Neuroprosthesis for Decoding Speech in a Paralyzed Person with Anarthria.

BACKGROUND: Technology to restore the ability to communicate in paralyzed persons who cannot speak has the potential to improve autonomy and quality of life. An approach that decodes words and sentences directly from the cerebral cortical activity of such patients may represent an advancement over existing methods for assisted communication. METHODS: We implanted a subdural, high-density, multielectrode array over the area of the sensorimotor cortex that controls speech in a person with anarthria (the loss of the ability to articulate speech) and spastic quadriparesis caused by a brain-stem stroke. Over the course of 48 sessions, we recorded 22 hours of cortical activity while the participant attempted to say individual words from a vocabulary set of 50 words. We used deep-learning algorithms to create computational models for the detection and classification of words from patterns in the recorded cortical activity. We applied these computational models, as well as a natural-language model that yielded next-word probabilities given the preceding words in a sequence, to decode full sentences as the participant attempted to say them. RESULTS: We decoded sentences from the participant's cortical activity in real time at a median rate of 15.2 words per minute, with a median word error rate of 25.6%. In post hoc analyses, we detected 98% of the attempts by the participant to produce individual words, and we classified words with 47.1% accuracy using cortical signals that were stable throughout the 81-week study period. CONCLUSIONS: In a person with anarthria and spastic quadriparesis caused by a brain-stem stroke, words and sentences were decoded directly from cortical activity during attempted speech with the use of deep-learning models and a natural-language model. (Funded by Facebook and others; ClinicalTrials.gov number, NCT03698149.).

Characteristics associated with inter-individual variability in financial distress in patients with breast cancer prior to and for 12 months following surgery.

PURPOSE: To evaluate for inter-individual differences in financial distress and identify demographic, clinical, and symptom characteristics associated with higher levels of financial distress. METHODS: Patients (n = 387) were enrolled prior to breast cancer surgery and followed for 12 months. Financial distress was measured using a 0 (no problem) to 10 (severe problem) numeric rating scale. Hierarchical linear modeling was used to evaluate for inter-individual differences in trajectories of financial distress and characteristics associated with financial distress at enrollment and over 12 months. RESULTS: Patients' mean age was 55.0 (± 11.7) years and the majority underwent breast conservation surgery (80.6%). Mean financial distress score prior to surgery was 3.3 (± 3.4; range 0 to 10). Unconditional model for financial distress demonstrated no significant changes over time (-0.006/month). Younger age, lower income, receipt of an axillary lymph node dissection and adjuvant chemotherapy, and lower attentional function were associated with higher preoperative levels of financial distress. CONCLUSION: Risk factors identified in this study can be used to inform clinicians regarding the need to initiate financial discussions and social work referrals for some patients. Additional clinical or system level interventions should be considered for vulnerable groups with these risk factors.

Cross-sectional examination of ultra-processed food consumption and adverse mental health symptoms.

OBJECTIVE: To explore whether individuals who consume higher amounts of ultra-processed food (UPF) have more adverse mental health symptoms. DESIGN: Using a cross-sectional design, we measured the consumption of UPF as a percentage of total energy intake in kilo-calories using the NOVA food classification system. We explored whether individuals who consume higher amounts of UPF were more likely to report mild depression, more mentally unhealthy days and more anxious days per month using multivariable analyses adjusting for potential confounding variables. SETTING: Representative sample from the United States National Health and Nutrition Examination Survey between 2007 and 2012. PARTICIPANTS: 10 359 adults aged 18+ without a history of cocaine, methamphetamine or heroin use. RESULTS: After adjusting for covariates, individuals with the highest level of UPF consumption were significantly more likely to report at least mild depression (OR: 1·81; 95 % CI1·09, 3·02), more mentally unhealthy (risk ratio (RR): 1·22; 95 % CI 1·18, 1·25) and more anxious days per month (RR: 1·19; 95 % CI 1·16, 1·23). They were also significantly less likely to report zero mentally unhealthy (OR: 0·60; 95 % CI 0·41, 0·88) or anxious days (OR: 0·65; 95 % CI 0·47, 0·90). CONCLUSIONS: Individuals reporting higher intakes of UPF were significantly more likely to report mild depression, more mentally unhealthy and more anxious days and less likely to report zero mentally unhealthy or anxious days. These data add important information to a growing body of evidence concerning the potential adverse effects of UPF consumption on mental health.

