Impaired Ethanol-Induced Sensitization and Decreased Cannabinoid Receptor-1 in a Model of Posttraumatic Stress Disorder

Background and Purpose Impaired striatal neuroplasticity may underlie increased alcoholism documented in those with posttraumatic stress disorder (PTSD). Cannabinoid receptor-1 (CB1) is sensitive to the effects of ethanol (EtOH) and traumatic stress, and is a critical regulator of striatal plasticity. To investigate CB1 involvement in the PTSD-alcohol interaction, this study measured the effects of traumatic stress using a model of PTSD, mouse single-prolonged stress (mSPS), on EtOH-induced locomotor sensitization and striatal CB1 levels. Methods Mice were exposed to mSPS, which includes: 2-h restraint, 10-min group forced swim, 15-min exposure to rat bedding odor, and diethyl ether exposure until unconsciousness or control conditions. Seven days following mSPS exposure, the locomotor sensitizing effects of EtOH were assessed. CB1, post-synaptic density-95 (PSD95), and dopamine-2 receptor (D2) protein levels were then quantified in the dorsal striatum using standard immunoblotting techniques. Results Mice exposed to mSPS-EtOH demonstrated impaired EtOH-induced locomotor sensitization compared to Control-EtOH mice, which was accompanied by reduced striatal CB1 levels. EtOH increased striatal PSD95 in control and mSPS-exposed mice. Additionally, mSPS-Saline exposure increased striatal PSD95 and decreased D2 protein expression, with mSPS-EtOH exposure alleviating these changes. Conclusions These data indicate that the mSPS model of PTSD blunts the behavioral sensitizing effects of EtOH, a response that suggests impaired striatal neuroplasticity. Additionally, this study demonstrates that mice exposed to mSPS and repeated EtOH exposure decreases CB1 in the striatum, providing a mechanism of interest for understanding the effects of EtOH following severe, multimodal stress exposure

Outcome of African-American compared to White-American patients with early-stage breast cancer, stratified by phenotype

BACKGROUND: Breast cancer mortality rates are 39% higher in the African-American (AA) women compared to White-American (WA) women despite the advances in overall breast cancer screening and treatments. Several studies have undertaken to identify the factors leading to this disparity in United States with possible effects of lower socioeconomic status and underlying aggressive biology. METHODS: A retrospective analysis was done using a prospectively maintained database of a metropolitan health system. Patients were selected based on diagnosis of early-stage breast cancer between 10/1998 and 02/2017, and included women over age of 18 with clinically node-negative disease. Patients were then stratified by phenotype confirmed by pathology and patient-identified race. RESULTS: A total of 2,298 women were identified in the cohort with 39% AA and 61% WA women. The overall mean age at the time of diagnosis for AA women was slightly younger at 60 years compared to 62 years for WA women (p = 0.003). Follow-up time was longer for the WA women at 95 months vs. 86 months in AA women. The overall 5-year survival was analyzed for the entire cohort, with the lowest survival occurring in patients with triple-negative breast cancer (TNBC). Phenotype distribution revealed a higher incidence of TNBC in AA women compared to WA women (AA 16% vs. WA 10%; p \u3c 0.0001). AA women also had higher incidence of HER2 positive cancers (AA 16.8% vs. WA 15.3%; p \u3c 0.0001). WA women had a significantly higher distribution of Non-TNBC/HER2-negative phenotype (AA 55% vs. WA 65%; p \u3c 0.0001). Furthermore, a subgroup analysis was done for a sentinel lymph node (SLN) negative cohort that showed higher rates of grade 3 tumors in AA (AA 35% vs. WA 23%; p \u3c 0.0001); and higher rates of grade 1 and grade 2 tumors in WA (30% vs. 21% and 44% vs. 40%). Despite higher grade tumors in AA women, five-year overall survival outcomes in SLN-negative cohort did not differ between AA and WA women when stratifying based on tumor subtype. CONCLUSION: Breast cancer survival disparities in AA and WA women with SLN-negative breast cancer are diminished when evaluated at early-stage cancers defined by SLN-negative tumors. Our evaluation suggests that when diagnosed early, phenotype does not contribute to racial survival outcomes. The lower survival rate in AA women with breast cancer may be attributed to later stage biology between the two races, or underlying socioeconomic disparities

