Clinical application of vancomycin TDM in ventilated patients with gastrointestinal cancer: a propensity-matched analysis.

BACKGROUND: Therapeutic drug monitoring (TDM) of vancomycin is widely recommended for clinical treatment. Due to the complexity of 24-h area under the curve (AUC) guided vancomycin monitoring in clinical practice, the vancomycin trough level remains the most common and practical method. The purpose of this study was designed to investigate the differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods, and further explore the clinical application of trough-guided vancomycin monitoring in patients with gastrointestinal cancer requiring mechanical ventilation. METHODS: We included a total of 78 gastrointestinal cancer patients who required mechanical ventilation due to various diseases. All patients included in this study were aged 18 years or older and were treated with intravenous vancomycin therapy for more than 2 days due to documented or suspected Gram-positive bacterial infections, and have at least one available vancomycin plasma concentration. First, we compared the safety and efficacies of vancomycin TDM based on different monitoring methods as trough-guided monitoring or AUC-guided monitoring. Then, based on whether the initial vancomycin concentration achieving the target trough concentration (less than 48 h), patients were divided into early and delayed groups, and the clinical factors were compared between them. The primary endpoints include the incidence of new-onset acute kidney injury (AKI) or renal replacement therapy (RRT), clinical success rate and 28-day all-cause mortality. Finally, the overall relationship between trough concentration and potential covariates is screened by univariate and multivariate analysis to explore potential information covariates. RESULTS: The research revealed that patients with gastrointestinal cancer exhibited significantly lower initial vancomycin trough concentrations (median [interquartile range (IQR)]: 6.90[5.28-11.20] mg/L). And there were no statistically significant differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods for the primary endpoint. Moreover, base on trough-guided vancomycin monitoring, the early group demonstrated a notably shorter duration of mechanical ventilation compared with the delayed group (χ2 = 4.532; p < 0.05; Fig. 2E). Propensity score weighting further confirmed that the duration of mechanical ventilation (χ2 = 6.607; p < 0.05; Fig. 2F) and duration of vasoactive agent (χ2 = 6.106; p < 0.05; Fig. 2D) were significantly shorter in the early group compared with delayed group. Multivariate regression analysis revealed that Cystatin C (Cys-C) was the most important variable for vancomycin target trough achievement (odds ratio, 5.274; 95% CI, 1.780 to 15.627; p = 0.003). CONCLUSIONS: Trough-guided vancomycin monitoring is a simple and effective marker of TDM for ventilated patients with gastrointestinal cancer. Timely achievement of target trough concentrations for vancomycin can improve partial clinical outcomes in Gram-positive bacterial infections. Cys-C level is a potentially valuable parameter for predicting the vancomycin concentration.

Prognostic and risk factor analysis of cancer patients after unplanned ICU admission: a real-world multicenter study.

To investigate the occurrence and 90-day mortality of cancer patients following unplanned admission to the intensive care unit (ICU), as well as to develop a risk prediction model for their 90-day prognosis. We prospectively analyzed data from cancer patients who were admitted to the ICU without prior planning within the past 7 days, specifically between May 12, 2021, and July 12, 2021. The patients were grouped based on their 90-day survival status, and the aim was to identify the risk factors influencing their survival status. A total of 1488 cases were included in the study, with an average age of 63.2 ± 12.4 years. The most common reason for ICU admission was sepsis (n = 940, 63.2%). During their ICU stay, 29.7% of patients required vasoactive drug support (n = 442), 39.8% needed invasive mechanical ventilation support (n = 592), and 82 patients (5.5%) received renal replacement therapy. We conducted a multivariate COX proportional hazards model analysis, which revealed that BMI and a history of hypertension were protective factors. On the other hand, antitumor treatment within the 3 months prior to admission, transfer from the emergency department, general ward, or external hospital, high APACHE score, diagnosis of shock and respiratory failure, receiving invasive ventilation, and experiencing acute kidney injury (AKI) were identified as risk factors for poor prognosis within 90 days after ICU admission. The average length of stay in the ICU was 4 days, while the hospital stay duration was 18 days. A total of 415 patients died within 90 days after ICU admission, resulting in a mortality rate of 27.9%. We selected 8 indicators to construct the predictive model, which demonstrated good discrimination and calibration. The prognosis of cancer patients who are unplanned transferred to the ICU is generally poor. Assessing the risk factors and developing a risk prediction model for these patients can play a significant role in evaluating their prognosis.

