Measure Of Reserve Research Articles

Altered cerebral blood flow and cerebrovascular function after voluntary exercise in adult mice.

The beneficial effects of physical exercise on brain health are well documented, yet how exercise modulates cerebrovascular function is not well understood. This study used continuous arterial spin labeling magnetic resonance imaging with a hypercapnic challenge to examine changes in cerebral blood flow and vascular function after voluntary exercise in healthy, adult mice. Thirty exercise mice and twenty-one control mice were imaged prior to the start of the exercise regime (at 12 weeks of age) and after 4 weeks of voluntary exercise. After the second in vivo imaging session, we performed high-resolution ex vivo anatomical brain imaging to correlate the structural brain changes with functional measures of flow and vascular reserve. We found that exercise resulted in increases in the normocapnic and hypercapnic blood flow in the hippocampus. Moreover, the change in normocapnic blood flow between pre-exercise and post-exercise was positively correlated to the hippocampal structure volume following exercise. There was no overall effect of voluntary exercise on blood flow in the motor cortex. Surprisingly, the hypercapnic hippocampal blood flow when measured prior to the start of exercise was predictive of subsequent exercise activity. Moreover, exercise was found to normalize this pre-existing difference in hypercapnic blood flow between mice.

Quantitative myocardial blush grade reserve during pharmacologic hyperaemia: a way to perform a real wireless fractional flow reserve measurement in patients with coronary artery disease and intermediate coronary lesions.

We investigated the relation between myocardial blush grade reserve (MBGreserve) and fractional flow reserve (FFR) measures. FFR is a marker of inducible myocardial ischaemia, which could guide percutaneous coronary intervention (PCI) and stent placement. However, it requires a pressure wire and is associated with additional costs and potential hazards. The aim of our study was to investigate the ability of MBG for the evaluation of functional significance in intermediate coronary lesions during pharmacologic hyperaemia. Fifty-six patients who underwent routine cardiac catheterisation for known or suspected coronary artery disease (CAD) and clinically indicated FFR measures in at least one coronary vessel were analysed. MBGreserve was assessed at baseline and during pharmacologic hyperaemia. Video densitometric parameters were then calculated by the ratio of maximal density (Gmax) and the time to reach maximum density (Tmax). Gmax/Tmax during hyperaemia divided by Gmax/Tmax at baseline provided the MBGreserve. A significant association was observed between MBGreserve and FFR. A cut-off value of MBGreserve=2.1 demonstrated sensitivity of 80% and specificity of 96% for the prediction of abnormal FFR of ≤0.8. MBGreserve increased in coronary territories that underwent PCI, reaching similarly high values compared to those observed in FFR-negative lesions. Quantitative MBGreserve is closely related to FFR measures and may obviate the need for pressure wire measurements in the interests of patient safety, time and costs.

Heart Rate Decreases During Head-Out-of-Water Immersion and With Lower-Body Weight Support: A Measure of Vagal Reserve?

Heart Rate Decreases During Head-Out-of-Water Immersion and With Lower-Body Weight Support: A Measure of Vagal Reserve?

Myocardial contractile reserve predicts left ventricular reverse remodeling and cardiac events in dilated cardiomyopathy

