4; 1.0%), temporary dysphagia (n = 2; 0.50%), and cable-bowstring phenomenon (n = 1; 0.25%). Data from our tertiary care center revealed eight patients (6 M: 2 F) with a mean age of 11.4 ± 6.2 years. Devices were removed for clinical ineffectiveness (n = 2), infection (n = 2), lead failures (n = 2), and increased lead impedance (n = 2). Mean total length of implantation was 44.4 ± 40.3 months. Mean follow-up was 44.8 ± 35.2 months. No complications were identified. CONCLUSIONS: Complete VNS device removal in pediatric patients is technically feasible with low reported complications. Working alongside neurosurgery, otolaryngologists offer unique expertise in dissection along the vagus nerve and may thus add value to the practice of VNS surgery.

Cardiovascular Risk Factors in Patients With Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

OBJECTIVE: The interruption of vascular supply to the inner ear is one of several proposed etiologies of sudden sensorineural hearing loss (SSNHL). The increased presence of cardiovascular risk factors may predispose patients to SSNHL through this pathway. This systematic review and meta-analysis studies the presence of cardiovascular risk factors in patients diagnosed with SSNHL. DATA SOURCES: Databases included PubMed/Medline, OVID, EMBASE, Cochrane, and Web of Science. REVIEW METHODS: Inclusion criteria included studies featuring SSNHL patients presenting with 1+ cardiovascular risk factors. Exclusion criteria included case reports and studies without outcome measures. Two investigators independently reviewed all manuscripts and performed quality assessments using validated tools. RESULTS: Of 532 identified abstracts, 27 studies met inclusion criteria (19 case-control, 4 cohorts, 4 case series). Of these, 24 underwent meta-analysis encompassing a total of 77,566 patients (22,620 SSNHL patients, 54,946 matched controls). The mean age was 50.43 years. SSNHL patients were more likely to have concomitant diabetes (odds ratio [OR] 1.61 [95% confidence interval [CI]: 1.31, 1.99; p < .00001]) and hypertension (OR 1.5 [95% CI: 1.16, 1.94; p = .002]). An increased standard mean difference of total cholesterol of 11.09 mg/dL (95% CI; 3.51, 18.67; p = .004) was noted in the SSNHL group compared with the controls. No significant differences in smoking, high-density lipoprotein, triglycerides, or body mass index were detected. CONCLUSION: Patients presenting with SSNHL have a significantly higher risk of concomitant diabetes, hypertension, and higher total cholesterol in comparison to matched controls. This may indicate a higher cardiovascular risk profile in this population. More prospective and matched cohort studies are needed to understand the role of cardiovascular risk factors in SSNHL.

Hearing Preservation in Observed Sporadic Vestibular Schwannoma: A Systematic Review.

OBJECTIVE: To characterize the natural history of hearing loss for patients presenting with serviceable hearing (SH) who undergo a wait-and-scan approach for sporadic vestibular schwannoma (VS) using aggregate time-to-event survival analysis. STUDY DESIGN: Systematic review. SETTING: Published international English literature, January 1, 2000 to May 31, 2020. PATIENTS: Patients with sporadic VS entering a wait-and-scan approach with SH at diagnosis. INTERVENTIONS: Observation with serial MRI and audiometry. RESULTS: In total, 3,652 patients from 26 studies were included for analysis. Mean age at diagnosis was 58.8 years (SD, 4.1). Mean follow-up was 49.2 months (SD, 26.5). In total, 755 patients (21%) failed conservative treatment and underwent radiosurgery or microsurgery at the time of last follow-up. The average loss to follow-up was 6.9% (SD, 11.1). A total of 1,674 patients had SH at the time of diagnosis. Survival rates for maintaining SH were 96% at 1 year, 77% at 3 years, 62% at 5 years, and 42% at 10 years following diagnosis. CONCLUSION: In this systematic review, aggregate data from 3,652 patients across 26 studies show consistent patterns in progression of hearing loss during observation for patients with sporadic VS as a function of time. As an easy-toremember conservative benchmark for those presenting with SH at diagnosis: approximately 75% retain SH at 3 years, 60% at 5 years, and 40% at 10 years.

Regenerative Properties of Autologous Fat Grafting in a Complicated Radiation-Induced Wound.

