Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer

Background

Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports.

Materials and Methods

Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms.

Results

In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36–3.45) and anxiety (RR, 1.48; 95% CI, 1.05–2.09).

Conclusion

Oncologists frequently underestimate patients’ depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms.

Implications for Practice

In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients’ mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients’ psychological health.

     

Is glial heme oxygenase-1 suppression in neurodegenerative disorders permissive for neural repair?

<正>‘Core’neuropathology of degenerative central nervous system(CNS)disorders The common human neurodegenerative disorders(Alzheimer’s disease(AD),Parkinson’s disease(PD),amyotrophic lateral sclerosis,etc.)vary with respect to risk factors,ages of onset,sex predilections,neuraxial regions affected,hallmark cellular inclusions,behavioral and neurological symptoms,and responses     

Topological analyses in APP/PS1 mice reveal that astrocytes do not migrate to amyloid-β plaques

Although the clustering of GFAP immunopositive astrocytes around amyloid-β plaques in Alzheimer’s disease has led to the widespread assumption that plaques attract astrocytes, recent studies suggest that astrocytes stay put in injury. Here we reexamine astrocyte migration to plaques, using quantitative spatial analysis and computer modeling to investigate the topology of astrocytes in 3D images obtained by two-photon microscopy of living APP/PS1 mice and WT littermates. In WT mice, cortical astrocyte topology fits a model in which a liquid of hard spheres exclude each other in a confined space. Plaques do not disturb this arrangement except at very large plaque loads, but, locally, cause subtle outward shifts of the astrocytes located in three tiers around plaques. These data suggest that astrocytes respond to plaque-induced neuropil injury primarily by changing phenotype, and hence function, rather than location.The role of astrocytes in amyloid-β deposition during Alzheimer’s disease—whether they prevent, potentiate, or have no effect on plaque formation—remains unknown. The peer-reviewed literature indicates that it is widely believed that amyloid-β plaques attract astrocytes, with statements such as “astrocytes migrate to amyloid-β plaques,” “amyloid-β plaques recruit astrocytes,” and variations thereof frequently appearing. The idea that astrocytes are attracted to plaques is an extension of the notion that astrocytes migrate to zones of injury (1, 2) and is mostly based on the immunohistochemical observation that amyloid-β deposits are typically surrounded by concentric rings of “reactive astrocytes,” defined by increased GFAP immunoreactivity and hypertrophy. However, recent studies question the capacity of astrocytes to move (3, 4). These suggest instead that astrocytes may be restricted to their birthplace (3), which in the neocortex seems to be within neuronal columns derived from radial glia (5). Recent stereological assessments of astrocytes in Alzheimer’s disease suggest that their most prominent change is phenotypic (i.e., GFAP immunoreactivity and hypertrophy) rather than proliferative (6). Thus, doubts have risen over the recruitment of astrocytes by plaques.Using the APPSwe/PS1dE9 (APP/PS1) double-transgenic mouse model of Alzheimer’s disease, we revisited the idea that astrocytes migrate to plaques. Our approach improved on the traditional GFAP immunohistochemical analysis postmortem in three ways. First, the analyses were performed in 3D reconstructions of images captured in vivo through cranial windows by two-photon microscopy. These materials are superior to sectioned specimens from fixed brains because they preserve true spatial relationships in 3D to great depths (up to 200 μm from the cortical surface), providing accurate positional information for each astrocyte. Second, astrocytes were labeled with sulforhodamine 101 (SR101), a selective fluorescent marker of reactive and nonreactive astrocytes (7), thus avoiding the bias of identifying only a subset of astrocytes as with GFAP. Third, astrocyte and plaque interactions were examined with two mathematical objects: the pair-correlation function g(r) and the characteristic length (L_C) of Voronoi cells. These combine global and plaque-centered perspectives and allow for quantitative comparisons to be made. The g(r) function was used to assess astrocyte topology, and we examined the effect of plaques on several tiers of astrocytes using L_C, a very sensitive approach that reveals changes in object position from the redistribution of astrocyte-associated domains approximated by Voronoi tessellation.Finally, we used simulations to help interpret astrocyte-to-astrocyte and astrocyte-to-plaque interactions and to investigate the effect on astrocyte topology of plaque loads in the upper limit of what could be present in older human patients.Using a statistical physics approach, we found that astrocytes resemble a liquid of objects of different sizes contained in a constant volume. This arrangement is globally unaltered by plaques except at the heaviest plaque loads.     