P067 Immune Checkpoint Inhibitor Colitis in a Community-Based Hospital System.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly changed the oncologic treatment landscape for a wide array of cancers over the past few decades. While these medications can produce a durable remission for patients they also come with a risk of inflammatory toxicities. With the widespread use of immune checkpoint inhibitors there have been increased reports of immune-related adverse events (irAEs) including severe gastrointestinal toxicities such as colitis. While multiple studies have assessed ICI colitis in tertiary care settings little is reported on the characteristics and treatment outcomes of ICI colitis in a community-based population. Additionally, the utility of gastroenterologists in the diagnosis and management of ICI colitis is poorly defined. The aim of this study is to report the characteristics and treatment outcomes of ICI colitis in a community-based hospital system. METHODS: This is a single-center retrospective case-series of patients with ICI colitis. Charts were reviewed from patients in the Prisma Health Upstate Network from 2/1/2016 to 12/31/2020. Potential cases of ICI colitis were identified using a diagnosis code of "toxic colitis", "indeterminate colitis", "unspecified colitis", and "noninfective gastroenteritis and colitis" (ICD-10 K52.1, K 52.3, K 52.89 and K52.9) as well as a prior infusion (within 12 months) of pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, durvalumab, or ipilimumab. Charts were abstracted for demographics, tumor type, checkpoint inhibitor used, mode of colitis diagnosis, endoscopic severity of inflammation, and treatments used. Study was approved by the Institutional Review Board at Prisma Health Upstate. RESULTS: The mean (±SD) age for the 37 patients was 64.1 ± 13.2 years. The patient population was predominantly male (62%) and Caucasian (100%). The cancer type in the patient population were melanoma (43.2%), non-small cell lung cancer (18.9%), renal cell carcinoma (10.8%), and other (27%). Patients with ICI colitis were most-commonly treated with ipilimumab (35.1%), nivolumab (35%), pembrolizumab (10.8%), and other (13.5%). The mean time to colitis onset was 25.7 ± 29.7 weeks. Over 56% of the patient population reported abdominal pain and 45.9% were hospitalized. Only 64.8% were evaluated by a gastroenterologist. Cross sectional abdominal imaging by computed tomography (CT) was obtained in 20 (54.0%) and showed colitis in 13. 54% obtained a colonoscopy with inflammation severity stratified into normal (25.0%), mild (40.0%), moderate (20.0%) and severe (15.0%). Endoscopic extent showed proctitis (0%), left-sided disease (5.0%), right-sided disease (5.0%), pancolitis (55.0%), and isolated ileal disease (25%). Histology showed 90.0% with active inflammation and 10.0% with microscopic colitis. Outcomes were resolution with steroids (64.8%), antibiotics (5.4%), biologic (10.8%), surgery (5.4%), hospice (8.1%). Of those that received biologic therapy, 6 received infliximab and 1 received vedolizumab. CONCLUSION: As immune checkpoint inhibitors gain approval in more cancer treatment ICI-colitis is being seen in a community-based setting. The most common treatment were steroids and often required a prolonged course. Biologic use in our series (18.9%) was much lower than prior reports from academic tertiary referral centers (>50%). Only 64.8% of patients saw a gastroenterologist for ICI-colitis symptoms. Early gastroenterology referral in the community setting could help to identify more severe disease and patients necessitating escalation to biologic therapy.

Cardiovascular Risk Factors in Young Adolescents: Results from the National Health and Nutrition Examination Survey 1988-2016.