BackgroundCatecholamine sensitivity estimated using a dobutamine stress test (DST) is recognized as a measure of the beta-adrenergic myocardial contractile reserve, which is involved with left ventricular reverse remodeling (LV-RR). We investigated whether the prognostic ability of the DST for LV-RR could predict cardiac events. MethodsThere was a total of 192 enrolled patients with dilated cardiomyopathy (DCM). DCM was defined as a LV ejection fraction (LV-EF) ≤45% and LV end-diastolic dimension (LVDd) ≥55mm. One hundred patients were subjected to micromanometer-based measurement of the maximal first derivative of LV pressure (LVdP/dtmax), an index of LV contractility, at baseline and following the infusion of dobutamine (10μg/kg/min) via a pigtail catheter. Percentage changes in LVdP/dtmax from the baseline to peak values under dobutamine stress (ΔLVdP/dtmax) were also calculated. After excluding 17 patients who received cardiac resynchronization therapy within 3 months of undergoing DST (n=15) and who did not receive follow-up echocardiography (n=2), 83 patients were enrolled (52.5±12.3 years). ResultsDuring the follow-up period (4.7±2.6 years), LV-RR was recognized in 49 of 83 patients (59.0%). A multivariate logistic regression analysis revealed that ΔLVdP/dtmax (hazard ratio: 1.024, p=0.007) and the symptom duration (hazard ratio: 0.977, p=0.003) were independent predictors of LV-RR. A receiver operating characteristic curve analysis revealed a ΔLVdP/dtmax cut-off value of 75.1% for LV-RR and a significantly lower cardiac event rate in the ΔLVdP/dtmax≥75.1% group (p=0.045). ConclusionsΔLVdP/dtmax estimated using DST was a useful predictor of LV-RR and cardiac events in patients with DCM.

Abstract P172: Exercise Hemodynamics of Heart Failure with Preserved Ejection Fraction: a Meta-Analysis

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with increased morbidity and mortality, and recalcitrant to available medical therapies. A major challenge in development of effective therapies for HFpEF is the heterogeneity in the underlying pathophysiological mechanisms, with numerous studies demonstrating conflicting findings. We conducted a meta-analysis to characterize the underlying exercise hemodynamic abnormalities that define HFpEF. Methods: 15 studies comparing hemodynamic parameters between HFpEF and normal or hypertensive controls were pooled. Standardized mean differences (SMD) in the exercise reserve (peak exercise - resting) measures of hemodynamic parameters between the HFpEF and control group were pooled using a random-effects model meta-analysis. Results: The meta-analysis included 627 HFpEF patients (age range: 57 - 74 years, 66% women, 80% with hypertension) and 365 normal controls (age range: 47 - 72 years, 58% women, 50% with hypertension). In pooled analysis, HFpEF patients had significantly lower peak oxygen uptake [SMD (95% CI): -1.8 (-1.9 to -1.6)]. HFpEF patients had significantly lower cardiac index (CI)[SMD (95% CI): -2.1 (-2.3 to -1.9)], heart rate (HR) [SMD (95% CI): -1.3 (-1.5 to -1.1)], stroke volume index (SVI)[SMD (95% CI): -0.78 (-0.94 to -0.61)] and arterio-venous oxygen difference (a-VO 2 Diff) reserve [SMD (95% CI): -0.68 (-0.91 to -0.44)]. HFpEF patients also had significantly greater increase in left ventricular filling (LV) pressure [SMD (95% CI): 2.03 (1.76 to 2.3)] and systemic vascular resistance (SVR) [SMD (95% CI): 1.20(0.94 to 1.45)] despite no change in LV end-diastolic volume reserve between groups. Conclusion: HFpEF patients have significantly reduced exercise capacity secondary to impaired central (decreased CI, SVI, HR reserve, and increased LV filling pressures without a change in LV diastolic reserve) and peripheral abnormalities (increased SVR and decreased a-VO 2 Diff).

Aging ovary and the role for advanced glycation end products

The hypothalamic gonadotropin-releasing hormone pulse generator, the pituitary gonadotropes, the ovaries, and the uterus play a crucial role in female fertility. A decline in reproductive performance represents a complex interplay of actions at all levels of the hypothalamic-pituitary-ovarian axis. Recently, in the field of female reproductive aging attention is drawn to the carbonyl stress theory. Advanced glycation end products (AGEs) contribute directly to protein damage, induce a chain of oxidative stress (OS) reactions, and increase inflammatory reactions. Here, we highlight some of the mechanisms underlying glycation damage in the ovary. Searches of electronic databases were performed. Articles relevant to possible role of OS, AGEs, and receptor for AGE (RAGE) in aging ovary were summarized in this interpretive literature review. Follicular microenvironment undergoes an increase in OS with aging. Data support the role of OS in ovulatory dysfunction because AGEs are well-recognized mediators of increased OS. RAGE and AGE-modified proteins with activated nuclear factor-kappa B are expressed in human ovarian tissue. It was suggested that accumulation of AGEs products at the level of the ovarian follicle might trigger early ovarian aging or could be responsible for reduced glucose uptake by granulosa cells, potentially altering follicular growth. Moreover, impaired methylglyoxal detoxification causing relevant damage to the ovarian proteome might be one of the mechanisms underlying reproductive aging. Further investigation of the role for the AGE-RAGE axis in the ovarian follicular environment is needed, and results could relate to assisted reproduction technology outcomes and new measures of ovarian reserve.

