Androgen deprivation increases frontopolar cortical thickness in prostate cancer patients: an effect of early neurodegeneration?

Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT leads to altered testosterone levels that may affect brain morphology as well as cognition. Considering the reliability of cortical thickness (CT) as a marker of cognitive and brain changes, e.g., in Alzheimer's disease, we assessed the impacts of ADT on CT and working memory. Thirty men with non-metastatic prostate cancer receiving ADT and 32 patients not receiving ADT (controls or CON), matched in age and years of education, participated in N-back task and quality-of-life (QoL) assessments as well as brain imaging at baseline and prospectively at 6 months. Imaging data were processed with published routines to estimate CT and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. ADT and CON did not differ in N-back performance or QoL across time points. Relative to CON, patients receiving ADT showed significantly higher frontopolar cortex (FPC) CT at 6-month follow-up vs. baseline. Follow-up vs. baseline FPC CT change correlated negatively with changes in 2-back correct response rate and in testosterone levels across all participants. In mediation analysis, FPC CT change mediated the association between testosterone level change and 2-back accuracy rate change. Increases in FPC CT following 6 months of ADT may reflect early neurodegenerative changes in response to androgen deprivation. While no significant impact on working memory or QoL was observed over 6 months, further research of longer duration of treatment is warranted to unravel the full spectrum of cognitive and neural consequences of ADT in prostate cancer patients.

Ligand-gated ion channels as potential biomarkers for ADT-mediated cognitive decline in prostate cancer patients.

Men with prostate cancer are at increased risk of developing cognitive decline by the use of second-generation androgen signaling inhibitors. To date, reliable and sensitive biomarkers that could distinguish men at high risk of cognitive dysfunction under androgen deprivation therapy (ADT) have not been characterized. We used high-throughput transcriptional profiling utilizing human prostate cancer cell culture models mimicking ADT, biomarker selection using minimal common oncology data elements-cytoscape, and bioinformatic analyses employing Advaita® iPathwayGuide and DisGeNET for identification of disease-related gene associations. Validation analysis of genes was performed on brain neuronal and glial cells by quantitative real-time polymerase chain reaction assay. Our systematic analysis of androgen deprivation-associated genes involved multiple biological processes, including neuroactive ligand-receptor interaction, axon guidance, cytokine-cytokine receptor interaction, and metabolic and cancer signaling pathways. Genes associated with neuroreceptor ligand interaction, including gamma-aminobutyric acid (GABA) A and B receptors and nuclear core proteins, were identified as top upstream regulators. Functional enrichment and protein-protein interaction network analysis highlighted the role of ligand-gated ion channels (LGICs) and their receptors in cognitive dysfunction. Gene-disease association assigned forgetfulness, intellectual disability, visuospatial deficit, bipolar disorder, and other neurocognitive impairment with upregulation of type-1 angiotensin II receptor, brain-derived neurotrophic factor, GABA type B receptor subunit 2 (GABBR2), GABRA3, GABRA5, GABRB1, glycine receptor beta, glutamate ionotropic receptor N-methyl-D-aspartate receptor (NMDA) type subunit 1, glutamate ionotropic receptor NMDA type subunit 2D, 5-hydroxytryptamine receptor 1D, interferon beta 1, and nuclear receptor subfamily 3 group C member 1 as top differentially expressed genes. Validation studies of brain glial cells, neurons, and patients on ADT demonstrated the association of these genes with cognitive decline. Our findings highlight LGICs as potential biomarkers for ADT-mediated cognitive decline. Further validation of these biomarkers may lead to future practical clinical use.

Does ADT Influence the Risk of Suicidal Ideation among US Veteran Prostate Cancer Patients Pre-Exposed to PTSD?

Post-traumatic stress disorder (PTSD) is defined as a mental health disease that has a high probability of developing among individuals who have experienced traumatic events [...].

Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I.

