Accelerating Healing and Relieving Pain: High-Intensity Laser Therapy for Paraneoplastic Cutaneous Vasculitis Associated with Multiple Myeloma.

BACKGROUND Leukocytoclastic vasculitis (LCV) is an atypical form of cutaneous paraneoplastic manifestation. Its association with multiple myeloma (MM) is even rarer and is associated with poor prognosis and short survival, regardless of the therapy instituted. Different treatment approaches are necessary. We present a case in which LCV was the first manifestation of MM, and high-intensity laser therapy (HILT) was used as an option to accelerate healing and control pain. CASE REPORT A 76-year-old woman presented with pain and paresthesia in her lower limbs, associated with palpable purpura. The clinical diagnosis was small-vessel vasculitis. Laboratory tests showed an elevated gamma globulin monoclonal peak on protein electrophoresis. The immunophenotypic study of bone marrow aspirates led to the diagnosis of MM. Due to pain refractory to conventional analgesics, and the progressive evolution of the lesions, despite corticosteroid therapy, we performed photo-biomodulation with a neodymium-doped yttrium aluminum garnet laser (Nd: YAG), wavelength 1064 nanometers, using a 7-mm probe and energy density 6 J/cm². After the first session, the patient was referred for pain management, and after 5 weeks, we observed complete healing in ulcerated lesions and involution of bullous lesions. CONCLUSIONS This case report shows the positive effects of the Nd: YAG laser in modulating healing and reducing pain. HILT is an innovative, non-invasive, and effective treatment and should be considered a promising technique to accelerate healing and controlling pain.

Inflorescence Emergence and Flowering Response of Olive Cultivars Grown in Olive Reference Collection of Portugal (ORCP).

In olive trees, fluctuations in the onset of phenological stages have been reported due to weather conditions. The present study analyses the reproductive phenology of 17 olive cultivars grown in Elvas (Portugal) in 3 consecutive years (2012-2014). Through 2017-2022, the phenological observations continued with four cultivars. The phenological observations followed the BBCH scale. Over the course of the observations, the bud burst (stage 51) occurred gradually later; a few cultivars did not follow this trend in 2013. The flower cluster totally expanded phase (stage 55) was achieved gradually earlier, and the period between stages 51-55 was shortened, especially in 2014. Date of bud burst showed a negative correlation with minimum temperature (Tmin) of November-December, and, in 'Arbequina' and 'Cobrançosa', the interval stage 51-55 showed a negative correlation with both the Tmin of February and the Tmax of April, whereas in 'Galega Vulgar' and 'Picual' there was instead a positive correlation with the Tmin of March. These two seemed to be more responsive to early warm weather, whereas 'Arbequina' and 'Cobrançosa' were less sensitive. This investigation revealed that olive cultivars behaved differently under the same environmental conditions and, in some genotypes, the ecodormancy release may be linked to endogenous factors in a stronger way.

Syphilis response policies and their assessments: A scoping review.

Syphilis is one of the most common sexually transmitted infections (STIs) worldwide and has shown a rising trend in recent years, according to a report published by the World Health Organization (WHO) in 2021. Given this problem, the present study aims to develop a scoping review of what has been done in the world after the publication of the global strategy for the elimination of STIs, with a specific focus on syphilis. Thus, we searched for papers on health policies in response to syphilis in Pubmed, Scopus, ScienceDirect, and EBSCO by CINAHL, as well as in official documents from international health organizations. The period from January 1, 2016, to August 14, 2022 was considered. Our search returned 880 papers addressing "Syphilis," "Health Policy," and "Health Policies" combined. Twenty-three papers fulfilled the inclusion and exclusion criteria according to two research questions set out for this scoping review. Our findings suggest that Brazil and Peru presented the greatest adequacy of the strategies provided by WHO in 2016 and the Pan American Health Organization (PAHO) in 2017, aiming tothe goals set out in the UN's 2030 Agenda for sustainable development. Among the studies found, six countries (Cuba, Thailand, Belarus, Armenia, Moldova, and Puerto Rico) reported the elimination of mother-to-child transmission (MTCT) of syphilis, but the most recent data are from 2016. Furthermore, it is essential to mention that no country has been found that has presented a comprehensive response to syphilis, noting the control or elimination of the disease in all key populations. Thus, it is necessary to constantly monitor national policies based on in-depth studies on the quality of the response, the challenges, and the national, regional, and global perspectives for the control of the disease until 2030, the year in which the SDGs will be reviewed. Systematic review registration: https://osf.io/x9er5/?view_only=0cc0062222ec45dcb2f4d41484d285b6, identifier: 10.17605/OSF.IO/X9ER5.

