Criteria for premium intraocular lens patient selection.

PURPOSE OF REVIEW: To discuss available premium intraocular lenses (IOLs), patient selection, and important considerations for each premium IOL. RECENT FINDINGS: We review important topics and considerations for premium IOL selection: specifically, toric, extended depth of focus (EDOF), multifocal/trifocal, light adjustable lenses (LALs), and small aperture IOLs. Toric lenses are an excellent option for patients with astigmatism. However, to achieve optimal patient satisfaction, it is critical to account for the ATR astigmatism contribution from the posterior cornea and high angle alphas. Additionally, examining the ocular surface prior to placement of EDOF/multifocal IOLs is important, yet the significance of HOAs on outcomes after implantation still must be elucidated more. Finally, recent studies reveal that the small aperture lens is a good alternative for those with corneal irregularities, and second generation LALs are a great option to achieve target refractions in those with less predictable refractive outcomes, such as in Fuchs' dystrophy or in eyes with previous refractive surgery.

Fecal microbiome and bile acid metabolome in adult short bowel syndrome.

Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to 2 yr to determine which patients will wean from PN. Here, we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Stool and sera were collected from healthy controls and from patients with SBS (n = 52) with ileostomy, jejunostomy, ileocolonic, and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling, and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS and serum amino acid analyses. Patients with SBS exhibited altered gut microbiota with reduced gut microbial diversity compared with healthy controls. We observed differences in the microbiomes of patients with SBS with ileostomy versus jejunostomy, jejunocolonic versus ileocolonic anastomoses, and PN dependence compared with those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in patients with SBS, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who were weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic aicd. Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select patients with SBS, promoting the ability to wean from PN. Proadaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.NEW & NOTEWORTHY Loss of intestinal surface area causes short bowel syndrome, intestinal failure, and parenteral nutrition dependence. We analyzed the gut microbiota and bile acid metabolome of a large cohort of short bowel syndrome adult patients with different postsurgical anatomies. We report a novel analysis of the microbiome of patients with ileostomy and jejunostomy. Enrichment of specific microbial and bile acid species may be associated with the ability to wean from parenteral nutrition.

Sensitivity of T1/T2-weighted ratio in detection of cortical demyelination is similar to magnetization transfer ratio using post-mortem MRI.

BACKGROUND: Detecting cortical demyelination using magnetic resonance imaging (MRI) in multiple sclerosis (MS) remains a challenge. Magnetization transfer ratio (MTR), T1-weighted/T2-weighted ratio (T1T2R), and T2-weighted (T2w) signal are sensitive to cortical demyelination, but their accuracy is unknown. OBJECTIVES: To quantify the sensitivity, specificity, and accuracy of postmortem T1T2R, MTR, and T2w in detecting cortical demyelination. METHODS: In situ postmortem MRIs from 9 patients were used to measure T1T2R, MTR, and T2w along the midline of cortical gray matter and classified as normal or abnormal. MRIs were co-registered and compared to hemispheric myelin staining. The sensitivity, specificity, and accuracy of T1T2R, MTR, and T2w in detecting cortical demyelination were measured. RESULTS: The mean age (standard deviation) at death was 64.7 (+/-13.7) years with a disease duration of 23.8 (+/-10.5) years. The sensitivity was 78% for MTR, 75% for T1T2R, and 63% for T2w. The specificity was 46% (T2w), 13% (T1T2R), and 29% (MTR). The accuracy was 71% (T2w), 39% (MTR), and 42% (T1T2R). There were no significant differences between different MRI measures in cortical demyelination or intracortical/subpial lesion detection. CONCLUSIONS: Although somewhat sensitive, the modest specificity of conventional MRI modalities for cortical demyelination indicates that they are influenced by cortical changes other than demyelination. Improved acquisition and post-processing are needed to reliably measure cortical lesion load.

Increased Risk of Advanced Colonic Adenomas and Timing of Surveillance Colonoscopy Following Solid Organ Transplantation.

