Notes

Immunomodulatory connection between G-CSF inside cancer malignancy: Therapeutic ramifications.
S acute care hospitals, COVID-19 was associated with high ICU admission and in-hospital mortality rates. Use of statins, angiotensin-converting enzyme inhibitors, and calcium channel blockers were associated with decreased odds of death. Understanding the potential benefits of unproven treatments will require future randomized trials.
The survival benefit of corticosteroids in septic shock remains uncertain.

To estimate the individual treatment effect (ITE) of corticosteroids in adults with septic shock in intensive care units using machine learning and to evaluate the net benefit of corticosteroids when the decision to treat is based on the individual estimated absolute treatment effect.

This cohort study used individual patient data from 4 trials on steroid supplementation in adults with septic shock as a training cohort to model the ITE using an ensemble machine learning approach. Data from a double-blinded, placebo-controlled randomized clinical trial comparing hydrocortisone with placebo were used for external validation. Vandetanib Data analysis was conducted from September 2019 to February 2020.

Intravenous hydrocortisone 50 mg dose every 6 hours for 5 to 7 days with or without enteral 50 μg of fludrocortisone daily for 7 days. The control was either the placebo or usual care.

All-cause 90-day mortality.

A total of 2548 participantsone strategy, -0.01 for treat all with hydrocortisone and fludrocortisone strategy, 0.06 for the treat by SAPS II strategy, and 0.31 for the treat by optimal individual model strategy. The net benefit of the SAPS II and the optimal individual model treatment strategies converged to zero for a smaller number willing to treat, but the individual model was consistently superior than model based on the SAPS II score.

These findings suggest that an individualized treatment strategy to decide which patient with septic shock to treat with corticosteroids yielded positive net benefit regardless of potential corticosteroid-associated side effects.
These findings suggest that an individualized treatment strategy to decide which patient with septic shock to treat with corticosteroids yielded positive net benefit regardless of potential corticosteroid-associated side effects.
The prevalence and severity of long-term health complications after exposure to sulfur mustard are unknown.

To investigate the long-term health outcomes among survivors exposed to sulfur mustard during the Iran-Iraq War.

In this retrospective cohort study, late-onset health complications of 64 190 Iranian survivors exposed to sulfur mustard during the Iran-Iraq War from 1980 to 1988 were investigated using descriptive statistics. Data involving affected organs and symptom severity were extracted from the Veterans and Martyr Affair Foundation (VMAF) database from 1980 to 2019. Assessments were conducted across 3 groups depending on whether survivors were (1) evacuated and admitted (EA) to a hospital; (2) not evacuated or admitted (NEA) to a hospital; or (3) evacuation or admission status was not documented.

Analysis of chronic symptom severity following exposure to sulfur mustard.

Mild, moderate, or severe rankings of symptoms in lungs, eyes, and skin of survivors exposed to sulfur mustard using datasions were observed more frequently among sulfur mustard-exposed survivors who had not been evacuated or hospitalized than among those who had been evacuated or hospitalized. These differences may be due to physiological response or dose of exposure. Close monitoring over an extended period may be required for detection of late pulmonary complications in individuals exposed to sulfur mustard.
Long-term control of node-positive (N1) prostate cancer, the incidence of which is increasing, is obtainable with aggressive treatment, and definitive external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT) is an increasingly preferred option. Caring for these patients is complex and may require resources more readily available at high-volume centers.

To evaluate the association between radiation facility case volume and overall survival (OS) in men with N1 prostate cancer.

This cohort study included 1899 men diagnosed with T1N1M0 to T4N1M0 prostate cancer treated with curative-intent EBRT and ADT between January 2004 and December 2016 at US facilities reporting to the National Cancer Database. Data analysis was performed from March to June 2020.

Treatment at a center with high vs low average cumulative facility volume (ACFV), defined as the total number of prostate radiation cases at an individual patient's treatment facility from 2004 until the year of that patient'swith treatment at a high-ACFV center. These results persisted after propensity score-based adjustment.

