Diffusion tensor imaging of the hippocampus and verbal memory performance: the RUN DMC study

Background: Cerebral small vessel disease (SVD) and hippocampal atrophy are related to verbal memory failures and may ultimately result in Alzheimer's disease. However, verbal memory failures are often present before structural changes on conventional MRI appear. Changes in microstructural integrity of the hippocampus, which cannot be detected with conventional MRI, may be the underlying pathological substrate. With diffusion tensor imaging (DTI), we investigated the relation between the microstructural integrity of the hippocampus and verbal memory performance in 503 nondemented elderly with SVD. Methods: The Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort study is a prospective cohort study among 503 nondemented elderly with cerebral SVD aged between 50 and 85 years. All participants underwent T1 MPRAGE, fluid‐attenuated inversion recovery, DTI scanning and the Rey Auditory Verbal Learning Test. After manual segmentation of the hippocampi, we calculated the mean diffusivity (MD) and fractional anisotropy in both hippocampi. The relation between memory performance and hippocampal DTI parameters was adjusted for age, sex, education, depressive symptoms, hippocampal, and white‐matter lesions volume and lacunar infarcts. Results: We found inverse relations between hippocampal MD and verbal memory performance (β = ?0.22; P < 0.001), immediate recall (β = ?0.22; P < 0.001), delayed recall (β = ?0.20; P < 0.001), and forgetting rate (β = ?0.13; P = 0.025), most pronounced in participants with a normal hippocampal volume. Conclusion: Microstructural integrity of the hippocampus assessed by DTI is related to verbal memory performance in elderly with SVD, also in participants with an intact appearing hippocampus. Changes in hippocampal microstructure may be an early marker of underlying neurodegenerative disease, before macrostructural (i.e., volumetric) changes occur. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Microvascular and macrovascular complications in type 2 diabetes Ghanaian residents in Ghana and Europe: The RODAM study

AimsTo compare microvascular and macrovascular complication rates among Ghanaians with type 2 diabetes (T2D) living in Ghana and in three European cities (Amsterdam, London and Berlin).MethodsData from the multicenter Research on Obesity and Diabetes among African Migrants (RODAM) study were analyzed. 650 Ghanaian participants with T2D (206 non-migrant and 444 migrants) were included. Logistic regression analyses were used to determine the association between migrant status and microvascular (nephropathy and retinopathy) and macrovascular (coronary artery disease (CAD), peripheral artery disease (PAD) and stroke) complications with adjustment for age, gender, socioeconomic status, alcohol, smoking, physical activity, hypertension, BMI, total-cholesterol, and HbA1c.ResultsMicrovascular and macrovascular complications rates were higher in non-migrant Ghanaians than in migrant Ghanaians (nephropathy 32.0% vs. 19.8%; PAD 11.2% vs. 3.4%; CAD 18.4% vs. 8.3%; and stroke 14.5% vs. 5.6%), except for self-reported retinopathy (11.0% vs. 21.6%). Except nephropathy and stroke, the differences persisted after adjustment for the above-mentioned covariates: PAD (OR 7.48; 95% CI, 2.16–25.90); CAD (2.32; 1.09–4.93); and retinopathy (0.23; 0.07–0.75).ConclusionsExcept retinopathy, the rates of microvascular and macrovascular complications were higher in non-migrant than in migrant Ghanaians with T2D. Conventional cardiovascular risk factors did not explain the differences except for nephropathy and stroke.     

The rationale for and long-term outcome of incomplete axillary staging in elderly women with primary breast cancer

Background

The proportion of elderly women diagnosed with breast cancer is rising. Standard treatment, including axillary staging, is often not given to these patients. This study aimed to investigate reasons to omit any surgical axillary staging or to refrain from completion axillary lymph node dissection (cALND) after positive-sentinel lymph node biopsy (SLNB); so-called “incomplete staging”. Furthermore, the impact of incomplete staging on regional control and survival in patients aged 75 or older was evaluated.

Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction

Left ventricular (LV) remodeling leads to congestive heart failure and is a main determinant of morbidity and mortality following myocardial infarction. Therapeutic options to prevent LV remodeling are limited, which necessitates the exploration of alternative therapeutic targets. Toll-like receptors (TLRs) serve as pattern recognition receptors within the innate immune system. Activation of TLR4 results in an inflammatory response and is involved in extracellular matrix degradation, both key processes of LV remodeling following myocardial infarction. To establish the role of TLR4 in postinfarct LV remodeling, myocardial infarction was induced in wild-type BALB/c mice and TLR4-defective C3H-Tlr4(LPS-d) mice. Without affecting infarct size, TLR4 defectiveness reduced the extent of LV remodeling (end-diastolic volume: 103.7+/-6.8 microL versus 128.5+/-5.7 microL; P<0.01) and preserved systolic function (ejection fraction: 28.2+/-3.1% versus 16.6+/-1.3%; P<0.01), as assessed by MRI. In the noninfarcted area, interstitial fibrosis, and myocardial hypertrophy were reduced in C3H-Tlr4(LPS-d) mice. In the infarcted area, however, collagen density was increased, which was accompanied by fewer macrophages, reduced inflammation regulating cytokine expression levels (interleukin [IL]-1alpha, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, tumor necrosis factor-alpha, interferon-gamma, granulocyte/macrophage colony-stimulating factor), and reduced matrix metalloproteinase-2 (4684+/-515 versus 7573+/-611; P=0.002) and matrix metalloproteinase-9 activity (76.0+/-14.3 versus 168.0+/-36.2; P=0.027). These data provide direct evidence for a causal role of TLR4 in postinfarct maladaptive LV remodeling, probably via inflammatory cytokine production and matrix degradation. TLR4 may therefore constitute a novel target in the treatment of ischemic heart failure.     

Interaction of acute lymphopblastic leukemia cells with C-type lectins DC-SIGN and L-SIGN

The C-type lectins DC-SIGN (CD209) and L-SIGN (CD299) recognize defined carbohydrates expressed on pathogens and cells. Those lectins are expressed on dendritic cells (DC) and/or on liver-sinusoidal endothelial cells. Both cell types modulate immune responses. In acute lymphoblastic leukemia (ALL), aberrant glycosylation of blast cells can alter their interaction with the C-type lectins DC-SIGN and L-SIGN, thereby affecting their immunological elimination. We investigated whether recombinant DC-SIGN and L-SIGN bind to blood or bone marrow cells from B- and T-ALL patients and compared that with binding of peripheral blood lymphocytes from healthy donors. It was found that increased binding of ALL cells to DC-SIGN and L-SIGN was observed compared to cells from healthy donors. Furthermore, L-SIGN bound a higher percentage of leukemic and normal cells than DC-SIGN. B-ALL bone marrow cells showed the highest binding to L-SIGN. DC-SIGN bound equally well to B-ALL and T-ALL cells. Within ALL subtypes, DC-SIGN binding was higher with mature T-ALL. Interestingly, our data demonstrate that increased binding of DC-SIGN and L-SIGN to peripheral leukemic cells from B-ALL patients is associated with poor survival. These data demonstrate that high binding of B-ALL peripheral blood cells to DC-SIGN and L-SIGN correlates with poor prognosis. Apparently, when B-ALL cells enter the blood circulation and are able to interact with DC-SIGN and L-SIGN the immune response is shifted toward tolerance. Additional studies are necessary to ascertain the possible role of these results in terms of disease pathogenesis and their potential as target to eradicate leukemic cells.     

Cross-cultural validation of the Itch Man Scale in pediatric burn survivors in a South African setting

IntroductionPruritus or itch is a common symptom after burn injuries. The Itch Man Scale has been recommended to assess itch severity in children. The aim of this prospective observational study was to perform a cross-cultural validation of the Itch Man Scale by comparing it with the Numeric Rating Scale (NRS) and the Toronto Pediatric Itch Scale.MethodAt Red Cross War Memorial Children’s Hospital in Cape Town, South Africa, parents of pediatric burn patients assessed their child’s itch with the Itch Man Scale, NRS and Toronto Pediatric Itch Scale. Children from the age of 6 years also rated the Itch Man Scale and NRS themselves. The Spearman rank order correlation between the different scales was calculated to determine construct validity.ResultsOver a two-month period, 255 pediatric burn survivors with a median age of 2.3 years (IQR 1.4–4.0) were included; 35 of them were aged 6–13 years. Parents’ Itch Man Scale ratings correlated significantly with parents’ NRS ratings (0.82, 95% CI 0.78–0.86) and with the Toronto Pediatric Itch Scale of the parent (0.80, 95% CI 0.75–0.84). The correlation between the older children’s Itch Man Scale rating and those of their parents was 0.66 (95% CI 0.37–0.83).ConclusionWe concluded that the Itch Man Scale has promising validity and is a user-friendly tool to use in clinical practice to determine the itch intensity in children younger than 13 years in a South African setting.     

