Search

Predictors for response to intensive therapy in AML have focused on baseline factors: percent leukemic blasts in marrow, cytogenetic/molecular genetic abnormalities, and presence of secondary AML. Non-baseline dynamic factors, occurring after induction but before response, may be useful for decisions related to salvage chemotherapy. We hypothesized white blood cell (WBC) count nadir after induction may be a real time indicator of treatment efficacy. We also examined whether time to stem cell transplant (SCT) or baseline molecular genetic abnormalities are associated with a low nadir. Data showed WBC nadir = 0 was a negative predictor for response to intensive induction and was correlated with reduced overall survival and progression free survival. Patients with WBC nadir = 0 did not have a significantly longer time to SCT, and none of the mutations increased the likelihood of reaching WBC nadir = 0. WBC nadir may be a useful real-time monitor in AML patients receiving intensive induction chemotherapy. [ABSTRACT FROM AUTHOR]

Full-length RNA-sequencing methods using long-read technologies can capture complete transcript isoforms, but their throughput is limited. We introduce multiplexed arrays isoform sequencing (MAS-ISO-seq), a technique for programmably concatenating complementary DNAs (cDNAs) into molecules optimal for long-read sequencing, increasing the throughput >15-fold to nearly 40 million cDNA reads per run on the Sequel IIe sequencer. When applied to single-cell RNA sequencing of tumor-infiltrating T cells, MAS-ISO-seq demonstrated a 12- to 32-fold increase in the discovery of differentially spliced genes. Programmable concatenation of cDNA molecules increases the throughput of PacBio sequencing about 15-fold. [ABSTRACT FROM AUTHOR]

Purpose: Telegenetics has become the predominant mode of cancer genetic counseling during the COVID-19 pandemic. We sought to identify potential patient-level contraindicators for telegenetic genetic counseling. Methods: We analyzed post-counseling (pre-result disclosure) follow-up data from a randomized noninferiority trial of a telephone genetic counseling versus usual care genetic counseling. Among 669 randomized participants, 600 completed pre-test counseling and 568 completed a 2-week follow-up assessment before receiving test results. In this analysis, we focused on genetic counseling outcomes (knowledge, decisional conflict, and distress). In multivariate models controlling for bivariate predictors of these outcomes, we tested our a priori hypotheses that pre-counseling numeracy, perceived stress, and race/ethnicity would moderate the outcomes of telephone genetic counseling versus usual care. Results: Only numeracy significantly moderated associations between mode of genetic counseling and outcomes. Higher numeracy was associated with higher post-counseling knowledge following telephone genetic counseling (p < 0.001), but not usual care (p = 0.450). Higher numeracy was also associated with lower distress following telephone genetic counseling (p = 0.009) but not usual care (p = 0.16). Neither perceived stress nor race/ethnicity exhibited differential impacts on telephone genetic counseling versus usual care (p s > 0.20). Conclusion: Although high numeracy was associated with higher levels of knowledge following telegenetic counseling, we did not identify any clinically significant patient-level contraindicators for telegenetic counseling. These results lend further confidence to the broad use of telegenetics. [ABSTRACT FROM AUTHOR]

Purpose: The assumption that patient–provider communication may mediate patients' sense of control over cancer to affect health outcomes has limited evidence. This study examines whether patient-perceived cancer care communication quality (PPCQ) mediates stress appraisal and coping behavior, affecting physical functioning across different racial groups. Methods: Two hundred and twenty Chinese American and 216 non-Hispanic White (NHW) women (ages 28–80) with stage 0–III breast cancer, 1–5 years post-diagnosis, and without recurrence, enrolled and completed a cross-sectional telephone survey. Physical functioning was measured by the NIH-PROMIS short form. Validated measures of PPCQ, patients' evaluation of their socioeconomic well-being, stress appraisal (perceived severity and control), use of coping strategies, treatment-related symptoms, and comorbidities were also assessed. Path analyses were used to examine the mediation for each racial group. Results: Regardless of race, treatment-related symptoms, comorbidities, and socioeconomic well-being were all directly related to physical functioning (p < 0.05). The impact of PPCQ on physical functioning was mediated by perceived control in the Chinese American group (p < 0.05), but not in the NHW group. Perceived severity and coping were not mediators of physical functioning in either group. Conclusions: The mediational pathway from PPCQ to perceived control to physical functioning in Chinese American survivors may be partially explained by their lower socioeconomic well-being and culturally valued conformity to physicians as a medical authority. These sociocultural dynamics reinforce the importance of cancer care communication. For NHW survivors, the impact of treatment-related symptoms and socioeconomic well-being on physical functioning outweighed their PPCQ and perceived control. [ABSTRACT FROM AUTHOR]