INTRODUCTION: Delayed wound healing and ulceration in radiated tissue is a surgical challenge. Autologous fat grafting can reverse skin changes secondary to radiation such as fibrosis, scarring, contracture, and pain. Adipose-derived stem cells are thought to contribute to the regenerative properties of fat. OBJECTIVE: In this case report, the authors discuss the role of fat grafting as a means for effective wound healing in a patient with a chronic nonhealing radiation-induced skin wound. CASE REPORT: The patient is a 79-year-old male with a history of medically complicated obesity who presented with a fluoroscopic radiation-induced wound that developed 11 years after non-ST-elevation myocardial infarction for which he underwent placement of 6 stents via percutaneous transluminal coronary angiography. The wound was complicated by several infections and remained refractory to multiple interventions despite topical steroid use, regular wound dressing changes, debridements, and hyperbaric oxygen therapy. In consideration of the patient's body mass index of greater than 50 kg/m2 and modest weight loss attempts, surgical intervention involving wide local resection and flap closure was not thought to be a solution. Fat grafting was performed 19 months after initial presentation, with near-complete healing evident 10 months after the procedure. CONCLUSIONS: Chronic nonhealing wounds can provide a tremendous burden to the patient in terms of time, costs, and morbidity. Despite enduring a prolonged 19-month course involving multiple failed interventions and several wound-related infections, the patient achieved wound healing via fat grafting. Earlier intervention with fat grafting may prove helpful to patients who do not show evidence of healing via other modalities and for whom flap surgery is not an option.

Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells.

Porphyromonas gingivalis is a member of the dysbiotic oral microbiome associated with oral inflammation and periodontal disease. Intriguingly, epidemiological studies link P. gingivalis to an increased risk of pancreatic cancer. Given that oral bacteria are detected in human pancreatic cancer, and both mouse and human pancreata harbor microbiota, we explored the involvement of P. gingivalis in pancreatic tumorigenesis using cell lines and a xenograft model. Live P. gingivalis induced proliferation of pancreatic cancer cells; however, surprisingly, this effect was independent of Toll-like receptor 2, the innate immune receptor that is engaged in response to P. gingivalis on other cancer and immune cells, and is required for P. gingivalis to induce alveolar bone resorption. Instead, we found that P. gingivalis survives inside pancreatic cancer cells, a trait that can be enhanced in vitro and is increased by hypoxia, a central characteristic of pancreatic cancer. Increased tumor cell proliferation was related to the degree of intracellular persistence, and infection of tumor cells with P. gingivalis led to enhanced growth in vivo. To the best of our knowledge, this study is the first to demonstrate the direct effect of exposure to P. gingivalis on the tumorigenic behavior of pancreatic cancer cell lines. Our findings shed light on potential mechanisms underlying the pancreatic cancer-periodontitis link.

Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism.

OBJECTIVE: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome. METHODS: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories. RESULTS: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; P=.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; P=.02); when adjusted for cancer, the relationship was no longer significant (P=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; P=.66). Similar cumulative rates for CRNMB were observed (P=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category. CONCLUSION: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03504007.

Is Continued Perioperative Antithrombotic Therapy Safe When Performing Direct Microlaryngoscopy?

OBJECTIVES/HYPOTHESIS: To evaluate whether antithrombotic status impacts the incidence of perioperative or postoperative bleeding in direct microlaryngoscopy (DML). STUDY DESIGN: Retrospective chart review. METHODS: Patients undergoing DML in a single surgeon's practice from September 2012 to September 2017 were studied. Included patients underwent DML with or without biopsy, balloon dilation, microsurgery, laser ablation, or vocal fold injection. Patients were stratified based on perioperative antithrombotic status and assessed for rates of peri- and postoperative bleeding and other complications. RESULTS: Of the 581 patients meeting inclusion criteria, 179 patients (31%) had a history of baseline antithrombotic therapy. Of these patients, 124 had perioperative continuation of their therapy. Medicated patients were older (P < .01), predominately male (P < .01), and increasingly comorbid (P < .01). Perioperative complications unrelated to bleeding occurred in 22 patients (4%), minor perioperative bleeding occurred in four patients (0.7%), and minor postoperative bleeding occurred in 12 of the 479 patients with recorded follow-up (2.5%). There were no postoperative bleeds requiring intervention or readmission, and no recorded thrombotic events during the peri- and postoperative period. There was no difference in perioperative bleeding based on baseline antithrombotic status (P = .81). Patients on baseline antithrombotic therapy were more likely to have a postoperative bleed in comparison to patients without history of antithrombotic use (P < .01). However, there were no significant differences in postoperative bleeding between patients on baseline anticoagulation who continued or ceased their medication perioperatively (P = .45). CONCLUSIONS: Perioperative continuation of antithrombotic medications appears to be safe when performing routine DML. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

Chronic rhinosinusitis in eosinophilic granulomatosis with polyangiitis: clinical presentation and antineutrophil cytoplasmic antibodies.

