Factors promoting and hindering resilience in youth with inflammatory bowel disease: A descriptive qualitative study.

AIM: To explore factors promoting and hindering resilience in youth with inflammatory bowel disease (IBD) based on Kumpfer's resilience framework. DESIGN: A descriptive qualitative study design with an interpretative approach was used. METHODS: Participants consisted of 10 youths with IBD from a tertiary hospital in Beijing (China) recruited using the purposive sampling method. Data were collected by semi-structured interviews from December 2020 to March 2021. The directed content analysis was performed for data analysis. RESULTS: Both promoting factors and hindering factors could be divided into personal factors and environmental factors. Thirteen themes were identified. The promoting factors included acceptance of illness, strict self-management, previous treatment experience, life goals, family support, medical support and peer encouragement. Stigma, lack of communication, negative cognition, societal incomprehension, economic pressure and academic and employment pressure were hindering factors. CONCLUSION: Health care professionals need to develop greater awareness of factors, stemming from both the individual and the outside world, that hinder or promote resilience in order to aid young patients with IBD. Building targeted nursing measures to excavate the internal positive quality of patients, provide external support and promote the development of resilience.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Extracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways.

Colonization of the vaginal space with bacteria such as Gardnerella vaginalis and Mobiluncus mulieris is associated with increased risk for STIs, bacterial vaginosis, and preterm birth, while Lactobacillus crispatus is associated with optimal reproductive health. Although host-microbe interactions are hypothesized to contribute to reproductive health and disease, the bacterial mediators that are critical to this response remain unclear. Bacterial extracellular vesicles (bEVs) are proposed to participate in host-microbe communication by providing protection of bacterial cargo, delivery to intracellular targets, and ultimately induction of immune responses from the host. We evaluated the proteome of bEVs produced in vitro from G. vaginalis, M. mulieris, and L. crispatus, identifying specific proteins of immunologic interest. We found that bEVs from each bacterial species internalize within cervical and vaginal epithelial cells, and that epithelial and immune cells express a multi-cytokine response when exposed to bEVs from G. vaginalis and M. mulieris but not L. crispatus. Further, we demonstrate that the inflammatory response induced by G. vaginalis and M. mulieris bEVs is TLR2-specific. Our results provide evidence that vaginal bacteria communicate with host cells through secreted bEVs, revealing a mechanism by which bacteria lead to adverse reproductive outcomes associated with inflammation. Elucidating host-microbe interactions in the cervicovaginal space will provide further insight into the mechanisms contributing to microbiome-mediated adverse outcomes and may reveal new therapeutic targets.

Home-based exercise in dialysis patients with end-stage renal disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Lack of exercise may reduce the quality of life, physical capability, and functional capability of dialysis patients. Home-based exercise seems to be a desirable form of low-cost intervention. But the effectiveness of this intervention in the dialysis population is still unclear. The purpose of this meta-analysis is to provide effective evidence to determine the impact of home-based exercise on functional capacity, physical capacity, muscular strength, biochemical parameters, and health-related quality of life among dialysis patients with end-stage renal disease (ESRD). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to May 2023, to identify potential randomized controlled trials (RCTs) assessing the effectiveness of home-based exercise in dialysis patients with ESRD. Two independent reviewers selected studies, extracted data, and assessed the risk of bias using the Cochrane tool. Evidence summary using fixed or random effects for meta-analysis. RESULTS: Twelve RCTs including 1008 dialysis patients met the inclusion criteria. The meta-analysis showed significant effects of home-based exercise on physical capacity. Seven studies reported the results of the 6-min walking test, compared with short-term (0-3 months) home-based exercise (P = 0.76), long-term (3-6 months) interventions (P < 0.001) can significantly improve the results of the 6-min walking test. The results showed that home-based exercise did significantly improve patients' VO2 peak (P = 0.007). Compared with center-based exercise or usual care, home exercise did not significantly improve handgrip strength, quality of life or CRP and other biochemical parameters (P > 0.05). CONCLUSION: The results showed that long-term home-based exercise can improve walking ability. In addition, home-based exercise had the benefit on the VO2 peak of ESRD patients receiving dialysis patients. However, there was no statistically significant difference in handgrip strength, health-related quality of life, CRP, and other biochemical parameters.

Analysis of hemorrhage upon ultrasound-guided percutaneous renal biopsy in China: a retrospective study.