BACKGROUND: Detection and removal of colonic adenomatous polyps (CAP) decreases colorectal cancer (CRC) development, particularly with more or larger polyps or polyps with advanced villous/dysplastic histology. Immunosuppression following solid organ transplantation (SOT) may accelerate CAP development and progression compared to average-risk population but the benefit of earlier colonoscopic surveillance is unclear. AIMS: Study the impact of maintenance immunosuppression post-SOT on developmental timing, multiplicity and pathological features of CAP, by measuring incidence of advanced CAP (villous histology, size ≥ 10 mm, ≥ 3 polyps, presence of dysplasia) post-SOT and the incidence of newly diagnosed CRC compared to average-risk age-matched population. METHODS: Single-center retrospective cohort study of SOT recipients. RESULTS: 295 SOT recipients were included and were compared with 291 age-matched average-risk controls. The mean interval between screening and surveillance colonoscopies between SOT and control groups was 6.3 years vs 5.9 years (p = 0.13). Post-SOT maintenance immunosuppression mean duration averaged 59.9 months at surveillance colonoscopy. On surveillance examinations, SOT recipients exhibited more advanced (≥ 10 mm) adenomas compared to matched controls (9.2% vs. 3.8%, p = 0.034; adjusted OR 2.38; 95% CI 1.07-5.30). CONCLUSION: SOT recipients appear at higher risk for developing advanced CAP, suggesting that earlier surveillance should be considered.

Same-sex marriage legalization associated with reduced implicit and explicit antigay bias.

The current research tested whether the passing of government legislation, signaling the prevailing attitudes of the local majority, was associated with changes in citizens' attitudes. Specifically, with ∼1 million responses over a 12-y window, we tested whether state-by-state same-sex marriage legislation was associated with decreases in antigay implicit and explicit bias. Results across five operationalizations consistently provide support for this possibility. Both implicit and explicit bias were decreasing before same-sex marriage legalization, but decreased at a sharper rate following legalization. Moderating this effect was whether states passed legislation locally. Although states passing legislation experienced a greater decrease in bias following legislation, states that never passed legislation demonstrated increased antigay bias following federal legalization. Our work highlights how government legislation can inform individuals' attitudes, even when these attitudes may be deeply entrenched and socially and politically volatile.

Functional Magnetic Resonance Imaging Correlates of Ventral Striatal Deep Brain Stimulation for Poststroke Pain.

OBJECTIVE: Deep brain stimulation (DBS) for pain has largely been implemented in an uncontrolled manner to target the somatosensory component of pain, with research leading to mixed results. We have previously shown that patients with poststroke pain syndrome who were treated with DBS targeting the ventral striatum/anterior limb of the internal capsule (VS/ALIC) demonstrated a significant improvement in measures related to the affective sphere of pain. In this study, we sought to determine how DBS targeting the VS/ALIC modifies brain activation in response to pain. MATERIALS AND METHODS: Five patients with poststroke pain syndrome who were blinded to DBS status (ON/OFF) and six age- and sex-matched healthy controls underwent functional magnetic resonance imaging (fMRI) measuring blood oxygen level-dependent activation in a block design. In this design, each participant received heat stimuli to the affected or unaffected wrist area. Statistical comparisons were performed using fMRI z-maps. RESULTS: In response to pain, patients in the DBS OFF state showed significant activation (p < 0.001) in the same regions as healthy controls (thalamus, insula, and operculum) and in additional regions (orbitofrontal and superior convexity cortical areas). DBS significantly reduced activation of these additional regions and introduced foci of significant inhibitory activation (p < 0.001) in the hippocampi when painful stimulation was applied to the affected side. CONCLUSIONS: These findings suggest that DBS of the VS/ALIC modulates affective neural networks.

Broadening the stimulus set: Introducing the American Multiracial Faces Database.

