Increased risk of cognitive impairment and more severe brain lesions in hypertensive compared to non‐hypertensive patients with cerebral small vessel disease

Although cerebral small vessel disease (SVD) is traditionally associated with aging and hypertension (HT), there are patients exhibiting sporadic SVD, free of HT. We aimed to investigate the differences in clinical and neuroradiological presentation in SVD patients in reference to the presence of HT as a risk factor (RF). Vascular RF, cognitive and functional status were evaluated in a cohort of 424 patients. Patients were classified in two groups based on the presence of HT. Severity of vascular lesions was assessed using 1.5 T magnetic resonance imaging with Age‐Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular (PV) and deep subcortical (DS) scores. No difference between groups in age and sex distribution was noted. In univariate analysis, HT was associated with vascular cognitive impairment (vCI) (OR 2.30, 1.53‐3.45, P < 0.0001), functional status (OR 1.47, 1.11‐1.95, P = 0.007), depression (OR 2.13, 1.23‐3.70, P = 0.007), tARWMC (OR 1.10, 1.05‐1.16 95% CI, P < 0.0001), Fazekas PV score (OR 1.34, 1.08‐1.67 95% CI, P = 0.008), Fazekas DS score (OR 1.95, 1.44‐2.63 95% CI, P < 0.0001) and total number of lacunes (OR 1.10, 1.02‐1.18 95% CI, P = 0.009). Multivariate logistic regression analysis indicated that HT was an independent RF for vCI (OR 1.74, 1.09‐2.76 95% CI, P = 0.020) and higher Fazekas DS score (OR 1.57, 1.11‐2.22 95% CI, P = 0.011). The Kaplan‐Meier curve of estimates of survival of SVD patients without vCI revealed a higher proportion of patients with HT progressing to vCI over time when compared to HT‐free cases. In patients with sporadic SVD, HT is a contributing factor to worse clinical outcomes and neuroradiological presentation.     

Quality control of involved field radiotherapy in the HD 13 and HD 14 trials

Introduction

As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings.

Methods

With the start of the fourth GHSG study generation (HD10–12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13–15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation.

Results

The expert panel analyzed the RT planning and application of 1037 (28?%) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85?% of cases and verification films in 87?%. RT was assessed as major violation in 46?% (HD13 = 38?%, HD14 = 52?%), minor violation in 9?% (HD13 = 9?%, HD14 = 9?%) and according to the protocol in 45?% (HD13 = 52?%, HD14 = 38?%).

Conclusion

The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of “modern RT” in malignant lymphoma.

     

Radiotherapy for aneurysmal bone cysts

Background

Aneurysmal bone cysts (ABC) are rapidly growing benign osseous lesions composed of blood-filled channels separated by fibrous septa. Since the value of external beam radiotherapy (EBRT) for ABC has not been well defined, the German Cooperative Group on Radiotherapy for Benign Diseases performed the national register study described herein.

Patients and methods

Five German institutions collected data regarding clinical features, treatment concepts, and outcome for patients with ABC who had been referred for local EBRT over the past 30 years.

Results

Between 1990 and 2015, 10 patients with ABC were irradiated (5 female/5 male). Median age was 23 years (range 14–40 years). Involved sites were: spine (n = 3), sacrum/pelvis (n = 2), shoulder/scapula (n = 2), humerus (n = 1), femur (n = 1), and radius (n = 1). The median EBRT total and fractional doses were 28?Gy (range 5–40?Gy) and 2?Gy (range 1–2?Gy), respectively. Median follow-up was 65 months (range 12–358 months). Persistent pain relief was achieved for all patients. However, long-term follow-up response data were only available for 7/10 patients. All 7 patients exhibited a radiological response and experienced no recurrent disease activity or pain during follow-up. Acute and late radiogenic toxicities ≥ grade 3 and secondary malignancies were also not observed.

Conclusion

Primary or adjuvant EBRT seems to be an effective and safe treatment option for persistent or recurrent ABC. Fractionated doses below 30?Gy may be recommended.

     

Does Each Menstrual Cycle Elicit a Distinct Effect on Olfactory and Gustatory Perception?

The obesity pandemic has brought forth a scientific interest in food intake and sensory perception interactions. Olfactory perception and gustatory perception are very complex and under the influence of many factors, including the menstrual cycle. This study aims to clarify conflicting findings on the influence of the menstrual cycle on olfactory and gustatory perception. Women were assessed during four consecutive phases of one complete cycle (mid-follicular, ovulatory, mid-luteal, and late luteal phases (N = 21)), in contrast to women measured across the same phases belonging to two menstrual cycles (N = 29). Additional control groups were men (N = 17), postmenopausal women (N = 14), oral contraceptive users (N = 10), and women with an anovulatory cycle (N = 8). Olfactory threshold, odor discrimination, and identification were tested using the “Sniffin Sticks“ test kit. Suprathreshold intensity and hedonic ratings for sweet, salty, sour, and bitter solutions were assessed. One-way ANOVA and ANOVA for repeated measurements was applied in the analysis, along with linear and trigonometric data fitting and linear mixed models. Linear increases in olfactory discrimination, identification, and overall olfactory performance were observed only in women followed across a complete menstrual cycle. Compared to other groups, these women displayed a cyclic pattern characterized by a predilection for sweet solution; reduced distaste for salty and sour solutions; and increased intensity perception of salty, sour, and bitter solutions towards the end of the cycle. These results suggest that a distinct hormonal milieu of a complete menstrual cycle may be affecting both olfactory and gustatory perception.     

