Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID‐19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized ...adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID‐19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID‐19 during the 9‐week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow‐up period of 52 days (IQR: 16‐66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin‐6 levels. In sum, hospitalized kidney transplant recipients with COVID‐19 have higher rates of acute kidney injury and mortality.
In this multinational cohort of 144 kidney transplanted patients from 11 transplant centers in the US and Europe who were hospitalized for COVID‐19, acute kidney injury occurred in 52% and respiratory failure requiring intubation occurred in 29%, with an overall mortality of 32%.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Context. Calcifediol has been proposed as a potential treatment for COVID-19 patients. Objective: To compare the administration or not of oral calcifediol on mortality risk of patients hospitalized ...because of COVID-19. Design: Retrospective, multicenter, open, non-randomized cohort study. Settings: Hospitalized care. Patients: Patients with laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the South of Spain. Intervention: Patients received calcifediol (25-hydroxyvitamin D3) treatment (0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or not. Main Outcome Measure: In-hospital mortality during the first 30 days after admission. Results: A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol (mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving such treatment (mortality rate of 20%; p < 0.01). Patients who received calcifediol after admission were more likely than those not receiving treatment to have comorbidity and a lower rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg, and age ≥ 65 years), acute respiratory distress syndrome (moderate or severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a multivariable logistic regression model, adjusting for confounders, there were significant differences in mortality for patients receiving calcifediol compared with patients not receiving it (OR = 0.16 (95% CI 0.03 to 0.80). Conclusion: Among patients hospitalized with COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was significantly associated with lower in-hospital mortality during the first 30 days. The observational design and sample size may limit the interpretation of these findings.
To determine the tumor tissue/cell distribution, functional associations, and clinical significance of PD-1, LAG-3, and TIM-3 protein expression in human non-small cell lung cancer (NSCLC).
Using ...multiplexed quantitative immunofluorescence, we performed localized measurements of CD3, PD-1, LAG-3, and TIM-3 protein in >800 clinically annotated NSCLCs from three independent cohorts represented in tissue microarrays. Associations between the marker's expression and major genomic alterations were studied in The Cancer Genome Atlas NSCLC dataset. Using mass cytometry (CyTOF) analysis of leukocytes collected from 20 resected NSCLCs, we determined the levels, coexpression, and functional profile of PD-1, LAG-3, and TIM-3 expressing immune cells. Finally, we measured the markers in baseline samples from 90 patients with advanced NSCLC treated with PD-1 axis blockers and known response to treatment.
PD-1, LAG-3, and TIM-3 were detected in tumor-infiltrating lymphocytes (TIL) from 55%, 41.5%, and 25.3% of NSCLC cases, respectively. These markers showed a prominent association with each other and limited association with major clinicopathologic variables and survival in patients not receiving immunotherapy. Expression of the markers was lower in EGFR-mutated adenocarcinomas and displayed limited association with tumor mutational burden. In single-cell CyTOF analysis, PD-1 and LAG-3 were predominantly localized on T-cell subsets/NKT cells, whereas TIM-3 expression was higher in NK cells and macrophages. Coexpression of PD-1, LAG-3, and TIM-3 was associated with prominent T-cell activation (CD69/CD137), effector function (Granzyme-B), and proliferation (Ki-67), but also with elevated levels of proapoptotic markers (FAS/BIM). LAG-3 and TIM-3 were present in TIL subsets lacking PD-1 expression and showed a distinct functional profile. In baseline samples from 90 patients with advanced NSCLC treated with PD-1 axis blockers, elevated LAG-3 was significantly associated with shorter progression-free survival.
PD-1, LAG-3, and TIM-3 have distinct tissue/cell distribution, functional implications, and genomic correlates in human NSCLC. Expression of these immune inhibitory receptors in TILs is associated with prominent activation, but also with a proapoptotic T-cell phenotype. Elevated LAG-3 expression is associated with insensitivity to PD-1 axis blockade, suggesting independence of these immune evasion pathways.
