The Prognostic Implications of Neutrophil-to-Lymphocyte Ratio in Olfactory Neuroblastoma.

OBJECTIVE: Olfactory neuroblastoma is a rare sinonasal malignancy with comparatively positive prognosis and survival, but with a range of biological behaviors that can be difficult to prognosticate with current means of risk stratification. Neutrophil-to-lymphocyte ratio (NLR) has been found across a diverse range of malignancies to be associated with poorer outcomes. This paper aims to elucidate the relationship of NLR with olfactory neuroblastoma to assess its prognostic value in this setting. STUDY DESIGN: Retrospective chart review. SETTING: A single tertiary care academic hospital. METHODS: The study cohort included all patients treated for initial presentation of olfactory neuroblastoma from 2004 to 2020. NLR was calculated from preoperative labs, and each patient was evaluated for Kadish staging, Hyams grade, intraoperative positive margin, use of adjuvant therapy, posttreatment recurrence, and death. All statistical analysis was conducted using R and relationship between NLR and variables was assessed via binomial logistic regression. RESULTS: Forty-four patients were included, 24 were male. Average age 52.8, average length of follow-up was 9.6 years. Patients were grouped by low (Kadish A/B) and advanced (Kadish C/D) stage, n = 23 and n = 21, respectively, and low (Hyams I/II) and high (Hyams III/IV) risk, n = 15 and n = 11, respectively. Advanced Kadish stage was associated with elevated NLR, odds ratio 5.69 [2.30, 20.7], P = .001. No other variables were associated with elevated NLR including Hyams grade, margin status, recurrence, and mortality. CONCLUSION: Higher Kadish grade is associated with elevated NLR which may provide novel prognostic value to current risk-stratifying systems.

Impact of puberty on procedure frequency for treatment of simple head and neck lymphatic and venous malformations.

OBJECTIVE: Puberty has been shown to accelerate growth of vascular malformations, including lymphatic (LM) and venous malformations (VM). This study aims to compare the number of procedures performed before and after puberty in patients with LM and VM to assess whether the onset of puberty results in higher treatment frequency. METHODS: A retrospective review of head and neck LM and VM patients who were evaluated between January 2009 and December 2019 was performed. Patient demographics, lesion characteristics, and procedural details were recorded. For the purposes of this study, 11 years or older in females and 12 years or older in males were the established cut-offs for the onset of puberty. RESULTS: After initial screening of 357 patients, 83 patients were included in the study based on inclusion criteria. There were 34 patients with LM (41 %) and 49 with VM (59 %). The mean age at diagnosis was 6.1 ± 10.9 years (LM: 4.2 ± 7.0, VM: 7.4 ± 12.9, p = 0.489). 68 patients underwent treatments, which included sclerotherapy, surgical excision, and/or laser. For all patients, the average number of lifetime treatments when initiated before puberty was 3.78 ± 2.81 and when initiated after puberty was 2.17 ± 1.37 (p = 0.022). Patients diagnosed pre-puberty were more likely to undergo treatments vs. those diagnosed after puberty (OR 10.00, 95 % CI: 2.61-38.28, p < 0.001). CONCLUSION: We found that the number of treatments was fewer in those who started treatment after puberty. This finding suggests that providers may elect to proceed with observation in asymptomatic patients, given that waiting until after the onset of puberty has not shown an increase in the procedural load on patients.

An Inherent Difference between Serine and Threonine Phosphorylation: Phosphothreonine Strongly Prefers a Highly Ordered, Compact, Cyclic Conformation.

