Comparison of heart transplant outcomes between recipients with pulsatile- vs continuous-flow LVAD.

OBJECTIVE: Continuous-flow (CF) left ventricular assist devices (LVADs) have replaced pulsatile flow (PF) LVADs irrespective of concerns from the physiologic changes/morbidity secondary to lack of pulsatility. Data comparing posttransplant outcomes in patients with CF vs PF LVADs are limited and conflicting. We used the Organ Procurement and Transplant Network database to compare posttransplant outcomes between CF and PF LVAD patients. METHODS: From 1 January 2005 to 31 December 2011, 3449 adult patients underwent primary heart alone transplantation. The cohort was restricted to 2741 recipients with LVAD at the time of transplant and divided into two groups: PF (Heartmate XVE) (n = 705) and CF (Heartmate II, HeartWare HVAD, and Jarvik 2000) (n = 2036). Endpoints were 30-day freedom from graft failure, 1-, and 5-year patient survival. Propensity score matching identified 705 pairs for adjusted comparisons. RESULTS: Among propensity-matched patients, 30-day freedom from graft failure after heart transplantation (PF = 94.8% vs CF = 95.2%, P > .7), and 1-, and 5-year patient survival (PF; 87.5% vs CF; 88.9%, P = .4, and PF;75.7% vs CF;77.5%, P = .3) were not different. CONCLUSION: Survival and freedom from graft failure after heart transplantation is similar between CF and PF LVADs. These findings are relevant as the use of CF devices increases despite physiologic changes related to the absence of pulsatility.

Papillary lesions of the breast: To excise or observe?

Papillary lesions of the breast range from benign to atypical to malignant. Although papillomas without frank cancer are benign, their management remains controversial. When a core needle biopsy of a lesion yields a diagnosis of intraductal papilloma with atypia, excision is generally recommended to rule out a concurrent malignant neoplasm. For intraductal papillomas without atypia, however, recommendations for excision versus observation are variable. The aims of this study are to evaluate the rate of concurrent malignancies for intraductal papilloma diagnosed on core needle biopsy and to assess the long-term risk of developing cancer after the diagnosis of a papillary lesion. This single institution retrospective study analyzed 259 patients that were diagnosed with intraductal papilloma (IDP) by core needle biopsy from 1995 to 2010. Patients were grouped by initial diagnosis into three groups (papilloma without atypia, papilloma with atypia, and papilloma with atypical duct hyperplasia or atypical lobular hyperplasia (ADH/ALH) and followed up for long-term outcomes. After a core needle biopsy showing IDP with atypia or IDP + ADH/ALH, surgical excision yielded a diagnosis of concomitant invasive or ductal in situ cancer in greater that 30% of cases. For intraductal papilloma without atypia, the likelihood of cancer was much lower. Moreover, even with excision, the finding of intraductal papilloma with atypia carries a significant risk of developing cancer long-term, and such patients should be followed carefully and perhaps should be considered for chemoprevention.

The Phenomenology of Tics and Tic-Like Behavior in TikTok.

BACKGROUND: Pediatricians and pediatric subspecialists worldwide have reported a marked increase in functional (conversion) disorders with tic-like behaviors during the COVID-19 pandemic. These patients often report frequent viewing of Tourette syndrome (TS) TikTok videos, suggesting disease modeling. We aimed to evaluate tic phenomenology in videos posted on TikTok. METHODS: The 100 most-viewed videos under #tourettes in TikTok were randomly assigned to two of three primary reviewers (<2 years independent practice), all pediatric neurologists specializing in movement disorders, for extraction and classification of tic phenomenology. Initial disagreements were solved by consensus. If not resolved, one of five senior reviewers (>2 years independent pediatric movement disorder practice) served as a tiebreaker. In addition, two primary and one senior reviewer rated each video on a Likert scale from 1 = "All the tics are typical of TS" to 5 = "None of the tics are typical of TS". Median scores and Spearman correlation between primary and senior reviewers were calculated. RESULTS: Six videos without tic-like behaviors were excluded. Most videos depicted coprophenomena (coprolalia: 53.2%; copropraxia: 20.2%), often with unusual characteristics. Frequently, videos demonstrated atypical phenomenology such as very strong influence by the environment (motor: 54.3%; phonic: 54.3%), aggression (19.1%), throwing objects (22.3%), self-injurious behaviors (27.7%), and long phrases (>3 words; 45.7%). Most videos portrayed atypical, nontic behaviors (median [IQR] Likert ratings: 5 [4-5]). Primary vs. senior rater scores demonstrated moderate agreement (r = 0.46; P < 0.001). CONCLUSIONS: TS symptom portrayals on highly viewed TikTok videos are predominantly not representative or typical of TS.

