Electroconvulsive Therapy Changes Immunological Markers in Patients With Major Depressive Disorder: A Scoping Review.

ABSTRACT: Major depressive disorder (MDD) is a highly prevalent and disabling condition. As such, understanding the causes of and treatment options for MDD is critical. Electroconvulsive therapy (ECT) remains the gold standard depression treatment, but the molecular mechanisms that underlie its effects are still largely unknown. One such explanation hinges on the immuno-inflammatory correlates of ECT treatment, given mounting evidence supporting the inflammatory hypothesis of depression. This review aims to provide an overview of the suggested immunomodulatory effects of ECT and the predictive value of immune biomarkers in relation to treatment outcomes and side effects. We conducted a preregistered, systematic literature search utilizing MEDLINE (PubMed), Embase (Elsevier), and PsycINFO (EBSCO) databases. We employed keywords related to MDD, ECT, gut microbiome, and the immune system. We only included human subjects research published between 1985 and January 13, 2021. Twenty-six unique studies were included in our analyses. Findings indicate a proinflammatory profile associated with MDD, with immune biomarkers exhibiting acute and chronic changes following ECT. Consistently, lower baseline interleukin 6 levels and higher C-reactive protein levels are correlated with a greater reduction in depressive symptoms following ECT. Furthermore, included studies emphasize the predictive value of peripheral immune changes, specifically interleukin 6 and tumor necrosis factor α, on cognitive outcomes following ECT. Given these results, further exploration of the potential roles of immunomodulatory effects on ECT treatment outcomes, as well as adverse cognitive side effects, is indicated.

Effects of Alcohol Reduction Interventions on Blood Pressure.

PURPOSE OF REVIEW: Much of alcohol's purported negative impact on a population's health can be attributed to its association with increased blood pressure, rates of hypertension, and incidence of cardiovascular disease (CVD). Less attention, however, has been placed on the association of the positive impact of alcohol reduction interventions on physical health. RECENT FINDINGS: This review delineates the evidence of blood pressure reductions as a function of alcohol reduction interventions based on current care models. The findings of this review suggest two things: (1) sufficient evidence exists for a relationship between alcohol reductions and blood pressure generally, and (2) little evidence exists for the relationship between alcohol reductions and blood pressure for any one care model currently employed in the health system. The evidence base would benefit from more studies using established alcohol reduction interventions examining the impact of these interventions on blood pressure.

Ketamine for treatment of mood disorders and suicidality: A narrative review of recent progress.

BACKGROUND: Mood disorders are a leading cause of morbidity. Many patients experience treatment-resistant depression (TRD), and suicide rates are rising. Faster-acting and more effective antidepressant medications are needed. Four decades of research has transformed the use of ketamine from an anesthetic to an outpatient treatment for major depressive disorder (MDD). Ketamine is a N-methyl-d-aspartate (NMDA) receptor antagonist and has been shown to rapidly improve mood symptoms and suicidal ideation by targeting the glutamate system directly. METHODS: We used the PubMed database to identify relevant articles published until September 1, 2020. We focused on meta-analyses, randomized controlled trials, and original observational studies. We included relevant studies for depression, MDD, TRD, bipolar disorder, anxiety, posttraumatic stress disorder (PTSD), suicide, ketamine, and esketamine. RESULTS: Both racemic ketamine and esketamine have been shown to rapidly treat depression and suicidality. There is evidence that ketamine can be helpful for anxiety and PTSD; however, more research is needed. Intranasal esketamine has been FDA approved to treat depression. CONCLUSIONS: This narrative review describes the evolution of ketamine to treat mood disorders and suicidality. We provide the evidence supporting recent developments using esketamine as well as unresolved issues in the field, such as dosing and safety.

Reciprocal Effects Between Depressive Symptoms and Pain in Veterans over 50 Years of Age or Older.

