Ramu Sudhagoni

Does Exercise Influence Pediatric Bone? A Systematic Review

BackgroundPeriods of growth are thought to be the best time to increase bone mineral content, bone area, and areal bone mineral density (aBMD) through increased loading owing to high rates of bone modeling and remodeling. However, questions remain regarding whether a benefit of exercise is seen at all bone sites, is dependent on pubertal status or sex of the child, or whether other factors such as diet modify the response to exercise.Questions/purposesWe asked: (1) Does bone-loading exercise in childhood consistently increase bone mineral content, bone area, or aBMD? (2) Do effects of exercise differ depending on pubertal status or sex? (3) Does calcium intake modify the bone response to exercise?MethodsA literature search identified 22 unique trials for inclusion in this meta-analysis of the effect of exercise on bone changes by bone site, pubertal status, and sex. Sample sizes ranged from 16 to 410 subjects 3 to 18 years old with length of intervention ranging from 3 to 36 months. Fifteen of 22 trials were randomized (child randomized in nine, classroom/school randomized in six) and seven were observational trials. Ten trials were Level 2 and 11 were Level 3 based on the Oxford Centre for Evidence-Based Medicine criteria. Random effects models tested the difference (intervention mean effect–control mean effect) in percent change in bone mineral content, bone area, and aBMD. Meta-regression was used to identify sources of heterogeneity and funnel plots were used to assess publication bias.ResultsChildren assigned to exercise had greater mean percent changes in bone mineral content and aBMD than children assigned to the control groups. Mean differences (95% CI) in bone mineral content percent change between intervention and control groups at total body (0.8; 95% CI, 0.3–1.3; p = 0.003), femoral neck (1.5; 95% CI, 0.5–2.5; p = 0.003), and spine (1.7; 95% CI, 0.4–3.1; p = 0.01) were significant with no differences in bone area (all p > 0.05). There were greater percent changes in aBMD in intervention than control groups at the femoral neck (0.6; 95% CI, 0.2–1.1; p = 0.006) and spine (1.2; 95% CI, 0.6–1.8; p < 0.001). Benefit of exercise was limited to children who were prepubertal (bone mineral content: total body [0.9; 95% CI, 0.2–1.7; p = 0.01], femoral neck [1.8; 95% CI, 0.0–3.5; p = 0.047], spine [3.7; 95% CI, 0.8–6.6; p = 0.01], and aBMD: femoral neck [0.6; 95% CI, −0.1–1.2; p = 0.07], spine [1.5; 95% CI, 0.7–2.3; p < 0.001]), with no differences among children who were pubertal (all p > 0.05). Changes in aBMD did not differ by sex (all p > 0.05), although the number of studies providing male-specific results was small (six of 22 eligible studies included boys). There was significant heterogeneity in bone mineral content and bone area for which a source could not be identified. Heterogeneity in spine aBMD was reduced by including calcium intake and intervention length as covariates. Three trials designed to determine whether calcium intake modified the bone response to exercise all reported a greater effect of exercise on leg bone mineral content in children randomized to receive supplemental calcium than those receiving placebo.ConclusionsExercise interventions during childhood led to 0.6% to 1.7% greater annual increase in bone accrual, with effects predominantly among children who were prepubertal. If this effect were to persist into adulthood, it would have substantial implications for osteoporosis prevention. It is important to identify sources of heterogeneity among studies to determine factors that might influence the bone response to increased exercise during growth.Level of EvidenceLevel II, therapeutic study.

Evaluation of a Trabecular Micro-Bypass Stent in Pseudophakic Patients With Open-Angle Glaucoma.