Definition and classification of hyperkinetic movements in childhood.

Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often nonrhythmic, brief shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back-and-forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials.

Plant traits and vegetation data from climate warming experiments along an 1100 m elevation gradient in Gongga Mountains, China.

Functional trait data enhance climate change research by linking climate change, biodiversity response, and ecosystem functioning, and by enabling comparison between systems sharing few taxa. Across four sites along a 3000-4130 m a.s.l. gradient spanning 5.3 °C in growing season temperature in Mt. Gongga, Sichuan, China, we collected plant functional trait and vegetation data from control plots, open top chambers (OTCs), and reciprocally transplanted vegetation turfs. Over five years, we recorded vascular plant composition in 140 experimental treatment and control plots. We collected trait data associated with plant resource use, growth, and life history strategies (leaf area, leaf thickness, specific leaf area, leaf dry matter content, leaf C, N and P content and C and N isotopes) from local populations and from experimental treatments. The database consists of 6,671 plant records and 36,743 trait measurements (increasing the trait data coverage of the regional flora by 500%) covering 11 traits and 193 plant taxa (ca. 50% of which have no previous published trait data) across 37 families.

Penalized negative binomial models for modeling an overdispersed count outcome with a high-dimensional predictor space: Application predicting micronuclei frequency.

Chromosomal aberrations, such as micronuclei (MN), have served as biomarkers of genotoxic exposure and cancer risk. Guidelines for the process of scoring MN have been presented by the HUman MicroNucleus (HUMN) project. However, these guidelines were developed for assay performance but do not address how to statistically analyze the data generated by the assay. This has led to the application of various statistical methods that may render different interpretations and conclusions. By combining MN with data from other high-throughput genomic technologies such as gene expression microarray data, we may elucidate molecular features involved in micronucleation. Traditional methods that can model discrete (synonymously, count) data, such as MN frequency, require that the number of explanatory variables (P) is less than the number of samples (N). Due to this limitation, penalized models have been developed to enable model fitting for such over-parameterized datasets. Because penalized models in the discrete response setting are lacking, particularly when the count outcome is over-dispersed, herein we present our penalized negative binomial regression model that can be fit when P > N. Using simulation studies we demonstrate the performance of our method in comparison to commonly used penalized Poisson models when the outcome is over-dispersed and applied it to MN frequency and gene expression data collected as part of the Norwegian Mother and Child Cohort Study. Our countgmifs R package is available for download from the Comprehensive R Archive Network and can be applied to datasets having a discrete outcome that is either Poisson or negative binomial distributed and a high-dimensional covariate space.

Use of the "dual construct" for the management of complex spinal reconstructions.

BACKGROUND CONTEXT: Surgical management of complex spinal reconstructions remains a clinical challenge, as pseudoarthrosis with subsequent rod breakage can occur. Increased rod density in the form of "satellite" or "outrigger" rods have been described; however, rod-fracture above or below satellite rods persist and can result in dissociation of the construct, loss of correction, and recurrence of deformity. The use of four distinct and mechanically independent rods (dual construct) reduces this concern. Since the original case description in 2006, there have been no other studies that use the dual construct for the surgical management of complex spinal reconstructions. PURPOSE: The purpose of this study is to review the long-term experience and surgical technique using the dual construct, and to present our complications, rod fracture rates, and outcomes for the surgical management of complex spinal reconstructions. STUDY DESIGN: This study used a surgical technique with case series outcomes. PATIENT SAMPLE: Patients were from a single-institute who underwent dual construct between 2010 and 2014 and who were available for 2-year follow-up. OUTCOME MEASURES: Radiographic and functional outcomes, complications, rod fracture rates, and revision surgery rates were the outcome measures. METHODS: A retrospective review was conducted from a single institution between 2010 and 2014, with a subsequent 2-year follow-up period. Extensive review of patients' medical record, radiographs, and advanced imaging where available was performed. Medical record was evaluated for patient demographics, surgical procedure, and complications. Radiographic measurements included presence or absence of implant failure and proximal junctional kyphosis or distal junctional kyphosis. RESULTS: A total of 36 patients underwent surgical reconstruction. The average estimated blood loss was 1,856 cc (range, 400-4,000 cc). The average length of stay was 7.3 days (range, 4-22 days). Clinical follow-up reported 21 patients (58.3%) with no or minimal pain. There were six deaths during the follow-up unrelated to the index procedure. Radiographic follow-up revealed three patients (8.3%) with rod fracture; one patient with one rod fracture, and two patients with two rod fractures. No patient had three or all four rod fractures. There were no screw fractures. None of the patients with rod fractures required revision surgery. CONCLUSIONS: The biggest advantage of the dual construct is that rod breakage, although uncommon, is typically minimal, or asymptomatic, and more importantly does not result in loss of alignment, and therefore has not required revision surgery. The dual construct approach is a safe alternative to traditional two-rod constructs, with encouraging outcomes at follow-up.