OBJECTIVE: Depression and chronic pain are major problems in American veterans, yet there is limited long-term research examining how they relate to one another in this population. This study examined the relationship between depressive symptoms and pain in U.S. veterans 50 years of age or older. METHODS: This study used data on veterans from the 2002-2016 waves of the Health and Retirement Study (n = 4,302), a large-scale observational study of Americans 50 years of age or older. Measures included a short form of the Center for Epidemiologic Studies Depression scale and two items assessing the presence and degree of pain. Analyses included random-intercept cross-lagged panel models (RI-CLPM). RESULTS: In the RI-CLPM, there were roughly equivalent cross-lagged effects between depressive symptoms and pain. There was also evidence that depressive symptoms and pain have a trait-like component and that these trait-like characteristics are associated. CONCLUSIONS: These findings indicate that depressive symptoms and pain in veterans are stable characteristics in American veterans 50 years of age or older. There appear to be reciprocal effects between the two, whereby deviations in one's typical depressive symptoms predict subsequent deviations in one's pain level and vice versa; however, the size of these effects is very small. These findings suggest that clinicians should treat both depressive symptoms and pain, rather than assume that treatment benefits in one domain will lead to major benefits in another.

Efficacy and safety of ketamine in the management of anxiety and anxiety spectrum disorders: a review of the literature.

Anxiety disorders are among the most prevalent psychiatric conditions. Despite many proven pharmacological and non-pharmacological treatments available, high rates of partial response and low rates of long-term remission remain. Ketamine has been receiving increasing attention as an interventional treatment modality in psychiatry, especially among refractory conditions, including major depressive disorder. There is limited yet growing evidence to support the use of ketamine in anxiety disorders. In this review of the literature, we present case reports, case series, and controlled trials demonstrating proof-of-concept for its potential role in the treatment of anxiety and anxiety spectrum disorders. Its unique mechanism of action, rapid onset, and high rate of response have driven its use in clinical practice. Ketamine is generally well tolerated by patients and has a limited side effect profile; however, the effects of long-term use are unknown. While there is a growing body of research and increasing clinical experience to suggest ketamine may have clinical applications in the treatment of refractory anxiety disorders, further research to determine long-term safety and tolerability is indicated.

Gadolinium deposition within the paediatric brain: no increased intrinsic T1-weighted signal intensity within the dentate nucleus following the administration of a minimum of four doses of the macrocyclic agent gadobutrol.

OBJECTIVES: To determine whether repeated administration of the macrocyclic gadolinium-based contrast agent (GBCA) gadobutrol in children is associated with T1-weighted hyperintensity within the dentate nucleus, an imaging surrogate for gadolinium deposition. METHODS: With institutional review board approval, we identified a cohort of eight patients aged 18 years or younger who underwent at least four gadobutrol-enhanced magnetic resonance imaging (MRI) examinations of the brain from 2013 to 2017. For comparison, we identified a cohort of 19 patients who underwent at least four gadopentetate dimeglumine-enhanced MRI examinations. For each examination, both dentate nuclei were contoured on unenhanced images; the mean dentate-to-pons signal intensity (DN-P SI) ratio was calculated. DN-P SI ratios from the first and last MRI exams were compared using Wilcoxon signed ranks tests and linear regression analyses. RESULTS: In the gadobutrol cohort, there was no significant change in the mean DN-P SI ratio from the first to the last scan (1.02 vs 1.02, p = 1.00). In the gadopentetate dimeglumine cohort, there was a significant increase in the mean DN-P SI ratio from the first to the last scan (1.05 vs 1.13, p = 0.003). After controlling for potentially confounding variables, the change in DN-P SI ratio from the first to the last scan was significantly lower for patients in the gadobutrol group than in the gadopentetate dimeglumine group (ß = -0.08, p = 0.04). CONCLUSIONS: Repeated administration of the macrocyclic GBCA gadobutrol in children was not associated with T1-weighted dentate hyperintensity, while the repeated administration of the linear GBCA gadopentetate dimeglumine was associated with T1-weighted dentate hyperintensity, presumably due to gadolinium deposition. KEY POINTS: • Gadolinium-based contrast agents are routinely used in magnetic resonance imaging. • Repeated administration of the macrocyclic agent gadobutrol in children was not associated with T1-weighted dentate hyperintensity.