BACKGROUND: An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality of life (QOL). We compared QOL in patients enrolled to SWOG S1400I, a substudy of the LungMAP biomarker-driven master protocol. METHODS: SWOG S1400I was a randomized phase III trial comparing nivolumab plus ipilimumab vs nivolumab for treatment of immunotherapy-naïve disease in advanced squamous cell lung cancer. The primary endpoint was the MD Anderson Symptom Inventory-Lung Cancer severity score at week 7 and week 13 with a target difference of 1.0 points, assessed using multivariable linear regression. A composite risk model for progression-free and overall survival was derived using best-subset selection. RESULTS: Among 158 evaluable patients, median age was 67.6 years and most were male (66.5%). The adjusted MD Anderson Symptom Inventory-Lung Cancer severity score was 0.04 points (95% confidence interval [CI] = -0.44 to 0.51 points; P = .89) at week 7 and 0.12 points (95% CI = -0.41 to 0.65; P = .66) at week 13. A composite risk model showed that patients with high levels of appetite loss and shortness of breath had a threefold increased risk of progression or death (hazard ratio [HR] = 3.06, 95% CI = 1.88 to 4.98; P < .001) and that those with high levels of both appetite loss and work limitations had a fivefold increased risk of death (HR = 5.60, 95% CI = 3.27 to 9.57; P < .001)-compared with those with neither risk category. CONCLUSIONS: We found no evidence of a benefit of ipilimumab added to nivolumab compared with nivolumab alone for QOL in S1400I. A risk model identified patients at high risk of poor survival, demonstrating the prognostic relevance of baseline patient-reported outcomes even in those with previously treated advanced cancer.

Effects of androgen deprivation on white matter integrity and processing speed in prostate cancer patients.

Studies have associated chemotherapy-elicited changes in cognitive function with impaired white matter integrity in cancer patients. Androgen deprivation therapy (ADT) may lead to cognitive deficits in prostate cancer patients; however, whether ADT influences white matter integrity has never been investigated. In a prospective study, 15 men with non-metastatic prostate cancer receiving ADT and 15 not receiving ADT (controls or CON), comparable in age and years of education, participated in N-back task, flankers' task, and quality-of-life (QoL) assessments. All participants underwent diffusion tensor imaging of the brain at baseline and at 6 months. Imaging data were processed with published routines. The results of a paired t-test of 6-month follow-up vs. baseline were evaluated at a corrected threshold for the whole brain each in ADT and CON. ADT patients showed significantly worse 1-back accuracy during follow-up, but the two groups did not differ in 2-back accuracy, 1- or 2-back reaction time (RT), flankers' task RT or QoL across time points. In ADT, significantly reduced fractional anisotropy (FA) was noted in the corpus callosum, forceps minor/anterior thalamic radiation, superior and posterior corona radiata. The differences in FA correlated significantly with changes in 2-back and flankers' task RT. No significant FA changes were noted during follow-up in CON. Six-month ADT affects white matter integrity, and the deficits were associated with slower processing speed. These findings add to the literature supporting the deleterious effects of androgen deprivation on the brain and cognition in prostate cancer patients.

Brief Report: Implementation of a Universal Prescreening Protocol to Increase Recruitment to Lung Cancer Studies at a Veterans Affairs Cancer Center.

Introduction: The oncology clinical trial recruitment process is time, labor, and resource intensive, and poor accrual rates are common. We describe the VA Connecticut Cancer Center experience of implementing a standardized, universal prescreening protocol and its impact on thoracic oncology research recruitment. Methods: Research coordinators prescreened potentially eligible patients with confirmed or suspected cancer from multiple clinical sources and entered relevant patient and research study information into a centralized electronic database. The database provided real-time lists of potential studies for each patient. This enabled the research team to alert the patient's oncologist in advance of clinic visits and to prepare documents needed for enrollment. Clinicians could ensure sufficient time and attention in clinic to the informed consent process, therefore maximizing enrollment opportunities. Patients were also monitored on waitlists for future studies. Results: From March 2017 to December 2020, a total of 1518 patients with lung nodules and suspected or confirmed lung cancers were prescreened. Of these, 379 patients were enrolled to a study, 103 patients declined participation, and 639 were monitored for future studies. Our prescreening protocol identified all new patients with lung cancer who were ultimately added to the cancer registry. We found a substantial increase in study enrollment after prescreening implementation. Conclusions: Universal prescreening was associated with improved patient enrollment to thoracic oncology studies. The protocol was integral in our VA becoming the top accruing VA site for National Cancer Institute's National Clinical Trials Network studies for 2019 to 2021.