Face-based perceptions form the basis for how people behave towards each other and, hence, are central to understanding human interaction. Studying face perception requires a large and diverse set of stimuli in order to make ecologically valid, generalizable conclusions. To date, there are no publicly available databases with a substantial number of Multiracial or racially ambiguous faces. Our systematic review of the literature on Multiracial person perception documented that published studies have relied on computer-generated faces (84% of stimuli), Black-White faces (74%), and male faces (63%). We sought to address these issues, and to broaden the diversity of available face stimuli, by creating the American Multiracial Faces Database (AMFD). The AMFD is a novel collection of 110 faces with mixed-race heritage and accompanying ratings of those faces by naive observers that are freely available to academic researchers. The faces (smiling and neutral expression poses) were rated on attractiveness, emotional expression, racial ambiguity, masculinity, racial group membership(s), gender group membership(s), warmth, competence, dominance, and trustworthiness. The large majority of the AMFD faces are racially ambiguous and can pass into at least two different racial categories. These faces will be useful to researchers seeking to study Multiracial person perception as well as those looking for racially ambiguous faces in order to study categorization processes in general. Consequently, the AMFD will be useful to a broad group of researchers who are studying face perception.

Reporting and Abstracting Variability in Technical Standards for Breast Cancer Operations.

BACKGROUND: The American College of Surgeons Commission on Cancer has incorporated documentation of critical elements outlined in Operative Standards for Cancer Surgery into revised standards for cancer center accreditation. This study assessed the current documentation of critical elements in partial mastectomy (PM) and sentinel lymph node biopsy (SLNB) operative reports. MATERIALS AND METHODS: Operative reports for PM + SLNB at a single academic institution from 2013 to 2018 were reviewed for compliance and surveyor interobserver reliability with the Oncologic Elements of Operative Record defined in Operative Standards and compared with a nonredundant American Society of Breast Surgeons Mastery of Breast Surgery (MBS) quality measure for specimen orientation. RESULTS: Ten reviewers each evaluated 66 PM + SLNB operative reports for 13 Oncologic Elements and one MBS measure. No operative records reported all critical elements for PM + SLNB or PM alone. Residents completed 36.4% of operative reports: Element documentation was similar for PM but varied significantly for SLNB between resident and attending authorship. Combined reporting performance and interrater reliability varied across all elements and was highest for the use of SLNB tracer (97.1% and κ = 0.95, respectively) and lowest for intraoperative assessment of SLNB (30.6%, κ = 0.43). MBS specimen orientation had both high proportion reported (87.0%) and interrater reliability (κ = 0.84). CONCLUSIONS: Adherence to reporting critical elements for PM and SLNB varied. Whether differential compliance was tied to discrepancies in documentation or reviewer abstraction, clarification of synoptic choices may improve reporting consistency. Evolving techniques or technologies will require continuous appraisal of mandated reporting for breast surgery.

Exascale applications: skin in the game.

As noted in Wikipedia, skin in the game refers to having 'incurred risk by being involved in achieving a goal', where 'skin is a synecdoche for the person involved, and game is the metaphor for actions on the field of play under discussion'. For exascale applications under development in the US Department of Energy Exascale Computing Project, nothing could be more apt, with the skin being exascale applications and the game being delivering comprehensive science-based computational applications that effectively exploit exascale high-performance computing technologies to provide breakthrough modelling and simulation and data science solutions. These solutions will yield high-confidence insights and answers to the most critical problems and challenges for the USA in scientific discovery, national security, energy assurance, economic competitiveness and advanced healthcare. This article is part of a discussion meeting issue 'Numerical algorithms for high-performance computational science'.

Introducing the Sociopolitical Motive × Intergroup Threat Model to Understand How Monoracial Perceivers' Sociopolitical Motives Influence Their Categorization of Multiracial People.

Researchers have used social dominance, system justification, authoritarianism, and social identity theories to understand how monoracial perceivers' sociopolitical motives influence their categorization of multiracial people. The result has been a growing understanding of how particular sociopolitical motives and contexts affect categorization, without a unifying perspective to integrate these insights. We review evidence supporting each theory's predictions concerning how monoracial perceivers categorize multiracial people who combine their ingroup with an outgroup, with attention to the moderating role of perceiver group status. We find most studies cannot arbitrate between theories of categorization and reveal additional gaps in the literature. To advance this research area, we introduce the sociopolitical motive × intergroup threat model of racial categorization that (a) clarifies which sociopolitical motives interact with which intergroup threats to predict categorization and (b) highlights the role of perceiver group status. Furthermore, we consider how our model can help understand phenomena beyond multiracial categorization.

Quality metrics of screening colonoscopies performed by PAs.

