Development of delirium: Association with old age,severe burns,and intensive care

BackgroundDelirium is defined as a disturbance of attention and awareness that develops over a short period of time, is a change from the baseline, and typically fluctuates over time. Burn care involves a high prevalence of known risk factors for delirium such as sedation, inflammation, and prolonged stay in hospital. Our aim was to explore the extent of delirium and the impact of factors associated with it for adult patients who have been admitted to hospital with burns.MethodsIn this retrospective study, all adult patients who had been admitted with burns during a four-year period were studied, including both those who were treated with intensive care and intermediate care only (no intensive care). Daily records of the assessment of delirium using the Nursing Delirium Screening Scale (Nu-DESC) were analysed together with age, sex, the percentage of total body surface area burned, operations, and numbers of wound care procedures under anaesthesia, concentrations of plasma C-reactive protein, and other clinical variables. Logistic regression was used to analyse factors that were associated with delirium and its effect on mortality, and linear regression was used to analyse its effect on the duration of hospital stay.ResultsFifty-one patients (19%) of the total 262 showed signs of delirium (Nu-DESC score of 2 or more) at least once during their stay in hospital. Signs of delirium were recorded in 42/89 patients (47%) who received intensive care, and in 9/173 (5%) who had intermediate care. Independent factors for delirium in the multivariable regression were: age over 74 years; number of operations and wound care procedures under anaesthesia; and the provision of intensive care (area under the curve 0.940, 95% CI 0.899–0.981). Duration of hospital stay, adjusted for age and burn size, was 13.2 (95% CI 7.4–18.9, p < 0.001) days longer in the group who had delirium. We found no independent effects of delirium on mortality.ConclusionWe found a strong association between delirium and older age, provision ofr intensive care, and number of interventions under anaesthesia. A further 5% of patients who did not receive intensive care also showed signs of delirium, which is a finding that deserves to be thoroughly investigated in the future.     

Association of Karnofsky Performance Status with waitlist mortality among older and younger adults awaiting kidney transplantation

Patients with end-stage renal disease (ESRD) have impaired functional status compared with the general population. We sought to explore the association between Karnofsky Performance Status (KPS) and death/delisting from the kidney transplantation waitlist and whether this association differed by age. Patients listed for single-organ kidney transplantation in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2015, to January 1, 2018, were included. We performed competing-risk regression analyses to determine the association between KPS (“Severely impaired”, “Moderately impaired”, “Non-impaired”) and death/delisting, with deceased-donor kidney transplantation as a competing risk. We tested for interactions between age and KPS on death/delisting. Of the 89,819 patients analyzed, 39% were impaired (KPS < 80) and 20% were aged ≥ 65 years. Older age and lower KPS were independently associated with higher risk of death/delisting (age 45-64 years, HR 1.97 [95% CI 1.73-2.24]; age ≥ 65 years, HR 3.62 [95% CI 3.33-3.92] compared with age < 45 years; moderately impaired, HR 1.68 [95% CI 1.45-1.95]; severely impaired, HR 4.80 [95% CI 3.71-6.21] compared with non-impaired). Lower KPS was associated with higher risk of death/delisting among all ages, but this effect was slightly less pronounced among individuals aged ≥ 65 years. Performance status should be used when counseling patients with ESRD on their risks for death/delisting.     

Donor-recipient age interaction and the impact on clinical results after heart transplantation

To evaluate the impact of donor-recipient age matching on clinical outcomes after heart transplantation, a total of 509 patients (January 1990-December 2018, mean follow-up 111 ± 80 months) were stratified into 4 groups (young-R/young-D, young-R/old-D, old-R/young-D, old-R/old-D) according to the recipient (young-R < 60, old-R ≥ 60 years) and the donor (young-D < 50, old-D ≥ 50 years) age. No difference was found among 30-day mortality (P = .11) and postoperative complications between groups. Both unadjusted and adjusted survival was significantly higher for group young-R/young-D than that of other groups, in which survival was similar [adjusted HR for mortality of 2.0(1.2-3.4), 2.1(1.4-3.8) and 2.5(1.6-4.1) for groups old-R/young-D, young-R/old-D, old-R/old-D, respectively]. Compared to other groups, the incidence of grade ≥ 2 CAV was significantly lower in old-R/young-D group [adjusted HR 0.4(0.2-0.7)]. Among young recipients, the rate of acute grade ≥ 2 rejection episodes was higher in those receiving an old donor graft (P = .04). Old recipient groups were more affected by neoplasms and severe renal failure than young recipient groups (P < .01). Employment of hearts from donors ≥50 years of age adversely affects survival in recipients <60 years of age but does not influence outcomes in older recipients. Also, donor and recipient ages seem to have opposite effects on incidence of rejections and CAV of high grade.     

Male age is more critical to sperm DNA integrity than routine semen parameters in Chinese infertile males

This retrospective study evaluated the correlation between the sperm DNA integrity results and infertile male age or sperm motility in 654 infertile men undergoing infertility evaluations from 2013 to 2016. The correlation between the results of sperm DNA integrity and male age was positive, while a negative correlation was detected between sperm DNA integrity and sperm motility in all subjects. According to age (≤30, 30–35 and ≥35), men with normozoospermia or abnormal semen parameters were, respectively, divided into groups 1, 2 and 3, or groups A, B and C. The sperm DNA fragmentation index (DFI) and DFI abnormality rates in groups 3 and C were highest among their respective cohorts. But they were not significantly different between groups within the same age range. Statistically significant differences were found in male age, progressive motility, as well as total motility between patients with normal DFIs and those with abnormal DFIs in group C, but not in group 3. Older (≥35 years) infertile men have increased sperm DNA fragmentation, independent of conventional semen parameters. Male age is more critical to sperm DNA integrity than routine semen parameters.     