OBJECTIVES: Lifestyle behaviors relevant to cardiovascular health are learned during childhood and continued into adulthood. Children and adolescents who participate in unhealthy behaviors have a higher lifetime risk of cardiovascular disease in adulthood. Public health institutions publish behavior and clinical recommendations designed for adolescents to reduce their lifetime cardiovascular risk. We assessed the prevalence and trends of cardiovascular-relevant behaviors and clinical tests among early adolescents using a nationally representative database. METHODS: In 2020, we compared the prevalence of cardiovascular risk factors among 1408 adolescents surveyed from 1988 to 1994 with that of 1812 adolescents surveyed from 2011 to 2016 by obtaining and comparing measures on physical activity, diet, body mass index, smoking status, cholesterol levels, hemoglobin A1c, sodium intake, and blood pressure. RESULTS: The prevalence of adherence to the current recommendations regarding physical activity, diet, and body weight declined over time. Conversely, the prevalence of adhering to recommendations to avoid smoking increased. Clinical indicators, including blood pressure control and normal measures of hemoglobin A1c and total serum cholesterol, showed mixed results, with more individuals showing signs of hyperglycemia, fewer showing signs of hypercholesterolemia, and the percentage of individuals with abnormal blood pressure remaining the same. The use of cardiometabolic medications also increased during the study period. Finally, the number of adolescents with all seven cardiovascular protective factors declined significantly during the study period, from 27.6% to 9.6%. CONCLUSIONS: Modern American teenagers aged 12 to 16 years have more cardiovascular risk factors relating mostly to diet, exercise, and obesity than those of a prior generation; however, smoking rates have also declined precipitously.

Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain.

BACKGROUND: Paclitaxel is an important chemotherapeutic agent for the treatment of breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a major dose-limiting toxicity that can persist into survivorship. While not all survivors develop PIPN, for those who do, it has a substantial negative impact on their functional status and quality of life. No interventions are available to treat PIPN. In our previous studies, we identified that the HIF-1 signaling pathway (H1SP) was perturbed between breast cancer survivors with and without PIPN. Preclinical studies suggest that the H1SP is involved in the development of bortezomib-induced and diabetic peripheral neuropathy, and sciatic nerve injury. The purpose of this study was to identify H1SP genes that have both differential methylation and differential gene expression between breast cancer survivors with and without PIPN. METHODS: A multi-staged integrated analysis was performed. In peripheral blood, methylation was assayed using microarray and gene expression was assayed using RNA-seq. Candidate genes in the H1SP having both differentially methylation and differential expression were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN. Then, candidate genes were evaluated for differential methylation and differential expression in public data sets of preclinical models of PIPN and sciatic nerve injury. RESULTS: Eight candidate genes were identified as both differential methylation and differential expression in survivors. Of the eight homologs identified, one was found to be differential expression in both PIPN and "normal" mice dorsal root ganglia; three were differential methylation in sciatic nerve injury versus sham rats in both pre-frontal cortex and T-cells; and two were differential methylation in sciatic nerve injury versus sham rats in the pre-frontal cortex. CONCLUSIONS: This study is the first to evaluate for methylation in cancer survivors with chronic PIPN. The findings provide evidence that the expression of H1SP genes associated with chronic PIPN in cancer survivors may be regulated by epigenetic mechanisms and suggests genes for validation as potential therapeutic targets.

Improved CoChR Variants Restore Visual Acuity and Contrast Sensitivity in a Mouse Model of Blindness under Ambient Light Conditions.

