Attributable mortality of acute kidney injury among critically ill patients with sepsis: a multicenter, retrospective cohort study.

BACKGROUND: Sepsis and acute kidney injury (AKI) are common severe diseases in the intensive care unit (ICU). This study aimed to estimate the attributable mortality of AKI among critically ill patients with sepsis and to assess whether AKI was an independent risk factor for 30-day mortality. METHODS: The information we used was derived from a multicenter prospective cohort study conducted in 18 Chinese ICUs, focusing on septic patients post ICU admission. The patients were categorized into two groups: those who developed AKI (AKI group) within seven days following a sepsis diagnosis and those who did not develop AKI (non-AKI group). Using propensity score matching (PSM), patients were matched 1:1 as AKI and non-AKI groups. We then calculated the mortality rate attributable to AKI in septic patients. Furthermore, a survival analysis was conducted comparing the matched AKI and non-AKI septic patients. The primary outcome of interest was the 30-day mortality rate following the diagnosis of sepsis. RESULTS: Out of the 2175 eligible septic patients, 61.7% developed AKI. After the application of PSM, a total of 784 septic patients who developed AKI were matched in a 1:1 ratio with 784 septic patients who did not develop AKI. The overall 30-day attributable mortality of AKI was 6.6% (95% CI 2.3 ∼ 10.9%, p = 0.002). A subgroup analysis revealed that the 30-day attributable mortality rates for stage 1, stage 2, and stage 3 AKI were 0.6% (95% CI -5.9 ∼ 7.2%, p = 0.846), 4.7% (95% CI -3.1 ∼ 12.4%, p = 0.221) and 16.8% (95% CI 8.1 ∼ 25.2%, p < 0.001), respectively. Particularly noteworthy was that stage 3 AKI emerged as an independent risk factor for 30-day mortality, possessing an adjusted hazard ratio of 1.80 (95% CI 1.31 ∼ 2.47, p < 0.001). CONCLUSIONS: The overall 30-day attributable mortality of AKI among critically ill patients with sepsis was 6.6%. Stage 3 AKI had the most significant contribution to 30-day mortality, while stage 1 and stage 2 AKI did not increase excess mortality.

Attributable mortality of ARDS among critically ill patients with sepsis: a multicenter, retrospective cohort study.

BACKGROUND: Both sepsis and acute respiratory distress syndrome (ARDS) are common severe diseases in the intensive care unit (ICU). There is no large-scale multicenter study to clarify the attributable mortality of ARDS among septic patients. This study aimed to evaluate the excess mortality of ARDS in critically ill patients with sepsis. METHODS: The data were obtained from a multicenter, prospective cohort study in 18 Chinese ICUs between January 2014 and August 2015. The study population was septic patients after ICU admission. The patients were categorized into two groups: those who developed ARDS (ARDS group) within seven days following a sepsis diagnosis and those who did not develop ARDS (non-ARDS group). Applying propensity score matching (PSM), patients were matched 1:1 as ARDS and non-ARDS groups. Mortality attributed to ARDS was calculated. Subsequently, we conducted a survival analysis to estimate the impact of ARDS on mortality. The primary endpoint was 30-day mortality after sepsis diagnosis. RESULTS: 2323 septic patients were eligible, 67.8% developed ARDS. After PSM, 737 patients with ARDS were matched 1:1 with 737 non-ARDS patients. ARDS's overall 30-day attributable mortality was 11.9% (95% CI 7.5-16.3%, p < 0.001). Subgroup analysis showed that the 30-day attributable mortality of mild, moderate, and severe ARDS was 10.5% (95% CI 4.0-16.8%, p < 0.001), 11.6% (95% CI 4.7-18.4%, p < 0.001) and 18.1% (95% CI 4.5-30.9%, p = 0.006), respectively. ARDS was an independent risk factor for 30-day mortality, with adjusted hazard ratios of 1.30 (95% CI 1.03-1.64, p = 0.027), 1.49 (95% CI 1.20-1.85, p < 0.001), and 1.95 (95% CI 1.51-2.52, p < 0.001) for mild, moderate, and severe ARDS, respectively. CONCLUSIONS: The overall 30-day attributable mortality of ARDS among critically ill patients with sepsis was 11.9%. Compared with mild and moderate ARDS, severe ARDS contributed more to death. ARDS was significantly associated with an increase in the 30-day mortality.