Optimization of COVID-19 vaccination and the role of individuals with a high number of contacts: A model based approach.

We report strong evidence of the importance of contact hubs (or superspreaders) in mitigating the current COVID-19 pandemic. Contact hubs have a much larger number of contacts than the average in the population, and play a key role on the effectiveness of vaccination strategies. By using an age-structures compartmental SEIAHRV (Susceptible, Exposed, Infected symptomatic, Asymptomatic, Hospitalized, Recovered, Vaccinated) model, calibrated from available demographic and COVID-19 incidence, and considering separately those individuals with a much greater number of contacts than the average in the population, we show that carefully choosing who will compose the first group to be vaccinated can impact positively the total death toll and the demand for health services. This is even more relevant in countries with a lack of basic resources for proper vaccination and a significant reduction in social isolation. In order to demonstrate our approach we show the effect of hypothetical vaccination scenarios in two countries of very different scales and mitigation policies, Brazil and Portugal.

Acute Limb Ischemia After Self-Injection of Crushed Morphine Tablets into the Radial Artery: Role of Infrared Thermography in the Assessment of Tissue Perfusion.

BACKGROUND This article presents a case involving complications after intentional injection of crushed tablets into the arterial circulation, its diagnosis, and the treatment adopted. The diagnosis process illustrates the potential of techniques based on thermal imaging as tools to assess tissue perfusion. Inadvertent intravenous injection of crushed tablets is more common, but there are few reports on arterial circulation, and no studies were found on the self-injection of crushed morphine tablets, particularly into the radial artery. CASE REPORT A 51-year-old man with alcoholism and a history of illegal drug usage intentionally self-injected 3 crushed morphine tablets into his right radial artery. The patient progressed with compartment syndrome, requiring decompressive fasciotomy of the right forearm and ischemia of the right fingers, which were amputated. He presented with rhabdomyolysis and required dialysis. The patient agreed to full heparinization, corticotherapy, and the use of nitroglycerin and prostaglandin E1. Due to the progression of the necrotic area, the patient underwent proximal phalanx excision and surgical reconstruction of the right-hand remnant. CONCLUSIONS The injection of morphine tablets into circulation caused severe complications, which led to the excision of the proximal phalanx and the surgical reconstruction of the remnant of the right hand. In the present case, infrared thermography proved to be an effective method in assessing tissue perfusion.

Attack rate and the price of SARS-CoV-2 herd immunity in Brazil.

We introduce a compartmental model with age structure to study the dynamics of the SARS-COV-2 pandemic. The contagion matrix in the model is given by the product of a probability per contact with a contact matrix explicitly taking into account the contact structure among different age groups. The probability of contagion per contact is considered as time dependent to represent non-pharmaceutical interventions, and is fitted from the time series of deaths. The approach is used to study the evolution of the COVID-19 pandemic in the main Brazilian cities and compared to two good quality serological surveys. We also discuss with some detail the case of the city of Manaus which raised special attention due to a previous report of three-quarters attack rate by the end of 2020. We discuss estimates for Manaus and all Brazilian cities with a total population of more than one million. We also estimate the attack rate with respect to the total population, in each Brazilian state by January, 1st 2021 and May, 23 2021.

Muscle Mass Assessed by Computed Tomography at the Third Lumbar Vertebra Predicts Patient Survival in Chronic Kidney Disease