BACKGROUND: Many communities face a shortage of qualified endoscopists. Training physician assistants (PAs) to perform colonoscopies can expand the availability of colorectal cancer screening. This study examined screening colonoscopy metrics and quality indicators among gastroenterologists, supervised PAs, and gastroenterology fellows. METHODS: Consecutive patients undergoing average-risk screening colonoscopy were stratified into one of three groups by endoscopist type. Procedure and pathology reports were reviewed for the technical performance and quality metrics of the providers. RESULTS: PAs performed comparably to gastroenterologists in technical performance and quality metrics, and demonstrated higher cecal intubation rates than their gastroenterologist colleagues. Comparisons of attending physicians and PAs grouped by years of experience also did not show notable differences in performance. CONCLUSIONS: In a supervised practice, PAs performed on par with their gastroenterology colleagues on established colonoscopy quality indicators. Following proper training, PAs can be employed in the provision of screening colonoscopy.

MR Imaging-based Estimation of Upper Motor Neuron Density in Patients with Amyotrophic Lateral Sclerosis: A Feasibility Study.

Purpose To determine if magnetic resonance (MR) imaging metrics can estimate primary motor cortex (PMC) motor neuron (MN) density in patients with amyotrophic lateral sclerosis (ALS). Materials and Methods Between 2012 and 2014, in situ brain MR imaging was performed in 11 patients with ALS (age range, 35-81 years; seven women and four men) soon after death (mean, 5.5 hours after death; range, 3.2-9.6 hours). The brain was removed, right PMC (RPMC) was excised, and MN density was quantified. RPMC metrics (thickness, volume, and magnetization transfer ratio) were calculated from MR images. Regression modeling was used to estimate MN density by using RPMC and global MR imaging metrics (brain and tissue volumes); clinical variables were subsequently evaluated as additional estimators. Models were tested at in vivo MR imaging by using the same imaging protocol (six patients with ALS; age range, 54-66 years; three women and three men). Results RPMC mean MN density varied over a greater than threefold range across patients and was estimated by a linear function of normalized gray matter volume (adjusted R2 = 0.51; P = .008; <10% error in most patients). When considering only sporadic ALS, a linear function of normalized RPMC and white matter volumes estimated MN density (adjusted R2 = 0.98; P = .01; <10% error in all patients). In vivo data analyses detected decreases in MN density over time. Conclusion PMC mean MN density varies widely in end-stage ALS possibly because of disease heterogeneity. MN density can potentially be estimated by MR imaging metrics. © RSNA, 2018 Online supplemental material is available for this article.

T1-/T2-weighted ratio differs in demyelinated cortex in multiple sclerosis.

Detecting cortical demyelination in patients with multiple sclerosis (MS) is difficult. Using magnetic resonance imaging (MRI), ratio maps of T1-weighted (T1w) and T2-weighted (T2w) images may be sensitive to cortical myelin levels. In this MRI-histological study, postmortem in situ scans were acquired from 6 cadavers with MS on a 3T MRI machine. Immunocytochemistry was used to correlate myelin status and cortical T1w/T2w measures. The results showed that the T1w/T2w values significantly differed between demyelinated and myelinated cortex (p < 0.001). The T1w/T2w ratio maps may be a relatively simple, clinically feasible method to assess cortical demyelination. Ann Neurol 2017;82:635-639.

Impact of immunoablation and autologous hematopoietic stem cell transplantation on gray and white matter atrophy in multiple sclerosis.