Phosphorylation and dephosphorylation of proteins by kinases and phosphatases are central to cellular responses and function. The structural effects of serine and threonine phosphorylation were examined in peptides and in proteins, by circular dichroism, NMR spectroscopy, bioinformatics analysis of the PDB, small-molecule X-ray crystallography, and computational investigations. Phosphorylation of both serine and threonine residues induces substantial conformational restriction in their physiologically more important dianionic forms. Threonine exhibits a particularly strong disorder-to-order transition upon phosphorylation, with dianionic phosphothreonine preferentially adopting a cyclic conformation with restricted ϕ (ϕ ∼ -60°) stabilized by three noncovalent interactions: a strong intraresidue phosphate-amide hydrogen bond, an n → π* interaction between consecutive carbonyls, and an n → σ* interaction between the phosphate Oγ lone pair and the antibonding orbital of C-Hß that restricts the χ2 side-chain conformation. Proline is unique among the canonical amino acids for its covalent cyclization on the backbone. Phosphothreonine can mimic proline's backbone cyclization via noncovalent interactions. The preferred torsions of dianionic phosphothreonine are ϕ,ψ = polyproline II helix > α-helix (ϕ ∼ -60°); χ1 = g-; χ2 ∼ +115° (eclipsed C-H/O-P bonds). This structural signature is observed in diverse proteins, including in the activation loops of protein kinases and in protein-protein interactions. In total, these results suggest a structural basis for the differential use and evolution of threonine versus serine phosphorylation sites in proteins, with serine phosphorylation typically inducing smaller, rheostat-like changes, versus threonine phosphorylation promoting larger, step function-like switches, in proteins.

Postoperative opioid-prescribing practices in otolaryngology: Evidence-based guideline outcomes.

Objectives: We previously reported that >50% of postoperative opioids prescribed at our institution went unused for common otolaryngologic procedures. Based on these findings, we instituted multimodal, evidence-based guidelines for postoperative pain management. In the second part of our multiphasic study, we evaluated the effects of these guidelines on (1) quantity of unused opioids, (2) patient satisfaction, and (3) institutional perceptions toward the opioid epidemic and prescribing guidelines. Methods: Standardized, procedure-specific opioid prescription guidelines were created using prospective data from the first phase of our study and evidence from current literature. Again, we examined sialendoscopy, parotidectomy, parathyroidectomy/thyroidectomy, and transoral robotic surgery (TORS). Patients were surveyed at their first postoperative appointment. Groups from Phases I and II were compared. Attending physicians were surveyed before the start of the multiphasic project and after prescribing guidelines were implemented. Results: Prescribing guidelines led to an average reduction in prescribed morphine milligram equivalents (MME) per patient by: 48% (sialendoscopy), 63% (parotidectomy), 60% (para/thyroidectomy), and 42% (TORS). Average used MME per patient for parotidectomy was significantly reduced (64%). The proportion of unused MME per patient and patient satisfaction scores did not significantly change after guidelines were implemented. Conclusion: Implementation of opioid-prescribing guidelines and the use of multimodal analgesia substantially reduced the amount of opioids prescribed across all procedures without impacting patient satisfaction. Level of Evidence: 2.

Validity of the American College of Radiology Thyroid Imaging Reporting and Data System in Children.

OBJECTIVE: To assess the validity of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for evaluating thyroid nodules in children. METHODS: Patients aged <19 years with thyroid nodule(s) evaluated by ultrasound (US) from 2007-2018 at a tertiary children's hospital were included. Two radiologists scored de-identified thyroid US images using ACR TI-RADS (from 1, "benign" to 5, "highly suspicious"). The radiologists recorded size and rated vascularity for each nodule. Ultrasound findings were compared to pathology results (operative cases, n = 91) and clinical follow-up without disease progression (non-operative cases, n = 15). RESULTS: Thyroid images from 115 patients were reviewed. Nine patients were excluded due to the absence of an evaluable nodule. Forty-seven benign and 59 malignant nodules were included. Median age at ultrasound was 15 years (range 0.9-18 years). Twenty (18.9%) patients were male. There was moderate agreement between TI-RADS levels assigned by the two raters (kappa = 0.57, p < 0.001). When the raters' levels were averaged, >3 as the threshold for malignancy correctly categorized the greatest percentage of nodules (68.9%). Eleven (18.6%) malignant nodules received a TI-RADS level of 2 (n = 3) or 3 (n = 8). Sensitivity, specificity, and positive and negative predictive values were 81.4%, 53.2%, 68.6%, and 69.4%, respectively. Although not part of TI-RADS, vascularity was similar between benign and malignant nodules (p = 0.56). CONCLUSION: In a pediatric population, TI-RADS can help distinguish between benign and malignant nodules with comparable sensitivity and specificity to adults. However, the positive and negative predictive values suggest TI-RADS alone cannot eliminate the need for FNA. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2394-2401, 2023.