Association of the Gross Appearance of Intratumoral Vascularity at MDCT With the Carbonic Anhydrase IX Score in Clear Cell Renal Cell Carcinoma.

OBJECTIVE: The purpose of this study was to determine whether qualitative MDCT features are associated with the carbonic anhydrase IX (CAIX) score of clear cell renal cell carcinoma (RCC). The CAIX score has been previously found to have prognostic significance for disease-free survival, overall survival, and lymph node involvement. MATERIALS AND METHODS: A cohort of 105 histologically proven clear cell RCCs in patients who underwent preoperative four-phase renal mass MDCT was derived from 2001 to 2013. Two genitourinary radiologists evaluated each lesion for the gross appearance of intratumoral vascularity, calcification, enhancement pattern, necrosis, margin, collecting system invasion, and renal vein invasion. Immunohistochemical analysis was used to determine the CAIX score (defined as the positive staining percentage multiplied by the staining intensity). Logistic and linear regression analyses were performed. RESULTS: In a linear regression model controlled for lesion size and stage, the gross appearance of intratumoral vascularity had a significant positive association with CAIX score (ß = 38.33, p = 0.010). In a logistic regression model controlled for lesion size and stage, the gross appearance of intratumoral vascularity had an odds ratio of 2.85 (p = 0.019) in differentiating clear cell RCCs with a CAIX score of 200-300 from clear cell RCCs with a CAIX score of 0-199. CONCLUSION: In clear cell RCCs, the gross appearance of intratumoral vascularity at MDCT was significantly associated with CAIX score, a prognostically significant molecular marker. Current assessment of CAIX score requires pathologic tissue sampling and immunohistochemical analysis. A noninvasive imaging biomarker that may help predict CAIX score may be of great clinical value.

Clear Cell Renal Cell Carcinoma: Identifying the Loss of the Y Chromosome on Multiphasic MDCT.

OBJECTIVE: The objective of our study was to investigate whether multiphasic MDCT enhancement can help identify clear cell renal cell carcinomas (RCCs) with the loss of the Y chromosome. MATERIALS AND METHODS: We derived a cohort of 43 clear cell RCCs in men who underwent preoperative four-phase renal mass MDCT from October 2000 to August 2013. Each lesion was segmented in its entirety on axial images. A computer-assisted detection algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. A 0.5-cm-diameter ROI was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as follows: [(maximal lesion attenuation - cortex attenuation) / cortex attenuation] × 100. Absolute attenuation and relative attenuation in each phase were compared using t tests. RESULTS: Both clear cell RCCs with the loss of the Y chromosome and clear cell RCCs without the loss of the Y chromosome exhibited peak enhancement in the corticomedullary phase. However, relative nephrographic attenuation of clear cell RCCs with the loss of Y was significantly less than that of clear cell RCCs without the loss of Y (mean, -8.9 vs 8.4 respectively; p = 0.013). A relative nephrographic attenuation threshold of -1.6 identified the loss of Y with an accuracy of 70% (30/43), sensitivity of 73% (16/22), and specificity of 67% (14/21). CONCLUSION: Multiphasic MDCT enhancement may assist in identifying the loss of the Y chromosome in clear cell RCCs; this result should be validated in a large prospective trial.

Performance of Relative Enhancement on Multiphasic MRI for the Differentiation of Clear Cell Renal Cell Carcinoma (RCC) From Papillary and Chromophobe RCC Subtypes and Oncocytoma.