Severe photoreceptor cell death in retinal degenerative diseases leads to partial or complete blindness. Optogenetics is a promising strategy to treat blindness. The feasibility of this strategy has been demonstrated through the ectopic expression of microbial channelrhodopsins (ChRs) and other genetically encoded light sensors in surviving retinal neurons in animal models. A major drawback for ChR-based visual restoration is low light sensitivity. Here, we report the development of highly operational light-sensitive ChRs by optimizing the kinetics of a recently reported ChR variant, Chloromonas oogama (CoChR). In particular, we identified two CoChR mutants, CoChR-L112C and CoChR-H94E/L112C/K264T, with markedly enhanced light sensitivity. The improved light sensitivity of the CoChR mutants was confirmed by ex vivo electrophysiological recordings in the retina. Furthermore, the CoChR mutants restored the vision of a blind mouse model under ambient light conditions with remarkably good contrast sensitivity and visual acuity, as evidenced by the results of behavioral assays. The ability to restore functional vision under normal light conditions with the improved CoChR variants removed a major obstacle for ChR-based optogenetic vision restoration.

Autoimmune retinopathy associated with monoclonal gammopathy of undetermined significance: a case report.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia and precursor to multiple myeloma. It has known ocular manifestations, but has not previously been shown to have an association with autoimmune retinopathy. CASE PRESENTATION: A 57 year-old female presented with 1 year of progressive, bilateral, peripheral vision loss, photopsias, and nyctalopia. Her fundus examination and extensive ancillary testing were concerning for hereditary versus autoimmune retinopathy. The patient was found to have anti-retinal antibodies against carbonic anhydrase II and enolase proteins with a negative genetic retinal dystrophy panel. Malignancy work-up was negative, but the patient was diagnosed with MGUS, a premalignant condition. The patient was treated with immunosuppressive therapies, with rituximab demonstrating the most robust therapeutic response with respect to patient symptoms and ophthalmic testing. CONCLUSIONS: MGUS should be considered as a potential etiology of autoimmune retinopathy in patients without other autoimmune or malignant disease processes. Immunosuppressive therapy may be helpful in limiting disease progression, with rituximab showing efficacy in retinopathy refractory to other agents.

Age-related differences in patient-reported and objective measures of chemotherapy-induced peripheral neuropathy among cancer survivors.

PURPOSE: While older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors. METHODS: Cancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory, and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (< 65 n = 260 versus ≥ 65 n = 165) using parametric and nonparametric tests. RESULTS: Among 425 cancer survivors with CIPN, mean age was 60.9 (SD 10.5). CIPN location did not differ by age (overall 68% hands and feet, 27% only feet, 5% only hands). For patient-reported measures, older survivors reported less severe pain in the hands and feet than younger survivors. In addition, older survivors reported lower interference with general activity, routine activities, normal work, enjoyment of life, sleep, mood, relations with other people, and sexual activity. No age differences in sensory and motor symptom scores were found. In contrast, for objective measures, older survivors had worse light touch and cold sensations in their feet and worse vibration detection in their hands and feet. CONCLUSIONS: Despite having worse light touch, cold, and vibration sensations, older cancer survivors with CIPN reported less severe pain and interference with activities. This discordance highlights the importance of including both patient-reported and objective measures to assess CIPN in cancer survivors to better evaluate this clinical condition.

Adaption of the Biopsychosocial Model of Chronic Noncancer Pain in Veterans.

Population: Veterans with chronic noncancer pain (CNCP) are a vulnerable population whose care remains a challenge for clinicians, policy-makers, and researchers. As a result of military experience, veterans are exposed to high rates of musculoskeletal injuries, trauma, psychological stressors (e.g., post-traumatic stress disorder, depression, anxiety, substance abuse), and social factors (e.g., homelessness, social isolation, disability, decreased access to medical care) that contribute to the magnitude and impact of CNCP. In the veteran population, sound theoretical models are needed to understand the specific physiological, psychological, and social factors that influence this unique experience. Objective: This paper describes an adaption of Gatchel and colleagues' biopsychosocial model of CNCP to veterans and summarizes research findings that support each component of the revised model. The paper concludes with a discussion of important implications for the use of this revised model in clinical practice and future directions for research. Conclusions: The adaption of the biopsychosocial model of CNCP for veterans provides a useful and relevant conceptual framework that can be used to guide future research and improve clinical care in this vulnerable population.