PURPOSE: Ultrasound-guided percutaneous renal biopsy (PRB) has been considered as a golden standard for CKD diagnosis and is employed to identify potential therapeutic targets since 1950s. Post-biopsy hemorrhage is the most common complication, while severe bleeding complication might cause nephrectomy or death. Therefore, how to reduce the occurrence of complications while ensuring the success of PRB is always a clinical research topic. METHODS: This study retrospectively collected and established a renal biopsy database of each patient who underwent ultrasound-guided PRB at a tertiary teaching hospital from September 2017 to December 2020 through the Health Information System. All the data were statistically processed by SPSS software. RESULTS: A total of 1146 patients underwent PRB for various reasons. The overall rate of post-biopsy hemorrhage was 37.70% (432/1146). Of those bleedings, minor bleeding after PRB was found in 337 (29.41%), middle bleeding 84 (7.33%), major bleeding 11 (0.96%). Besides that, there were 96 patients (8.38%) reported their discomfort symptoms. There was no death. Females were at significantly increased risk of hemorrhagic complication than males (OR = 2.017, CI = 1.531-2.658). While the risk for hemorrhagic complication significantly decreased as BMI and platelet before renal biopsy increased (OR = 0.956, CI = 0.924-0.989; OR = 0.998, CI = 0.996-1.000). As the APTT time prolonged, the risk for hemorrhagic complication significantly increased (OR = 1.072, CI = 1.023-1.123). Those patients whose albumin were higher, also had higher risk for hemorrhagic complication than other patients (OR = 1.020, CI = 1.000-1.041). Specifically, postoperative urination within 4 h increased the risk for hemorrhagic complication (OR = 1.741, CI = 1.176-2.576). CONCLUSION: Our analysis finds that the incidence of post-biopsy bleeding complication is 37.70%, and its risk is associated with female, lower BMI, lower platelet before renal biopsy, prolonged APTT, higher albumin, and postoperative urination within 4 h. The findings highlighted the importance of perioperative management for renal biopsy, including adequate risk assessment, tailored careful observation after PRB. And medical staff should pay more attention to fluid management after ultrasound-guided PRB.

Urgent-start peritoneal dialysis in the hemophilia a patient with chronic kidney disease: A case report.

Key Clinical Message: This case illustrates that under comprehensive management of individual and clinical needs, urgent-start peritoneal dialysis can be performed safely without bleeding complications in patients with hemophilia A who developed end-stage renal disease. Patients in these cases can benefit from synthetic strategy. Abstract: Hemophilia A is a serious inherited bleeding disorder resulting from a deficiency of coagulation factor VIII (FVIII). Chronic kidney disease (CKD) involvement in hemophilia is relatively rare, but there has been an upward trend in the survival time of patients with prolonged hemophilia. Although peritoneal dialysis (PD) is often used as the first treatment modality for renal replacement treatment, limited data are available on comprehensive management in the hemophilia A population, especially for urgent-start PD. A 56-year-old man who had hemophilia A, was diagnosed with CKD 3 years ago and developed end-stage renal disease was admitted to our hospital after contracting pneumonia and undergoing subsequent Type I respiratory failure. Urgent-start PD improved his condition and health outcomes, and protected his residual renal function. This case is the first study of a Chinese male patient with hemophilia A who developed end-stage renal disease. We summarize the clinical treatment and nursing care strategies of urgent-start PD in a hemophilia A patient with end-stage renal disease. This case illustrates that under comprehensive management of individual and clinical needs, urgent-start PD can be performed safely without bleeding complications in patients with hemophilia A.

Intrauterine colonization with Gardnerella vaginalis and Mobiluncus mulieris induces maternal inflammation but not preterm birth in a mouse model.

