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Telomere Length Changes during Critical Illness: A Prospective, Observational Study.

ABSTRACT: OBJECTIVE:evaluation of telomere length change in acutely ill adult patients. DESIGN:Blood samples were drawn on the first and seventh day of intensive care unit (ICU) stay to assess telomere length using a polymerase chain reaction (PCR)-based technique. Demographic data collected included age, weight, admission diagnosis, baseline laboratory values (pH, C- reactive protein (CRP), serum albumin level, white blood cell count (WBC) count, platelet count), and baseline SOFA and APACHE II scores. Additional data collected during the ICU stay included a repeated WBC count, the presence of positive blood cultures and outcome data, including death in the ICU or following discharge, whether ventilated or not at ICU discharge, and destination following discharge, i.e., medical ward or rehabilitation. SETTING:General ICU in tertiary hospital. PATIENTS:Forty patients admitted to the ICU within 72 h of hospital admission suffering from an acute illness were included in this prospective, observational study. MAIN RESULTS:Of the 40 patients studied, telomere shortening was noted in 21, telomere lengthening in 11, and no significant change in the other eight. The age of patients demonstrating telomere shortening was statistically significantly younger (45.4 vs. 61.5 years, p < 0.023) compared to those showing increased telomere length. In addition, a significant correlation was observed between the difference in telomere length and the corresponding difference in WBC count (telomere shortening was associated with a decreased WBC count and vice versa). A trend toward shortening was seen in patients with sepsis (p = 0.07). No significant correlations were found for any other demographic or outcome parameter and changes in telomere length. CONCLUSION:Changes in telomere length, both shortening and lengthening, were evident in the acute setting, but no associations between such changes with outcome were noted. Further studies in more homogeneous groups of patients appear to be warranted.

SUBMITTER: Zribi B

PROVIDER: S-EPMC6826589 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Telomere Length Changes during Critical Illness: A Prospective, Observational Study.

Zribi Benjamin B Uziel Orit O Lahav Meir M Mesilati Stahy Ronit R Singer Pierre P

Genes 20190927 10

<h4>Objective</h4>evaluation of telomere length change in acutely ill adult patients.<h4>Design</h4>Blood samples were drawn on the first and seventh day of intensive care unit (ICU) stay to assess telomere length using a polymerase chain reaction (PCR)-based technique. Demographic data collected included age, weight, admission diagnosis, baseline laboratory values (pH, C- reactive protein (CRP), serum albumin level, white blood cell count (WBC) count, platelet count), and baseline SOFA and APAC ...[more]

PMID: 31569793

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Project description:PURPOSE:For patients suffering from prolonged critical illness, it is unknown whether and when the hypothalamus-pituitary-adrenal axis alterations recover, and to what extent adrenocortical function parameters relate to sepsis/septic shock, to clinical need for glucocorticoid treatment, and to survival. METHODS:Patients still in ICU on day 7 (N?=?392) and 20 matched healthy subjects were included. Morning blood and 24-h urine were collected daily and cosyntropin tests (250 µg) performed weekly, repeated 1 week after ICU discharge on the regular ward. RESULTS:In all patients free of glucocorticoid treatment up until ICU day 28 (N?=?347), plasma ACTH always remained low/normal, whereas free cortisol remained high (P???0.002) explained by reduced binding proteins (P???0.02) and suppressed cortisol breakdown (P???0.001). Beyond ICU day 28 (N?=?64 long-stayers), plasma (free)cortisol was no longer elevated. One week after ICU discharge, plasma ACTH and (free)cortisol always rose to supra-normal levels (P???0.006), most pronounced in long-stayers. Long-stayers always showed low incremental total (P???0.001), but normal incremental free cortisol responses to weekly cosyntropin tests, explained by low cortisol plasma binding proteins. Sepsis/septic shock patients were not different from others, patients subsequently receiving glucocorticoids (N?=?45) were not different from those who did not, and non-survivors were distinguishable from survivors only by higher (free)cortisol. CONCLUSIONS:Irrespective of sepsis/septic shock, need for glucocorticoids and survival, low cortisol plasma binding proteins and suppressed cortisol breakdown determine systemic (free)cortisol availability in prolonged critical illness, the latter no longer elevated beyond ICU day 28. The uniform rise in ACTH and cortisol to supra-normal levels 1 week after ICU discharge indicates recovery of a central adrenocortical suppression while in ICU. Low cortisol plasma binding invalidates the cosyntropin test.