The effects of lifelong cognitive lifestyle on executive function in older people with Parkinson's disease.

Active lifelong cognitive lifestyles increase cognitive reserve and have beneficial effects on global cognition, cognitive decline and dementia risk in Parkinson's disease (PD). Executive function is particularly impaired even in early PD, and this impacts on quality of life. The effects of lifelong cognitive lifestyle on executive function in PD have not been studied previously. This study examined the association between lifelong cognitive lifestyle, as a proxy measure of cognitive reserve, and executive function in people with PD. Sixty-nine people diagnosed with early PD without dementia were recruited as part of the Bilingualism as a protective factor in Age-related Neurodegenerative Conditions study. Participants completed a battery of tests of executive function. The Lifetime of Experiences Questionnaire was completed as a comprehensive assessment of lifelong cognitive lifestyle. Non-parametric correlations compared clinical measures with executive function scores. Cross-sectional analyses of covariance were performed comparing the performance of low and high cognitive reserve groups on executive function tests. Correlational analyses showed that better executive function scores were associated with younger age, higher levodopa dose and higher Lifetime of Experiences Questionnaire scores. Higher cognitive reserve was associated with better motor function, but high and low cognitive reserve groups did not differ in executive function. Cognitive reserve, although associated with global cognition, does not appear to be associated with executive function. This differential effect may reflect the specific cognitive profile of PD. The long-term effects of cognitive reserve on executive function in PD require further exploration. Copyright © 2017 John Wiley & Sons, Ltd.

Preoperative Evaluation of the Elderly Surgical Patient

The following is a detailed approach to the preoperative evaluation of the elderly surgical patient. A focus is placed on physiologic changes in the elderly that predispose them to complications and a systems-based approach to appropriate perioperative evaluation. Specifically, recommendations on the workup of cardiovascular, pulmonary, and renal systems are discussed. We also introduce the concept of frailty as a measure of an elderly patient's overall physiologic reserve. Finally, a diagnostic approach to common elderly-specific disease processes such as decreased functional status, malnutrition, and delirium is outlined. Throughout, an emphasis is placed on how to carefully assess this specific patient population and optimize preoperative functional status to improve surgical outcomes in the elderly. This review has 1 figure, 4 tables, and 62 references.

Abstract WP437: Sleep Apnea and Cerebral Blood Flow: the Role of Autoregulation

Objective: Obstructive sleep apnea (OSA) is a stroke risk factor and is increasingly recognized as a risk factor for cognitive impairment. Altered cerebral autoregulation may play a role in these relationships. We measured the association between OSA and two forms of cerebral autoregulation: (1) dynamic cerebral autoregulation (DCA), which plays a homeostatic role; and (2) vasomotor reactivity (VMR), which is a measure of cerebrovascular reserve. We hypothesized that both VMR and DCA would be impaired in subjects with OSA. Methods: We recruited subjects with untreated OSA. VMR and DCA were measured with continuous transcranial Doppler (TCD) of the middle cerebral arteries (MCA). DCA was measured with phase shift analysis where lower degrees of phase shift indicate greater impairment; values <24 degrees are abnormal. VMR was measured as % change in MCA velocity in response to 5% CO2 inhalation; values <2% change are abnormal. We assessed the relationship between apnea-hypopnea index (AHI) and autoregulation using bivariate correlations (Pearson coefficient). We also assessed the association between moderate to severe OSA (AHI≥15) and abnormal autoregulation (Fisher’s exact test). Results: Twelve subjects were enrolled; 11 had TCD data. Mean age was 53 (SD 11) and the majority had moderate to severe OSA (median AHI 27, IQR 16-37). Mean VMR (% change in MCA velocity) was 3.1 (SD 0.7); mean phase shift was 34 degrees (SD 15). There was a moderate association between AHI and phase shift (r=-0.40); the correlation with VMR was weaker (r=-0.25). The proportion of subjects with abnormal DCA was greater among those with moderate-severe OSA compared to those with mild OSA (66.7% vs. 0%, p=0.2). No enrolled subjects had abnormal VMR. Conclusion: Moderate to severe OSA is associated with abnormal dynamic cerebral autoregulation and normal vasomotor reactivity. The mechanism underlying this dissociation may involve OSA-mediated inflammation and endothelial dysfunction. Further study may clarify how this dissociation relates to increased risk of cerebral ischemia among patients with OSA.