PROBLEM: Preterm birth (PTB) remains a leading cause of childhood mortality. Recent studies demonstrate that the risk of spontaneous PTB (sPTB) is increased in individuals with Lactobacillus-deficient vaginal microbial communities. One proposed mechanism is that vaginal microbes ascend through the cervix, colonize the uterus, and activate inflammatory pathways leading to sPTB. This study assessed whether intrauterine colonization with either Gardnerella vaginalis and Mobiluncus mulieris alone is sufficient to induce maternal-fetal inflammation and induce sPTB. METHOD OF STUDY: C56/B6J mice, on embryonic day 15, received intrauterine inoculation of saline or 108 colony-forming units of G. vaginalis (n = 30), M. mulieris (n = 17), or Lactobacillus crispatus (n = 16). Dams were either monitored for maternal morbidity and sPTB or sacrificed 6 h post-infusion for analysis of bacterial growth and cytokine/chemokine expression in maternal and fetal tissues. RESULTS: Six hours following intrauterine inoculation with G. vaginalis, M. mulieris, or L. crispatus, live bacteria were observed in both blood and amniotic fluid, and a potent immune response was identified in the uterus and maternal serum. In contrast, only a limited immune response was identified in the amniotic fluid and the fetus after intrauterine inoculation. High bacterial load (108 CFU/animal) of G. vaginalis was associated with maternal morbidity and mortality but not sPTB. Intrauterine infusion with L. crispatus or M. mulieris at 108 CFU/animal did not induce sPTB, alter pup viability, litter size, or maternal mortality. CONCLUSIONS: Despite inducing an immune response, intrauterine infusion of live G. vaginalis or M. mulieris is not sufficient to induce sPTB in our mouse model. These results suggest that ascension of common vaginal microbes into the uterine cavity alone is not causative for sPTB.

Intelligent Electrocardiogram Analysis in Medicine: Data, Methods, and Applications.

Electrocardiogram (ECG) is a low-cost, simple, fast, and non-invasive test. It can reflect the heart's electrical activity and provide valuable diagnostic clues about the health of the entire body. Therefore, ECG has been widely used in various biomedical applications such as arrhythmia detection, disease-specific detection, mortality prediction, and biometric recognition. In recent years, ECG-related studies have been carried out using a variety of publicly available datasets, with many differences in the datasets used, data preprocessing methods, targeted challenges, and modeling and analysis techniques. Here we systematically summarize and analyze the ECG-based automatic analysis methods and applications. Specifically, we first reviewed 22 commonly used ECG public datasets and provided an overview of data preprocessing processes. Then we described some of the most widely used applications of ECG signals and analyzed the advanced methods involved in these applications. Finally, we elucidated some of the challenges in ECG analysis and provided suggestions for further research.

The impact of blood pressure on the risk of postbiopsy bleeding during the whole procedure of percutaneous kidney biopsy.

PURPOSE: To investigate whether BP is related to postbiopsy bleeding in patients undergoing native percutaneous kidney biopsy (PKB) and to evaluate the dynamic changes in blood pressure (BP) pre- and post-kidney biopsy. METHODS: A retrospective cross-sectional study was conducted. The whole-procedural systolic (SBP) and diastolic (DBP) BP for patients undergoing ultrasound-guided native PKB from October 2017 to December 2020 were recorded in the study. Propensity score matching was used to minimize selection bias. SBP and DBP were analyzed as the main risk factors for bleeding complications. Receiver operating characteristic (ROC) curves were employed to explore the optimal BP thresholds to differentiate between bleeding and nonbleeding. The rates of major bleeding complications were analyzed according to BP thresholds through logistic analysis. RESULTS: Of 1146 biopsies, 432 (37.7%) patients suffered from postbiopsy bleeding, 88 (7.7%) patients had major bleeding complications, and 344 (30.0%) patients had minor bleeding complications. In the original data, for patients with SBP ≥ 160 mmHg before PKB, the rate of major bleeding complications was 17.6% (7.5% for SBP < 160 mmHg), and the rate of major bleeding complications was 19.0% in patients with DBP ≥ 100 mmHg (7.5% for DBP < 100 mmHg). For patients with DBP ≥ 85 mmHg to 100 mmHg after PKB, the rate of major bleeding complications ranged from 9.5 to 17.5%. The rate of major bleeding complications was lower (6.6-7.3%) in patients with DBP < 100 mmHg to 85 mmHg. CONCLUSION: Patients who have high-level BP during the native PKB perioperative period are at higher risk for postbiopsy bleeding. High-level BP here does not refer to traditional hypertension according to the guidelines for the diagnosis and treatment of hypertension, but rather BP above a certain threshold related to bleeding risk.

