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Critical Care (London, England) Jul 2023Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent... (Review)
Review
Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent literature are presented. Low-dose enteral nutrition (EN) or parenteral nutrition (PN) can be started within 48 h of admission. While EN is preferred route of delivery, new data highlight PN can be given safely without increased risk; thus, when early EN is not feasible, provision of isocaloric PN is effective and results in similar outcomes. Indirect calorimetry (IC) measurement of energy expenditure (EE) is recommended by both European/American guidelines after stabilization post-ICU admission. Below-measured EE (~ 70%) targets should be used during early phase and increased to match EE later in stay. Low-dose protein delivery can be used early (~ D1-2) (< 0.8 g/kg/d) and progressed to ≥ 1.2 g/kg/d as patients stabilize, with consideration of avoiding higher protein in unstable patients and in acute kidney injury not on CRRT. Intermittent-feeding schedules hold promise for further research. Clinicians must be aware of delivered energy/protein and what percentage of targets delivered nutrition represents. Computerized nutrition monitoring systems/platforms have become widely available. In patients at risk of micronutrient/vitamin losses (i.e., CRRT), evaluation of micronutrient levels should be considered post-ICU days 5-7 with repletion of deficiencies where indicated. In future, we hope use of muscle monitors such as ultrasound, CT scan, and/or BIA will be utilized to assess nutrition risk and monitor response to nutrition. Use of specialized anabolic nutrients such as HMB, creatine, and leucine to improve strength/muscle mass is promising in other populations and deserves future study. In post-ICU setting, continued use of IC measurement and other muscle measures should be considered to guide nutrition. Research on using rehabilitation interventions such as cardiopulmonary exercise testing (CPET) to guide post-ICU exercise/rehabilitation prescription and using anabolic agents such as testosterone/oxandrolone to promote post-ICU recovery is needed.
Topics: Humans; Intensive Care Units; Nutritional Support; Critical Care; Nutritional Status; Enteral Nutrition; Critical Illness
PubMed: 37403125
DOI: 10.1186/s13054-023-04539-x -
Frontiers in Endocrinology 2023To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH)....
OBJECTIVE
To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities.
METHODS
National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3-16 years at GH start during year 1987-1998, with AH in 2003-2011. Of the 144 prepubertal girls with TS, 132 girls were followed to AH (intention to treat), while 43 girls reduced dose or stopped treatment prematurely, making n=89 for Per Protocol population. Age at GH start was 3-9 years (young; n=79) or 9-16 years (old; n=53). Treatment given were recombinant human (rh)GH (Genotropin Kabi Peptide Hormones, Sweden) 33 or 67 µg/kg/day, oral ethinyl-estradiol (2/3) or transdermal 17β-estradiol (1/3), and, after age 11 years, mostly oxandrolone. Gain in height, AH, and age at PO and at AH were evaluated.
RESULTS
At GH start, height was -2.8 (versus non-TS girls) for all subgroups and mean age for young was 5.7 years and that of old was 11.6 years. There was a clear dose-response in both young and old TS girls; the mean difference was (95%CI) 0.66 (-0.91 to -0.26) and 0.57 (-1.0 to -0.13), respectively. The prepubertal gain (1.3-2.1) was partly lost during puberty (-0.4 to -2.1). Age/height at PO ranged from 13 years/-0.42 for GH to 15.2 years/-1.47 for GH. At AH, GH group became tallest (17.2 years; 159.9 cm; -1.27 SDS; total gain, 1.55) compared to GH group being least delayed (16.1 years; 157.1 cm; -1.73 SDS; total, 1.08). The shortest was the GH group (17.3 years; 153.7 cm: -2.28 SDS; total gain, 0.53), and the most delayed was the GH group, (18.5 years; 156.5 cm; -1.82 SDS; total gain, 0.98).
CONCLUSION
For both young and old TS girls, there was a GH-dose growth response, and for the young, there was less delayed age at PO and at AH. All four groups reached an AH within normal range, despite partly losing the prepubertal gain during puberty. Depending on age at diagnosis, low age at start with higher GH dose resulted in greater prepubertal height gain, permitting estrogen to start earlier at normal age and attaining normal AH at normal age, favoring physiological treatment and possibly also bone health, hearing, uterine growth and fertility, psychosocial wellbeing during adolescence, and the transition to adulthood.
