The impact of race and ethnicity on diffuse large B-cell lymphoma outcomes within the veterans health administration (VHA).

We performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. The 3178 patients who met inclusion criteria were predominantly male (97%) and white (75%). Median age of diagnosis for Black patients was 63 years vs 69 years for the entire cohort (p < 0.001). However, patients in each race/ethnicity subgroup presented with similar rates of stage I/II and III/IV disease, IPI score, cell of origin and HIT status. Outcomes analysis revealed similar treatment, response rates, median overall survival, and 1-, 3-, and 5-year survival across all subgroups. Hispanic patients had a 21% lower risk of death (HR = 0.79) than white patients, and Black patients had no significant difference in survival (HR = 0.98). This large retrospective study shows that when standard of care therapy is given within an equal access system, short-term treatment and survival outcomes are the same for all races.

Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

BACKGROUND AND AIMS: The utility of serial liver stiffness measurements (LSM) to predict decompensation in patients with compensated advanced chronic liver disease (cACLD) remains unclear. We aimed to validate whether comparing serial LSM is superior to using the current LSM to predict liver-related events (LRE) in patients with cACLD. APPROACH AND RESULTS: In this retrospective analysis of an international registry, patients with cACLD and serial LSM were followed up until index LRE. We compared the performance of both the dynamic LSM changes and the current LSM in predicting LRE using Cox regression analysis, considering time zero of follow-up as the date of latest liver stiffness measurement. In all, 480 patients with cACLD with serial LSM were included from 5 countries. The commonest etiology of cACLD was viral (53%) and MASLD (34%). Over a median follow-up of 68 (IQR: 45 -92) months, 32% experienced a LSM decrease to levels below 10kPa (resolved cACLD) and 5.8% experienced LRE. Resolved cACLD were more likely to be nondiabetic and had better liver function. While a higher value of the current LSM was associated with higher LREs, LSM changes over time (LSM slope) were not associated with LRE. In multivariable Cox regression, neither the prior LSM nor the LSM slope added predictive value to latest liver stiffness measurement. CONCLUSIONS: Once the current LSM is known, previous LSM values do not add to the prediction of LREs in patients with cACLD.

Combination of Fibrosis-4, liver-stiffness measurement, and Fibroscan-AST score to predict liver-related outcomes in nonalcoholic fatty liver disease.

INTRODUCTION: Noninvasive tests, such as Fibrosis-4 (FIB-4), liver-stiffness measurement (LSM) by vibration-controlled transient elastography, and Fibroscan-AST (FAST), are frequently used for risk stratification in NAFLD. The comparative performance of FIB-4 and LSM and FAST to predict clinical outcomes of patients with NAFLD remained unclear. We aim to evaluate the performance of FIB-4, LSM, and FAST scores to predict clinical outcomes in patients with NAFLD. METHODS: We included consecutive adult patients with NAFLD with transient elastography performed between 2015 and 2022 from the United States and Singapore. Patients with NAFLD stratified based on baseline FIB-4, LSM, and FAST score were followed up until clinical outcomes notably liver-related events (LREs), LREs or death, death, and major adverse cardiac events. RESULTS: A total of 1262 patients with NAFLD (63% with obesity and 37% with diabetes) with vibration-controlled transient elastography were followed up for median 3.5 years. FIB-4 stratified patients with NAFLD into low-risk (<1.3), intermediate-risk (1.3-2.67), and high-risk (>2.67) in 59.4%, 31.5%, and 9.1%, respectively. No LRE occurred with baseline FIB-4 <1.3, regardless of LSM and FAST score. Higher FIB-4 was associated with a higher risk of LREs within each LSM category. FIB-4 had a higher area under the received operating characteristic curve than LSM or FAST score to predict LRE. CONCLUSIONS: In this multicenter international study, FIB-4 and LSM synergistically predicted the risk of LRE. In patients with FIB-4 <1.3, vibration-controlled transient elastography may incorrectly classify up to 10% of the patients as high risk. FIB-4 should be incorporated into risk stratification in NAFLD even among patients who underwent VCTE.

Functional characterization of Alzheimer's disease genetic variants in microglia.