Hypothalamic connectivities predict individual differences in ADT-elicited changes in working memory and quality of life in prostate cancer patients.

Androgen deprivation therapy (ADT) has been associated with adverse effects on cognition. However, we currently lack understanding of the neurobiology and prognostic markers of these effects. Given that ADT acts via the hypothalamus-pituitary-gonadal axis, we assessed whether baseline hypothalamic resting state functional connectivity (rsFC) could predict changes in working memory and quality of life in prostate cancer patients following androgen deprivation. In a prospective observational study, 28 men with non-metastatic prostate cancer receiving ADT and 38 patients not receiving ADT (controls), matched in age, years of education and Montreal Cognitive Assessment score, participated in brain imaging at baseline, and N-back task and quality-of-life (QoL) assessments at baseline and at 6 months follow-up. Imaging data were processed with published routines and evaluated at a corrected threshold. ADT and control groups did not differ in N-back performance or QoL across time points. In ADT, the changes in 0-back correct response rate (follow-up-baseline) were correlated with baseline hypothalamus-precentral gyrus rsFC; the changes in 1-back correct response rate and reaction time were each correlated with hypothalamus-middle frontal gyrus and superior parietal lobule rsFC. The changes in physical well-being subscore of QoL were correlated with baseline hypothalamus-anterior cingulate and cuneus rsFC. The hypothalamus rsFCs predicted N-back and QoL change with an area under the receiver operating characteristic curve of 0.93 and 0.73, respectively. Baseline hypothalamus-frontoparietal and salience network rsFC's predict inter-subject variations in the changes in working-memory and QoL following 6 months of ADT. Whether and how hypothalamic rsFCs may predict the cognitive and QoL effects with longer-term ADT remain to be investigated.

Aggressive End-of-Life Care in the Veterans Health Administration versus Fee-for-Service Medicare among Patients with Advanced Lung Cancer.

Background: Unlike fee-for-service Medicare, the Veterans Health Administration (VHA) allows for the provision of concurrent care, incorporating cancer treatment while in hospice. Methods: We compared trends of aggressive care at end of life between Medicare and VHA decedents with advanced nonsmall cell lung cancer from 2006 to 2012, and the relation between regional level end-of-life care between Medicare and VHA beneficiaries. Results: Among 18,371 Veterans and 25,283 Medicare beneficiaries, aggressive care at end of life decreased 15% in VHA and 4% in SEER (Surveillance, Epidemiology, and End Results)-Medicare (p < 0.001). Hospice use significantly increased within both cohorts (VHA 28%-41%; SM 60%-73%, p < 0.001). Veterans receiving care in regions with higher hospice admissions among Medicare beneficiaries were significantly less likely to receive aggressive care at end of life (adjusted odds ratio: 0.13, 95% confidence interval: 0.08-0.23, p < 0.001). Conclusions: Patients receiving lung cancer care in the VHA had a greater decline in aggressive care at end of life, perhaps due to increasing concurrent care availability.

The effects of androgen deprivation on working memory and quality of life in prostate cancer patients: The roles of hypothalamic connectivity.

BACKGROUND: Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT alters testosterone levels via its action on the hypothalamus-pituitary-gonadal axis and may influence hypothalamic functions. Given the wide regional connectivity of the hypothalamus and its role in regulating cognition and behavior, we assessed the effects of ADT on hypothalamic resting state functional connectivity (rsFC) and their cognitive and clinical correlates. METHODS: In a prospective observational study, 22 men with nonmetastatic prostate cancer receiving ADT and 28 patients not receiving ADT (controls), matched in age, years of education, and Montreal Cognitive Assessment score, participated in N-back task and quality of life (QoL) assessments and brain imaging at baseline and at 6 months. Imaging data were processed with published routines and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. RESULTS: ADT and control groups did not differ in N-back performance or QoL across time points. Relative to controls, patients receiving ADT showed significantly higher hypothalamus-right mid-cingulate cortex (MCC) and precentral gyrus (PCG) rsFC during follow-up versus baseline. Further, the changes in MCC and PCG rsFC were correlated positively with the change in QoL score and 0-back correct response rate, respectively, in patients with undergoing ADT. CONCLUSION: Six-month ADT affects hypothalamic functional connectivity with brain regions critical to cognitive motor and affective functions. Elevated hypothalamic MCC and PCG connectivity likely serve to functionally compensate for the effects of ADT and sustain attention and overall QoL. The longer-term effects of ADT remain to be investigated.