Validation of a Dynamic Measure of Current Cognitive Reserve in a Longitudinally Assessed Sample of Healthy Older Adults: The Tasmanian Healthy Brain Project.

Cognitive reserve (CR) is a theoretical construct describing the underlying cognitive capacity of an individual that confers differential levels of resistance to, and recovery from, brain injuries of various types. To date, estimates of an individual's level of CR have been based on single proxy measures that are retrospective and static in nature. To develop a measure of dynamic change in CR across a lifetime, we previously identified a latent factor, derived from an exploratory factor analysis of a large sample of healthy older adults, as current CR (cCR). In the present study, we examined the longitudinal results of a sample of 272 older adults enrolled in the Tasmanian Healthy Brain Project. Using results from 12-month and 24-month reassessments, we examined the longitudinal validity of the cCR factor using confirmatory factor analyses. The results of these analyses indicate that the cCR factor structure is longitudinally stable. These results, in conjunction with recent results from our group demonstrating dynamic increases in cCR over time in older adults undertaking further education, lend weight to this cCR measure being a valid estimate of dynamic change in CR over time.

Single Nucleotide Polymorphisms (SNPs) Associated with Cognitive Impairment in Patients Treated with Hematopoietic Cell Transplantation (HCT): A Longitudinal Study

Purpose: Pre-HCT, HCT-related, and post-HCT therapeutic exposures place HCT recipients at risk for cognitive impairment, albeit with significant inter-individual variability in the risk, suggesting a role for genetic susceptibility. We hypothesized that the following mechanisms could impact cognitive functioning: impaired capacity to effectively pump genotoxic agents out of the cell, maintain telomere homeostasis, repair damaged DNA, in addition to reduced neural repair capacity and neurotransmitter activity.Methods: We established a prospective longitudinal cohort of patients with hematologic malignancies receiving HCT at a single institution. Comprehensive assessment of 8 domains of cognitive functioning (executive function; processing speed; working memory; auditory memory; visual memory; verbal speed; verbal fluency; and fine motor dexterity) using a battery of 14 standardized tests was performed at predefined time-points: pre-HCT, 6m, 1y, 2y, and 3y post-HCT. Intelligence quotient (IQ) was assessed pre-HCT as a measure of cognitive reserve. Demographic variables (age, sex, race, education, and income) were self-reported and clinical variables (primary diagnosis, conditioning regimen, type of HCT, risk of relapse at HCT, and remission status post-HCT) were abstracted from patient medical records. Blood or saliva for DNA were obtained pre-HCT. We used the Global Deficit Score (GDS), a widely accepted summary score of cognitive impairment, to represent the overall neuropsychological performance. (Carey et al. 2004; Blackstone et al. 2012) GDS ≥0.50 was used to indicate cognitive impairment - a cutoff previously shown to yield an optimal balance between sensitivity and specificity in classifying impairment. Generalized estimating equation models were fitted to test the association of each individual SNP with GDS, adjusting for time of neurocognitive testing, age at HCT, sex, race, pre-HCT IQ, and HCT type. Genetic association analysis involved 985 carefully-curated SNPs in 68 candidate genes. The number of independent tests was 326 (excluding SNPs in Linkage Disequilibrium) yielding an overall p-value threshold of 1.5 x 10-4using Bonferroni correction for multiple testing.Results: The study cohort included 277 patients (58.5% males; 68.6% non-Hispanic whites; median age at HCT: 51.6y, range: 19-73); 148 (53.4%) received an autologous HCT and 129 (46.6%) allogeneic HCT (41.9% matched related and 58.1% matched unrelated). Most common primary diagnoses were non-Hodgkin lymphoma (42.6%) and multiple myeloma (36.5%) in autologous HCT recipients, and acute myeloid leukemia (54.3%) in allogeneic HCT recipients. Factors significantly associated with higher risk of cognitive impairment included: age at HCT ≥50 years (odds ratio (OR)=2.85, 95% CI, 1.3-6.1, p=0.007), male gender (OR=2.62, 95%CI, 1.3-5.1, p=0.005), race other than non-Hispanic white (OR=2.83, 95%CI, 1.4-5.9, p=0.005), and pre-HCT IQ ≤ median (OR=6.58, 95%CI, 3.2-13.3, p<0.0001). Four SNPs were significantly associated with cognitive impairment: rs11837182(OR=4.2, 95%CI, 2.1-8.5, p=4.2 x 10-5) on SLCO1A2 (blood brain barrier);rs330792 (OR=9.2, 95%CI, 4.0-21.1, p=1.2 x 10-7) on MSH6 (DNA repair), rs4725015 (OR=10.7, 95%CI, 4.9-23.5, p=3.6 x 10-9) on RPA3 (DNA repair), and rs16900343 (OR=4.2, 95%CI, 2.0-8.9, p=1.3 x 10-4) on XRCC4 (DNA repair). We also conducted mechanism-specific analyses using the Bonferroni-corrected p-value threshold for each mechanism of cognitive impairment, based on the number of independent SNPs associated with each mechanism. Four additional associations were found to be statistically significant: rs4148734 (OR=6.1, 95%CI, 2.3-16.5, p=3.1 x 10-4) and rs10259849 (OR=6.1, 95%CI, 2.3-16.4, p=3.1 x 10-4) on ABCB1 (blood brain barrier, p-value threshold=1.04 x 10-3), and rs718742 (OR=3.7, 95%CI,1.8-7.7, p=4.3 x 10-4) and rs17152302 (OR=4.0, 95%CI, 1.8-8.6, p=4.1 x 10-4) on PINX1 (telomere homeostasis, p-value threshold=8.7 x 10-4).Conclusion: Our findings provide preliminary evidence for the role of blood brain barrier transporters, telomere homeostasis and DNA repair in the pathogenesis of cognitive impairment after HCT. These findings may help identify HCT recipients at highest risk for cognitive impairment, thus facilitating targeted interventions. DisclosuresNo relevant conflicts of interest to declare.

Impact of tamoxifen therapy on fertility in breast cancer survivors

To determine whether tamoxifen use is associated with decreased ovarian reserve and decreased likelihood of having a child after a breast cancer diagnosis, using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women Study. Population-based cohort study. Not applicable. Three hundred ninety-seven female breast cancer survivors aged 22-45years whose cancer was diagnosed between ages 20 and 35years and who were at least 2years after diagnosis; 108 survivors also participated in a clinic visit. None. Time to first child after cancer diagnosis, clinical measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC]) after cancer. Women who had ever used tamoxifen were substantially less likely to have a child after the breast cancer diagnosis (hazard ratio [HR] 0.29; 95% confidence interval [CI], 0.16, 0.54) than women who had never used tamoxifen. After adjusting for age at diagnosis, exposure to an alkylating agent, and race, the HR was 0.25 (95% CI, 0.14, 0.47). However, after adjusting for potential confounders, women who had used tamoxifen had an estimated geometric mean AMH level 2.47 times higher (95% CI, 1.08, 5.65) than women who had never taken tamoxifen. Antral follicle count was also higher in the tamoxifen group compared with the tamoxifen nonusers when adjusted for the same variables (risk ratio 1.21; 95% CI, 0.84, 1.73). Breast cancer survivors who had used tamoxifen were less likely to have a child after breast cancer diagnosis compared with survivors who never used tamoxifen. However, tamoxifen users did not have decreased ovarian reserve compared with the tamoxifen nonusers.