A 5-Year Evaluation of the Implementation of Triple Diagnostics for Early Detection of Severe Necrotizing Soft Tissue Disease: A Single-Center Cohort Study

World Journal of Surgery - The standardized approach with triple diagnostics (surgical exploration with visual inspection, microbiological and histological examination) has been proposed as the...     

What are the essential features of resilience for informal caregivers of people living with dementia? A Delphi consensus examination

Objectives: Few studies have examined what might enable or prevent resilience in carers of people with dementia. Consequently, there are limited insights as to how it should be understood, defined and measured. This creates challenges for research, and also practice in terms of how it might best be promoted. This study aimed to address these limitations and add new insights, identifying the essential features of resilience in dementia caregiving.

Methods: A Delphi consensus study was conducted, consulting a multi-disciplinary panel of informal caregivers and experts with relevant professional expertise. Panellists rated the relevance of various statements addressing essential components of resilience; ‘adversity’ and ‘successful caregiving’ on a 5-point Likert scale. Based on the median and Inter Quartile Range, the most relevant statements with moderate consensus were proposed in Round 2 in which panellists selected up to five statements in order of importance.

Results: Moderate consensus was reached for all statements after two rounds. Patients’ behavioural problems and feeling competent as a caregiver were selected by both caregivers and professionals as essential resilience features. Caregivers also emphasized the importance of social support, the quality of the relationship with their relative and enjoying spending time together. Professionals considered coping skills, experiencing positive aspects of caregiving, and a good quality of life of caregivers most relevant.

Conclusion: The essential elements of resilience selected from multiple stakeholder perspectives can be used to select appropriate outcomes for intervention studies and give guidance to policy to support caregivers more effectively and better tailored to their needs.     

The Effect of A Geriatric Assessment on Treatment Decisions for Patients with Lung Cancer

Background

Decision-making for older patients with lung cancer can be complex and challenging. A geriatric assessment (GA) may be helpful and is increasingly being used since 2005 when SIOG advised to incorporate this in standard work-up for the elderly with cancer. Our aim was to evaluate the value of a geriatric assessment in decision-making for patients with lung cancer.

Methods

Between January 2014 and April 2016, data on patients with lung cancer from two teaching hospitals in the Netherlands were entered in a prospective database. Outcome of geriatric assessment, non-oncologic interventions, and suggested adaptations of oncologic treatment proposals were evaluated.

Results

83 patients (median age 79 years) were analyzed with a geriatric assessment, of which 59% were treated with a curative intent. Half of the patients were classified as ECOG PS 0 or 1. The majority of the patients (78%) suffered from geriatric impairments and 43% (n?=?35) of the patients suffered from three or more geriatric impairments (out of eight analyzed domains). Nutritional status was most frequently impaired (52%). Previously undiagnosed impairments were identified in 58% of the patients, and non-oncologic interventions were advised for 43%. For 33% of patients, adaptations of the oncologic treatment were proposed. Patients with higher number of geriatric impairments more often were advised a reduced or less intensive treatment (p?<?0.001).

Conclusion

A geriatric assessment uncovers previously unknown health impairments and provides important guidance for tailored treatment decisions in patients with lung cancer. More research on GA-stratified treatment decisions is needed.

     

Victims' influence on intimate partner violence revictimization: a systematic review of prospective evidence

Foa, Cascardi, Zoellner and Feeny developed two models of women's influence on intimate partner violence (IPV), which integrate victim-related variables associated with the cessation or continuation of partner violence (i.e., repeat IPV). One of the models focuses on psychological factors while the other centers on environmental factors. Central to both models are three key factors: partner violence; psychological difficulties; and resilience. Despite the appeal of these models, empirical, prospective research that specifically tests these models appears to be lacking. This article describes a systematic review of the available literature that examines the prospective link between the three key factors of the models and the risk of IPV revictimization. A synthesis of 15 studies reveals that Foa et al.'s models of revictimization are partly supported by prior prospective research. It is beyond doubt that the key factor partner violence (involving the severity and frequency of prior IPV) is a strong predictor for IPV revictimization; the evidence regarding victims' psychological difficulties and resilience is more mixed. Findings are discussed in terms of implications for practice and research and might enable practitioners to help victims to take control of their situations and to contribute to their empowerment. The importance of future prospective research into dynamic, victim-related variables is emphasized, in order to further support Foa's models of victims' influence on IPV revictimization.