Assessment of BMI and Venous Thromboembolism Rates in Patients on Standard Chemoprophylaxis Regimens After Undergoing Free Tissue Transfer to the Head and Neck.

Importance: Venous thromboembolism (VTE) is a severe complication after free tissue transfer to the head and neck (H&N). Enoxaparin 30 mg twice daily (BID) is a common regimen for chemoprophylaxis. However, differences in enoxaparin metabolism based on body weight may influence its efficacy and safety profile. Objective: To assess the association between BMI and postoperative VTE and hematoma rates in patients treated with prophylactic enoxaparin 30 mg BID. Design, Setting, and Participants: This was a retrospective review of a prospectively collected cohort from 2012 to 2022. Postoperative VTE, hematoma, and free flap pedicle thrombosis were recorded within 30 days of index surgery. The setting was a tertiary academic referral center. Participants included patients undergoing H&N reconstruction with free flaps that received fixed-dose subcutaneous enoxaparin 30 mg BID postoperatively. Statistical analysis was conducted from April to May 2022. Main Outcomes and Measures: Outcomes include incidence of VTE, hematoma, and flap pedicle thrombosis events within 30 days of the surgery. Univariate and multivariable regression models were used to evaluate associations between BMI and other patient factors with these outcomes. Results: Among the 765 patients included, 262 (34.24%) were female; mean (SD) age was 60.85 (12.64) years; and mean (SD) BMI was 26.36 (6.29). The rates of VTE and hematoma in the cohort were 3.92% (30 patients) and 5.09% (39 patients), respectively. After adjusting for patient factors, BMI was the only factor associated with VTE (OR, 1.07; 95% CI, 1.015-1.129). Obesity (BMI >30) was associated with increased odds of VTE (OR, 2.782; 95% CI, 1.197-6.564). Hematoma was not associated with BMI (OR, 0.988; 95% CI, 0.937-1.041). Caprini score of at least 9 was not associated with VTE (OR, 1.259; 95% CI, 0.428-3.701). Conclusions and Relevance: This cohort study found that obesity was associated with an increased risk of VTE in patients after microvascular H&N reconstruction and while on standard postoperative chemoprophylaxis regimens. This association may suggest insufficient VTE prophylaxis in this group and a potential indication for weight-based dosing.

Seated vs. standing workstations: A pilot study.

ABSTRACT: Although nurses are constantly on their feet caring for patients, they still work on the computer at seated or standing workstations. This study examines workers' self-reported pain and discomfort while using these two workstation designs and their risk of developing musculoskeletal disorders.

An Update on Nontumorous Disorders of the Salivary Glands and Their Management for Internists.

Salivary disease may present as pain or swelling in unilateral or bilateral salivary glands. Symptoms may be periprandial or recurrent and inflammatory. If a patient fails conservative treatment, they should be referred to an otolaryngologist. If there is no clear cause based on history and physical examination, sialendoscopy can be performed to directly visualize tissues, provide a diagnosis, drive treatment plans, and sometimes concurrently provide therapeutic intervention. Based on the pathology visualized on sialendoscopy, treatment options include endoscopic intervention, Botox, and gland-preserving surgical techniques, which promote healing of glandular tissue, ultimately preserving function.

Diagnostic Value of TI-RADS Classification System and Next Generation Genetic Sequencing in Indeterminate Thyroid Nodules.