Background: Recently recognized as a distinct entity, a myxoid glioneuronal tumor (MGNT) is a rare, low-grade central nervous system tumor. MGNTs are commonly located at the septumpellucidum or in the third ventricle, increasing the likelihood of tumor or treatment-related damage to adjacent structures critical formemory, such as the fornix. Though there have been a handful of case reports of neurosurgical and oncological outcomes of MGNTs, memory outcomes following resection of MGNTs adjacent to the fornix have not been previously reported. Methods: We present a case of a high functioning female for whom an MRI revealed an incidental finding of an intraventricular tumor adjacent to the fornix bilaterally. The patient underwent resection of the tumor followed by MRI surveillance without additional oncologic intervention. Due to reported cognitive problems, the patient was referred for serial neuropsychological evaluations. Results: Post-operative MRI following resection revealed cytotoxic edema followed by selective, progressive atrophy of the bilateral anterior fornices. Post-surgically, the patient developed an isolated verbal memory impairment, which persisted one-year post resection with minimal improvement. The memory impairment impacted the patient's everyday functioning, including the ability to work in a cognitively demanding job. Conclusion: This unique case demonstrates the critical role of the bilateral fornix in verbal memory and underscores the importance of a careful risk/benefit analysis when considering neurosurgical intervention to MGNTs and other intracranial lesions adjacent to this structure during neurosurgical planning. [ABSTRACT FROM AUTHOR]

Genetic counseling and testing (GCT) inform cancer management for persons at risk for hereditary breast and ovarian cancer (HBOC). Community‐based organizations (CBOs) may play a role in identifying at‐risk Latinx individuals to connect them to GCT but data are lacking. Two academic centers and their four CBO partners planned to implement a validated questionnaire for HBOC risk screening ("HBOC risk screening tool"). This study aimed to assess CBO's preferences for HBOC risk screening tools, as well as the barriers and facilitators anticipated for future implementation. Pre‐implementation focus groups were conducted with CBO's staff. Discussions centered on current practices to identify and refer at‐risk patients. During the discussion, staff were asked to select one out of five validated HBOC risk screening tools to implement and to discuss anticipated barriers/facilitators for implementation. The four focus groups were coded and qualitative analyzed following the Consolidated Framework for Implementation Research (CFIR) and Health Equity domains. All CBOs chose the Family History Screen 7 (FHS‐7). Participants (N = 35) highlighted how the FHS‐7 was easy to adapt to better fit the target population and changing guidelines. They had positive attitudes toward implementing the screening tool, stressed how the culture of the organization positioned them to reach the target population, and noted barriers in different CFIR domains (e.g., low knowledge about HBOC and GCT referrals; scarce available resources). Participants pointed to barriers related to health equity domains including limited access to GCT and follow‐up care for uninsured and underinsured populations, challenges obtaining accurate family history, and immigration‐related barriers. CBOs highlighted the importance of partnering with other stakeholders to overcome barriers. Findings emphasize the need to develop multi‐level implementation strategies to overcome barriers and leverage facilitators. This study can inform the development of implementation toolkits for CBOs to implement HBOC screening tools to advance health equity. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) have transformed the management of cancer, producing durable responses in a subset of treated patients across multiple malignancies. Immune-mediated diarrhea and colitis (imDC) occurs in up to 20% of ICI-treated patients. The risk of ICI imDC is dependent upon the agent and is commoner with anti-CTLA-4 compared to anti-PD-1 ICIs. Generally, imDC is treated with steroids and agents targeting TNFα or α4β7 integrin. However, the management of steroids and/or biologic refractory imDC is unclear. We present a case of imDC in a 68-year-old female who failed to respond clinically, biochemically and immunohistochemically to corticosteroids, infliximab and vedolizumab. A trial of tofacitinib, a pan-JAK inhibitor, led to rapid clinical, biochemical and immunohistochemical control of imDC. ICIs result in a striking accumulation of cytotoxic and proliferative CD8 + T cells within tumor. However, the cellular and molecular mechanisms underlying imDC remain unclear. Herein, we observed significant T cell enrichment; and the successful treatment with tofacitinib highlights the potential of multiple convergent inflammatory pathways in imDC and inflammatory colitis. [ABSTRACT FROM AUTHOR]

