Publications by authors named "Marilly Palettas"

32 Publications

Perioperative do-not-resuscitate orders: Trainee experiential learning in preserving patient autonomy and knowledge of professional guidelines.

Medicine (Baltimore) 2021 Mar;100(11):e24836

Department of Anesthesiology, Ohio State University Wexner Medical Center, Columbus, Ohio.

Abstract: Anesthesiologists and surgeons have demonstrated a lack of familiarity with professional guidelines when providing care for surgical patients with a do-not-resuscitate (DNR) order. This substantially infringes on patient's self-autonomy; therefore, leading to substandard care particularly for palliative surgical procedures. The interventional nature of surgical procedures may create a different mentality of surgical "buy-in," that may unintentionally prioritize survivability over maintaining patient self-autonomy. While previous literature has demonstrated gains in communication skills with simulation training, no specific educational curriculum has been proposed to specifically address perioperative code status discussions. We designed a simulated standardized patient actor (SPA) encounter at the beginning of post-graduate year (PGY) 2, corresponding to the initiation of anesthesiology specific training, allowing residents to focus on the perioperative discussion in relation to the SPA's DNR order.Forty four anesthesiology residents volunteered to participate in the study. PGY-2 group (n = 17) completed an immediate post-intervention assessment, while PGY-3 group (n = 13) completed the assessment approximately 1 year after the educational initiative to ascertain retention. PGY-4 residents (n = 14) did not undergo any specific educational intervention on the topic, but were given the same assessment. The assessment consisted of an anonymized survey that examined familiarity with professional guidelines and hospital policies in relation to perioperative DNR orders. Subsequently, survey responses were compared between classes.Study participants that had not participated in the educational intervention reported a lack of prior formalized instruction on caring for intraoperative DNR patients. Second and third year residents outperformed senior residents in being aware of the professional guidelines that detail perioperative code status decision-making (47%, 62% vs 21%, P = .004). PGY-3 residents outperformed PGY-4 residents in correctly identifying a commonly held misconception that institutional policies allow for automatic perioperative DNR suspensions (85% vs 43%; P = .02). Residents from the PGY-3 class, who were 1 year removed the educational intervention while gaining 1 additional year of clinical anesthesiology training, consistently outperformed more senior residents who never received the intervention.Our training model for code-status training with anesthesiology residents showed significant gains. The best results were achieved when combining clinical experience with focused educational training.
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http://dx.doi.org/10.1097/MD.0000000000024836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982162PMC
March 2021

Post-Cesarean Delivery Analgesic Outcomes in Patients Maintained on Methadone and Buprenorphine: A Retrospective Investigation.

J Pain Res 2020 30;13:3513-3524. Epub 2020 Dec 30.

Department of Anesthesiology, The Ohio State University Medical Center, Columbus, OH, USA.

Background: Despite the increasing prevalence of opioid use disorder (OUD) in pregnant women, there are limited studies on their anesthesia care and analgesic outcomes after cesarean delivery (CD).

Methods: Patients with OUD on either buprenorphine or methadone maintenance therapy who underwent CD at our institution from 2011 to 2018 were identified. Anesthetic details and analgesic outcomes, including daily opioid consumption and pain scores, were compared between patients maintained on buprenorphine and methadone. Analgesic outcomes were also evaluated according to anesthetic type (neuraxial or general anesthesia) and daily buprenorphine/methadone dose to determine if these factors impacted pain after delivery.

Results: A total of 146 patients were included (buprenorphine n=99 (67.8%), methadone n=47 (32.2%)). Among all patients: 74% had spinal/CSE, 15% epidural, and 11% general anesthesia. Anesthesia types were similar among buprenorphine and methadone patients. For spinal anesthetics, intrathecal fentanyl (median 15 µg) and morphine (median 100 µg) were commonly given (97.2% and 96.3%, respectively), and dosed similarly between groups. Among epidural anesthetics, epidural morphine (median 2 mg) was commonly administered (90.9%), while fentanyl (median 100 µg) was less common (54.5%). Buprenorphine and methadone groups consumed similar amounts of oxycodone equivalents per 24 hours of hospitalization (80.6 vs 76.3 mg; =0.694) and had similar peak pain scores (8.3 vs 8.0; =0.518). Daily methadone dose correlated weakly with opioid consumption (R=0.3; =0.03), although buprenorphine dose did not correlate with opioid consumption or pain scores. General anesthesia correlated with greater oxycodone consumption in the first 24 hours (median 156.1 vs 91.7 mg; =0.004) and greater IV PCA use (63% vs 7%; <0.001) compared to neuraxial anesthesia.

Conclusion: Patients on buprenorphine and methadone had similar high opioid consumption and pain scores after CD. The anesthetic details and analgesic outcomes reported in this investigation may serve as a useful reference for future prospective investigations and aid in the clinical care of these patients.
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http://dx.doi.org/10.2147/JPR.S284874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779306PMC
December 2020

Clinical impact of interruption in adjuvant Trastuzumab therapy in patients with operable HER-2 positive breast cancer.

Cardiooncology 2020 Nov 5;6(1):26. Epub 2020 Nov 5.

Stefanie Spielman Comprehensive Breast Cancer, The Ohio State University, Columbus, OH, 43210, USA.

Background: Trastuzumab-induced cardiotoxicity (TIC) can lead to early discontinuation of adjuvant therapy, however there is limited evidence on long-term survival outcomes in patients with operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) experiencing treatment interruption or discontinuation.

Methods: The primary objective of the study was to evaluate disease-free survival (DFS) in non-metastatic, HER2-positive, female BC patients who experienced treatment interruption or early discontinuation of trastuzumab therapy. Clinical and histopathological data were collected on 400 patients at The Ohio State University, an NCI-designated comprehensive cancer center between January 2005 and December 2015. Treatment interruption was defined as any delay of ≥2 weeks during trastuzumab therapy, including permanent cessation prior to completing planned therapy. TIC was defined as LVEF < 50% or > 15 points decline from baseline as evaluated by 2D echocardiogram after initiation of (neo) adjuvant therapy. DFS was defined as the time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as the time from diagnosis to death or last known follow up. OS/DFS estimates were generated using Kaplan-Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHR) for OS/DFS.

Results: A total of 369 patients received trastuzumab therapy; 106 (29%) patients experienced treatment interruption at least once and 42 (11%) permanently discontinued trastuzumab prior to completing planned therapy. TIC was the most common reason for interruption (66 patients, 62%). The median duration of trastuzumab in patients with treatment interruption was 11.3 months (range: 0.5-16.9) with 24 (23%) patients receiving ≤6 months of therapy. This duration includes the time delay related to treatment interruption. Patients with any treatment interruption had worse DFS (aHR: 4.4, p = 0.001) and OS (aHR: 4.8, p < 0.001) after adjusting for age, stage, grade, ER, node status and TIC.

