Citations

AbstractObjectiveTo systematically evaluate the efficacy and effectiveness of percutaneous interventional treatments for prevention of migraine through a qualitative and (when possible) quantitative analysis.MethodsAn expert panel was asked to develop recommendations for the multidisciplinary preventive treatment of migraine, including interventional strategies. The committee conducted a systematic review and (when evidence was sufficient) a meta-analytic review by using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and the modified Cochrane Risk of Bias analysis available in the Covidence data management program. Clinical questions addressed adults with migraine who should be offered prevention. Examined outcomes included headache days, acute medication use, and functional impairment. Acute management of migraine was outside the scope of this guideline.ResultsThe committee screened 1,195 studies and assessed 352 by full text, yielding 16 randomized controlled trials that met the inclusion criteria.Recommendations and ConclusionsAs informed by evidence related to the preselected outcomes, adverse event profile, cost, and values and preferences of patients, onabotulinumtoxinA received a strong recommendation for its use for chronic migraine prevention and a weak recommendation against its use for episodic migraine prevention. Greater occipital nerve blocks received a weak recommendation for their use for chronic migraine prevention. For greater occipital nerve block, steroid received a weak recommendation against its use vs the use of local anesthetic alone. Occipital nerve with supraorbital nerve blocks, sphenopalatine ganglion blocks, cervical spine percutaneous interventions, and implantable stimulation all received weak recommendations for their use for chronic migraine prevention. The committee found insufficient evidence to assess trigger point injections in migraine prevention and highly discouraged the use of intrathecal medication.

PURPOSE This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)–negative. METHODS An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS The Expert Panel reviewed abstracts from the literature review and retained 14 articles. RECOMMENDATIONS Patients with triple-negative, programmed cell death ligand-1–positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1–negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2–negative MBC for whom chemotherapy is being considered should be offered single–agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible. Additional information is available at www.asco.org/breast-cancer-guidelines .

Abstract Background Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers, and clinicians led us to conduct a survey to identify opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals. Methods In summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates including the European Association of Neuro-Oncology (EANO), Asian Society for Neuro-Oncology (ASNO), Society for Neuro-Oncology Latin America (SNOLA) and Society for Neuro-Oncology Sub-Saharan Africa (SNOSSA). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career service metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic, and sexual identity. Standard descriptive statistics characterized the study population. Results The 386 respondents were predominantly female (58%) with a median age range of 40–49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology field. Conclusions The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.

Background: Tissue reperfusion is a critical determinant of outcomes after intra-arterial therapy (IAT). However, there is no standardized method for grading angiographic reperfusion. We sought to compare the two most commonly used reperfusion scales, TIMI and modified TICI (m-TICI), for predicting good long-term outcome following IAT. Methods: From a multicenter database, we evaluated acute stroke patients presenting with middle cerebral artery (MCA) M1 occlusions who underwent IAT. Clinical and angiographic data were collected. Reperfusion for each case was graded using the TIMI and m-TICI scales. The primary distinction between these scales is that partial reperfusion (TIMI 2) is sub-divided into minor (m-TICI 2A: <50%) and major (m-TICI 2B: 50-99%) grades in the m-TICI system. The performance of these scales for predicting a good 90-day outcome (mRS 0-2) was evaluated using the c-statistic. Results: There were 313 acute stroke patients with MCA M1 segment occlusions who underwent IAT at 6 academic centers; 171 (54.6%) were female. Mean age was 65.3±16.5 years. There were 157 (50.2%) right-sided strokes. Median baseline NIHSS score was 17 (IQR 15-20). Good outcome at 90 days was achieved in 32.5%. For predicting good outcome, the c-statistic was significantly higher for m-TICI (0.74 vs. 0.68; p<0.0001). The threshold that maximized predictive accuracy was m-TICI ≥2B (sensitivity 78%, specificity 65%; figure). Conclusions: The modified TICI scale is superior to the TIMI scale for predicting clinical outcome after IAT, and should be the standard tool for grading angiographic reperfusion. An m-TICI score ≥2B (≥50% reperfusion) is the optimal biomarker for successful reperfusion.