Objectives: Dysregulation of BCL‐2 family members has been reported in acute lymphocytic leukemia (ALL), with various BH3‐dependencies of the leukemic clone. We conducted a multicenter retrospective cohort of patients with relapsed/refractory B or T ALL, with ven‐chemotherapy or ven‐navitoclax combinations, to assess efficacy and safety. Methods: Seventeen patients were included in the analysis, median age was 32 years, with 6 B‐ALL and 11 T‐ALL patients. Nine patients received venetoclax combined with chemotherapy, and 13 patients received venetoclax in combination with navitoclax, vincristine and asparaginase, of which 5 were already exposed to venetoclax in previous lines. Results: ORR was 55% and 46% among the ven‐chemotherapy and the ven‐navitoclax‐chemotherapy, respectively. Most of the responders proceeded to an allogenic bone marrow transplant in both cohorts. The most common adverse effects of the ven‐navitoclax combination were infectious complications and hepatotoxicity. Conclusions: Our data demonstrated the possible efficacy of ven‐chemotherapy and ven‐navitoclax in r/r ALL with moderate toxicity. [ABSTRACT FROM AUTHOR]

Purpose: High-volume hospitals are associated with improved surgical outcomes for acoustic neuromas (ANs). Due to the benign and slow-growing nature of ANs, many patients travel to geographically distant cities, states, or countries for their treatment. However, the impact of travel burden to high-volume centers, as well as its relative benefit are poorly understood. We compared post-operative outcomes between AN patients that underwent treatment at local, low-volume hospitals with those that traveled long distances to high-volume hospitals. Methods: The National Cancer Database was used to analyze AN patients that underwent surgery (2004–2015). Patients in the lowest quartile of travel distance and volume (Short-travel/Low-Volume: STLV) were compared to patients in the highest quartile of travel distance and volume (Long-travel/High-Volume: LTHV). Only STLV and LTHV cases were included for analysis. Results: Of 13,370 cases, 2,408 met inclusion criteria. STLV patients (n = 1,305) traveled a median of 6 miles (Interquartile range [IQR] 3–9) to low-volume centers (median 2, IQR 1–3 annual cases) and LTHV patients (n = 1,103) traveled a median of 143 miles [IQR 103–230, maximum 4,797] to high-volume centers (median 34, IQR 28–42 annual cases). LTHV patients had lower Charlson/Deyo scores (p = 0.001), mostly received care at academic centers (81.7% vs. 39.4%, p < 0.001), and were less likely to be minorities (7.0% vs. 24.2%, p < 0.001) or underinsured (4.2% vs. 13.8%, p < 0.001). There was no difference in average tumor size. On multivariable analysis, LTHV predicted increased likelihood of gross total resection (odds ratio [OR] 5.6, 95% confidence interval [CI] 3.8–8.4, p < 0.001), longer duration between diagnosis and surgery (OR 1.3, 95% CI 1.0-1.6, p = 0.040), decreased length of hospital stay (OR 0.5, 95% CI 0.4–0.7, p < 0.001), and greater overall survival (Hazard Ratio [HR] 0.6, 95% CI 0.4–0.95, p = 0.029). There was no significant difference in 30-day readmission on adjusted analysis. Conclusion: Although traveling farther to high-volume centers was associated with greater time between diagnosis and treatment for AN patients, they experienced superior postoperative outcomes compared to patients who received treatment locally at low-volume centers. Enabling access and travel to high-volume centers may improve AN patient outcomes. [ABSTRACT FROM AUTHOR]

Telephone genetic counseling (TGC) is accepted as standard clinical care for people seeking hereditary cancer risk assessment. TGC has been shown to be non-inferior to in-person genetic counseling, but trials have been conducted with a predominantly highly educated, non-Hispanic White population. This article describes the process of culturally adapting a TGC protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at risk for hereditary breast and ovarian cancers. The adaptation process included two phases. Phase 1 involved a review of the literature and recommendations from an expert team including community partners. Phase 2 included interviews and a pilot with the target population (n = 14) to collect feedback about the adapted protocol and booklet following steps from the Learner Verification and Revision Framework. We describe the adaptation process and report the main adaptations following the Framework for Reporting Adaptations and Modifications to Evidence-based Interventions (FRAME). Adaptations in Phase 1 were responsive to the target population needs and characteristics (e.g. delivered in Spanish at an appropriate health literacy level, addressing knowledge gaps, targeting cultural values). Phase 2 interviews were crucial to refine details (e.g. selecting words) and to add components to address GCT barriers (e.g. saliva sample video). Cultural adaptations to evidence-based TGC protocols can increase the fit and quality of care for historically underserved populations. As TGC visits become routine in clinical care, it is crucial to consider the needs of diverse communities to adequately promote equity and justice in cancer care. [ABSTRACT FROM AUTHOR]

