on behalf of the PENUT Trial Consortium* Objective To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo. Study designWe performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. ResultsThe prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values at days 0, 7, 9, and 14). At 22-26 months of cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m 2 , 35.8% had urine albumin/creatinine ratio >30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (P < .04). This association remained even after controlling for gestational age, site, and sibship (aOR 0.6; 95% CI 0.39-0.92). We did not find statistically significant differences between treatment groups in eGFR, albumin/creatinine ratio, rates of SBP >95th percentile, or DBP >90th or >95th percentiles at the 2 year follow-up visit.Conclusions ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA.Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA.

Changes in the hemodynamic function of muscle are speculated as a causal mechanism for reduced motor capabilities with aging in Type 2 diabetes mellitus (DM). The focus of this study was to evaluate changes in muscle oxygenation during sustained force production in postmenopausal women with DM compared with controls. Near-infrared spectroscopy was used to monitor deoxyhemoglobin and oxyhemoglobin in the flexor digitorum superficialis. Sensorimotor function and health state covariates were also assessed. Increased deoxyhemoglobin was found during force production, whereas oxyhemoglobin remained constant. Changes were found in the time structure of the hemodynamic data during force production. No between-group differences were found; instead, measures covaried with the health state. Sex-based differences in the manifestation of DM-related sensorimotor dysfunction are likely. These data indicate that basic cardiovascular health measures may be more beneficial to monitoring hyperemic status and muscle function in postmenopausal women with DM, compared with DM diagnosis.

Significance: Deficits in sensorimotor function in persons with type II diabetes mellitus (PwDM) have traditionally been considered a result of peripheral nerve damage. Emerging evidence has suggested that factors outside of nerve damage due to type II diabetes mellitus, such as impaired hemodynamic function, contribute significantly to both sensory and motor deficits in PwDM. Aim: The focus of the current study was to evaluate functional cortical hemodynamic activity during sensory and motor tasks in PwDM. Approach: Functional near-infrared spectroscopy was used to monitor oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) across the cortex during sensory and motor tasks involving the hands. Results: Decline in HbO across sensory and motor regions of interest was found in PwDM with simultaneous deficits in manual motor tasks, providing the first evidence of functional cortical hemodynamic activity deficits relating to motor dysfunction in PwDM. Similar deficits were neither specifically noted in HbR nor during evaluation of sensory function. Health state indices, such as A 1c , blood pressure, body mass index, and cholesterol, were found to clarify group effects. Conclusions: Further work is needed to clarify potential sex-based differences in PwDM during motor tasks as well as the root of reduced cortical HbO indices but unchanged HbR indices in PwDM.

Older adults with Type II Diabetes Mellitus (DM) experience mild cognitive impairment, specifically in the domain of recall/ working memory. No consistent causative structural cortical deficits have been identified in persons with DM (PwDM). Memory deficits may be exacerbated in older adult females, who are at the highest risk of cardiovascular decline due to DM. The focus of the current study was to evaluate functional cortical hemodynamic activity during memory tasks in postmenopausal PwDM. Functional Near Infrared Spectroscopy (fNIRS) was used to monitor oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) during memory-based tasks in a cross-sectional sample of postmenopausal women with DM. Twenty-one community-dwelling DM females (age = 65 ± 6 years) and twenty-one age-and sex-matched healthy controls (age = 66 ± 6 years) were evaluated. Working memory performance (via N-back) was evaluated while study participants donned cortical fNIRS. Health state, metabolic data, and menopausal status data were also collected. Deficits in working memory accuracy were found in the DM group as compared to controls. Differences in HbO responses emerged in the DM group. The DM group exhibited altered PFC activity magnitudes and increased functional cortical activity across ROIs compared to controls. HbO and HbR responses were not associated with worsened health state measures. These data indicate a shift in cortical activity patterns with memory deficits in postmenopausal PwDM. This DM-specific shift of HbO is a novel finding that is unlikely to be detected by fMRI. This underscores the value of using non-MRI-based neuroimaging techniques to evaluate cortical hemodynamic function to detect early mild cognitive impairment.

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