Candidate cis-regulatory elements (cCREs) in microglia demonstrate the most substantial enrichment for Alzheimer's disease (AD) heritability compared to other brain cell types. However, whether and how these genome-wide association studies (GWAS) variants contribute to AD remain elusive. Here we prioritize 308 previously unreported AD risk variants at 181 cCREs by integrating genetic information with microglia-specific 3D epigenome annotation. We further establish the link between functional variants and target genes by single-cell CRISPRi screening in microglia. In addition, we show that AD variants exhibit allelic imbalance on target gene expression. In particular, rs7922621 is the effective variant in controlling TSPAN14 expression among other nominated variants in the same cCRE and exerts multiple physiological effects including reduced cell surface ADAM10 and altered soluble TREM2 (sTREM2) shedding. Our work represents a systematic approach to prioritize and characterize AD-associated variants and provides a roadmap for advancing genetic association to experimentally validated cell-type-specific phenotypes and mechanisms.

Effects of social determinants of health on mortality and incident liver-related events and cardiovascular disease in steatotic liver disease.

BACKGROUND: Social determinants of health (SDOH) are becoming increasingly recognised as mediators of human health. In the setting of metabolic dysfunction-associated steatotic liver disease (MASLD), most of the literature on SDOH relates to individual-level risk factors. However, there are very limited data on neighbourhood-level SDOH in MASLD. AIM: To assess whether SDOH impact fibrosis progression in patients who already have MASLD. METHODS: This was a retrospective cohort study of patients with MASLD seen at Michigan Medicine. The primary predictors were two neighbourhood-level SDOH, 'disadvantage' and 'affluence'. The primary outcomes were mortality, incident liver-related events (LREs) and incident cardiovascular disease (CVD). We modelled these outcomes using Kaplan-Meier statistics for mortality and competing risk analyses for LREs and CVD, using a 1-year landmark. RESULTS: We included 15,904 patients with MASLD with median follow-up of 63 months. Higher affluence was associated with lower risk of overall mortality (hazard ratio 0.49 [0.37-0.66], p < 0.0001 for higher vs. lower quartile), LREs (subhazard ratio 0.60 [0.39-0.91], p = 0.02) and CVD (subhazard ratio 0.71 [0.57-0.88], p = 0.0018). Disadvantage was associated with higher mortality (hazard ratio 2.08 [95% confidence interval 1.54-2.81], p < 0.0001 for the highest vs. lowest quartile) and incident CVD (subhazard ratio 1.36 [95% confidence interval 1.10-1.68], p < 0.0001). These findings were robust across several sensitivity analyses. DISCUSSION: Neighbourhood-level SDOH are associated with mortality, incidence of LREs and incident CVD in patients with steatotic liver disease. Interventions aimed at disadvantaged neighbourhoods may improve clinical outcomes.

Recall patterns and risk of primary liver cancer for subcentimeter ultrasound liver observations: a multicenter study.

BACKGROUND: Patients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC). AIMS: The aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound. METHODS: We conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1 cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively. RESULTS: Of 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7 cm (interquartile range: 0.5-0.8 cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3-6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2-47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10 ng/mL (HR: 4.01, 95% CI, 1.85-8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95-12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27-5.08). CONCLUSIONS: Recall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3-6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.

Clinical Consequences of Incidental Durotomy during Full-Endoscopic Lumbar Decompression Surgery in Relation to Intraoperative Epidural Pressure Measurements.