RATIONALE AND OBJECTIVES: This study aims to evaluate the diagnostic accuracy, inter-reader, and intra-reader variability of the ACR Thyroid Imaging Reporting and Data System (TI-RADS) for risk-stratification of indeterminate thyroid nodules using next generation genetic sequencing and tissue histology as a reference standard. MATERIALS AND METHODS: Retrospective chart review was performed on all patients who underwent thyroid ultrasound for a nodule with subsequent fine-needle aspiration ± surgical resection from January 2017 to August 2018. Four radiologists with expertise in thyroid ultrasound assessed imaging twice, ≥1 month apart. Results of cytology and next generation genetic sequencing were used as a reference standard for high versus low risk of malignancy in each nodule. Inter-reader reliability between readers and intra-reader reliability between replicate self-reads for TI-RADS categorization were assessed. Univariate analysis, kappa statistics, and receiver operating characteristic curve were calculated. RESULTS: One hundred and thirty six nodules across 121 patients met inclusion criteria. 84.6% of patients were female and average age was 55.8 ± 14.1 years. One hundred and eighteen of 135 nodules (87%) had indeterminate cytology (Bethesda III or IV). One of 23 high-risk mutations was identified in 30.1% (42) of the nodules. Of the 52 patients who had surgery, 24 (47.1%) had confirmed malignant disease on surgical pathology. Inter-reader reliability between the four radiologists was marginal, κ = 0.293. Intra-reader reliability ranged from marginal to good, κ = 0.337 to κ = 0.560, respectively. The area under the receiver operating characteristic curve was 0.509, and no optimal TI-RADS Level for identifying high-risk nodules existed. CONCLUSION: The ACR TI-RADS classification system performs with low inter-reader and intra-reader reliability when assessing the genetic risk of nodules with indeterminate cytology.

Incorporation of a Machine Learning Algorithm With Object Detection Within the Thyroid Imaging Reporting and Data System Improves the Diagnosis of Genetic Risk.

BACKGROUND: The role of next generation sequencing (NGS) for identifying high risk mutations in thyroid nodules following fine needle aspiration (FNA) biopsy continues to grow. However, ultrasound diagnosis even using the American College of Radiology's Thyroid Imaging Reporting and Data System (TI-RADS) has limited ability to stratify genetic risk. The purpose of this study was to incorporate an artificial intelligence (AI) algorithm of thyroid ultrasound with object detection within the TI-RADS scoring system to improve prediction of genetic risk in these nodules. METHODS: Two hundred fifty-two nodules from 249 patients that underwent ultrasound imaging and ultrasound-guided FNA with NGS with or without resection were retrospectively selected for this study. A machine learning program (Google AutoML) was employed for both automated nodule identification and risk stratification. Two hundred one nodules were used for model training and 51 reserved for testing. Three blinded radiologists scored the images of the test set nodules using TI-RADS and assigned each nodule as high or low risk based on the presence of highly suspicious imaging features on TI-RADS (very hypoechoic, taller-than-wide, extra-thyroidal extension, punctate echogenic foci). Subsequently, the TI-RADS classification was modified to incorporate AI for T4 nodules while treating T1-3 as low risk and T5 as high risk. All diagnostic predictions were compared to the presence of a high-risk mutation and pathology when available. RESULTS: The AI algorithm correctly located all nodules in the test dataset (100% object detection). The model predicted the malignancy risk with a sensitivity of 73.9%, specificity of 70.8%, positive predictive value (PPV) of 70.8%, negative predictive value (NPV) of 73.9% and accuracy of 72.4% during the testing. The radiologists performed with a sensitivity of 52.1 ± 4.4%, specificity of 65.2 ± 6.4%, PPV of 59.1 ± 3.5%, NPV of 58.7 ± 1.8%, and accuracy of 58.8 ± 2.5% when using TI-RADS and sensitivity of 53.6 ± 17.6% (p=0.87), specificity of 83.3 ± 7.2% (p=0.06), PPV of 75.7 ± 8.5% (p=0.13), NPV of 66.0 ± 8.8% (p=0.31), and accuracy of 68.7 ± 7.4% (p=0.21) when using AI-modified TI-RADS. CONCLUSIONS: Incorporation of AI into TI-RADS improved radiologist performance and showed better malignancy risk prediction than AI alone when classifying thyroid nodules. Employing AI in existing thyroid nodule classification systems may help more accurately identifying high-risk nodules.

