Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection - A DRAGON collaborative analysis of 306 patients

Background: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. Methods: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. Results: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p &lt; 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR ≥2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. Conclusion: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.</p

Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease

Peer reviewedPublisher PD

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Abstract: Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Cognitive Remediation in Psychiatric Disorders: State of the Evidence, Future Perspectives, and Some Bold Ideas

Many people with psychiatric disorders experience impairments in cognition. These deficits have a significant impact on daily functioning and sometimes even on the further course of their disease. Cognitive remediation (CR) is used as an umbrella term for behavioral training interventions to ameliorate these deficits. In most but not all studies, CR has proven effective in improving cognition and enhancing everyday functional outcomes. In this paper, after quickly summarizing the empirical evidence, practical advice to optimize the effects of CR interventions is provided. We advocate that CR interventions should be as fun and motivating as possible, and therapists should at least consider using positively toned emotional stimuli instead of neutral stimuli. Participants should be screened for basic processing deficits, which should be trained before CR of higher-order cognitive domains. CR should stimulate metacognition and utilize natural settings to invoke social cognition. Wherever possible, CR tasks should link to tasks that participants face in their everyday life. Therapists should consider that participants might also benefit from positive side effects on symptomatology. Finally, the CR approach might even be utilized in settings where the treatment of cognitive impairments is not a primary target

&ldquo;Mmm, Smells like Coffee!&rdquo;: How a Brief Odor Identification Test Could Help to Identify People with Mild Cognitive Impairment and Dementia

(1) Background: Dementia and mild cognitive impairment (MCI) are still underdiagnosed in the general population. Impaired odor identification has been identified as an early marker of MCI and dementia. We aimed to compare the additional diagnostic value of two odor identification tests to a cognitive screening test in detecting MCI or dementia. (2) Methods: The Sniffin&rsquo; Sticks odor identification test (SS-OIT), a brief odor identification test (B-OIT) requiring the identification of coffee scent, and the Mini-Mental State Exam (MMSE) were administered to a consecutive series of 174 patients (93 with dementia, 42 with mild cognitive impairment, and 39 without cognitive impairment) referred for neuropsychological testing. (3) Results: Both participants with dementia and with MCI exhibited impairments in odor identification. The SS-OIT and the B-OIT were substantially correlated. Complementing MMSE scores with the SS-OIT or the B-OIT similarly improved the diagnostic accuracy of individuals with dementia and MCI. (4) Conclusions: People with suspected dementia or MCI may already benefit from brief odor identification tests. Although these tests require little additional time, they can notably increase sensitivity for dementia or MCI

Cognitive Remediation in Psychiatric Disorders: State of the Evidence, Future Perspectives, and Some Bold Ideas

Many people with psychiatric disorders experience impairments in cognition. These deficits have a significant impact on daily functioning and sometimes even on the further course of their disease. Cognitive remediation (CR) is used as an umbrella term for behavioral training interventions to ameliorate these deficits. In most but not all studies, CR has proven effective in improving cognition and enhancing everyday functional outcomes. In this paper, after quickly summarizing the empirical evidence, practical advice to optimize the effects of CR interventions is provided. We advocate that CR interventions should be as fun and motivating as possible, and therapists should at least consider using positively toned emotional stimuli instead of neutral stimuli. Participants should be screened for basic processing deficits, which should be trained before CR of higher-order cognitive domains. CR should stimulate metacognition and utilize natural settings to invoke social cognition. Wherever possible, CR tasks should link to tasks that participants face in their everyday life. Therapists should consider that participants might also benefit from positive side effects on symptomatology. Finally, the CR approach might even be utilized in settings where the treatment of cognitive impairments is not a primary target.</jats:p

&ldquo;Try to Build This Bunny as Fast as Possible without Using Red or Pink Bricks&rdquo;: How Simple Assembly Tasks Might Aid in Detecting People with Mild Cognitive Impairment and Dementia

(1) Background: Dementia and mild cognitive impairment (MCI) are still underdiagnosed in the general population. Impaired odor identification has been identified as an early marker of MCI and dementia. We aim to investigate whether short tasks, in which simple forms must be assembled from single building blocks based on a template or while considering specific re-strictions, could increase the diagnostic quality of established cognitive screening tests in detecting MCI or dementia. (2) Methods: A brief assembly test, where participants had to assemble simple animal shapes from Lego&reg; Duplo&reg; building blocks, the Frontal Assessment Battery, and the Mini-Mental State Exam (MMSE) were administered to a consecutive series of 197 patients (89 with mild dementia, 62 with mild cognitive impairment, and 46 without cognitive impairment) referred for neuropsychological testing. (3) Results: Both participants with dementia and with MCI performed badly in the assembly tasks. The assembly tasks and the Frontal Assessment Battery were substantially correlated. Complementing MMSE scores with the assembly tasks improved the diagnostic accuracy of individuals with dementia and MCI. (4) Conclusions: People with suspected dementia or MCI may already benefit from simple assembly tasks. Although these tests require little additional time, they can notably increase sensitivity for dementia or MCI