OBJECTIVE: Muscle mass is a key element for the evaluation of nutritional disturbances in patients with chronic kidney disease (CKD). Low muscle mass is associated with increased morbidity and mortality. The assessment of muscle mass by computed tomography at the third lumbar vertebra region (CTMM-L3) is an accurate method not subject to errors from fluctuation in the hydration status. Therefore, we aimed at investigating whether CTMM-L3 was able to predict mortality in nondialyzed CKD 3-5 patients. METHODS: This is a prospective observational cohort study. We evaluated 223 nondialyzed CKD patients (60.3 ± 10.6 years; 64% men; 50% diabetics; glomerular filtration rate 20.7 ± 9.6 mLmin1.73 m2). Muscle mass was measured by CTMM-L3 using the Slice-O-Matic software and analyzed according to percentile adjusted by gender. Nutritional parameters, laboratory data, and comorbidities were evaluated, and mortality was followed up for 4 years. RESULTS: During the study period, 63 patients died, and the main cause of death was cardiovascular disease. Patients who died were older, had lower hemoglobin and albumin, as well as lower muscle markers. CTMM-L3 below the 25th percentile was associated with higher mortality according to the Kaplan-Meier curve (P = .017) and in Cox regression analysis (crude hazard ratio, 1.87 [95% confidence interval, 1.11-3.16]), also when adjusting for potential confounders (hazard ratio 1.83 [95% confidence interval 1.02-3.30]). CONCLUSION: Low muscle mass measured by computed tomography at the third lumbar vertebra region is an independent predictor of increased mortality in nondialyzed CKD patients.

Muscle Mass Assessed by Computed Tomography at the Third Lumbar Vertebra Predicts Patient Survival in Chronic Kidney Disease.

OBJECTIVE: Muscle mass is a key element for the evaluation of nutritional disturbances in patients with chronic kidney disease (CKD). Low muscle mass is associated with increased morbidity and mortality. The assessment of muscle mass by computed tomography at the third lumbar vertebra region (CTMM-L3) is an accurate method not subject to errors from fluctuation in the hydration status. Therefore, we aimed at investigating whether CTMM-L3 was able to predict mortality in nondialyzed CKD 3-5 patients. METHODS: This is a prospective observational cohort study. We evaluated 223 nondialyzed CKD patients (60.3 ± 10.6 years; 64% men; 50% diabetics; glomerular filtration rate 20.7 ± 9.6 mLmin1.73 m2). Muscle mass was measured by CTMM-L3 using the Slice-O-Matic software and analyzed according to percentile adjusted by gender. Nutritional parameters, laboratory data, and comorbidities were evaluated, and mortality was followed up for 4 years. RESULTS: During the study period, 63 patients died, and the main cause of death was cardiovascular disease. Patients who died were older, had lower hemoglobin and albumin, as well as lower muscle markers. CTMM-L3 below the 25th percentile was associated with higher mortality according to the Kaplan-Meier curve (P = .017) and in Cox regression analysis (crude hazard ratio, 1.87 [95% confidence interval, 1.11-3.16]), also when adjusting for potential confounders (hazard ratio 1.83 [95% confidence interval 1.02-3.30]). CONCLUSION: Low muscle mass measured by computed tomography at the third lumbar vertebra region is an independent predictor of increased mortality in nondialyzed CKD patients.

The association between plasma proteomics and incident cardiovascular disease identifies MMP-12 as a promising cardiovascular risk marker in patients with chronic kidney disease

BACKGROUND AND AIMS: Previous proteomics efforts in patients with chronic kidney disease (CKD) have predominantly evaluated urinary protein levels. Therefore, our aim was to investigate the association between plasma levels of 80 cardiovascular disease-related proteins and the risk of major adverse cardiovascular events (MACE) in patients with CKD. METHODS: Individuals with CKD stages 3-5 (eGFR below 60 ml min-1 [1.73 m]-2) from three community-based cohorts (PIVUS, ULSAM, SAVA), one diabetes cohort (CARDIPP) and one cohort with peripheral artery disease patients (PADVA) with information on 80 plasma protein biomarkers, assessed with a proximity extension assay, and follow-up data on incident MACE, were used as discovery sample. To validate findings and to asses generalizability to patients with CKD in clinical practice, an outpatient CKD-cohort (Malnutrition, Inflammation and Vascular Calcification (MIVC)) was used as replication sample. RESULTS: In the discovery sample (total n = 1316), 249 individuals experienced MACE during 7.0 ± 2.9 years (range 0.005-12.9) of follow-up, and in the replication sample, 71 MACE events in 283 individuals over a mean ± SD change of 2.9 ± 1.2 years (range 0.1-4.0) were documented. Applying Bonferroni correction, 18 proteins were significantly associated with risk of MACE in the discovery cohort, adjusting for age and sex in order of significance, GDF-15, FGF-23, REN, FABP4, IL6, TNF-R1, AGRP, MMP-12, AM, KIM-1, TRAILR2, TNFR2, CTSL1, CSF1, PlGF, CA-125, CCL20 and PAR-1 (p < 0.000625 for all). Only matrix metalloproteinase 12 (MMP-12) was significantly associated with an increased risk of MACE in the replication sample (hazard ratio (HR) per SD increase, 1.36, 95% CI (1.07-1.75), p = 0.013). CONCLUSIONS: Our proteomics analyses identified plasma MMP-12 as a promising cardiovascular risk marker in patients with CKD.