Effect of Gender, Age, and Profound Disease on Upper Airway Stimulation Outcomes.

OBJECTIVE: To evaluate treatment outcomes of upper airway stimulation (UAS) in obstructive sleep apnea (OSA) patients based on patient age, gender, and preoperative disease severity. METHODS: Retrospective chart review of patients undergoing UAS from 2014 to 2018 at a tertiary care center. Data collected included demographic information, implantation records, and pre- and postoperative polysomnography (PSG) results. Profound OSA was defined as AHI >65 and age ≥65 was considered advanced age. The primary outcome measured was initial treatment response, defined as a post-operative AHI <20 with a >50% reduction from baseline. RESULTS: 145 patients underwent UAS at our institution including 98 males and 47 females with a mean age of 61.7 ± 11.5 years, mean BMI of 29.1 ± 3.9 kg/m2, and mean preoperative AHI of 34.1 ± 18.2 events/hour. After surgery, patients had a significantly lower mean AHI of 8.6 ± 15.0 events/hour (<0.001). Older patients had a lower initial treatment response rate (78%) when compared to their younger counterparts (94%) (P = 0.005). Male gender and profound disease status did not significantly impact treatment response rates; young age was the only variable found to predict early treatment response on multivariate analysis (P = 0.003). CONCLUSION: Although the overall OSA population showed significant postoperative AHI reduction with UAS, patients age ≥65 years were less likely to have an initial response to treatment, when compared to their younger counterparts. A larger proportion of elderly patients and patients with profound OSA had residual moderate disease (AHI > 15) after UAS. LEVEL OF EVIDENCE: 4.

Elevated Central and Mixed Apnea Index after Upper Airway Stimulation.

OBJECTIVE: Upper airway stimulation (UAS) is used to treat patients with moderate to severe obstructive sleep apnea (OSA). The aim of this study is to report the incidence and potential predictors of elevated central and mixed apnea index (CMAI) after UAS. STUDY DESIGN: Retrospective chart review of patients undergoing UAS. SETTING: Tertiary care center. SUBJECTS AND METHODS: Included patients underwent UAS for OSA at our institution between 2014 and 2018. Data collected included demographic information, implantation records, and pre- and postoperative polysomnography (PSG) results. CMAI ≥5 was considered elevated. Post hoc univariate analysis was performed to evaluate factors associated with elevated CMAI. RESULTS: In total, 141 patients underwent UAS at our institution. This included 94 men and 47 women with a mean age of 61.2 ± 11.0 years and a mean body mass index of 29.1 ± 3.9 kg/m2. Five patients had an elevated CMAI after surgery during UAS titration. Demographics, comorbid conditions, and device settings were not associated with an elevated postoperative CMAI (P > .05). CONCLUSION: The occurrence of an elevated CMAI after surgery may represent treatment-emergent events. Demographics, comorbid conditions, and UAS device settings were not associated with central and mixed apneic events. LEVEL OF EVIDENCE: 4.

Machine Learning by Ultrasonography for Genetic Risk Stratification of Thyroid Nodules.