Engaging Patients in Decisions About Cancer Screening: Exploring the Decision Journey Through the Use of a Patient Portal.

INTRODUCTION: Engaging patients to make informed choices is paramount but difficult in busy practices. This study sought to engage patients outside the clinical setting to better understand how they approach cancer screening decisions, including their primary concerns and their preferences for finalizing their decision. METHODS: Twelve primary care practices offering patients an online personal health record invited eligible patients to complete a 17-item online interactive module. Among 11,458 registered users, invitations to complete the module were sent to adults aged 50-74 years who were overdue for colorectal cancer screening and to women aged 40-49 years and men aged 55-69 who had not undergone a recent mammogram or prostate-specific antigen test, respectively. RESULTS: The module was started by 2,355 patients and completed by 903 patients. Most respondents (76.8%) knew they were eligible for screening. Preferred next steps were talking to the clinician (76.6%), reading/research (28.6%), and consulting trusted friends/family (16.4%). Priority topics included how much screening improves life expectancy, comparative test performance, and the prevalence/health risks of the cancer. Leading fears were getting cancer/delayed detection (79.2%), abnormal results (40.5%), and testing complications (39.1%), the last referring to false test results, medical complications, or unnecessary treatments. Men eligible for prostate-specific antigen screening were more likely than women eligible for mammography to express concerns about testing complications and to prioritize weighing pros and cons over gut feelings (p<0.05). CONCLUSIONS: Although this sample was predisposed to screening, most patients wanted help in finalizing their decision. Many wanted to weigh the pros and cons and expressed fears of potential harms from screening. Understanding how patients approach decisions may help design more effective engagement strategies.

A retrospective comparison of intraoperative CT and fluoroscopy evaluating radiation exposure in posterior spinal fusions for scoliosis.

BACKGROUND: Radiation exposure is a concern in the field of medicine. Deformity spine surgeons depend on modalities that have high exposure through scoliosis x-rays or computed tomography. The use of fluoroscopy has increased with the increased use of pedicle screws. Recently other 3-D imaging devices with navigation have also been brought onto the market to improve accuracy of screw placement. There is concern that because of the use of CT, the radiation dose to the patient is increased, however there is little literature that directly compares the amount of radiation using the 3-D devices to traditional fluoroscopy. Although we know intraoperative CT decreases the amount of radiation to the surgeon and operating room staff, there is limited comparison data for exposure to patients. Our study focused on a comparison of radiation exposure data for pediatric scoliosis patients receiving posterior spinal fusions using traditional fluoroscopy and the Medtronic O-arm in an effort to determine the method most likely to decrease radiation exposure in the pediatric population. METHODS: Retrospective review of data in patient charts from two pediatric surgeons practicing in both a University and private hospital setting. Data collected included age, weight, height, diagnosis, Cobb angle, fusion levels, number of screws, and number of hooks, O-arm spins, fluoro doses and O-arm doses. Effective dose was calculated using output measures and radiation doses were compared along a continuum that took into account the amount of correction as indicated by Cobb angle. RESULTS: A total of 57 patients, 25 using the O-arm and 32 using traditional fluoroscopy, were analyzed. Effective dose was calculated and then compared as a factor correlated to curve severity. At lower angles of correction we found no statistically significant difference between methods in terms of effective radiation dose. There was no statistically significant divergence until a Cobb angle correction of greater than 74 degrees, where the Oarm dose was shown to be lower by comparison. CONCLUSION: We found that regardless of the methods used there is still a significant radiation dose that is utilized in scoliosis procedures. The two methods analyzed did not display statistically significant differences in effective dose for the average case. Safely managing radiation exposure for pediatric patients is of the utmost priority. Healthcare professionals, however, face repeated exposure to radiation over the course of a long career. In our data set the O-Arm system does not increase overall exposure for patients and decreases radiation doses for providers and thereby provides a safe alternative to traditional fluoroscopy without compromising accuracy of implant placement or patient care.Level of Evidence: III.