Association between the levels of urinary cell cycle biomarkers and non-recovery of renal function among critically ill geriatric patients with acute kidney injury.

The lack of early renal function recovery among geriatric patients with acute kidney injury (AKI) in the intensive care unit (ICU) is a commonly observed and acknowledged poor prognostic factor, especially for older adults. However, no reliable prognostic biomarker is available for identifying individuals at risk of renal non-recovery or mortality in older adults. In this prospective observational cohort study, we enrolled critically ill older adults (aged ≥ 60 years) with AKI from the ICU and followed their disease progression. The primary endpoint was renal non-recovery within seven days of follow-up, while the secondary endpoint was the determinants of 30-day mortality after AKI. We assessed the predictive accuracy using receiver operating characteristic curves and performed between-group comparisons using the log-rank test. Among 209 older adults, 117 (56.0%) experienced renal recovery. Multiple regression analysis revealed that urine levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) multiplied by insulin-like growth factor-binding protein 7 (IGFBP7) ([TIMP-2]*[IGFBP7]), AKI stages 2-3, and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were independently associated with renal non-recovery. The regression model incorporating [TIMP-2]*[IGFBP7] demonstrated a fair predictive value (AUC 0.774, p < 0.001), with the optimal threshold set at 0.81 (ng/mL)2/1000. When [TIMP-2]*[IGFBP7] was combined with AKI severity and the APACHE score, the AUC increased to 0.851. In conclusion, urine [TIMP-2]*[IGFBP7] is a reliable biomarker associated with renal non-recovery in critically ill older adults, and its predictive efficacy can be further enhanced when combined with AKI severity and the APACHE score.

Postoperative plasma presepsin as a biomarker of postoperative infectious complications in different surgical departments: A meta-analysis and systematic review.

BACKGROUND: High rates of postoperative infection persist after different surgical procedures, encompassing surgical site infections (SSIs), remote infections, sepsis, and septic shock. Our aim was to assess presepsin's diagnostic accuracy for postoperative infections in patients across surgical procedures. METHOD: We conducted a comprehensive search in seven databases, extracting data independently. Using STATA 14.0, we calculated pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and Under the receiver operator curve and 95 â€‹% confidence interval (AUC, 95 â€‹% CI) as primary outcomes, with secondary outcomes involving sensitivity and specificity in subgroup analyses. RESULTS: This meta-analysis of 14 studies (1891 cases) evaluated presepsin's diagnostic value for postoperative infectious complications. Results include sensitivity of 77 â€‹% (70-83), specificity of 81 â€‹% (71-88), DOR of 14 (8-26), AUC of 84 (80-87), PLR of 4 (3-6), and NLR of 0.28 (0.21-0.38). Presepsin exhibits promise as a diagnostic tool for postoperative infections. CONCLUSION: In summary, compared to conventional markers like C-reactive protein (CRP) and procalcitonin (PCT), presepsin demonstrated superior sensitivity and specificity for detecting postoperative infectious complications across various surgical procedures.

Diagnostic Accuracy of Procalcitonin for Infection After Adult Liver Transplantation: A Meta-Analysis and Systematic Review.

Background: Post-operative infection remains a major cause of morbidity and mortality in adults early after liver transplantation (LT). Procalcitonin (PCT) may be a good test method for early diagnosis of post-operative infection and determining its severity. This study was performed to assess the diagnostic accuracy of PCT as a biomarker for infection after LT. Patients and Methods: A meta-analysis and systematic review was conducted for studies reporting diagnostic performance of PCT for infection in adults after LT. Observational studies were evaluated for their reporting of diagnostic accuracy, relevance, and quality. Results: Ten eligible studies assessing 730 patients were included in this meta-analysis and systematic review summarizing the diagnostic value of PCT for post-operative infection in adult liver transplantation. Pooled sensitivity and specificity with corresponding 95% confidence interval were 69% (95% confidence interval [CI], 54-81; heterogeneity I2 = 82.4%) and 88% (95% CI, 82-92; I2 = 52.7%), respectively. The diagnostic odd ratio (DOR) was 16 (95% CI, 10-25; I2 = 76.4%). The summary receiver operator characteristic (SROC) of PCT for post-operative infection was 0.88. There was a wide range of variability in the cutoff values, ranging from 0.22 to 42.80 ng/mL. Heterogeneity was reduced by excluding studies that focused on pediatric LT recipients. Conclusions: Procalcitonin is a moderately accurate diagnostic marker for post-operative infection in adult LT. Additionally, the diagnostic performance can be improved by combining it with other inflammatory biomarkers. This article provides the research direction for post-operative infection control.

