Methods: Patients undergoing primary, elective 1–3 level ACDF for radiculopathy at a single academic center between 2015 and 2021 were identified retrospectively. Cervical FS was evaluated using axial T2-weighted MRI images via a validated grading scale. The maximum degree of stenosis was used for multilevel disease. Motor symptoms were classified using encounters at their final preoperative and first postoperative visits, with examinations ≤3/5 indicating weakness. PROMs were obtained preoperatively and at 1-year follow-up. Bivariate analysis was used to compare outcomes based on stenosis severity, followed by multivariable analysis. Results: This study included 354 patients, 157 with moderate stenosis and 197 with severe stenosis. Overall, 58 patients (16.4%) presented with upper extremity weakness ≤3/5. A similar number of patients in both groups presented with baseline motor weakness (13.5% vs. 16.55, p =0.431). Postoperatively, 97.1% and 87.0% of patients with severe and moderate FS, respectively, experienced full motor recovery (p =0.134). At 1-year, patients with severe neuroforaminal stenosis presented with significantly worse 12-item Short Form Survey Physical Component Score (PCS-12) (33.3 vs. 37.3, p =0.049) but demonstrated a greater magnitude of improvement (Δ PCS-12: 5.43 vs. 0.87, p =0.048). Worse stenosis was independently associated with greater ΔPCS-12 at 1-year (β =5.59, p =0.022). Conclusions Patients with severe FS presented with worse preoperative physical health. While ACDF improved outcomes and conferred similar motor recovery in all patients, those with severe FS reported much better improvement in physical function.

Background: Right ventricular pacing (RVP) increases heart failure, AF, and death rates in pacemaker patients and ventricular arrhythmias (VAs) in defibrillator patients. However, the impact of RVP on VAs burden and its clinical significance in pacemaker patients with normal range LVEF of > 50–55% remains unknown. We sought to evaluate the relationship of RVP and VAs and its clinical impact in a pacemaker patient population. Methods: Records of 105 patients who underwent de novo dual-chamber pacemaker implant or a generator change (Medtronic™ or Boston Scientific™) for AV block and sinus node disease at a tertiary care center between September 1, 2015, and September 1, 2016, were retrospectively reviewed. Results: Data from 105 patients (51% females, mean age 76 ± 1 years, mean LVEF 61 ± 0.7%) without history of VAs (98.2%) were reviewed over 1044 ± 23 days. Dependent patients (100% RVP) exhibited the lowest VAs burden when compared to < 100% RVP (isolated PVCs, PVC runs of < 4 beats, and NSVT; p ≤ 0.001). Patients with < 1% RVP also exhibited low VA burden with intermediate RVP (1–99.9%) being most arrhythmogenic for PVC runs (p = 0.04) and for isolated PVCs (p = 0.006). Antiarrhythmics/beta and calcium channel blockers use and stress tests performed to evaluate VAs which were positive requiring intervention did not differ significantly. Burden of > 1/h of PVC runs and increasing PVC runs/h were significantly associated with hospitalization (p = 0.04) and all-cause mortality (p = 0.03), respectively. Conclusions In pacemaker patients with normal range LVEF (> 50–55%), 100% RVP is associated with the lowest burden of NSVT. Furthermore, patients with < 1% RVP also exhibit low VA burden; however, intermittent RVP seems to significantly correlate with non-sustained VAs.

Objective: This study estimated nationally representative medical expenditures of gynecologic cancers, described treatment patterns and assessed key risk factors associated with the economic burden in the United States. Methods: A retrospective repeated measures design was used to estimate the effect of gynecologic cancers on medical expenditures and utilization among women. Data were extracted from the Medical Expenditure Panel Survey (weighted sample of 609,787 US adults) from 2007 to 2014. Using the behavioral model of health services utilization, characteristics of cancer patients were examined and compared among uterine, cervical, and ovarian cancer patients. Multivariable linear regression models were conducted on medical expenditure with a prior logarithmic transformation. Results: The estimated annual medical expenditure attributed to gynecologic cancers was $3.8 billion, with an average cost of $6,293 per patient. The highest annual cost per person was ovarian cancer ($13,566), followed by uterine cancer ($6,852), and cervical cancer ($2,312). The major components of medical costs were hospital inpatient stays (53%, $2.03 billion), followed by office-based visits (15%, $559 million), and outpatient visits (13%, $487 million). Two key prescription expenditures were antineoplastic hormones (10.3%) and analgesics (9.2%). High expenditures were significantly associated with being a married woman (p<0.001), having private health insurance (p<0.001), being from a low- and middleincome family (p<0.001), or living in the Midwest or the South (p<0.001). Conclusion The key risk factors and components were well described for the economic burden of gynecologic cancers. With a growing population of cancer patients, efforts to reduce the burden of gynecologic cancers are warranted.

