The quality evaluation system of a famous traditional Chinese medicine Huaganjian decoction was established.

Huaganjian decoction (HGJD) has been widely used clinically to treat liver injuries and gastritis. However, the quality evaluation system for HGJD is not perfect. In this study, paeoniflorin, hesperidin, geniposide, naringin, and quercetin were employed as quality markers. The quantitative analysis of these five components in HGJD was conducted using a high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry method. This method underwent validation for linearity, precision, accuracy, repeatability, and recovery. In summary, a reliable quantitative method was successfully employed to establish a comprehensive quality evaluation of HGJD.

A nomogram prediction model for treatment failure in primary membranous nephropathy.

BACKGROUND: Primary membranous nephropathy (PMN) has a heterogeneous natural course. Immunosuppressive therapy is recommended for PMN patients at moderate or high risk of renal function deterioration. Prediction models for the treatment failure of PMN have rarely been reported. METHODS: This study retrospectively studied patients diagnosed as PMN by renal biopsy at Sichuan Provincial People's Hospital from January 2017 to December 2020. Information on clinical characteristics, laboratory test results, pathological examination, and treatment was collected. The outcome was treatment failure, defined as the lack of complete or partial remission at the end of 12 months. Simple logistic regression was used to identify candidate predictive variables. Forced-entry stepwise multivariable logistic regression was used to develop the prediction model, and performance was evaluated using C-statistic, calibration plot, and decision curve analysis. Internal validation was performed by bootstrapping. RESULTS: In total, 310 patients were recruited for this study. 116 patients achieved the outcome. Forced-entry stepwise multivariable logistic regression indicated that PLA2Rab titer (OR = 1.002, 95% CI: 1.001-1.004, p = 0.003), inflammatory cells infiltration (OR = 2.753, 95% CI: 1.468-5.370, p = 0.002) and C3 deposition on immunofluorescence (OR = 0.217, 95% CI: 0.041-0.964, p = 0.049) were the three independent risk factors for treatment failure of PMN. The final prediction model had a C-statistic (95% CI) of 0.653 (0.590-0.717) and a net benefit of 23%-77%. CONCLUSIONS: PLA2R antibody, renal interstitial inflammation infiltration, and C3 deposition on immunofluorescence were the three independent risk factors for treatment failure in PMN. Our prediction model might help identify patients at risk of treatment failure; however, the performance awaits improvement.

Effects of problem-based learning on delivering medical and nursing education: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is still a lack of high-level evidence on the effects of problem-based learning (PBL) in general medical and nursing education. AIMS: We aimed to summarize current evidence on the effects of PBL in delivering medical and nursing education from randomized controlled trials (RCTs). METHODS: A systematic search was performed in MEDLINE, EMBASE, Cochrane Central Library, and CINAHL Complete. RCTs that assessed the effects of a PBL module in delivering medical education were eligible. Outcomes included knowledge, performance, and satisfaction. The risk of bias was assessed according to Cochrane handbook guidelines. Standardized mean differences with 95% confidence intervals of each outcome between PBL and control groups were pooled using a random-effects model. RESULTS: In all, 22 RCTs with 1969 participants were included. Both pooled analyses of changes in scores compared with baseline and absolute post-interventional scores favored PBL module in knowledge and performance. The satisfaction degree was also higher in participants receiving PBL methods. Publication bias might exist in satisfaction; however, not in knowledge and performance. Eleven of the 22 studies were assessed as having a high risk of bias. LINKING EVIDENCE TO ACTION: Compared with traditional lecture-based modules, PBL delivered medical education in different medical science specialities more efficiently from both theoretical knowledge and practice skill perspectives. The feedback from participants receiving PBL methods was more positive than that from those receiving traditional methods. However, the high heterogeneity and low quality of the included studies prevented drawing definite conclusions.

Estimation of 24-h Urine Protein Excretion Using Urine Albumin-to-Creatinine Ratio from an In-Hospital Population.