In this study an interactive decision aid (DA) for men diagnosed with localized prostate cancer was adapted, extended and pre-tested. The DA's prototype was based on a literature review and other empirically tested DAs. Semi-structured interviews with 12 men (age 65–80) diagnosed with localized prostate cancer were conducted to get feedback on content, usability, and the DA's layout. The interviews were analyzed using thematic analysis and themes were identified using deductive and inductive coding. Participants found the accessibility of the information and the explicit values clarification tool helpful. Four themes were identified: (1) usability and design, (2) content and knowledge, (3) deciding factors of decision-making, and (4) social support. Participants valued receiving extensive and realistic information on surgery/radiation therapy side effects and getting unbiased presentations of treatment options. Following the thematic analysis, the DA was revised and tested in a survey among 11 newly diagnosed prostate cancer patients (age 60–74). The participants valued the DA and found it helpful when making a treatment decision, and all reported that they would recommend it to others making a prostate cancer treatment decision. The DA is currently being tested in a randomized clinical trial (RCT). This is the first DA developed for prostate cancer patients in Iceland and if the results of the RCT show that it is more effective than standard care in assisting newly diagnosed patients with their treatment decision, the DA can be easily translated and adapted to cultures similar to Iceland such as the Nordic countries. [ABSTRACT FROM AUTHOR]

Stimulator of interferon genes (STING) is an intracellular sensor of cyclic di-nucleotides involved in the innate immune response against pathogen- or self-derived DNA. STING trafficking is tightly linked to its function, and its dysregulation can lead to disease. Here, we systematically characterize genes regulating STING trafficking and examine their impact on STING-mediated responses. Using proximity-ligation proteomics and genetic screens, we demonstrate that an endosomal sorting complex required for transport (ESCRT) complex containing HGS, VPS37A and UBAP1 promotes STING degradation, thereby terminating STING-mediated signaling. Mechanistically, STING oligomerization increases its ubiquitination by UBE2N, forming a platform for ESCRT recruitment at the endosome that terminates STING signaling via sorting in the lysosome. Finally, we show that expression of a UBAP1 mutant identified in patients with hereditary spastic paraplegia and associated with disrupted ESCRT function, increases steady-state STING-dependent type I IFN responses in healthy primary monocyte-derived dendritic cells and fibroblasts. Based on these findings, we propose that STING is subject to a tonic degradative flux and that the ESCRT complex acts as a homeostatic regulator of STING signaling. STING is an intracellular sensor of pathogen- or host-derived DNA. In this study, the authors identify an ESCRT complex that regulates STING degradation, thus acting as a homeostatic regulator of STING signalling and type-I interferon responses. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the direct and indirect effects of a web-based, Protection Motivation Theory (PMT)–informed breast cancer education and decision support tool on intentions for risk-reducing medication and breast MRI among high-risk women. Women with ≥ 1.67% 5-year breast cancer risk (N = 995) were randomized to (1) control or (2) the PMT-informed intervention. Six weeks post-intervention, 924 (93% retention) self-reported PMT constructs and behavioral intentions. Bootstrapped mediations evaluated the direct effect of the intervention on behavioral intentions and the mediating role of PMT constructs. There was no direct intervention effect on intentions for risk-reducing medication or MRI (p's ≥ 0.12). There were significant indirect effects on risk-reducing medication intentions via perceived risk, self-efficacy, and response efficacy, and on MRI intentions via perceived risk and response efficacy (p's ≤ 0.04). The PMT-informed intervention effected behavioral intentions via perceived breast cancer risk, self-efficacy, and response efficacy. Future research should extend these findings from intentions to behavior. ClinicalTrials.gov Identifier: NCT03029286 (date of registration: January 24, 2017). [ABSTRACT FROM AUTHOR]

Background Serum protein reflects albumin and globulin levels, both of which can be altered in inflammatory bowel disease (IBD). The implications of a high globulin fraction in IBD are unknown. We hypothesized that a high globulin fraction may function independently of albumin as a biomarker of disease severity in IBD patients over a multiyear period. Methods This was an observational study from a prospective IBD registry of a tertiary care center. High globulin fraction was defined as an elevated globulin level >4 g/dL. Data collected included patient demographics, medication exposures, quality-of-life scores, disease activity, emergency department visits, telephone calls, hospitalizations, and IBD-related surgeries over a 4-year period. Comparisons between patients with a high globulin fraction and those without were performed using Pearson's chi-squared, Student's and Mann-Whitney tests. Multivariate analyses were used to assess the relationship between high globulin fraction and healthcare utilization. Results A total of 1767 IBD patients with a 4-year follow up were included: 53.5% female, mean age 48.4±15.1 years, and 65.4% with Crohn's disease. Of these patients, 446 (25.2%) presented with elevated globulin fraction. Patients with a high globulin fraction were more likely to be hospitalized during the study period. This result remained significant after multivariate analysis for both Crohn's disease patients and those with ulcerative colitis. Conclusion A high globulin fraction is independently associated with greater disease severity and healthcare utilization in IBD patients, and may function as a routinely available biomarker of a more severe future disease trajectory. [ABSTRACT FROM AUTHOR]