OBJECTIVE: A growing interest in extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue strategy for refractory adult out-of-hospital cardiac arrest (OHCA) currently exists. This study aims to determine current standards of care and practice variation for ECPR patients in the USA and Korea. METHODS: In December 2015, we surveyed centers from the Korean Hypothermia Network (KORHN) Investigators and the US National Post-Arrest Research Consortium (NPARC) on current targeted temperature management and ECPR practices. This project analyzes the subsection of questions addressing ECPR practices. We summarized survey results using descriptive statistics. RESULTS: Overall, 9 KORHN and 4 NPARC centers reported having ECPR programs and had complete survey data available. Two KORHN centers utilized extracorporeal membrane oxygenation only for postarrest circulatory support in patients with refractory shock and were excluded from further analysis. Centers with available ECPR generally saw a high volume of OHCA patients (10/11 centers care for >75 OHCA a year). Location of, and providers trained for cannulation varied across centers. All centers in both countries (KORHN 7/7, NPARC 4/4) treated comatose ECPR patients with targeted temperature management. All NPARC centers and four of seven KORHN centers reported having a standardized hospital protocol for ECPR. Upper age cutoff for eligibility ranged from 60 to 75 years. No absolute contraindications were unanimous among centers. CONCLUSION: A wide variability in practice patterns exist between centers performing ECPR for refractory OHCA in the US and Korea. Standardized protocols and shared research databases might inform best practices, improve outcomes, and provide a foundation for prospective studies.
Adult* ; Cardiopulmonary Resuscitation* ; Catheterization ; Coma ; Extracorporeal Membrane Oxygenation ; Heart Arrest ; Humans ; Hypothermia ; Korea ; Out-of-Hospital Cardiac Arrest* ; Practice Guidelines as Topic ; Prospective Studies ; Research Personnel ; Shock ; Standard of Care

BACKGROUND AND PURPOSE: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT). METHODS: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale. RESULTS: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus. CONCLUSIONS: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD.
Activities of Daily Living ; Alzheimer Disease* ; Cerebrovascular Circulation ; Cerebrovascular Disorders ; Cognition ; Cognition Disorders ; Dementia ; Depression ; Ergolines ; Follow-Up Studies ; Frontal Lobe ; Humans ; Nicergoline* ; Parietal Lobe ; Perfusion* ; Pilot Projects* ; Prefrontal Cortex ; Somatosensory Cortex ; Therapeutic Uses ; Tomography, Emission-Computed, Single-Photon

PURPOSE: The selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 bispecific natural killer (NK) cell engager (BiKE), consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified interleukin (IL)-15 crosslinker capable of stimulating NK effector cells was introduced. MATERIALS AND METHODS: DNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE). The construct was tested for its specificity using flow cytometry, cytotoxic determinations using chromium release assays, and lytic degranulation. IL-15–mediated expansion was measured using flow-based proliferation assays. The level of interferon (IFN)-γ release was measured because of its importance in the anti-cancer response. RESULTS: 1615133 TriKE induced NK cell–mediated cytotoxicity and NK expansion far greater than that achieved with BiKE devoid of IL-15. The drug binding and induction of cytotoxic degranulation was CD133+ specific and the anti-cancer activity was improved by integrating the IL-15 cross linker. The NK cell–related cytokine release measured by IFN-γ detection was higher than that of BiKE. NK cytokine release studies showed that although the IFN-γ levels were elevated, they did not approach the levels achieved with IL-12/IL-18, indicating that release was not at the supraphysiologic level. CONCLUSION: 1615133 TriKE enhances the NK cell anti-cancer activity and provides a self-sustaining mechanism via IL-15 signaling. By improving the NK cell performance, the new TriKE represents a highly active drug against drug refractory relapse mediated by CSCs.
Antibody-Dependent Cell Cytotoxicity ; Chromium ; DNA Shuffling ; Flow Cytometry ; Humans ; Interferons ; Interleukin-15 ; Interleukins ; Killer Cells, Natural ; Ligation ; Neoplastic Stem Cells ; Recurrence ; Sensitivity and Specificity

Osteoactivin is a heavily glycosylated protein shown to have a role in bone remodeling. Previous studies from our lab have shown that mutation in Osteoactivin enhances osteoclast differentiation but inhibits their function. To date, a classical receptor and a signaling pathway for Osteoactivin-mediated osteoclast inhibition has not yet been characterized. In this study, we examined the role of Osteoactivin treatment on osteoclastogenesis using bone marrow-derived osteoclast progenitor cells and identify a signaling pathway relating to Osteoactivin function. We reveal that recombinant Osteoactivin treatment inhibited osteoclast differentiation in a dose-dependent manner shown by qPCR, TRAP staining, activity and count. Using several approaches, we show that Osteoactivin binds CD44 in osteoclasts. Furthermore, recombinant Osteoactivin treatment inhibited ERK phosphorylation in a CD44-dependent manner. Finally, we examined the role of Osteoactivin on receptor activator of nuclear factor-κ B ligand (RANKL)-induced osteolysis in vivo. Our data indicate that recombinant Osteoactivin inhibits RANKL-induced osteolysis in vivo and this effect is CD44-dependent. Overall, our data indicate that Osteoactivin is a negative regulator of osteoclastogenesis in vitro and in vivo and that this process is regulated through CD44 and ERK activation.
Bone Remodeling ; In Vitro Techniques ; Osteoclasts ; Osteolysis ; Phosphorylation ; Stem Cells