BACKGROUND There is little information available on quantitative description of the relationship between urine albumin-to-creatinine ratio (ACR) and 24-h urine protein excretion (24-h UPE). Here, we developed a calculation tool for 24-h UPE using the urine ACR and limited information on the request form. MATERIAL AND METHODS This was a retrospective and observational study. All individuals with same-day urine ACR and 24-h UPE tests in Sichuan Provincial People's Hospital from September 1, 2018 to December 31, 2019 were enrolled. Correlation and agreement between urine ACR and 24-h UPE were evaluated using correlation analysis and an intraclass correlation coefficient, respectively. The Durbin-Watson test and ANOVA were used to assess the performance of the calculation tool, and reliability of the prediction equation was evaluated in the validation group using residual error analysis. RESULTS A total of 906 participants were enrolled, including 639 participants in the development group and 267 in the validation group. Natural logarithm transformation was applied to remove skewness. Natural logarithm-transformed urine ACR correlated well with natural-logarithm-transformed 24-h UPE (Pearson coefficient=0.908; P<0.001) and the agreement was consistently good (overall ICC=0.938; 95% CI: 0.928-0.947; P<0.001). The multivariable regression model had good performance (R²=0.864) and high accuracy, demonstrated by results of residual error analysis. CONCLUSIONS We provide a practical calculation tool to estimate total protein excretion using urine ACR and readily accessible variables. However, 24-h UPE is still mandatory when proteinuria is over 10 g/day or when most proteinuria may not be of glomerular origin.

Value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission: a case report and literature review.

BACKGROUNDS: Published literatures on repeat renal biopsy of AL amyloidosis have basically reached a consensus that amyloid material deposit does not disappear or diminish after satisfactory hematologic response, regardless of renal response. However, the need of a repeat renal biopsy in such situation is still controversial. CASE PRESENTATION: Here we reported a case of histologically confirmed λ Type renal AL amyloidosis who had been classified as Stage I and low risk at initial diagnosis. The patient received a total of six courses of CyBorD chemotherapy. She had achieved complete hematologic remission after two courses of chemotherapy but consistently had large amount of proteinuria over 10 g/day during follow up. A repeat renal biopsy was performed nine months after the first one and indicated mild to moderate increase of amyloid deposits as well as significant glomerulosclerosis and interstitial lesions, suggesting a lack of histological renal improvement despite her satisfactory hematologic response. CONCLUSIONS: This case indicated renal involvement in AL amyloidosis could progress after successful hematologic treatment, and supported the value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission.

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.

New Criterion to Evaluate Acute-on-Chronic Kidney Injury Based on the Creatinine Reference Change.

BACKGROUND: The lack of consensus criteria of acute on chronic kidney injury (ACKI) affects the judgment for its clinical prognosis. METHODS: In this study, we analyzed the data from 711,615 hospitalized adults who had at least 2 serum creatinine (SCr) tests within 30 days. We estimated the reference change value (RCV) of SCr given initial SCr level in adults without known risks of acute kidney injury other than chronic kidney disease (CKD). We proposed a criterion for ACKI based on the RCV of SCr (cROCK), which defined ACKI as a ≥25% increase in SCr in 7 days. We validated cROCK by its association with the risks of in-hospital mortality, death after discharge, and CKD progression in a large cohort of patients with CKD stage 3. RESULTS: In 21,661 patients with CKD stage 3, a total of 3,145 (14.5%), 1,512 (7.0%), and 221 (1.0%) ACKI events were detected by both cROCK and Kidney Disease Improving Global Outcomes (KDIGO), cROCK only, and KDIGO only, respectively. cROCK detected 40% more ACKI events than KDIGO. Compared with patients without ACKI by both definitions, those with cROCK- but not KDIGO-defined ACKI had a significantly increased risk of in-hospital mortality (hazard ratio [HR] 5.53; 95% CI 3.75-8.16), death after discharge (HR 1.51; 95% CI 1.21-1.83), and CKD progression (OR 5.65; 95% CI 3.05-10.48). CONCLUSIONS: RCV-based criterion (cROCK) for ACKI is clinically valid in that it has a substantially improved sensitivity in identifying patients with high risk of adverse outcomes.

Efficacy and safety of direct-acting antiviral-based treatment in hepatitis C virus infected patients with chronic renal function impairment: An updated systemic review and meta-analysis.