Objectives：Despite the great impact the migration has had in economic, social and health-related fields, and the repercussions of alcohol consumption on them, few data exist concerning the extent of ...alcohol consumption in migrant workers. The aims of this study were to identify workers with a hazardous drinking problem by means of a self-reported questionnaire (Alcohol Use Disorders Identification Test-AUDIT) and a biomarker (carbohydrate-deficient transferrin-CDT) and to ascertain associated risk factors. Methods：A cross-sectional survey was conducted using a random sample of 385 migrant workers, undergoing a routine health examination as part of occupational health services. Results：The results showed that 13.8% (n=53) of the workers were screened as positive with the AUDIT (>-8) and/or CDT (>2.6) and identified as hazardous drinkers and that 53.8% (n=207) were teetotallers. Being a man (OR：2.0), working in the construction industry (OR：2.8) or agriculture (OR：2.2), being resident in Spain for more than 7 years (OR：2.3) and sharing a house with friends were the factors most closely associated with hazardous drinking. Conclusions：Prevention-orientated programs, adjusted to the characteristics of each country and the origin of the migrants themselves, should be instituted to modify the drinking habits of migrant workers considered at risk.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The use of the new International Association of the Diabetes and Pregnancy Study Groups criteria (IADPSGC) for the diagnosis of gestational diabetes mellitus (GDM) results in an increased prevalence ...of GDM. Whether their introduction improves pregnancy outcomes has yet to be established. We sought to evaluate the cost-effectiveness of one-step IADPSGC for screening and diagnosis of GDM compared with traditional two-step Carpenter-Coustan (CC) criteria.
GDM risk factors and pregnancy and newborn outcomes were prospectively assessed in 1,750 pregnant women from April 2011 to March 2012 using CC and in 1,526 pregnant women from April 2012 to March 2013 using IADPSGC between 24 and 28 weeks of gestation. Both groups received the same treatment and follow-up regimes.
The use of IADPSGC resulted in an important increase in GDM rate (35.5% vs. 10.6%) and an improvement in pregnancy outcomes, with a decrease in the rate of gestational hypertension (4.1 to 3.5%: -14.6%, P < 0.021), prematurity (6.4 to 5.7%: -10.9%, P < 0.039), cesarean section (25.4 to 19.7%: -23.9%, P < 0.002), small for gestational age (7.7 to 7.1%: -6.5%, P < 0.042), large for gestational age (4.6 to 3.7%: -20%, P < 0.004), Apgar 1-min score <7 (3.8 to 3.5%: -9%, P < 0.015), and admission to neonatal intensive care unit (8.2 to 6.2%: -24.4%, P < 0.001). Estimated cost savings was of €14,358.06 per 100 women evaluated using IADPSGC versus the group diagnosed using CC.
The application of the new IADPSGC was associated with a 3.5-fold increase in GDM prevalence in our study population, as well as significant improvements in pregnancy outcomes, and was cost-effective. Our results support their adoption.
The consumption of orange juice may lead to reduced oxidative stress and may enhance the antioxidant defense system.
The aim was to evaluate the effects of the intake of orange juice containing ...either normal (NPJ) or high (HPJ) concentrations of polyphenols (299 and 745 mg/d, respectively) on the antioxidant defense system, oxidative stress biomarkers, and clinical signs of metabolic syndrome in 100 nonsmoking subjects who were either overweight or obese.
A randomized, double-blind crossover study was conducted over two 12-wk periods with a 7-wk washout period. The effects on enzymatic and nonenzymatic blood antioxidant defense systems, urinary and plasma oxidative stress biomarkers, and clinical signs of metabolic syndrome were evaluated before and after an intervention with both of the orange juices. Paired t tests and linear mixed-effects models were used to evaluate the effects of juice, time, and interactions.
The intake of either NPJ or HPJ led to a decrease in urinary 8-hydroxy-2'-deoxyguanosine (NPJ: 935 ± 134 to 298 ± 19 ng/mg creatinine; HPJ: 749 ± 84 to 285 ± 17 ng/mg creatinine), 8-iso-prostaglandin F2α (NPJ: 437 ± 68 to 156 ± 14 ng/mg creatinine; HPJ: 347 ± 43 to 154 ± 13 ng/mg creatinine), erythrocyte catalase, and glutathione reductase activities. A decrease was also observed in body mass index, waist circumference, and leptin (all P < 0.05). The NPJ intervention decreased systolic and diastolic blood pressures (systolic blood pressure: 128 ± 1 to 124 ± 2 mm Hg; diastolic blood pressure: 79 ± 1 to 76 ± 1 mm Hg), whereas the HPJ intervention increased erythrocyte superoxide dismutase (SOD) activity (17.7 ± 1.5 to 23.1 ± 1.7 U/mg hemoglobin).