The association between plasma proteomics and incident cardiovascular disease identifies MMP-12 as a promising cardiovascular risk marker in patients with chronic kidney disease.

BACKGROUND AND AIMS: Previous proteomics efforts in patients with chronic kidney disease (CKD) have predominantly evaluated urinary protein levels. Therefore, our aim was to investigate the association between plasma levels of 80 cardiovascular disease-related proteins and the risk of major adverse cardiovascular events (MACE) in patients with CKD. METHODS: Individuals with CKD stages 3-5 (eGFR below 60 ml min-1 [1.73 m]-2) from three community-based cohorts (PIVUS, ULSAM, SAVA), one diabetes cohort (CARDIPP) and one cohort with peripheral artery disease patients (PADVA) with information on 80 plasma protein biomarkers, assessed with a proximity extension assay, and follow-up data on incident MACE, were used as discovery sample. To validate findings and to asses generalizability to patients with CKD in clinical practice, an outpatient CKD-cohort (Malnutrition, Inflammation and Vascular Calcification (MIVC)) was used as replication sample. RESULTS: In the discovery sample (total n = 1316), 249 individuals experienced MACE during 7.0 ± 2.9 years (range 0.005-12.9) of follow-up, and in the replication sample, 71 MACE events in 283 individuals over a mean ± SD change of 2.9 ± 1.2 years (range 0.1-4.0) were documented. Applying Bonferroni correction, 18 proteins were significantly associated with risk of MACE in the discovery cohort, adjusting for age and sex in order of significance, GDF-15, FGF-23, REN, FABP4, IL6, TNF-R1, AGRP, MMP-12, AM, KIM-1, TRAILR2, TNFR2, CTSL1, CSF1, PlGF, CA-125, CCL20 and PAR-1 (p < 0.000625 for all). Only matrix metalloproteinase 12 (MMP-12) was significantly associated with an increased risk of MACE in the replication sample (hazard ratio (HR) per SD increase, 1.36, 95% CI (1.07-1.75), p = 0.013). CONCLUSIONS: Our proteomics analyses identified plasma MMP-12 as a promising cardiovascular risk marker in patients with CKD.

Somatic Embryogenesis from Mature Embryos of Olea europaea L. cv. 'Galega Vulgar' and Long-Term Management of Calli Morphogenic Capacity.

Several olive cultivars, characterized by high-quality olive oil show agronomical issues such as excessive vigor, high susceptibility to biotic and abiotic stresses, and low propagation ability. They are strong candidates for breeding based on new technologies to improve their performance in a short period of time. For this reason, the first step is developing efficient somatic embryogenesis (SE) protocols. Somatic embryogenesis in olive is highly genotype-dependent for both adult tissues and mature embryos as initial explants, requiring the development of specific protocols for each genotype. Trials using cotyledons and radicles as initial explants, isolated from ripe seeds from the Portuguese olive cv. 'Galega vulgar', gave more than 95% calli development. Radicles proved to be the most responsive tissue for SE induction, with an average of 2 embryos per callus after callus transfer to expression medium, and 14 embryos per callus after subculture on the olive cyclic embryogenesis medium (ECO). Embryogenic competence could be recovered after several subcultures on ECO medium that maintained cyclic embryogenesis for an indeterminate period of time. Embryo conversion and plant acclimatization were also attained with high success rates. Media management for cyclic embryogenesis maintenance is of general importance for SE protocols in any olive genotype. Somatic embryogenesis was thus attained for the first time in embryo-derived explants of cv. 'Galega vulgar'.

Regulation of sterol content and biosynthetic gene expression during flower opening and early fruit development in olive.