It is essential that primary care physicians have a solid fund of knowledge of the diagnosis and management of common eye conditions as well as ocular emergencies, as management of these diseases commonly involves appropriate referral to an ophthalmologist. Thus, it is crucial to receive comprehensive clinical knowledge of ophthalmic disease in the primary care setting during medical school. This study investigated how well prepared medical students are to diagnose and manage common ocular conditions. The study used scores from a standardized 12-question quiz administered to fourth-year medical students (N=97; 88% response rate) and second-year medical students (N=97; 97% response rate). The quiz comprising diagnosis and referral management questions covered the most frequently tested ophthalmology topics on board exams and assessed students' ability to recognize when referral to an ophthalmologist is appropriate. Fourth-year medical students had quiz scores ranging from 0%-94.5% with an average score of 68.7%. Second-year students had quiz scores ranging from 27.2%-86.4%, with an average score of 63.8%. Passing rate was 70%. Student's t-test showed fourth-year students had a significantly higher quiz average (P=0.003). In general, both classes performed better on diagnostic questions (fourth-year, 73.7%; second year, 65.8%) rather than on management questions (fourth-year, 64.8%; second year, 61.8%). Both second-year and fourth-year students on average fell short on passing the ophthalmology proficiency quiz, and in general students were more adept at diagnosing rather than managing ocular conditions and emergencies.
Diagnosis ; Disease Management ; Emergencies ; Financial Management ; Humans ; Ophthalmology ; Physicians, Primary Care ; Primary Health Care ; Referral and Consultation ; Schools, Medical ; Students, Medical*

As medical students enter the role of physician, clinical outcomes not only rely on their mastery of clinical knowledge, but also on the effectiveness in which they can communicate with patients and family members. While students typically have numerous opportunities to practice clinical communication with adult patients, such practice in pediatric settings is limited. This study examines if simulated patient (SP) encounters strengthen third-year medical students' communication skills during the pediatrics clerkship. During 2011-2013, three SP encounters (comprising 3 pediatric scenarios) were incorporated into a pediatrics clerkship at one United States medical school to give students a safe venue to practice advanced communication with observation and direct feedback. Third-year medical students engaged in the scenarios and received both written and oral feedback from an evaluator observing the encounter. With IRB approval, students' self-perceived confidence and abilities at performing the advanced communication skills were measured using an eight-item, Likert scale questionnaire administered pre and post the SP encounter. Pre- and post-questionnaires (n=215; response rate, 96%) analyzed using a Wilcoxon-matched pairs signed-rank test demonstrated statistically significant increases in students' perception of their confidence and abilities regarding their performance (P<0.05; Bonferroni correction, P<0.006). There was an increases in student confidence and self-perceived ability in: first, communicating with children and family members of young patients; second, managing confrontational situations involving parents; third, performing a thorough psychosocial history with an adolescent; and fourth, using Evidence Based Medicine to motivate parents.
Adolescent ; Adult ; Child ; Ethics Committees, Research ; Evidence-Based Medicine ; Humans ; Parents ; Pediatrics ; Schools, Medical ; Students, Medical ; United States ; Surveys and Questionnaires

BACKGROUND AND OBJECTIVES: In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure trial, ultrafiltration (UF) removed volume more effectively than usual care (UC). Hypothetically, UF may be superior to UC due to increased sodium (Na) removal and less neurohormonal activation. We compared UF and UC in a randomized pilot trial of target weight guided therapy for acute decompensated heart failure (ADHF). SUBJECTS AND METHODS: Sixteen patients with ADHF were enrolled and target weights established prospectively, prior to randomization to UC or UF. UF patients did not receive diuretics and UC patients were all treated with a continuous furosemide drip. All urine and ultrafiltrate were collected and Na concentrations measured. RESULTS: Similar volumes were removed in UC and UF groups (110105 mL and 107415 mL, respectively) and the UF group also produced 45325 mL of urine. Na concentration was 138+/-6 meq/L in the ultrafiltrate, 85+/-73 meq/L in the UC group's urine, and 26+/-23 meq/L in the UF group's urine. Given the relevant associated volumes, total meq of the Na removed was similar (1168 in UC vs. 1216 in UF). The UF group produced isotonic ultrafiltrate and a higher volume of dilute urine than anticipated. CONCLUSION: In a randomized pilot study of target weight guided therapy with UC or UF for ADHF, there were no differences in total volumes or Na removed, and lengths of hospital stays were similar. Isotonic fluid loss by UF was accompanied by the production of very dilute urine.
Diuretics ; Furosemide ; Heart Failure* ; Humans ; Length of Stay ; Pilot Projects* ; Prospective Studies ; Random Allocation ; Sodium* ; Ultrafiltration* ; Weights and Measures