Catechol-O-Methyltransferase Gene Polymorphisms and the Risk of Chemotherapy-Induced Prospective Memory Impairment in Breast Cancer Patients with Varying Tumor Hormonal Receptor Expression.

BACKGROUND Existing research evidence indicates that breast cancer patients have different degrees of cognitive dysfunction after chemotherapy, and polymorphisms in 3 genes (catechol-O-methyltransferase, COMT; apolipoprotein E, APOE; and brain-derived neurotrophic factor, BDNF) have been associated with cognitive impairment. However, the role of these 3 gene polymorphisms in modulating cognitive impairment in breast cancer survivors with varying hormonal receptor expression is not clear at present. To explore the effects of genetic polymorphisms in BDNF, APOE, and COMT on the regulation of prospective memory impairments induced by chemotherapy in breast cancer patients with various expression levels of estrogen receptor (ER) and progesterone receptor (PR). MATERIAL AND METHODS A total of 232 patients with breast cancer (113 with ER-/PR- and 119 with ER+/PR+) were evaluated before and after chemotherapy for cognitive function, including prospective memory. Following previously published sequencing procedures, we assessed 6 single-nucleotide polymorphisms (SNPs), including BDNF (rs6265), APOE (rs429358, rs7412), and COMT (rs165599, rs4680, rs737865). RESULTS The patients showed poorer prospective memory scores after chemotherapy than before chemotherapy. Furthermore, the ER-/PR- group showed poorer event-based prospective memory (EBPM) scores than the ER+/PR+ group (z=-7.831, p<0.01) after chemotherapy. The patients with the COMT rs737865G/G genotype, compared with those with the A/A and A/G genotypes, showed a linear EBPM performance (ß=1.499, 95% confidence interval (CI)=1.017~2.211) and were less likely to have memory impairment. In contrast, APOE and BDNF polymorphisms did not influence cognitive performance. CONCLUSIONS The patterns of hormonal receptor expression may be related to prospective memory impairments induced by chemotherapy in breast cancer patients. Furthermore, the COMT polymorphism (rs737865) was linearly related to the extent of deficits in EBPM and may represent a potential genetic marker of risk for cognitive deficits triggered by chemotherapy in patients with breast cancer.

Concurrent Hospice Care and Cancer-Directed Treatment for Advanced Lung Cancer and Receipt of Aggressive Care at the End of Life in the Veteran's Health Administration.

Background: Aggressive care at the end of life (EOL) is a persistent issue for patients with stage IV nonsmall cell lung cancer (NSCLC). We evaluated the use of concurrent care (CC) with hospice care and cancer-directed treatment simultaneously within the Veteran's Health Administration (VHA) and aggressive care at the EOL. Objective: To determine whether VHA facility-level CC is associated with changes in aggressive care at the EOL. Design/Setting: Veterans with stage IV NSCLC who died between 2006 and 2012 and received lung cancer care within the VHA. Measurements: The primary outcome was aggressive care at EOL (i.e., hospital admissions, chemotherapy, and intensive care unit) within the last month of life. To compare aggressive care across VHA facilities, we used a random intercept multilevel logistic regression model to examine the association between facility-level CC within each study year (<10%, 10% to 19%, and ≥20%) and aggressive care at the EOL among the decedents as a binary outcome. Results: In total, 18,371 veterans with NSCLC at 154 VHA facilities were identified. Facilities delivering CC for ≥20% of veterans (high CC) increased from 20.0% in 2006 to 43.2% in 2012 (p < 0.001). Overall, hospice care significantly increased and aggressive care at EOL decreased over the study period. However, facility-level CC adoption was not associated with any difference in aggressive care at EOL (adjusted odds ratio high CC vs. low CC: 0.91 [95% CI, 0.79 to 1.05], p = 0.21). Conclusions: Although the VHA adoption of CC increased hospice use among patients with NSCLC, additional measures may be needed to decrease aggressive care at the EOL.