OBJECTIVE: To further determine the efficacy and safety of direct-acting antiviral (DAA)-based treatments in hepatitis C virus (HCV) infected patients with renal function impairment. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched for relevant studies. All studies assessing the efficacy and safety of DAA-based treatments against HCV infection in patients with renal impairment and HCV infection were eligible for inclusion. Outcomes assessed included efficacy outcomes and safety outcomes. Summary estimates were obtained using an inverse-variance weighted random effect model and Freeman-Tukey double arcsine transformation. RESULTS: Twenty-seven studies (n = 1048 participants) were included. The majority of included studies were of fair quality with Newcastle-Ottawa scale scores between 4 and 6. The pooled virologic response rates at the end of treatment or 4, 12, 24 weeks after treatment (ie, EOTR, SVR4, SVR12 and SVR24 rates) were 97.0% (95% confidence interval [CI], 94.0%-99.0%), 80.9% (95% CI, 49.3%-98.7%), 94.1% (95% CI, 91.6%-96.3%) and 89.6% (95% CI, 75.5%-98.1%), respectively. The pooled relapse rate was 6.4% (95% CI, 3.4%-10.4%). The pooled incidence of adverse events and severe adverse events leading to discontinuation were 47.6% (95% CI, 35.0%-60.4%) and 2.9% (95% CI, 1.4%-5.0%), respectively. High heterogeneity among studies exists for SVR4 and SVR24 rates. Formal statistical testing did not identify the presence of publication bias for all measured outcomes except the relapse rate. CONCLUSION: The results support the efficacy and safety of DAA-based treatments in this population. Future studies with better design, larger sample size and longer follow up will be the next step. SUMMARY AT A GLANCE This systematic review evaluated the efficacy and safety of direct-acting antiviral based therapies in hepatitis C infection in patients with renal impairment. The majority of studies were of fair quality only. These therapies were found to be highly efficacious although there were high rates of adverse events.

A New Criterion for Pediatric AKI Based on the Reference Change Value of Serum Creatinine.

BACKGROUND: Current definitions of AKI do not take into account serum creatinine's high variability in children. METHODS: We analyzed data from 156,075 hospitalized children with at least two creatinine tests within 30 days. We estimated reference change value (RCV) of creatinine on the basis of age and initial creatinine level in children without kidney disease or known AKI risk, and we used these data to develop a model for detecting pediatric AKI on the basis of RCV of creatinine. We defined pediatric AKI according to pediatric reference change value optimized for AKI in children (pROCK) as creatinine increase beyond RCV of creatinine, which was estimated as the greater of 20 µmol/L or 30% of the initial creatinine level. RESULTS: Of 102,817 children with at least two serum creatinine tests within 7 days, 5432 (5.3%) had AKI as defined by pROCK compared with 15,647 (15.2%) and 10,446 (10.2%) as defined by pediatric RIFLE (pRIFLE) and Kidney Disease Improving Global Outcomes (KDIGO), respectively. Children with pROCK-defined AKI had significantly increased risk of death (hazard ratio, 3.56; 95% confidence interval, 3.15 to 4.04) compared with those without AKI. About 66% of patients with pRIFLE-defined AKI and 51% of patients with KDIGO-defined AKI, mostly children with initial creatinine level of <30 µmol/L, were reclassified as non-AKI by pROCK, and mortality risk in these children was comparable with risk in those without AKI by all definitions. CONCLUSIONS: pROCK criterion improves detection of "true" AKI in children compared with earlier definitions that may lead to pediatric AKI overdiagnosis.

Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone.