BACKGROUND: In this study we aim to describe presenting characteristics and identify prognostic factors for disease resolution in patients with chronic rhinosinusitis (CRS) in the setting of eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients evaluated at a tertiary care center with diagnoses of EGPA and CRS were identified. Descriptive statistics were obtained. Univariate analysis was used to search for prognostic factors associated with higher Lund-Mackay score at presentation and disease resolution. RESULTS: Forty-four patients were included with a mean age of 52.7 (standard deviation, 14) years. Twenty-one patients (47.7%) were female, all had a diagnosis of asthma, and 36 (83.7%) had eosinophils >10%. Common presenting symptoms for CRS included nasal discharge (87.9%) followed by nasal congestion (83.9%) and facial pain and pressure (83.8%). Medical management of CRS included systemic corticosteroids (93.2%) and systemic antibiotics (75%). Surgical intervention occurred in 29 patients (67%). Nine patients (20.5%) had resolution of sinus symptoms, including 4 with imaging confirmation. Fourteen patients (31.8%) had continued CRS, but with improved symptoms, whereas 9 patients (20.5%) had continued CRS with no improvement in symptoms. Eleven patients (25%) were lost to follow-up and 4 (9.1%) died. Univariate analysis did not show antineutrophil cytoplasmic antibody positivity, presence of peripheral eosinophilia, gender, age, or absence of systemic therapy to be predictive of higher Lund-Mackay score at presentation or predictive of disease resolution. CONCLUSION: CRS in patients with EGPA is often refractory to medical and surgical management. Treatment of these patients should occur in a multidisciplinary setting.

Quantifying Tertiary Referral Center Bias in Vestibular Schwannoma Research.

OBJECTIVE: The majority of research influencing our understanding of vestibular schwannoma (VS) comes from large tertiary referral centers, and as a consequence, is inherently prone to referral bias. The objective of the current study was to characterize tertiary referral center bias in VS research. STUDY DESIGN: Single-institution retrospective clinical, audiometric, and radiologic review. SETTING: One tertiary referral center. PATIENTS: One hundred twenty-three patients with sporadic VS treated at our institution, consisting of a local cohort of all 41 VS patients residing in the same US county as our medical center and a referral cohort of 82 patients from outside counties matched 2:1 based on age, sex, and year of diagnosis. INTERVENTION: Surgical resection, stereotactic radiosurgery (SRS), observation. MAIN OUTCOME MEASURES: Clinical manifestations, audiometric and radiologic findings, elected treatment modality. RESULTS: Local patients had significantly longer follow-up after initial presentation compared to referral patients (median 4.0 vs 2.2 yr; p = 0.007). Referral patients were significantly less likely to have an incidental VS diagnosis (1% vs. 29%; p < 0.001) and presented with worse symptomatology such as hearing loss (80% vs. 54%; p = 0.002), dizziness (72% vs. 44%; p = 0.002), headache (29% vs. 15%; p = 0.075), and other cranial nerve dysfunction (11% vs. 0%; p = 0.029). Audiometrically, referral patients had significantly poorer word recognition scores at presentation (median 70% vs. 90%; p = 0.043). Local patients were more likely to have tumors confined to the IAC compared with referral patients, and had significantly smaller tumors when restricted to this region (median 4.0 vs 6.5 mm; p = 0.005). Referral patients were significantly more likely to undergo definitive management with either radiosurgery or microsurgery following primary evaluation compared to local patients (48% vs. 24%; p = 0.013). CONCLUSION: These data suggest that the majority of existing literature surrounding VS likely suffers from referral bias, whereby disease characteristics and management decisions are distinct from that of the general VS patient population.

Alloplastic Facial Implants: A Systematic Review and Meta-Analysis on Outcomes and Uses in Aesthetic and Reconstructive Plastic Surgery.

