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Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
Journal of Thoracic Disease Apr 2024Extracorporeal membrane oxygenation (ECMO) has recently emerged as a critical support system for lung function in patients awaiting lung transplantation. This...
BACKGROUND
Extracorporeal membrane oxygenation (ECMO) has recently emerged as a critical support system for lung function in patients awaiting lung transplantation. This meta-analysis investigates the prognostic factors of lung transplantation following ECMO bridging therapy.
METHODS
A comprehensive search was conducted in PubMed, Cochrane Library, Embase, CINAHL, Web of Science, Scopus, and ProQuest databases from inception to August 11, 2023. Included were cohort or case-control studies focusing on prognostic factors of lung transplantation with ECMO bridging therapy. Data extraction was performed independently, and study quality was assessed. A meta-analysis was carried out using RevMan 5.4 and Stata17.0 software to aggregate mortality rates and pertinent prognostic factors of ECMO as a bridge to lung transplantation.
RESULTS
The search identified eight trials encompassing 1,086 participants. The prognosis of patients undergoing lung transplantation with ECMO bridging was significantly associated with several factors: prolonged ECMO support [odds ratio 1.07, 95% confidence interval (CI): 1.02-1.12, I=77%], deterioration in liver and kidney function (odds ratio 3.62, 95% CI: 2.37-5.54, I=0%), and complications during ECMO (odds ratio 2.24, 95% CI: 1.45-3.44, I=5%).
CONCLUSIONS
Prolonged ECMO support, declining liver and kidney functions, and complications during ECMO are vital prognostic factors in lung transplantation following ECMO bridging therapy.
PubMed: 38738255
DOI: 10.21037/jtd-23-1709 -
International Journal of Cardiology.... Jun 2024The aim is to discuss efficacy and safety of exercise-based cardiac rehabilitation (CR) programmes in participants with implantable cardiac devices compared with usual... (Review)
Review
AIM
The aim is to discuss efficacy and safety of exercise-based cardiac rehabilitation (CR) programmes in participants with implantable cardiac devices compared with usual care.
METHODS
MEDLINE, EMBASE and Cochrane databases were searched from inspection till July 15, 2022. Randomized controlled trials were included if they enrolled adult participants with implantable cardiac devices and tested exercise-based CR interventions in comparison with any control. Risk of bias was assessed, and endpoints data were pooled using random-effects model.
RESULTS
Sixteen randomized trials enrolling 2053 participants were included. Study interventions differed between studies in terms of programme components, setting, exercise intensity, and follow-up. All studies included physical exercise component. In both implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) groups, exercise training in CR programmes improved peak oxygen uptake (VO) [(mean difference (MD) 2.08 ml/kg/min; 95 % CI: 1.44-2.728, p < 0.0001; = 99 %) and (MD 2.24 ml/kg/min; 95 % CI: 1.43-3.04, p < 0.0001; = 96 %), respectively] and 6-min walk test in ICD group (MD 41.51 m; 95 % CI: 15.19-67.82 m, p = 0.002; = 95 %) compared with usual care. In CRT group, there was no statistically significant improvement in left ventricular ejection fraction change between comparison groups. The results were consistent in subgroup analysis according to high or low-to-moderate exercise intensity for change in peak VO and ejection fraction in CRT group. There was no difference in number of ICD shocks between the comparators.
CONCLUSION
Exercise-based CR programmes appear to be safe when enrolling participants with implantable cardiac devices and leading to favourable functional outcomes.
PubMed: 38737437
DOI: 10.1016/j.ijcrp.2024.200255 -
Deuterium-Depleted Water in Cancer Therapy: A Systematic Review of Clinical and Experimental Trials.Nutrients May 2024Chemotherapy exhibits numerous side effects in anti-tumour therapy. The clinical experiments indicated that deuterium-depleted water (DDW) monotherapy or in combination... (Review)
Review
Chemotherapy exhibits numerous side effects in anti-tumour therapy. The clinical experiments indicated that deuterium-depleted water (DDW) monotherapy or in combination with chemotherapy was beneficial in inhibiting cancer development. To further understand the potential mechanism of DDW in cancer therapy, we performed a systematic review. The data from experiments published over the past 15 years were included. PubMed, Cochrane and Web of Science (January 2008 to November 2023) were systemically searched. Fifteen studies qualified for review, including fourteen in vivo and in vitro trials and one interventional trial. The results showed that DDW alone or in combination with chemotherapy effectively inhibited cancer progression in most experiments. The combination treatment enhances the therapeutic effect on cancer compared with chemotherapeutic monotherapy. The inhibitory role of DDW in tumours is through regulating the reactive oxygen species (ROS)-related genes in Kelch-like ECH-associated protein 1 (Keap 1) and Nuclear erythroid 2-related factor 2 (Nrf2) signalling pathways, further controlling ROS production. An abnormal amount of ROS can inhibit the tumour progression. More extensive randomized controlled trials should be conducted to evaluate the accurate effect of DDW in Keap1-Nrf2 signalling pathways.