Project description:BACKGROUND:Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consumption and/or unhealthy nutrition. We investigated whether critically ill children admitted to the PICU have shorter-than-normal telomeres, and whether early parenteral nutrition (PN) independently affects telomere length when adjusting for known determinants of telomere length. METHODS:Telomere length was quantified in leukocyte DNA from 342 healthy children and from 1148 patients who had been enrolled in the multicenter, randomised controlled trial (RCT), PEPaNIC. These patients were randomly allocated to initiation of PN within 24 h (early PN) or to withholding PN for one week in PICU (late PN). The impact of early PN versus late PN on the change in telomere length from the first to last PICU-day was investigated with multivariable linear regression analyses. RESULTS:Leukocyte telomeres were 6% shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825) telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in healthy children (P <?0.0001)). Adjusted for potential baseline determinants and leukocyte composition, early PN was associated with telomere shortening during PICU stay as compared with late PN (estimate early versus late PN -0.021 T/S-units, 95% CI -0.038; 0.004, P = 0.01). Other independent determinants of telomere length identified in this model were age, gender, baseline telomere length and fraction of neutrophils in the sample from which the DNA was extracted. Telomere shortening with early PN was independent of post-randomisation factors affected by early PN, including longer length of PICU stay, larger amounts of insulin and higher risk of infection. CONCLUSIONS:Shorter than normal leukocyte telomeres are present in critically ill children admitted to the PICU. Early initiation of PN further shortened telomeres, an effect that was independent of other determinants. Whether such telomere-shortening predisposes to long-term consequences of paediatric critical illness should be further investigated in a prospective follow-up study. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01536275 . Registered on 16 February 2012.

Project description:IntroductionTelomere biology plays a fundamental role in maintaining the integrity of the genome and cell, and shortened telomeres have been linked to several age-related diseases. The initial (newborn) telomere length (TL) represents a critically important feature of the telomere biology system. Exposure to a variety of adverse prenatal conditions such as maternal stress, suboptimal diet, obesity, and obstetric complications, is associated with shorter offspring TL at birth and in adult life. Many, if not all, of these exposures are believed to have an inflammatory component. In this context, stress-related immunological processes during pregnancy may constitute a potential additional biological pathway because they can affect telomere length and telomerase activity via transcriptions factors such as cyclic adenosine monophosphate-dependent transcription factor (ATF7) and nuclear factor-kappa B (NF-κB). Thus, in the present study we examined the hypothesis that maternal pro-inflammatory state across pregnancy, operationalized as the balance between tumor necrosis factor (TNF)-α, a major pro-inflammatory cytokine, and interleukin-10 (IL-10), the major anti-inflammatory cytokine, is associated with newborn leukocyte telomere length (LTL) at birth.Methods and materialsParticipants were healthy women (N = 112) recruited in early pregnancy. Concentrations of TNF- α and IL-10 were quantified in early, mid and late pregnancy from maternal blood samples. Telomere length was assessed in newborn blood samples soon after birth.ResultsAfter adjusting for maternal age, maternal pre-pregnancy BMI, birth weight percentile, and infant sex, a higher mean TNF-α/IL-10 ratio across pregnancy was significantly associated with shorter newborn TL (β = -.205, p = .030). Newborn TL was, on average, 10% shorter in offspring of women in the upper compared to lower quartile of the TNF-α/IL-10 ratio during pregnancy.DiscussionThese findings provide new evidence in humans for a potential "programming" mechanism linking maternal systemic pro-inflammatory processes during pregnancy with the initial (newborn) setting of her offspring's telomere system.

Project description:ObjectivesRobotic-assisted laparoscopic prostatectomy (RALP) is typically conducted in steep Trendelenburg position (STP). This study investigated the influence of permanent 45° STP and capnoperitoneum on haemodynamic parameters during and after RALP.DesignProspective observational study.SettingHaemodynamic changes were recorded with transpulmonary thermodilution and pulse contour analysis in men undergoing RALP under standardised anaesthesia.ParticipantsInformed consent was obtained from 51 patients scheduled for elective RALP in a University Medical Centre in Germany.InterventionsHeart rate, mean arterial pressure, central venous pressure (CVP), Cardiac Index (CI), systemic vascular resistance (SVR), Global End-Diastolic Volume Index (GEDI), global ejection fraction (GEF), Cardiac Power Index (CPI) and stroke volume variation (SVV) were recorded at six time points: 20 min after induction of anaesthesia (T1), after insufflation of capnoperitoneum in supine position (T2), after 30 min in STP (T3), when controlling Santorini's plexus in STP (T4), before awakening in supine position (T5) and after 45 min in the recovery room (T6). Adverse cardiac events were registered intraoperatively and postoperatively.ResultsAll haemodynamic parameters were significantly changed by capnoperitoneum and STP during RALP and partly normalised at T6. CI, GEF and CPI were highest at T6 (CI: 3.9 vs 2.2 L/min/m²; GEF: 26 vs 22%; CPI: 0.80 vs 0.39 W/m²; p<0.001). CVP was highest at T4 (31 vs 7 mm Hg, p<0.001) and GEDI at T6 (819 vs 724 mL/m², p=0.005). Mean SVR initially increased (T2) but had decreased by 24% at T6 (p<0.001). SVV was highest at T5 (12 vs 9%, p<0.001). Two of the patients developed cardiac arrhythmia during RALP and one patient suffered postoperative cardiac ischaemia.ConclusionsRALP led to pronounced perioperative haemodynamic changes. The combination of increased cardiac contractility and heart rate reflects a hyperdynamic situation during and after RALP. Anaesthesiologists should be aware of unnoticed pre-existing heart failure to worsen during STP in patients undergoing RALP.

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Telomere Length Changes during Critical Illness: A Prospective, Observational Study.

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Telomere Length Changes during Critical Illness: A Prospective, Observational Study.

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