Urinary cell cycle biomarkers for the prediction of renal non-recovery in patients with septic acute kidney injury: a prospective study.

BACKGROUND: Poor prognosis has been associated with the absence of renal recovery after acute kidney injury (AKI). This study aimed to investigate whether urinary biomarkers at 0 and 24 h could be used independently or in conjunction with a clinical model to predict renal non-recovery in septic AKI. METHODS: A prospective observational study was conducted to measure the urinary levels of insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) at the time of AKI diagnosis (0 h) and 24 h later. Renal non-recovery within 7 days was defined as the outcome. The predictive value of urinary biomarkers for renal non-recovery in septic AKI was assessed using the area under the curve (AUC). RESULTS: A total of 198 individuals with septic AKI were included in the final analysis. Among them, 38.9% (n = 77) did not experience renal recovery within 7 days. The combination of urinary IGFBP7 and TIMP-2 at the initial time point demonstrated prognostic value for non-recovery of renal function, with an AUC of 0.782. When [TIMP-2]*[IGFBP7] was measured at 0 h, the clinical prognostic model, incorporating AKI stage 2-3 and the non-renal sequential organ failure assessment score, showed an improved AUC of 0.822 (with a sensitivity of 88.3% and specificity of 59.5%). CONCLUSIONS: The combination of urinary [TIMP-2]*[IGFBP7] at 0 h exhibited moderate predictive ability for renal non-recovery in cases of septic AKI. However, there is potential to enhance the prognostic capabilities of the [TIMP-2]*[IGFBP7]-clinical prediction model.

Predictive Value of Perioperative Cardiac Troponin I in Patients Undergone Liver Transplantation: A Retrospective Cohort Study.

Objective: To examine the change rule and clinical significance of cardiac troponin I (cTnI) in the perioperative period of liver transplantation in adults, as well as its association with 28-day mortality. Methods: This was a retrospective cohort study: patients who underwent elective orthotopic liver transplantation (OLT) in Beijing Chao-Yang Hospital between June 2015 and June 2020 were selected, and plasma cTnI values were collected through the electronic medical record system within 7 days after surgery. Furthermore, the baseline clinical data of these patients were collected, and the change curve of cTnI values following liver transplantation was plotted. Using univariate and multivariate logistic regression models, the relationship between the level of postoperative cTnI and short-term mortality was investigated. The primary study endpoint was mortality within 28 days after surgery. Results: We included 414 patients who had undergone liver transplantation in this study, 48 of whom died within 28 days after surgery. cTnI, a specific marker of myocardial injury, could predict that the postoperative cardiovascular complications were higher in the death group and significantly affect the short-term prognosis of patients; however, its prognostic cut-off value was approximately 0.545 ng/mL (13×URL), indicating that a minor elevation of cTnI after liver transplantation did not significantly affect the prognosis. Moreover, a comparison of the baseline data and postoperative ICU management scores of the two groups revealed that diabetes, maximum value of cTnI >0.545 ng/mL within 7 days, and the need for postoperative renal replacement therapy (RRT) were independent prognostic factors of death within 28 days after liver transplantation. Conclusion: Within 7 days after surgery, an increase in cTnI to the maximum value of 0.545 ng/mL (13×URL) could have a significant impact on the short-term prognosis of patients. Diabetes and postoperative RRT were two independent prognostic factors for liver transplantation perioperative mortality.

Analysis of urinary C-C motif chemokine ligand 14 (CCL14) and first-generation urinary biomarkers for predicting renal recovery from acute kidney injury: a prospective exploratory study.