Topics: Female; Adolescent; Humans; Adult; Child, Preschool; Child; Human Growth Hormone; Growth Hormone; Turner Syndrome; Sweden; Body Height; Puberty; Estradiol
PubMed: 37529614
DOI: 10.3389/fendo.2023.1197897 -
British Journal of Anaesthesia Mar 2024Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) is a clinical endotype of chronic critical illness. PICS consists of a self-perpetuating cycle... (Review)
Review
Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) is a clinical endotype of chronic critical illness. PICS consists of a self-perpetuating cycle of ongoing organ dysfunction, inflammation, and catabolism resulting in sarcopenia, immunosuppression leading to recurrent infections, metabolic derangements, and changes in bone marrow function. There is heterogeneity regarding the definition of PICS. Currently, there are no licensed treatments specifically for PICS. However, findings can be extrapolated from studies in other conditions with similar features to repurpose drugs, and in animal models. Drugs that can restore immune homeostasis by stimulating lymphocyte production could have potential efficacy. Another treatment could be modifying myeloid-derived suppressor cell (MDSC) activation after day 14 when they are immunosuppressive. Drugs such as interleukin (IL)-1 and IL-6 receptor antagonists might reduce persistent inflammation, although they need to be given at specific time points to avoid adverse effects. Antioxidants could treat the oxidative stress caused by mitochondrial dysfunction in PICS. Possible anti-catabolic agents include testosterone, oxandrolone, IGF-1 (insulin-like growth factor-1), bortezomib, and MURF1 (muscle RING-finger protein-1) inhibitors. Nutritional support strategies that could slow PICS progression include ketogenic feeding and probiotics. The field would benefit from a consensus definition of PICS using biologically based cut-off values. Future research should focus on expanding knowledge on underlying pathophysiological mechanisms of PICS to identify and validate other potential endotypes of chronic critical illness and subsequent treatable traits. There is unlikely to be a universal treatment for PICS, and a multimodal, timely, and personalised therapeutic strategy will be needed to improve outcomes for this growing cohort of patients.
Topics: Animals; Humans; Critical Illness; Syndrome; Immunosuppression Therapy; Inflammation; Chronic Disease; Research
PubMed: 38177003
DOI: 10.1016/j.bja.2023.11.052 -
Burns & Trauma 2024Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on...
BACKGROUND
Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX.
METHODS
The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions.
RESULTS
More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, = 0.01).
CONCLUSIONS
The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.
PubMed: 38650969
DOI: 10.1093/burnst/tkad063 -
Human Molecular Genetics Feb 2024Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three...
A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models.
Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three SMN-augmentation therapies are clinically approved that significantly slow down disease progression, they are unfortunately not cures. Thus, complementary SMN-independent therapies that can target key SMA pathologies and that can support the clinically approved SMN-dependent drugs are the forefront of therapeutic development. We have previously demonstrated that prednisolone, a synthetic glucocorticoid (GC) improved muscle health and survival in severe Smn-/-;SMN2 and intermediate Smn2B/- SMA mice. However, long-term administration of prednisolone can promote myopathy. We thus wanted to identify genes and pathways targeted by prednisolone in skeletal muscle to discover clinically approved drugs that are predicted to emulate prednisolone's activities. Using an RNA-sequencing, bioinformatics, and drug repositioning pipeline on skeletal muscle from symptomatic prednisolone-treated and untreated Smn-/-; SMN2 SMA and Smn+/-; SMN2 healthy mice, we identified molecular targets linked to prednisolone's ameliorative effects and a list of 580 drug candidates with similar predicted activities. Two of these candidates, metformin and oxandrolone, were further investigated in SMA cellular and animal models, which highlighted that these compounds do not have the same ameliorative effects on SMA phenotypes as prednisolone; however, a number of other important drug targets remain. Overall, our work further supports the usefulness of prednisolone's potential as a second-generation therapy for SMA, identifies a list of potential SMA drug treatments and highlights improvements for future transcriptomic-based drug repositioning studies in SMA.
Topics: Mice; Animals; Pharmaceutical Preparations; Drug Repositioning; Muscular Atrophy, Spinal; Muscle, Skeletal; Gene Expression Profiling; Prednisolone; Disease Models, Animal; Survival of Motor Neuron 1 Protein
PubMed: 37947217
DOI: 10.1093/hmg/ddad192 -
Frontiers in Pharmacology 2023The Internet has become an important source for easy access to doping substances, where people and athletes may acquire, outside pharmacies and without a (medical)...