Background: Seizures, neurological deficits, bradycardia, and, in the worst cases, cardiac arrest may occur following incidental durotomy during routine lumbar endoscopy. Therefore, we set out to measure the intraoperative epidural pressure during lumbar endoscopic decompression surgery. Methods: We conducted a retrospective observational cohort study to obtain intraoperative epidural measurements with an epidural catheter-pressure transducer assembly through the spinal endoscope on 15 patients who underwent lumbar endoscopic decompression of symptomatic lumbar herniated discs and spinal stenosis. The endoscopic interlaminar technique was employed. Results: There were six (40.0%) female and nine (60.0%) male patients aged 49.0667 ± 11.31034, ranging from 36 to 72 years, with an average follow-up of 35.15 ± 12.48 months. Three of the fifteen patients had seizures with durotomy and one of these three had intracranial air on their postoperative brain CT. Another patient developed spinal headaches and diplopia on postoperative day one when her deteriorating neurological function was investigated with a brain computed tomography (CT) scan, showing an intraventricular hemorrhage consistent with a Fisher Grade IV subarachnoid hemorrhage. A CT angiogram did not show any abnormalities. Pressure recordings in the epidural space in nine patients ranged from 20 to 29 mm Hg with a mean of 24.33 mm Hg. Conclusion: Most incidental durotomies encountered during lumbar interlaminar endoscopy can be managed without formal repair and supportive care measures. The intradural spread of irrigation fluid and intraoperatively used drugs and air entrapment through an unrecognized durotomy should be suspected if patients deteriorate in the recovery room. Ascending paralysis may cause nausea, vomiting, upper and lower motor neuron symptoms, cranial nerve palsies, hypotension, bradycardia, and respiratory and cardiac arrest. The recovery team should be prepared to manage these complications.

Identification of the Magna Radicular Artery Entry Foramen and Adamkiewicz System: Patient Selection for Open versus Full-Endoscopic Thoracic Spinal Decompression Surgery.

BACKGROUND: Casually cauterizing the radicular magna during routine thoracic discectomy may have dire consequences. METHODS: We performed a retrospective observational cohort study on patients scheduled for decompression of symptomatic thoracic herniated discs and spinal stenosis who underwent a preoperative computed tomography angiography (CTA) to assess the surgical risks by anatomically defining the foraminal entry level of the magna radicularis artery into the thoracic spinal cord and its relationship to the surgical level. RESULTS: Fifteen patients aged 58.53 ± 19.57, ranging from 31 to 89 years, with an average follow-up of 30.13 ± 13.42 months, were enrolled in this observational cohort study. The mean preoperative VAS for axial back pain was VAS of 8.53 ± 2.06 and reduced to a postoperative VAS of 1.60 ± 0.92 (p < 0.0001) at the final follow-up. The Adamkiewicz was most frequently found at T10/11 (15.4%), T11/12 (23.1%), and T9/10 (30.8%). There were eight patients where the painful pathology was found far from the AKA foraminal entry-level (type 1), three patients with near location (type 2), and another four patients needing decompression at the foraminal (type 3) entry-level. In five of the fifteen patients, the magna radicularis entered the spinal canal on the ventral surface of the exiting nerve root through the neuroforamen at the surgical level requiring a change of surgical strategy to prevent injury to this important contributor to the spinal cord's blood supply. CONCLUSIONS: The authors recommend stratifying patients according to the proximity of the magna radicularis artery to the compressive pathology with CTA to assess the surgical risk with targeted thoracic discectomy methods.

Higher mortality among lean patients with non-alcoholic fatty liver disease despite fewer metabolic comorbidities.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) can develop in individuals who are not overweight. Whether lean persons with NAFLD have lower mortality and lower incidence of cirrhosis, cardiovascular diseases (CVD), diabetes mellitus (DM) and cancer than overweight/obese persons with NAFLD remains inconclusive. We compared mortality and incidence of cirrhosis, CVD, DM and cancer between lean versus non-lean persons with NAFLD. METHODS: This is a retrospective study of adults with NAFLD in a single centre from 2012 to 2021. Primary outcomes were mortality and new diagnosis of cirrhosis, CVD, DM and cancer. Outcomes were modelled using competing risk analysis and Cox proportional hazards regression analysis. RESULTS: A total of 18,594 and 13,420 patients were identified for cross-sectional and longitudinal analysis respectively: approximately 11% lean, 25% overweight, 28% class 1 obesity and 35% class 2-3 obesity. The median age was 51.0 years, 54.6% were women. The median follow-up was 49.3 months. Lean patients had lower prevalence of metabolic diseases at baseline and lower incidence of cirrhosis and DM than non-lean patients and no difference in CVD, any cancer or obesity-related cancer during follow-up. However, lean patients had significantly higher mortality with incidence per 1000 person-years of 16.67, 10.11, 7.37 and 8.99, respectively, in lean, overweight, obesity class 1 and obesity class 2-3 groups respectively. CONCLUSIONS: Lean patients with NAFLD had higher mortality despite lower incidence of cirrhosis and DM, and similar incidence of CVD and cancer and merit similar if not more attention as non-lean patients with NAFLD.

