Glaucoma: Hot topics in Pharmacology

BACKGROUND: Glaucoma comprises a group of neurodegenerative diseases resulting in retinal ganglion cell death within the optic nerve head. It is projected to affect almost 80 million people worldwide by 2020. The condition's asymptomatic nature translates to over half of glaucoma sufferers being unaware of their condition. By the time of diagnosis, irreversible blindness is likely to have occurred. Prime areas of glaucoma research therefore include identification and optimization of risk factors for the disease, accurate and early diagnostic tools and novel therapeutic methods. METHODS: The goal of this review was to summarize main areas of latest glaucoma research into risk factors of glaucoma, diagnostic tools and treatments. PubMed was used to search for terms including glaucoma risk factors, glaucoma diagnostics, glaucoma treatment, glaucoma drug delivery and glaucoma IOP. RESULTS: The evidence for risk factors of low CSF pressure, IOP, smoking, vascular risk factors and light toxicity is described. Latest diagnostic and monitoring techniques for glaucoma include SD-OCT, DARC and IOP telemetry. Current and emerging medical and surgical treatments in glaucoma are discussed. Rho kinase inhibitors have the potential to both lower IOP and also provide neuroprotection, several of which are in clinical trials. Several other new medical treatments such as calcium channel blockers and neurotrophic agents also have the capacity to provide neuroprotection. Minimally Invasive Glaucoma Surgery (MIGS) devices provide an improved safety profile compared to traditional trabeculectomy; the latest ab interno and ab externo devices are described. Novel drug delivery methods, including punctual plugs and contact lenses, help overcome the challenges with patient adherence. CONCLUSION: The ultimate goals are to reduce the individual patient risk factors associated with glaucoma, diagnose the condition early and to find treatments that not only reduce IOP but also reverse neurodegeneration of RGCs. The usage of combinations of novel medical and surgical treatments may help maximize IOP reduction and neuroprotection

Necrotizing enterocolitis: clinical characteristics and outcome of a cohort of 106 cases at a children’s hospital in North China

Introduction: Necrotizing enterocolitis (NEC) in neonates, especially in the preterm, is a life-threatening condition. This study aims to analyze the clinical profile of NEC to get an insight for better understanding and management.  Method: This was a retrospective analysis of neonatal NEC during the six-year period from 2014 to 2019. The prevalence and time for the development of NEC, clinical profile (term and preterm, low birth weight, gender, breast and formula feeding, abdominal distension, vomiting, hematochezia, apnea, fever, altered mental status, blood transfusion, breast or formula-fed, intestinal perforation, Bell’s stage and time for the development of NEC) and maternal factors (gestational hypertension, diabetes, premature rupture of membranes PROM, intrauterine fetal distress, placenta previa) were analyzed. Features in preterm and term neonates were compared. Ethical approval was obtained.  Result: There were 106 NEC (0.87% of 12,184 neonatal admissions), 62 (58.49%) male, 90 (84.91%) preterm, and 85 (80.19%) LBW. Overall, 88 (83.02%) were Bell’s stage II, and severe stage III was seen in eight (19.04%) out of 42 babies with formula feeding as compared to one (1.56%) out of 64 in breastfeeding. The median time for the development of NEC was 6 days of life. The yearly prevalence of NEC per thousand neonates admitted during 6-years increased from 2.90 in 2014 to 12.06 in 2019. Overall mortality was 14 (13.20%).  Conclusion: The yearly incidence of NEC increased with a higher incidence in preterm, in low birth weight and formula-fed neonates

Contemporary hormone therapy with LHRH agonists for prostate cancer: avoiding osteoporosis and fracture.

© 2015 Polish Urological Association. All Rights Reserved.Introduction Prostate cancer is a large clinical burden across Europe. It is, in fact, the most common cancer in males, accounting for more than 92,300 deaths annually throughout the continent. Prostate cancer is androgen-sensitive; thus an androgen deprivation therapy (ADT) is often used for treatment by reducing androgen to castrate levels. Several ADT agents have achieved benefits with effective palliation, but, unfortunately, severe adverse events are frequent. Contemporary ADT (Luteinising Hormone Releasing Hormone agonist - LHRHa injections) can result in side effects that include osteoporosis and fractures, compromising quality of life and survival.  Methods In this review we analysed the associated bone toxicity consequent upon contemporary ADT and based on the literature and our own experience we present future perspectives that seek to mitigate this associated toxicity both by development of novel therapies and by better identification and prediction of fracture risk. Results Preliminary results indicate that parenteral oestrogen can mitigate associated osteoporotic risk and that CT scans could provide a more accurate indicator of overall bone quality and hence fracture risk.  Conclusions As healthcare costs increase globally, cheap and effective alternatives that achieve ADT, but mitigate or avoid such bone toxicities, will be needed. More so, innovative techniques to improve both the measurement and the extent of this toxicity, by assessing bone health and prediction of fracture risk, are also required

Korean Brain Rehabilitation Registry for Rehabilitation of Persons with Brain Disorders: Annual Report in 2009