Propofol is widely used in clinical practice, including non-obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post-natal day 30. Two hours before each MWM trial, histone deacetylase 2 (HDAC2) inhibitor, suberoylanilide hydroxamic acid (SAHA), Senegenin (SEN, traditional Chinese medicine), hippyragranin (HGN) antisense oligonucleotide (HGNA) or vehicle were given to the offspring. The protein levels of HDAC2, acetylated histone 3 (H3) and 4 (H4), cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), N-methyl-D-aspartate receptor (NMDAR) 2 subunit B (NR2B), HGN and synaptophysin in offspring's hippocampus were determined by Western blot or immunofluorescence test. It was discovered that infusion with propofol in maternal rats on E7 leads to impairment of learning and memory in offspring, increased the protein levels of HDAC2 and HGN, decreased the levels of acetylated H3 and H4 and phosphorylated CREB, NR2B and synaptophysin. HDAC2 inhibitor SAHA, Senegenin or HGN antisense oligonucleotide reversed all the changes. Thus, present results indicate exposure to propofol during the early gestation impairs offspring's learning and memory via inhibiting histone acetylation. SAHA, Senegenin and HGN antisense oligonucleotide might have therapeutic value for the adverse effect of propofol.

The value of non-invasive measurement of cardiac output and total peripheral resistance to categorize significant changes of intradialytic blood pressure: a prospective study.

BACKGROUND: Blood pressure (BP) is currently the main hemodynamic parameter used to assess the influence of fluid removal during hemodialysis session. Since BP is dependent on cardiac output (CO) and total peripheral resistance (TPRI), investigating these parameters may help to better understand the influence of fluid removal on patient's hemodynamics. We used a novel non-invasive whole-body bio-impedance cardiography device, recently validated in hemodialysis patients, to examine mechanisms of intradialytic hemodynamics in a Chinese dialysis population. METHODS: Chronic hemodialysis patients in Sichuan Provincial People's Hospital were enrolled. Demographic data and dialysis prescriptions were collected. Hemodynamic measurements were made pre-treatment, every 20 min during treatment and immediately after treatment in each random dialysis session. These included blood pressure, cardiac index (CI), total peripheral resistance (TPRI) and cardiac power index (CPI). Patients were divided into 5 hemodynamic groups as per their major hemodynamic response to fluid removal: low CPI, low TPRI, high TPRI, High CPI and those with normal hemodynamics. RESULTS: Twenty-seven patients were enrolled, with 12 (44.4%) males. The average age was 65 ± 12 y. The average body mass index (BMI) was 23.7 ± 3.9 kg/m2. 12 (44.4%) patients were diabetic. Three hundred twenty-four hemodynamic measurements were made. Weight, BMI, total fluid removal, pretreatment systolic BP, CI, TPRI and CI differed significantly among the 5 hemodynamic groups.11.1% of patients had low CPI, 25.9% had low TPRI, 18.5% had high CPI, 3.7% had high TPRI and 40.7% had normal hemodynamics. Hemodynamic differences among the 5 subgroups were significant. CONCLUSION: This technology provides multi-dimensional insight into intradialytic hemodynamic parameters, which may be more informative than blood pressure only. Using hemodynamic parameters to describe patients' status is more specific and accurate, and could help to work out specific and effective therapeutic actions according to underlying abnormalities.

Renal replacement therapy in acute kidney injury from a Chinese cross-sectional study: patient, clinical, socioeconomic and health service predictors of treatment.

BACKGROUND: Renal replacement therapy (RRT) is important to support critically ill patients with acute kidney injury (AKI). This study, a part of a nation-wide survey for AKI conducted by the ISN AKF 0 by 25 China Consortium, aims to study the current RRT practical situation and problems in China. METHODS: The current study is a part of a nation-wide survey for AKI conducted by ISN AKF 0 by 25 China Consortium. The survey included 44 sites all over the country, including 22 academic hospitals in big cities and 22 local hospitals in smaller cities or rural areas. Of the 44 sites, all have access to PD and IHD, 93.5% are capable to perform CRRT. Of total 7604 AKI cases, 896 cases (11.8%) had indications for RRT and were included in the current abstract. RESULTS: of the 896 patients that had indications for RRT, only 59.3% received RRT. Patients who were older, male, from lower income areas, in local hospitals, or with severe comorbidities, were less likely to receive RRT. RRT treatment was associated with lower mortality (OR = 0.58, 95%CI 0.38-0.89). The RRT modalities were continuous renal replacement therapy (CRRT) in 53.9%, intermittent hemodialysis (IHD) in 38.0%, CRRT complemented by IHD in 6.2%, CRRT complemented by peritoneal dialysis (PD) in 0.8% and PD in 1.1%. Of the subgroup of patients receiving RRT who did not have an indication for modality of CRRT, 36.8% in fact received CRRT, and their medical cost and mortality rate was higher (7944[4248, 16,055] vs. 5100[2948, 9396] US dollars, p < 0.001 and 10.6% vs. 4.4%, p = 0.047, respectively) compared with those treated with other RRT modalities). CONCLUSIONS: Extrapolated to the whole of China our results indicate that an estimated 139,000 patients with an indication of RRT are under treated without RRT over a year. Non-clinical factors influence RRT prescription for severe AKI patients. CRRT may be over-utilized in the treatment of severe AKI and the use of PD is extremely rare. These findings have implications for the effective application of medical resources in the treatment of severe AKI.

Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF-TrkB signalling pathway.

The brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) (BDNF-TrkB) signalling pathway plays a crucial role in regulating learning and memory. Synaptophysin provides the structural basis for synaptic plasticity and depends on BDNF processing and subsequent TrkB signalling. Our previous studies demonstrated that maternal exposure to propofol during late stages of pregnancy impaired learning and memory in rat offspring. The purpose of this study is to investigate whether the BDNF-TrkB signalling pathway is involved in propofol-induced learning and memory impairments. Propofol was intravenously infused into pregnant rats for 4 hrs on gestational day 18 (E18). Thirty days after birth, learning and memory of offspring was assessed by the Morris water maze (MWM) test. After the MWM test, BDNF and TrkB transcript and protein levels were measured in rat offspring hippocampus tissues using real-time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. The levels of phosphorylated-TrkB (phospho-TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure to propofol on day E18 impaired spatial learning and memory of rat offspring, decreased mRNA and protein levels of BDNF and TrkB, and decreased the levels of both phospho-TrkB and synaptophysin in the hippocampus. Furthermore, the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) reversed all of the observed changes. Treatment with 7,8-DHF had no significant effects on the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory of offspring by disturbing the BDNF-TrkB signalling pathway. The TrkB agonist 7,8-DHF might be a potential therapy for learning and memory impairments induced by maternal propofol exposure.

Suboptimal vitamin K status and its risk factors in a population of Chinese chronic haemodialysis patients.

AIMS: Vitamin K deficiency is known to be common in haemodialysis patients and associates with adverse outcomes in this population, particularly vascular calcification. We aimed to investigate the vitamin K status in a population of Chinese haemodialysis (HD) patients. METHODS: We collected demographic and biochemical data from a population of maintenance HD (MHD) patients in our unit and a control group composed of healthy subjects from our outpatient clinic. Fasting serum samples from all subjects were collected for the measurement of known vitamin K-dependent proteins i.e. matrix Gla protein (MGP), osteocalcin (OC) and uncarboxylated osteocalcin (ucOC). We also quantified the fraction of ucOC to total OC (%ucOC). Differences of these parameters between groups were analyzed and risk factors of vitamin K deficiency based on the definition as per %ucOC were investigated. RESULTS: We enrolled 93 MHD patients as a test group and 93 healthy subjects as a control group. There was no significant difference in MGP between groups (4.0 ± 2.8 pg/mL in MHD vs 4.2 ± 1.2 pg/mL in control; P = 0.676). Mean %ucOC was significantly greater in the MHD patients as compared to control subjects (76.4 ± 20.0% in MHD vs 48.56 ± 15.5%; P < 0.001). Time on dialysis and low-density lipoprotein cholesterol level appeared to be indicators of vitamin K deficiency, with the former being an independent risk factor. CONCLUSIONS: Defining Vitamin K deficiency by %ucOC, suboptimal vitamin K levels appear common in Chinese MHD patients. Time on dialysis and LDL cholesterol level predict vitamin K deficiency.

Relationship of cystatin-C change and the prevalence of death or dialysis need after acute kidney injury: a meta-analysis.