BACKGROUND: Acute kidney injury (AKI) is a frequent syndrome in the intensive care unit (ICU). AKI patients with kidney function recovery have better short-term and long-term prognoses compared with those with non-recovery. Numerous studies focus on biomarkers to distinguish them. To better understand the predictive performance of urinary biomarkers of renal recovery in patients with AKI, we evaluated C-C motif chemokine ligand 14 (CCL14) and two first-generation biomarkers (cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin) in two ICU settings. METHODS: We performed a prospective study to analyze urinary biomarkers for predicting renal recovery from AKI. Patients who developed AKI after ICU admission were enrolled and urinary biomarkers including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), CCL14, and neutrophil gelatinase-associated lipocalin (NGAL) were detected on the day of AKI diagnosis. The primary endpoint was non-recovery from AKI within 7 days. The individual discriminative ability of CCL14, [TIMP-2] × [IGFBP7] and NGAL to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC). RESULTS: Of 164 AKI patients, 64 (39.0%) failed to recover from AKI onset. CCL14 showed a fair prediction ability for renal non-recovery with an AUC of 0.71 (95% CI 0.63-0.77, p < 0.001). [TIMP-2] × [IGFBP7] showed the best prediction for renal non-recovery with an AUC of 0.78 (95% CI 0.71-0.84, p < 0.001). However, NGAL had no use in predicting non-recovery with an AUC of 0.53 (95% CI 0.45-0.60, p = 0.562). A two-parameter model (non-renal SOFA score and AKI stage) predicted renal non-recovery with an AUC of 0.77 (95% CI 0.77-0.83, p = 0.004). When [TIMP-2] × [IGFBP7] was combined with the clinical factors, the AUC was significantly improved to 0.82 (95% CI 0.74-0.87, p = 0.049). CONCLUSIONS: Urinary CCL14 and [TIMP-2] × [IGFBP7] were fair predictors of renal non-recovery from AKI. Combing urinary [TIMP-2] × [IGFBP7] with a clinical model consisting of non-renal SOFA score and AKI stage enhanced the predictive power for renal non-recovery. Urinary CCL14 showed no significant advantage in predicting renal non-recovery compared to [TIMP-2] × [IGFBP7].

The attributable mortality of sepsis for acute kidney injury: a propensity-matched analysis based on multicenter prospective cohort study.

BACKGROUND: Both sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI). METHODS: A propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3-5. The primary outcome was hospital death of AKI patients. RESULTS: A total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8-13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3-20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1-5.9%, p = 0.825). CONCLUSIONS: The attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis. REGISTRATION FOR THE MULTICENTER PROSPECTIVE COHORT STUDY: registration number ChiCTR-ECH-13003934.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression.

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Calprotectin as a diagnostic marker for sepsis: A meta-analysis.

Introduction: Sepsis is a life-threatening condition, and biomarkers are needed to diagnose sepsis fast and accurately. We aimed to perform this meta-analysis to investigate the diagnostic value of calprotectin on sepsis in critically ill patients. Methods: The investigators searched MEDLINE, Embase, Web of Science and Cochrane Library. Studies were included if they assessed the diagnostic accuracy of serum calprotectin for sepsis in intensive care unit (ICU). We estimated its diagnostic value and explored the source of heterogeneity. The bivariate model and the hierarchical summary receiver operating characteristic (HSROC) curve were used in the meta-analysis. Results: Six records assessing 821 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were separately as 0.77, 0.85, 5.20, 0.27, respectively. The Fagan's nomogram showed post-test probabilities of 91% and 35% for positive and negative outcomes, respectively. Subgroup analysis indicated that sepsis definition could be a possible source of heterogeneity, but there's no sufficient data to investigate sepsis-3 definition. Sensitivity analysis suggested that two studies could affect the stability of pooled results. Conclusion: On the basis of our meta-analysis, calprotectin is a helpful marker for early diagnosis of sepsis on ICU admission.

A clinical herbal prescription Gu-Shu-Kang capsule exerted beneficial effects on the musculoskeletal system of dexamethasone-treated mice by acting on tissue IGF-1 signalling pathway.