Objectives  To analyze the relationship between preoperative and intraoperative auditory brain stem response (ABR) characteristics and hearing outcomes in patients with vestibular schwannomas (VS) undergoing hearing preservation (HP) surgery via a middle cranial fossa (MCF) approach. Design  Prospective study. Setting  Academic tertiary skull base referral center. Methods  Pre- and postoperative pure-tone average (PTA) and word recognition score (WRS) were examined. Intraoperative ABR wave III latency, wave V latency, and amplitude were recorded. HP was defined as postoperative WRS ≥50%. Participants  Adult patients with VS and WRS ≥50% who underwent MCF tumor resection between November 2017 and September 2019. Main Outcome Measures  Postoperative hearing outcomes. Results  Sixty patients were included. Mean tumor size was 9.2 mm (range, 3–17). HP rates were 56.7% for the cohort and 69.7% for tumors <10 mm. A complete loss of wave V was associated with an 82.9% increase in postoperative PTA (p  < 0.001) and 97.2% decrease in WRS (p  < 0.001), whereas a diminished wave V was correlated with 62.7% increase in PTA (p  < 0.001) and 55.7% decrease in WRS (p  = 0.006). A diminished or absent wave V, but not increased wave III/V latency or decreased wave V amplitude, was correlated with a decline in postoperative hearing class (r  = 0.735, p  < 0.001). Receiver-operating characteristic analysis demonstrated that a stable wave V has the highest accuracy in predicting HP (sensitivity of 82.6%, specificity of 84.8%). Conclusion  Of the examined preoperative and intraoperative ABR characteristics, a stable wave V intraoperatively was the strongest predictor of HP after MCF resection of VS. Level of Evidence  Level III. [ABSTRACT FROM AUTHOR]

Objectives  Dispersion of bone dust in the posterior fossa during retrosigmoid craniectomy for vestibular schwannoma (VS) resection could be a source of meningeal irritation and lead to development of persistent postoperative headaches (POH). We aim to determine risk factors, including whether the presence of bone spicules that influence POH after retrosigmoid VS resection. Design  Present study is a retrospective case series. Setting  The study was conducted at a tertiary skull-base referral center. Participants  Adult patients undergoing VS resection via a retrosigmoid approach between November 2017 and February 2020 were included for this study. Main Outcome Measures  Development of POH lasting ≥ 3 months is the primary outcome of this study. Results  Of 64 patients undergoing surgery, 49 had complete data (mean age, 49 years; 53% female). Mean follow-up time was 2.4 years. At latest follow up, 16 (33%) had no headaches, 14 (29%) experienced headaches lasting <3 months, 19 (39%) reported POH lasting ≥3 months. Twenty-seven (55%) patients had posterior fossa bone spicules detectable on postoperative computed tomography (CT). Age, gender, body mass index, length of stay, tumor diameter, size of craniectomy, the presence of bone spicules, or the amount of posterior petrous temporal bone removed from drilling did not differ significantly between patients with POH and those without. On multivariate logistic regression, patients with POH were less likely to have preoperative brainstem compression by the tumor (odds ratio [OR] = 0.21, p  = 0.028) and more likely to have higher opioid requirements during hospitalization (OR = 1.023, p  = 0.045). Conclusion  The presence of bone spicules in the posterior fossa on postoperative CT did not contribute to headaches following retrosigmoid craniectomy approach for VS resection. [ABSTRACT FROM AUTHOR]

Background We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. Methods Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. Results A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P <.01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r  = 0.89, P  < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. Conclusions Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency. [ABSTRACT FROM AUTHOR]

