Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double‐blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects’ mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m², 55% were women, and 222 completed the 12‐month follow‐up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low‐dose arm, and 36 ng/mL in the high‐dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C‐terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high‐dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high‐dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high‐dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.     

A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer

PURPOSE: Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are more vulnerable to disease relapse after surgery and who may benefit from additional therapy. PATIENTS AND METHODS: The study was performed between January 1997 and December 1999, in which 180 patients with histopathologically proved invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic exenteration. After surgery, patients were regularly followed for a minimum of 2 years. RESULTS: Our patients included 141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade, and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004, respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and higher risk groups, respectively. CONCLUSION: Although this prognostic index appears to be of a significant clinical relevance, it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic factors responsible for the heterogeneity of bladder cancer.     

Inhibition of cell survival, viability and proliferation by dentin adhesives after direct and indirect exposure in vitro

Objectives

The influence of dentin adhesive systems (Scotchbond Multi-Purpose, XP Bond, Xeno V, Clearfil Protect Bond, AdheSE) on cell survival, viability and proliferation was characterized after direct and indirect exposure using different cell culture techniques.

Materials and methods

The primers and cured bonding parts were directly exposed to cells using cell culture inserts, and complete materials were analyzed in a dentin barrier test. Cell responses were examined in 3T3 mouse fibroblasts after 24- and 72-h exposure periods by the estimation of total cell numbers (survival), apoptosis (viability) and cell proliferation.

Results

Cell numbers were effectively reduced by the primers of AdheSE, Protect Bond, and Scotchbond Multi-Purpose as well as XP bond after direct exposure in a cell culture insert test device. Likewise, Scotchbond Multi-Purpose primer induced a rate of apoptosis (93.9%) even higher than detected with Protect Bond primer (91.6%). Cell proliferation was entirely inhibited by primers and by Xp Bond as well. The Scotchbond Multi-Purpose was most cytotoxic in a dentin barrier test device after a 24-h indirect exposure. It also increased the percentage of cells in apoptosis to 15.4% compared to untreated controls.

Conclusion

Unpolymerized primers of dentin adhesives were more cytotoxic than polymerized bonding counterparts. Moreover, total etch dentin adhesives were more cytotoxic than self-etch adhesives.

Clinical relevance

When dentin adhesives are used in deep cavities without a protective dentin barrier the leachable hydrophobic and hydrophilic component of dentin adhesive systems can penetrate to the pulp and may induce cytotoxic responses in pulp tissues.     

Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study

BACKGROUND AND PURPOSE:Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up.MATERIALS AND METHODS:We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis.RESULTS:At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR  = 12.1; 95% CI, 3.5–42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3–2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3–2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7–6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm³ [IQR, 0.97–1.16 cm³] versus 0.86 cm³ [IQR, 0.73–1.00 cm³]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13–31%] versus 2% [IQR, 0–14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8–24%] versus 0% [IQR, 0–5%]; P < .001).CONCLUSIONS:Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

Atherosclerosis in the carotid arteries is one of the leading causes of ischemic stroke with arterio-arterial embolism as the main mechanism.^1,2 The degree of lumen stenosis and the symptomatic status of the patient are currently used for risk assessment and treatment decision-making.^3,4 Patients with severe (≥70%) and moderate (50%–69%) carotid artery stenosis benefit from carotid endarterectomy; however, the number needed to treat to prevent recurrent stroke is relatively high.⁵ Moreover, almost half of neurologic events occur in patients with a low degree of stenosis.^6,7 This finding has triggered investigations into other markers that may help to identify patients with a high risk of recurrent stroke. Much attention has been paid to markers of atherosclerosis, like plaque composition and plaque ulceration, with the aim of identifying vulnerable plaques.⁸ These vulnerable plaques have a high risk of rupture, which results in thrombus formation and embolization of plaque material and/or thrombus migrating into the intracranial circulation, thereby causing vascular occlusion and a subsequent ischemic stroke.²Plaque composition is predictive of future cerebrovascular events.^9-12 Atherosclerotic plaque ulceration, visible as plaque-surface disruption, which is a marker of previous plaque rupture, is also correlated with recurrent symptoms and associated with a higher risk of ischemic stroke.^13,14 However, the relation between vulnerable plaque components and plaque rupture is rarely investigated. Both plaque composition and ulceration can be assessed in vivo with different imaging modalities, but MR imaging is the best technique to assess plaque composition due to its superior soft-tissue contrast,¹⁵ whereas MDCTA exceeds MR imaging in the detection of plaque ulcerations due to its excellent spatial resolution with the possibility of multiplanar reconstruction.^16,17Most previous studies investigated the relation between plaque ulcerations and plaque features using a cross-sectional study design. Generally, it was found that intraplaque hemorrhage (IPH), large lipid-rich necrotic core (LRNC), and thinning or ruptured fibrous cap were associated with the presence of ulcerations,^18-21 while the presence of calcifications was inversely related to ulcerations.¹⁹ A prospective study in asymptomatic patients with severe carotid artery stenosis revealed that LRNC volume was a predictor of new surface disruption.^22,23 The aim of the current study was to investigate, in symptomatic patients with mild-to-moderate (30%–69%) carotid artery stenosis, which plaque components at baseline are predictive of plaque rupture at follow-up.     

Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients

Background: The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. Objective: The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin^®) and compare it with the innovator product Eprex^®, as a standard rHuEPO. Methods: One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80–120 IU/kg/week in 2–3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. Results: A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p < 0.001). However, these factors were not significantly different between the groups, neither at baseline nor at the end of study (p > 0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. Conclusion: Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.     

A Case Report of Ablepharon-Macrostomia Syndrome with Amniotic Membrane Grafting

We describe a rare case of an infant who was born with multiple congenital anomalies, including the absence of eyelids. This patient had many dysmorphic features consistent with a severe phenotype of ablepharon-macrostomia syndrome (AMS) including a fish-like appearance of the mouth, rudimentary ears, absence of body hair, thin skin, absent nipples, abdominal distension, and genital abnormalities. Upon presentation, there was severe exposure keratopathy causing large bilateral sterile ulcers culminating in corneal melting of both eyes. An amniotic membrane graft was used to attempt to maintain the corneal surface integrity. However, because of the late presentation, the corneas could not be salvaged. Extensive surgical reconstruction of both eyelids and bilateral penetrating keratoplasty was ultimately performed successfully to protect the ocular surfaces while trying to maximize the visual potential. Early amniotic membrane grafting may be done at the bedside and may help preserve the ocular in patients with severe eyelid deformities until more definitive treatment is performed.Key Words: Ablepharon, Macrostomia, Congenital eyelid anomalies, Absent hair, Absent eyelids     

Association of IL-8 gene polymorphisms with non small cell lung cancer in Tunisia: A case control study

Interleukin 8 (IL-8), is a proinflammatory chemokine, has been reported to have angiogenic activity and to be responsible for tumor-associated angiogenesis in several cancers. In this study, we aimed to study the (IL-8) gene polymorphism in relation with risk development of non small cell lung cancer in Tunisian patient. Two single nucleotide polymorphisms (−251T/A [rs4073], +781C/T [rs2227306]) of the IL-8 gene were screened in 170 patients with NSCLC and 225 healthy controls by PCR–RFLP.