Androgen Deprivation Therapy and Cognitive Function in Prostate Cancer.

PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) is widely used in prostate cancer. Interest in assessing how ADT impacts cognition is growing. RECENT FINDINGS: Studies in animals and humans suggest that androgens may affect cognitive function. However, extant studies utilizing common neurocognitive tests have not consistently demonstrated ADT-induced cognitive impairment. Retrospective analyses investigating the association between ADT and risk of dementia in large electronic patient databases have also produced conflicting results. There is only limited data on ADT-induced changes in the brain as detected by functional imaging. It remains unclear whether cognitive deficits can occur in a patient undergoing ADT. Commonly used neurocognitive tests may not be optimal for detection of more subtle but clinically relevant cognitive impairment. While large electronic patient databases are attractive sources of information, their heterogeneity, complexity, and potential reporting biases can be a challenge. Better tools are needed to assess the cognitive impact of ADT prospectively.

The dorsolateral prefrontal cortex is selectively involved in chemotherapy-related cognitive impairment in breast cancer patients with different hormone receptor expression.

To investigate chemotherapy-related cognitive impairment (CRCI) in breast cancer patients with different hormone receptor (HR) expression and its neural mechanisms, forty BC patient were enrolled in this study and were divided into two groups. HR+ group was composed of twenty-one patients with Estrogen Receptor (ER)+/Progesterone Receptor (PR) +, HR- group included nineteen patients with ER-/PR-. A battery of neuropsychological tests and resting-state functional magnetic resonance imaging (rs-fMRI) examinations were administered to all subjects. The functional connectivity of the dorsolateral prefrontal cortex (DLPFC) of the patients was calculated from the resting-state fMRI data, and the correlation between the DLPFC's connectivity and the neuropsychological test was analyzed. The functional connectivity (FC) of the left dorsolateral prefrontal cortex (DLPFC) with the left precuneus (PCU), the right DLPFC with the right precuneus and the right superior frontal gyrus (SFG) of the HR- group were significantly increased compared to the HR+ group. Meanwhile, a significant positive correlation was found between the post-chemotherapy prospective memory (PM) score and the functional connectivity of the left DLPFC with the left precuneus in the HR- group. These findings suggest that different hormone receptor expression in patients with breast cancer may be associated with CRCI and provide evidence that the DLPFC functional connectivity (FC) strength may be selectively involved in CRCI in HR- group breast cancer patients, especially in regard to the subjective prospective memory.

Prolonged Response to Pembrolizumab in Spindle Cell Squamous Cell Carcinoma Metastatic to the Central Nervous System.

BACKGROUND: Cutaneous squamous cell carcinoma is a common type of skin cancer, with aggressive metastatic or locally advanced disease representing an uncommon minority of presentations. Emerging data have supported the Food and Drug Administration approval of the anti-PD1 human monoclonal antibody cemiplimab in select patients with advanced disease. However, there is limited data regarding durability of effect and generalizability of anti-PD1 effectiveness across therapies. Additionally, information regarding applicability of these regimens to the rare spindle cell variant and to central nervous system metastases for cutaneous squamous cell carcinoma is unfortunately limited. CASE PRESENTATION: A 72-year-old gentleman presented with facial neurological deficits and a dermal nodule and was diagnosed with spindle cell squamous cell carcinoma with perineural invasion. His course was notable for early intracranial metastasis with progressive neurological deficits despite recurrent radiation therapy with intermittent response. When progressive left-sided weakness prompted imaging evaluation that was concerning for disease recurrence after exhaustion of radiation therapy options, the patient was started on systemic therapy with the anti-PD-1 monoclonal antibody treatment prior to the approval of cemiplimab. Pembrolizumab was chosen due to the fact that the patient was ineligible for clinical trials and for its every 21-day dosing. With this treatment, he has achieved a durable clinical response, resulting in near resolution of neurological deficits and more than a year of progression-free survival to date, despite aggressive intracranial disease. CONCLUSIONS: This case suggests that anti-PD-1 therapy with pembrolizumab may represent an effective and well-tolerated treatment for patients with metastatic spindle cell squamous cell carcinoma including patients with metastatic disease to the central nervous system.