Where in-vivo imaging meets cytoarchitectonics: the relationship between cortical thickness and neuronal density measured with high-resolution [18F]flumazenil-PET

MRI-based measurements of surface cortical thickness (SCT) have become a sensitive tool to quantify changes in cortical morphology. When comparing SCT to histological cortical thickness maps, a good correspondence can be found for many but not all human brain areas. Discrepancies especially arise in the sensory motor cortex, where histological cortical thickness is high, but SCT is very low. The aim of this study was to determine whether the relationship between cortical thickness and neuronal density is the same for different cytoarchitectonic areas throughout homo- and heterotypical isocortex. We assessed this relationship using high-resolution [(18)F]-labelled flumazenil (FMZ) PET and SCT-mapping. FMZ binds to the benzodiazepine GABA(A) receptor complex which is localized on axo-dendritic synapses, with a cortical distribution closely following the local density of neurons. SCT and voxelwise FMZ binding potential (BP(ND)) were assessed in ten healthy subjects. After partial volume correction, two subsets with a differential relationship between SCT and BP(ND) were identified: a fronto-parietal homotypical subset where neuronal density is relatively constant and mainly independent of SCT, and a subset comprising heterotypical and mainly temporal and occipital homotypical regions where neuronal density is negatively correlated with SCT. This is the first in-vivo study demonstrating a differential relationship between SCT, neuronal density and cytoarchitectonics in humans. These findings are of direct relevance for the correct interpretation of SCT-based morphometry studies, in that there is no simple relationship between apparent cortical thickness and neuronal density, here attributed to FMZ binding, holding for all cortical regions.     

Injury and repair of tendons and ligaments

Tendons and ligaments are fibrous connective tissues that facilitate stability and motion of joints. Significant dysfunction and disability may result from suboptimal healing of tendon and ligament injuries. Extensive research continues to further understand the complex healing pathways that are involved when these structures are damaged. The combination of advances in tissue engineering, surgery, and rehabilitation will provide new pathways of improving tendon and ligament healing.     

Cefoxitin, a Semisynthetic Cephamycin Antibiotic: Susceptibility Studies

Cefoxitin, 3-carbamoyloxymethyl-7-alpha-methoxy-7-[2-(2-thienyl)acetamido]-3-cephem-4- carboxylic acid, is a new semisynthetic cephamycin with broad antibacterial activity. It is highly active against gram-negative microorganisms including indole-positive Proteus and Serratia strains, which are ordinarily reistant to the cephalosporins. Cefoxitin is also highly active against many strains of Escherichia coli and Proteus mirabilis which are resistant to the cephalosporins. Furthermore, E. coli and Klebsiella strains which are susceptible to the cephalosporins are generally more susceptible to the cephamycin analog. The susceptibility of the gram-positive bacteria falls well within the effective range of the antibiotic for gram-negative organisms, but cefoxitin is less active than cephalothin or cephaloridine. As is the case with the cephalosporins, strains of Pseudomonas and group D streptococci are resistant to cefoxitin. Changes in pH, inoculum density, and growth medium have no significant effect on the activity of the antibiotic.     

Human tau increases amyloid β plaque size but not amyloid β‐mediated synapse loss in a novel mouse model of Alzheimer's disease

Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ‐plaques and synapse loss, with rTg21221 mice, which overexpress wild‐type human tau. When compared to the APP/PS1 mice without human tau, the cross‐sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque‐associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild‐type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque‐associated synapse loss.