Evaluation of a Multidisciplinary Team Approach for Generating Survivorship Care Plan Treatment Summaries in Patients With Breast Cancer

INTRODUCTION: The optimal structure for survivorship care plan (SCP) programs and methodology for generating treatment summaries (TSs) has not yet been defined, but the Commission on Cancer and the National Accreditation Program for Breast Centers both mandate that participating oncology programs implement SCP-TS processes for patients that have completed treatment. METHODS: We used the Institute for Healthcare Improvement\u27s Plan-Do-Study-Act model for conducting a quality improvement project evaluating two different SCP-TS programs implemented at the Henry Ford Health System/Henry Ford Cancer Institute\u27s Breast Oncology Program in Detroit, Michigan. System I involved TSs drafted by nonspecialist breast clinic staff; System II involved TSs vetted through a multidisciplinary breast specialist conference approach. Accuracy of basic documentation entries related to dates and components of treatment were compared for the two approaches. RESULTS: Seventy-one System I and 93 System II documents were reviewed. Documentation was accurate in at least 90% of documents for both systems regarding delivery of chemotherapy and/or endocrine therapy and for documenting the identity of the various members of the cancer treatment team. Both systems had notable inaccuracies in documenting type of surgery performed, but System II had fewer inaccuracies than System I (33.78% v 51.67%, respectively; P = .05). System II, compared with System I, had fewer inaccuracies in documenting date of diagnosis (9.68% v 25.35%, respectively; P = .01) and had less missing information for dose of radiation delivered (9.33% v 33.9%, respectively; P \u3c .01). CONCLUSION: A multidisciplinary team approach to drafting and reviewing SCP-TS documents improved content accuracy for our program, but ongoing education regarding documentation of various surgical procedures is warranted

Evaluation of a Multidisciplinary Team Approach for Generating Survivorship Care Plan Treatment Summaries in Patients With Breast Cancer

INTRODUCTION:: The optimal structure for survivorship care plan (SCP) programs and methodology for generating treatment summaries (TSs) has not yet been defined, but the Commission on Cancer and the National Accreditation Program for Breast Centers both mandate that participating oncology programs implement SCP-TS processes for patients that have completed treatment. METHODS:: We used the Institute for Healthcare Improvement\u27s Plan-Do-Study-Act model for conducting a quality improvement project evaluating two different SCP-TS programs implemented at the Henry Ford Health System/Henry Ford Cancer Institute\u27s Breast Oncology Program in Detroit, Michigan. System I involved TSs drafted by nonspecialist breast clinic staff; System II involved TSs vetted through a multidisciplinary breast specialist conference approach. Accuracy of basic documentation entries related to dates and components of treatment were compared for the two approaches. RESULTS:: Seventy-one System I and 93 System II documents were reviewed. Documentation was accurate in at least 90% of documents for both systems regarding delivery of chemotherapy and/or endocrine therapy and for documenting the identity of the various members of the cancer treatment team. Both systems had notable inaccuracies in documenting type of surgery performed, but System II had fewer inaccuracies than System I (33.78% v 51.67%, respectively; P = .05). System II, compared with System I, had fewer inaccuracies in documenting date of diagnosis (9.68% v 25.35%, respectively; P = .01) and had less missing information for dose of radiation delivered (9.33% v 33.9%, respectively; P \u3c .01). CONCLUSION:: A multidisciplinary team approach to drafting and reviewing SCP-TS documents improved content accuracy for our program, but ongoing education regarding documentation of various surgical procedures is warranted

Clinicopathological Evaluation of the Potential Anatomic Pathways of Systemic Metastasis from Primary Breast Cancer Suggests an Orderly Spread Through the Regional Lymph Nodes

