Short- and long-term motor outcome of STN-DBS in Parkinson’s Disease: focus on sex differences

Neurological Sciences - Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for patients with Parkinson’s disease (PD) with motor complications; the contribution...     

Clinical prognostic factors associated with outcome in patients with renal cell cancer with prior tyrosine kinase inhibitors or immunotherapy treated with everolimus

BackgroundThe mTOR inhibitor, everolimus, is approved for the treatment of metastatic renal cell carcinoma (RCC). However, prognostic models are needed to determine the patients who would most benefit from this therapy. We have developed a model based on clinical parameters and patient stratification into risk groups to predict patients with RCC who will derive the most benefit from treatment with everolimus.MethodsWe assessed retrospective data on 57 patients with RCC who received everolimus after previous treatment with immunotherapy or tyrosine kinase inhibitors to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). In the original phase II study, patients received 10 mg of everolimus daily without interruption and were assessed every other week for the first 8 weeks on therapy and every 4 weeks thereafter. Kaplan-Meier analysis was used to calculate OS and PFS. Univariate and multivariate analyses were constructed using the Cox proportional hazards model and a stepwise procedure to validate the data.ResultsWe grouped patients according to risk: 0 prognostic factors indicated favorable risk, 1 to 2 factors intermediate risk, and≥3 factors poor risk. We found notable differences in median OS (29.6 mo for favorable risk, 14.3 mo for intermediate risk, and 7.2 mo for poor risk). Three risk factors (prior radiation treatment, no lung metastasis present at the start of treatment, and lymphocytes<25 cells/µl) in the multivariate analysis were found to be associated with PFS, and 4 risk factors were found to be associated with OS (bone metastasis at start of treatment, LDH>1.5×upper limit of normal, alkaline phosphatase>120 U/l, and lymphocytes<25 cells/µl).ConclusionsOur prognostic model includes 3 readily available clinical parameters for PFS and 4 readily available clinical parameters for OS to help stratify patients into poor, intermediate, and favorable prognosis groups for the treatment of everolimus in clear cell RCC. These intriguing results warrant further study in a larger patient population to validate the findings.     

Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

Control of hypertension with medication: a comparative analysis of national surveys in 20 countries

Objective

To examine hypertension management across countries and over time using consistent and comparable methods.

Methods

A systematic search identified nationally representative health examination surveys from 20 countries containing data from 1980 to 2011 on blood pressure measurements, the diagnosis and treatment of hypertension and its control with antihypertensive drugs. For each country, the prevalence of hypertension (i.e. systolic blood pressure ≥ 140 mmHg or antihypertensive use) and the proportion of hypertensive individuals whose condition was diagnosed, treated or controlled with medications (i.e. systolic pressure < 140 mmHg) were estimated.

Findings

The age-standardized prevalence of hypertension varied between countries: for individuals aged 35 to 49 years, it ranged from around 12% in Bangladesh, Egypt and Thailand to around 30% in Armenia, Lesotho and Ukraine; for those aged 35 to 84 years, it ranged from 20% in Bangladesh to more than 40% in Germany, the Russian Federation and Turkey. The age-standardized percentage of hypertensive individuals whose condition was diagnosed, treated or controlled was highest in the United States of America: for those aged 35 to 49 years, it was 84%, 77% and 56%, respectively. Percentages were especially low in Albania, Armenia, the Islamic Republic of Iran and Turkey. Although recent trends in prevalence differed in England, Japan and the United States, treatment coverage and hypertension control improved over time, particularly in England.

Conclusion

Globally the proportion of hypertensive individuals whose condition is treated or controlled with medication remains low. Greater efforts are needed to improve hypertension control, which would reduce the burden of noncommunicable diseases.     

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.