Prevalence of Sexual Function and Vibrator Use Among Urogynecology Patients.

IMPORTANCE: Urogynecology patients often present with sexual dysfunction; limited information on vibrator utilization to improve sexual function in this population exists. OBJECTIVE: The aim of this study was to assess patient knowledge of and receptivity to vibrator use. STUDY DESIGN: We conducted a cross-sectional, survey-based cohort study. The survey included patient characteristics, Pelvic Floor Distress Inventory-20 (PFDI-20), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form 12, and vibrator use questions. Our primary outcome was vibrator utilization rates comparing younger (<65) and older (≥65 years) urogynecology patients. RESULTS: Of 213 distributed, 165 (78%) surveys were analyzed. Of these, 104 participants (63%) were aged <65 years and 61 (37%) were ≥65 years. Baseline characteristics were similar between groups (all P's > 0.05). Older patients reported less vibrator utilization than younger patients (30% vs 64%, P ≤ 0.001) and were less likely to be sexually active with a partner (36% vs 62%, P = 0.002) or masturbate (23% vs 51%, P ≤ 0.001). Most patients (76%) thought physicians should discuss vibrators with patients who would like to improve their sexual function with no differences between age groups (71% vs 80%, P = 0.17). Among women receptive to vibrator use, in a multivariable analysis, patients who reported masturbation (odds ratio [OR], 13.8; 95% confidence interval [CI], 2.80-67.71), vibrator use in the past (OR, 24.4; 95% CI, 6.65-89.53), or who believed physicians should discuss vibrators in a clinical setting (OR, 11.66; 95% CI, 2.9-46.81) were more receptive to vibrator use to improve sexual function. Age did not influence receptivity. CONCLUSIONS: Vibrator utilization is greater among younger than older patients. Most urogynecologic patients think health care providers should discuss vibrator use with patients who wish to improve sexual function.

The Longitudinal Neurophysiological Adaptation of a Division I Female Lacrosse Player Following Anterior Cruciate Rupture and Repair: A Case Report.

Background: Neurophysiological adaptation following anterior cruciate ligament (ACL) rupture and repair (ACLR) is critical in establishing neural pathways during the rehabilitation process. However, there is limited objective measures available to assess neurological and physiological markers of rehabilitation. Purpose: To investigate the innovative use of quantitative electroencephalography (qEEG) to monitor the longitudinal change in brain and central nervous systems activity while measuring musculoskeletal function during an anterior cruciate ligament repair rehabilitation. Case Description: A 19 year-old, right-handed, Division I NCAA female lacrosse midfielder suffered an anterior cruciate ligament rupture, with a tear to the posterior horn of the lateral meniscus of the right knee. Arthroscopic reconstruction utilizing a hamstring autograft and a 5% lateral meniscectomy was performed. An evidence-based ACLR rehabilitation protocol was implemented while using qEEG. Outcomes: Central nervous system, brain performance and musculoskeletal functional biomarkers were monitored longitudinally at three separate time points following anterior cruciate injury: twenty-four hours post ACL rupture, one month and 10 months following ACLR surgery. Biological markers of stress, recovery, brain workload, attention and physiological arousal levels yielded elevated stress determinants in the acute stages of injury and were accompanied with noted brain alterations. Brain and musculoskeletal dysfunction longitudinally reveal a neurophysiological acute compensation and recovering accommodations from time point one to three. Biological responses to stress, brain workload, arousal, attention and brain connectivity all improved over time. Discussion: The neurophysiological responses following acute ACL rupture demonstrates significant dysfunction and asymmetries neurocognitively and physiologically. Initial qEEG assessments revealed hypoconnectivity and brain state dysregulation. Progressive enhanced brain efficiency and functional task progressions associated with ACLR rehabilitation had notable simultaneous improvements. There may be a role for monitoring CNS/brain state throughout rehabilitation and return to play. Future studies should investigate the use of qEEG and neurophysiological properties in tandem during the rehabilitation progression and return to play.

Does Ending a Posterior Construct Proximally at C2 Versus C3 Impact Patient Reported Outcomes in Degenerative Cervical Myelopathy Patients up to 24 months After the Surgery?