Long-term effects of executive function training among veterans with chronic TBI.

Objective: To investigate long-term effects of GOALS executive function training in Veterans with chronic TBI. In a recently completed study Veterans with chronic TBI showed improvement immediately post-GOALS but not control training on measures of executive function, functional task performance, and emotion regulation. We now examine the long-term maintenance of post-GOALS training changes in the same sample. Setting: San Francisco VA Health Care System (SFVAHCS), and VA Northern California Health-Care System (VANCHS) in Martinez. Participants and Design: 24 Veterans with chronic TBI were assessed at baseline, post-GOALS training, and long-term follow-up 6+ months following completion of training with a structured telephone interview, neuropsychological and complex functional performance measures, and self-report measures of daily and emotional functioning. Results: Participants reported an increased likelihood of involvement in competitive employment/volunteering at follow-up (61%) compared to baseline (26%; χ2 = 5.66, p < .01, ѱ = .35). Repeated measures MANOVAS indicated improvement on attention/executive function (F = 13.85, p < .01, partial η2 = .42), complex functional task performance (GPS Total: F = 9.12, p < .01, partial η2 = .38) and daily functioning (MPAI Total: F = 3.23, p < .05, partial η2 = .21), and reduction in overall mood disturbance (POMS Total: F = 3.42, p < .05, partial η2 = .22) at follow-up relative to baseline. Discussion: Training in attention regulation applied to participant-defined goals is associated with meaningful long-term improvement in cognitive skills, emotion regulation, and daily functioning in Veterans with chronic TBI.

OUTCOMES OF REPEAT PARS PLANA VITRECTOMY AFTER FAILED SURGERY FOR PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: To evaluate outcomes of repeat pars plana vitrectomy for proliferative vitreoretinopathy after previous failed pars plana vitrectomy. METHODS: This is a retrospective case series including 51 eyes of 50 patients who underwent repeat surgery after failed previous pars plana vitrectomy for proliferative vitreoretinopathy from 2000 to 2015 at the Kresge Eye Institute, Detroit, MI. Patients were classified into successful and unsuccessful groups. Success was defined as retinal reattachment, silicone oil removed, and best-corrected visual acuity (BCVA) ≥5/200 at the final follow-up visit. RESULTS: Forty-three eyes (84.3%) were successfully reattached at the last follow-up. Seventeen (33.3%) eyes were deemed successful and 34 (66.7%) eyes unsuccessful according to our criteria. Compared with the successful group, eyes in the unsuccessful group had more eyes with preoperative BCVA <5/200 (P < 0.001), preoperative BCVA of hand motion or worse (P = 0.002), preoperative flare ≥Grade 2+ (P = 0.03), preoperative posterior breaks (P = 0.02), previous retinectomy (P = 0.04), and final postoperative hypotony (intraocular pressure ≤ 5 mmHg) (P = 0.005). Eyes with silicone oil removed were more likely to have BCVA ≥5/200 (P < 0.001) at the final follow-up visit. Location of patients >100 miles (P = 0.04) from Detroit and preoperative BCVA of hand motion or worse (P = 0.01) were significantly associated with failure in the logistic regression analysis. CONCLUSION: Success after repeat surgery for proliferative vitreoretinopathy should include ambulatory vision, retinal reattachment, and silicone oil removal. We identified several preoperative and perioperative factors that were associated with success in the bivariate and logistic analyses. The decision to perform surgical reoperation in these patients should be based on multiple factors, most importantly preoperative BCVA.

Prevalence of HCV Infection in Adults with Congenital Heart Disease and Treatment with Direct Antiviral Agents.