Conclusions: Treatment interruption or early discontinuation of trastuzumab therapy in early HER2-positive BC, most often from TIC, is an independent prognostic marker for worse DFS and OS in operable HER2-positive BC. Future prospective studies should consider targeting at-risk populations and optimizing cardiac function to avoid interruption in trastuzumab therapy.
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http://dx.doi.org/10.1186/s40959-020-00081-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643282PMC
November 2020

A prospective observational cohort study to evaluate patients' experience during sequential cataract surgery under monitored anesthesia care and topical anesthesia.

Medicine (Baltimore) 2020 Nov;99(47):e21834

Department of Anesthesiology.

Cataract surgery is the most common ambulatory surgery at our outpatient surgery center. Several studies have shown that patients with bilateral cataracts may experience different levels of anxiety, pain, and awareness during the first and second cataract extraction.A prospective observational cohort study was conducted at The Ohio State University Wexner Medical Center Eye and Ear Institute in order to compare anxiety, general comfort, awareness, and pain levels in patients undergoing sequential cataract surgeries. Likert and numerical rating scale were used to assess the outcomes. Patients receiving monitored anesthesia care and topical anesthesia were included.A total of 198 patients were enrolled in this study, 116 patients (59%) were female and 157 patients (78%) were Caucasians with a median age of 67 years among participants. Patients with rating "no anxiety" or feeling "somewhat anxious" were significantly higher during surgery 2 (P =< .001). Most of the patients felt "extremely comfortable" during surgery 1 when compared to surgery 2 (54% vs 42.9%; P = .08). No significant differences were found between surgeries regarding intraoperative awareness (P = .16). Overall, patients experienced mild pain during both procedures (92.4% in surgery 1 compared to 90.4% in surgery 2; P = .55). During the postoperative visit, 54% of the patients associated surgery 2 with less anxiety levels, 53% with no differences in general comfort, 60% felt more aware, and 59% had no differences in pain levels.Previous exposure to surgery could have been associated with a significant reduction in anxiety levels reported during surgery 2. Non-pharmacological strategies aiming to reduce perioperative anxiety may be considered an alternative or additional approach to premedication in patients undergoing consecutive cataract surgeries.
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http://dx.doi.org/10.1097/MD.0000000000021834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676552PMC
November 2020

The role of indocyanine green fluorescence in endoscopic endonasal skull base surgery and its imaging correlations.

J Neurosurg 2020 Nov 13:1-11. Epub 2020 Nov 13.

Departments of1Neurological Surgery.

Objective: The use of endoscope-integrated indocyanine green (E-ICG) has recently been introduced in skull base surgery. The quantitative correlation between E-ICG and T1-weighted gadolinium-enhanced (T1WGd) images for skull base tumors has not been previously assessed, to the authors' knowledge. In this study, the authors investigated the indications for use and the limitations of E-ICG and sought to correlate the endoscopic fluorescence pattern with MRI contrast enhancement.

Methods: Following IRB approval, 20 patients undergoing endoscopic endonasal skull base surgery between June 2017 and August 2018 were enrolled in the study. Tumor fluorescence was measured using a blue color value and blood fluorescence as a control. Signal intensities (SIs) of tumor T1WGd images were measured and the internal carotid artery (ICA) SI was used as a control. For pituitary adenoma, the pituitary gland fluorescence was also measured. The relationships between ICG fluorescence and MRI enhancement measurements were analyzed.

Results: Data showed that in pituitary adenoma there was a strong correlation between the ratios of gland/blood fluorescence to gland/ICA SI (n = 8; r = 0.92; p = 0.001) and tumor/blood fluorescence to tumor/ICA SI (n = 9; r = 0.82; p = 0.006). In other pathologies there was a strong correlation between the ratios of tumor/blood fluorescence and tumor/ICA SI (n = 9; r = 0.74; p = 0.022). The ICG fluorescence allowed perfusion assessment of the pituitary gland as well as of the nasoseptal flaps. Visualization of the surrounding vasculature was also feasible.

Conclusions: Defining the indications and understanding the limitations are critical for the effective use of E-ICG. Tumor fluorescence seems to correlate with preoperative MRI contrast enhancement.
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http://dx.doi.org/10.3171/2020.6.JNS192775DOI Listing
November 2020

The effect of supplemental high Fidelity simulation training in medical students.

BMC Med Educ 2020 Nov 10;20(1):421. Epub 2020 Nov 10.

Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Simulation-based education (SBE) with high-fidelity simulation (HFS) offers medical students early exposure to the clinical environment, allowing development of clinical scenarios and management. We hypothesized that supplementation of standard pulmonary physiology curriculum with HFS would improve the performance of first-year medical students on written tests of pulmonary physiology.

Methods: This observational pilot study included SBE with three HFS scenarios of patient care that highlighted basic pulmonary physiology. First-year medical students' test scores of their cardio-pulmonary curriculum were compared between students who participated in SBE versus only lecture-based education (LBE). A survey was administered to the SBE group to assess their perception of the HFS.

Results: From a class of 188 first-year medical students, 89 (47%) participated in the SBE and the remaining 99 were considered as the LBE group. On their cardio-pulmonary curriculum test, the SBE group had a median score of 106 [IQR: 97,110] and LBE group of 99 [IQR: 89,105] (p < 0.001). For the pulmonary physiology subsection, scores were also significantly different between groups (p < 0.001).

Conclusions: Implementation of supplemental SBE could be an adequate technique to improve learning enhancement and overall satisfaction in preclinical medical students.
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http://dx.doi.org/10.1186/s12909-020-02322-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653704PMC
November 2020

Novel heterozygous truncating titin variants affecting the A-band are associated with cardiomyopathy and myopathy/muscular dystrophy.

Mol Genet Genomic Med 2020 10 20;8(10):e1460. Epub 2020 Aug 20.

The Ohio State University Wexner Medical Center, The Ohio State University, Columbus, OH, USA.

Background: Variants in TTN are frequently identified in the genetic evaluation of skeletal myopathy or cardiomyopathy. However, due to the high frequency of TTN variants in the general population, incomplete penetrance, and limited understanding of the spectrum of disease, interpretation of TTN variants is often difficult for laboratories and clinicians. Currently, cardiomyopathy is associated with heterozygous A-band TTN variants, whereas skeletal myopathy is largely associated with homozygous or compound heterozygous TTN variants. Recent reports show pathogenic variants in TTN may result in a broader phenotypic spectrum than previously recognized.