This first annual report provides a description of patients discharged from rehabilitation facilities in Korea based on secondary data analysis of Korean Brain Rehabilitation Registry V1.0 subscribed in 2009. The analysis included 1,697 records of patients with brain disorders including stroke, traumatic brain injury, brain tumor and other disorders from 24 rehabilitation facilities across Korea. The data comprised 1,380 cases of stroke, 104 cases of brain injury, 55 cases of brain tumor, and 58 cases of other brain diseases. The functional status of each patient was measured using the Korean version of the Modified Barthel Index (KMBI). The average change in the KMBI score was 15.9 for all patients in the inpatient rehabilitation facility. The average length of stay for inpatient rehabilitation was 36.9 days. The transfer rates to other hospitals were high, being 62.4% when all patients were considered. Patients with brain disorders of Korea in 2009 and measurable functional improvement was observed in patients. However, relatively high percentages of patients were not discharged to the community after inpatient rehabilitation. Based on the results of this study, consecutive reports of the status of rehabilitation need to be conducted in order to provide useful information to many practitioners

Cabozantinib in progressive medullary thyroid cancer

Purpose Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with medullary thyroid cancer (MTC) in phase I. Patients and Methods We conducted a double-blind, phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomly assigned (2:1) to cabozantinib (140 mg per day) or placebo. The primary end point was progression-free survival (PFS). Additional outcome measures included tumor response rate, overall survival, and safety. Results The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.40; P < .001). Prolonged PFS with cabozantinib was observed across all subgroups including by age, prior TKI treatment, and RET mutation status (hereditary or sporadic). Response rate was 28% for cabozantinib and 0% for placebo; responses were seen regardless of RET mutation status. Kaplan-Meier estimates of patients alive and progression-free at 1 year are 47.3% for cabozantinib and 7.2% for placebo. Common cabozantinib-associated adverse events included diarrhea, palmar-plantar erythrodysesthesia, decreased weight and appetite, nausea, and fatigue and resulted in dose reductions in 79% and holds in 65% of patients. Adverse events led to treatment discontinuation in 16% of cabozantinib-treated patients and in 8% of placebo-treated patients. Conclusion Cabozantinib (140 mg per day) achieved a statistically significant improvement of PFS in patients with progressive metastatic MTC and represents an important new treatment option for patients with this rare disease. This dose of cabozantinib was associated with significant but manageable toxicity

3-D Wave Propagation in Cylindrical Single Crystal Solid-Liquid Bodies

The large difference in the ultrasonic velocity between the solid and the liquid phases of most semiconducting materials results in reflection/refraction of ultrasound at solid-liquid interfaces and an interest in using laser ultrasonics for sensing solid-liquid interfaces during single crystal growth. Using a ray tracing analysis, a set of measured ultrasonic time of flight (TOF) projection data can yield the ray paths connecting the source to the receiver, which can subsequently be used to reconstruct the solid-liquid interface. In previous work [1] 2-D wave propagation in cylindrical single crystal solid-liquid bodies was used to explore the feasibility of using ultrasound to characterize solid-liquid interfaces during vertical Bridgman growth of semiconductor materials. Detailed study of ray paths, wavefronts and TOF for ultrasound propagating in both transverse and diametral planes of liquid-solid single crystal (Ge) bodies was reported. Numerical simulations indicated that the magnitude and direction of the group velocity, the solid:liquid velocity ratio and the curvature of the interface together controlled the ray bending behavior and thus determined the ultrasonic data across the interface. Knowledge of ray paths at the interface enabled reconstruction of the interface using a small set of ultrasonic TOF’s

Ki67 Antigen as a Predictive Factor for Prognosis of Sinonasal Mucosal Melanoma

ObjectivesSinonasal mucosal melanoma is a rare and aggressive disease. The aim of this study was to analyze the clinical features of patients with sinonasal mucosal melanoma and to determine the role of Ki67 antigen as a predictor of prognosis in sinonasal mucosal melanoma.MethodsThis was a retrospective case-series study at a single institution, an academic tertiary referral center. From 1995 to 2007, 27 patients with sinonasal mucosal melanoma were reviewed retrospectively, and the expression of Ki67 antigen was assessed by immunohistochemistry.ResultsThe overall 5-yr survival rate was 33.9%. No significant differences were observed in 5-yr survival according to age, sex, stage, or the presence of melanin. The rates of local failure, regional failure, and distant failure were 37.0%, 14.8%, and 11.1%, respectively. Patients with spindle or mixed cell types had better prognoses than those with other cell types. At a cut-off value of 35%, patients with lower Ki67 scores showed better survival than those with higher Ki67 scores.ConclusionThe presence of spindle or mixed cell types may indicate a better prognosis than other cell types. Ki67 immunostaining may be a useful predictor of prognosis in patients with mucosal malignant melanoma of the sinonasal tract

Conceivable security risks and authentication techniques for smart devices

With the rapidly escalating use of smart devices and fraudulent transaction of users’ data from their devices, efficient and reliable techniques for authentication of the smart devices have become an obligatory issue. This paper reviews the security risks for mobile devices and studies several authentication techniques available for smart devices. The results from field studies enable a comparative evaluation of user-preferred authentication mechanisms and their opinions about reliability, biometric authentication and visual authentication techniques