Factors associated with vision loss in Black or Hispanic patients 1 year after standalone or combined Ahmed glaucoma valve surgery.

PURPOSE: To determine factors associated with vision loss 1 year after Ahmed glaucoma valve (AGV) surgery in Black or Hispanic patients, who bear disproportionate glaucoma burdens yet have been underrepresented in pivotal trials. METHODS: This retrospective study included Black or Hispanic patients who received AGVs standalone or combined with phacoemulsification and/or cyclodestructive lasers. Univariate and multivariate generalized estimating equations evaluated the effects of baseline, surgical, and postoperative factors on vision loss of two Snellen lines or more at the 1-year follow-up visit. The primary term was the hypertensive phase (HP), which signified an intraocular pressure (IOP) reading > 21 mmHg within the first 3 postoperative months after reduction below 22 in the first week, without other tube malfunction. RESULTS: Of 241 eyes from 186 patients, vision loss of ≥ 2 lines at the 1-year follow-up visit occurred in 21.6% (N = 52). Vision loss of ≥ 2 lines occurred in 52.5% of eyes at week 1, 36.9% of eyes at month 1, and 27.0% of eyes at month 3. Between 6 months and 1 year, vision loss frequencies stabilized. In the multivariate model, HP (OR = 4.71 (2.14, 10.38)), total quadrants with split fixation (1.47 (1.20, 1.81)), follow-up non-glaucomatous eye pathology (2.89 (1.44, 5.80)), and concurrent cataract surgery (0.42 (0.22, 0.82)) each met significance (p < 0.05). CONCLUSION: Post-AGV vision loss in the early follow-up period among Black or Hispanic patients was often transient. Hypertensive phase and split fixation each increased the odds of vision loss at 1 year, while concurrent cataract surgery decreased the odds.

Characterization of microvascular disease in pediatric sickle cell disease using nailfold capillaroscopy.

Sickle cell disease (SCD) is a disorder with repetitive vaso-occlusive crises resulting in microvascular obstruction and tissue ischemia that may lead to multi-organ ischemia and dysfunction. Nailfold videocapillaroscopy (NFC) is an imaging technique utilized in clinical rheumatology to visualize capillaries located near the fingertip. To characterize NFC abnormalities in the setting of pediatric SCD, we performed NFC using a video capillaroscope on 8 digits in 44 stable SCD patients and 65 age matched healthy controls. Mean capillary number was lower (6.4 ± 1.3 vs 7.5 ± 1.8, p = 0.001) in the SCD group compared to controls. The percentage of dilated capillaries was similar (7.1 ± 8.3 vs. 5.9 ± 8.2, p = 0.4). The large majority of capillaries visualized in the SCD and control groups were normal capillary types per the EULAR definition, with a similar percentage of normal, nonspecific capillary morphologies and abnormal types. Regarding normal capillary sub-types, the SCD group and controls exhibited similar percentages of stereotype hairpin shapes, and tortuous or once or twice crossing type capillaries. On multivariate analyses, mean capillary number was independently associated with SCD after adjusting for age, body mass index, systolic blood pressure and gender. In conclusion, pediatric SCD is associated with lower capillary number but similar percentage of dilated capillaries and morphology on NFC. In our SCD cohort, capillary number was unrelated to our available markers of disease severity, including history of sickle crises, previous hospitalization for crises or Hemoglobin F levels.

Exploring chronic and transient tumor hypoxia for predicting the efficacy of hypoxia-activated pro-drugs.

Hypoxia, a low level of oxygen in the tissue, arises due to an imbalance between the vascular oxygen supply and oxygen demand by the surrounding cells. Typically, hypoxia is viewed as a negative marker of patients' survival, because of its implication in the development of aggressive tumors and tumor resistance. Several drugs that specifically target the hypoxic cells have been developed, providing an opportunity for exploiting hypoxia to improve cancer treatment. Here, we consider combinations of hypoxia-activated pro-drugs (HAPs) and two compounds that transiently increase intratumoral hypoxia: a vasodilator and a metabolic sensitizer. To effectively design treatment protocols with multiple compounds we used mathematical micro-pharmacology modeling and determined treatment schedules that take advantage of heterogeneous and dynamically changing oxygenation in tumor tissue. Our model was based on data from murine pancreatic cancers treated with evofosfamide (as a HAP) and either hydralazine (as a vasodilator), or pyruvate (as a metabolic sensitizer). Subsequently, this model was used to identify optimal schedules for different treatment combinations. Our simulations showed that schedules of HAPs with the vasodilator had a bimodal distribution, while HAPs with the sensitizer showed an elongated plateau. All schedules were more successful than HAP monotherapy. The three-compound combination had three local optima, depending on the HAPs clearance from the tissue interstitium, each two-fold more effective than baseline HAP treatment. Our study indicates that the three-compound therapy administered in the defined order will improve cancer response and that designing complex schedules could benefit from the use of mathematical modeling.

A cross-sectional study to test equivalence of low- versus intermediate-flip angle dynamic susceptibility contrast MRI measures of relative cerebral blood volume in patients with high-grade gliomas at 1.5 Tesla field strength.

Introduction: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients. Methods: This was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC). Results: Twenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV. Conclusion: Our study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload.

Outcomes of Sutureless Ahmed Glaucoma Valve Surgery: A Retrospective Study.