Methods: Here we report the results of a multisite study that characterized the phenotypes of probands with variants in TTN. We investigated TTN genotype-phenotype correlations in probands with skeletal myopathy and/or cardiomyopathy. Probands with TTN truncating variants (TTNtv) or pathogenic missense variants were ascertained from two academic medical centers. Variants were identified via clinical genetic testing and reviewed according to the American College of Medical Genetics criteria. Clinical and family history data were documented via retrospective chart review. Family studies were performed for probands with atypical phenotypes.

Results: Forty-nine probands were identified with TTNtv or pathogenic missense variants. Probands were classified by clinical presentation: cardiac (n = 30), skeletal muscle (n = 12), or both (cardioskeletal, n = 7). Within the cardioskeletal group, 5/7 probands had heterozygous TTNtv predicted to affect the distal (3') end of the A-band. All cardioskeletal probands had onset of proximal-predominant muscle weakness before diagnosis of cardiovascular disease, five pedigrees support dominant transmission.

Conclusion: Although heterozygous TTNtv in the A-band is known to cause dilated cardiomyopathy, we present evidence that these variants may in some cases cause a novel, dominant skeletal myopathy with a limb-girdle pattern of weakness. These findings emphasize the importance of multidisciplinary care for patients with A-band TTNtv who may be at risk for multisystem disease.
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http://dx.doi.org/10.1002/mgg3.1460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549586PMC
October 2020

Trends in Acute Pain Management for Renal Colic in the Emergency Department at a Tertiary Care Academic Medical Center.

J Endourol 2020 11 22;34(11):1195-1202. Epub 2020 Oct 22.

Department of Urology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Renal colic secondary to kidney stone disease is a common reason for emergency department (ED) visits and often leads to patients receiving narcotic medications. The objective of this study was to describe longitudinal analgesia prescribing patterns for kidney stone patients acutely managed in the ED. This was a retrospective chart review of patients who presented to the ED between 2013 and 2018 and were subsequently diagnosed with a kidney stone. Encounters during which opioids and nonopioids were administered in the ED and prescribed at discharge were stratified by year, race, ethnicity, insurance status, gender, and location of ED (main academic campus and community-based campus). Patients were excluded if they required hospital admission or a stone-related procedure related to the ED encounter. We reviewed 1620 total encounters for 1376 unique patients. Frequency of patients receiving opioids in the ED decreased from 81% in 2013 to 57% in 2018 ( < 0.001). During the same time period, nonopioid administration in the ED remained relatively unchanged (64% 67%). The proportion of patients prescribed opioids at discharge decreased from 77% to 59% ( < 0.001), while nonopioid prescriptions at discharge increased from 32% to 41% ( = 0.010). Frequency of administering both a narcotic and non-narcotic during the same ED encounter decreased over the 5-year period from 27% to 8% ( < 0.001). Opioids are being given less both during the ED encounter and at discharge for acute renal colic, while nonopioid prescribing is increasing. These trends may be due to increasing physician awareness to opioid addiction, or as a result of stricter legislation prohibiting opioid prescribing.
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http://dx.doi.org/10.1089/end.2020.0402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698984PMC
November 2020

Features, Outcomes, and Management Strategies of Male Breast Cancer: A Single Institution Comparison to Well-Matched Female Controls.

Eur J Breast Health 2020 Jul 20;16(3):201-207. Epub 2020 May 20.

Stefanie Spielman Comprehensive Breast Cancer, The Ohio State University, Columbus, OH, USA.

Objective: The primary objective of this study was to delineate differences in management, overall and distant disease-free survival in males diagnosed with breast cancer and treated at The Ohio State University Comprehensive Cancer Center as compared to comprehensively matched female subjects. Secondary objectives included assessment of clinical and histopathologic features and recurrence score, as measured by Oncotype DX and the modified Magee equation #2.

Materials And Methods: This single institution retrospective study compared male and comprehensively matched female patients (1:2) with stage I-III breast cancer between 1994 and 2014. Recurrence risk was estimated using a modified Magee equation. Overall survival and distant disease-free survival were estimated and compared using Kaplan-Meier and Log-rank methods.

Results: Forty-five male breast cancer patients were included (stage I: 26.7%; stage II: 53.3%; stage III: 20.0%; hormone receptor positive: 97.8%; human epidermal growth factor receptor 2 negative: 84.4%) with a median age of 63.8 (43.0-79.4) years at diagnosis. Intermediate and low recurrence scores were most common in male and female patients respectively; mean score was similar between groups (20.3 vs. 19.8). The proportion of male breast cancer patients treated with adjuvant chemotherapy and post-mastectomy radiation was lower compared to female patients (42.2% vs. 65.3%, p=0.013; 22.7% vs. 44.4%, p=0.030, respectively). Overall survival and distant disease-free survival between male and female patients were similar.

Conclusion: Male breast cancer patient outcomes were similar compared to well-matched female patients suggesting that breast cancer specific factors are more prognostic than gender.
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http://dx.doi.org/10.5152/ejbh.2020.5536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337913PMC
July 2020

Fournier's Gangrene in Females: Presentation and Management at a Tertiary Center.

Urology 2020 Jun 9. Epub 2020 Jun 9.

Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address:

Objective: To report and compare presentation and management of Fournier's Gangrene (FG) in female vs male patients at a single tertiary care center.

Methods: Patient demographics, clinical characteristics, treatments and outcomes were summarized and compared between males and females who were treated for FG from 2011 to 2018 at a single institution.

Results: Of the 143 patients treated for FG at our institution, 33 (23%) were female. Female patients were predominantly white (82%), with a median (IQR) age of 55 (46, 59). Median female boby mass index (BMI) was 42.1 (32, 50.4). Female patients' wound cultures were polymicrobial mix of gram positive and gram negative organisms. Median number of debridements for females was 2 (1,3). The most common anatomic region of gangrene involvement in females was labia (76%) followed by perineum (55%) and gluteus/buttocks (42%). Mortality rate during initial admission was 6% for females. Female patients had a higher median BMI than males (42.1 vs 33.7 respectively; P = .003). FG severity index, length of hospital stay, number of debridements, and wound cultures were comparable to males. The surgical team managing initial debridements differed with females managed primarily by general surgery and males primarily by urology. Mortality rate was comparable to men (6% vs 7%, P >.05).