Topics: Humans; Neoplasms; Deuterium; Water; Reactive Oxygen Species; Antineoplastic Agents; NF-E2-Related Factor 2; Signal Transduction; Kelch-Like ECH-Associated Protein 1; Animals; Clinical Trials as Topic
PubMed: 38732643
DOI: 10.3390/nu16091397 -
Critical Care (London, England) May 2024An increasing number of patients requires extracorporeal membrane oxygenation (ECMO) for life support. This supportive modality is associated with nosocomial infections... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An increasing number of patients requires extracorporeal membrane oxygenation (ECMO) for life support. This supportive modality is associated with nosocomial infections (NIs). This systematic review and meta-analysis aim to assess the incidence and risk factors of NIs in adult.
METHODS
We searched PubMed, Scopus, Web of Science, and ProQuest databases up to 2022. The primary endpoint was incidence of NI. Secondary endpoints included time to infection, source of infection, ECMO duration, Intensive care and hospital length of stay (LOS), ECMO survival and overall survival. Incidence of NI was reported as pooled proportions and 95% confidence intervals (CIs), while dichotomous outcomes were presented as risk ratios (RR) as the effective index and 95% CIs using a random-effects model.
RESULTS
Among the 4,733 adult patients who received ECMO support in the 30 included studies, 1,249 ECMO-related NIs per 1000 ECMO-days was observed. The pooled incidence of NIs across 18 studies involving 3424 patients was 26% (95% CI 14-38%).Ventilator-associated pneumonia (VAP) and bloodstream infections (BSI) were the most common NI sources. Infected patients had lower ECMO survival and overall survival rates compared to non-infected patients, with risk ratio values of 0.84 (95% CI 0.74-0.96, P = 0.01) and 0.80 (95% CI 0.71-0.90, P < 0.001), respectively.
CONCLUSION
Results showed that 16% and 20% lower of ECMO survival and overall survival in patients with NI than patients without NI, respectively. However, NI increased the risk of in-hospital mortality by 37% in infected patients compared with non-infected patients. In addition, this study identified the significant positive correlation between ECMO duration and ECMO-related NI.
Topics: Humans; Extracorporeal Membrane Oxygenation; Cross Infection; Incidence; Risk Factors; Adult
PubMed: 38730424
DOI: 10.1186/s13054-024-04946-8 -
BioMed Research International 2024Many COVID-19 patients display adverse symptoms, such as reduced physical ability, poor quality of life, and impaired pulmonary function. Therefore, this systematic...
INTRODUCTION
Many COVID-19 patients display adverse symptoms, such as reduced physical ability, poor quality of life, and impaired pulmonary function. Therefore, this systematic review is aimed at evaluating the effectiveness of physical exercise on various psychophysiological indicators among COVID-19 patients who may be at any stage of their illness (i.e., critically ill, hospitalized, postdischarge, and recovering).
METHODS
A systematic search was conducted in PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar from 2019 to 2021. Twenty-seven studies, which assessed a total of 1525 patients, were included and analysed.
RESULTS
Overall, data revealed significant improvements in the following parameters: physical function, dyspnoea, pulmonary function, quality of life (QOL), lower limb endurance and strength, anxiety, depression, physical activity level, muscle strength, oxygen saturation, fatigue, C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-), lymphocyte, leukocytes, and a fibrin degradation product (D-dimer).
CONCLUSIONS
Physical training turns out to be an effective therapy that minimises the severity of COVID-19 in the intervention group compared to the standard treatment. Therefore, physical training could be incorporated into conventional treatment of COVID-19 patients. More randomized controlled studies with follow-up evaluations are required to evaluate the long-term advantages of physical training. Future research is essential to establish the optimal exercise intensity level and assess the musculoskeletal fitness of recovered COVID-19 patients. This trial is registered with CRD42021283087.
