Background
Periods 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/purposes
We 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?
Methods
A 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.
Results
Children 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.
Conclusions
Exercise 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 Evidence
Level II, therapeutic study.
Low fibrinogen and platelet counts are associated with bleeding and the need for transfusion. In this study, we investigated whether the Quantra® QPlus® parameters Fibrinogen Contribution (FCS) and ...Platelet Contribution (PCS) to clot stiffness could predict commonly used fibrinogen and platelet transfusion thresholds in patients undergoing major surgical procedures.
This study used data from a multicenter, prospective observational study of adult patients undergoing cardiac or major orthopedic surgery. Quantra and laboratory assays were performed in parallel at multiple time points. Logistic regression models were used to assess the ability of FCS and PCS to predict fibrinogen and platelet thresholds used to guide transfusions. Receiver operating characteristics (ROC) curves were analyzed to determine the diagnostic accuracy and the optimal FCS and PCS values corresponding to the laboratory-based thresholds.
The areas under the ROC curves (AUCs) for FCS at fibrinogen thresholds of <120, 150, and 200 mg/dl ranged from 0.96 to 0.89. Similarly, for PCS at platelet thresholds of <50, 80, 100,000/μl, AUCs ranged from 0.95 to 0.89. The proposed optimal FCS and PCS cutoff values showed high negative predictive value and high sensitivity and specificity (both >86%) at the lowest fibrinogen and platelet threshold levels.
This study identifies potential cutoff values for QPlus FCS and PCS proposed for use in place of or in conjunction with laboratory-based assays fibrinogen and platelet thresholds to guide transfusion decisions in surgical patients. These cut-off values will need to be validated in future studies.
•Low fibrinogen and low platelet counts are often associated with critical bleeding.•Quantra QPlus parameters FCS and PCS were measured in surgical patients.•FCS showed high sensitivity and specificity for low fibrinogen levels.•PCS showed high sensitivity and specificity for low platelet counts.•FCS and PCS can accurately predict fibrinogen and platelet transfusion thresholds.
To evaluate the safety and efficacy of the iStent trabecular microbypass stent in combination with cataract surgery in patients with open-angle glaucoma (OAG).
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.
The mean preoperative IOP was 19.13±6.34 mmHg. At 2 years postoperation, mean IOP was 15.17±3.53 mmHg (
<0.0001). The mean number of glaucoma medications was 1.19±1.00 preoperatively and 0.61±0.96 (
<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.
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.
CD8
+
T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4
+
T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte ...antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8
+
T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4
+
T cells. Altogether, CD8
+
T cell anti-HIV activity was evaluated in more than 200 co-cultures. Marked heterogeneity in HIV-1 replication levels was observed among the co-cultures sharing a common CD8
+
T cell source. The co-cultures that exhibited greater than 50% reduction in HIV production were found to have significantly increased numbers of matching HLA class I alleles (Yates chi-square = 54.21;
p
< 0.001). With CD8
+
T cells from HIV controllers and asymptomatic viremic individuals, matching HLA-B and/or HLA-C alleles were more predictive of strong anti-HIV activity than matching HLA-A alleles. Overall, HLA class I genotype matches were more closely associated with CD8
+
T cell anti-HIV activity than supertype pairings. Antibodies against HLA class I and CD3 reduced the CD8
+
T cell anti-HIV activity. Stimulated CD8
+
T cells exhibited increased anti-HIV activity and reduced dependency on HLA compatibility. These findings provide evidence that the maximal suppression of HIV replication by CD8
+
T cells requires the recognition of multiple epitopes. These studies provide insight for HIV vaccine development, and the analytic approach can be useful for the functional characterization of HLA class I alleles and tentative HLA class I supertypes.
To identify the visual performance of radial keratotomy (RK) patients that have undergone cataract surgery with implantation of an extended depth of focus (EDOF) intraocular lens (IOL).
Retrospective ...chart review with questionnaire.
Medical charts of patients with a history of RK that had undergone phacoemulsification with implantation of the Tecnis Symfony IOL (J&J Vision) were reviewed. Data collected included preoperative demographics, number of RK incisions, pupil size, and preoperative visual acuity and manifest refraction. Primary outcome measures of the study included postoperative uncorrected distance visual acuity (UCVA) and manifest refraction spherical equivalent (SE) at each follow-up visit. Secondary outcomes included results from a telephone questionnaire assessing visual performance and satisfaction.
Twenty-four eyes of 12 patients were included. UCVA improved from an average Snellen equivalent 20/73 preoperatively to 20/33 at an average final follow-up of 6 months (
=0.0011), while average manifest SE improved from +1.68 D to -0.18 D (
<0.0001). At final follow-up, 15 of 24 eyes (62.5%) were at or within 0.5 D of target refraction, while 20 of 24 eyes (83.3%) were at or within 1.0 D. In total, 79% of eyes (19 of 24) had UCVA of 20/40 or better at distance. In the survey, 78% of patients reported satisfaction with their vision after surgery and 44% of patients reported being spectacle free for all tasks.