Conclusion: Female patients with FG have greater BMI but similar clinical presentation, microbiologic characteristics and mortality rate compared to men. Urologists have little involvement during initial management for females at our institution.
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http://dx.doi.org/10.1016/j.urology.2020.05.056DOI Listing
June 2020

The Effects of Patient Positioning on the Outcome During Posterior Cranial Fossa and Pineal Region Surgery.

Front Surg 2020 13;7. Epub 2020 Mar 13.

Department of Anesthesiology, Stony Brook Medicine, Stony Brook, NY, United States.

Surgery on posterior cranial fossa (PCF) and pineal region (PR) carries the risks of intraoperative trauma to the brainstem structures, blood loss, venous air embolism (VAE), cardiovascular instability, and other complications. Success in surgery, among other factors, depends on selecting the optimal patient position. Our objective was to find associations between patient positioning, incidence of intraoperative complications, neurological recovery, and the extent of surgery. This observational study was conducted in two medical centers: The Ohio State University Wexner Medical Center (USA) and The Burdenko Neurosurgical Institute (Russian Federation). Patients were distributed in two groups based on the surgical position: sitting position (SP) or horizontal position (HP). The inclusion criteria were adult patients with space-occupying or vascular lesions requiring an open PCF or PR surgery. Perioperative variables were recorded and summarized using descriptive statistics. The post-treatment survival, functional outcome, and patient satisfaction were assessed at 3 months. A total of 109 patients were included in the study: 53 in SP and 56 in HP. A higher proportion of patients in the HP patients had >300 mL intraoperative blood loss compared to the SP group (32 vs. 13%; = 0.0250). Intraoperative VAE was diagnosed in 40% of SP patients vs. 0% in the HP group ( < 0.0001). However, trans-esophageal echocardiographic (TEE) monitoring was more common in the SP group. Intraoperative hypotension was documented in 28% of SP patients compared to 9% in HP group ( = 0.0126). A higher proportion of SP patients experienced a new neurological symptom compared to the HP group (49 vs. 29%; = 0.0281). The extent of tumor resection, postoperative 3-months survival, functional outcome, and patient satisfaction were not different in the groups. The SP was associated with, less intraoperative bleeding, increased intraoperative hypotension, VAE, and postoperative neurological deficit. More HP patients experienced macroglossia and increased blood loss. At 3 months, there was no difference of parameters between the two groups. ClinicalTrials.gov: registration number NCT03364283.
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http://dx.doi.org/10.3389/fsurg.2020.00009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082226PMC
March 2020

Incidence of pathogenic, likely pathogenic, and uncertain ALS variants in a clinic cohort.

Neurol Genet 2020 Feb 13;6(1):e390. Epub 2020 Jan 13.

Department of Internal Medicine (J.R.) and Department of Neurology (J.R., A.Q., S.J.K.), The Ohio State University Wexner Medical Center; Department of Biomedical Informatics (M.P.), Center for Biostatistics, The Ohio State University Wexner Medical Center; College of Medicine (L.V., R.P.), The Ohio State University Wexner Medical Center; and Department of Biological Chemistry & Pharmacology (S.J.K.), The Ohio State University Wexner Medical Center, Columbus.

Objective: To determine the incidence of amyotrophic lateral sclerosis (ALS) genetic variants in a clinic-based population.

Methods: A prospective cohort of patients with definite or probable ALS was offered genetic testing using a testing algorithm based on family history and age at onset.

Results: The incidence of pathogenic (P) or likely pathogenic (LP) variants was 56.0% in familial ALS (fALS); 11.8% in patients with ALS with a family history of dementia, and 6.8% in sporadic ALS ( < 0.001). expansions accounted for the majority (79%) of P or LP variants in fALS cases. Variants of uncertain significance were identified in 20.0% of fALS cases overall and in 35.7% of -negative cases. P or LP variants were detected in 18.5% of early-onset cases (onset age <50 years); the incidence of P or LP variants was not significantly different between family history types in this group.

Conclusions: Our data suggest that the incidence of P and LP variants in genes other than is lower than expected in Midwestern fALS cases compared with research cohorts and highlights the challenge of variant interpretation in ALS. An accurate understanding of the incidence of pathogenic variants in clinic-based ALS populations is necessary to prioritize targets for therapeutic intervention and inform clinical trial design.
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http://dx.doi.org/10.1212/NXG.0000000000000390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984133PMC
February 2020

Efficacy of different dosing schedules of capecitabine for metastatic breast cancer: a single-institution experience.

Invest New Drugs 2020 10 14;38(5):1605-1611. Epub 2020 Jan 14.

Stefanie Spielman Comprehensive Breast Center, The Ohio State University, Columbus, OH, USA.

Purpose Capecitabine is widely used as a single agent on a 21-day cycle in the management of metastatic breast cancer (MBC). Our primary objective was to compare the standard dosing of capecitabine (Arm A: days 1-14 on 21-day cycle) to biweekly dosing (Arm B: days 1-7 and 15-21 on 28-day cycle) using retrospective data analysis. Methods 166 patients with MBC treated with single agent capecitabine at The Ohio State University from 2002 to 2014 were considered eligible. Median time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier (KM) methods. KM curves were compared using log-rank tests with Holm's correction for multiplicity. Results Patients were grouped by dose schedule into one of three arms: Arm A (21-day cycle; capecitabine given at 1000 mg/m orally, twice daily on days 1-14 of 21-day cycle); Arm B (28-day cycle; capecitabine given at 1000 mg/m orally, twice daily on days 1-7 and 15-21 of 28-day cycle); and Arm C (changeover regimen where patients started on the 21-day cycle, but changed to a 28-day cycle for tolerability). No difference was found in TTF or OS for patients with MBC between those who received capecitabine on either standard dosing (Arm A) and those on a biweekly cycle (Arm B or C). Overall, 41% of patients required dose reduction. Conclusions Our single institution experience showed that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions.
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http://dx.doi.org/10.1007/s10637-020-00891-9DOI Listing
October 2020

Assessment of outcomes and novel immune biomarkers in metaplastic breast cancer: a single institution retrospective study.

World J Surg Oncol 2020 Jan 14;18(1):11. Epub 2020 Jan 14.

Stefanie Spielman Comprehensive Breast Cancer, The Ohio State University, Columbus, OH, USA.

Background: Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear.

Methods: We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples.

Results: Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1-19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02).

Conclusions: Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.
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http://dx.doi.org/10.1186/s12957-019-1780-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961248PMC
January 2020

Clevidipine use after first-line treatment failure for perioperative hypertension in neurosurgical patients: A single-center experience.