Topics: Humans; Adaptation, Physiological; Anxiety; COVID-19; Exercise; Exercise Therapy; Muscle Strength; Quality of Life; SARS-CoV-2
PubMed: 38726292
DOI: 10.1155/2024/3325321 -
Frontiers in Pharmacology 2024The role of esketamine in pediatric gastrointestinal endoscopy is still unclear. This study aims to evaluate the efficacy and safety of esketamine for pediatric...
OBJECTIVE
The role of esketamine in pediatric gastrointestinal endoscopy is still unclear. This study aims to evaluate the efficacy and safety of esketamine for pediatric gastrointestinal endoscopy.
METHODS
Clinical trials of esketamine for pediatric gastrointestinal endoscopy were searched in eight common databases, up to October 2023. These clinical trials were included in the meta-analysis and trial sequential analysis (TSA). The risk ratio (RR) and weighted mean difference (WMD) were used as the effect sizes for dichotomous variables and continuity variables, respectively. When the heterogeneity test showed I < 50%, the fixed effects model was used for the meta-analysis and TSA; Otherwise, the random effects model was used for them.
RESULTS
In terms of efficacy endpoints, the meta-analysis showed that compared with placebo or blank, esketamine significantly decreased recovery time by 2.34 min (WMD -2.34; 95% Confidence interval [CI] -3.65, -1.02; = 0.0005) and propofol consumption by 0.70 mg/kg (WMD -0.70; 95% CI -0.98, -0.43; < 0.00001), and increased mean heart rate by 4.77 beats/min (WMD 4.77; 95% CI 2.67, 6.87; < 0.00001) and mean arterial pressure by 3.10 mmHg (WMD 3.10; 95% CI 1.52, 4.67; = 0.0001), while induction time and mean blood oxygen remained comparable. TSA indicated conclusive evidence for these benefits. In terms of safety endpoints, the meta-analysis revealed that esketamine significantly reduced involuntary movements by 59% (RR 0.41; 95% CI 0.22, 0.76; = 0.005) and choking by 51% (RR 0.49; 95% CI 0.26, 0.92; = 0.03), while significantly increasing dizziness by 98% (RR 1.98; 95% CI 1.11, 3.56; = 0.02) and there were no significant differences in total adverse events, respiratory depression, and vomiting. TSA demonstrated conclusive evidence for involuntary movements and dizziness. Low-dose analysis showed that esketamine at ≤0.3 mg/kg significantly reduced recovery time, propofol consumption and involuntary movements, and significantly increasing mean heart rate, with no increase in dizziness. The Begg's test ( = 0.327) and the Egger's test ( = 0.413) indicated no significant publication bias, yet the funnel plot suggested potential publication bias.
CONCLUSION
Esketamine is an effective adjuvant anesthesia for children undergoing gastrointestinal endoscopy. However, the general dose of esketamine may increase the risk of dizziness, which can be avoided by administering a low dose (≤0.3 mg/kg).
PubMed: 38725661
DOI: 10.3389/fphar.2024.1379101 -
Critical Care (London, England) May 2024Re-intubation secondary to post-extubation respiratory failure in post-operative patients is associated with increased patient morbidity and mortality. Non-invasive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Re-intubation secondary to post-extubation respiratory failure in post-operative patients is associated with increased patient morbidity and mortality. Non-invasive respiratory support (NRS) alternative to conventional oxygen therapy (COT), i.e., high-flow nasal oxygen, continuous positive airway pressure, and non-invasive ventilation (NIV), has been proposed to prevent or treat post-extubation respiratory failure. Aim of the present study is assessing the effects of NRS application, compared to COT, on the re-intubation rate (primary outcome), and time to re-intubation, incidence of nosocomial pneumonia, patient discomfort, intensive care unit (ICU) and hospital length of stay, and mortality (secondary outcomes) in adult patients extubated after surgery.
METHODS
A systematic review and network meta-analysis of randomized and non-randomized controlled trials. A search from Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from inception until February 2, 2024 was performed.
RESULTS
Thirty-three studies (11,292 patients) were included. Among all NRS modalities, only NIV reduced the re-intubation rate, compared to COT (odds ratio 0.49, 95% confidence interval 0.28; 0.87, p = 0.015, I = 60.5%, low certainty of evidence). In particular, this effect was observed in patients receiving NIV for treatment, while not for prevention, of post-extubation respiratory failure, and in patients at high, while not low, risk of post-extubation respiratory failure. NIV reduced the rate of nosocomial pneumonia, ICU length of stay, and ICU, hospital, and long-term mortality, while not worsening patient discomfort.