Importance: Thyroid nodules are common incidental findings. Ultrasonography and molecular testing can be used to assess risk of malignant neoplasm. Objective: To examine whether a model developed through automated machine learning can stratify thyroid nodules as high or low genetic risk by ultrasonography imaging alone compared with stratification by molecular testing for high- and low-risk mutations. Design, Setting, and Participants: This diagnostic study was conducted at a single tertiary care urban academic institution and included patients (n = 121) who underwent ultrasonography and molecular testing for thyroid nodules from January 1, 2017, through August 1, 2018. Nodules were classified as high risk or low risk on the basis of results of an institutional molecular testing panel for thyroid risk genes. All thyroid nodules that underwent genetic sequencing for cytological results with Bethesda System categories III and IV were reviewed. Patients without diagnostic ultrasonographic images within 6 months of fine-needle aspiration or who received definitive treatment at an outside medical center were excluded. Main Outcomes and Measures: Thyroid nodules were categorized by the model as high risk or low risk using ultrasonographic images. Results were compared using genetic testing. Results: Among the 134 lesions identified in 121 patients (mean [SD] age, 55.7 [14.2] years; 102 women [84.3%]), 683 diagnostic ultrasonographic images were selected. Of the 683 images, 556 (81.4%) were used for training the model, 74 (10.8%) for validation, and 53 (7.8%) for testing. Most nodules had no mutation (75 [56.0%]), whereas 43 nodules (32.1%) had a high-risk mutation and 16 (11.9%) had an unknown or a low-risk mutation (χ2 = 39.060; P < .001). In total, 228 images (33.4%) were of nodules classified as genetically high risk (n = 43), and 455 (66.6%) were of low-risk nodules (n = 91). The model performed with a sensitivity of 45% (95% CI, 23.1%-68.5%), a specificity of 97% (95% CI, 84.2%-99.9%), a positive predictive value of 90% (95% CI, 55.2%-98.5%), a negative predictive value of 74.4% (95% CI, 66.1%-81.3%), and an overall accuracy of 77.4% (95% CI, 63.8%-97.7%). Conclusions and Relevance: The study found that the model developed through automated machine learning could produce high specificity for identifying nodules with high-risk mutations on molecular testing. This finding shows promise for the diagnostic applications of machine learning interpretation of sonographic imaging of indeterminate thyroid nodules.

Evaluation of oncologic outcomes in head and neck cancer patients ≥80 years old based on adherence to NCCN guideline for postoperative adjuvant treatment.

BACKGROUND: There is a paucity of literature characterizing outcomes in older adult patients with head and neck cancer (HNC). This study aims to describe patients from this group, their adherence to National Comprehensive Cancer Network (NCCN) adjuvant treatment guidelines, and the impact of guideline adherence on overall survival (OS). METHODS: In this retrospective cohort study, we reviewed all patients ≥80 years old with HNC who underwent surgery with curative intent from 2008 to 2016. Adherence to NCCN guidelines was determined in blinded fashion, and quality metrics and OS were compared. RESULTS: One hundred fifty-nine patients met inclusion criteria. The majority of patients (n = 94, 59%) underwent treatment in accordance with NCCN recommendations while 65 (41%) deviated from NCCN guidelines. The two cohorts did not demonstrate a difference in 2-year OS (62% vs 66%, P = .50). CONCLUSION: Older adult patient outcomes were not different when treatment deviated from NCCN guidelines.

Assessment of quality and consistency of monoclonal antibodies for CB1 and CB2 in head and neck squamous cell carcinoma.

BACKGROUND: Marijuana has numerous roles as an agonist in the endocannabinoid signaling system (ESS). This study evaluated monoclonal antibodies across experimental techniques to establish a framework for studying ESS receptors, CB1 and CB2. METHODS: Tissue from five patients with head and neck cancer were used to generate cell lines and formalin-fixed paraffin-embedded (FFPE) sections, which were analyzed by western blot (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Subgroup analysis was performed on FFPE sections from 8 marijuana users and 10 controls by IHC. Results were compared across methods for consistency. RESULTS: In all patients, WB and IF were CB1 positive, whereas IHC was negative. Select samples were CB2 positive by WB, but failed IF and IHC applications. In subgroup analysis, 1 of 8 users and 3 of 10 nonusers were CB1 positive. CONCLUSIONS: Interpretation of CB1/CB2 antibody data should be performed cautiously and confirmation of findings across multiple experimental methods is recommended.

Therapeutic Cannabis and Endocannabinoid Signaling System Modulator Use in Otolaryngology Patients.