Autonomous cortisol secretion (ACS) affects up to 50% of patients with adrenal adenomas. Despite the limited evidence, clinical guidelines recommend measurement of serum concentrations of dehydroepiandrosterone-sulfate (DHEA-S) and corticotropin (ACTH) to aid in the diagnosis of ACS. Our objective was to determine the accuracy of serum concentrations of DHEA-S and ACTH in diagnosing ACS. We conducted a retrospective single center study of adults with adrenal adenoma evaluated between 2000−2020. Main outcome measure was diagnostic accuracy of DHEA-S and ACTH. ACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. Of 468 patients, ACS was diagnosed in 256 (55%) patients with a median post-DST cortisol of 3.45 mcg/dL (range, 1.9–32.7). Patients with ACS demonstrated lower serum concentrations of DHEA-S (35 vs. 87.3 mcg/dL, p < 0.0001) and ACTH (8.3 vs. 16 pg/mL, p < 0.0001) compared to patients with non-functioning adrenal tumors (NFAT). Serum DHEA-S concentration <40 mcg/dL diagnosed ACS with 84% specificity and 81% PPV, while serum ACTH concentration <10 pg/mL diagnosed ACS with 75% specificity and 78% PPV. The combination of serum concentrations of DHEA-S <40 mcg/dL and ACTH <10 pg/mL diagnosed ACS with the highest accuracy with 92% specificity and 87% PPV. Serum concentrations of DHEA-S and ACTH provide additional value in diagnosing ACS.

Background: We performed a multicenter prospective clinical registry across 11 centers to study the association between histopathological characteristics of retrieved clots and imaging, stroke etiology and clinical outcomes. Materials and Methods: Following IRB approval at the 11 centers, patients were enrolled in the STRIP registry. All retrieved emboli were sent for histopathological analysis with H&E and MSB staining. Demographic variables, comorbidities, stroke etiology, imaging findings and procedural details were collected for each case. We studied the association between clot histopathology and imaging findings, stroke etiology and and revascularization outcomes. Student’s t-test was used for continuous variables and chi-squared testing for categorical variables. Results: To date, 1022 patients have been included. There was a significant correlation between platelet rich clots and the absence of hyperdensity on non-contrast CT [p=0.321, p=0.003) and a significant inverse correlation between the percentage of platelets and mean HU on NCCT (p=-0.243, p=0.025). The proportion of platelet-rich clots (55.0% versus 21.2%, p=0.005) and the percentage of platelet content (22.1% versus 13.9%, p=0.03) was significantly higher in patient with large artery atherosclerosis compared to those with a cardioembolic etiology. There was no correlation between RBC density, WBC density, fibrin density or platelet density and revascularization outcomes with stent-retrievers. However, we have found that with aspiration alone, patients with platelet rich clots are less likely to be fully revascularized (i.e. TICI 2c/3) than non-platelet rich clots (OR=0.36, 95%CI=0.12-0.81, P<.0001). Meanwhile, patients with RBC rich clots are more likely to be completely revascularized with aspiration alone than those with RBC poor clots (OR=2.71, 95%CI=1.25-3.24, P=0.02). Conclusions: Interim analysis of the STRIP registry suggests that the platelet content of a clot may be the most revealing factor in determining a clot’s etiology, imaging features and revascularization outcome. Platelet rich clots are less dense on NCCT, are associated with a large artery atherosclerosis source and are less likely to be completely revascularized with aspiration alone.