An EDOF lens implant can produce good visual outcomes and satisfaction in patients with a history of RK.
Background
Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States. Descriptive epidemiology of pancreatic cancer in South Dakota has not been studied before.
...Materials and Methods
All cases of pancreatic cancer reported to the SD Cancer Registry between January 2005 and December 2014 were included in the study. Variables collected included demographics, geographical location including county of residence and zip codes, date of diagnosis, date of last contact or follow-up, size and location of the tumor, grade of the tumor, diagnostic modality as well as therapeutic interventions. Log rank test was used to compare survival curves. Kaplan-Meier product limit estimates were provided. Data was analyzed using SAS 9.1.4 software.
Results
One thousand sixty-four cases of pancreatic cancer were reported. Median age was 73 years. Cumulative age-adjusted incidence rate for pancreatic cancer for 2005–2014 was 11.1. Cumulative age-adjusted mortality rate for pancreatic cancer for 2005–2014 was 10.2. Almost half of these patients had distant metastasis at the time of presentation (
n
= 536; 50.4%). Overall, median survival was 5 months. Median survival for patients under the age of 60 years was 9.5 months as opposed to median survival for patients 60 years or older which was 3.9 months. Median survival of patients with well-differentiated, moderately differentiated, and poorly differentiated tumors, was 20.8 months, 8.2 months and 6.3 months respectively (
p
value = 0.0017).
Conclusion
Incidence of pancreatic cancer in South Dakota is similar to the national trends in the United States. Age at presentation, location of tumor in pancreas, and biological behavior of tumor were all predictors of survival in patients with pancreatic cancer.
Purpose To evaluate the safety and efficacy of a trabecular microbypass stent (iStent) combined with cataract surgery in patients with pseudoexfoliation glaucoma (PXG). Setting Vance Thompson Vision, ...Sioux Falls, South Dakota, USA. Design Retrospective case series. Methods Eyes with PXG had implantation of 1 stent. Data were collected preoperatively and postoperatively through 24 months. Data included intraocular pressure (IOP), number of glaucoma medications, the incidence of postoperative IOP pressure spikes of 15 mm Hg or higher at any timepoint, and the need for additional surgery. Results The series included 115 eyes. The mean preoperative IOP was 20.00 mm Hg ± 6.95 (SD). One year postoperatively, the mean IOP was 15.54 ± 3.83 mm Hg ( P < .01). At 2 years, the mean IOP was 14.51 ± 2.79 ( P < .01). The mean number of glaucoma medications was 1.41 ± 1.04 preoperatively and 0.71 ± 0.94 2 years postoperatively ( P < .01), indicating a 50% reduction in medication use. Postoperatively, 7 eyes (6%) had an IOP spike of 15 mm Hg or higher above the baseline IOP; the spikes responded to topical therapy. Ninety-eight percent of patients with an IOP of 20 mm Hg or higher achieved a reduction in IOP at the last follow-up. Conclusion Trabecular microbypass stent implantation during cataract surgery safely and effectively lowered IOP and medication use in patients with mild to severe PXG.
To evaluate the safety and efficacy of intravitreal administration of a steroid and antibiotics during cataract surgery compared with the typical postoperative topical regimen in preventing ...postoperative inflammation, pain, cystoid macular edema (CME), and endophthalmitis.
Private practice, Sioux Falls, South Dakota, USA.
Retrospective case series.
The study group included eyes that had an intravitreal injection of triamcinolone–moxifloxacin–vancomycin at the time of cataract surgery with concomitant trabecular microbypass stent insertion. The control eyes had the same procedure but were prescribed topical antibiotics, steroids, and nonsteroidal antiinflammatory drugs postoperatively. Data were recorded preoperatively and 1 day, 1 week, 1 month, and 3 months postoperatively. Primary outcomes included the number of glaucoma medications, intraocular pressure (IOP), and IOP spikes of at least 15 mm Hg from baseline.
There were 234 eyes in the study group and 249 eyes in the control group. The mean reduction in glaucoma medications was 0.24 drops in the study group and 0.80 drops in the control group 3 months postoperatively, whereas the mean IOP reduction was 2.59 mm Hg in the study group and 3.63 mm Hg in the control group. Pressure spikes were detected at 54 (5.7%) of 936 postoperative visits in the study group and at 37 (3.7%) of 996 visits in the control group. There were no cases of severe inflammation, CME, infection, or retinal detachments.
Both groups had similar postoperative pressure reductions and incidence of IOP spikes. The results indicate that intravitreal injections of a steroid and antibiotics might be a safe option for glaucomatous eyes having cataract surgery with trabecular microbypass stent insertion.
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:CD4 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.
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.
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.
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 (
=0.021) and (
=0.023), respectively.
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.
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