The Prevalence and Factors That Impact Frailty in Inflammatory Bowel Disease Patients Hospitalized in a Tertiary Hospital in China.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) is rapidly increasing in China. Beyond disease management, frailty is an important predictor of adverse outcomes in IBD patients, which has not been well investigated. This study aimed to assess frailty status and explore the impact factors in IBD inpatients. METHODS: A total of 372 IBD inpatients were recruited from July 2021 to November 2021 at Peking Union Medical College Hospital. All the participants were surveyed by face-to-face questionnaires, including demographic characteristics, disease conditions, lifestyle, psychology, social support, and frailty. The impact factors of frailty were further assessed by multinomial logistic regression analysis. RESULTS: The participants' median age was 31.00 (Q1: 24.00, Q3: 40.00) years. The overall prevalence of prefrailty and frailty in IBD patients was 59.4% (n = 221) and 14% (n = 52), respectively, and was higher for frailty in females (17.2%) than in males (12.3%). Increased body mass index (odds ratio (OR) 0.917; 95% confidence interval (CI) 0.860-0.978), increased erythrocyte sedimentation rate (OR 1.039; 95% CI: 1.002-1.077), sleep impairment (OR 5.160; 95% CI: 2.394-11.119), and depression (OR 9.480; 95% CI: 3.602-24.949) were independently significantly correlated with prefrailty (p < 0.05). Increased body mass index (OR 0.744; 95% CI: 0.654-0.848), increased erythrocyte sedimentation rate (OR 1.052; 95% CI: 1.011-1.096), sleep impairment (OR 5.832; 95% CI: 2.092-16.260), and depression (OR 10.041; 95% CI: 2.740-36.793) were independently significantly correlated with frailty. Among the factors, whether for frailty or prefrailty, the strongest impact factor was depression. CONCLUSIONS: IBD inpatients are prone to frailty. Comprehensive management focused on the prevention of frailty is warranted to improve the overall prognosis.

HA-ResNet: Residual Neural Network With Hidden Attention for ECG Arrhythmia Detection Using Two-Dimensional Signal.

Arrhythmia is an abnormal heart rhythm, a common clinical problem in cardiology. Long-term or severe arrhythmia may lead to stroke and sudden cardiac death. The electrocardiogram (ECG) is the most commonly used tool to diagnose arrhythmia. However, the traditional diagnosis relies on experts for manual interpretation, which is time-consuming and laborious. In recent years, many automatic arrhythmia detection methods have emerged due to advancements in deep learning. These methods can reduce manual intervention and improve diagnostic efficiency. However, extracting useful features from raw ECG signals for arrhythmia detection is still challenging due to the low frequency of ECG signals and noise distribution. In this paper, we propose a novel hidden attention residual network (HA-ResNet) for automated arrhythmia classification. In this model, the one-dimensional ECG signals are first converted into two-dimensional images and fed into an embedding layer to obtain the relevant shallow features in ECG. Then, a hidden attention layer combining Squeeze-and-Excitation (SE) block and Bidirectional Convolutional LSTM (BConvLSTM) is used to further capture the deep Spatio-temporal features. We evaluate our HA-ResNet on two public datasets and achieve F1 scores of 96.0%, 96.7%, and 87.6% on 2 s segments, 5 s segments, and 10 s segments, respectively, which significantly outperform the existing state-of-the-art approaches. The experimental results demonstrate the effectiveness and generalization of our method.

Effects of aromatherapy on fatigue, quality of sleep and quality of life in patients with inflammatory bowel disease: A feasibility study.

BACKGROUND: Fatigue, poor sleep quality and poor quality of life (QoL) are recognised as common problems for patients with inflammatory bowel disease (IBD). This study aimed to evaluate feasibility and effect of aromatherapy on these problems in patients with IBD. METHODS: Seventy IBD patients from a tertiary hospital in China were randomly assigned to an intervention group and a control group. During the 8-week intervention, the intervention group received aromatherapy through the skin and by inhalation, and the control group received routine nursing care. All patients were administered questionnaires at two sessions-the Multidimensional Fatigue Inventory, the Inflammatory Bowel Disease Questionnaire and the Pittsburgh Sleep Quality Index-before and after the intervention. The clinical trial registration number is ChiCTR2100045889. RESULTS: Postintervention fatigue and sleep problems were relieved in the intervention group compared with the control group (P < 0.05). Moreover, QoL scores improved significantly in the intervention group (P < 0.05). CONCLUSION: These results suggested that aromatherapy may be an effective complementary treatment method to relieve fatigue and sleep problems and improve quality of life in IBD patients.

MCA-net: A multi-task channel attention network for Myocardial infarction detection and location using 12-lead ECGs.