Should symptomatic menopausal women be offered hormone therapy?

UNLABELLED: Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms. MAJOR FINDINGS: Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause. CONCLUSIONS: Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.

Should symptomatic menopausal women be offered hormone therapy?

UNLABELLED: Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms. MAJOR FINDINGS: Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause. CONCLUSIONS: Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.

Redefining the Pediatric Phenotype of X-Linked Monocarboxylate Transporter 8 (MCT8) Deficiency: Implications for Diagnosis and Therapies.

X-linked monocarboxylate transporter 8 (MCT8) deficiency results from a loss-of-function mutation in the monocarboxylate transporter 8 gene, located on chromosome Xq13.2 (Allan-Herndon-Dudley syndrome). Affected boys present early in life with neurodevelopment delays but have pleasant dispositions and commonly have elevated serum triiodothyronine. They also have marked axial hypotonia and quadriparesis but surprisingly little spasticity early in their disease course. They do, however, have subtle involuntary movements, most often dystonia. The combination of hypotonia and dystonia presents a neurorehabilitation challenge and explains why spasticity-directed therapies have commonly produced suboptimal responses. Our aim was to better define the spectrum of motor disability and to elucidate the neuroanatomic basis of the motor impairments seen in MCT8 deficiency using clinical observation and brain magnetic resonance imaging (MRI) in a cohort of 6 affected pediatric patients. Our findings identified potential imaging biomarkers and suggest that rehabilitation efforts targeting dystonia may be more beneficial than those targeting spasticity in the prepubertal pediatric MCT8 deficiency population.

A novel variant of aquaporin 3 is expressed in killifish (Fundulus heteroclitus) intestine.

Killifish (Fundulus heteroclitus) are euryhaline teleosts that are widely used in environmental and toxicological studies, and they are tolerant to arsenic, in part due to very low assimilation of arsenic from the environment. The mechanism of arsenic uptake by the intestine, a major route of arsenic uptake in humans is unknown. Thus, the goal of this study was to determine if aquaglyceroporins (AQPs), which transport water and other small molecules including arsenite across cell membranes, are expressed in the killifish intestine, and whether AQP expression is affected by osmotic stress. Through RT-PCR and sequence analysis of PCR amplicons, we demonstrated that the intestine expresses kfAQP3a and kfAQP3b, two previously identified variants, and also identified a novel variant of killifish AQP3 (kfAQP3c) in the intestine. The variants likely represent alternate splice forms. A BLAST search of the F. heteroclitus reference genome revealed that the AQP3 gene resides on a single locus, while an alignment of the AQP3 sequence among 384 individuals from eight population ranging from Rhode Island to North Carolina revealed that its coding sequence was remarkably conserved with no fixed polymorphism residing in the region that distinguishes these variants. We further demonstrate that the novel variant transports arsenite into HEK293T cells. Whereas kfAQP3a, which does not transport arsenite, was expressed in both freshwater (FW) and saltwater (SW) acclimated fish, kfAQP3b, an arsenic transporter, was expressed only in FW acclimated fish, and kfAQP3c was expressed only in SW acclimated fish. Thus, we have identified a novel, putative splice variant of kfAQP3, kfAQP3c, which transports arsenic and is expressed only in SW acclimated fish.

Family history in juvenile Huntington disease: do the signs point to "yes" or "very doubtful"?

Juvenile Huntington disease (JHD)-Huntington disease (HD) with an onset ≤20 years-accounts for approximately 10% of all HD cases. Like the adult form of the disorder, JHD is a hereditary neurodegenerative disease characterized by dementia and behavioral changes, caused by an expanded CAG repeat within the first exon of the huntingtin (HTT) gene on chromosome 4.(1) Unlike the adult form, JHD tends to present with a rigid-dystonic picture or nonspecific motor and neuropsychological signs rather than chorea.(2,3.)