Effects of 0.005% latanoprost on ocular anterior structures and ciliary body thickness

Purpose: To assess the effects of 0.005% latanoprost on the anterior segment geometry and ciliary body thickness using ultrasound biomicroscopy. Intraocular pressure, refraction, visual acuity, and pupil size were also evaluated. Patients and Methods: Thirty patients with untreated ocular hypertension or primary open-angle glaucoma (mean age: 59.3 +/- 9.9 years) were recruited into this prospective, controlled, open trial. Before and after 1 week of 0.005% latanoprost administration, the following parameters were tested: refraction, visual acuity, pupil diameter, intraocular pressure, 5 conventional ultrasonographic A-scan variables, 16 ultrasound biomicroscopy parameters, and the ultrasound biomicroscopy ciliary body thicknesses at a distance of 1500 mu (CBT1), 2000 mu (CBT2), and 2500 mu (CBT3) from the scleral spur. Results: Latanoprost 0.005% caused a marked intraocular pressure-lowering effect in all patients (from 22.8 +/- 3.1 mm Hg to 14.1 +/- 2.9 mmHg; -38%, P < 0.0001), without any refractive, visual acuity, or papillary alterations. The A-scan echobiometry variables were unchanged, while ultrasound biomicroscopy confirmed a significant posttreatment increase of CBT2 (from 434 +/- 140 mu to 536 +/- 127 mu; + 102 mu, P = 0.01) and CBT3 (from 319 +/- 103 mu to 412 +/- 100 mu; +93 mu, P = 0.003) compared with controls (CBT2: from 493 +/- 165 mu, to 473 +/- 135 mu, -20 mu, P = NS; CBT3: from 388 +/- 130 mu to 365 +/- 87 mu, -23 mu, P = NS). None of the changes observed in the other UBM parameters was statistically significant. No significant correlation was detected between ciliary body thickness increase and intraocular pressure-lowering effect. Conclusion: The increase of ciliary body thickness, which was measured in vivo by ultrasound biomicroscopy and associated with the intraocular pressure-lowering effect, indirectly supports the mechanism of uveoscleral outflow enhancement induced by latanoprost. These data are in agreement with the biochemical hypothesis of the passage of the aqueous flow through the extracellular spaces of the ciliary muscle

To Bleed or Not to Bleed : a Prediction Based on Individual Gene Profiling Combined With Dose-Volume Histogram Shapes in Prostate Cancer Patients Undergoing Three-Dimensional Conformal Radiation Therapy

Purpose: The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume histograms (DVHs), some patients treated for prostate cancer exhibit late rectal bleeding (LRB) and others with poor DVHs do not. Thirty-five genes involved in DNA repair/radiation response were analyzed in patients accrued in the AIROPROS 0101 trial, which investigated the correlation between LRB and dosimetric parameters. Methods and Materials: Thirty patients undergoing conformal radiotherapy with prescription doses higher than 70 Gy (minimum follow-up, 48 months) were selected: 10 patients in the low-risk group (rectal DVH with the percent volume of rectum receiving more than 70 Gy [V70Gy] < 20% and the percent volume of rectum receiving more than 50 Gy [V50Gy] < 55%) with Grade 2 or Grade 3 (G2-G3) LRB, 10 patients in the high-risk group (V70Gy > 25% and V50Gy > 60%) with G2-G3 LRB, and 10 patients in the high-risk group with no toxicity. Quantitative reverse-transcriptase polymerase chain reaction was performed on RNA from lymphoblastoid cell lines obtained from Epstein-Barr virus-immortalized peripheral-blood mononucleated cells and on peripheral blood mononucleated cells. Interexpression levels were compared by using the Kruskal-Wallis test. Results: Intergroup comparison showed many constitutive differences: nine genes were significantly down-regulated in the low-risk bleeder group vs. the high-risk bleeder and high-risk nonbleeder groups: AKR1B1 (p = 0.019), BAZ1B (p = 0.042), LSM7 (p = 0.0016), MRPL23 (p = 0.015), NUDT1 (p = 0.0031), PSMB4 (p = 0.079), PSMD1 (p = 0.062), SEC22L1 (p = 0.040), and UBB (p = 0.018). Four genes were significantly upregulated in the high-risk nonbleeder group than in the other groups: DDX17 (p = 0.048), DRAP1 (p = 0.0025), RAD23 (p = 0.015), and SRF (p = 0.024). For most of these genes, it was possible to establish a cut-off value that correctly classified most patients. Conclusions: The predictive value of sensitivity and resistance to LRB of the genes identified by the study is promising and should be tested in a larger data set

Interferon-B but not Glatiramer acetate stimulates CXCL10 secretion in primary cultures of thyrocytes: A clue for understanding the different risks of thyroid dysfunctions in patients with multiple sclerosis treated with either of the two drugs

Autoimmune thyroid disease (AITD) has been reported in patients with multiple sclerosis (MS) receiving interferon-beta (IFN-β), but not in those receiving Glatiramer acetate (GA). CXCL10 is a chemokine playing a pathogenetic role in AITD and MS. Our aim was to evaluate the effects on CXCL10 secretion of IFN-β and GA, alone and in combination with TNF-α, in primary cultures of thyrocytes (PCT). Significant and dose-dependent secretions of CXCL10 were induced by IFN-β but not GA. TNF-α synergistically increased IFN-β induced CXCL10 secretion. These results may provide an explanation for the occurrence of AITD during IFN-β, but not during GA, treatment for MS

IDegLira for the Real-World Treatment of Type 2 Diabetes in Italy: Protocol and Interim Results from the REX Observational Study

Introduction: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). Methods: Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2–3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients’ baseline characteristics and the clinical reasons for IDegLira treatment initiation. Results: Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0–20.0) units in the BOT group and 42 (30.0–52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). Conclusions: IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients’ outcomes after IdegLira treatment under routine clinical care