OBJECTIVE: The objective of our study was to investigate the performance of relative enhancement on multiphasic MRI to differentiate clear cell renal cell carcinoma (RCC) from other RCC subtypes (papillary and chromophobe) and oncocytoma. MATERIALS AND METHODS: For this study, we derived a cohort of 34 clear cell RCCs, nine oncocytomas, 12 papillary RCCs, and 10 chromophobe RCCs with a preoperative multiphasic dynamic contrast-enhanced MRI study with up to four phases (i.e., unenhanced, corticomedullary, nephrographic, excretory) from 2005 to 2016. These groups were evaluated for multiphasic enhancement and were compared using Kruskal-Wallis and Mann-Whitney tests. ROC curves were constructed and logistic regression analyses were performed to evaluate the performance of multiphasic enhancement in differentiating clear cell RCCs from the other three groups. RESULTS: Clear cell RCCs exhibited significantly greater relative signal intensity compared with uninvolved renal cortex in the corticomedullary phase (mean, 2.9) than oncocytomas (-21.7, p = 0.001), papillary RCCs (-53.0, p < 0.001), and chromophobe RCCs (-21.0, p < 0.001). Relative signal intensity in the corticomedullary phase differentiated clear cell RCCs from oncocytomas with an AUC of 0.90 and with an accuracy of 84% (32/38), sensitivity of 90% (27/30), and specificity of 63% (5/8) after controlling for lesion size, patient age, and patient sex. Relative corticomedullary signal intensity differentiated clear cell RCCs from oncocytomas and other RCC subtypes with an AUC of 0.93 and with an accuracy of 90% (53/59), sensitivity of 90% (27/30), and specificity of 90% (26/29) after controlling for lesion size, patient age, and patient sex. CONCLUSION: Multiphasic MRI enhancement may assist in differentiating clear cell RCC from oncocytomas and other RCC subtypes, if validated in prospective studies.

Structure-based design and development of (benz)imidazole pyridones as JAK1-selective kinase inhibitors.

The mammalian Janus Kinases (JAK1, JAK2, JAK3 and TYK2) are intracellular, non-receptor tyrosine kinases whose activities have been associated in the literature and the clinic with a variety of hyperproliferative diseases and immunological disorders. At the onset of the program, it was hypothesized that a JAK1 selective compound over JAK2 could lead to an improved therapeutic index relative to marketed non-selective JAK inhibitors by avoiding the clinical AEs, such as anemia, presumably associated with JAK2 inhibition. During the course of the JAK1 program, a number of diverse chemical scaffolds were identified from both uHTS campaigns and de novo scaffold design. As part of this effort, a (benz)imidazole scaffold evolved via a scaffold-hopping exercise from a mature chemical series. Concurrent crystallography-driven exploration of the ribose pocket and the solvent front led to analogs with optimized kinome and JAK1 selectivities over the JAK2 isoform by targeting several residues unique to JAK1, such as Arg-879 and Glu-966.

The discovery of reverse tricyclic pyridone JAK2 inhibitors. Part 2: lead optimization.

This communication discusses the discovery of novel reverse tricyclic pyridones as inhibitors of Janus kinase 2 (JAK2). By using a kinase cross screening approach coupled with molecular modeling, a unique inhibitor-water interaction was discovered to impart excellent broad kinase selectivity. Improvements in intrinsic potency were achieved by utilizing a rapid library approach, while targeted structural changes to lower lipophilicity led to improved rat pharmacokinetics. This multi-pronged approach led to the identification of 31, which demonstrated encouraging rat pharmacokinetics, in vivo potency, and excellent off-target kinase selectivity.

Thiophene carboxamide inhibitors of JAK2 as potential treatments for myleoproliferative neoplasms.

A series of carboxamide-substituted thiophenes demonstrating inhibition of JAK2 is described. Development of this chemical series began with the bioisosteric replacement of a urea substituent by a pyridyl ring. Issues of chemical and metabolic stability were solved using the results of both in vitro and in vivo studies, ultimately delivering compounds such as 24 and 25 that performed well in an acute PK/PD model measuring p-STAT5 inhibition.

Qualitative and quantitative MDCT features for differentiating clear cell renal cell carcinoma from other solid renal cortical masses.