Introduction: The Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE) study (ClinicalTrials.gov identifier: NCT00836017), a multicenter, prospective, observational registry, was designed to identify real-world practices and outcomes for patients with cervical dystonia (CD) treated with onabotulinumtoxinA (onabotA). This secondary analysis from CD PROBE aims to determine the impact of presentation subtype on onabotA utilization and CD severity. Materials and Methods: The study cohort includes those who completed all 3 treatments, 4 office visits, and had data recorded for all assessments. Patient outcomes were assessed with the Cervical Dystonia Impact Profile (CDIP-58), Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and determination of CD severity. Treatment interval, dose, and adverse events (AEs) were also recorded. Data were stratified according to prior exposure to botulinum toxins (BoNTs) and analyzed with descriptive statistics. Results: Torticollis was the most common presentation subtype in the study cohort (N = 350); the proportion of patients with torticollis was highest in those with severe disease. At each treatment, between 40.7 and 65.2% of those categorized as severe shifted to moderate or mild severity after treatment. Sustained improvements in CDIP-58 and TWSTRS were observed regardless of prior exposure to BoNTs. Dosing of onabotA generally increased from injection 1 to injection 3 and tended to be lower for patients naïve to BoNT. Median time interval between injections for the study cohort was 94.0 to 97.5 days. The most common AEs (dysphagia, muscular weakness) and injection intervals were similar between naïve vs. non-naïve patients; there were no serious treatment-related AEs. Conclusions: This secondary cohort analysis from CD PROBE demonstrates that three repeat treatments with onabotA at intervals consistent with labeling attenuated disease severity and neck pain, resulting in sustained improvements in physician- and patient-reported outcomes. No new safety signals were identified. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the BRCA1 and BRCA2 (BRCA1/2) genes are associated with elevated cancer risks in men and women. Due to a founder effect, Ashkenazi Jewish individuals are at higher risk for carrying three specific BRCA1/2 pathogenic variants. There have been recent calls for population screening in this population because many carriers do not have family histories suggestive of hereditary cancer. One approach could be to integrate optional BRCA1/2 testing into routinely offered reproductive carrier screening for recessive and X-linked disorders. However, the differing goals of these types of testing (i.e., personal health risks versus family planning) raise questions about the implications for patient education and informed consent. To this end, we aimed to determine interest, attitudes, and preferences regarding integrating such testing by electronically surveying 331 Ashkenazi Jewish participants in JScreen — a national, not-for-profit, at-home carrier screening program focused on genetic risks in Jewish communities. We found that while 41% of participants had plans to pursue BRCA1/2 testing, 93% would have opted for such testing if offered as an add-on to reproductive carrier screening. This was particularly true of those with higher perceived cancer risk and more positive attitudes toward genetic testing. With respect to preferences about delivery of this service, more than 85% of participants preferred remote (telephone, print, or web-based) genetic education rather than traditional genetic counseling. These results suggest that offering optional BRCA1/2 testing within the context of reproductive carrier screening might provide opportunities for cancer prevention without overburdening scarce genetic counseling resources. [ABSTRACT FROM AUTHOR]

Objective: As germline genetic referral becomes increasingly routine as part of the care of newly diagnosed breast cancer patients, it is important to understand the psychosocial impact of genetic counseling at the time of diagnosis. We examined the psychosocial and quality of life (QOL) impact of providing proactive rapid genetic counseling and testing (RGCT) in the immediate aftermath of a breast cancer diagnosis. Methods: We randomized 330 patients in a 2:1 ratio to proactive rapid genetic counseling (RGCT; N = 222) versus usual care (UC; N = 108). Participants completed a baseline telephone survey before randomization and definitive surgery and a follow‐up survey at 1‐month post‐randomization. We evaluated the impact of RGCT versus UC on breast cancer genetic knowledge, distress, QOL, and decisional conflict. Given that 43% of UC participants and 86% of RGCT participants completed genetic counseling prior to the 1‐month assessment, we also evaluated the impact of genetic counseling participation over and above group assignment. Results: The RGCT intervention led to increased breast cancer genetic knowledge relative to UC but did not differentially impact other study outcomes. Across groups patients who participated in genetic counseling had significantly increased knowledge and improved QOL compared to those who did not participate in genetic counseling. Conclusions: While prior research has documented the impact of genetic counseling and testing on surgical decisions, these results confirm that participation in genetic counseling at the time of diagnosis can yield improvements in knowledge and QOL in the short‐term. [ABSTRACT FROM AUTHOR]

The superior sagittal sinus (SSS) is a midline structure of the superficial cerebral venous system that drains the anterior cerebral hemispheres. Hypoplasia of the rostral SSS is a known variant, although associated complications are rare. A woman in her 30s presented for evaluation of a symptomatic left-sided acoustic neuroma and was found to have an incidental chronic subdural haematoma (SDH) over the left frontoparietal convexity without trauma or precipitating event. The SDH expanded on serial imaging and the patient eventually underwent left-sided frontoparietal craniotomy for haematoma evacuation. Haematological evaluation was benign, but angiography revealed absence of the anterior half of the SSS. We report the first case of spontaneous SDH in the setting of hypoplastic rostral SSS. [ABSTRACT FROM AUTHOR]