INTRODUCTION: This study compared the safety and efficacy of sutureless Ahmed glaucoma valve surgery (AGV standalone) to sutureless AGV plus cataract surgery (AGV-CEIOL) in Black or Hispanic patients. METHODS: Records from Black or non-white Hispanic patients who received either AGV standalone or AGV-CEIOL from 2014 to 2019 at a Bronx, New York practice were reviewed. All surgeries were performed using a sutureless technique with Tisseel fibrin glue. Primary outcomes included failure (defined as intraocular pressure (IOP) > 21 mmHg, ≤ 5 mmHg, or reduced by < 20% after the first 3 months; loss of light perception; or reoperation for glaucoma), hypertensive phase, IOP changes, and medication changes. Secondary outcomes included postoperative complications and interventions. RESULTS: A total of 203 eyes that received AGV standalone (n = 78) or AGV-CEIOL (n = 125) were analyzed. Mean follow-up duration was 42.2 ± 17.5 months, with similar cohort-specific intervals (P = 0.68). Failure among AGV-CEIOLs (44.8%, n = 56) and AGV standalones (47.4%, n = 37) occurred at similar frequencies; log-rank testing indicated comparable 5-year survival (P = 0.56). Mean IOP among AGV-CEIOLs (15.8 ± 12.1 mmHg) was greater than standalones (8.6 ± 5.1 mmHg) at post-op day 1 (P < 0.001). The AGV-CEIOL group had a 60% lower odds of experiencing a hypertensive phase after adjustment for baseline group differences (P = 0.01). Five-year IOP reduction was similar between groups in the multivariable model (P = 0.45). There were no significant differences in medications (P > 0.05 at all time points) or in total complications (P = 0.28). More standalones required reoperation (39.7%, n = 31) compared to AGV-CEIOLs (21.6%, n = 24; P = 0.007). CONCLUSIONS: Sutureless AGV-CEIOL was noninferior to sutureless AGV standalone when performed in Black or non-white Hispanic patients. The combined group experienced the hypertensive phase less frequently despite higher day 1 IOP.

Maternal reproductive history and premenopausal risk of hypertension and cardiovascular disease: a Danish cohort study.

OBJECTIVES: The metabolic changes of pregnancy resemble a cardiovascular risk profile and may persist postpartum, with body mass index (BMI) as a potential modifier. We examined the association between the number of live-birth pregnancies and maternal premenopausal risks of hypertension and cardiovascular disease (CVD), accounting for pre-pregnancy BMI as well as abortions and stillbirths. DESIGN: A prospective cohort study. SETTING: Mothers from the Danish National Birth Cohort (1996 to 2002). For each of these women, registry data on all pregnancies from 1973 to 2011 were obtained, as were self-reported pre-pregnancy weight and height. PARTICIPANTS: A total of 44 552 first-time mothers in the Danish National Birth Cohort. OUTCOME MEASURES: Risks of hypertension and CVD during and between live-birth pregnancies separately and combined as live-birth cycles. RESULTS: After adjustment for abortions, stillbirths, pre-pregnancy BMI and other covariates, a higher risk of hypertension was observed in the first (HR 1.53, 95% CI: 1.37 to 1.72) and fourth and subsequent live-birth cycles (HR 1.72, 95% CI: 1.15 to 2.58), compared with the second. However, as number of live-birth pregnancies increased, risk of hypertension decreased during live-birth pregnancies and increased between live-birth pregnancies (tests for trend, p<0.01). For CVD, we found an overall J-shaped but non-significant association with number of live-birth pregnancies. No interaction with pre-pregnancy BMI (<25 versus ≥25 kg/m2) was observed. CONCLUSIONS: Premenopausal women had the highest risk of hypertension and CVD during their first live-birth pregnancy and after their fourth live-birth pregnancy. All risks were independent of BMI before the first live-birth pregnancy and of number of abortions and stillbirths.

Predictors of the effect of bariatric surgery on knee osteoarthritis pain.

INTRODUCTION: Bariatric surgery reduces obesity and knee osteoarthritis (OA) pain, but some patients improve more than others. We aimed to identify characteristics that predict this knee pain improvement. METHODS: We reviewed NYU Langone Health bariatrics records (2002-2015) and called eligible patients reporting pre-operative knee pain. Patients were asked to rate their pain on a 10-point scale at three time points: before surgery, one year post-surgery, and time of survey administration. Subjects were asked about pre-operative knee injuries and surgeries, presence of OA in other joints, and OA family history. Data were analyzed using paired t-tests and ANOVA. RESULTS: Of 125 eligible patients reporting knee pain, we analyzed the 120 patients who had laparoscopic gastric band (LAGB) surgery. The cohort was 78.3% female, with an average age at surgery of 49.7 ± 10.2 years. There was no correlation between pre-operative body mass index (BMI) and knee pain reduction at one year post-LAGB, but the subgroup with the most BMI improvement reported the most knee improvement (p = 0.043). We found significantly better pain reduction after one year in younger patients (p = 0.009). Those with prior knee injuries improved less than those who were injury-free (p = 0.044), but a history of prior knee surgery was not similarly significant. Patients with multifocal OA improved less (p = 0.001). CONCLUSION: Younger knee OA patients and those without prior knee injury or other OA involvement, experience more knee pain relief from LAGB weight loss surgery. LAGB may be a viable treatment option for knee OA pain, irrespective of the degree of obesity.

Cyclin A2 promotes DNA repair in the brain during both development and aging.

Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.