Presynaptic proteins complexin-I and complexin-II differentially influence cognitive function in early and late stages of Alzheimer's disease.

Progressive accumulation of Alzheimer's disease-related pathology is associated with cognitive dysfunction. Differences in cognitive reserve may contribute to individual differences in cognitive function in the presence of comparable neuropathology. The protective effects of cognitive reserve could contribute differentially in early versus late stages of the disease. We investigated presynaptic proteins as measures of brain reserve (a subset of total cognitive reserve), and used Braak staging to estimate the progression of Alzheimer's disease. Antemortem evaluations of cognitive function, postmortem assessments of pathologic indices, and presynaptic protein analyses, including the complexins I and II as respective measures of inhibitory and excitatory terminal function, were assayed in multiple key brain regions in 418 deceased participants from a community study. After covarying for demographic variables, pathologic indices, and overall synapse density, lower brain complexin-I and -II levels contributed to cognitive dysfunction (P<0.01). Each complexin appeared to be dysregulated at a different Braak stage. Inhibitory complexin-I explained 14.4% of the variance in global cognition in Braak 0-II, while excitatory complexin-II explained 7.3% of the variance in Braak V-VI. Unlike other presynaptic proteins, complexins did not colocalize with pathologic tau within neuritic plaques, suggesting that these functional components of the synaptic machinery are cleared early from dystrophic neurites. Moreover, complexin levels showed distinct patterns of change related to memory challenges in a rat model, supporting the functional specificity of these proteins. The present results suggest that disruption of inhibitory synaptic terminals may trigger early cognitive impairment, while excitatory terminal disruption may contribute relatively more to later cognitive impairment.

Stress and Cognitive Reserve as independent factors of neuropsychological performance in healthy elderly.

Exposure to high levels of cortisol and self-reported stress, as well as cognitive reserve, have been linked to Alzheimer's disease pathology. However, there are no studies on the interaction of these variables. The present study aims to assess the associations of measures of cortisol, self-reported stress, and cognitive reserve with neuropsychological performance in healthy elderly people; besides, to test the interactions between these variables. Cross-sectional analyzes were conducted using data on stress, cognitive reserve and clinical conditions in 145 healthy elderly adults. A neuropsychological battery was used to assess executive functions, verbal memory and processing speed. Measurement of salivary cortisol at the circadian nadir was taken. A negative association between different stress measures and performance on tasks of memory, executive functions and processing speed was observed. Elderly people with higher cognitive reserve showed superior performance on all neuropsychological measures. No significant interaction between stress and cognitive reserve to neuropsychological performance was observed. These results indicate that older adults with high levels of stress and reduced cognitive reserve may be more susceptible to cognitive impairment.

Frailty, Length of Stay, and Mortality in Kidney Transplant Recipients: A National Registry and Prospective Cohort Study.

To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and mortality. Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality. We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOS: negative binomial regression; LOS ≥2 weeks: logistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis). Frailty was independently associated with longer LOS [relative risk = 1.15, 95% confidence interval (CI): 1.03-1.29; P = 0.01] and LOS ≥2 weeks (odds ratio = 1.57, 95% CI: 1.06-2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI: 1.30-1.86; P < 0.001; frail hazard rate = 0.97, 95% CI: 0.79-1.19, P = 0.80; P for interaction = 0.001). Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS.

Cognitive reserve moderates long-term cognitive and functional outcome in cerebral small vessel disease

BackgroundCerebral small vessel disease (SVD) is characterised by progressive white matter hyperintensities (WMH), cognitive decline and loss of functional independence. The correspondence between neuroimaging findings and the severity of clinical...

A 5-item frailty index based on NSQIP data correlates with outcomes following paraesophageal hernia repair.