Background: Breast density increases breast cancer risk and decreases mammographic detection. We evaluated a personalized web-based intervention designed to improve breast cancer risk communication between women and their providers. Materials and Methods: This was a secondary outcome analysis of an online randomized trial. Women aged 40–69 years were randomized, February 2017–May 2018, to a control (n = 503) versus intervention website (n = 492). The intervention website included information about breast density, personalized breast cancer risk, chemoprevention, and magnetic resonance imaging. Participants self-reported communication about density with providers (yes/no) at 6 weeks and 12 months. We used logistic regression with generalized estimating equations to evaluate the association of study arm with density communication. In secondary analyses, we tested if the intervention was associated with indicators of patient activation (breast cancer worry, perceived risk, or health care use). Results: Women (mean age 62 years) in the intervention versus control arm were 2.39 times (95% confidence interval [CI] = 1.37–4.18) more likely to report density communication at 6 weeks; this effect persisted at 12 months (odds ratio [OR] = 1.71, 95% CI = 1.25–2.35). At 6 weeks, this effect was only significant among women who reported (OR = 3.23, 95% CI = 1.24–8.40) versus did not report any previous density discussions (OR = 1.64, 95% CI = 0.83–3.26). A quarter of women in each arm never had a density conversation at any time during the study. Conclusions: Despite providing personalized density and risk information, the intervention did not promote density discussions between women and their providers who had not had them previously. This intervention is unlikely to be used clinically to motivate density conversations in women who have not had them before. Clinical trial registration number NCT03029286. [ABSTRACT FROM AUTHOR]

Health and safety concerns during the COVID-19 pandemic required many face-to-face United States schools to suddenly shut their doors, moving classes to virtual learning environments. Amidst concerns of technology overuse, adolescents across the country saw dramatic increases in both personal screen time use and social isolation as they learned to navigate online schooling. Understanding the impact of the pandemic-related shutdowns upon adolescent well-being, learning, and social life is critical for designing effective online learning experiences, but research provides few insights from the adolescent perspective. This mixed methods study works to fill this gap by investigating adolescent needs and perceptions during the pandemic. The main questions asked are: To what extent does adolescent well-being during the pandemic differ from pre-pandemic well-being? What factors do adolescents view as influences upon their learning during the imposed shift to online schooling? What social changes and concerns do adolescents report during the pandemic? Twenty-one adolescents completed Likert scale surveys and participated in semi-structured one-to-one interviews. Results showed a significant decrease in positive affect and a significant increase in negative affect during the pandemic, suggesting a decline in well-being. The majority of participants reported high distractibility and noted the lure of entertaining technology, but also described their smartphones as "connecting" and "necessary". Social interactions were a priority for all participants, but participants agreed that opportunities for social connectedness in online education were limited. The challenges of online learning, the importance of identifying and responding to student needs, and suggested strategies for online education are discussed. [ABSTRACT FROM AUTHOR]

Advances in neuroscience reveal how individual brains change as learning occurs. Translating this neuroscience into practice has largely been unidirectional, from researchers to teachers. However, how teachers view and incorporate neuroscience ideas in their classroom practices remains relatively unexplored. Previously fourteen non-science teachers participated in a 3-week three credit graduate course focusing on foundational ideas in neuroscience. The current work was undertaken to gain insight into if and how individual teachers choose to later apply the proposed set of educational neuroscience concepts (ENCs) in their classrooms. This qualitative follow-up study examined commonalities in how teachers of diverse ages and subjects utilized their new neuroscience understandings. To this end, a year after the course, all participants assessed their perceived usefulness of the ENCs in a survey. Six of those teachers permitted classroom observations and participated in interviews that focused on how the ENCs may have influenced their lesson planning and teaching. The survey revealed that irrespective of subject areas or grade levels taught, teachers found the ENCs useful as organizing principles for their pedagogy now and in the future. Overall teachers estimated that the ENCs' influence on lesson design had increased from 51% prior to the course to an estimated 90% for future lessons. A cross-case analysis of classroom observations and interviews revealed how teachers used ENCs to inform their pedagogical decisions, organize actions in their classroom, influence their understanding of students, and respond to individual contexts. Teachers recognized the importance of student agency for engaging them in the learning process. The ENCs also offered teachers explanations that affirmed known practices or helped justify exploring untried techniques. The foundational neuroscience concepts offered a small group of teachers a lens to reconsider, re-envision and re-design their lessons. Some teachers applied these ideas more broadly or frequently than others. This case study provided insights into how teachers can directly apply neuroscience knowledge to their practice and views of students. [ABSTRACT FROM AUTHOR]