Oxymetazoline hydrochloride ophthalmic solution, 0.1%, boosts the effects of botulinum toxin on blepharospasm: a case series.

BACKGROUND: Oxymetazoline hydrochloride ophthalmic solution (0.1%) is a medication used to treat blepharoptosis. Patients who suffer from blepharoptosis have low-lying eyelids that can hinder their vision. Oxymetazoline hydrochloride ophthalmic solution (0.1%) is prescribed to patients to improve their vision by lifting the upper eyelids. Blepharospasm consists of involuntary, bilateral orbicularis oculi muscle movements that result in twitching and eyelid closure. Botulinum toxin is a treatment used to treat blepharospasm by preventing muscle contraction; but it is not always effective. CASE PRESENTATION: The effects of treatment with both oxymetazoline hydrochloride ophthalmic solution (0.1%) and botulinum toxin are assessed in three patients: (1) Patient A, a 58-year-old Filipina woman; (2) patient B, a 62-year-old Korean woman; and (3) patient C, A 57-year-old Vietnamese woman. All patients had been diagnosed with blepharoptosis as well as blepharospasm. Each patient was given an opportunity to complete an optional survey to assess not only the efficacy of oxymetazoline hydrochloride ophthalmic solution (0.1%) together with botulinum toxin but also their perceived stress during the past month. CONCLUSIONS: Administering botulinum toxin for the treatment of blepharospasm in patients A and B yielded the expected results; adding oxymetazoline hydrochloride ophthalmic solution (0.1%), a medical treatment for ptosis, to the treatment regimen yielded an unexpected reduction of blepharospasm. We propose that botulinum toxin and oxymetazoline hydrochloride ophthalmic solution (0.1%) can have a synergistic effect on reducing blepharospasm when used concomitantly. We present three cases in which combined use of botulinum toxin with oxymetazoline hydrochloride ophthalmic solution (0.1%) reduced blepharospasm, and propose possible reasons for such effects. We also discuss previous literature in agreement with the results of our cases.

eHealth Tools That Assess and Track Health and Well-being in Children and Young People: Systematic Review.

BACKGROUND: eHealth tools that assess and track health outcomes in children or young people are an emerging type of technology that has the potential to reform health service delivery and facilitate integrated, interdisciplinary care. OBJECTIVE: The aim of this review is to summarize eHealth tools that have assessed and tracked health in children or young people to provide greater clarity around the populations and settings in which they have been used, characteristics of digital devices (eg, health domains, respondents, presence of tracking, and connection to care), primary outcomes, and risks and challenges of implementation. METHODS: A search was conducted in PsycINFO, PubMed or MEDLINE, and Embase in April 2020. Studies were included if they evaluated a digital device whose primary purpose was to assess and track health, focused on children or young people (birth to the age of 24 years), reported original research, and were published in peer-reviewed journals in English. RESULTS: A total of 39 papers were included in this review. The sample sizes ranged from 7 to 149,329 participants (median 163, mean 5155). More studies were conducted in urban (18/39, 46%) regions than in rural (3/39, 8%) regions or a combination of urban and rural areas (8/39, 21%). Devices were implemented in three main settings: outpatient health clinics (12/39, 31%), hospitals (14/39, 36%), community outreach (10/39, 26%), or a combination of these settings (3/39, 8%). Mental and general health were the most common health domains assessed, with a single study assessing multiple health domains. Just under half of the devices tracked children's health over time (16/39, 41%), and two-thirds (25/39, 64%) connected children or young people to clinical care. It was more common for information to be collected from a single informant (ie, the child or young person, trained health worker, clinician, and parent or caregiver) than from multiple informants. The health of children or young people was assessed as a primary or secondary outcome in 36% (14/39) of studies; however, only 3% (1/39) of studies assessed whether using the digital tool improved the health of users. Most papers reported early phase research (formative or process evaluations), with fewer outcome evaluations and only 3 randomized controlled trials. Identified challenges or risks were related to accessibility, clinical utility and safety, uptake, data quality, user interface or design aspects of the device, language proficiency or literacy, sociocultural barriers, and privacy or confidentiality concerns; ways to address these barriers were not thoroughly explored. CONCLUSIONS: eHealth tools that assess and track health in children or young people have the potential to enhance health service delivery; however, a strong evidence base validating the clinical utility, efficacy, and safety of tools is lacking, and more thorough investigation is needed to address the risks and challenges of using these emerging technologies in clinical care. At present, there is greater potential for the tools to facilitate multi-informant, multidomain assessments and longitudinally track health over time and room for further implementation in rural or remote regions and community settings around the world.