Medicine (Baltimore) 2020 Jan;99(1):e18541

The Ohio State University Medical Center, Department of Anesthesiology.

Perioperative hypertension is a common occurrence in the neurosurgical population, where 60% to 90% of the patients require treatment for blood pressure (BP) control. Nicardipine and clevidipine have been commonly used in neurocritical settings. This retrospective, observational study assessed the effectivity of the administration of clevidipine after nicardipine treatment failure in neurosurgical patients.We retrospectively reviewed the medical charts of adult patients who were admitted to our neurosurgical department and received clevidipine after nicardipine treatment failure for the control of BP. The primary effectivity outcome was the comparison of the percentage of time spent at targeted SBP goals during nicardipine and clevidipine administration, respectively.A total of 12 adult patients treated with clevidipine after nicardipine treatment failure and were included for data analysis. The median number of events that required dose-titration was 20.5 vs 17 during the administration of nicardipine and clevidipine, respectively (P = .534). The median percentage of time spent at targeted SBP goal was 76.2% during the administration of nicardipine and 93.4% during the administration of clevidipine (P = .123).Our study suggests that clevidipine could be an alternative effective drug with an acceptable benefit/risk ratio in the neurosurgical population that fails to achieve BP control with nicardipine treatment.
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http://dx.doi.org/10.1097/MD.0000000000018541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946217PMC
January 2020

HTLV-1 CTCF-binding site is dispensable for in vitro immortalization and persistent infection in vivo.

Retrovirology 2019 12 21;16(1):44. Epub 2019 Dec 21.

Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA.

Background: Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The exact mechanism(s) through which latency and disease progression are regulated are not fully understood. CCCTC-binding factor (CTCF) is an 11-zinc finger, sequence-specific, DNA-binding protein with thousands of binding sites throughout mammalian genomes. CTCF has been shown to play a role in organization of higher-order chromatin structure, gene expression, genomic imprinting, and serve as a barrier to epigenetic modification. A viral CTCF-binding site (vCTCF-BS) was previously identified within the overlapping p12 (sense) and Hbz (antisense) genes of the HTLV-1 genome. Thus, upon integration, HTLV-1 randomly inserts a vCTCF-BS into the host genome. vCTCF-BS studies to date have focused primarily on HTLV-1 chronically infected or tumor-derived cell lines. In these studies, HTLV-1 was shown to alter the structure and transcription of the surrounding host chromatin through the newly inserted vCTCF-BS. However, the effects of CTCF binding in the early stages of HTLV-1 infection remains unexplored. This study examines the effects of the vCTCF-BS on HTLV-1-induced in vitro immortalization and in vivo viral persistence in infected rabbits.

Results: HTLV-1 and HTLV-1∆CTCF LTR-transactivation, viral particle production, and immortalization capacity were comparable in vitro. The total lymphocyte count, proviral load, and Hbz gene expression were not significantly different between HTLV-1 and HTLV-1∆CTCF-infected rabbits throughout a 12 week study. However, HTLV-1∆CTCF-infected rabbits displayed a significantly decreased HTLV-1-specific antibody response compared to HTLV-1-infected rabbits.

Conclusions: Mutation of the HTLV-1 vCTCF-BS does not significantly alter T-lymphocyte transformation capacity or early in vivo virus persistence, but results in a decreased HTLV-1-specific antibody response during early infection in rabbits. Ultimately, understanding epigenetic regulation of HTLV-1 gene expression and pathogenesis could provide meaningful insights into mechanisms of immune evasion and novel therapeutic targets.
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http://dx.doi.org/10.1186/s12977-019-0507-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925871PMC
December 2019

CSF Protein Level and Short-Term Prognosis in Guillain-Barré Syndrome.

J Clin Neuromuscul Dis 2019 Dec;21(2):118-119

Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI.

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http://dx.doi.org/10.1097/CND.0000000000000259DOI Listing
December 2019

Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.

Breast Cancer Res 2019 07 17;21(1):80. Epub 2019 Jul 17.

The Comprehensive Cancer Center, College of Medicine, The Ohio State University, 460 West 12th Avenue, Columbus, OH, 43210, USA.

Background: A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood.

Methods: We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer.

Results: Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for < 6 months vs ≥ 6 months showed significant enrichment of Notch signaling pathway genes, along with a trend for enrichment for luminal progenitor gene signature similar to what is observed in BRCA1 mutation carriers and basal-like breast tumors.

Conclusions: We report here for the first time that forced or abrupt involution of the mammary glands following pregnancy and lack of breastfeeding results in expansion of luminal progenitor cells, higher inflammation, proliferation, and ductal hyperplasia, a known risk factor for developing breast cancer.
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http://dx.doi.org/10.1186/s13058-019-1163-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637535PMC
July 2019

Reducing Fluoroscopy Time in Percutaneous Nephrolithotomy.

J Endourol 2019 05 8;33(5):369-374. Epub 2019 Apr 8.

1 Department of Urology, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Reducing fluoroscopy time (FT) during percutaneous nephrolithotomy (PCNL) is an opportunity for stewardship of ionizing radiation in stone patients. We present our initial results of a radiation reduction protocol (RRP) used during PCNL with fluoroscopy-guided access by the urologist. Retrospective chart review of all PCNL cases performed between January and October 2017, divided in two groups: pre-RRP (group 1) and post-RRP (group 2). Fluoroscopy was performed using low-dose and pulsed mode. Measures implemented to reduce FT include (1) one-spot images, (2) reliance on tactile feedback, and (3) using shorter segments of live fluoroscopy. The primary outcome was FT. Eighty-nine PCNL procedures were performed in 89 patients, 45 in group 1 and 44 in group 2. Overall median (interquartile range) age, body mass index (BMI), and stone burden (largest axial diameter) was 56 (45-66) years, 31.3 (27-37.4) kg/m, and 27.7 (19-41) mm, respectively, and were comparable in both the groups. The median (range) FT in group 1 and group 2 was 240 (56.0-916.0) and 65.5 (13.0-561.0) seconds ( < 0.0001), respectively. There was no correlation between FT and increasing BMI and stone burden. Overall stone-free rate was 57% (58% and 57% in group 1 and group 2, respectively,  = 0.5995), with 10 patients (11%) undergoing ancillary procedures. Overall and major (Clavien 3a+) complications occurred in 10 (11%) and 5 (6%) cases, respectively, in the overall cohort. FT in PCNL can be significantly reduced by adapting simple techniques and being increasingly vigilant of its usage, thereby reducing radiation exposure to the surgeon and the patient.
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http://dx.doi.org/10.1089/end.2018.0837DOI Listing
May 2019

Muscle contractility dysfunction precedes loss of motor unit connectivity in SOD1(G93A) mice.