OBJECTIVE: The purpose of this study was to differentiate clear cell renal cell carcinoma (RCC) from other solid renal masses on four-phase MDCT. MATERIALS AND METHODS: Our study cohort included all pathologically proven solid renal masses that underwent pretreatment four-phase MDCT at our institution from 2001 to 2012. Both retrospective qualitative analysis (blinded dual-radiologist evaluation of morphologic features: enhancement pattern, lesion contour, neovascularity, and calcification) and quantitative analysis (mean absolute and relative attenuation and changes in attenuation across phases) were performed. ANOVA with post-hoc analysis, Pearson chi-square tests, and ROC analysis were used. RESULTS: One hundred fifty-six consecutive patients (99 men, 57 women) with a mean age of 62.7 years (range, 26-91 years) had 165 solid renal masses (median size, 3.0 cm): 86 clear cell RCCs, 36 papillary RCCs, 10 chromophobe RCCs, 23 oncocytomas, and 10 lipid-poor angiomyolipomas. Kappa for interradiologist agreement regarding morphologic features was 0.33-0.76. There were significant associations between histologic subtype and enhancement pattern (p < 0.001), lesion contour (p < 0.014), and neovascularity (p < 0.001). Clear cell RCC had the highest mean relative corticomedullary attenuation (p < 0.02). Clear cell RCC had greater deenhancement than oncocytoma (p < 0.001); deenhancement less than 50 HU or relative corticomedullary attenuation greater than 0% differentiated clear cell RCC from oncocytoma with a positive predictive value of 90%. Lipid-poor angiomyolipoma had the highest mean absolute unenhanced attenuation (p < 0.01); absolute unenhanced attenuation greater than 45 HU and relative corticomedullary attenuation less than 10% differentiated lipid-poor angiomyolipoma from clear cell RCC with a negative predictive value of 97%. CONCLUSION: Four-phase MDCT renal attenuation profiles enable differentiation of clear cell RCC from other solid renal cortical masses, most notably papillary RCC and lipid-poor angiomyolipoma.

Clear cell renal cell carcinoma: multiphasic MDCT enhancement can predict the loss of chromosome 8p.

PURPOSE: To investigate whether imaging features on multiphasic multidetector computed tomography (MDCT) can predict the loss of chromosome 8p in clear cell renal cell carcinomas (RCCs), a cytogenetic abnormality associated with a higher tumor grade and greater risk of recurrence. METHODS: With IRB approval for this HIPAA-compliant retrospective study, we queried our institution's pathology database to derive all histologically proven cases of clear cell RCC with preoperative multiphasic MDCT with as many as four phases (unenhanced, corticomedullary, nephrographic, and excretory) from January 2000 to July 2010. Of 170 clear cell RCCs with preoperative multiphasic MDCT, 105 clear cell RCCs, representing 98 unique patients, had karyotypes of the resected specimens. Lesions were evaluated for magnitude and pattern of enhancement, contour, neovascularity, calcifications, and size. RESULTS: The corticomedullary phase mean enhancement of clear cell RCCs with a loss of 8p was significantly greater than that of clear cell RCCs without a loss of 8p (169.5 vs. 127.2 HU, p = 0.004). A threshold of 165 HU predicted the loss of 8p in clear cell RCCs with an accuracy of 78% (69/88), a specificity of 81% (62/77), and a negative predictive value of 94% (62/66). There were no significant differences in the pattern of enhancement, contour, neovascularity, calcification, or size between clear cell RCCs with a loss of 8p and those without this abnormality. CONCLUSION: Enhancement on multiphasic MDCT can predict the loss of 8p in clear cell RCCs and can thus provide a non-invasive means of guiding further management, including surgery, ablation, watchful waiting, or medical management.

Association Between 18F-FDG PET Activity and HER2 Status in Breast Cancer Brain Metastases.

