Analysis of risk factors associated with diffuse alveolar haemorrhage in patients with ANCA-associated vasculitis and construction of a risk prediction model using line graph.

OBJECTIVES: This study aims to analyse the risk factors associated with diffuse alveolar haemorrhage (DAH) in patients with ANCA-associated vasculitis (AAV) and construct a risk prediction model using line graph. METHODS: A retrospective study was conducted from January 2012 to May 2023 at the First Clinical College of Three Gorges University, focusing on patients diagnosed with AAV. Clinical and laboratory data were collected from these patients. The potential predictors subsets of high-risk AAV combined with DAH were screened by LASSO regression and 10-fold cross-validation method, and determined by using multivariate Logistic regression analysis, then were used for developing a prediction nomogram for high-risk AAV combined with DAH using the R software. ROC curve analysis was used to validate the model's stability. Internal validation was performed using a bootstrap method. The discrimination of the nomogram was determined by calculating the average consistency index(C-index). The calibration curve was used to assess the calibration of the nomogram. RESULTS: A total of 234 patients with AAV were included, among whom 85 developed DAH, with an incidence rate of 36%, and the average age was 63±12. Multivariable logistic regression analysis showed that Age [OR=1.037 (95%CI: 1.006, 1.071), p=0.019], platelet count (PLT) [OR=0.996 (95%CI: 0.992, 0.999), p=0.029], ESR [OR=1.028 (95%CI: 1.015, 1.042), p<0.01], HB [OR=0.978 (95%CI: 0.959, 0.996), p=0.024], and haematuria [OR=3.77 (95%CI: 1.677, 8.976), p=0.001] were found to be independent predictors of AAV combined with DAH and were used to construct a nomogram. The AUCROC values of the nomogram for DAH in AAV patients was 0.852 (95%CI: 0.801, 0.903), and the C-index could reach 0.824 after internal verification, showing good differentiation and consistency. CONCLUSIONS: The new nomogram, which included age, Hb, ESR, PLT and haematuria as variables, had the potential to predict the risk of AAV patients complicated with DAH.

A simplified and sensitive LC-APCI-MS/MS method for the quantification of propofol: Application to a bioequivalence study in healthy Chinese subjects.

OBJECTIVES: Propofol has become the preferred anesthetic in recent years due to its desirable pharmacologic properties. However, propofol possesses a very narrow therapeutic window between the favorable clinical effect and potentially lethal toxicity, therefore, a rapid, simplified, and sensitive liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) method is presented in this study for the quantification of propofol in human plasma using the isotope-labeled internal standard (IS) of propofol-d17, and then applied in a bioequivalence study. MATERIALS AND METHODS: Sample preparation was accomplished through simple one-step precipitation of plasma protein with acetonitrile. Chromatographic separation was acquired on an ACE Excel 3 Super C18 column (2.1 × 50 mm, 3 µm) using gradient elution at a flow rate of 0.5 mL/min. The MS detection was achieved in the negative ion APCI by multiple reaction monitoring (MRM) mode using the transitions of m/z 177.2 → 161.0 for propofol and m/z 194.2 → 174.2 for IS, respectively. 30 healthy Chinese subjects were enrolled in the open-label, randomized, two-period, two-sequence, cross-over bioequivalence study after single-dose intravenous administration of propofol medium-chain triglyceride and long-chain triglyceride (MCT/LCT). RESULTS: The current method was precise and accurate at a linearity range of 4.00 - 1,000 ng/mL without severe interference from the plasma matrix. The inter- and intra-batch precision (2.3 to 15.8%) and accuracy (-4.4 to 3.0%), IS-normalized matrix effect (coefficient of variation ≤ 4.6%), extraction recovery (107.1 - 117.1%), stability (coefficient of variation ≤ 8.0%), and dilution integrity were all within the acceptable range. The 90% confidence intervals (CIs) of the ratios of the geometric means (test/reference) were 86.44 - 104.88% for Cmax, 96.30 - 104.52% for AUC0-t, and 96.56 - 105.05% for AUC0-∞, which were all within the predefined bioequivalence range of 80 - 125%. Besides, both propofol MCT/LCT preparations were well tolerated in healthy Chinese subjects, and there were no serious adverse events during the study. CONCLUSION: The method is more simplified and sensitive than the previously reported modes of propofol detection. The two propofol MCT/LCT preparations were considered to be bioequivalent.

Roxithromycin regulates intestinal microbiota and alters colonic epithelial gene expression.

The specialty of gastroenterology will be affected profoundly by the ability to modify the gastrointestinal microbiota through the use of antibiotics. This study investigated the in vivo effect of roxithromycin on gut bacteria and gene expression of colonic epithelial cells (CECs) using microbial 16S rDNA and colonic epithelial cell RNA sequencing, respectively. The results showed that roxithromycin distinctly lowered the microbial diversity in both the small intestine and cecum and altered the compositions of bacteria at both the phylum and genus levels, including the reduction of some bacteria beneficial to the hosts' health. Eight decreased and 8 increased genera in the small intestine and 17 decreased and 4 increased genera of bacteria in the cecum were most affected by roxithromycin consumption. This consumption further altered the CECs' expression of multiple genes. Thirty-one genes, which were significantly enriched in seven KEGG pathways and related to immune response, wound healing, and fibrosis, were significantly affected. Roxithromycin ingestion in healthy hosts, therefore, might lead to some undesirable consequences via affecting hosts' gut microbiota and CECs. Our work offers a more comprehensive understanding of the impact of consuming roxithromycin on human health.