OBJECTIVES: Hepatitis C virus (HCV) infection affects >3% of the US population, which over time can lead to cirrhosis and hepatocellular carcinoma. The lack of a reliable screening method for HCV before 1992 resulted in a higher prevalence of the virus in adults with congenital heart disease who underwent corrective surgery that required blood transfusions. Direct-acting antiviral agents such as sofosbuvir/ledipasvir have significantly increased the efficacy of HCV therapy, although use of these medications in adults with congenital heart disease has not been described. METHODS: Ours was a retrospective study of 188 adults with congenital heart conditions who had cardiac surgery before 1992. These patients were screened for HCV using HCV antibody followed by HCV RNA if the screening test was positive. RESULTS: Of the 188 adults, 116 (43% male patients, 24-70 years) were screened for the HCV antibody, demonstrating that 104 individuals were negative and 12 subjects were positive for the virus. Subsequently, further testing for the presence of HCV demonstrated 11 of 12 were infected, with an overall prevalence of 9.5%. Five individuals chose to be treated with sofosbuvir/ledipasvir and 5 of 5 have successfully cleared the virus and are considered cured. CONCLUSIONS: Adults with congenital heart disease who underwent cardiac surgery before 1992 warrant being screened for HCV, and, if testing positive, may be considered for therapy using direct-acting antiviral agents with close monitoring for cardiac complications.

Associations between genetic and epigenetic variations in cytokine genes and mild persistent breast pain in women following breast cancer surgery.

Persistent pain following breast cancer surgery is a significant problem. Both inherited and acquired mechanisms of inflammation appear to play a role in the development and maintenance of persistent pain. In this longitudinal study, growth mixture modeling was used to identify persistent breast pain phenotypes based on pain assessments obtained prior to and monthly for 6months following breast cancer surgery. Associations between the "no pain" and "mild pain" phenotypes and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. The methylation status of the CpG sites found in the promoters of genes associated with pain group membership was determined using bisulfite sequencing. In the multivariate analysis, three SNPs (i.e., interleukin 6 (IL6) rs2069840, C-X-C motif chemokine ligand 8 (CXCL8) rs4073, tumor necrosis factor (TNF) rs1800610) and two TNF CpG sites (i.e., c.-350C, c.-344C) were associated with pain group membership. These findings suggest that variations in IL6, CXCL8, and TNF are associated with the development and maintenance of mild persistent breast pain. CpG methylation within the TNF promoter may provide an additional mechanism through which TNF alters the risk for mild persistent breast pain after breast cancer surgery. These genetic and epigenetic variations may help to identify individuals who are predisposed to the development of mild levels of persistent breast pain following breast cancer surgery.

Child-Turcotte-Pugh Class is Best at Stratifying Risk in Variceal Hemorrhage: Analysis of a US Multicenter Prospective Study.

GOALS/BACKGROUND: Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort study, we aimed to (1) describe clinical outcomes of AVH and their predictors; (2) compare predictors of 6-week mortality. STUDY: Prospective 15-center US cohort of patients with cirrhosis presenting with endoscopically proven AVH, all of whom received antibiotics, vapreotide (a somatostain analog) infusion and endoscopic band ligation. Patients were enrolled between August 2006 and April 2008. Primary outcome was 6-week mortality. Secondary outcome was 5-day treatment failure. The prognostic value of Child-Turcotte-Pugh (CTP) class, Model for End-stage Liver Disease (MELD) score and a recent recalibrated MELD were compared. RESULTS: Seventy eligible patient were enrolled; 18 (26%) patients died within 6-weeks of index bleed. Demographic, clinical, and laboratory data were compared between survivors and nonsurvivors. Multivariate models showed that admission CTP or the MELD score (separately) were independent predictors of survival. The discriminative values of CTP (area under receiver operating characteristic: 0.75) and MELD (area under receiver operating characteristic: 0.79) were good and not significantly different (P=0.27). However, calibration (correlation between observed and predicted mortality) test was significantly better for CTP than for MELD, with the recently described recalibrated MELD model having the worst agreement. Predicted mortality for CTP-A was <10%, CTP-B 10% to 30%; and CTP-C >33%. CONCLUSIONS: AVH mortality of 26% in the United States is in the upper range limit compared with recent series but may be due to inclusion of patients with more advanced cirrhosis. CTP score has the best overall performance in the prediction of 6-week mortality and is best at stratifying risk.