Purpose: The objective of this study was to evaluate whether uptake on 18F-fluorodeoxyglucose (18F-FDG) PET could help differentiate HER2-positive from HER2-negative breast cancer brain metastases. Methods: In this retrospective, cross-sectional study of a cohort of 14 histologically proven breast cancer brain metastases, we analyzed both preoperative 18F-FDG PET/CT and HER2 status of the resected/biopsied brain specimens. The maximum standardized uptake values (SUVmax) of the lesions were normalized to contralateral normal white matter and compared using Mann-Whitney U tests. Results: The study cohort was comprised of 12 women with breast cancer with a mean age of 59 years (range: 43-76 years) with a total of 14 distinct brain metastatic lesions. The SUVmax ratio of HER2-positive breast cancer brain metastases was significantly greater than that of HER2-negative lesions (3.98 vs 1.79, U = 38.00, p = 0.008). Conclusion: The SUVmax ratio may help to identify the HER2 status of breast cancer brain metastases, if validated prospectively.

Clear cell renal cell carcinoma: discrimination from other renal cell carcinoma subtypes and oncocytoma at multiphasic multidetector CT.

PURPOSE: To determine whether enhancement at multiphasic multidetector computed tomography (CT) can help differentiate clear cell renal cell carcinoma (RCC) from oncocytoma, papillary RCC, and chromophobe RCC. MATERIALS AND METHODS: With institutional review board approval for this HIPAA-compliant retrospective study, the pathology database was queried to derive a cohort of 298 cases of RCC and oncocytoma with preoperative multiphasic multidetector CT with as many as four phases (unenhanced, corticomedullary, nephrographic, and excretory). A total of 170 clear cell RCCs, 57 papillary RCCs, 49 oncocytomas, and 22 chromophobe RCCs were evaluated for multiphasic enhancement and compared by using t tests. Cutoff analysis was performed to determine optimal threshold levels to discriminate among the four groups. RESULTS: Mean enhancement of clear cell RCCs and oncocytomas peaked in the corticomedullary phase; mean enhancement of papillary and chromophobe RCCs peaked in the nephrographic phase. Enhancement of clear cell RCCs was greater than that of oncocytomas in the corticomedullary (125 HU vs 106 HU, P = .045) and excretory (80 HU vs 67 HU, P = .034) phases. Enhancement of clear cell RCCs was greater than that of papillary RCCs in the corticomedullary (125 HU vs 54 HU, P < .001), nephrographic (103 HU vs 64 HU, P < .001), and excretory (80 HU vs 54 HU, P < .001) phases. Enhancement of clear cell RCCs was greater than that of chromophobe RCCs in the corticomedullary (125 HU vs 74 HU, P < .001) and excretory (80 HU vs 60 HU, P = .008) phases. Thresholding of enhancement helped to discriminate clear cell RCC from oncocytoma, papillary RCC, and chromophobe RCC with accuracies of 77% (83 of 108 cases), 85% (101 of 119 cases), and 84% (81 of 97 cases). CONCLUSION: Enhancement at multiphasic multidetector CT, if prospectively validated, may assist in the discrimination of clear cell RCC from oncocytoma, papillary RCC, and chromophobe RCC.

Association of lesion contour and lesion composition on MR with HER2 status in breast cancer brain metastases.

BACKGROUND AND PURPOSE: With the development of HER2-directed therapies, identifying non-invasive imaging biomarkers of HER2 status in breast cancer brain metastases has become increasingly important, particularly given the risks of tissue sampling within the brain and the possibility of a change in receptor expression from the primary tumor to the brain metastasis. The purpose of this study was to evaluate whether lesion contour and composition on MR could help identify the HER2 status of breast cancer brain metastases. MATERIALS AND METHODS: We derived a cohort of 34 women with a mean age of 55 years (range: 31-81 years) with a total of 47 distinct histologically proven breast cancer brain metastases with preoperative contrast-enhanced brain MR and HER2 immunohistochemistry and/or fluorescent in-situ hybridization (FISH) of the resected/biopsied brain specimens from 2018 to 2021. Two fellowship-trained neuroradiologists evaluated the lesion contour and lesion composition of each lesion. Logistic regression analyses were performed. RESULTS: In a logistic regression model, an irregular contour had an odds ratio of 170 (p = 0.007) in differentiating HER2-positive from HER2-negative lesions. In a logistic regression model, when compared to a predominantly cystic lesion composition, a solid lesion composition had an odds ratio of 17 (p = 0.016) in differentiating HER2-positive from HER2-negative lesions. CONCLUSION: Lesion contour and lesion composition on MR were significantly associated with the HER2 status of breast cancer brain metastases. Current assessment of HER2 status requires tissue sampling and immunochemical and/or FISH analyses. A non-invasive imaging biomarker that may help predict HER2 status may be of great clinical value.