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The primary objective was to evaluate the impact of the upper instrumented level (UIV) being at C2 vs C3 in posterior cervical construct on patient reported outcomes (PROs) up to 24 months after surgery for cervical degenerative myelopathy (DCM). Secondary objectives were to compare operative time, intra-operative blood loss (IOBL), length of stay (LOS), adverse events (AEs) and re-operation. METHODOLOGY: Patients who underwent a posterior cervical instrumented fusion (3 and + levels) with a C2 or C3 UIV, with 24 months follow-up were analyzed. PROs (NDI, EQ5D, SF-12 PCS/MCS, NRS arm/neck pain) were compared using ANCOVA. Operative duration, IOBL, AEs, and re-operation were compared. Subgroup analysis was performed on patient presenting with pre-operative malalignment (cervical sagittal vertical axis ≥40 mm and/or T1slope- cervical lordosis >15°). RESULTS: 173 patients were included, of which 41 (24%) had a C2 UIV and 132 (76%) a C3 UIV. There was no statistically significant difference between the groups for the changes in PROs up to 24 months. Subgroup analysis of patients with pre-operative malalignment showed a trend towards greater improvement in the NDI at 12 months with a C2 UIV (P = .054). Operative time, IOBL and peri-operative AEs were more in C2 group (P < .05). There was no significant difference in LOS and re-operation (P > .05). CONCLUSION: In this observational study, up to 24 months after surgery for posterior cervical fusion in DCM greater than 3 levels, PROs appear to evolve similarly.

Back Dominant Pain Has Equal Outcomes to Radicular Dominant Pain Following Posterior Lumbar Fusion in Adult Isthmic Spondylolisthesis: A CSORN Study.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: This study aimed to determine how the surgeon-determined and patient-rated location of predominant pain influences patient-rated outcomes at 1-year after posterior lumbar fusion in adult isthmic spondylolisthesis. METHODS: We retrospectively reviewed consecutive patients prospectively enrolled in the Canadian Spine Outcomes and Research Network national registry between 2009 and 2017 that underwent posterior lumbar fusion for isthmic spondylolisthesis. Using longitudinal mixed-model repeated-measures analysis the change from baseline in patient-reported outcome measures (PROMs) at 1 year after surgery was compared between surgeon-determined groups (back vs. radicular) and between patient-rated pain groups (back, leg, and equal) derived from preoperative pain scores on the numerical rating scale (NRS). RESULTS: 83/252 (33%) patients had a surgeon-determined chief complaint of back pain, while 103 (41%) patients rated their back pain as the predominant pain location, and 78 (31%) rated their back and leg pain to be equal. At baseline patients in the surgeon-determined radicular group had worse NRS-leg pain than those in the back-pain group but equal NRS-back pain. At baseline patients in the patient-rated equal pain group had similar back pain compared to the patient-rated back pain group and similar leg pain compared to the patient-rated leg pain group. All PROMs improved post-operatively and were not different between the 2 groups at 1 year. CONCLUSIONS: Our study found no difference in outcome, irrespective of whether a surgeon determines the patient's primary pain complaint back or radicular dominant, or the patient rates pain in one location greater than another.

Changes in cerebral arterial pulsatility and hippocampal volume: a transcranial doppler ultrasonography study.

The physiological mechanisms of age-related cognitive decline remain unclear, in no small part due to the lack of longitudinal studies. Extant longitudinal studies focused on gross neuroanatomy and diffusion properties of the brain. We present herein a longitudinal analysis of changes in arterial pulsatility - a proxy for arterial stiffness - in two major cerebral arteries, middle cerebral and vertebral. We found that pulsatility increased in some participants over a relatively short period and these increases were associated with hippocampal shrinkage. Higher baseline pulsatility was associated with lower scores on a test of fluid intelligence at follow-up. This is the first longitudinal evidence of an association between increase in cerebral arterial stiffness over time and regional shrinkage.

Patients undergoing surgery for lumbar spinal stenosis experience unique courses of pain and disability: A group-based trajectory analysis.