Muscle Nerve 2019 02 21;59(2):254-262. Epub 2018 Dec 21.

Department of Biological Chemistry and Pharmacology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Introduction: Electrophysiological measurements are used in longitudinal clinical studies to provide insight into the progression of amyotrophic lateral sclerosis (ALS) and the relationship between muscle weakness and motor unit (MU) degeneration. Here, we used a similar longitudinal approach in the Cu/Zn superoxide dismutase (SOD1[G93A]) mouse model of ALS.

Methods: In vivo muscle contractility and MU connectivity assays were assessed longitudinally in SOD1(G93A) and wild type mice from postnatal days 35 to 119.

Results: In SOD1(G93A) males, muscle contractility was reduced by day 35 and preceded MU loss. Muscle contractility and motor unit reduction were delayed in SOD1(G93A) females compared with males, but, just as with males, muscle contractility reduction preceded MU loss.

Discussion: The longitudinal contractility and connectivity paradigm employed here provides additional insight into the SOD1(G93A) mouse model and suggests that loss of muscle contractility is an early finding that may precede loss of MUs and motor neuron death. Muscle Nerve 59:254-262, 2019.
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http://dx.doi.org/10.1002/mus.26365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340745PMC
February 2019

Learning, Life, and Lactation: Knowledge of Breastfeeding's Impact on Breast Cancer Risk Reduction and Its Influence on Breastfeeding Practices.

Breastfeed Med 2018 12 25;13(10):651-656. Epub 2018 Oct 25.

Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

The protective effects of breastfeeding against developing breast cancer are well known; however, it is unknown whether women are aware of this breastfeeding benefit. The aim of this investigation was to determine whether mothers received information about breast cancer risk reduction during breastfeeding counseling and whether this knowledge affected their decision to initiate and sustain breastfeeding. The survey was conducted at The Ohio State University Comprehensive Cancer Center with women aged 18-50 who had at least one live birth. Participants were recruited through primary care practice and a national clinical research registry. Six hundred sixty-seven (92%) of the 724 respondents breastfed. Over half of them (56%), that is, 407 women (60.4% Caucasian, 46.9% African American), were aware before their most recent childbirth that breastfeeding reduced the risk of breast cancer. Of the 407 women, 36.4% said this knowledge affected their decision to breastfeed. Of the 39 who did not breastfeed, 23 women (59.0%) responded that awareness of risk reduction would have influenced their decision to breastfeed. Only 120 of 724 respondents (16.6%) received this information from healthcare providers. Women with this knowledge breastfed longer than those without this knowledge (13.2 versus 9.3 months;  < 0.001). More Caucasian women (76.4%) breastfed any one child for more than 6 months compared with African American women (63.2%;  = 0.011; chi-squared test). While several factors affect the initiation and duration of breastfeeding, this study demonstrates that knowledge of association between breastfeeding and breast cancer risk reduction may influence breastfeeding practices. Our study illustrates the need for improved counseling for mothers by healthcare providers regarding this benefit.
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http://dx.doi.org/10.1089/bfm.2018.0170DOI Listing
December 2018

Comparing the Efficacy of IV Ibuprofen and Ketorolac in the Management of Postoperative Pain Following Arthroscopic Knee Surgery. A Randomized Double-Blind Active Comparator Pilot Study.

Front Surg 2018 3;5:59. Epub 2018 Oct 3.

Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, United States.

Acute postoperative pain following knee arthroscopy is common in orthopedic surgeries. Managing pain postoperatively combines usage of opioids and non-steroidal anti-inflammatory drugs. The aim of this clinical study was to assess the efficacy of two different analgesic treatment regimens: intravenous (IV) ibuprofen and IV ketorolac for the treatment of postoperative pain pertaining to arthroscopic knee surgery. This was a single center, randomized, double-blind, parallel, active comparator clinical pilot study. Subjects were randomized to receive either IV ibuprofen, administered as two 800 mg doses or IV ketorolac, administered as a single 30 mg dose. Subjects in the ibuprofen group received 800 mg of IV ibuprofen within 2 h prior to surgery and a repeated second dose 4 h after the initial dose if they had not been discharged. Subjects in the ketorolac group received IV ketorolac 30 mg at the end of surgery, as per the manufacturer's recommendations. Pain assessments and opioid consumption data were collected up to 24 h postoperatively. Of 53 randomized subjects, 51 completed the study. There were 20 subjects in the ibuprofen group and 31 subjects in the ketorolac group. The median (IQR) visual analog scale (VAS) pain score at resting upon post-anesthesia care unit (PACU) arrival was 33 (12, 52) vs. 9 (2, 25) ( = 0.0064) for the ketorolac and ibuprofen group, respectively. The median (IQR) visual analog scale (VAS) pain score at movement upon PACU arrival was 38 (20, 61) vs. 15 (6, 31) ( = 0.0018) for the ketorolac and ibuprofen group, respectively. Median VAS pain scores during movement taken at subsequent 30 min intervals in the ibuprofen group were less than half that of those reported in the ketorolac group for up to 90 min after arriving in PACU. The median VAS pain scores at rest and movement in the course of 120 min-24 h after PACU arrival was not statistically significant in both groups. Rescue opioid medication during PACU stay was required in 55.0% ( = 11) and 83.9% ( = 26), with a mean amount of narcotic consumption (oral morphine conversion) of 5.53 ± 5.89 mg vs. 19.92 ± 15.63 mg for the ibuprofen and ketorolac group, respectively ( < 0.001). However, opioid consumption during the first 24 h after PACU discharge was not statistically significant (-value = 0.637). The mean time to first rescue medication was 77.62 ± 33.03 and 55.78 ± 35.37 for the ibuprofen and ketorolac group, respectively (-value = 0.0456). There were no significant differences in patient satisfaction and documented adverse events during the first 24 h. This pilot study showed that the use of preemptive IV ibuprofen 800 mg could be considered to reduce postoperative pain and opioid consumption. Future prospective clinical trials using similar regimens should be conducted in order to gain a better understanding of how to best provide perioperative analgesic regimens. www.ClinicalTrials.gov, identifier NCT01650519.
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http://dx.doi.org/10.3389/fsurg.2018.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178884PMC
October 2018

An evaluation of veterinary allergen extract content and resultant canine intradermal threshold concentrations.

Vet Dermatol 2018 Dec 3;29(6):496-e167. Epub 2018 Sep 3.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp St., Columbus, OH, 43210, USA.