OBJECTIVES: 1) review benefits and risks of cannabis use, with emphasis on otolaryngic disease processes; 2) define and review the endocannabinoid signaling system (ESS); and 3) review state and federal regulations for the use and research of cannabis and ESS modulators. METHODS: This manuscript is a review of the current literature relevant to the stated objectives. RESULTS: Cannabis (marijuana) use is increasing. It is the most widely used illicit substance in the world. There is increasing interest in its therapeutic potential due to changing perceptions, new research, and legislation changes controlling its use. The legal classification of cannabis is complicated due to varied and conflicting state and federal laws. There are currently two synthetic cannabinoid drugs that are FDA approved. Current indications for use include chemotherapy-related nausea and vomiting, cachexia, and appetite loss. Research has demonstrated potential benefit for use in many other pathologies including pain, inflammatory states, and malignancy. Data exists demonstrating potential antineoplastic benefit in oral, thyroid, and skin cancers. CONCLUSIONS: ESS modulators may play both a causal and therapeutic role in several disorders seen in otolaryngology patients. The use of cannabis and cannabinoids is not without risk. There is a need for further research to better understand both the adverse and therapeutic effects of cannabis use. With increasing rates of consumption, elevated public awareness, and rapidly changing legislation, it is helpful for the otolaryngologist to be aware of both the adverse manifestations of use and the potential therapeutic benefits when talking with patients.

A novel hematopoietic progenitor cell mobilization regimen, utilizing bortezomib and filgrastim, for patients undergoing autologous transplant.

Adequate hematopoietic progenitor cell (HPC) collection is critical for patients undergoing autologous HPC transplant (AHPCT). Historically, 15 - 30% of patients failed HPC mobilization with granulocyte-colony stimulating factor (G-CSF) alone. Bortezomib, a proteasome inhibitor, has been shown to down regulate very late antigen-4 (VLA-4), an adhesion molecule expressed on HPCs. In this pilot study, bortezomib was administered on days -11 and -8 at a dose of 1.3 mg/m2 intravenously (IV) or subcutaneously (SQ), followed by G-CSF 10 mcg/kg SQ, on days -4 to -1 prior to HPC collection (Day 1). Nineteen patients, with multiple myeloma (n = 12) or non-Hodgkin lymphoma (n = 7) undergoing AHPCT for the first time, were enrolled. Patients were excluded if they had worse than grade II neuropathy or platelet count less than 100 x 109 /L. Bortezomib was well tolerated and all patients had adequate HPC collections with no mobilization failures. One patient (6%) had a CD34+ cell count of 3.9 cells/µL on Day 1 and received plerixafor per institutional algorithm. Eleven patients completed HPC collection in 1 day and eight in 2 days. All patients underwent AHPCT and had timely neutrophil and platelet engraftment. Comparison with a historical control group of 70 MM and lymphoma patients, who were mobilized with G-CSF, showed significantly higher CD 34+ cells/kg collected in the bortezomib mobilization study group. Bortezomib plus G-CSF is an effective HPC mobilizing regimen worth investigating further in subsequent studies. J. Clin. Apheresis 31:559-563, 2016. © 2015 Wiley Periodicals, Inc.

The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study.

Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy; however, clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking. The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor, mood, and other quality-of-life symptoms in post-menopausal women. This was a prospective, observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1, 2003 and October 1, 2010 in a community pharmacy. Data collection included patient demographics, comorbidities, hormone regimens, and therapeutic outcomes. Patients rated their vasomotor, mood, and quality-of-life symptoms as absent, mild, moderate, or severe at baseline, at one to three months follow-up, and three to six months follow-up. Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test. A total of 200 patients met study criteria; 160 received topical bioidentical hormone replacement therapy, and 40 received sublingual bioidentical hormone replacement therapy. Most sublingually-treated patients (70%) received an estrogen combination and 100% received progesterone. Nearly half (43%) of the topically treated patients received an estrogen combination (43%) and 99% received progesterone. The percentage of sublingually treated patients reporting "moderate" or "severe" symptoms was significantly reduced at one to three months follow-up for the following target symptoms: hot flashes (31%, P = 0.04), night sweats (38%, P < 0.01), irritability (36%, P = 0.01), anxiety (42%, P < 0.01), emotional lability (38%, P < 0.01), sleep disturbances (35%, P < 0.01), memory loss (35%, P = 0.04), fatigue (33%, P = 0.04), and libido (26%, P = 0.03). Similar reductions were seen at three to six months follow-up compared to baseline. Patients who received topical therapy did not experience significant symptom reductions at one to three months follow-up; however, significant symptom reduction was seen at three to six months for the following: emotional lability (31%, P < 0.01), irritability (29%, P = 0.02), and night sweats (20%, P = 0.04). Compounded sublingual bioidentical hormone replacement therapy is effective in reducing vasomotor, mood, and quality-of-life symptoms experienced in post-menopausal women. Topical therapy does not appear to improve symptoms as extensively or rapidly as sublingual therapy.

The effect of statin therapy on the incidence of infections: a retrospective cohort analysis.

BACKGROUND: Statins have been postulated to prevent infection through immunomodulatory effects. OBJECTIVES: To compare the incidence of infections in statin users to that in nonusers within the same health care system. METHODS: This was a retrospective cohort study of patients enrolled as Tricare Prime or Plus in the San Antonio military multimarket. Statin users were patients who received a statin for at least 3 months between October 1, 2004 and September 30, 2005. Nonusers were patients who did not receive a statin within the study period (October 1, 2003-September 30, 2009). Inpatient and outpatient International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes were used to determine the incidence of infections during the follow-up period (October 1, 2005-September 30, 2009) via multivariable regression analysis and time to infection via Cox regression analysis. RESULTS: Of 45,247 patients who met the study criteria, 12,981 (29%) were statin users and 32,266 were nonusers. After adjustments for age, gender, Charlson Comorbidity Score, tobacco use, alcohol abuse/dependence, health care utilization and use of specific medication classes, statin use was associated with an increased incidence of common infections (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.06-1.19) but not influenza or fungal infections (OR: 1.06, 95% CI: 0.80-1.39; OR: 0.97; 95% CI: 0.91-1.04, respectively). Time-to-first infection was similar in statin users and nonusers in all infection categories examined. CONCLUSIONS: Statin use was associated with an increased incidence of common infections but not influenza or fungal infections. This study does not support a protective role of statins in infection prevention; however, the influence of potential confounders cannot be excluded.

Trends in catheter-associated urinary tract infections among a national cohort of hospitalized adults, 2001-2010.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) have become a major public health concern in the United States. This study provides national estimates of CAUTI incidence, mortality, and associated hospital length of stay (LOS) over a 10-year period. METHODS: This was a retrospective analysis of the National Hospital Discharge Surveys from 2001 to 2010. Adults age ≥18 years with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code for urinary catheter placement or other major procedure were included. Urinary tract infections were identified by ICD-9-CM code. Data weights were applied to derive national estimates. Predictors of CAUTI were identified using a logistic regression model. RESULTS: These data represent 70.4 million catheterized patients, 3.8 million of whom developed a CAUTI. The incidence of CAUTIs decreased from 9.4 cases/100 catheterizations in 2001 to 5.3 cases/100 catheterizations in 2010. Mortality in patients with a CAUTI declined from 5.4% in 2001 to 3.7% in 2010. Median (interquartile range [IQR]) hospital LOS also declined, from 9 days (IQR, 5-16 days) in 2001 to 7 days (IQR, 4-12 days) in 2010. Independent predictors of CAUTI included female sex, emergency hospital admission, transfer from another facility, and Medicaid payment (P < .0001 for all variables). CONCLUSIONS: The incidence of CAUTIs in US hospitals declined over the study period. Furthermore, patients with these infections experienced lower hospital mortality and shorter hospital LOS.