Background: A systematic and meta-analysis was conducted to examine the evidence of the effects of botulinum toxin A on chronic tension-type headache. Methods: Cochrane, Embase, Ovid, ProQuest, PubMed, Scopus, Web-of-Science databases, and ClinicallTrials.gov registry were systematically searched for studies examining the effects of botulinum toxin A on tension-type headaches. The records were screened by two independent reviewers using pre-determined eligibility criteria. DerSimonian Liard random-effects meta-analyses were performed using the ‘meta’ package (5.2-0) in R (4.2.0). Risk of bias and quality of evidence were assessed using the Cochrane Collaboration’s Tool RoB 2 and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Clinical significance was determined using pre-defined minimal clinically important differences. Results: Eleven controlled trials were included (390 botulinum toxin A, 297 controls). Botulinum toxin A was associated with significant improvements in standardized headache intensity (−0.502 standard deviations [−0.945, −0.058]), headache frequency (−2.830 days/month [−4.082, −1.578]), daily headache duration (−0.965 [−1.860, −0.069]) and the frequency of acute pain medication use (−2.200 days/month [−3.485, −0.915]) vs controls. Botulinum toxin A-associated improvements exceeded minimal clinically important differences for headache intensity, frequency, and acute pain medication use. A 79% (28%, 150%) greater response rate was observed for botulinum toxin A vs controls in improving chronic tension-type headache. Treatment of eight chronic tension-type headache patients was sufficient to elicit a therapeutic response in one patient. Conclusions: Corroborating the current mechanistic evidence, our meta-analysis supports the utility of botulinum toxin A for managing chronic tension-type headaches. However, due to limitations in the quality of evidence, adequately-powered high-quality controlled trials examining the effects of Botulinum toxin A on chronic tension-type headache are warranted. Registration: Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020178616)

Social determinants of health (SDOH) are important contributors to poor stroke-related outcomes. While some have suggested that this association is driven by the increased incidence of stroke observed with poor SDOH, others have raised concerns regarding disparities in acute stroke care. This study aimed to determine the association between SDOH and the administration of thrombolytic therapy and mechanical thrombectomy among patients with acute ischemic stroke. A retrospective cohort analysis was conducted using Texas Emergency Department Public Use Data (2016-2019), including adult patients diagnosed with acute ischemic stroke. The risk ratios (RRs) of administering thrombolysis and thrombectomy based on variables representing SDOH and a collective measure (Social Vulnerability Index [SVI]) were computed using mixed-effects Poisson regression models accounting for the nested nature of patients in hospitals and neighborhoods. The Charlson comorbidity score was considered as a covariate. Of the 139,852 patients with ischemic stroke (female, 51.7%; White, 67.2%; Black, 16.6%; Hispanic, 25.1%), 16,831 (12.3%) received thrombolytic therapy and 5,951 (4.3%) received mechanical thrombectomy. Age older than 65 years (RR 0.578 [0.537-0.621]) vs 18-45 years, Black (RR 0.801 [0.761-0.844]) vs White, Hispanic (RR 0.936 [0.895-0.98]) vs non-Hispanic, Medicare/Medicaid/Veterans Affairs (VA) (RR 0.917 [0.882-0.954]) or uninsured (RR 0.883 [0.833-0.935]) vs private insurance, and rural (RR 0.782 [0.723-0.845]) vs urban dwelling were less likely to be associated with thrombolysis. Patients in the highest quintile based on the SVI were less likely to receive thrombolysis than those in the lowest quintile (RR 0.926 [0.867-0.989]). Patients were less likely to receive thrombectomy if they were 65 years and older (RR 0.787 [0.691-0.895]), belonged to the Black race (RR 0.745 [0.679-0.818]) or Hispanic ethnicity (RR 0.919 [0.851-0.992]), had Medicare/Medicaid/VA insurance (RR 0.909 [0.851-0.971]), or were from a rural area (RR 0.909 [0.851-0.971]). Similarly, SVI decreased the likelihood of undergoing mechanical thrombectomy (RR 0.842 [0.747-0.95]). Despite many improvements in stroke management, SDOH continue to be a significant driver of treatment access for acute ischemic stroke. While our findings are limited to Texas, our results should raise awareness and promote more studies regarding the effects of these SDOH at the national and international levels.

Neoadjuvant chemotherapy (NAC) can affect pathological complete response (pCR) in breast cancers; the resection that follows identifies patients with residual disease who are then offered second-line therapies. Circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAMLs) in the blood can be used as potential biomarkers for predicting pCR before resection. CTCs are of epithelial origin that undergo epithelial-to-mesenchymal transition to become more motile and invasive, thereby leading to invasive mesenchymal cells that seed in distant organs, causing metastasis. Additionally, CAMLs in the blood of cancer patients are reported to either engulf or aid the transport of cancer cells to distant organs. To study these rare cancer-associated cells, we conducted a preliminary study where we collected blood from patients treated with NAC after obtaining their written and informed consent. Blood was collected before, during, and after NAC, and Labyrinth microfluidic technology was used to isolate CTCs and CAMLs. Demographic, tumor marker, and treatment response data were collected. Non-parametric tests were used to compare pCR and non-pCR groups. Univariate and multivariate models were used where CTCs and CAMLs were analyzed for predicting pCR. Sixty-three samples from 21 patients were analyzed. The median(IQR) pre-NAC total and mesenchymal CTC count/5 mL was lower in the pCR vs. non-pCR group [1(3.5) vs. 5(5.75); p = 0.096], [0 vs. 2.5(7.5); p = 0.084], respectively. The median(IQR) post-NAC CAML count/5 mL was higher in the pCR vs. non-pCR group [15(6) vs. 6(4.5); p = 0.004]. The pCR group was more likely to have >10 CAMLs post-NAC vs. non-pCR group [7(100%) vs. 3(21.4%); p = 0.001]. In a multivariate logistic regression model predicting pCR, CAML count was positively associated with the log-odds of pCR [OR = 1.49(1.01, 2.18); p = 0.041], while CTCs showed a negative trend [Odds Ratio (OR) = 0.44(0.18, 1.06); p = 0.068]. In conclusion, increased CAMLs in circulation after treatment combined with lowered CTCs was associated with pCR.