CONTEXT: Gu-Shu-Kang (GSK) is a clinical traditional Chinese medicine prescription for the treatment of primary osteoporosis. OBJECTIVE: This study investigates the protection of GSK against dexamethasone (Dex)-induced disturbance of musculoskeletal system in male mice and to identify the underlying mechanism. MATERIALS AND METHODS: Male C57BL/6 mice in Dex-treated groups were orally administered (i.g.) with vehicle, low dose (0.38 g/kg), middle dose (0.76 g/kg), or high dose (1.52 g/kg) of GSK for 8 weeks. A control group was designed without any treatment. The quadriceps femoris, tibialis anterior and gastrocnemius were harvested. Molecular expression was determined by RT-PCR and immunoblotting. RESULTS: Treatment with GSK enhanced weight-loaded swimming time (from 411.7 ± 58.4 s in Dex group to 771.4 ± 87.3 s in GSK-M) and grip strength (from 357.8 ± 23.9 g in Dex group to 880.3 ± 47.6 g in GSK-M). GSK produced a rise in cross-sectional area of myofibers and promoted a switching of glycolytic-to-oxidative myofiber. The administration with GSK affected expression of muscle regulatory factors shown by the down-regulation in MuRF-1 and atrogin-1 and the up-regulation in myogenic differentiation factor (MyoD) and myosin heavy chain (MHC). GSK stimulated tissue IGF-1 signalling pathway (IGF-1R/PI3K/Akt), not only in skeletal muscle but also in bone associated with the amelioration of trabecular bone mineral density and the improvement of osteogenesis. CONCLUSIONS: These findings revealed the potential mechanisms involved in the beneficial effects of Gu-Shu-Kang on musculoskeletal system in mice with challenging to dexamethasone, and this prescription may have applications in management for muscle atrophy and osteoporosis triggered by glucocorticoid.

Comparative Study of M(â ¡)Al (M=Co, Ni) Layered Double Hydroxides for Silicone Foam: Characterization, Flame Retardancy, and Smoke Suppression.

To compare the different actions of the two representative transition metal cations of Co2+ and Ni2+ in layered double hydroxides (LDHs), CoAl-LDH and NiAl-LDH intercalated with CO32- were synthesized, and the chemical structures, microstructures, and surface areas thereof were successfully characterized. Then, the two LDHs were utilized as flame retardants and smoke suppressants for silicone foam (SiF). The densities, flame retardancy, smoke suppression, thermal stabilities, and compressive strengths of the two SiF/LDHs nanocomposites were investigated. The introduction of LDHs slightly decreased the density of SiF due to the catalytic actions of Co and Ni during the foaming process of SiF. With respect to the flame retardancy, the addition of only 1 phr of either CoAl-LDH or NiAl-LDH could effectively improve the limiting oxygen index of SiF from 28.7 to 29.6%. Based on the results of vertical flame testing and a cone calorimeter test, the flame retardancy and fire safety of the SiF were effectively enhanced by the incorporation of LDHs. In addition, owing to the good catalytic action and large specific surface area (NiAl-LDH: 174.57 m2 g-1; CoAl-LDH: 51.47 m2 g-1), NiAl-LDH revealed higher efficiencies of flame retardancy and smoke suppression than those of CoAl-LDH. According to the results of energy-dispersive X-ray spectroscopy, Co and Ni participated in the formation of protective char layers, which inhibited the release of SiO2 into the gas phase. Finally, the influences on the thermal decomposition and compressive strength for SiF resulting from the addition of LDHs are discussed.