Polyploidy and microbiome associations mediate similar responses to pathogens in Arabidopsis.

It has become increasingly clear that the microbiome plays a critical role in shaping the host organism's response to disease. There also exists mounting evidence that an organism's ploidy level is important in their response to pathogens and parasites. However, no study has determined whether or how these two factors influence one another. We investigate the effect of whole-genome duplication in Arabidopsis thaliana on the above-ground (phyllosphere) microbiome and determine the interacting impacts of ploidy and microbiome on disease outcome. Using seven independently derived synthetic autotetraploid Arabidopsis accessions and a synthetic leaf-associated bacterial community, we confirm that polyploids are generally more resistant to the model pathogen Pseudomonas syringae pv. Tomato DC3000. Polyploids fare better against the pathogen than diploids do, regardless of microbial inoculation, whereas diploids harboring an intact microbiome have lower pathogen densities than those without. In addition, diploids have elevated numbers of defense-related genes that are differentially expressed in the presence of their phyllosphere microbiota, whereas polyploids exhibit some constitutively activated defenses, regardless of colonization by the synthetic community. These results imply that whole-genome duplication can enhance immunity, resulting in a decreased dependence on the microbiome for protection against pathogens.

Intraocular pressure improvement in patients receiving teprotumumab for the treatment of thyroid eye disease: a case series.

BACKGROUND: Teprotumumab is a novel treatment that reduces inflammation and symptoms caused by thyroid eye disease. There are limited data on teprotumumab's effect on intraocular pressure. CASE PRESENTATION: We report nine patients diagnosed with thyroid eye disease whose intraocular pressure decreased during teprotumumab treatment for 8 weeks: patient 1, a 67-year-old Hispanic woman; patient 2, an 86-year-old African-American man; patient 3, a 71-year-old Caucasian woman; patient 4, a 72-year-old Hispanic woman; patient 5, a 65-year-old Caucasian woman; patient 6, a 54-year-old Caucasian man; patient 7, a 54-year-old Asian man; patient 8, a 31-year-old Asian woman; patient 9, a 60-year-old Caucasian woman. The diagnosis of thyroid eye disease was based on increased redness, swelling, and excessive tearing; abnormal proptosis, lid retraction, and diplopia measurements were also taken during physical examination. Intraocular pressure in primary, lateral gaze, and upgaze was documented. There was significant (p = 0.0397) improvement of primary gaze eye pressure from pre-teprotumumab infusions (baseline) to completion of the treatment course. CONCLUSIONS: Teprotumumab significantly decreased the intraocular pressure for patients during the duration of the study. Teprotumumab is a novel medication that is approved for the primary treatment of thyroid eye disease in both acute and chronic thyroid eye disease. Previous treatments used to treat thyroid eye disease include glucocorticoids, radiotherapy, or orbital decompression surgery; however, these treatments all have significant limitations. Teprotumumab is an effective noninvasive alternative for decreasing symptoms of thyroid eye disease and, as shown, also lowers intraocular pressure. However, teprotumumab should not be used as a substitute for glaucoma medications; its ability to lower intraocular pressure may be in addition to lowering periorbital pressure and retro-orbital pressure.