BACKGROUND: Immunoablation and autologous hematopoietic stem cell transplantation (IA/aHSCT) halts relapses, white matter (WM) lesion formation, and pathological whole-brain (WB) atrophy in multiple sclerosis (MS) patients. Whether the latter was due to effects on gray matter (GM) or WM warranted further exploration. OBJECTIVE: To model GM and WM volume changes after IA/aHSCT to further understand the effects seen on WB atrophy. METHODS: GM and WM volume changes were calculated from serial baseline and follow-up magnetic resonance imaging (MRI) ranging from 1.5 to 10.5 years in 19 MS patients treated with IA/aHSCT. A mixed-effects model with two predictors (total busulfan dose and baseline T1-weighted WM lesion volume "T1LV") characterized the time-courses after IA/aHSCT. RESULTS: Accelerated short-term atrophy of 2.1% and 3.2% occurred in GM and WM, respectively, on average. Both busulfan dose and T1LV were significant predictors of WM atrophy, whereas only busulfan was a significant predictor of GM atrophy. Compared to baseline, a significant reduction in GM atrophy, not WM atrophy, was found. The average rates of long-term GM and WM atrophy were -0.18%/year (standard error (SE): 0.083) and -0.07%/year (SE: 0.14), respectively. CONCLUSION: Chemotherapy-related toxicity affected both GM and WM. WM was further affected by focal T1-weighted lesion-related pathologies. Long-term rates of GM and WM atrophy were comparable to those of normal-aging.

Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial.

BACKGROUND: Strong immunosuppression, including chemotherapy and immune-depleting antibodies followed by autologous haemopoietic stem-cell transplantation (aHSCT), has been used to treat patients with multiple sclerosis, improving control of relapsing disease. We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis. METHODS: We did this phase 2 single-arm trial at three hospitals in Canada. We enrolled patients with multiple sclerosis, aged 18-50 years with poor prognosis, ongoing disease activity, and an Expanded Disability Status Scale of 3.0-6.0. Autologous CD34 selected haemopoietic stem-cell grafts were collected after mobilisation with cyclophosphamide and filgrastim. Immunoablation with busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin was followed by aHSCT. The primary outcome was multiple sclerosis activity-free survival (events were clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, and sustained progression of Expanded Disability Status Scale score). This study was registered at ClinicalTrials.gov, NCT01099930. FINDINGS: Between diagnosis and aHSCT, 24 patients had 167 clinical relapses over 140 patient-years with 188 Gd-enhancing lesions on 48 pre-aHSCT MRI scans. Median follow-up was 6.7 years (range 3.9-12.7). The primary outcome, multiple sclerosis activity-free survival at 3 years after transplantation was 69.6% (95% CI 46.6-84.2). With up to 13 years of follow-up after aHSCT, no relapses occurred and no Gd enhancing lesions or new T2 lesions were seen on 314 MRI sequential scans. The rate of brain atrophy decreased to that expected for healthy controls. One of 24 patients died of transplantation-related complications. 35% of patients had a sustained improvement in their Expanded Disability Status Scale score. INTERPRETATION: We describe the first treatment to fully halt all detectable CNS inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs. Furthermore, many of the patients had substantial recovery of neurological function despite their disease's aggressive nature. FUNDING: Multiple Sclerosis Scientific Research Foundation.

Brain atrophy after bone marrow transplantation for treatment of multiple sclerosis.

BACKGROUND: A cohort of patients with poor-prognosis multiple sclerosis (MS) underwent chemotherapy-based immune ablation followed by immune reconstitution with an autologous hematopoietic stem cell transplant (IA/aHSCT). This eliminated new focal inflammatory activity, but resulted in early acceleration of brain atrophy. OBJECTIVE: We modeled the time course of whole-brain volume in 19 patients to identify the baseline predictors of atrophy and to estimate the average rate of atrophy after IA/aHSCT. METHODS: Percentage whole-brain volume changes were calculated between the baseline and follow-up magnetic resonance imaging (MRI; mean duration: 5 years). A mixed-effects model was applied using two predictors: total busulfan dose and baseline volume of T1-weighted white-matter lesions. RESULTS: Treatment was followed by accelerated whole-brain volume loss averaging 3.3%. Both the busulfan dose and the baseline lesion volume were significant predictors. The atrophy slowed progressively over approximately 2.5 years. There was no evidence that resolution of edema contributed to volume loss. The mean rate of long-term atrophy was -0.23% per year, consistent with the rate expected from normal aging. CONCLUSION: Following IA/aHSCT, MS patients showed accelerated whole-brain atrophy that was likely associated with treatment-related toxicity and degeneration of "committed" tissues. Atrophy eventually slowed to that expected from normal aging, suggesting that stopping inflammatory activity in MS can reduce secondary degeneration and atrophy.