AIM: Cystatin-C (CysC) has been demonstrated as a sensitive and reliable biomarker to predict the onset of acute kidney injury (AKI). However, there are few studies concerned about the relationship between CysC and the outcomes of AKI. The aim of the present study was to determine whether CysC elevation prior to definite diagnosis of AKI is related to higher prevalence of death and dialysis need outcome. METHODS: A meta-analysis was conducted by searching PubMed, EMBASE and Cochrane Library database using the terms related to AKI combined with 'cystatin-C'. Bibliographies of relevant papers were reviewed manually. Eligible studies were those investigating death and dialysis need outcomes after AKI with CysC measurement, and were limited to English articles. Non-human studies were excluded. Random effect Mantel-Haenszel statistical method was used. RESULTS: Six studies were finally enrolled, consisting of 2332 patients. All of these studies were hospital-based prospective cohort studies. The follow-up duration varied from 5 days to 1 year. The odds ratio values for baseline CysC elevation and death as well as baseline CysC elevation and dialysis need were 2.34 (95% confidence interval [CI] 1.46-3.75) and 4.40 (95% CI 1.58-12.22), respectively (both P < 0.05). CONCLUSION: Patients with CysC elevated prior to AKI diagnosis have higher risk to develop death and need dialysis during short- and long-term follow-up after AKI, thus having worse outcomes. This population deserves more careful observation and might benefit from more frequent follow-up visits in the clinic. Future work is needed to get a consensus cut-off value defining CysC elevation.

Hyperuricemia and acute kidney injury secondary to spontaneous tumor lysis syndrome in low risk myelodysplastic syndrome.

BACKGROUND: This is a rare instance of acute kidney injury caused by hyperuricemia due to spontaneous tumor lysis syndrome and also the first case of spontaneous tumor lysis syndrome reported in association with myelodysplastic syndrome. CASE PRESENTATION: A 53-year-old man presented with abrupt oliguria. Laboratory findings on admission included hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis and rapidly rising serum creatinine, which were consistent with acute tumor lysis syndrome in the absence of precipitating chemotherapy or radiotherapy. After hemodialysis and oral uric acid lowering therapy, serum uric acid levels returned to normal range and renal function rapidly recovered. The patient was diagnosed as myelodysplastic syndrome eleven months later. CONCLUSIONS: Occult malignancy including solid tumors and hematological malignancies should be carefully evaluated in the case of unexplainable acute kidney injury with hyperuricemia. Aggressive investigations should be thoroughly considered and repeated in this population.

Suberoylanilide hydroxamic acid attenuates cognitive impairment in offspring caused by maternal surgery during mid-pregnancy.

Some pregnant women have to experience non-obstetric surgery during pregnancy under general anesthesia. Our previous studies showed that maternal exposure to sevoflurane, isoflurane, propofol, and ketamine causes cognitive deficits in offspring. Histone acetylation has been implicated in synaptic plasticity. Propofol is commonly used in non-obstetric procedures on pregnant women. Previous studies in our laboratory showed that maternal propofol exposure in pregnancy impairs learning and memory in offspring by disturbing histone acetylation. The present study aims to investigate whether HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) could attenuate learning and memory deficits in offspring caused by maternal surgery under propofol anesthesia during mid-pregnancy. Maternal rats were exposed to propofol or underwent abdominal surgery under propofol anesthesia during middle pregnancy. The learning and memory abilities of the offspring rats were assessed using the Morris water maze (MWM) test. The protein levels of histone deacetylase 2 (HDAC2), phosphorylated cAMP response-element binding (p-CREB), brain-derived neurotrophic factor (BDNF), and phosphorylated tyrosine kinase B (p-TrkB) in the hippocampus of the offspring rats were evaluated by immunofluorescence staining and western blot. Hippocampal neuroapoptosis was detected by TUNEL staining. Our results showed that maternal propofol exposure during middle pregnancy impaired the water-maze learning and memory of the offspring rats, increased the protein level of HDAC2 and reduced the protein levels of p-CREB, BDNF and p-TrkB in the hippocampus of the offspring, and such effects were exacerbated by surgery. SAHA alleviated the cognitive dysfunction and rescued the changes in the protein levels of p-CREB, BDNF and p-TrkB induced by maternal propofol exposure alone or maternal propofol exposure plus surgery. Therefore, SAHA could be a potential and promising agent for treating the learning and memory deficits in offspring caused by maternal nonobstetric surgery under propofol anesthesia.