CONCLUSIONS
In post-operative patients receiving NRS after extubation, NIV reduced the rate of re-intubation, compared to COT, when used for treatment of post-extubation respiratory failure and in patients at high risk of post-extubation respiratory failure.
Topics: Humans; Noninvasive Ventilation; Respiratory Insufficiency; Network Meta-Analysis; Intensive Care Units; Postoperative Period; Length of Stay
PubMed: 38720332
DOI: 10.1186/s13054-024-04924-0 -
Frontiers in Neurology 2024It is essential to link the theoretical framework of any neurophysiotherapy approach with a detailed analysis of the central motor control mechanisms that influence...
INTRODUCTION
It is essential to link the theoretical framework of any neurophysiotherapy approach with a detailed analysis of the central motor control mechanisms that influence motor behavior. Vojta therapy (VT) falls within interventions aiming to modify neuronal activity. Although it is often mistakenly perceived as exclusively pediatric, its utility spans various functional disorders by acting on central pattern modulation. This study aims to review the existing evidence on the effectiveness of VT across a wide range of conditions, both in the adult population and in pediatrics, and analyze common therapeutic mechanisms, focusing on motor control modulation.
AIM
The goals of this systematic review are to delineate the existing body of evidence concerning the efficacy of Vojta therapy (VT) in treating a broad range of conditions, as well as understand the common therapeutic mechanisms underlying VT with a specific focus on the neuromodulation of motor control parameters.
METHODS
PubMed, Cochrane Library, SCOPUS, Web of Science, and Embase databases were searched for eligible studies. The methodological quality of the studies was assessed using the PEDro list and the Risk-Of-Bias Tool to assess the risk of bias in randomized trials. Methodological quality was evaluated using the Risk-Of-Bias Tool for randomized trials. Random-effects meta-analyses with 95% CI were used to quantify the change scores between the VT and control groups. The certainty of our findings (the closeness of the estimated effect to the true effect) was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).
RESULTS
Fifty-five studies were included in the qualitative analysis and 18 in the meta-analysis. Significant differences in cortical activity ( = 0.0001) and muscle activity ( = 0.001) were observed in adults undergoing VT compared to the control, as well as in balance in those living with multiple sclerosis ( < 0.03). Non-significant differences were found in the meta-analysis when evaluating gross motor function, oxygen saturation, respiratory rate, height, and head circumference in pediatrics.
CONCLUSION
Although current evidence supporting VT is limited in quality, there are indications suggesting its potential usefulness for the treatment of respiratory, neurological, and orthopedic pathology. This systematic review and meta-analysis show the robustness of the neurophysiological mechanisms of VT, and that it could be an effective tool for the treatment of balance in adult neurological pathology. Neuromodulation of motor control areas has been confirmed by research focusing on the neurophysiological mechanisms underlying the therapeutic efficacy of VT.https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=476848, CRD42023476848.
PubMed: 38711552
DOI: 10.3389/fneur.2024.1391448 -
Cardiovascular Revascularization... Apr 2024Use of Intra-Aortic Balloon Pump (IABP) in combination with Impella has been described as an alternative strategy for mechanical circulatory support (MCS) in patients... (Review)
Review
BACKGROUND
Use of Intra-Aortic Balloon Pump (IABP) in combination with Impella has been described as an alternative strategy for mechanical circulatory support (MCS) in patients with cardiogenic shock (CS). We provide a systematic review aimed to explore the effectiveness of this paired MCS approach.
METHODS
We conducted a comprehensive systematic search in MEDLINE, Scopus, and Cochrane databases to identify all studies that investigated dual MCS with IABP and Impella.
RESULTS
Our search strategy identified 12 articles, including 1 randomized controlled trial, 1 retrospective study, 1 case series, 7 case report and 2 animal studies. Rationale for this combined MCS strategy stems from an observed reduction in myocardial oxygen demand/supply ratio compared to the use of each device alone, without determining significant variations in left ventricular work. Nonetheless, this combined approach also leads to a 30-40 % decline in Impella flow, increasing the risk of bleeding, Impella displacement, as well as triggering positioning and pressure alarms. Additionally, hemolytic risk data yielded inconclusive results. Importantly, there were no notable disparities in mortality rates when comparing the combined strategy to the use of each device individually.
CONCLUSION
At the current state-of-the-art, there are no conclusive data demonstrating net clinical benefits of combining Impella with IABP. Considering the substantial risks of morbidity associated, we recommend against its use in clinical practice.
PubMed: 38697884
DOI: 10.1016/j.carrev.2024.04.296