Potassium Channel Candidate Genes Predict the Development of Secondary Lymphedema Following Breast Cancer Surgery.

BACKGROUND: Potassium (K) channels play an important role in lymph pump activity, lymph formation, lymph transport, and the functions of lymph nodes. No studies have examined the relationship between K channel candidate genes and the development of secondary lymphedema (LE). OBJECTIVE: The study purpose was to evaluate for differences in genotypic characteristics in women who did (n = 155) or did not (n = 387) develop upper extremity LE following breast cancer treatment based on an analysis of single-nucleotide polymorphisms (SNPs) and haplotypes in 10 K channel genes. METHODS: Upper extremity LE was diagnosed using bioimpedance resistance ratios. Logistic regression analyses were used to identify those SNPs and haplotypes that were associated with LE while controlling for relevant demographic, clinical, and genomic characteristics. RESULTS: Patients with LE had a higher body mass index, had a higher number of lymph nodes removed, had more advanced disease, received adjuvant chemotherapy, received radiation therapy, and were less likely to have undergone a sentinel lymph node biopsy. One SNP in a voltage-gated K channel gene (KCNA1 rs4766311), four in two inward-rectifying K channel genes (KCNJ3 rs1037091 and KCNJ6 rs2211845, rs991985, rs2836019), and one in a two-pore K channel gene (KCNK3 rs1662988) were associated with LE. DISCUSSION: These preliminary findings suggest that K channel genes play a role in the development of secondary LE.

Effects of somatosensory electrical stimulation on motor function and cortical oscillations.

BACKGROUND: Few patients recover full hand dexterity after an acquired brain injury such as stroke. Repetitive somatosensory electrical stimulation (SES) is a promising method to promote recovery of hand function. However, studies using SES have largely focused on gross motor function; it remains unclear if it can modulate distal hand functions such as finger individuation. OBJECTIVE: The specific goal of this study was to monitor the effects of SES on individuation as well as on cortical oscillations measured using EEG, with the additional goal of identifying neurophysiological biomarkers. METHODS: Eight participants with a history of acquired brain injury and distal upper limb motor impairments received a single two-hour session of SES using transcutaneous electrical nerve stimulation. Pre- and post-intervention assessments consisted of the Action Research Arm Test (ARAT), finger fractionation, pinch force, and the modified Ashworth scale (MAS), along with resting-state EEG monitoring. RESULTS: SES was associated with significant improvements in ARAT, MAS and finger fractionation. Moreover, SES was associated with a decrease in low frequency (0.9-4 Hz delta) ipsilesional parietomotor EEG power. Interestingly, changes in ipsilesional motor theta (4.8-7.9 Hz) and alpha (8.8-11.7 Hz) power were significantly correlated with finger fractionation improvements when using a multivariate model. CONCLUSIONS: We show the positive effects of SES on finger individuation and identify cortical oscillations that may be important electrophysiological biomarkers of individual responsiveness to SES. These biomarkers can be potential targets when customizing SES parameters to individuals with hand dexterity deficits. TRIAL REGISTRATION: NCT03176550; retrospectively registered.

LOGIQ E9 Shear Wave Elastrography for Detection of Liver Fibrosis in Patients with Chronic Hepatitis C Virus.