Phytosterols are lipophilic membrane components essential not only for diverse cellular functions but also are biosynthetic precursors of the plant hormone, brassinosteroid (BR). However, the interaction between phytosterol and BR during early fleshy-fruit growth remains largely uncharacterized. In olive, phytosterols are important lipids because they affect oil quality, but phytosterol composition during flowering and early fruit development has not been explored. Here, we first investigated the temporal changes in phytosterol composition, and biosynthetic gene expression that occurred during olive flower opening and early fruit growth. Next, we analyzed the interrelationship between phytosterol and BR, whose levels we manipulated through the application of exogenous BRs (24-epibrassinolide, EBR) or a BR biosynthesis inhibitor (brassinazole, Brz). In this report, the profiling of phytosterol measurement revealed that ß-sitosterol is the most abundant in olive reproductive organs. Our data demonstrate that both OeCYP51 and OeSMT2 genes are upregulated during floral anthesis in good agreement with the rise in cholesterol and ß-sitosterol contents in olive flower. By contrast, the OeCYP51 and OeSMT2 genes displayed different expression patterns during early olive-fruit development. Furthermore, our data show that exogenous EBR enhanced the early olive-fruit growth, as well as the OeSMT2 transcript and ß-sitosterol levels, but decreased the OeCYP51 transcript, squalene, campesterol and cholesterol levels, whereas the Brz treatment exerted the opposite effect. Overall, our findings indicate an up-regulation of ß-sitosterol biosynthesis by BR at the transcriptional level during early olive-fruit growth, providing a valuable tool to unravel the physiological function of SMT2 in future studies.

Muscle mass assessment by computed tomography in chronic kidney disease patients: agreement with surrogate method

Background/objectives Patients with chronic kidney disease (CKD) are subjected to muscle wasting. Therefore, it is important to investigate surrogate methods that enable the assessment of muscle mass loss in the clinical setting. We aimed to analyze the agreement between computed tomography (CT) and surrogate methods for the assessment of muscle mass in non-dialysis CKD patients. Subjects/methods Cross-sectional study including 233 non-dialysis patients on CKD stages 3 to 5 (61±11 years; 64% men; glomerular filtration rate 22 (14­33) mL/min/1.73m2). The muscle mass was evaluated by CT and bioelectrical impedance, skinfold thicknesses, midarm muscle circumference (MAMC), the predictive equations of Janssen and Baumgartner and the physical examination of muscle atrophy from the subjective global assessment. Results In males, the MAMC showed the best agreement with CT as indicated by the kappa test (k=0.57, P<0.01), sensitivity (S=68%), specificity (S=89%) and accuracy (area under the curve­AUC=0.78), followed by the Baumgartner equation (kappa=0.46, P<0.01; sensitivity=60%; specificity=87% and AUC=0.73). In female, the Baumgartner equation showed the best agreement with CT (kappa=0.43, P<0.01; sensitivity=57%; specificity=86% and AUC=0.71). (AU)

Muscle mass assessment by computed tomography in chronic kidney disease patients: agreement with surrogate methods.

BACKGROUND/OBJECTIVES: Patients with chronic kidney disease (CKD) are subjected to muscle wasting. Therefore, it is important to investigate surrogate methods that enable the assessment of muscle mass loss in the clinical setting. We aimed to analyze the agreement between computed tomography (CT) and surrogate methods for the assessment of muscle mass in non-dialysis CKD patients. SUBJECTS/METHODS: Cross-sectional study including 233 non-dialysis patients on CKD stages 3 to 5 (61 ± 11 years; 64% men; glomerular filtration rate 22 (14-33) mL/min/1.73 m2). The muscle mass was evaluated by CT and bioelectrical impedance, skinfold thicknesses, midarm muscle circumference (MAMC), the predictive equations of Janssen and Baumgartner and the physical examination of muscle atrophy from the subjective global assessment. RESULTS: In males, the MAMC showed the best agreement with CT as indicated by the kappa test (k = 0.57, P < 0.01), sensitivity (S = 68%), specificity (S = 89%) and accuracy (area under the curve-AUC = 0.78), followed by the Baumgartner equation (kappa = 0.46, P < 0.01; sensitivity = 60%; specificity = 87% and AUC = 0.73). In female, the Baumgartner equation showed the best agreement with CT (kappa = 0.43, P < 0.01; sensitivity = 57%; specificity = 86% and AUC = 0.71). CONCLUSIONS: The MAMC and Baumgartner equation showed the best agreement with CT for the assessment of muscle mass in non-dialysis CKD patients.

Modulation of sphingolipid long-chain base composition and gene expression during early olive-fruit development, and putative role of brassinosteroid.