Depression involved in self-reported prospective memory problems in survivors of breast cancer who have received chemotherapy.

To investigate the relationship between depression and the self-reported prospective memory (SPM) problems in breast cancer survivors who have received chemotherapy.Sixty-three breast cancer patients were administered with self-rating depression scale (SDS) and the prospective memory questionnaire as part of extensive neuropsychological assessments before and after chemotherapy. The performance of SDS and SPM were compared, with the level of significance set at P < .05.Compared with the group before chemotherapy, there is a significant difference on the SPM score (t = 6.069, P = .000) in breast cancer patients after chemotherapy. Further, there is also a significant difference on the SPM score (t = -4.348, P = .000) between the patients with and without depression group after chemotherapy.The present result indicated that the depression in breast cancer survivors after chemotherapy may be involved in their chemotherapy-induced SPM impairment.

Transcriptome­wide piRNA profiling in human gastric cancer.

Piwi­interacting RNAs (piRNAs) comprise the largest class of non­coding RNAs. They represent a molecular feature shared by all non­aging biological systems, including germline and somatic cancer stem cells, which display an indefinite capacity of renewal and proliferation and are potentially immortal. They have been identified in animal stomachs, but their relationship with human gastric cancers remains largely unclear. The present study aimed to identify the piRNAs associated with human gastric cancers across the whole transcriptome. Fresh tumor tissues and adjacent non­tumorous tissues from stomachs were examined using a piRNA microarray (23,677 piRNAs) that was then validated by qPCR. The differential expression of piRNAs between cases and controls was analyzed. The transposable elements (TEs) that are potentially targeted by the risk piRNAs were searched. The expression of the nearest genes that are complementary to the sequences of the piRNAs was examined in the stomach tissue. The regulatory effects of genome­wide significant and replicated cancer­risk DNA variants on the piRNA expression in stomach were tested. Based on the findings, we identified a total of 8,759 piRNAs in human stomachs. Of all, 50 were significantly (P<0.05) and differentially (>2­fold change) expressed between the cases and controls, and 64.7% of the protein­coding genes potentially regulated by the gastric cancer­associated piRNAs were expressed in the human stomach. The expression of many cancer­associated piRNAs was correlated with the genome­wide and replicated cancer­risk SNPs. In conclusion, we conclude that piRNAs are abundant in human stomachs and may play important roles in the etiological processes of gastric cancers.

Neural correlates of chemotherapy-induced emotion regulation impairment in breast cancer patients.

To investigate the chemotherapy-induced emotion regulation impairment and its neural correlates in breast cancer (BC) patients by event-related potentials (ERP), seventeen BC patients were investigated on emotion regulation paradigms while undergoing the recording of an event-related potential (ERP) both before and after chemotherapy. The performance of behavioral and ERP was compared for the data collected before and after chemotherapy (BCB and BCA, respectively). The correlation of the difference between the peak and the latency of each component before and after chemotherapy were compared with the difference in behavior (RT and AR). BC patients showed a lower accuracy rate in both explicit and implicit emotion identification in BCA compared to that in BCB. Further, both the N1 and P2 components were significantly delayed. The peak values of the N1 and P2 in BCA were significantly higher than those in BCB, whereas the peak value of the N2 in BCA was significantly lower than that in BCB. There was a positive correlation between the difference in latency at the CZ (r=0.88), F3 (r=0.97) and FZ (r=0.85) points in the N1 component and the RT. The difference in latency at the FCZ point in the N2 (r=0.88) component is positively correlated with the AR. The difference in peak value at the CPZ (r=0.89) point in the N1 component is positively correlated with the RT. Both the implicit and explicit emotional processing was compromised in BC patients following chemotherapy. These emotional processing deficits may be related to the changes of the N1, N2 and P2 of the ERP.