Widely-used response criteria, conditional upon count recovery, were developed for acute myeloid leukemia (AML) in the context of intensive chemotherapy (IC). Extending these definitions to continuously-administered venetoclax-based therapies might underestimate responses. Best practices for venetoclax-based therapies mandate interruption after an end-of-cycle 1 bone marrow biopsy shows morphologic remission with cytopenias. We analyzed 435 patients with newly-diagnosed AML and follow-up response assessments. Of the 101 who responded to venetoclax + azacitidine, overall survival for patients whose response was upgraded due to count recovery during a 14-day post-disease assessment period, from complete remission (CR) with incomplete recovery of blood counts to CR, was not different compared to patients who did not need the 14-day period for count recovery. These results were distinct from 138 IC patients. Although sample sizes for the comparison groups were small, and conclusions are exploratory and must be verified, these findings support consideration of new response criteria for venetoclax-based regimens. [ABSTRACT FROM AUTHOR]

This paper presents a process evaluation of a culturally targeted narrative video about hereditary breast and ovarian cancer (HBOC) for Latina women at risk for HBOC. Spanish‐speaking Latina women at risk for HBOC participated in a single arm study (n = 40). Participants watched the video developed by the authors and responded to surveys. We used mixed methods to assess theoretical constructs that are hypothesized mediators of narrative interventions (i.e., transportation or engagement, identification with characters, emotions) and implementation outcomes (e.g., acceptability). Descriptive statistics summarized theoretical constructs and implementation outcomes. We conducted Mann–Whitney U tests to assess the differences in theoretical and implementation outcomes between participants who were affected versus. unaffected and participants with different levels of education and health literacy. We used the consensual qualitative research framework to analyze qualitative data. Participants' mean age was 47.1 years (SD = 9.48). Most participants were high school graduates or less (62.5%). Acceptability of the video was extremely high (Md = 10.0, IQR = 0.2, scale 1–10). Most (82.5%) suggested video dissemination be through social media. Participants were highly engaged (Md = 5.7, IQR = 1.5, scale 1–7), strongly identified with the main character (Md = 8.7, IQR = 2.6, scale 1–10), and reported experiencing mostly positive emotions (Md = 9.5, IQR = 2.8, scale 1–10). Participants with low health literacy and affected participants reported a significantly higher identification with the main character (p<.05). Qualitative data reinforced the quantitative findings. Women reported gaining knowledge, correcting misconceptions, and feeling empowered. Our culturally targeted video is highly acceptable and targets mechanisms of behavior change for narrative interventions. The video is easily disseminable and can be used as an education tool for patients including affected and unaffected women and patients with different education and health literacy levels. Future studies should test the impact of the video in enhancing genetic counseling and testing uptake. [ABSTRACT FROM AUTHOR]

Objective: To identify clinical predictors of facial nerve (FN) outcomes after microsurgical resection of vestibular schwannoma (VS).Study Design: Prospective cohort study.Setting: Academic medical center.Methods: Consecutive patients undergoing VS resection from November 2017 to October 2019 were included. FN function was evaluated with the House-Brackmann (HB) scale and stratified into good (HB I-II) and poor (HB III-VI) function. Analyses included descriptive statistics, correlation, and logistic regression.Results: Of 256 patients who met criteria (mean age, 47.7 years; 62.5% female), 227 (88.7%) achieved good FN function postoperatively and 238 (93.0%) at latest follow-up (mean, 154.8 days). Operative approaches consisted of translabyrinthine (50.8%), retrosigmoid (25.0%), and middle fossa craniotomies (24.2%). Extent of resection was decided intraoperatively, and gross or near total resection was accomplished in 237 (92.6%) cases. Postoperative HB grade correlated with latest HB grade (0.615, P < .001). Factors associated with good postoperative FN function included small tumor size (≤15 mm; odds ratio [OR], 2.425; P = .042), gross or near total resection (OR, 3.170; P = .041), and ≥100-µV intraoperative FN electromyographic response to a 0.05-mA stimulus (OR, 22.242; P < .001). Factors associated with good FN function at latest follow-up included gross total resection (OR, 7.764; P = .003) and ≥100-µV FN electromyographic response (OR, 8.518; P < .001), accounting for surgical approach and tumor size.Conclusion: Microsurgical resection of VS can be accomplished with excellent FN outcomes. Gross total resection and ≥100-µV intraoperative FN electromyographic response predicted excellent FN outcomes. Immediate postoperative FN function is a prognosticator of long-term FN function. [ABSTRACT FROM AUTHOR]