BACKGROUND: Two conflicting hypotheses as to how breast cancer (BC) accesses the systemic circulation dominated the 20th century and affected surgical treatment. We hypothesized that tumor lymphovascular invasion (LVI) at the primary tumor site favors lymphatic and not blood vessel, capillaries, and systemic metastases (Smets) are dependent upon regional lymph node (RLN) mets. METHODS: Data from BC patients undergoing RLN biopsy was professionally abstracted and maintained in a prospective, precisely managed, single-institution database. Associations of RLN, LVI, and Smets were estimated by univariate and multivariate backward logistic regression models and patient-affiliated demographic, clinicopathologic, treatment type, and molecular marker data. RESULTS: Of 3329 patients, followed 1-22 years (mean 7.8), 463 of 3329 (13.9%) showed LVI, 742 of 3329 (22.3%) had RLN mets, and 262 of 3329 (7.9%) had Smets. Smets occurred in 52 of 252 (21% with LVI+/RLN+); 116 of 2301 (5% with LVI-/RLN-); 65 of 465 (14% with LVI-/RLN+); and 17 of 207 (8% with LVI+/RLN-), p = 0.021 for association between LVI and Smets for RLN+ patients but not for RLN- patients (p = 0.051). Positive RLN, larger tumor size, and higher grade (all p \u3c 0.001) were predictive of Smets by the multivariable model, whereas positive LVI was not. CONCLUSIONS: LVI predicts RLN mets in BC. RLN is critical to Smets from BC, whereas LVI on its own is not. Smets occur significantly more commonly when both LVI and RLN mets occur together. LVI is, thus, likely to be primarily lymphatic invasion, and rarely, blood vessel invasion, supporting the Halsted paradigm. LVI and RLN together predict clinical outcome better than either alone

Breast cancer patients are interested in telemedicine

Introduction: Telemedicine is enhancing or replacing many aspects of traditional in-office healthcare. The role of telemedicine in the complex care of breast cancer (BC) patients remains unclear. Methods: Via a survey at their initial BC appointment, patients self-reported demographics such as age, race, distance from hospital and education level. Patients answered ten Likert questions about perceptions of telemedicine. Wilcoxon signed rank tests assessed whether overall the respondents reported more or less than neutral interest or concerns due to each of the ten considerations. Wilcoxon rank sum tests and Spearman\u27s rank correlations were used for univariate analysis to assess if responses varied by patient characteristic. Multiple regression assessed for associations. Results: 51 female BC patients completed the survey. 31 patients were White, 19 were \u3c60, and 17 lived over 20 miles from the hospital. 30 patients answered telemedicine could save time, 34 answered telemedicine could improve their access to care, and 35 answered telemedicine could decrease wait time, with Likert responses of \u274\u27/Agree or \u275\u27/ Strongly Agree. No significant associations were observed between interest in telemedicine (gauged by responses to the Likert score questions) and respondent characteristics. The questions that were associated with greater interest in telemedicine had to do with easier access, less waiting time and reduced exposure to infectious diseases. Each of these variables had a median Likert response of \u274\u27/Agree with signed rank test p-values ≤0.010. The question which denoted the most concern about telemedicine involved the use of technology, although the median for that question was \u273\u27/neutral. Finally, the overall median of the directionally aligned Likert responses was 3.4 partway between neutral and agree (indicating more interest/less concern). The signed rank test p-value for this average was 0.009. Conclusions: BC patients are interested in telemedicine. Since age, race, distance from hospital, and education level, are not predictors of interest in telemedicine, providers can consider offering these opportunities to everyone, as healthcare continues to become more personalized

Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured mice

Introduction: Civilians and military personnel develop a range of physical and psychosocial impairments following traumatic brain injury (TBI), including alcohol abuse. As a consequence, increased rates of alcohol misuse magnify TBI-induced pathologies and impede rehabilitation efforts. Therefore, a developed understanding of the mechanisms that foster susceptibility of the injured brain to alcohol sensitivity and the response of the injured brain to alcohol is imperative for the treatment of TBI patients. Alcohol sensitivity has been demonstrated to be increased following experimental TBI and, in additional studies, regulated by presynaptic vesicle release mechanisms, including synapsin phosphorylation. Materials and Methods: Mice were exposed to controlled midline impact of the intact skull and assessed for cortical, hippocampal, and striatal expression of phosphorylated synapsin I and II in response to high-dose ethanol exposure administered 14 days following injury, a time point at which injured mice demonstrate increased sedation after ethanol exposure. Results and Discussion: Immunoblot quantitation revealed that TBI alone, compared to sham controls, significantly increased phosphorylated synapsin I and II protein expression in the striatum. In sham controls, ethanol administration significantly increased phosphorylated synapsin I and II protein expression compared to saline-treated sham controls; however, no significant increase in ethanol-induced phosphorylated synapsin I and II protein expression was observed in the striatum of injured mice compared to saline-treated TBI controls. A similar expression pattern was observed in the cortex although restricted to increases in phosphorylated synapsin II. Conclusion: These data show that increased phosphorylated synapsin expression in the injured striatum may reflect a compensatory neuroplastic response to TBI which is proposed to occur as a result of a compromised presynaptic response of the injured brain to high-dose ethanol. These results offer a mechanistic basis for the altered ethanol sensitivity observed following experimental TBI and contribute to our understanding of alcohol action in the injured brain