Frailty is a measure of physiologic reserve associated with increased vulnerability to adverse outcomes following surgery in older adults. The 'accumulating deficits' model of frailty has been applied to the NSQIP database, and an 11-item modified frailty index (mFI) has been validated. We developed a condensed 5-item frailty index and used this to assess the relationship between frailty and outcomes in patients undergoing paraesophageal hernia (PEH) repair. The NSQIP database was queried for ICD-9 and CPT codes associated with PEH repair. Subjects ≥60years who underwent PEH repair between 2011 and 2013 were included. Five of the 11 mFI items present in the NSQIP data on the most consistent basis were selected for the condensed index. Univariate and multivariate logistic regressions were used to determine the validity of the 5-item mFI as a predictor of postoperative mortality, complications, readmission, and non-routine discharge. A total of 3711 patients had data for all variables in the 5-item index, while 885 patients had complete data to calculate the 11-item mFI. After controlling for competing risk factors, including age, ASA score, wound classification, surgical approach, and procedure timing (emergent vs non-emergent), we found the 5-item mFI remained predictive of 30-day mortality and patients being discharged to a location other than home (p<0.05). A weighted Kappa was calculated to assess agreement between the 5-item and 11-item mFI and was found to be 0.8709 (p<0.001). Frailty, as assessed by the 5-item mFI, is a reasonable alternative to the 11-item mFI in patients undergoing PEH repair. Utilization of the 5-item mFI allows for a significantly increased sample size compared to the 11-item mFI. Further study is necessary to determine whether the condensed 5-item mFI is a valid measure to assess frailty for other types of surgery.

Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients with Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting).

No randomized study has investigated the value of optical coherence tomography (OCT) in optimizing the results of percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndromes. We conducted a multicenter, randomized study involving 240 patients with non-ST-segment elevation acute coronary syndromes to compare OCT-guided PCI (use of OCT pre- and post-PCI; OCT-guided group) to fluoroscopy-guided PCI (angiography-guided group). The primary end point was the functional result of PCI assessed by the measure of post PCI fractional flow reserve. Secondary end points included procedural complications and type 4a periprocedural myocardial infarction. Safety was assessed by the rate of acute kidney injury. OCT use led to a change in procedural strategy in 50% of the patients in the OCT-guided group. The primary end point was improved in the OCT-guided group, with a significantly higher fractional flow reserve value (0.94±0.04 versus 0.92±0.05, P=0.005) compared with the angiography-guided group. There was no significant difference in the rate of type 4a myocardial infarction (33% in the OCT-group versus 40% in the angiography-guided group, P=0.28). The rates of procedural complications (5.8%) and acute kidney injury (1.6%) were identical in each group despite longer procedure time and use of more contrast medium in the OCT-guided group. Post-PCI OCT revealed stent underexpansion in 42% of patients, stent malapposition in 32%, incomplete lesion coverage in 20%, and edge dissection in 37.5%. This led to the more frequent use of poststent overdilation in the OCT-guided group versus the angiography-guided group (43% versus 12.5%, P<0.0001) with lower residual stenosis (7.0±4.3% versus 8.7±6.3%, P=0.01). In patients with non-ST-segment elevation acute coronary syndromes, OCT-guided PCI is associated with higher postprocedure fractional flow reserve than PCI guided by angiography alone. OCT did not increase periprocedural complications, type 4a myocardial infarction, or acute kidney injury. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01743274.

Diminished but not declining: longitudinal androgen production and follicular measures of ovarian reserve in cancer survivors compared to healthy controls

Diminished but not declining: longitudinal androgen production and follicular measures of ovarian reserve in cancer survivors compared to healthy controls

Biomarkers of ovarian reserve as predictors of infertility

Diminished ovarian reserve (DOR), as determined by low antimüllerian hormone (AMH) and high, early follicular phase follicle stimulating hormone (FSH) levels in serum, have been associated with earlier menopause and low egg yield in response to ovarian stimulation. Some studies suggest women with DOR have a lower probability of pregnancy after assisted reproductive technology. Thus, it is presumed that DOR is a cause of infertility. We sought to determine if measures of ovarian reserve would be significantly associated with infertility.