Our results show that the consumption of either NPJ or HPJ protected against DNA damage and lipid peroxidation, modified several antioxidant enzymes, and reduced body weight in overweight or obese nonsmoking adults. Only blood pressure and SOD activity were influenced differently by the different flavanone supplementations. This trial was registered at clinicaltrials.gov as NCT01290250.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND: This study was designed to evaluate and compare antioxidant capacity and radical scavenging activity of naringin and its aglycone by different in vitro assays. The effects of flavanones ...on lipid peroxidation, glutathione (GSH) oxidation and DNA cleavage were also assessed.RESULTS: The results showed that naringenin exhibited higher antioxidant capacity and hydroxyl and superoxide radical scavenger efficiency than naringin. Our results evidenced that glycosylation attenuated the efficiency in inhibiting the enzyme xanthine oxidase and the aglycone could act like a more active chelator of metallic ions than the glycoside. Additionally, naringenin showed a greater effectiveness in the protection against oxidative damage to lipids in a dose-dependent manner. Both flavanones were equally effective in reducing DNA damage. However, they show no protective effect on oxidation of GSH.CONCLUSION: The data obtained support the importance of characterizing the ratio naringin/naringenin in foods when they are evaluated for their health benefits.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Despite advancements in the global dialog surrounding sex and gender equity, an important gap persists with women markedly underrepresented in major roles within health care leadership.
We examined ...the extent of women’s representation in prominent positions within parenteral and enteral nutrition (PEN) societies worldwide over a span of 2 decades.
This retrospective analysis explored the sex distribution of society chairs, conference presidents, and editor-in-chief positions across 64 PEN societies between 2003 and 2022. Additionally, data on the first and last authors of endorsed clinical guidelines were collected from the 2 leading societies.
Over the past 20 y, women held society chair positions in 34.4% of cases. The representation shifted from 30% during the decade from 2003 to 2012 to 40.5% from 2013 to 2022. Throughout these years, the numbers consistently ranged from 0 to 10; however, the median shifted upward from 1 during the first decade to 4 in the subsequent decade (P = 0.04). Of 420 congress presidencies, ∼30% were women. In endorsed guidelines, women were the first authors in 27.1% of cases (P < 0.001) and the last in 28.9% (P < 0.001) compared with men. Of the 123 journal editor-in-chief positions, women occupied 23 (18.7%).
Over the last 2 decades, women have been consistently underrepresented in prominent leadership roles in PEN societies globally. Although there has been a noticeable shift toward more women in chair positions, true sex equality remains elusive. Moreover, sex disparities are even more pronounced in positions, such as conference presidents, authors of major guidelines, and editors-in-chief of society-affiliated journals. These data underscore the pressing need to enhance efforts toward sex equality across these domains.
J. Neurochem. (2012) 120, 259–268.
Autophagy is an important process which plays a key role in cellular homeostasis by degrading cytoplasmic components in the lysosomes, which facilitates recycling. ...Alterations to normal autophagy have been linked to excitotoxicity, but the mechanisms governing its signal transduction remain unclear. The aim of this study was to explore the role of autophagy in neuronal excitotoxic death by delivering small interfering RNA (siRNA) to rat cortical neurons, using a dendrimer to silence the autophagy‐related gene 6 (beclin 1) and to determine the role of autophagy in excitotoxicity. We have found that the dendrimer is very efficient to deliver siRNA to rat cortical neurons, leading to almost complete removal of the target protein Beclin 1. In addition, NMDA increases autophagy markers, such as the protein levels of Beclin 1, the microtubule‐associated light chain 3 (LC3) B‐II/LC3B‐I ratio, and monodansylcadaverine (MDC) labeling in rat cortical neurons. Moreover, NMDA also increases the formation of autophagosomes observed under a transmission electron microscope. Silencing beclin 1 expression blocked NMDA‐induced autophagy. Moreover, Beclin 1 removal potentiated NMDA‐induced neuronal death indicating that autophagy plays a protective role during excitotoxicity and suggesting that targeting autophagy might be a helpful therapeutic strategy in neurodegenerative diseases.
siRNA unveils the role of autophagy in excitotoxic deathThis study was performed to identify the role of autophagy in excitotoxic death by knocking down autophagic proteins using dendrimer‐delivered siRNA. The most relevant finding is that autophagy plays a neuroprotective role during excitotoxicity and that it is possible to knock down neuronal proteins using a dendrimer‐delivered siRNA. The conclusion is relevant because it indicates that the autophagic pathway might be a therapeutic target in neurodegenerative diseases and that it is possible to dissect neuronal signaling pathways using dendrimer‐delivered specific siRNA.
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