OBJECTIVES: Shear wave elastography (SWE) is an emerging technology that assesses hepatic fibrosis. The aim of our study was to determine the diagnostic accuracy of General Electric (GE) Healthcare's LOGIQ E9 SWE in patients with chronic hepatitis C virus using liver biopsy as the reference standard. METHODS: The liver stiffness of 43 subjects with hepatitis C virus was assessed using LOGIQ E9 SWE immediately before they underwent liver biopsy. The Fibrosis-4 Index (FIB-4) and Aspartate Aminotransferase-to-Platelet Index (APRI) were calculated, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: Mild hepatic fibrosis (F0-F2) was noted in 30 of the 43 (69.7%) patients and advanced disease (F3-F4) was seen in 13 of the 43 (30.3%) individuals. Using the GE LOGIQ E9 SWE proposed cutoff value of ≥9.4 kPa for advanced fibrosis, the sensitivity, specificity, PPV, and NPV were only 69.2%, 73.3%, 52.9%, and 84.6%, respectively. The post hoc analysis identified best cutoff values of <9.4 and ≥12 kPa, thereby classifying 76% of patients with an NPV of 84.6% and a PPV of 85.7%. The Aminotransferase-to-Platelet Index results were as follows: 83.3%, sensitivity, 95.2% specificity, 83.3% PPV, and 95.2% NPV in 27 of the individuals (37% remained unclassifiable). The FIB-4 Index demonstrated 100% sensitivity, 76.9% specificity, 66.6% PPV, and 100% NPV; however, 24 (56%) of the patients were classified within the indeterminate range. CONCLUSIONS: In our cohort, the proposed GE LOGIQ value of ≥9.4 kPa did not adequately discriminate subjects with advanced fibrosis. Further prospective evaluation of our post hoc analyses is warranted to identify the ideal cutoff values for the LOGIQ E9 system.

Neurorehabilitation: motor recovery after stroke as an example.

The field of neurorehabilitation aims to translate neuroscience research toward the goal of maximizing functional recovery after neurological injury. A growing body of research indicates that the fundamental principles of neurological rehabilitation are applicable to a broad range of congenital, degenerative, and acquired neurological disorders. In this perspective, we will focus on motor recovery after acquired brain injuries such as stroke. Over the past few decades, a large body of basic and clinical research has created an experimental and theoretical foundation for approaches to neurorehabilitation. Recent randomized clinical trials all emphasize the requirement for intense progressive rehabilitation programs to optimally enhance recovery. Moreover, advances in multimodal assessment of patients with neuroimaging and neurophysiological tools suggest the possibility of individualized treatment plans based on recovery potential. There are also promising indications for medical as well as noninvasive brain stimulation paradigms to facilitate recovery. Ongoing or planned clinical studies should provide more definitive evidence. We also highlight unmet needs and potential areas of research. Continued research built upon a robust experimental and theoretical foundation should help to develop novel treatments to improve recovery after neurological injury.

Association between an interleukin 1 receptor, type I promoter polymorphism and self-reported attentional function in women with breast cancer.

Subgroups of patients with breast cancer may be at greater risk for cytokine-induced changes in cognitive function after diagnosis and during treatment. The purposes of this study were to identify subgroups of patients with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) predictors of subgroup membership. Self-reported attentional function was evaluated in 397 patients with breast cancer using the Attentional Function Index before surgery and for six months after surgery (i.e., seven time points). Using growth mixture modeling, three attentional function latent classes were identified: High (41.6%), Moderate (25.4%), and Low-moderate (33.0%). Patients in the Low-moderate class were significantly younger than those in the High class, with more comorbidities and lower functional status than the other two classes. No differences were found among the classes in years of education, race/ethnicity, or other clinical characteristics. DNA was recovered from 302 patients' samples. Eighty-two single nucleotide polymorphisms among 15 candidate genes were included in the genetic association analyses. After controlling for age, comorbidities, functional status, and population stratification due to race/ethnicity, IL1R1 rs949963 remained a significant genotypic predictor of class membership in the multivariable model. Carrying the rare "A" allele (i.e., GA+AA) was associated with a twofold increase in the odds of belonging to a lower attentional function class (OR: 1.98; 95% CI: 1.18, 3.30; p=.009). Findings provide evidence of subgroups of women with breast cancer who report distinct trajectories of attentional function and of a genetic association between subgroup membership and an IL1R1 promoter polymorphism.