PROBLEM: Myocardial infarction (MI) is a classic cardiovascular disease (CVD) that requires prompt diagnosis. However, due to the complexity of its pathology, it is difficult for cardiologists to make an accurate diagnosis in a short period. AIM: In the clinical, MI can be detected and located by the morphological changes on a 12-lead electrocardiogram (ECG). Therefore, we need to develop an automatic, high-performance, and easily scalable algorithm for MI detection and location using 12-lead ECGs to effectively reduce the burden on cardiologists. METHODS: This paper proposes a multi-task channel attention network (MCA-net) for MI detection and location using 12-lead ECGs. It employs a channel attention network based on a residual structure to efficiently capture and integrate features from different leads. On top of this, a multi-task framework is used to additionally introduce the shared and complementary information between MI detection and location tasks to further enhance the model performance. RESULTS: Our method is evaluated on two datasets (The PTB and PTBXL datasets). It achieved more than 90% accuracy for MI detection task on both datasets. For MI location tasks, we achieved 68.90% and 49.18% accuracy on the PTB dataset, respectively. And on the PTBXL dataset, we achieved more than 80% accuracy. CONCLUSION: Numerous comparison experiments demonstrate that MCA-net outperforms the state-of-the-art methods and has a better generalization. Therefore, it can effectively assist cardiologists to detect and locate MI and has important implications for the early diagnosis of MI and patient prognosis.

A coregulator shift, rather than the canonical switch, underlies thyroid hormone action in the liver.

Thyroid hormones (THs) are powerful regulators of metabolism with major effects on body weight, cholesterol, and liver fat that have been exploited pharmacologically for many years. Activation of gene expression by TH action is canonically ascribed to a hormone-dependent "switch" from corepressor to activator binding to thyroid hormone receptors (TRs), while the mechanism of TH-dependent repression is controversial. To address this, we generated a mouse line in which endogenous TRß1 was epitope-tagged to allow precise chromatin immunoprecipitation at the low physiological levels of TR and defined high-confidence binding sites where TRs functioned at enhancers regulated in the same direction as the nearest gene in a TRß-dependent manner. Remarkably, although positive and negative regulation by THs have been ascribed to different mechanisms, TR binding was highly enriched at canonical DR4 motifs irrespective of the transcriptional direction of the enhancer. The canonical NCoR1/HDAC3 corepressor complex was reduced but not completely dismissed by TH and, surprisingly, similar effects were seen at enhancers associated with negatively as well as positively regulated genes. Conversely, coactivator CBP was found at all TH-regulated enhancers, with transcriptional activity correlating with the ratio of CBP to NCoR rather than their presence or absence. These results demonstrate that, in contrast to the canonical "all or none" coregulator switch model, THs regulate gene expression by orchestrating a shift in the relative binding of corepressors and coactivators.

Rapamycin maintains NAD+/NADH redox homeostasis in muscle cells.

Rapamycin delays multiple age-related conditions and extends lifespan in organisms ranging from yeast to mice. However, the mechanisms by which rapamycin influences longevity are incompletely understood. The objective of this study was to investigate the effect of rapamycin on NAD+/NADH redox balance. We report that the NAD+/NADH ratio of C2C12 myoblasts or differentiated myotubes significantly decreases over time in culture, and that rapamycin prevents this effect. Despite lowering the NADH available to support ATP generation, rapamycin increases ATP availability, consistent with lowering energetic demand. Although rapamycin did not change the NAD+/NADH ratio or steady-state ATP concentration in the livers, kidneys, or muscles of young mice, optical redox imaging revealed that rapamycin caused a substantial decline in the NADH content and an increase in the optical redox ratio (a surrogate of NAD+/NADH redox ratio) in muscles from aged mice. Collectively, these data suggest that rapamycin favors a more oxidized NAD+/NADH ratio in aged muscle, which may influence metabolism and the activity of NAD+-dependent enzymes. This study provides new insight into the mechanisms by which rapamycin might influence the aging process to improve health and longevity among the aging population.

Graphene Oxide Covalently Grafted Fe2B@SiO2 Nanoparticles for Epirubicin Loading and Releasing.

In this work, stable superparamagnetic core-shell Fe2B@SiO2 nanoparticles were prepared by "one pot" chemical reduction of ferric ion salts with NaBH4 and silica shell coating in the presence of citric acid stabilizer. The X-ray (XRD) and selection of electron diffraction (SAED) revealed that Fe2B@SiO2 nanoparticles were chiefly composed of silica shell and Fe2B with a small amount of α-Fe. Then, graphene oxide (GO) was assembled onto core-shell Fe2B@SiO2 nanoparticles for Epirubicin (EPI) loading and releasing, and the adsorption isotherm of EPI on Fe2B@SiO2@GO was analyzed. The results showed, the adsorption process includes two steps, due to the π-π stacking effect of EPI on the Fe2B@SiO2@GO. The EPI loading efficiency of the magnetic nanoparticles was as high as 90%, while the EPI-loaded core-shell Fe2B@SiO2 nanoparticles showed an obvious pH controlled drug release behavior, and showed lower cumulative release rate when pH is 7.4 than that when pH is 5.7. The prepared nanoparticles demonstrated potential application in killing tumor cells while minimizing the toxicity to normal tissues.