Mobile health contingency management for smoking cessation among veterans experiencing homelessness: A comparative effectiveness trial.

Tobacco cessation is reduced in U.S. military veterans experiencing homelessness. Mobile contingency management (mCM) is a promising treatment for tobacco use among populations experiencing homelessness, but past CM studies have largely been small, have relied on in-person follow-up, and/or lacked long-term biochemically verified abstinence measures. Veterans who smoked and were experiencing homelessness (N = 127) were randomly assigned to mCM treatment (4 weeks of mCM, 5 weeks of telehealth counseling, and the option of 12 weeks of pharmacotherapy) or VA standard care (3 biweekly group sessions and clinically appropriate pharmacotherapy), and all participants were randomly assigned to a $100 longer-term financial incentive for abstinence at 3-month follow-up. Participants were followed at 3-, 6-, and 12-months post-randomization, with the a priori main outcome designated as biochemically verified prolonged abstinence (with lapses) at 6-month follow-up. At 6-months, participants in the mCM group were significantly more likely to meet criteria for prolonged abstinence (OR = 3.1). Across time points, veterans in the mCM group had twice the odds of prolonged abstinence as those in the standard care group. However, by the 12-month follow-up, there was no statistically significant group difference in abstinence. Cost-effectiveness analysis indicated a modest increase in cost ($1,133) associated with an increase of one quality-adjusted life year saved for the intervention compared to standard care. mCM is a cost-effective approach to smoking cessation among veterans experiencing homelessness. Considering waning potency of this and other tobacco cessation interventions at 12-month follow-up, it is crucial to implement strategies to sustain abstinence for individuals experiencing homelessness.

Association of Relative Cerebral Blood Volume from Dynamic Susceptibility Contrast-Enhanced Perfusion MR with HER2 Status in Breast Cancer Brain Metastases.

RATIONALE AND OBJECTIVES: With the development of HER2-directed therapies, identifying non-invasive imaging biomarkers of HER2 expression in breast cancer brain metastases has become increasingly important. The purpose of this study was to investigate whether relative cerebral blood volume (rCBV) from dynamic susceptibility contrast-enhanced (DSC) perfusion MR could help identify the HER2 status of breast cancer brain metastases. MATERIALS AND METHODS: With IRB approval for this HIPAA-compliant cross-sectional study and a waiver of informed consent, we queried our institution's electronic medical record to derive a cohort of 14 histologically proven breast cancer brain metastases with preoperative DSC perfusion MR and HER2 analyses of the resected/biopsied brain specimens from 2011-2021. The rCBV of the lesions was measured and compared using Mann-Whitney tests. Receiver operating characteristic analyses were performed to evaluate the performance of rCBV in identifying HER2 status. RESULTS: The study cohort was comprised of 14 women with a mean age of 56 years (range: 32-81 years) with a total of 14 distinct lesions. The rCBV of HER2-positive breast cancer brain metastases was significantly greater than the rCBV of HER2-negative lesions (8.02 vs 3.97, U=48.00, p=0.001). rCBV differentiated HER2-positive lesions from HER2-negative lesions with an area under the curve of 0.98 (standard error=0.032, p<0.001). The accuracy-maximizing rCBV threshold (4.8) was associated with an accuracy of 93% (13/14), a sensitivity of 100% (7/7), and a specificity of 86% (6/7). CONCLUSION: rCBV may assist in identifying the HER2 status of breast cancer brain metastases, if validated in a large prospective trial.