OBJECTIVE: Identify patient subgroups defined by trajectories of pain and disability following surgery for degenerative lumbar spinal stenosis, and investigate the construct validity of the subgroups by evaluating for meaningful differences in clinical outcomes. METHODS: We recruited patients with degenerative lumbar spinal stenosis from 13 surgical spine centers who were deemed to be surgical candidates. Study outcomes (leg and back pain numeric rating scales, modified Oswestry disability index) were measured before surgery, and after 3, 12, and 24 months. Group-based trajectory models were developed to identify trajectory subgroups for leg pain, back pain, and pain-related disability. We examined for differences in the proportion of patients achieving minimum clinically important change in pain and disability (30%) and clinical success (50% reduction in disability or Oswestry score ≤22) 12 months from surgery. RESULTS: Data from 548 patients (mean[SD] age = 66.7[9.1] years; 46% female) were included. The models estimated 3 unique trajectories for leg pain (excellent outcome = 14.4%, good outcome = 49.5%, poor outcome = 36.1%), back pain (excellent outcome = 13.1%, good outcome = 45.0%, poor outcome = 41.9%), and disability (excellent outcome = 30.8%, fair outcome = 40.1%, poor outcome = 29.1%). The construct validity of the trajectory subgroups was confirmed by between-trajectory group differences in the proportion of patients meeting thresholds for minimum clinically important change and clinical success after 12 postoperative months (p < .001). CONCLUSION: Subgroups of patients with degenerative lumbar spinal stenosis can be identified by their trajectories of pain and disability following surgery. Although most patients experienced important reductions in pain and disability, 29% to 42% of patients were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. These findings may inform appropriate expectation setting for patients and clinicians and highlight the need for better methods of treatment selection for patients with degenerative lumbar spinal stenosis.

Treatment of Mild Cervical Myelopathy: Factors Associated With Decision for Surgical Intervention.

STUDY DESIGN: Prospective Cohort OBJECTIVE.: The aim of this study was to evaluate which demographic, clinical, or radiographic factors are associated with selection for surgical intervention in patients with mild cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Surgery has not been shown superior to best conservative management in mild CSM comparative studies; trials of conservative management represent an acceptable alternative to surgical decompression. It is unknown what patients benefit from surgery. METHODS: This is a prospective study of patients with mild CSM, defined as modified Japanese Orthopaedic Association Score (mJOA) ≥15. Patients were recruited from seven sites contributing to the Canadian Spine Outcomes Research Network. Demographic, clinical, radiographic and health related quality of life data were collected on all patients at baseline. Multivariate logistic regression modeling was used to identify factors associated with surgical intervention. RESULTS: There were 122 patients enrolled, 105 (86.0%) were treated surgically, and 17 (14.0%) were treated nonoperatively. Overall mean age was 54.8 years (SD 12.6) with 80 (65.5%) males. Bivariate analysis revealed no statistically significant differences between surgical and nonoperative groups with respect to age, sex, BMI, smoking status, number of comorbidities and duration of symptoms; mJOA scores were significantly higher in the nonoperative group (16.8 [SD 0.99] vs. 15.9 [SD 0.89], P < 0.001). There was a statistically significant difference in Neck Disability Index, SF12 Physical Component, SF12 Mental Component Score, EQ5D, and PHQ-9 scores between groups; those treated surgically had worse baseline questionnaire scores (P < 0.05). There was no difference in radiographic parameters between groups. Multivariable analysis revealed that lower quality of life scores on EQ5D were associated with selection for surgical management (P < 0.018). CONCLUSION: Patients treated surgically for mild cervical myelopathy did not differ from those treated nonoperatively with respect to baseline demographic or radiographic parameters. Patients with worse EQ5D scores had higher odds of surgical intervention. LEVEL OF EVIDENCE: 3.

The Novel Methods for Analysis of Exosomes Released from Endothelial Cells and Endothelial Progenitor Cells.

Exosomes (EXs) are cell-derived vesicles that mediate cell-cell communication and could serve as biomarkers. Here we described novel methods for purification and phenotyping of EXs released from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads and fluorescence quantum dots (Q-dots®) techniques. EXs from the culture medium of ECs and EPCs were isolated and detected with cell-specific antibody conjugated microbeads and second antibody conjugated Q-dots by using nanoparticle tracking analysis (NTA) system. The sensitivities of the cell origin markers for ECs (CD105, CD144) and EPCs (CD34, KDR) were evaluated. The sensitivity and specificity were determined by using positive and negative markers for EXs (CD63), platelets (CD41), erythrocytes (CD235a), and microvesicles (Annexin V). Moreover, the methods were further validated in particle-free plasma and patient samples. Results showed that anti-CD105/anti-CD144 and anti-CD34/anti-KDR had the highest sensitivity and specificity for isolating and detecting EC-EXs and EPC-EXs, respectively. The methods had the overall recovery rate of over 70% and were able to detect the dynamical changes of circulating EC-EXs and EPC-EXs in acute ischemic stroke. In conclusion, we have developed sensitive and specific microbeads/Q-dots fluorescence NTA methods for EC-EX and EPC-EX isolation and detection, which will facilitate the functional study and biomarker discovery.