Efficacy and safety of implantable vascular support in the treatment of arteriovenous fistula: A single-arm meta-analyses.

BACKGROUND AND OBJECTIVES: VasQ (Laminate Medical Technologies, Israel) is an external support device for autologous arteriovenous fistula (AVF) designed to improve anastomotic blood flow and reduce neointimal hyperplasia. However, different studies have shown that the efficacy of the VasQ device in improving AVF is inconsistent. The purpose of this study was to conduct a meta-analysis to further evaluate the efficacy and safety of the VasQ device. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Two reviewers independently searched studies published in PubMed, EMBASE, Cochrane, Web of Science, CNKI, and Wan Fang databases from inception to 2023. The Cochrane Systematic Evaluation Bias Risk Tool Version 1 was used to assess the risk of RCTS bias. The ROBINS-I tool was used to assess the risk of bias in non-randomized studies. A Single-arm meta-analysis was performed, and a random effects model was used for all analyses. RESULTS: We identified six trials involving 146 patients and conducted a meta-analysis. The results showed that after 6 months of VasQ device treatment, the primary patency rate of AVF was [76.4% (95%CI: 0.608-0.920), p < 0.01] while the secondary patency rate was [76.5% (95%CI: 0.572-0.958), p < 0.01]. The maturity rate of AVF 1 month after surgery was [88.5% (95%CI: 0.818-0.952), p = 0.46]. The incidence of anastomotic stenosis was [8.9% (95%CI: 0.015-0.163), p = 0.23], and the incidence of anastomotic venous thrombosis was [10% (95%CI: 0.035-0.179), p = 0.38]. CONCLUSIONS: Meta-analysis data of this study show that the VasQ device has a good effect in improving the patency rate of AVF and does not increase the occurrence of adverse events. However, due to the limitation of the number and quality of included studies, more high-quality studies are needed to confirm this in the future.

The efficacy and safety of SGLT2 inhibitors in patients with non-diabetic chronic kidney disease: a systematic review and meta-analysis.

PURPOSE: In recent years, increasing evidence has shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) drugs have potential renoprotective effects in patients with diabetes mellitus (DM). However, the renal protective effect of SGLT2i in non-diabetic nephropathy patients has not been extensively demonstrated. In this systematic review and meta-analysis, we aimed to evaluate the renal protective effect and safety of SGLT2i in non-diabetic nephropathy patients. METHODS: we searched for relevant clinically randomised controlled trials and analyzed the effects of SGLT2i on estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (UACR), and systolic blood pressure (SBP) and the incidence of adverse events in patients with non-diabetic nephropathy. RESULTS: We collated and analysed clinical data from six groups of patients with nondiabetic nephropathy. It was found that the SGLT2i significantly delayed the decline in eGFR [MD = 1.35 ml/min/1.73 m2, 95% CI 0.84, 1.86), P < 0.0001]. Furthermore, the SGLT2i significantly reduced UACR [MD = - 24.47% l, 95% CI (- 38.9, -10.04), P = 0.0009], and showed a greater decrease in SBP [MD = - 4.13 mmHg, 95% CI (- 7.49, - 0.77), P = 0.02]. There was no significant difference in the incidence of adverse reactions between dapagliflozin/empagliflozin and the control group [OR = 1.14, 95% CI (0.88, 1.47), P = 0.33]. CONCLUSION: This study shows that SGLT2i help to delay the progression of non-diabetic kidney disease. Therefore, SGLT2i may contribute to the general treatment of nondiabetic nephropathy.

The safety and efficacy of tolvaptan in the treatment of patients with autosomal dominant polycystic kidney disease: A systematic review and meta-analysis.

BACKGROUND: The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD. METHODS: Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software. RESULTS: We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD=1.89, 95% CI (0.74, 3.04), P=0.001] and total kidney volume (TKV) [MD=-3.32, 95% CI (-4.57, -2.07), P<0.001] were delayed in tolvaptan group compared with placebo group in ADPKD patients. The use of tolvaptan delayed TKV progression in the different-month subgroups [MD=-69.99, 95% CI (-91.05, -48.94), P<0.001]. Tolvaptan reduced renal pain [RR=0.66, 95% CI (0.54, 0.81), P<0.001] and hematuria events [RR=0.55, 95% CI (0.41, 0.74), P<0.001] in ADPKD patients. However, the prevalence of thirst [RR=2.75, 95% CI (2.34, 3.24), P<0.001] and nocturia events [RR=3.01, 95% CI (1.27, 7.11), P=0.01] were increased in tolvaptan group. There is no significant difference of hypertension events [RR=0.92, 95% CI (0.82, 1.03), P=0.13] in tolvaptan group compared placebo group. CONCLUSIONS: This meta-analysis suggests that tolvaptan may improve clinical progression in patients with ADPKD without significantly increasing the risk of adverse reactions.