The role of the user within the medical device design and development process: medical device manufacturers' perspectives

Background  

Academic literature and international standards bodies suggest that user involvement, via the incorporation of human factors engineering methods within the medical device design and development (MDDD) process, offer many benefits that enable the development of safer and more usable medical devices that are better suited to users' needs. However, little research has been carried out to explore medical device manufacturers' beliefs and attitudes towards user involvement within this process, or indeed what value they believe can be added by doing so.     

The role of paclitaxel in the development and treatment of multidrug resistant cancer cell lines

Paclitaxel (PTX) is used for treatment of wide range of solid tumors, but its efficacy is often limited by appearance of multidrug resistance (MDR). We explored the MDR induced by PTX in human colon cancer DLD1 and glioblastoma U87 cell lines. After confirmation of the cross-resistance to other anticancer agents in newly established DLD1-TxR and U87-TxR, we analyzed the mRNA expression of membrane transporters involved in MDR. The cells had increased levels of mdr1 gene expression, while mrp1 was decreased. Flow cytometry analyzes showed that the accumulation of P-glycoprotein (P-gp) substrates (rhodamine 123 and doxorubicin) was significantly lower in DLD1-TxR and U87-TxR compared to DLD1 and U87, respectively. The significant depletion of gst-π gene expression and glutathione (GSH) concentration was observed in U87-TxR. The analysis of cell cycle kinetics revealed extensive cell death in colon cancer cells that were accumulated in subG0 phase after PTX treatment, while glioblastoma cells died during interphase (G1, S or G2). The secretion of vascular endothelial growth factor (VEGF) was inhibited by single PTX treatment of colon cancer and in continuous treatment of glioblastoma cell lines. In conclusion, continuous PTX treatment caused the over-expression of P-gp and acquisition of MDR in colon cancer and glioblastoma cell lines, while some mechanisms of MDR and tumor progression such as GSH detoxification system and VEGF secretion were suppressed. Hence, the present results implicate that PTX is an important clinical tool for colon cancer and glioblastoma treatment even in the presence of MDR.     

What are the differences between younger and older patients with symptomatic small vessel disease?

Objective

Although typically linked to aging, small vessel disease (SVD) is also observed in younger adult patients, with common vascular risk factors (RF). We aimed to investigate features of SVD occurrence at an early adult age.

Patients and methods

Vascular RF, functional and cognitive status and severity of lesions on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale were analyzed in 200 consecutive patients with cerebral SVD admitted to a tertiary neurological hospital. Variables were compared between younger (35–55 years) and older (>56 years) patients.

Results

In this study, 63 (31.5%) of patients were 55 years or younger. Both age groups had comparable RF profiles, but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9; 95% CI 1.5–5.5; p = 0.002). Younger patients had better functional (OR 1.8; 95% CI 1.3–2.5; p = 0.0001) and cognitive (χ² 13.94; p = 0.0009) status compared to older patients. However, two thirds of younger patients had some degree of cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean 12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0–1.18; p = 0.001). There was a strong correlation in both groups between functional score, cognitive status and ARWMC score (p < 0.0001).

Conclusion

In our dataset, younger patients with SVD shared common vascular RF with older patients. In the group aged ≤55, better functional and cognitive status and less severe MRI changes were noted. However, a substantial number of younger SVD patients presenting with TIA or ischemic stroke had various deficits.     

The Role of Radiation Therapy in Locally Advanced Breast Cancer

Abstract: The purpose of the study was to evaluate and compare the impact of postoperative radiotherapy, whether it was based on the clinical stage at presentation of the disease or on the pathological downstaged disease after initial chemotherapy for non‐inflammatory locally advanced breast cancer (LABC). We retrospectively analyzed locoregional recurrence (LRR), relapse free survival (RFS), overall survival (OS) and disease free survival (DFS) in 55 patients treated for non‐inflammatory LABC with neoadjuvant chemotherapy and surgery with or without radiotherapy. The mean follow‐up was 55 months. The 3‐year OS was 74%, DFS 73% and RFS 87%. The OS and DFS benefit was seen in those receiving radiation, with a mean OS of 89 months versus 68 months (p = 0.029) and mean DFS of 72 months versus 54 months (p = 0.029). Total LRR was 11% (8% versus 17% in the non‐radiotherapy group, p = 0.349) and mean RFS of 95 months versus 86 months (p = 0.164). If the treatment planning was to be based on the original extent of the disease, then all patients in our study should have received adjuvant radiotherapy. Significantly lower OS and DFS without the addition of radiotherapy suggests that indication for radiation treatment should be based on the clinical pre‐chemotherapy stage rather than the pathological post‐chemotherapy stage. Radiation should therefore always be considered regardless of the response to initial chemotherapy for non‐inflammatory LABC.