Endothelial progenitor cells and neural progenitor cells synergistically protect cerebral endothelial cells from Hypoxia/reoxygenation-induced injury via activating the PI3K/Akt pathway.

BACKGROUND: Protection of cerebral endothelial cells (ECs) from hypoxia/reoxygenation (H/R)-induced injury is an important strategy for treating ischemic stroke. In this study, we investigated whether co-culture with endothelial progenitor cells (EPCs) and neural progenitor cells (NPCs) synergistically protects cerebral ECs against H/R injury and the underlying mechanism. RESULTS: EPCs and NPCs were respectively generated from inducible pluripotent stem cells. Human brain ECs were used to produce an in vitro H/R-injury model. Data showed: 1) Co-culture with EPCs and NPCs synergistically inhibited H/R-induced reactive oxygen species (ROS) over-production, apoptosis, and improved the angiogenic and barrier functions (tube formation and permeability) in H/R-injured ECs. 2) Co-culture with NPCs up-regulated the expression of vascular endothelial growth factor receptor 2 (VEGFR2). 3) Co-culture with EPCs and NPCs complementarily increased vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in conditioned medium, and synergistically up-regulated the expression of p-Akt/Akt and p-Flk1/VEGFR2 in H/R-injured ECs. 4) Those effects could be decreased or abolished by inhibition of both VEGFR2 and tyrosine kinase B (TrkB) or phosphatidylinositol-3-kinase (PI3K). CONCLUSIONS: Our data demonstrate that EPCs and NPCs synergistically protect cerebral ECs from H/R-injury, via activating the PI3K/Akt pathway which mainly depends on VEGF and BDNF paracrine.

Accuracy of identifying acute stroke admissions in a Michigan Stroke Registry.

INTRODUCTION: The accurate identification of acute stroke cases is an essential requirement of hospital-based stroke registries. We determined the accuracy of acute stroke diagnoses in Michigan hospitals participating in a prototype of the Paul Coverdell National Acute Stroke Registry. METHODS: From May through November 2002, registry teams (ie, nurse and physician) from 15 Michigan hospitals prospectively identified all suspect acute stroke admissions and classified them as stroke or nonstroke. Medical chart data were abstracted for a random sample of 120 stroke and 120 nonstroke admissions. A blinded independent physician panel then classified each admission as stroke, nonstroke, or unclassifiable, and the overall accuracy of the registry was determined. RESULTS: The physician panel reached consensus on 219 (91.3%) of 240 admissions. The panel identified 105 stroke admissions, 93 of which had been identified by the registry teams (sensitivity = 88.6%). The panel identified 114 nonstroke admissions, all of which had been identified as nonstrokes by the registry teams (specificity = 100%). The positive and negative predictive value of the registry teams' designation was 100% and 90.5%, respectively. The registry teams' assessment of stroke subtype agreed with that of the panel in 78.5% of cases. Most discrepancies were related to the distinction between ischemic stroke and transient ischemic attack. CONCLUSION: The accuracy of hospitals participating in a hospital-based stroke registry to identify acute stroke admissions was very good; hospitals tended to underreport rather than to overreport stroke admissions. Stroke registries should periodically conduct studies to ensure that the accuracy of case ascertainment is maintained.

Infarction involving the insula and risk of mortality after stroke.

BACKGROUND: Cerebral infarction involving the insula has been associated with decreased survival following stroke. We hypothesized that infarct volume may reduce this association. METHODS: The subjects were acute stroke patients who had consented to 2-year follow-up after stroke as part of the Michigan Acute Stroke Care Overview and Treatment Surveillance System registry. One hundred and eleven subjects exhibited areas of acute ischemic infarction on neuroimaging studies, 25 of whom had infarction involving the insula. Cox proportional hazard ratios (HR) were calculated to determine the association between mortality and acute infarction involving the insula, infarct volume, and other factors known to affect survival after stroke. RESULTS: In unadjusted analysis, subjects with insula infarction had a nonsignificant twofold increase in 1-year mortality (HR = 2.1, 95% CI 0.6-7.0; p = 0.25). When adjusted for infarct volume, however, the HR for insula infarction was reduced to the null value (HR = 1.0, 95% CI 0.2-4.1; p = 1.00), indicating that the effect of insula infarction was entirely confounded by infarct volume. CONCLUSIONS: Insula infarction was associated with a nonsignificant twofold increase in mortality after stroke; however, this association was completely eliminated after adjusting for infarct volume. Infarct volume thus should be considered in future studies of insula infarction and mortality.