Correlation between Psychosocial Distress and Quality of Life in Patients with Nasopharyngeal Carcinoma following Radiotherapy.

The aim of this study was to investigate the relationship between psychosocial distress and quality of life (QOL) in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Fifty-three patients with an initial diagnosis of NPC were enrolled in this study. The psychological Distress Thermometer (DT) and Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) were conducted before and after radiotherapy in NPC patients. We compared the differences in psychological distress and QOL before and after radiotherapy and analyzed the correlation between psychological distress and QOL after radiotherapy. The performance on the DT was 6.60 ± 1.42 and 2.81 ± 1.43 before and after chemotherapy, respectively, with a significant difference between the time points (t = -13.73, P < 0.01). The performance on the FACT-H&N was 68.30 ± 6.14 and 39.84 ± 6.14 before and after chemotherapy, respectively, with a significant difference between the time points (t = -19.9, P< 0.01). There was a significant negative correlation between the DT score and the FACT-H&N score (r = -3.64, P< 0.01). Patients with NPC experience different degrees of psychological distress, an important factor that affects quality of life, after radiotherapy.

Diminished gray matter density mediates chemotherapy dosage-related cognitive impairment in breast cancer patients.

To investigate chemotherapy dosage-related cognitive impairment and its neural mechanisms in breast cancer (BC) patients. Twenty-eight breast cancer patients after each chemotherapy cycle and matched 29 healthy control subjects underwent structural magnetic resonance imaging. Voxel-based morphometry analysis was performed to compare group differences in the gray matter for the whole brain. Furthermore, mediation analysis was conducted to explore the role of brain structures in chemotherapy dosage-related cognitive impairment. Voxel-based morphometry analysis was performed in gray matter for the whole brain of BC patients after chemotherapy. The results revealed that the gray matter density in the left inferior frontal gyrus, right middle frontal gyrus, right fusiform area, and bilateral cerebellum was decreased in the BC patients compared to controls. The number of chemotherapy cycles was negatively associated with general cognitive capacity, verbal fluency and digit span performance in the BC patients. In addition, decreased gray matter density in the right middle frontal gyrus could mediate the chemotherapy dosage effects on verbal fluency performance. These findings indicate that the dose-response relationship between chemotherapy and cognitive impairment may depend on the decreases in gray matter density of the frontal cortical structures.

Bullous hemorrhagic dermatosis is an under-recognized side effect of full dose low-molecular weight heparin: a case report and review of the literature.

Bullous hemorrhagic dermatosis (BHD) is a systemic side-effect of low molecular weight heparin, characterized by multiple intra-epidermal hemorrhages distant from the site of injection. There have been several small case series and literature reviews on BHD, but none have captured a complete set of reported patients. We sought to describe a case of BHD with late diagnosis and completely summarize the existing English and Spanish literature with searches of Pubmed, Scopus, Ovid Embase and Ovid Medline. After narrowing to 33 relevant reports, we describe 90 reported cases worldwide from 2004 to 2017, in addition to a new case from our institution as a means of comparison. We found that BHD was common in elderly men (mean age 72 ± 12; male:female, 1.9:1) and typically occurred within 7 days of administration of anticoagulation (median 7 days ± 6.4) usually with enoxaparin use (66% of cases). Lesions occurred primarily on the extremities only (67.9% of cases). Coagulation testing was most often normal before administration, and the majority of patients had coagulation testing in therapeutic range during treatment. Most practitioners stopped anticoagulation if continued therapeutic intervention was no longer required (57% of cases), or changed therapy to another anticoagulation if continued treatment was required (14.3% of cases). Therapy was continued outright in 23% of patients. The lesions usually resolved within 2 weeks (mean days, 13.0 ± 7.4). There was no difference in time to resolution between patients who continued the culprit anticoagulant or changed to a different anticoagulant, and those who discontinued anticoagulation altogether (13.9 days vs. 12.1, p = 0.49). Four deaths have been reported in this clinical context, two specified as intracranial hemorrhage. These deaths were unrelated to the occurrence of BHD. Continuation of low-molecular weight heparins appeared to be safe in patients with BHD.