The Internet has become an important source for easy access to doping substances, where people and athletes may acquire, outside pharmacies and without a (medical) prescription. These online websites do not always offer quality-assured products, and are outside the regular distribution channels of medicines. The aim of this study was to estimate the availability and accessible information on the Internet about the sale of three doping substances (oxandrolone, DHEA, androstenedione). Cross-sectional exploratory study, being an observation at a point in time of the online availability of these three doping substances (WADA S1 category: anabolic agents), purchased from Spain, Puerto Rico, Canada, United States, Ukraine and Russia. The characteristics of the websites, the countries the webs sold to, the pharmaceutical forms offered and the recommendations for its use were analyzed by using a computer tool designed . There were significant differences between countries in the number of webpages that sold the products (Chi-square test, < 0.05). Oxandrolone was available for purchase mainly when buying from Spain (27.12%) and Ukraine (26.58%), in websites dedicated to sports (77.26%). For DHEA, most of the pages offered it if the search was done from Canada (23.34%) and Russia (21.44%). Products containing androstenedione or DHEA are claimed to enhance sports performance or for sports use without providing details. Compared to the total number of websites checked, the proportion of pharmacies offering these products was low, ranging from 4.86% for DHEA to 15.79% for androstenedione. The three substances selected are easily available without control through the Internet. Only a small number of websites offering them were online pharmacies, and requested a prescription. Most of the doping substances are purchased from the country where they are requested. Product information described benefits for sports performance, but did not do the same with their side effects. It would be advisable for these products to be sold through pharmacies, to guarantee their quality and provide evidence-based information on their safe use, benefits and risks, and only with a prescription. Athletes should be encouraged to consult health professionals about those supplements suitable for their type of training and sports objectives.
PubMed: 38111382
DOI: 10.3389/fphar.2023.1305080 -
Cureus Mar 2024Introduction Severe thermal burns are a catastrophic injury. Those surviving the initial insult are subject to life-long disability, prolonged hospital admission,...
Introduction Severe thermal burns are a catastrophic injury. Those surviving the initial insult are subject to life-long disability, prolonged hospital admission, nutritional issues and poor wound healing. Oxandrolone has been shown to reduce hospital duration and promote lean body mass. Despite not being licenced for use in burns trauma within the United Kingdom (UK), services across the country utilise Oxandrolone in the management of severe burns. We aim to analyse the use of Oxandrolone in major burns across burns services within the UK. Methods We conducted a survey across all burn centres and units across the UK. Any burns service provider with experience in patient management of patients sustaining burns with a total body surface area >15% was included. All services were identified using the British Burns Association website. We conducted a survey of all centres and units and contacted them via telephone through the trust's switchboard. Responses were accepted from any healthcare staff familiar with the day-to-day in-patient care of patients on the ward. Services with no in-patient services were excluded. Results A total of 24 burns centres and services responded to our survey. Twelve of the respondents were in a burns unit and 12 were in a burns centre. Eight respondents were paediatric facilities, and the remaining 16 dealt with adult burns. In total, 16/24 (66.6%) services reported using Oxandrolone. Conversely, 8/24 (33.3%) burns services denied using Oxandrolone. 7/12 (58.3%) burns units use Oxandrolone in the management of burns. 5/12 (42.7%) burns units do not use Oxandrolone in severe burns. 9/12 (75%) of burns centres described using Oxandrolone, whilst the remaining 3/12 (25%) did not. Discussion Oxandrolone is used varyingly across burns services across the UK. Burns centres were more likely to use Oxandrolone compared to units. We also find that more paediatric services used Oxandrolone in comparison to adult services. Studies have shown that the benefit of Oxandrolone is not age-dependent. Further work is required to assess the impact of this medication on patients with severe burns and national guidance would help further improve burns management across the UK.
PubMed: 38681282
DOI: 10.7759/cureus.57167 -
Forensic Science International Mar 2024The administration of new psychoactive substances (NPS), in particular synthetic cannabinoid receptor agonists (SCRAs), via e-cigarettes, within prison settings has been...
The administration of new psychoactive substances (NPS), in particular synthetic cannabinoid receptor agonists (SCRAs), via e-cigarettes, within prison settings has been well publicized. This study provides an overview of five e-cigarette case samples seized from Scottish prisons between May 2022 and July 2023 where the anabolic-androgenic steroids (AASs) mestanolone and oxandrolone were identified following gas chromatography-mass spectrometry (GC-MS) analysis. These e-cigarette samples represented 2.9% of all samples containing e-cigarette cartridges (n = 170) and 9.4% of all samples found to contain AASs (n = 53) seized during the same time period. The AASs were detected in combination with other drugs, including cocaine, Δ-tetrahydrocannabinol (Δ-THC), SCRAs and nicotine. This represents a new and novel route of administration for AASs.
Topics: Electronic Nicotine Delivery Systems; Anabolic Androgenic Steroids; Prisons; Gas Chromatography-Mass Spectrometry; Cannabinoid Receptor Agonists
PubMed: 38359752
DOI: 10.1016/j.forsciint.2024.111965