Aging, vascular risk, and cognition: blood glucose, pulse pressure, and cognitive performance in healthy adults.

Advanced age is associated with decline in many areas of cognition as well as increased frequency of vascular disease. Well-described risk factors for vascular disease, such as diabetes and arterial hypertension, have been linked to cognitive deficits beyond those associated with aging. To examine whether vascular health indices such as fasting blood glucose levels and arterial pulse pressure can predict subtle deficits in age-sensitive abilities, the authors studied 104 healthy adults (ages 18 to 78) without diagnoses of diabetes or hypertension. Whereas results revealed a classic pattern of age-related differences in cognition, preprandial blood glucose level and pulse pressure independently and differentially affected cognitive performance. High-normal blood glucose levels were associated with decreased delayed associative memory, reduced accuracy of working memory processing among women, and slower working memory processing among men. Elevated pulse pressure was associated with slower perceptual-motor processing. Results suggest that blood glucose levels and pulse pressure may be sensitive indicators of cognitive status in healthy adults; however, longitudinal research is needed to determine whether such relatively mild elevations in this select group predict age-related cognitive declines.

Synergistic effects of the MTHFR C677T polymorphism and hypertension on spatial navigation.

Navigation skills deteriorate with age, but the mechanisms of the decline are poorly understood. Part of the decrement may be due to age-related vascular risk factors. The T allele in a C677T variant in methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated plasma homocysteine, which is detrimental to vascular integrity and has been linked to cognitive decline. We inquired if a combination of physiological (hypertension) and genetic (MTHFR 677T) vascular risks has a synergistic negative impact on cognitive performance in otherwise healthy adults. We tested 160 participants (18-80 years old) on a virtual water maze. Advanced age, female sex, and hypertension were associated with poorer performance. However, hypertensive carriers of the T allele performed significantly worse than the rest of the participants at all ages. These findings indicate that hypertension combined with a genetic vascular risk factor may significantly increase risk for cognitive impairment.

Brain-derived neurotrophic factor Val66Met and blood glucose: a synergistic effect on memory.

Age-related declines in episodic memory performance are frequently reported, but their mechanisms remain poorly understood. Although several genetic variants and vascular risk factors have been linked to mnemonic performance in general and age differences therein, it is unknown whether and how they modify age-related memory declines. To address that question, we investigated the effect of Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism that affects secretion of BDNF, and fasting blood glucose level (a vascular risk factor) on episodic memory in a sample of healthy volunteers (age 19-77). We found that advanced age and high-normal blood glucose levels were associated with reduced recognition memory for name-face associations and poorer prose recall. However, elevated blood glucose predicted lower memory scores only in carriers of the BDNF 66Met allele. The effect on associative memory was stronger than on free recall. These findings indicate that even low-level vascular risk can produce negative cognitive effects in genetically susceptible individuals. Alleviation of treatable vascular risks in such persons may have a positive effect on age-related cognitive declines.

Effect of pretreatment with statins on ischemic stroke outcomes.

BACKGROUND AND PURPOSE: Statins reduce the risk of stroke in at-risk populations and may improve outcomes in patients taking statins before an ischemic stroke (IS). Our objectives were to examine the effects of pretreatment with statins on poor outcome in IS patients. METHODS: Over a 6-month period all acute IS admissions were prospectively identified in 15 hospitals participating in a statewide acute stroke registry. Poor stroke outcome was defined as modified Rankin score >/=4 at discharge (ie, moderate-severe disability or death). Multivariable logistic regression models and matched propensity score analyses were used to quantify the effect of statin pretreatment on poor outcome. RESULTS: Of 1360 IS patients, 23% were using statins before their stroke event and 42% had a poor stroke outcome. After multivariable adjustment, pretreatment with statins was associated with lower odds of poor outcome (OR=0.74, 95% CI 0.52, 1.02). A significant interaction (P<0.01) was found between statin use and race. In whites, statins were associated with statistically significantly lower odds of poor outcome (OR=0.61, 95% CI 0.42, 0.86), but in blacks statins were associated with a nonstatistically significant increase in poor outcome (OR=1.82, 95% CI 0.98, 3.39). Matched propensity score analyses were consistent with the multivariable model results. CONCLUSIONS: Pretreatment with statins was associated with better stroke outcomes in whites, but we found no evidence of a beneficial effect of statins in blacks. These findings indicate the need for further studies, including randomized trials, to examine differential effects of statins on ischemic stroke outcomes among whites and blacks.