Adverse renal outcomes following targeted therapies in renal cell carcinoma: a systematic review and meta-analysis.

Introduction: To clarify the prevalence of adverse renal outcomes following targeted therapies in renal cell carcinoma (RCC). Methods: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Central Library. Studies that had reported adverse renal outcomes following targeted therapies in RCC were eligible. Outcomes included adverse renal outcomes defined as either renal dysfunction as evidenced by elevated serum creatinine levels or the diagnosis of acute kidney injury, or proteinuria as indicated by abnormal urine findings. The risk of bias was assessed according to Cochrane handbook guidelines. Publication bias was assessed using Funnel plot analysis and Egger Test. Results: The occurrences of the examined outcomes, along with their corresponding 95% confidence intervals (CIs), were combined using a random-effects model. In all, 23 studies including 10 RCTs and 13 observational cohort studies were included. The pooled incidence of renal dysfunction and proteinuria following targeted therapies in RCC were 17% (95% CI: 12%-22%; I2 = 88.5%, p < 0.01) and 29% (95% CI: 21%-38%; I2 = 93.2%, p < 0.01), respectively. The pooled incidence of both types of adverse events varied substantially across different regimens. Occurrence is more often in polytherapy compared to monotherapy. The majority of adverse events were rated as CTCAE grades 1 or 2 events. Four studies were assessed as having low risk of bias. Conclusion: Adverse renal outcomes reflected by renal dysfunction and proteinuria following targeted therapies in RCC are not uncommon and are more often observed in polytherapy compared to monotherapy. The majority of the adverse events were of mild severity. Systematic Review Registration: Identifier CRD42023441979.

[18F] AlF-NOTA-FAPI-04 PET/CT for non-invasive assessment of tubular injury in kidney diseases.

Background: [18F] AlF-NOTA-FAPI-04 is a novel positron emission tomography (PET) ligand, which specifically targets fibroblast activation protein (FAP) expression as a FAP inhibitor (FAPI). We analysed the diagnostic value of [18F] AlF-NOTA-FAPI-04 PET/CT for the non-invasive assessment of kidney interstitial inflammation and fibrosis in different renal pathologies. Methods: Twenty-six patients (14 males and 12 females; mean age, 50.5 ± 16.5 years) with a wide range of kidney diseases and 10 patients (six males and four females; mean age, 55.4 ± 8.6 years) without known evidence of renal disease as disease controls underwent [18F] AlF-NOTA-FAPI-04 PET/CT imaging. Kidney tissues obtained from kidney biopsies were stained with haematoxylin and eosin, periodic acid-Schiff, Masson's trichome, and periodic acid-silver methenamine. Immunohistochemical staining was also performed to assess the expression of α-smooth muscle actin (αSMA) and FAP. Renal parenchymal FAPI uptake reflected by maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) measurements on PET/CT was analysed against pathohistological findings. Results: We found that renal parenchymal FAPI uptake was significantly higher in patients with various kidney diseases than in control patients in this study (SUVmax = 4.3 ± 1.8 vs 1.9 ± 0.4, SUVmean=3.9 ± 1.7 vs 1.5 ± 0.4, respectively; all P < 0.001). All kidney diseases, both in acute and chronic kidney disease, had increased renal parenchymal uptake to varying degrees. The correlation analysis indicated a positive association between the SUVmax and the tubulointerstitial inflammation (TII), interstitial fibrosis and tubular atrophy (IF/TA), and TII + IF/TA scores (r = 0.612, 0.681, and 0.754, all P < 0.05), and between the SUVmean and the TII, IF/TA, and TII + IF/TA scores (r = 0.603, 0.700, and 0.748, all P < 0.05). Furthermore, we found significant positive correlations between both SUVmax and the SUVmean with SMA and FAP staining scores (r = 0.686 and 0.732, r = 0.667 and 0.739, respectively; both P < 0.001). Conclusions: [18F] AlF-NOTA-FAPI-04 PET/CT is clinically available for the comprehensive and non-invasive assessment of tubular injury in various kidney diseases.