Vitamin D Supplementation Improves Handgrip Strength in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction: In postmenopausal women, vitamin D deficiency (as defined by the circulating level of 25(OH)D being below 20 ng/ml (50 nmol/L)) is a regular occurrence. The effect of vitamin D supplementation on the muscle function of postmenopausal women has been controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines and summarizes the effects of vitamin D supplementation on the muscular strength and mobility of postmenopausal women. Methods: RCTs that met the inclusion criteria for this study were identified by searching PubMed, EMBASE, and the Cochrane Library. Postmenopausal women who were included in the study were exposed to RCTs assessing the effectiveness of vitamin D supplements. Meta-analysis data were extracted by two independent reviewers and screened for methodological quality. RCTs that did not meet the minimum requirement for assessment were excluded. In the meta-analysis, the effect size (weighted mean differences, WMD) of handgrip strength (HGS) and timed-up and go test (TUG) with a 95% confidence interval (CI) was obtained to compare reported results across the included RCTs. Results: A total of 19 trials were included in this systematic review, among which 13 trials were eligible for the meta-analysis. In the 13 included studies, supplementing with vitamin D produced a weighted mean difference of 0.876 kg (95% CI = 0.180 to 1.571, P = 0.014, I2 = 68.5%) for HGS, a measurement of muscle strength. However, an insignificant decrease of 0.044 s was observed after analyzing the TUG (95% CI = -0.979 to 0.892, P = 0.927, I2 = 95%). According to subgroup analysis, vitamin D supplementation increased HGS in patients over the age of 60 (P = 0.001), in those without calcium supplementation (P = 0.032), and in those whose baseline vitamin D level was greater than 75 nmol/L (30 ng/ml) (P = 0.003). Conclusions: Taking into account the studies in this systematic review, vitamin D supplementation improved muscle strength in postmenopausal women. However, an insignificant result was demonstrated in terms of mobility after vitamin D supplementation.

Cell cycle arrest biomarkers for predicting renal recovery from acute kidney injury: a prospective validation study.

BACKGROUND: Acute kidney injury (AKI) is a common disease in the intensive care unit (ICU). AKI patients with nonrecovery of renal function have a markedly increased risk of death compared with patients with recovery. The current study aimed to explore and validate the utility of urinary cell cycle arrest biomarkers for predicting nonrecovery in patients who developed AKI after ICU admission. METHODS: We prospectively and consecutively enrolled 379 critically ill patients who developed AKI after admission to the ICU, which were divided into a derivation cohort (194 AKI patients) and a validation cohort (185 AKI patients). The biomarkers of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected at inclusion immediately after AKI diagnosis (day 0) and 24 h later (day 1). The optimal cut-off values of these biomarkers for predicting nonrecovery were estimated in the derivation cohort, and their predictive accuracy was assessed in the validation cohort. The primary endpoint was nonrecovery from AKI (within 7 days). RESULTS: Of 379 patients, 159 (41.9%) patients failed to recover from AKI onset, with 79 in the derivation cohort and 80 in the validation cohort. Urinary [TIMP-2]*[IGFBP7] on day 0 showed a better prediction ability for nonrecovery than TIMP-2 and IGFBP7 alone, with an area under the reciever operating characteristic curve (AUC) of 0.751 [95% confidence interval (CI) 0.701-0.852, p < 0.001] and an optimal cut-off value of 1.05 ((ng/mL)2/1000). When [TIMP-2]*[IGFBP7] was combined with the clinical factors of AKI diagnosed by the urine output (UO) criteria, AKI stage 2-3 and nonrenal SOFA score for predicting nonrecovery, the AUC was significantly improved to 0.852 (95% CI 0.750-0.891, p < 0.001), which achieved a sensitivity and specificity of 88.8% (72.9, 98.7) and 92.6% (80.8, 100.0), respectively. However, urine [TIMP-2]*[IGFBP7], TIMP-2 alone, and IGFBP7 alone on day 1 performed poorly for predicting AKI recovery. CONCLUSION: Urinary [TIMP-2]*[IGFBP7] on day 0 showed a fair performance for predicting nonrecovery from AKI. The predictive accuracy can be improved when urinary [TIMP-2]*[IGFBP7] is combined with the clinical factors of AKI diagnosed by the UO criteria, AKI stage 2-3 and nonrenal SOFA score.

The attributable mortality of new-onset acute kidney injury among critically ill patients: a propensity-matched analysis based on a multicentre prospective cohort study.

PURPOSE: This study aimed to evaluate the attributable mortality of new-onset acute kidney injury (AKI). METHODS: The data in the present study were derived from a multi-center, prospective cohort study in China that was performed at 18 Chinese ICUs. A propensity-matched analysis was performed between matched patients with and without AKI selected from all eligible patients to estimate the attributable mortality of new-onset AKI. RESULTS: A total of 2872 critically ill adult patients were eligible. The incidence of new-onset AKI was 29.1% (n = 837). After propensity score matching, 788 patients with AKI were matched 1:1 with 788 controls (patients without AKI). Thirty-day mortality was significantly higher among the patients with AKI than among their matched controls (25.5% versus 17.4%, p < 0.001). Subgroup analysis in terms of AKI classification showed that there was no significant difference (p = 0.509) in 30-day mortality between patients with stage 1 AKI and their matched controls. The attributable mortality values of stage 2 and stage 3 AKI were 12.4% [95% confidence interval (CI) 2.6-21.8%, p = 0.013] and 16.1% (95% CI 8.2-23.8%, p < 0.001), respectively. The attributable mortality of persistent AKI was 15.7% (95% CI 8.8-22.4%, p = 0.001), while no observable difference in 30-day mortality was identified between transient AKI patients and their matched non-AKI controls (p = 0.229). CONCLUSION: The absolute excess 30-day mortality that is statistically attributable to new-onset AKI is substantial (8.1%) among general ICU patients. However, neither stage 1 AKI nor transient AKI increases 30-day mortality.

Development of a Multivariable Prediction Model for Citrate Accumulation in Liver Transplant Patients Undergoing Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation.

INTRODUCTION: Patients with impaired citrate metabolism may experience citrate accumulation (CA), which causes life-threatening metabolic acidosis and hypocalcemia. CA poses a challenge for clinicians when deciding on the use of regional citrate anticoagulation (RCA) for patients with liver dysfunction. This study aimed to develop a prediction model integrating multiple clinical variables to assess the risk of CA in liver transplant patients. METHODS: This single-center prospective cohort study included postoperative liver transplant patients who underwent continuous renal replacement therapy (CRRT) with RCA. The study end point was CA. A prediction model was developed using a generalized linear mixed-effect model based on the Akaike information criterion. The predictive values were assessed using the receiver operating characteristic curve and bootstrap resampling (times = 500) to estimate the area under the curve (AUC) and the corresponding 95% confidence interval (CI). A nomogram was used to visualize the model. RESULTS: This study included 32 patients who underwent 133 CRRT sessions with RCA. CA occurred in 46 CRRT sessions. The model included lactate, norepinephrine >0.1 µg/kg/min, alanine aminotransferase, total bilirubin, and standard bicarbonate, which were tested before starting each CRRT session and body mass index, diabetes mellitus, and chronic kidney disease as predictors. The AUC of the model was 0.867 (95% CI 0.786-0.921), which was significantly higher than that of the single predictor (p < 0.05). A nomogram visualized the prediction model. CONCLUSIONS: The prediction model integrating multiple clinical variables showed a good predictive value for CA. A nomogram visualized the model for easy application in clinical practice.

Vitamin D/Vitamin D Receptor Signaling Attenuates Skeletal Muscle Atrophy by Suppressing Renin-Angiotensin System.

The nutritional level of vitamin D may affect musculoskeletal health. We have reported that vitamin D is a pivotal protector against tissue injuries by suppressing local renin-angiotensin system (RAS). This study aimed to explore the role of the vitamin D receptor (VDR) in the protection against muscle atrophy and the underlying mechanism. A cross-sectional study on participants (n = 1034) in Shanghai (China) was performed to analyze the association between vitamin D level and the risk of low muscle strength as well as to detect the circulating level of angiotensin II (Ang II). In animal studies, dexamethasone (Dex) was applied to induce muscle atrophy in wild-type (WT) and VDR-null mice, and the mice with the induction of muscle atrophy were treated with calcitriol for 10 days. The skeletal muscle cell line C2C12 and the muscle satellite cells were applied in in vitro studies. The increased risk of low muscle strength was correlated to a lower level of vitamin D (adjusted odds ratio [OR] 0.58) accompanied by an elevation in serum Ang II level. Ang II impaired the myogenic differentiation of C2C12 myoblasts as illustrated by the decrease in the area of myotubes and the downregulation of myogenic factors (myosin heavy chain [MHC] and myogenic differentiation factor D [MyoD]). The phenotype of muscle atrophy induced by Dex and Ang II was aggravated by VDR ablation in mice and in muscle satellite cells, respectively, and mediated by RAS and its downstream phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 (PI3K/Akt/FOXO1) signaling. Calcitriol treatment exhibited beneficial effects on muscle function as demonstrated by the increased weight-loaded swimming time, grip strength, and fiber area, and improved fiber type composition via regulating ubiquitin ligases and their substrates MHC and MyoD through suppressing renin/Ang II axis. Taken together, VDR protects against skeletal muscle atrophy by suppressing RAS. Vitamin D could be a potential agent for the prevention and treatment of skeletal muscle atrophy. © 2021 American Society for Bone and Mineral Research (ASBMR).

Predictive utility of postoperative serum myoglobin in acute kidney injury after liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common and multifactorial complication after liver transplantation (LT). Myoglobin (Mb) which can be served as O2 storage and delivery depot is present in muscles and cardiac myocytes. Previous studies had shown the close relationship between Mb and AKI. But there is a lack of clinical studies for Mb with the risk of AKI due to LT. This study was performed to determine the association between the serum level of Mb and incidence of AKI in patients underwent LT. METHODS: The clinical data of 140 consecutive adult patients who underwent LT at our center from June 2018 to August 2020 were analyzed in this study. One hundred and fifteen patients met the inclusion criteria. The performances of postoperative laboratory variables (including serum Mb) were evaluated. The outcomes after LT, including the duration of intensive care unit (ICU) stay, hospital stay and 28-day mortality, were also measured. RESULTS: We divided 115 patients into AKI group (n=44) and non-AKI group (n=71). Serum Mb on post-operative day 0 (POD0) was significantly higher in AKI group than those in non-AKI group (P<0.001). According to univariate and multivariable logistic regression analysis, the levels of serum albumin (P=0.024), alanine transaminase (P=0.007) and Mb (P=0.006) on POD0 were independently associated with development of new AKI. The area under curve (AUC) of serum Mb after LT immediately had the best value for predicting AKI [AUC: 0.755, sensitivity: 63.6%, specificity: 77.3%, 95% confidence interval (CI): 0.661-0.849], its cut-off value was 957 ng/mL. CONCLUSIONS: Postoperative serum Mb was an independent risk factor for new AKI and could increase the accuracy of predicting the occurrence of post-LT AKI. TRIAL REGISTRATION: The study was registered in Chinese Clinical Trial Registry (registration number: ChiCTR2100044257).

Risk factors, clinical features and outcome of new-onset acute kidney injury among critically ill patients: a database analysis based on prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) newly-emerged in intensive care unit (ICU), has not been thoroughly studied in previous researches, is likely to differ from AKI developed before ICU admission. This study aimed to evaluate the incidence, risk factors, clinical features and outcome of new-onset AKI in critically ill patients. METHODS: The data of present study derived from a multicenter, prospective cohort study in17 Chinese ICUs (January 2014 - August 2015). The incidence, risk factors, clinical features and survival analysis of new-onset AKI were assessed. RESULTS: A total of 3374 adult critically ill patients were eligible. The incidence of new-onset AKI was 30.0 % (n = 1012). Factors associated with a higher risk of new-onset AKI included coronary heart disease, hypertension, chronic liver disease, use of nephrotoxic drugs, sepsis, SOFA score, APACHEII score and use of vasopressors. The new-onset AKI was an independent risk factor for 28-day mortality (adjusted hazard ratio, 1.643; 95 % CI, 1.370-1.948; P < 0.001). 220 (21.7 %) patients received renal replacement therapy (RRT), 71 (32.3 %) of them were successfully weaning from RRT. More than half of the new-onset AKI were transient AKI (renal recovery within 48 h). There was no statistical relationship between transient AKI and 28-day mortality (hazard ratio, 1.406; 95 % CI, 0.840-1.304; P = 0.686), while persistent AKI (non-renal recovery within 48 h) was strongly associated with 28-day mortality (adjusted hazard ratio, 1.486; 95 % CI, 1.137-1.943; P < 0.001). CONCLUSIONS: New-onset AKI is common in ICU patients and is associated with significantly higher 28-day mortality. Only persistent AKI, but not transient AKI is associated with significantly higher 28-day mortality.