Sentinel Lymph Node Positivity in Clinically Node Negative Breast Cancer Patients After Neoadjuvant Chemotherapy: Opportunities to Defer Intraoperative Frozen Section Analysis

INTRODUCTION: Neoadjuvant chemotherapy (NACT) is frequently implemented in a breast cancer treatment plan. In clinically node negative (cN0) patients following NACT, it is routine to perform sentinel lymph node (SLN) biopsy with intraoperative frozen section analysis with subsequent axillary lymph node dissection (ALND) if metastatic disease were detected. We aim to define the rate of sentinel node positivity (ypN1 (sn)) at our institution in patients who presented as cN0 and received NACT. METHODS: Using our IRB approved breast cancer database a retrospective chart review was performed for all T1-T3, cN0 primary breast cancer cases who underwent NACT from 2016 to 2021 and have undergone a subsequent definitive operation at our institution. Demographics, clinical characteristics, tumor biology and staging were recorded. We stratified by hormone receptor (HR) and HER2 status defined as: HR negative (0%), HR weakly positive (1-10%), HR positive ( \u3e11%), HER2 negative (0, 1+, 2+ negative by FISH), HER2 positive (3+, 2+ positive by FISH). RESULTS: We identified 139 cN0 cases undergoing NACT from 2016 to 2021. Forty were excluded, leaving 99 for analysis. Of these, 8 (8 %) were found to be ypN1(sn). Of the 71 HER2 negative cases, we found 32 HR negative (triple negative) and 11 HR weakly positive, none of which (0%) were found to be ypN1(sn), and 28 HR positive of which 7 (25%) were found to be ypN1(sn). Of the 28 HER2 positive cases, we found 11 HR negative and 3 HR weakly positive cases, none of which (0%) were found to be ypN1, and 14 HR positive of which 1 (7%) was found to be a micrometastasis (ypN1mic(sn)). CONCLUSIONS: Our results show that for the more aggressive tumor subtypes, including HR negative and HR weakly positive, the rate of ypN1(sn) after NACT in cN0 patients was 0%. These results suggest that frozen section could be avoided at the time of surgery for these patients in lieu of permanent pathology, due to he negligible likelihood of finding ypN1(sn) and thus needing ALND

Brief report: Global health initiatives and breast oncology capacity-building in Africa

INTRODUCTION: Global health initiatives provide exciting opportunities for capacity-building in low- and middle-income countries but data regarding how African clinicians characterize the most effective partnerships are lacking. METHODS: We surveyed attendees at two Breast Cancer in Africa symposia sponsored through a surgeon-led global breast cancer research collaborative. Respondents ranked their preferences for needs from American global health partnerships. RESULTS: 399 African attendees responded (170 at the 2017 Ghana conference; 229 at the 2018 Ethiopia conference). Physicians comprised 41.1% of respondents; nurses 20.1% and medical students 27.6%. Ancillary hospital staff comprised the remaining 11.2%. Among clinicians, 75.7% ranked educational/training programs or donation of medical supplies as the highest-priority needs compared to only 20.4% ranking direct monetary support as the highest-priority need (P \u3c 0.0001). CONCLUSIONS: Our survey study found that African clinicians prioritize training programs and donation of medical/hospital supplies above direct monetary support as their highest-value needs from global health initiatives