Whole genome duplication and dispersed duplication characterize the evolution of the plant PINOID gene family across plant species.

PINOID is a kinase belonging to the AGCVIII family, which regulates the polar distribution of PIN proteins and plays an important role in plant geotropism. However, the origin and evolutionary history of this gene family is not fully known. In this study, we identified 79 similar sequences across 17 plant species genomes (PINOID, D6PK, PINOID2, "hypothetical kinase"). Our results show that the AGCVIII kinase family may have originated from related "Hypothetical Kinases" that come out sister to the rest of the gene family members. These kinases differentiated their functions are found in different plant classes: D6PK in moss and PINOID and PINOID2 evolving in angiosperms including the pioneer plant Amborella trichopoda. Our study investigates the evolution of PINOID kinases from a phylogenetic perspective giving us insight into how this important plant signal transduction network switch evolved to play a fundamental and important function in plant growth and development. We highlight the importance of whole genome duplications and dispersed duplications as opposed to tandem duplications in the evolution of this gene family.

Substance of choice, impact of heroin or opium on treatment retention in a multicentre randomised controlled trial in Iran.

INTRODUCTION: In the Middle East and Asia, illicit opioid use exists across a spectrum between heroin and opium. The impact of primary opioid of choice on opioid agonist treatment retention has not been well evaluated previously, especially for opium tincture, an increasingly popular form of opioid agonist treatment in Iran. This study investigates the relationship between primary opioid of choice, namely heroin or opium, and retention in opium tincture and methadone treatment. METHODS: Participants with opioid use disorder (n = 204) were randomised to receive opium tincture or methadone. All participants were categorised as mainly using opium or heroin. Bivariate analyses between treatment retention and primary opioid of choice (P < 0.05) and logistic regression were conducted. RESULTS: Among the 191 participants included in this analysis, heroin was the primary substance of choice for 135 participants (70.7%) and opium for 56 (29.3%). Bivariate analysis showed that the opium group was more likely to be satisfied with family situation, employed and retained in treatment than the heroin group while less likely to experience incarceration and use multiple substances. When adjusting for covariates, primary opioid of choice was not significantly associated with retention in either methadone or opium tincture treatment arm. DISCUSSION AND CONCLUSIONS: Positive factors, such as employment, housing and family support, seem to collectively explain the higher retention in treatment among those who primarily use opium compared to those who use heroin. To optimise retention in opioid agonist treatment, biopsychosocial care models should be further evaluated to improve psychosocial functioning.

Continuous treatment with guselkumab maintains clinical responses through 4 years in patients with moderate-to-severe psoriasis: results from VOYAGE 1.

OBJECTIVES: To evaluate the efficacy of guselkumab through four years of continuous treatment for psoriasis. METHODS: In the phase 3 VOYAGE 1 trial, 837 patients with moderate-to-severe psoriasis were randomized to receive guselkumab 100 mg every-8-weeks, placebo, or adalimumab 40 mg every-2-weeks. Patients in the placebo and adalimumab groups crossed over to receive guselkumab at weeks 16/52, respectively; eligible patients received open-label guselkumab through week 204. Efficacy endpoints (i.e., PASI 75/90/100, IGA 0/1, and IGA 0) were analyzed in the guselkumab group using different methodologies: prespecified treatment failure rules (TFR, patients discontinued due to lack of efficacy, psoriasis worsening, or protocol-prohibited psoriasis treatment considered nonresponders); nonresponder imputation (NRI, patients with missing data counted as nonresponders); and As Observed (OBS, no imputation). Safety was evaluated through week 204. RESULTS: At week 204, PASI 90 response rates were 82.2%, 68.4%, and 84.3%, respectively, based on TFR, NRI, and OBS analyses; corresponding proportions at week 52 were 79.7%, 75.5%, and 80.6%. Similarly, PASI 75, PASI 100, IGA 0/1, and IGA 0 responses were maintained from week 52 through week 204. No new safety signals were identified. CONCLUSIONS: High efficacy response rates were maintained through four years of continuous guselkumab treatment for psoriasis.

HPRep: Quantifying Reproducibility in HiChIP and PLAC-Seq Datasets.