Purpose of the Study:The purpose of the study was to evaluate the safety and efficacy of the iStent Trabecular Micro-Bypass stent in pseudophakic patients with open-angle glaucoma. Methods:Retrospective, consecutive case series from October 2012 to May 2015 with no exclusion criteria. The series comprised 42 pseudophakic eyes with open-angle glaucoma that were implanted with 1 iStent. Data were collected preoperatively, and postoperative data were collected at 1 day, 1 week, 1, 3 and 6 months, 1 year, 18 months and 2 years. Data included intraocular pressure (IOP), number of glaucoma medications, the incidence of postoperative IOP pressure spikes ≥15 mm Hg at any timepoint, and the need for additional surgery. Results:The mean preoperative IOP was 20.26±6.00 mm Hg. At 1 year postoperatively, the mean IOP was 16.34±3.78 mm Hg (P<0.01). At 2 years postoperatively, the mean IOP was 13.62±4.55 (P<0.01). The mean number of glaucoma medications was 1.95±1.01 preoperative and 1.69±1.28 (P>0.05) at 1 year postoperatively. Postoperatively, 3 eyes (7%) experienced an IOP increase of 15 mm Hg above their baseline IOP that responded to topical therapy. In total, 96% of patients with an IOP≥19 mm Hg achieved a reduction in IOP at their last collected follow-up. Conclusions:The insertion of the iStent Trabecular Micro-Bypass stent effectively lowers IOP in pseudophakic patients with open-angle glaucoma. Although medication use was not significantly reduced postoperatively at 1 year, 80% of patients either experienced a reduction or no change in medication use. The safety profile appears favorable with a low rate of IOP spikes and only 1 patient requiring additional surgery.

Longitudinal effects of fat and lean mass on bone accrual in infants

There are conflicting reports on the influence of lean and fat mass on bone accrual during childhood. No infants studies have been reported that describe the influence of changes in body composition with changes in bone accrual during the first year of life. The objective of this research was to test the hypothesis that greater gains in lean mass will have a positive effect on bone mineral content (BMC) accrual, while greater gains in fat mass will have a negative effect on BMC accrual in infants. Longitudinal data from 3 previous infant studies were used. Linear mixed models, adjusting for age, sex, dietary calcium, and length were used to investigate longitudinal and cross-sectional associations between total body BMC and lean and fat mass in the individual studies and in a combined analysis. In both individual and combined analyses, we found that lean and fat mass were positively associated with whole body BMC accrual (all, P<0.001). The cross-sectional association of BMC and dietary calcium was negative in one study (P<0.05). No differences in BMC change between sexes were observed in three studies. Our results showed positive cross-sectional and longitudinal associations between total body BMC and lean mass in infants. In contradiction to our hypothesis for fat mass, we found a positive cross-sectional and longitudinal association between total body BMC and fat mass in infants.

Clinical evaluation of a trabecular microbypass stent with phacoemulsification in patients with open-angle glaucoma and cataract

Purpose To evaluate the safety and efficacy of the iStent trabecular microbypass stent in combination with cataract surgery in patients with open-angle glaucoma (OAG). Methods Retrospective, consecutive case series from October 2012 to December 2015 with no exclusion criteria. The series comprised of 350 eyes with OAG and cataract. Data were collected both preoperatively and postoperatively at day 1 week 1, months 1, 3, 6, 12, 18, and 24. Data included intraocular pressure (IOP), number of glaucoma medications, visual acuity, the incidence of postoperative IOP pressure spikes of greater than ≥15 mmHg at any time point, and need for additional surgery. Results The mean preoperative IOP was 19.13±6.34 mmHg. At 2 years postoperation, mean IOP was 15.17±3.53 mmHg (P<0.0001). The mean number of glaucoma medications was 1.19±1.00 preoperatively and 0.61±0.96 (P<0.0001) at 2 years postoperation. At 1 day postoperatively, 31 eyes (12.4%) experienced an IOP increase of 15 mmHg above their baseline IOP that responded to topical therapy. Two patients required additional tube shunt surgery. Conclusion The insertion of the iStent trabecular microbypass stent in combination with cataract surgery effectively lowers IOP in OAG patients. The magnitude of IOP reduction was more significant in patients with higher preoperative pressure. Medication use was also significantly reduced postoperatively. The safety profile appears favorable with a low rate of IOP spikes and only two eyes (<1%) requiring additional surgery.

Brief Report: Increased Expression of the Type I Interferon Receptor on CD4+ T Lymphocytes in HIV-1-Infected Individuals.