Nicotinamide mononucleotide preserves mitochondrial function and increases survival in hemorrhagic shock.

Hemorrhagic shock depletes nicotinamide adenine dinucleotide (NAD) and causes metabolic derangements that, in severe cases, cannot be overcome, even after restoration of blood volume and pressure. However, current strategies to treat acute blood loss do not target cellular metabolism. We hypothesized that supplemental nicotinamide mononucleotide (NMN), the immediate biosynthetic precursor to NAD, would support cellular energetics and enhance physiologic resilience to hemorrhagic shock. In a rodent model of decompensated hemorrhagic shock, rats receiving NMN displayed significantly reduced lactic acidosis and serum IL-6 levels, two strong predictors of mortality in human patients. In both livers and kidneys, NMN increased NAD levels and prevented mitochondrial dysfunction. Moreover, NMN preserved mitochondrial function in isolated hepatocytes cocultured with proinflammatory cytokines, indicating a cell-autonomous protective effect that is independent from the reduction in circulating IL-6. In kidneys, but not in livers, NMN was sufficient to prevent ATP loss following shock and resuscitation. Overall, NMN increased the time animals could sustain severe shock before requiring resuscitation by nearly 25% and significantly improved survival after resuscitation (P = 0.018), whether NMN was given as a pretreatment or only as an adjunct during resuscitation. Thus, we demonstrate that NMN substantially mitigates inflammation, improves cellular metabolism, and promotes survival following hemorrhagic shock.

Arginine vasopressin, copeptin, and the development of relative AVP deficiency in hemorrhagic shock.

BACKGROUND: Arginine vasopressin (AVP) is critical for maintaining vasomotor tone and low levels have been associated with the development of irreversible shock. We investigated the clinical relationship between AVP, copeptin (the C-terminal fragment of the AVP precursor), and the development of relative AVP deficiency following hemorrhagic shock. METHODS: A prospective, observational study of 21 hypotensive (SBP<90 mmHg X 2) or presumptively bleeding trauma patients was conducted. Demographics, mechanism of injury, vital signs, laboratory values, transfusions, crystalloid volume, and blood samples were collected on arrival and serially for 48 h. AVP and copeptin were measured post hoc. RESULTS: AVP and copeptin levels were markedly elevated on admission, but decreased rapidly over time (p < 0.001). AVP and copeptin levels were positively correlated on admission (r = 0.769, p < 0.001), in the ICU (r = 0.768, p < 0.001), and at 48 h (r = 0.537, p = 0.02). Initial AVP and copeptin levels predicted the need for ≥10 unit blood product transfusion (AUC = 81% and 87%, respectively). The development of a relative AVP deficiency occurred frequently and was associated with an increased need for blood product transfusion. CONCLUSION: Copeptin correlates well with AVP and initial values predict the need for massive transfusion in trauma patients. Copeptin demonstrates promise as a clinical biomarker in hemorrhagic shock.

Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock.

OBJECTIVE: Hemorrhagic shock may contribute to acute kidney injury (AKI) by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin 1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. METHODS: Using a decompensated hemorrhagic shock model, male Long-Evans rats (n = 6 per group) were killed prior to hemorrhage (sham), at severe shock, and following either lactated Ringer's (LR) resuscitation or LR + RSV resuscitation (RSV: 30 mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen, and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (complexes I, II, and IV) using high-resolution respirometry. Total mitochondria reactive oxygen species were measured using fluorometry, and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. Quantitative polymerase chain reaction was used quantify mRNA from peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α) SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. RESULTS: Resveratrol supplementation during resuscitation restored mitochondrial respiratory capacity and decreased mitochondrial reactive oxygen species and lipid peroxidation. Compared with standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both superoxide dismutase 2 and catalase expression. Although RSV was associated with decreased lactate production, pH, blood urea nitrogen, and serum creatinine values did not differ between resuscitation strategies. CONCLUSIONS: Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock.