Digital Physical Activity and Exercise Interventions for People Living with Chronic Kidney Disease: A Systematic Review of Health Outcomes and Feasibility.

Physical activity is essential to interrupt the cycle of deconditioning associated with chronic kidney disease (CKD). However, access to targeted physical activity interventions remain under-supported due to limited funding and specialised staff. Digital interventions may address some of these factors. This systematic review sought to examine the evidence base of digital interventions focused on promoting physical activity or exercise and their effect on health outcomes for people living with CKD. Electronic databases (PubMed, CINAHL, Embase, Cochrane) were searched from 1 January 2000 to 1 December 2023. Interventions (smartphone applications, activity trackers, websites) for adults with CKD (any stage, including transplant) which promoted physical activity or exercise were included. Study quality was assessed, and a narrative synthesis was conducted. Of the 4057 records identified, eight studies (five randomised controlled trials, three single-arm studies) were included, comprising 550 participants. Duration ranged from 12-weeks to 1-year. The findings indicated acceptability and feasibility were high, with small cohort numbers and high risk of bias. There were inconsistent measures of physical activity levels, self-efficacy, body composition, physical function, and psychological outcomes which resulted in no apparent effects of digital interventions on these domains. Data were insufficient for meta-analysis. The evidence for digital interventions to promote physical activity and exercise for people living with CKD is limited. Despite popularity, there is little evidence that current digital interventions yield the effects expected from traditional face-to-face interventions. However, 14 registered trials were identified which may strengthen the evidence-base.

Ischemic Hepatitis and Septic Shock Secondary to Murine Typhus Infection in Pregnancy.

Infection with murine typhus may be associated with significant morbidity. With nonspecific symptoms and laboratory abnormalities, diagnosis may be challenging. In this case, a pregnant patient presented with complaints of fevers and myalgias. Her laboratory results included severe transaminitis as well as thrombocytopenia and hyponatremia. She ultimately required vasopressor support and intensive care unit admission despite fluid resuscitation and broad-spectrum antibiotics. Empiric doxycycline was initiated due to suspicion for murine typhus, which laboratory testing later confirmed. Her clinical status improved with these interventions. This was a severe case of murine typhus resulting in septic shock and ischemic hepatitis. It is important to know the typical findings of murine typhus and consider it in a differential diagnosis, especially when practicing in endemic areas.

Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.

Congenital disorders of glycosylation (CDG) are a group of rare autosomal recessive genetic disorders caused by pathogenic variants in genes coding for N-glycosylated glycoproteins, which play a role in folding, degrading, and transport of glycoproteins in their pathway. ALG12-CDG specifically is caused by biallelic pathogenic variants in ALG12. Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities. In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder. We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing.

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.

Differentiation of Idiopathic Central Precocious Puberty From Premature Thelarche Using Principal Component Analysis.

CONTEXT: Nonprogressive premature thelarche (PT) is a self-limiting variant of early puberty, while idiopathic central precocious puberty (ICPP) is a disorder that causes progressive development of secondary sexual characteristics and often requires treatment. The diagnostic differentiation between these conditions is important but can be challenging since they often both initially present clinically with isolated breast development. OBJECTIVE: To describe relevant clinical variables in a large cohort of girls referred for early puberty, and to evaluate clinical and biochemical parameters to distinguish between girls with ICPP and PT. METHODS: This retrospective study included 1361 girls referred with signs of early puberty to a single, tertiary center from 2009 to 2019. We evaluated clinical presentation, medical history, growth velocity, bone age, hormonal serum concentrations, and gonadotropin-releasing hormone (GnRH) test results. RESULTS: Central precocious puberty was diagnosed in 11% (ICPP: n = 143, organic CPP: n = 11) girls, whereas 8% (n = 91 girls) presented with PT. Receiver operating characteristic (ROC) analysis showed several biochemical and anthropometric markers as potential parameters to differentiate between ICPP and PT; however, none were individually adequate. Principal component analysis (PCA)-derived clinical and hormone profiles could predict girls with ICPP from girls with PT with a specificity of 90% and sensitivity of 84%, outperforming any single marker. CONCLUSION: Differentiation of girls with ICPP and PT can be supported by individual clinical and biochemical parameters. However, dimension reduction of clinical and hormonal profiles by PCA improved the diagnostic value, which in the future may support the diagnostic process as a supplement to the GnRH test in evaluation of pubertal disorders.

Clinical Manifestations and Risk Factors Associated with 14 Deaths following Swarm Wasp Stings in a Chinese Tertiary Grade A General Hospital: A Retrospective Database Analysis Study.

INTRODUCTION: The objective was to evaluate the poisoning severity score (PSS) as an early prognostic predictor in patients with wasp stings and identify associated clinical characteristics and risk factors for mortality. METHODS: A total of 363 patients with wasp stings at Suining Central Hospital between January 2016 and December 2018 were enrolled. Within the first 24 h of admission, the poisoning severity score (PSS) and the Chinese expert consensus on standardized diagnosis and treatment of wasp stings (CECC) were utilized for severity classification, and their correlation was examined. Patients were then divided into survival and death groups based on discharge status. Logistic regression analysis was employed to analyze factors influencing patients' outcomes. RESULTS: The mortality of wasp sting patients was 3.9%. The PSS and CECC were found to correlate for severity classification. Additionally, female gender, age, number of stings, and PSS were identified as independent risk factors for mortality in wasp sting patients. Combining these four factors yielded an AUC of 0.962 for predicting death. CONCLUSIONS: PSS aids in early severity classification of wasp stings. Female gender, age, number of stings, and PSS were independent mortality risk factors in these patients.

Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway.

BACKGROUND: High dosage of dexamethasone (Dex) is an effective treatment for multiple diseases; however, it is often associated with severe side effects including muscle atrophy, resulting in higher risk of falls and poorer life quality of patients. Cell therapy with mesenchymal stem cells (MSCs) holds promise for regenerative medicine. In this study, we aimed to investigate the therapeutic efficacy of systemic administration of adipose-derived mesenchymal stem cells (ADSCs) in mitigating the loss of muscle mass and strength in mouse model of DEX-induced muscle atrophy. METHODS: 3-month-old female C57BL/6 mice were treated with Dex (20 mg/kg body weight, i.p.) for 10 days to induce muscle atrophy, then subjected to intravenous injection of a single dose of ADSCs ([Formula: see text] cells/kg body weight) or vehicle control. The mice were killed 7 days after ADSCs treatment. Body compositions were measured by animal DXA, gastrocnemius muscle was isolated for ex vivo muscle functional test, histological assessment and Western blot, while tibialis anterior muscles were isolated for RNA-sequencing and qPCR. For in vitro study, C2C12 myoblast cells were cultured under myogenic differentiation medium for 5 days following 100 [Formula: see text]M Dex treatment with or without ADSC-conditioned medium for another 4 days. Samples were collected for qPCR analysis and Western blot analysis. Myotube morphology was measured by myosin heavy chain immunofluorescence staining. RESULTS: ADSC treatment significantly increased body lean mass (10-20%), muscle wet weight (15-30%) and cross-sectional area (CSA) (~ 33%) in DEX-induced muscle atrophy mice model and down-regulated muscle atrophy-associated genes expression (45-65%). Hindlimb grip strength (~ 37%) and forelimb ex vivo muscle contraction property were significantly improved (~ 57%) in the treatment group. Significant increase in type I fibres (~ 77%) was found after ADSC injection. RNA-sequencing results suggested that ERK1/2 signalling pathway might be playing important role underlying the beneficial effect of ADSC treatment, which was confirmed by ERK1/2 inhibitor both in vitro and in vivo. CONCLUSIONS: ADSCs restore the pathogenesis of Dex-induced muscle atrophy with an increased number of type I fibres, stronger muscle strength, faster recovery rate and more anti-fatigue ability via ERK1/2 signalling pathway. The inhibition of muscle atrophy-associated genes by ADSCs offered this treatment as an intervention option for muscle-associated diseases. Taken together, our findings suggested that adipose-derived mesenchymal stem cell therapy could be a new treatment option for patient with Dex-induced muscle atrophy.

Effect of kidney disease on all-cause and cardiovascular mortality in patients undergoing coronary angiography.

Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is associated with increased mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular disease (CVD). Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. The aim of our study was to investigate the relationship between acute and CKD and mortality in patients undergoing CAG. The cohort study included 49,194 patients in the multicenter cohort from January 2007 to December 2018. Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis are used to examine the association between kidney disease and all-cause and cardiovascular mortality. In the present study, 13,989 (28.4%) patients had kidney disease. During follow-up, 6144 patients died, of which 4508 (73.4%) were due to CVD. AKI without CKD (HR: 1.54, 95% CI: 1.36-1.74), CKD without AKI (HR: 2.02, 95% CI: 1.88-2.17), AKI with CKD (HR: 3.26, 95% CI: 2.90-3.66), and end-stage kidney disease (ESKD; HR: 5.63, 95% CI: 4.40-7.20) were significantly associated with all-cause mortality. Adjusted HR (95% CIs) for cardiovascular mortality was significantly elevated among patients with AKI without CKD (1.78 [1.54-2.06]), CKD without AKI (2.28 [2.09-2.49]), AKI with CKD (3.99 [3.47-4.59]), and ESKD (6.46 [4.93-8.46]). In conclusion, this study shows that acute or CKD is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.Impact StatementWhat is already known on this subject? Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined.What do the results of this study add? This study shows that kidney disease is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. AKI and CKD are independent predicators for mortality in patients undergoing CAG.What are the implications of these findings for clinical practice and/or further research? These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.

Characterization of Risk Prediction Models for Acute Kidney Injury: A Systematic Review and Meta-analysis.

Importance: Despite the expansion of published prediction models for acute kidney injury (AKI), there is little evidence of uptake of these models beyond their local derivation nor data on their association with patient outcomes. Objective: To systematically review published AKI prediction models across all clinical subsettings. Data Sources: MEDLINE via PubMed (January 1946 to April 2021) and Embase (January 1947 to April 2021) were searched using medical subject headings and text words related to AKI and prediction models. Study Selection: All studies that developed a prediction model for AKI, defined as a statistical model with at least 2 predictive variables to estimate future occurrence of AKI, were eligible for inclusion. There was no limitation on study populations or methodological designs. Data Extraction and Synthesis: Two authors independently searched the literature, screened the studies, and extracted and analyzed the data following the Preferred Reporting Items for Systematic Review and Meta-analyses guideline. The data were pooled using a random-effects model, with subgroups defined by 4 clinical settings. Between-study heterogeneity was explored using multiple methods, and funnel plot analysis was used to identify publication bias. Main Outcomes and Measures: C statistic was used to measure the discrimination of prediction models. Results: Of the 6955 studies initially identified through literature searching, 150 studies, with 14.4 million participants, met the inclusion criteria. The study characteristics differed widely in design, population, AKI definition, and model performance assessments. The overall pooled C statistic was 0.80 (95% CI, 0.79-0.81), with pooled C statistics in different clinical subsettings ranging from 0.78 (95% CI, 0.75-0.80) to 0.82 (95% CI, 0.78-0.86). Between-study heterogeneity was high overall and in the different clinical settings (eg, contrast medium-associated AKI: I2 = 99.9%; P < .001), and multiple methods did not identify any clear sources. A high proportion of models had a high risk of bias (126 [84.4%]) according to the Prediction Model Risk Of Bias Assessment Tool. Conclusions and Relevance: In this study, the discrimination of the published AKI prediction models was good, reflected by high C statistics; however, the wide variation in the clinical settings, populations, and predictive variables likely drives the highly heterogenous findings that limit clinical utility. Standardized procedures for development and validation of prediction models are urgently needed.

Association of malnutrition with all-cause and cardiovascular mortality in patients with mild to severe chronic kidney disease undergoing coronary angiography: a large multicenter longitudinal study.

PURPOSE: Evidence on the prognostic impact of malnutrition was focused on patients with advanced kidney disease. The relationships between malnutrition and all-cause and cardiovascular mortality in patients with different severity of chronic kidney disease (CKD) have not been adequately addressed. We aimed to reveal the prevalence of malnutrition and its prognostic value in patients with different severity of CKD undergoing coronary angiography (CAG). METHODS: This was a multicenter, longitudinal, and retrospective cohort study of 12,652 patients with non-dialysis dependent CKD (defined as estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) undergoing CAG from five tertiary hospitals between January 2007 and December 2020. The controlling nutritional status (CONUT) score was applied to assess nutritional status. Cox regression models and competing risk Fine and Gray models were used to examine the relationships between malnutrition, all-cause and cardiovascular mortality. Further stratified analysis was performed according to baseline CKD severity (mild, moderate and severe, defined by eGFR < 30, 30-44 and 45-59 ml/min/1.73 m2). RESULTS: During a median follow-up of 5.5 years (interquartile range: 3.2 to 8.6 years), 3801 patients (30.0%) died, and 2150 (17.0%) definitely died of cardiovascular disease. After controlling for confounders, patients had higher all-cause mortality (mild, moderate, and severe vs. absent: HR 1.27, 95 CI % [1.17-1.39]; HR 1.54, 95 CI % [1.39-1.71]; HR 2.22, 95 CI % [1.78-2.77], respectively; P for trend < 0.001) and cardiovascular mortality (mild, moderate and severe vs. absent: HR 1.35, 95 CI % [1.21-1.52]; HR 1.67, 95 CI % [1.45-1.92]; HR 2.10, 95 CI % [1.55-2.85], respectively; P for trend < 0.001) with the severity of malnutrition. In further stratified analysis, a similar prognostic impact of malnutrition was observed in patients with mild to moderate CKD, while mild malnutrition did not seem to have a consistent effect on severe CKD patients. CONCLUSION: Malnutrition is common among patients with mild to severe CKD undergoing CAG and is strongly associated with increased risk of all-cause and cardiovascular mortality. Malnutrition seems to have a modestly stronger impact on mortality in patients with mild to moderate CKD. This study was registered at Clinicaltrials.gov as NCT05050877.

Renal Insufficiency Increases the Combined Risk of Left Ventricular Hypertrophy and Dysfunction in Patients at High Risk of Cardiovascular Diseases.

BACKGROUND: The identification of asymptomatic structural and functional cardiac abnormalities can help us to recognize early and intervene in patients at pre-heart failure (HF). However, few studies have adequately evaluated the associations of renal function and left ventricular (LV) structure and function in patients at high risk of cardiovascular diseases (CVD). METHODS: Patients undergoing coronary angiography and/or percutaneous coronary interventions were enrolled from the Cardiorenal ImprovemeNt II (CIN-II) cohort study, and their echocardiography and renal function were assessed at admission. Patients were divided into five groups according to their estimated glomerular filtration rate (eGFR). Our outcomes were LV hypertrophy and LV systolic and diastolic dysfunction. Multivariable logistic regression analyses were conducted to investigate the associations of eGFR with LV hypertrophy and LV systolic and diastolic dysfunction. RESULTS: A total of 5610 patients (mean age: 61.6 ± 10.6 years; 27.3% female) were included in the final analysis. The prevalence of LV hypertrophy assessed by echocardiography was 29.0%, 34.8%, 51.9%, 66.7%, and 74.3% for the eGFR categories >90, 61-90, 31-60, 16-30, and ≤15 mL/min per 1.73 m2 or for patients needing dialysis, respectively. Multivariate logistic regression analysis showed that subjects with eGFR levels of ≤15 mL/min per 1.73 m2 or needing dialysis (OR: 4.66, 95% CI: 2.96-7.54), as well as those with eGFR levels of 16-30 (OR: 3.87, 95% CI: 2.43-6.24), 31-60 (OR: 2.00, 95% CI: 1.64-2.45), and 61-90 (OR: 1.23, 95% CI: 1.07-1.42), were significantly associated with LV hypertrophy. This reduction in renal function was also significantly associated with LV systolic and diastolic dysfunction (all P for trend <0.001). In addition, a per one unit decrease in eGFR was associated with a 2% heightened combined risk of LV hypertrophy and systolic and diastolic dysfunction. CONCLUSIONS: Among patients at high risk of CVD, poor renal function was strongly associated with cardiac structural and functional abnormalities. In addition, the presence or absence of CAD did not change the associations. The results may have implications for the pathophysiology behind cardiorenal syndrome.

Podocyte Infolding Glomerulopathy: A Case Series Report and Literature Review.

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a peculiar and very rare manifestation in renal pathology. Its underlying pathogenesis mechanism and clinical characteristics remain unclear due to sparse reports. OBJECTIVE: To further elucidate the clinical profile of PIG by carefully reporting our four cases and a comprehensive review of cases in the literature. METHODS: This study retrospectively reviewed four cases of PIG from 2010 to 2022 in our centre. Clinical and pathological profiles were reported. PIG cases in the literature were searched in the MEDLINE database and analysed together with our cases. RESULTS: Four cases of PIG identified from our centre and 40 cases from the current literature were reported. The pooled analysis of these 44 cases indicated 79.5% (35/44) were females, 93.2% (41/44) were East Asians, and 63.6% (28/44) were reported in Japan. The average age was 42.0 ± 12.5 years old. The average amount of proteinuria at the time of renal biopsy was 3.06 ± 3.2 g/day. The most reported comorbidities were connective tissue diseases, mainly systemic lupus erythematosus, and 20.5% (9/44) of the cases did not have any contaminant disease. Most of the cases (81.8%, 36/44) had been treated with immunosuppressants, of which a combination of corticosteroids and one other type of immunosuppressant was most commonly reported. In addition, 45.4% (20/44) and 34.1% (15/44) of the cases had achieved complete response and partial response, respectively, after treatment. Whole exosome sequencing indicated mutations in the INF2 gene. CONCLUSIONS: PIG is a rare condition and seen in relatively younger populations, often associated with connective tissue diseases clinically and one or two other glomerulopathies histologically. The outcomes following immunosuppressive treatment are relatively good. Mutations in INF2 might be involved in the development of PIG; however, the implications of these results need to be investigated.

Prediction Models of Primary Membranous Nephropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Several statistical models for predicting prognosis of primary membranous nephropathy (PMN) have been proposed, most of which have not been as widely accepted in clinical practice. METHODS: A systematic search was performed in MEDLINE and EMBASE. English studies that developed any prediction models including two or more than two predictive variables were eligible for inclusion. The study population was limited to adult patients with pathologically confirmed PMN. The outcomes in eligible studies should be events relevant to prognosis of PMN, either disease progression or response profile after treatments. The risk of bias was assessed according to the PROBAST. RESULTS: In all, eight studies with 1237 patients were included. The pooled AUC value of the seven studies with renal function deterioration and/or ESRD as the predicted outcomes was 0.88 (95% CI: 0.85 to 0.90; I2 = 77%, p = 0.006). The paired forest plots for sensitivity and specificity with corresponding 95% CIs for each of these seven studies indicated the combined sensitivity and specificity were 0.76 (95% CI: 0.64 to 0.85) and 0.84 (95% CI: 0.80 to 0.88), respectively. All seven studies included in the meta-analysis were assessed as high risk of bias according to the PROBAST tool. CONCLUSIONS: The reported discrimination ability of included models was good; however, the insufficient calibration assessment and lack of validation studies precluded drawing a definitive conclusion on the performance of these prediction models. High-grade evidence from well-designed studies is needed in this field.

Hemorrhagic Stroke in Pregnancy.

Hemorrhagic stroke carries a high risk of disability and mortality. The obstetrical population is at increased risk. Prompt diagnosis and maternal stabilization with a multidisciplinary approach are the mainstays in management. Computed tomography head is the diagnostic imaging of choice and is considered safe in pregnancy. Fetal status optimization before neurosurgery and delivery should be considered if the fetus is viable or if worsening maternal condition. Obstetric indications guide the mode of delivery. Cesarean delivery may be indicated to reduce increasing intracranial pressure. Neuraxial anesthesia should be considered to minimize catecholamine surges, reduce sedation, and control blood pressures.

Artificial intelligence for the prediction of acute kidney injury during the perioperative period: systematic review and Meta-analysis of diagnostic test accuracy.

BACKGROUND: Acute kidney injury (AKI) is independently associated with morbidity and mortality in a wide range of surgical settings. Nowadays, with the increasing use of electronic health records (EHR), advances in patient information retrieval, and cost reduction in clinical informatics, artificial intelligence is increasingly being used to improve early recognition and management for perioperative AKI. However, there is no quantitative synthesis of the performance of these methods. We conducted this systematic review and meta-analysis to estimate the sensitivity and specificity of artificial intelligence for the prediction of acute kidney injury during the perioperative period. METHODS: Pubmed, Embase, and Cochrane Library were searched to 2nd October 2021. Studies presenting diagnostic performance of artificial intelligence in the early detection of perioperative acute kidney injury were included. True positives, false positives, true negatives and false negatives were pooled to collate specificity and sensitivity with 95% CIs and results were portrayed in forest plots. The risk of bias of eligible studies was assessed using the PROBAST tool. RESULTS: Nineteen studies involving 304,076 patients were included. Quantitative random-effects meta-analysis using the Rutter and Gatsonis hierarchical summary receiver operating characteristics (HSROC) model revealed pooled sensitivity, specificity, and diagnostic odds ratio of 0.77 (95% CI: 0.73 to 0.81),0.75 (95% CI: 0.71 to 0.80), and 10.7 (95% CI 8.5 to 13.5), respectively. Threshold effect was found to be the only source of heterogeneity, and there was no evidence of publication bias. CONCLUSIONS: Our review demonstrates the promising performance of artificial intelligence for early prediction of perioperative AKI. The limitations of lacking external validation performance and being conducted only at a single center should be overcome. TRIAL REGISTRATION: This study was not registered with PROSPERO.

Impact of renal-replacement therapy strategies on outcomes for patients with chronic kidney disease: a secondary analysis of the STARRT-AKI trial.

PURPOSE: To assess whether pre-existing chronic kidney disease (CKD) modified the relationship between the strategy for renal-replacement theraphy (RRT) initiation and clinical outcomes in the STARRT-AKI trial. METHODS: This was a secondary analysis of a multi-national randomized trial. We included patients who had documented pre-existing estimated glomerular filtration rate (eGFR) data prior to hospitalization, and we defined CKD as an eGFR ≤ 59 mL/min/1.73 m2. The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the effect of RRT initiation strategy on outcomes by CKD status. RESULTS: We studied 1121 patients who had pre-hospital measures of kidney function. Of these, 432 patients (38.5%) had CKD. The median (IQR) baseline serum creatinine was 130 (114-160) and 76 (64-90) µmol/L for those with and without CKD, respectively. Patients with CKD were older and more likely to have cardiovascular comorbidities and diabetes mellitus. Patients with CKD had higher 90-day mortality (47% vs. 40%, p < 0.001) compared to those without CKD, though this was not significant after covariate adjustment (adjusted odds ratio [aOR], 1.05; 95% CI, 0.79-1.41). Patients with CKD were more likely to remain RRT dependent at 90 days (14% vs. 8%; aOR, 1.89; 95% CI, 1.05-3.43). CKD status did not modify the effect of RRT initiation strategy on 90-day mortality. Among patients with CKD, allocation to the accelerated strategy conferred more than threefold greater odds of RRT dependence at 90 days (aOR 3.18; 95% CI, 1.41-7.91) compared with the standard strategy, whereas RRT initiation strategy had no effect on this outcome among those without CKD (aOR 0.71; 95% CI, 0.34-1.47, p value for interaction, 0.009). CONCLUSION: In this secondary analysis of the STARRT-AKI trial, an accelerated strategy of RRT initiation conferred a higher risk of 90-day RRT dependence among patients with pre-existing CKD; however, no effect was observed in the absence of CKD.

Folate regulates RNA m5C modification and translation in neural stem cells.

BACKGROUND: Folate is an essential B-group vitamin and a key methyl donor with important biological functions including DNA methylation regulation. Normal neurodevelopment and physiology are sensitive to the cellular folate levels. Either deficiency or excess of folate may lead to neurological disorders. Recently, folate has been linked to tRNA cytosine-5 methylation (m5C) and translation in mammalian mitochondria. However, the influence of folate intake on neuronal mRNA m5C modification and translation remains largely unknown. Here, we provide transcriptome-wide landscapes of m5C modification in poly(A)-enriched RNAs together with mRNA transcription and translation profiles for mouse neural stem cells (NSCs) cultured in three different concentrations of folate. RESULTS: NSCs cultured in three different concentrations of folate showed distinct mRNA methylation profiles. Despite uncovering only a few differentially expressed genes, hundreds of differentially translated genes were identified in NSCs with folate deficiency or supplementation. The differentially translated genes induced by low folate are associated with cytoplasmic translation and mitochondrial function, while the differentially translated genes induced by high folate are associated with increased neural stem cell proliferation. Interestingly, compared to total mRNAs, polysome mRNAs contained high levels of m5C. Furthermore, an integrative analysis indicated a transcript-specific relationship between RNA m5C methylation and mRNA translation efficiency. CONCLUSIONS: Altogether, our study reports a transcriptome-wide influence of folate on mRNA m5C methylation and translation in NSCs and reveals a potential link between mRNA m5C methylation and mRNA translation.