Alliin alters gut microbiota and gene expression of colonic epithelial tissues.

Alliin is a natural organosulfur-containing phytochemical in garlic. It is possible that alliin can regulate the gut microbiota for its strong antimicrobial activity against many pathogens. Here, we assessed whether alliin impacts the distal small intestinal bacteria, hence the cecal microbiota, thus altering the gene expression of colonic epithelial tissues (CETs). Eighty mg/kg alliin was orally administered to rats for 14 days, and the 16S rDNA from small intestinal and cecal microbiota as well as mRNA from CETs were sequenced and analyzed. The results showed that alliin consumption affected microbiota composition in both the small intestine and cecum, although there was only one specific genus, Allobaculum that was significantly altered in the rat cecum. The altered composition of microbiota indirectly impacted 174 genes in the CETs. Specifically, five genes, including RT1-Ba, RT1-Bb, Cd80, Madcam1, and Aicda, indicated this consumption related to the intestinal immune network for IgA production. PRACTICAL APPLICATIONS: We firstly reported alliin consumption in vivo potentially affected the intestinal immunity of healthy rats by slightly alteration of microbiota composition in small intestine and cecum. The alteration subsequently amplified, resulting in the change of the colonic epithelial expression of several genes related to the intestinal immune network for IgA production. Hence, we suggested the alliin consumption may potentially affect the immune system of healthy individuals by alteration of gut microbiota and epithelial gene expression.

The safety and efficacy of tolvaptan in the treatment of patients with autosomal dominant polycystic kidney disease: A systematic review and meta-analysis / Seguridad y eficacia de tolvaptan en el tratamiento de los pacientes con enfermedad renal poliquística autosómica dominante: Revisión sistemática y metaanálisis

Background The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD. Methods Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software. Result We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD=1.89, 95% CI (0.74, 3.04), P=0.001] and total kidney volume (TKV) [MD=−3.32, 95% CI (−4.57, −2.07), P<0.001] were delayed in tolvaptan group compared with placebo group in ADPKD patients. The use of tolvaptan delayed TKV progression in the different-month subgroups [MD=−69.99, 95% CI (−91.05, −48.94), P<0.001]. Tolvaptan reduced renal pain [RR=0.66, 95% CI (0.54, 0.81), P<0.001] and hematuria events [RR=0.55, 95% CI (0.41, 0.74), P<0.001] in ADPKD patients. However, the prevalence of thirst [RR=2.75, 95% CI (2.34, 3.24), P<0.001] and nocturia events [RR=3.01, 95% CI (1.27, 7.11), P=0.01] were increased in tolvaptan group. There is no significant difference of hypertension events [RR=0.92, 95% CI (0.82, 1.03), P=0.13] in tolvaptan group compared placebo group. Conclusions This meta-analysis suggests that tolvaptan may improve clinical progression in patients with ADPKD without significantly increasing the risk of adverse reactions (AU)

Antecedentes La progresión irreversible de la enfermedad renal poliquística autosómica dominante (ERPAD) a enfermedad renal en etapa final (ESRD) es demorada por tolvaptan. Por tanto, nuestro objetivo fue estimar y calcular sistemáticamente la eficacia y seguridad de tolvaptan en el tratamiento de ERPAD. Métodos Dos revisores buscaron de manera independiente todos los estudios publicados sobre ensayos controlados aleatorizados en las bases de datos de PubMed, Embase, Web of Science y Cochrane, extrayendo datos, evaluando el riesgo de sesgo y calificando la calidad de la evidencia. Los datos fueron analizados utilizando el software RevMan. Resultados Identificamos ocho ensayos, que incluyeron 2.135 pacientes. Tanto la reducción de la tasa de filtración glomerular estimada (eGFR) [MD=1,89, IC 95% (0,74, 3,04), p=0,001] como el volumen renal total (VRT) [MD=−3,32, IC 95% (−4,57, −2,07), p<0,001] se demoraron en el grupo tolvaptan, en comparación con el grupo placebo en los pacientes con ERPAD. El uso de tolvaptan demoró la progresión del VRT en los subgrupos de diferentes meses [MD=−69,99, IC 95% (−91,05, −48,94), p<0,001]. Tolvaptan redujo el dolor renal [RR=0,66, IC 95% (0,54, 0,81), p<0,001] y los episodios de hematuria [RR=0,55, IC 95% (0,41, 0,74), p<0,001] en los pacientes con ERPAD. Sin embargo, la prevalencia de episodios de sed [RR=2,75, IC 95% (2,34, 3,24), p<0,001] y nocturia [RR=3,01, IC 95% (1,27, 7,11), p=0,01] se incrementó en el grupo tolvaptan. No existe diferencia significativa en cuanto a episodios de hipertensión [RR=0,92, IC 95% (0,82, 1,03), p=0,13] en el grupo tolvaptan, en comparación con el grupo placebo. Conclusiones Este metaanálisis sugiere que tolvaptan puede mejorar la progresión clínica en los pacientes con ERPAD, sin incrementar significativamente el riesgo de reacciones adversas (AU)