Background: Limited information is available for dogs on threshold concentrations (TCs), and the protein composition of common allergenic extracts produced by different manufacturers.

Hypothesis/objectives: To characterize the protein heterogeneity of tree, grass, weed and mite allergens from different lots of allergenic extracts, and to determine intradermal TCs for healthy dogs using extracts from two manufacturers.

Animals: Twenty five privately owned, clinically healthy dogs and ten purpose-bred beagle dogs.

Methods And Materials: Protein concentration and heterogeneity of 11 allergens from two manufacturers were evaluated using a Bradford-style assay and SDS-PAGE. Intradermal testing was performed with 11 allergens from each company at four dilutions. Immediate reactions were subjectively scored (0 to 4+), and objectively measured (mm) and their percentage concordance evaluated. Model-based TCs were determined by fitting positive reactions (≥2+) at 15 min to generalized estimating equations.

Results: Allergen extract protein quantity and composition varied within and between manufacturers despite sharing the same PNU/mL values. Model-based TCs of one weed, five trees, two grasses and a house dust mite were determined for extracts from Manufacturer 1 (M1), and for extracts of three weeds, three trees and two grasses from Manufacturer 2 (M2). Receiver operating characteristic curve analyses determined a percentage concordance of the objective and subjective measurements of 77.3% for M1 and 75% for M2 allergens.

Conclusions And Clinical Importance: Veterinary allergen extracts labelled as the same species and PNU/mL are not standardized; they show heterogeneity in composition and potency within and between manufacturers. Variability in extract content may require adjustment of intradermal testing concentrations.
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http://dx.doi.org/10.1111/vde.12686DOI Listing
December 2018

Time to treatment failure of palbociclib and letrozole as second-line therapy or beyond in hormone receptor-positive advanced breast cancer.

J Oncol Pharm Pract 2019 Sep 22;25(6):1374-1380. Epub 2018 Aug 22.

1 The Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA.

Purpose: The management of endocrine therapy resistance is one of the most challenging facets of advanced breast cancer treatment. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant in postmenopausal women with disease progression following endocrine therapy. However, treatment responsiveness of tumors to palbociclib after multiple lines of endocrine therapy is not clearly established. The purpose of this study was to determine the efficacy of palbociclib and letrozole in patients pretreated with one or more lines of endocrine therapy.

Methods: This was a single-center, retrospective cohort study of all postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer patients who received palbociclib and letrozole as a second-line endocrine therapy or beyond (and no prior cyclin-dependent kinases 4 and 6 inhibitor therapy) between February 1, 2015, and July 31, 2016. The primary objective was to evaluate time to treatment failure of palbociclib in combination with letrozole as a second-line of therapy or beyond.

Results: Fifty-three patients meeting eligibility criteria were included in the analysis. For the primary outcome, the median time to treatment failure of palbociclib and letrozole was 6.3 months (95% CI 3.1-7.4 months). Progression-free survival of palbociclib and letrozole therapy was 6.4 months (95% CI 4.9-8.3 months).

Conclusions: Palbociclib and letrozole therapy is a viable, effective treatment option for metastatic breast cancer patients who were not exposed to cyclin-dependent kinases 4 and 6 inhibitors as a first-line endocrine therapy. The benefits of palbociclib and letrozole therapy were seen without excessive toxicity, and although neutropenia was common, it may be managed with dose reduction.
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http://dx.doi.org/10.1177/1078155218794847DOI Listing
September 2019

Re: Thompson et al.: Predictors of a Successful Urology Resident Using Medical Student Application Materials (Urology 2017;108:22-28).

Urology 2018 05 9;115:189-190. Epub 2018 Feb 9.

Center for Biostatistics, Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH.

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http://dx.doi.org/10.1016/j.urology.2018.01.039DOI Listing
May 2018

Time to consider integration of a formal robotic-assisted surgical training program into obstetrics/gynecology residency curricula.

J Robot Surg 2018 Sep 28;12(3):517-521. Epub 2017 Dec 28.

Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, The Ohio State University, 320 W. 10th Avenue, Starling Loving M210, Columbus, OH, 43210, USA.

The objectives of the study were to describe robotic-assisted surgery training programs currently being used by ACGME-accredited obstetrics and gynecology (OB/Gyn) residency programs and to explore residents' attitudes towards their robotic surgery training curricula to evaluate resident desire for robotics training. We conducted a cross-sectional study of OB/Gyn residents for the 2015-2016 academic year. Participants completed a 31-item online questionnaire regarding their robotic-assisted surgical training and associated perspectives. Analyses of these data were primarily descriptive. In total, 98.9% of included respondents (N = 177) reported availability of a surgical robot at their training institution, and 35.0% of participants reported not having any structured robotics training program at their institution. The most commonly used training modalities included online modules (62.2%), dual-assist console (55.1%) and virtual reality simulation (50.3%). The most commonly reported barriers to completing a robots training were a lack of personal time (56.2%) and availability of the virtual reality simulator or access to the robotic equipment (29.2%). OB/Gyn residents desire robotics training and are exposed to a wide variety of training modalities. The ACGME should consider recommending the incorporation of a standardized formal robotics training program as part of the OB/Gyn residency curriculum.
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http://dx.doi.org/10.1007/s11701-017-0775-0DOI Listing
September 2018

Prospective Analysis of Lipid Composition Changes with Antiretroviral Therapy and Immune Activation in Persons Living with HIV.

Pathog Immun 2017 6;2(3):376-403. Epub 2017 Oct 6.

School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, Columbus, Ohio.

Background: Lipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lyso-phosphatidylcholine, LPC) and their saturated (SaFA), mono-unsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described.

Methods: Plasma lipid concentrations and their fatty acid composition were measured by differential mobility spectroscopy in samples from 35 treatment-naive HIV+ participants beginning raltegravir (RAL)-based ART and from HIV- individuals (n = 13) matched for age and sex.

Results: The levels of SaFA, including palmitic (16:0) and stearic (18:0) acid were enriched in HIV+ participants (pre- and post-ART), and SaFA levels were often positively correlated with levels of immune activation (ie, IL-6, sCD14, and TNFR1) at baseline and week 48. Levels of PUFAs (including 18:3, 20:4, and 20:5) were lower in HIV+ participants at baseline compared to levels in HIV- participants ( < 0.01), and levels of these PUFAs were increased following 48 weeks of ART. Levels of PUFAs were often inversely related to immune activation. Levels of LPC were increased in HIV+ participants, both pre- and post-ART vs HIV- participants, and the composition of LPC was enriched for SaFAs among HIV+ individuals. At week 48, several LPC molecules containing SaFAs were positively correlated with levels of sCD14, D-dimer, and TNFR1 ( < 0.01), and levels of PUFA-containing LPC (18:3, 20:5, 22:5, 22:6) were positively correlated with CD4+ T cell counts and inversely correlated with sCD14 and IL-6 ( < 0.01).