Some studies report an increase of resting muscle sympathetic nerve activity (MSNA) during the midluteal (ML) phase of the menstrual cycle when compared to the early follicular phase (EF), while others do not. The inconsistent findings may be due, in part, to variable surges in estradiol and progesterone. We tested the hypothesis that the degree of sympathoexcitation during the ML phase (ΔMSNA) is associated with changes in estradiol (ΔE 2 ) and progesterone (ΔP). Retrospective analysis of previous studies with recordings of mean arterial pressure (MAP), MSNA, E 2 , and P during both EF and ML phases yielded 30 eumenorrheic women (age, 18–51 yrs). ML phase increased E 2 (37±2 to 117±9 pg/ml; p<.001), P (1±0 to 11±1 ng/ml; p<.001), and MSNA (12±1 to 15±1 bursts/min; p=.02), but did not alter MAP (83±2 to 83±2 mmHg; p=.91). ΔMSNA was correlated to ΔE 2 (r=−.50, p=.005) and ΔE 2 /ΔP (r=−.52, p=.004), but not ΔP (r=.21, p=.26). There was no association between ΔMAP and ΔE 2 (r=−.13, p=.49), ΔP (r=−.04, p=.83), or ΔE 2 /ΔP (r<.01, p=.98). In conclusion, sympathoexcitatory responses to the ML phase appear to be associated with the degree of sex steroid surges. While E 2 had a stronger influence on MSNA than P, it is worthy to note that a strong association with ΔMSNA persisted when both ΔE 2 and ΔP were considered. This dynamic interaction between E 2 , P, and MSNA likely explains previously reported inconsistencies in the field. Supported by NIH.

We tested the hypothesis that ventilation (VE) and the hypoxic ventilatory response (HVR) during hyperthermia would be attenuated when carotid body chemosensitivity is blunted by an IV infusion of dopamine (2 µg/kg/min) vs. IV saline. We studied 9 subjects (1 woman, 32 ± 2 years, 25.7 ± 0.7 kg/m2) over two randomized dopamine and saline study visits. We measured VE and HVR (3 minutes at: room air, 16% O2, and 10% O2) at baseline and during normothermia (NORMInf) and hyperthermia (HYPInf) (core temperature 1.2‐1.5°C above baseline) infusion conditions. VE increased during HYPInf vs. NORMInf during dopamine (8.2 ± 0.3 vs. 10.2 ± 1.1 L/min; P = 0.04) and saline (8.9 ± 0.3 vs. 9.7 ± 0.5 L/min; P = 0.04) with no difference between conditions (P = 0.95). HVR during saline increased from baseline (0.30 ± 0.1 L/min/%SaO2; P < 0.01) and NORMInf (0.42 ± 0.1 L/min/%SaO2; P = 0.02) to HYPInf (0.77 ± 0.2 L/min/%SaO2). HVR did not change throughout the dopmaine visit (baseline = 0.38 ± 0.1; NORMInf = 0.27 ± 0.1; HYPInf 0.42 ± 0.1 L/min/%SaO2; P > 0.46). Dopamine HVR was lower than saline during HYPInf (P < 0.01). These data indicate that carotid body chemosensitivity to hypoxia is augmented during hyperthermia and that low dose dopamine was unable to lower normoxic VE during hyperthermia. Grant Funding Source : Supported by NIH R01DK090541 and RO1HL61388

The relationship between mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and total peripheral resistance (TPR) is altered in young women versus men and postmenopausal women due to endogenous sex hormone differences. Exogenous sex hormones in the form of oral contraceptive pills (OCPs) may further affect this relationship. We performed a retrospective review of 136 premenopausal women in whom MSNA and arterial pressure were measured, including 78 women with natural menstrual cycles in the early follicular phase (26±1 yr) and 58 women in the placebo phase of OCPs (24±1 yr). TPR and cardiac output (CO) were measured in a subset of women in whom continuous intra‐arterial blood pressure was recorded. Compared to those with natural menstrual cycles, women on OCPs had greater MAP (89±1 vs. 84±1 mmHg, p<0.01) and tended to have lower MSNA (15±1 vs. 18±1 bursts/100 heart beats, p=0.06). MAP and MSNA were positively correlated (r=0.22, p<0.05), TPR and MSNA were positively associated (r=0.41, p<0.05) and CO and MSNA (r=‐0.44, p<0.05) were inversely associated in naturally cycling women (n=26) but not in women on OCPs (r=0.15, r=0.11, r=‐0.01, respectively; p>0.05; n=38). In contrast to naturally cycling women, there appears to be no relationship between MSNA and hemodynamics in women on OCPs, suggesting that these women may regulate their blood pressure differently than women. Grant Funding Source : Supported by NIH