HiChIP and PLAC-Seq are emerging technologies for studying genome-wide long-range chromatin interactions mediated by the protein of interest, enabling more sensitive and cost-efficient interrogation of protein-centric chromatin conformation. However, due to the unbalanced read distribution introduced by protein immunoprecipitation, existing reproducibility measures developed for Hi-C data are not appropriate for the analysis of HiChIP and PLAC-Seq data. Here, we present HPRep, a stratified and weighted correlation metric derived from normalized contact counts, to quantify reproducibility in HiChIP and PLAC-Seq data. We applied HPRep to multiple real datasets and demonstrate that HPRep outperforms existing reproducibility measures developed for Hi-C data. Specifically, we applied HPRep to H3K4me3 PLAC-Seq data from mouse embryonic stem cells and mouse brain tissues as well as H3K27ac HiChIP data from human lymphoblastoid cell line GM12878 and leukemia cell line K562, showing that HPRep can more clearly separate among pseudo-replicates, real replicates, and non-replicates. Furthermore, in an H3K4me3 PLAC-Seq dataset consisting of 11 samples from four human brain cell types, HPRep demonstrated the expected clustering of data that could not be achieved by existing methods developed for Hi-C data, highlighting the need for a reproducibility metric tailored to HiChIP and PLAC-Seq data.

Clinical Anatomy of Human Donor C7 Nerve Roots for Surgical Transfer in Patients with Spastic Arm Paralysis.

BACKGROUND: Contralateral C7 (CC7) nerve transfer has successfully restored hand function in patients with spastic hemiplegia from chronic central nervous system injuries. However, little is known about the morphology and anatomy of the donor C7 nerve root in patients undergoing this procedure. This study quantified intraoperative measurements of donor C7 nerve roots during CC7 transfer surgery for spastic hemiplegia in patients treated at a high-volume center to describe observed anatomical variations for successful direct anastomosis. METHODS: A database of images from 21 patients (2 females, 19 males) undergoing CC7 surgery was searched for photographic data that contained a standard ruler measuring donor C7 nerve root length after surgical sectioning and before transfer. Two independent observers analyzed these images and recorded C7 nerve root diameter, length, and branch lengths. RESULTS: Mean (SD) values of donor C7 nerve measurements were length, 53.5 (8.0) mm; diameter, 5.1 (0.9) mm; branch length following surgical sectioning, 18.3 (6.3) mm. Right-sided donor C7 nerve roots yielded significantly longer branches compared with left-sided donor C7 nerve roots (P = 0.01). Other patient factors such as age, sex, or laterality of brain injury did not influence intraoperative anatomy. CONCLUSIONS: We report detailed intraoperative measurements of the donor C7 root during CC7 nerve transfer for spastic hemiplegia. These findings describe existing variation in surgical C7 nerve root anatomy in patients undergoing this procedure and may serve as a general reference for the expected donor C7 length in successful direct anastomosis.

Rhopressa-induced corneal edema: a case report.

BACKGROUND: Rhopressa (netarsudil) has recently been added to the arsenal of treatment for open-angle glaucoma. It is an effective norepinephrine transporter and Rho-associated protein kinase (ROCK) inhibitor used to decrease intraocular pressure (IOP), with the most common side effect being conjunctival hyperemia. CASE PRESENTATION: We report a unique case of Rhopressa-induced corneal edema in a 79-year-old African-American woman, which resolved after discontinuation. She had a history of smoking one cigarette per day and did not consume alcohol. She had no history of corneal edema or uveitis. CONCLUSIONS: Previous case reports have documented patients with Rhopressa-induced corneal edema; however, they have all had a preexisting history of corneal edema or uveitis. We believe that this is a unique case of Rhopressa-induced corneal edema in a relatively healthy eye. While Rhopressa is effective in managing glaucoma, there may be effects of treatment that are still unknown. We will discuss clinical findings of our case, along with a review of previous literature on Rhopressa and novel ROCK inhibitors. We hope that we can add to the existing body of literature and invite further investigation of Rhopressa and ROCK inhibitors and their effects on the cornea.