Sphingolipids are abundant membrane components and signalling molecules in various aspects of plant development. However, the role of sphingolipids in early fleshy-fruit growth has rarely been investigated. In this study, we first investigated the temporal changes in sphingolipid long-chain base (LCB) content, composition, and gene expression that occurred during flower opening and early fruit development in olive (Olea europaea L. cv Picual). Moreover, the interaction between sphingolipid and the plant hormone, brassinosteroid (BR), during the early fruit development was also explored. For this, BR levels were manipulated through the application of exogenous BRs (24-epibrassinolide, EBR) or a BR biosynthesis inhibitor (brassinazole, Brz) and their effects on early fruit development, sphingolipid LCB content, and gene expression were examined in olive fruit at 14 days post-anthesis (DPA). We here show that sphingolipid with C-4 hydroxylation and Δ8 desaturation with a preference for (E)-isomer formation are quantitatively the most important sphingolipids in olive reproductive organs. In this work, the total LCB amount significantly decreased at the anthesis stage, but olive sphingosine-1-phosphate lyase (OeSPL) gene was expressed exclusively in flower and upregulated during the anthesis, revealing an association with the d18:1(8E) accumulation. However, the LCB content increased in parallel with the upregulation of the expression of genes for key sphingolipid biosynthetic and LCB modification enzymes during early fruit development in olive. Likewise, we found that EBR exogenously applied to olive trees significantly stimulated the fruit growth rate whereas Brz inhibited fruit growth rate after 7 and 14 days of treatment. In addition, this inhibitory effect could be counteracted by the application of EBR. The promotion of early fruit growth was accompanied by the down-regulation of sphingolipid LCB content and gene expression in olive fruit, whereas Brz application raised levels of sphingolipid LCB content and gene expression in olive fruit after 7 and 14 days of treatment. Thus, our data indicate that endogenous sphingolipid LCB and gene-expression levels are intricately controlled during early fruit development and also suggest a possible link between BR, the sphingolipid content/gene expression, and early fruit development in olive.

Global prevalence of protein-energy wasting in kidney disease: A meta-analysis of contemporary observational studies from the international society of renal nutrition and metabolism

Objective: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. Methods: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. Results: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. Conclusion: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Global Prevalence of Protein-Energy Wasting in Kidney Disease: A Meta-analysis of Contemporary Observational Studies From the International Society of Renal Nutrition and Metabolism.

OBJECTIVE: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. METHODS: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. RESULTS: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. CONCLUSION: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Intramuscle fat infiltration in non-dialysis CKD: clinical determinants and association with mortality

BACKGROUND: Intramuscle fat infiltration (IFI) is an important feature of aging currently understood as a cause of muscle weakness in elderly. Compared to healthy controls, IFI has been reported elevated in chronic kidney disease (CKD) patients. Its determinants and consequences, however, are unknown. METHODS: Cross-sectional study with mortality follow-up of 195 nephrology-referred patients with non-dialysis CKD stages 3-5. Mean age was 60±11 years, 61% were men and glomerular filtration rate (creatinine clearance) was 25±12 ml/min/1.73 m2 . We used computed tomography (CT) scan (Slice-O-Matic software version 5.0) of the third lumbar vertebra to quantify the degree of IFI (reported as % of fat within muscle area). Muscles evaluated by CT were psoas, transversus abdominis, rectus abdominis, external and internal obliques, erector spinae and quadratus lumborum. Coronary artery calcification score (CAC) was evaluated by CT, muscle strength by dynamometry (handgrip strength, HGS) and shown as standard values to normative tables. RESULTS: IFI was higher in women than in men (9.7±6 vs 6.3±4%, P 0.05), and was positively correlated (Spearman test) with age (rho =0.37), Charlson comorbidity score (rho=0.19), CAC (r=0.16) and CT-derived visceral (rho=0.37) and subcutaneous fat (rho =0.57). IFI was negatively associated with HGS (rho=-0.25) and CT-derived skeletal muscle mass (rho=-0.37)...(AU)

Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes

ABSTRACT: Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30­77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularized Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (±SD) of 6.4 ± 2.3 years. We replicated associations (<5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)- 12, IL-27 subunit α (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardio vascular event.

Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes.

AIMS/HYPOTHESIS: Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. METHODS: We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. RESULTS: Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (±SD) of 6.4 ± 2.3 years. We replicated associations (<5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit α (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. CONCLUSIONS/INTERPRETATION: We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.