BACKGROUND: Alloplastic materials in facial surgery have been used successfully for various applications in the reconstructive restoration or aesthetic augmentation of the facial skeleton. The objective of this study was to conduct a comprehensive systematic review of alloplastic implant materials utilized to augment the facial skeleton stratified by anatomical distribution, indication, specific material used, and respective outcomes. METHODS: A comprehensive systematic review on alloplastic facial implant data was conducted utilizing Medline/PubMed database. Articles were stratified by (1) anatomic localization in the face, as well as (2) alloplastic material. RESULTS: A total of 17 studies (n = 2100 patients, follow-up range = 1 month-27 years) were included. Overall, mersilene mesh implants were associated with the highest risk of infection (3.38%). Methyl methacrylate implants were associated with the highest rate of hematoma (5.98%). Implants placed in the malar region (2.67%) and frontal bones (2.50%) were associated with the highest rates of infection. Implants placed in the periorbital region were associated with the highest rate of inflammation (8.0%), explantation (8.0%), and poor cosmetic outcome (17.0%). Porous implants were shown to be more likely to potentiate infection than non-porous implant types. CONCLUSIONS: Alloplastic facial implants are a reliable means of restoring facial symmetry and achieving facial skeletal augmentation with a relatively low complication profile. It is important for plastic surgeons to understand the relative risks for each type of implant to develop postoperative complications or poor long-term cosmetic results. Interestingly, porous implants were shown to be more likely to potentiate infection than non-porous implant types. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Serum 25-hydroxyvitamin D and bone turnover markers in Palestinian postmenopausal osteoporosis and normal women.

This study evaluated the association of vitamin D and bone markers with the development osteoporosis in Palestinian postmenopausal women. Even though vitamin D deficiency was very high for the recruited subjects, it was not associated with osteoporosis except for bones of the hip. Age and obesity were the strongest determining factors of the disease. PURPOSE: The purpose of this study was to investigate the association of bone mineral density (BMD) with serum vitamin D levels, parathyroid hormone (PTH), calcium, obesity, and bone turnover markers in Palestinian postmenopausal women. METHODS: Three hundred eighty-two postmenopausal women (≥45 years) were recruited from various women clinics for BMD assessment (131 women had osteoporosis and 251 were normal and served as controls). Blood samples were obtained for serum calcium, PTH, 25(OH)D, bone formation (N-terminal propeptide (PINP)), and bone resorption (serum C-terminal telopeptide of type I collagen (CTX1)) markers. RESULTS: Women with osteoporosis had statistically significant lower mean weight, height, body mass index (BMI), and serum calcium (p < 0.05) compared to controls. No significant differences were detected between the mean values of bone turnover markers (CTX and PINP), 25(OH)D, and PTH of the two groups. Women with vitamin D deficiency (severe and insufficiency) represented 85.9% of the study subjects. Multiple and logistic regression showed that age and BMI significantly affected BMD and vitamin D had a significant association with BMD only at the lumbar spine. BMI was positively correlated with BMD and PTH but negatively correlated with vitamin D. Logistic regression showed that the odds ratio (OR) for having osteoporosis decreased with increasing BMI (overweight OR = 0.11, p = 0.053; obese OR = 0.05, p = 0.007). CONCLUSIONS: There was no direct correlation between BMD and PTH, bone turnover markers, and vitamin D except at the lumbar spine. A negative correlation between BMD and age and a positive correlation with BMI were observed. The protective effect of obesity on osteoporosis was complicated by the effect of obesity on vitamin D and PTH.

Phosphatidyl inositol-3 kinase (PIK3CA) E545K mutation confers cisplatin resistance and a migratory phenotype in cervical cancer cells.

The phosphatidylinositol-3 kinase (PI3K)/Akt/mTOR signaling pathway is activated in many human cancers. Previously, we reported that patients with early stage cervical cancer whose tumours harbour PIK3CA exon 9 or 20 mutations have worse overall survival in response to treatment with radiation and cisplatin than patients with wild-type PIK3CA. The purpose of this study was to determine whether PIK3CA-E545K mutation renders cervical cancer cells more resistant to cisplatin and/or radiation, and whether PI3K inhibition reverses the phenotype. We found that CaSki cells that are heterozygous for the PIK3CA-E545K mutation are more resistant to cisplatin or cisplatin plus radiation than either HeLa or SiHa cells that express only wild-type PIK3CA. Similarly, HeLa cells engineered to stably express PIK3CA-E545K were more resistant to cisplatin or cisplatin plus radiation than cells expressing only wild-type PIK3CA or with PIK3CA depleted. Cells expressing the PIK3CA-E545K mutation also had constitutive PI3K pathway activation and increased cellular migration and each of these phenotypes was reversed by treatment with the PI3K inhibitor GDC-0941/Pictilisib. Our results suggests that cervical cancer patients whose tumours are positive for the PIK3CA-E545K mutation may benefit from PI3K inhibitor therapy in concert with standard cisplatin and radiation therapy.