Background: Type I interferons (IFN1s; eg, interferon-alpha and interferon-beta) are potent cytokines that inhibit the replication of human immunodeficiency virus-1 (HIV-1) and other viruses. The antiviral and immunoregulatory activities of IFN1 are mediated through ligand–receptor interactions with the IFN1 receptor complex (IFNAR). Variation in the cell-surface density of IFNAR could play a role in HIV-1 pathogenesis. Methods: In this cross-sectional study of fresh whole blood, we used flow cytometry to evaluate the expression of IFNAR2 on lymphocyte subsets from HIV-1–infected (n = 33) and HIV-1–uninfected (n = 22) individuals. Results: In comparison with healthy blood bank donors, we observed that the HIV-1–infected individuals, particularly those having advanced to disease, exhibited the increased expression of IFNAR2 on CD4+ T cells (relative fluorescence intensity 6.9 vs. 9.0; P = 0.027). The CD4+:CD4neg T-cell IFNAR2 expression-level ratio provides an internally standardized measure of this alteration. The observed increased expression of IFNAR2 was largely restricted to CD4+ T cells that expressed the chemokine receptor CXCR4 and lacked the expression of CCR5. Conclusions: HIV-1–infected individuals exhibit an increased expression of the IFN1 receptor on CD4+ T cells. The level of IFNAR2 expression seems to increase with disease progression. These findings provide insight for the immunologic alterations associated with HIV-1 infection and possibly new therapeutic approaches.

Multiple Comparisons of Parametric Models in Longitudinal Studies

In longitudinal analysis, interest lies often in comparing parametric models over time. For example, if the trend over time is linear, commonly a test is performed to evaluate whether the rate of change in the mean response is the same for all treatment groups. For parametric models, treatment profiles can easily be compared using confidence bands. The authors propose simultaneous confidence bands and discuss two methods of calculating the associated critical point for comparing several parametric models over time. This issue has never been addressed before in the context of longitudinal studies. An example illustrates the proposed method.

Evaluation of a Trabecular Microbypass Stent With Cataract Extraction in Severe Primary Open-angle Glaucoma

Purpose: To evaluate the safety and efficacy of a trabecular microbypass stent combined with cataract surgery in patients with severe open-angle glaucoma. Patients: The series included 59 eyes with severe primary open-angle glaucoma and severe visual field loss as defined by American Academy of Ophthalmology preferred practice pattern criteria. Materials and Methods: Retrospective case series. Patients were implanted with 1 trabecular microbypass stent with concomitant cataract surgery. Primary outcome measures were intraocular pressure (IOP) and number of glaucoma medications. Safety measures included postoperative IOP pressure spikes ≥15 mm Hg or IOP<6 mm Hg at any time point, and the need for additional surgery. Results: The mean preoperative IOP was 19.25±6.97 mm Hg. Postoperatively, the mean IOP was 14.38±3.63 mm Hg (P<0.01) at 12 months and 14.92±3.86 mm Hg (P<0.01) at 24 months. The mean number of glaucoma medications was 2.27±1.06 preoperatively and 1.63±1.17 (P<0.01) at 24 months postoperative, indicating a 28% reduction in medication use. In total, 4 (7%) eyes required additional surgery. In total, 5 eyes (8%) experienced IOP spikes ≥15 mm Hg, 14 (24%) eyes had IOP spikes ≥10 mm Hg. Overall 55% of eyes had a 20% IOP reduction after 24 months of surgery. Eyes with baseline IOP⩽19 had a mean reduction of 2.24 mm Hg 36 months after surgery. Conclusions: Trabecular microbypass stent implantation during cataract surgery safely and effectively lowers IOP and medication use in patients with severe primary open-angle glaucoma.

Influences on rebubble rate in Descemet's membrane endothelial keratoplasty

Purpose Descemet’s membrane endothelial keratoplasty (DMEK) is a minimally invasive partial corneal transplant procedure used in patients with failing endothelial membranes. This study aims to identify those factors which influence the need for a rebubble of the corneal graft. Methods A total of 94 eyes that received DMEK between March 2014 and January 2016 at Vance Thompson Vision were used in the study. Demographic and graft data were collected from the patients and donors, and perioperative statistics of the procedures. A logistical regression was used to compare eyes that did and did not require a rebubble. Results Among those characteristics that were included (patient age/sex, donor age/sex, death to processing time, donation to surgery time, death to procurement time, specular cell count density, burping procedure, postoperative day 1 intraocular pressure [IOP], and postoperative week 1 IOP, concurrent phacoemulsification, and how well the Descemet graft was centered), only a lower specular cell count density of the corneal graft, and a graft that was not well-centered correlated with needing a rebubble due to partial graft detachment (p=0.021) and (p=0.023), respectively. Conclusion An increased specular cell count density may allow for better placement of the corneal graft by allowing for better unfolding in DMEK procedures. A well-centered graft may decrease postoperative complications by increasing adherence. Additionally, postoperative management of IOP may not affect the rebubble rate, and therefore should be left to the discretion of the provider to determine whether it is necessary.