Conclusions: The composition of the lipidome is altered in HIV infection and changes when ART is administered. Alterations in SaFAs were generally associated with inflammatory markers and may contribute to comorbid disease pathogenesis.
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http://dx.doi.org/10.20411/pai.v2i3.218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663243PMC
October 2017

Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache.

Plast Reconstr Surg Glob Open 2017 Mar 28;5(3):e1270. Epub 2017 Mar 28.

Department of Plastic Surgery, The Ohio State University Medical Center, and Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio.

Background: Onabotulinumtoxin A (BOTOX) is an FDA-approved treatment for chronic migraine headaches (MHs) that involves on-label, high-dose administration across 31 anatomic sites. Anatomically specific peripheral nerve trigger sites have been identified that contribute to MH pathogenesis and are amenable to both BOTOX injection and surgical decompression. These sites do not always correlate with the on-label FDA-approved injection pattern, but represent a more targeted approach. The efficacy of peripheral nerve-directed BOTOX injection as an independent long-term therapeutic option has not been investigated.

Methods: The technique for peripheral nerve-directed therapeutic long-term BOTOX injection is described. A retrospective review was subsequently completed for 223 patients with MH. Sixty-six patients elected to proceed with diagnostic BOTOX injections. Of these, 24 continued long-term therapeutic BOTOX injections, whereas 42 matriculated to surgery. Outcomes were tracked.

Results: Initial outcomes included significant improvement in migraine headache index (MHI) (53.5 ± 83.0, < 0.006), headache days/mo (9.2 ± 12.7, < 0.0009), and migraine severity (2.6 ± 2.5, < 0.00008) versus baseline. MHI improved from the initiation of diagnostic injections to the establishment of steady-state injections ( < 0.002), and further improved over time ( < 0.05, mean follow-up 615 days) with no desensitization observed. Decompressive surgery resulted in significant improvement in MHI (100.8 ± 109.7, < 0.0000005), headache days/mo (10.8 ± 12.7, < 0.000002), migraine severity (3.0 ± 3.8, < 0.00001), and migraine duration in hours (16.8 ± 21.6, < 0.0007). MHI improvement with surgery was better than long-term BOTOX injections ( < 0.05).

Conclusions: Though inferior to surgical decompression, preliminary data demonstrate that targeted peripheral nerve-directed BOTOX injection is an effective primary therapy for MH representing a possible alternative to nondirected BOTOX injection with decreased dosage requirements and potentially decreased cost.
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http://dx.doi.org/10.1097/GOX.0000000000001270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404453PMC
March 2017

Quantitative biomechanical assessment of trunk control in Huntington's disease reveals more impairment in static than dynamic tasks.

J Neurol Sci 2017 May 27;376:29-34. Epub 2017 Feb 27.

Physical Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University, 453 West 10th Ave, Columbus, OH 43210, United States. Electronic address:

Postural instability is common in individuals with Huntington's disease (HD), yet little is known about control of the trunk during static and dynamic activities. We compared the trunk motion of 41 individuals with HD and 36 controls at thoracic and pelvic levels during sitting, standing, and walking using wearable iPod sensors. We also examined the ability of individuals with HD to respond to an auditory cue to modify trunk position when the pelvis moved >8° in sagittal or frontal planes during sitting using custom software. We found that amplitude of thoracic and pelvic trunk movements was significantly greater in participants with HD, and differences were more pronounced during static (i.e. sitting, standing) than dynamic (i.e. walking) tasks. In contrast to the slow, smooth sinusoidal trunk movements of controls, individuals with HD demonstrated rapid movements with varying amplitudes that continuously increased without stabilizing. Ninety-seven percent of participants with HD were able to modify their trunk position in response to auditory cues. Our results demonstrate that wearable iPod sensors are clinically useful for rehabilitation professionals to measure and monitor trunk stability in persons with HD. Additionally, auditory cueing holds potential as a useful training tool to improve trunk stability in HD.
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http://dx.doi.org/10.1016/j.jns.2017.02.054DOI Listing
May 2017

Serum brain-derived neurotrophic factor (BDNF) across pregnancy and postpartum: Associations with race, depressive symptoms, and low birth weight.

Psychoneuroendocrinology 2016 12 27;74:69-76. Epub 2016 Aug 27.

Center for Biostatistics, The Ohio State University, Columbus, OH, USA.

Background: Brain-derived neurotrophic factor (BDNF) is implicated as a causal factor in major depression and is critical to placental development during pregnancy. Longitudinal data on BDNF across the perinatal period are lacking. These data are of interest given the potential implications for maternal mood and fetal growth, particularly among Black women who show ∼2-fold greater risk for delivering low birth weight infants.

Methods: Serum BDNF, serum cortisol, and depressive symptoms (per CES-D) were assessed during each trimester and 4-11 weeks postpartum among 139 women (77 Black, 62 White). Low birth weight (<2500g) was determined via medical record.

Results: Serum BDNF declined considerably from 1st through 3rd trimesters (ps≤0.008) and subsequently increased at postpartum (p<0.001). Black women exhibited significantly higher serum BDNF during the 1st trimester, 2nd trimester, and postpartum (ps≤0.032) as well as lower serum cortisol during the 2nd and 3rd trimester (ps≤0.01). Higher serum cortisol was concurrently associated with lower serum BDNF in the 2nd trimester only (p<0.05). Controlling for race, serum BDNF at both the 2nd and 3rd trimester was negatively associated with 3rd trimester depressive symptoms (ps≤0.02). In addition, women delivering low versus healthy weight infants showed significantly lower serum BDNF in the 3rd trimester (p=0.004). Women delivering low versus healthy weight infants did not differ in depressive symptoms at any time point during pregnancy (ps≥0.34).

Conclusions: Serum BDNF declines considerably across pregnancy in Black and White women, with overall higher levels in Blacks. Lower serum BDNF in late pregnancy corresponds with higher depressive symptoms and risk for low birth weight in Black and White women. However, the predictive value of serum BDNF in pregnancy is specific to within-race comparisons. Potential links between racial differences in serum BDNF and differential pregnancy-related cortisol adaptation require further investigation.
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http://dx.doi.org/10.1016/j.psyneuen.2016.08.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166606PMC
December 2016