This cohort study found a significant association of facility case volume with long-term outcomes in men with N1 prostate cancer undergoing EBRT with ADT. Specifically, treatment at a facility with high radiation case volume was independently associated with longer OS. Further studies should focus on identifying which factors unique to high-volume centers may be responsible for this benefit.
This cohort study found a significant association of facility case volume with long-term outcomes in men with N1 prostate cancer undergoing EBRT with ADT. Specifically, treatment at a facility with high radiation case volume was independently associated with longer OS. Further studies should focus on identifying which factors unique to high-volume centers may be responsible for this benefit.We have recently demonstrated that dietary nitrate, a source of nitric oxide (NO) via the nitrate → nitrite → NO enterosalivary pathway, can improve muscle contractility in healthy older men and women. link2 Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. A pilot randomized, double-blind, placebo-controlled crossover study was therefore performed to determine the effects of ingesting 3.3 mL/kg of concentrated beetroot juice containing 0, 200, or 400 µmol/kg of nitrate in 9 healthy older subjects (mean age 70 ± 1 years). Maximal knee extensor power (Pmax) and speed (Vmax) were measured ~2.5 hours after nitrate ingestion using isokinetic dynamometry. Blood pressure was monitored periodically throughout each study. Pmax (in W/kg) was higher (p less then .05) after the lower dose (3.9 ± 0.4) compared to the placebo (3.7 ± 0.4) or higher dose (3.7 ± 0.4). Vmax (in rad/s) also tended to be higher (p = .08) after the lower dose (11.9 ± 0.7) compared to the placebo (10.8 ± 0.8) or higher dose (11.2 ± 0.8). Eight out of 9 subjects achieved a higher Pmax and Vmax after the lower versus the higher dose. These dose-related changes in muscle contractility generally paralleled changes in breath NO levels. No significant changes were found in systolic, diastolic, or mean arterial blood pressure. A lower dose of nitrate increases muscle speed and power in healthy older individuals, but these improvements are lost at a higher dose. Blood pressure, on the other hand, is not reduced even with a higher dose.
Advanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. link3 However, epidemiological evidence that high-protein diets increase AGEs is lacking.

We examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6±2.9 y; 52% female; 37% black).

CML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults <0.8 g/kg/d (n=1077), 0.8 to <1.2 g/kg/d (n=922), and ≥1.2 g/kg/d (n=440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression modelined similar across groups.
Higher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.
Retirement is a potential trigger for cognitive aging as it may be a stressful life event accompanied by changes in everyday activities. However, the consequences of retirement may differ across institutional contexts which shape retirement options. Comparing memory trajectories before and after retirement in 17 European countries, this study aims to identify cross-national differences in the association between retirement and memory decline.

Respondents to the longitudinal Survey of Health, Aging, and Retirement in Europe (SHARE; N = 8,646) aged 50+ who were in paid work at baseline and retired during the observation period completed up to 6 memory assessments (immediate and delayed word recall) over 13 years. Three-level (time points, individuals, and countries) linear mixed models with country-level random slopes for retirement were estimated to evaluate whether memory decline accelerated after retirement and if this association differed between countries.

On average, retirement was associated with a moderate decrement in word recall (b = -0.273, 95% CI -0.441, -0.104) and memory decline accelerated after retirement (b = -0.044, 95% CI -0.070, -0.018). Significant between-country heterogeneity in memory decline after retirement existed (variance = 0.047, 95% CI (0.013, 0.168). Memory decline after retirement was more rapid in Italy, Greece, Czech Republic, Poland, Portugal, and Estonia compared to Northern and Central European countries.

Memory decline postretirement was faster in Mediterranean and eastern European countries, which are characterized by less generous welfare systems with comparatively low pension benefits. Evaluation of resources that could protect retirees from memory decline would be valuable.
Memory decline postretirement was faster in Mediterranean and eastern European countries, which are characterized by less generous welfare systems with comparatively low pension benefits. Evaluation of resources that could protect retirees from memory decline would be valuable.Vitamin A (VA) and its pro-vitamin carotenoids are naturally occurring lipophilic compounds involved in several cellular processes and metabolic pathways. Despite their broad spectrum of activities in the general population, dietary deficiencies of these compounds can potentially affect pregnancy outcomes. Since maternal nutritional status and diet composition during pregnancy and lactation can have long-lasting effects in offspring until adulthood, this study presents an overview of VA and the role of pro-VA carotenoids during pregnancy and lactation - the nutrition, metabolism, and biological effects in the offspring. The review aimed to discuss the pro-VA carotenoids and VA-associated pathways and summarize the results with reference to gestational disorders, and VA and pro-VA carotenoids as preventive agents. Also, considering that obesity, overweight, and metabolic diseases are major public health concerns worldwide, fetal and neonatal development is discussed, highlighting the physiological role of these molecules in obesity prevention.
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