Subjective insomnia symptoms and sleep duration are not related to hypothalamic–pituitary–adrenal axis activity in older adults

Insomnia symptoms are highly prevalent in depressed older adults. This study investigates the association between hypothalamic–pituitary–adrenal (HPA) axis activity and symptoms of insomnia, respectively, sleep duration among 294 depressed and 123 non‐depressed older adults of the Netherlands Study of Depression in Older people (NESDO) study. Insomnia symptoms were defined as clinically relevant when having a score ≥ 10 points on the Women's Health Initiative Insomnia Rating Scale (WHIIRS). Sleep duration was categorized in short (≤ 6 h per night), normal (7–8 h per night) and long (≥ 9 h per night) duration. Salivary cortisol levels were used to assess the following cortisol parameters for HPA axis activity: area under the curve with respect to the increase (AUCi) and to the ground (AUCg), diurnal slope, evening cortisol level and dexamethasone suppression ratio. Clinically relevant insomnia symptoms were present in 46% of the participants. Thirty‐two per cent of the participants were short sleepers, whereas 16% were long sleepers. However, univariate analyses showed no differences in any of the HPA axis parameters between people with and without insomnia symptoms or between the three groups with different sleep duration. In addition, no significant interaction was found between a diagnosis of depression or the severity of depressive symptoms and any of the cortisol parameters in relation to insomnia symptoms or sleep duration.     

Next-generation sequencing technology a new tool for killer cell immunoglobulin-like receptor allele typing in hematopoietic stem cell transplantation

Killer cell Immunoglobulin-like Receptor (KIR) genes are a family of genes located together within the leukocyte receptor cluster on human chromosome 19q13.4. To date, 17 KIR genes have been identified including nine inhibitory genes (2DL1/L2/L3/L4/L5A/L5B, 3DL1/L2/L3), six activating genes (2DS1/S2/S3/S4/S5, 3DS1) and two pseudogenes (2DP1, 3DP1) classified into group A (KIR A) and group B (KIR B) haplotypes. The number and the nature of KIR genes vary between the individuals. In addition, these KIR genes are known to be polymorphic at allelic level (907 alleles described in July 2017). KIR genes encode for receptors which are predominantly expressed by Natural Killer (NK) cells. KIR receptors recognize HLA class I molecules and are able to kill residual recipient leukemia cells, and thus reduce the likelihood of relapse. KIR alleles of Hematopoietic Stem Cell (HSC) donor would require to be known (Alicata et al. Eur J Immunol 2016) because the KIR allele polymorphism may affect both the KIR⁺ NK cell phenotype and function (Gagne et al. Eur J Immunol 2013; Bari R, et al. Sci Rep 2016) as well as HSCT outcome (Boudreau et al. JCO 2017). The introduction of the Next Generation Sequencing (NGS) has overcome current conventional DNA sequencing method limitations, known to be time consuming. Recently, a novel NGS KIR allele typing approach of all KIR genes was developed by our team in Nantes from 30 reference DNAs (Maniangou et al. Front in Immunol 2017). This NGS KIR allele typing approach is simple, fast, reliable, specific and showed a concordance rate of 95% for centromeric and telomeric KIR genes in comparison with high-resolution KIR typing obtained to those published data using exome capture (Norman PJ et al. Am J Hum Genet 2016). This NGS KIR allele typing approach may also be used in reproduction and to better study KIR⁺ NK cell implication in the control of viral infections.     

Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia: Implications for Prophylaxis

Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR], .42; 95% confidence interval [CI], .26 to .70; P?=?.0008), grade II-IV aGVHD (HR, .24; 95% CI, .10 to .56; P?=?.001), and cGVHD (HR, .32; 95% CI, .19 to .54; P?<?.001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .36; 95% CI, .20 to .65; P?=?.0007) and in 2009-2013 (HR, .24; 95% CI. .11 to .53; P?=?.0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .23; 95% CI, .08 to .65; P?=?.0056) and 2009-2013 (HR, .16; 95% CI, .04 to .67; P?=?.0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.     

Effect of LSR polymorphism on blood lipid levels and age‐specific epistatic interaction with the APOE common polymorphism

The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B and ApoE receptor that participates in the removal of triglyceride‐rich lipoproteins during the postprandial phase. LSR gene is located upstream of APOE, an important risk factor for cardiovascular disease (CVD). Since the APOE common polymorphism significantly affects the variability of lipid metabolism, this study aimed to determine the potential impact of a functional SNP rs916147 in LSR gene on lipid traits in healthy subjects and to investigate potential epistatic interaction between LSR and APOE. Unrelated healthy adults (N = 432) and children (N = 328, <18 years old) from the STANISLAS Family Study were used. Age‐specific epistasis was observed between APOE and LSR, reversing the protective effect of APOE ε2 allele on cholesterol, ApoE and low‐density lipoprotein levels (β: .114, P: .777 × 10^?8, β: .125, P: .639 × 10^?3, β: .059, P: .531 × 10^?3, respectively). This interaction was verified in an independent adult population (n = 1744). These results highlight the importance of the LSR polymorphism and reveal the existence of complex molecular links between LSR and ApoE for the regulation of lipid levels, revealing potential new pathways of interest in type III hyperlipidemia and its involvement in CVD pathology.