Expression Patterns and Functional Analysis of Three SmTAT Genes Encoding Tyrosine Aminotransferases in Salvia miltiorrhiza.

Tyrosine aminotransferase (TAT, E.C. 2.6.1.5) is a pyridoxal phosphate-dependent aminotransferase that is widely found in living organisms. It catalyzes the transfer of the amino group on tyrosine to α-ketoglutarate to produce 4-hydroxyphenylpyruvic acid (4-HPP) and is the first enzyme for tyrosine degradation. Three SmTATs have been identified in the genome of Salvia miltiorrhiza (a model medicinal plant), but their information is very limited. Here, the expression profiles of the three SmTAT genes (SmTAT1, SmTAT2, and SmTAT3) were studied. All three genes expressed in different tissues and responded to methyl jasmonate stimuli. SmTAT proteins are localized in the cytoplasm. The recombinant SmTATs were subjected to in vitro biochemical properties. All three recombinant enzymes had TAT activities and SmTAT1 had the highest catalytic activity for tyrosine, followed by SmTAT3. Also, SmTAT1 preferred the direction of tyrosine deamination to 4-HPP, while SmTAT2 preferred transamination of 4-HPP to tyrosine. In parallel, transient overexpression of SmTATs in tobacco leaves revealed that all three SmTAT proteins catalyzed tyrosine to 4-HPP in vivo, with SmTAT1 exhibiting the highest enzymatic activity. Overall, our results lay a foundation for the production of tyrosine-derived secondary metabolites via metabolic engineering or synthetic biology in the future.

Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

Expert Consensus on Acute Respiratory Failure in Critically Ill Cancer Patients (2023).

Objective This consensus aims to provide evidence-based recommendations on common questions in the diagnosis and treatment of acute respiratory failure (ARF) for critically ill cancer patients.Methods We developed six clinical questions using the PICO (Population, Intervention, Comparison, and Outcome) principle in diagnosis and treatment for critical ill cancer patients with ARF. Based on literature searching and meta-analyses, recommendations were devised. The GRADE (Grading of Recommendation Assessment, Development and Evaluation) method was applied to each question to reach consensus in the expert panel. Results The panel makes strong recommendations in favor of (1) metagenomic next-generation sequencing (mNGS) tests may aid clinicians in rapid diagnosis in critically ill cancer patients suspected of pulmonary infections; (2) extracorporeal membrane oxygenation (ECMO) therapy should not be used as a routine rescue therapy for acute respiratory distress syndrome in critically ill cancer patients but may benefit highly selected patients after multi-disciplinary consultations; (3) cancer patients who have received immune checkpoint inhibitor therapy have an increased incidence of pneumonitis compared with standard chemotherapy; (4) critically ill cancer patients who are on invasive mechanical ventilation and estimated to be extubated after 14 days may benefit from early tracheotomy; and (5) high-flow nasal oxygen and noninvasive ventilation therapy can be used as a first-line oxygen strategy for critically ill cancer patients with ARFs. A weak recommendation is: (6) for critically ill cancer patients with ARF caused by tumor compression, urgent chemotherapy may be considered as a rescue therapy only in patients determined to be potentially sensitive to the anticancer therapy after multidisciplinary consultations. Conclusions The recommendations based on the available evidence can guide diagnosis and treatment in critically ill cancer patients with acute respiratory failure and improve outcomes.

Daurisoline suppresses esophageal squamous cell carcinoma growth in vitro and in vivo by targeting MEK1/2 kinase.

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancers and has a high mortality rate worldwide. The 5-year survival rate of ESCC patients in developing countries is <20%. Hence, there is an urgent need for developing new and effective treatments that are based on newly-discovered emerging molecules and pathways to prevent ESCC occurrence and recurrence. We investigated the effects of Daurisoline, a bis-benzylisoquinoline alkaloid extracted from the rhizome of menisperum dauricum, on ESCC cell proliferation and elucidated the molecular mechanisms underlying its functions. To explore the effects of Daurisoline on ESCC growth in vitro and in vivo, cell proliferation assays and anchorage-independent growth assays were performed and a patient-derived xenograft (PDX) model was established. Subsequently, phosphoproteomics, molecular docking analysis, pull down assays, mutation experiments and in vitro kinase assay were performed to explore the mechanism of Daurisoline's function on ESCC. Daurisoline inhibited ESCC proliferation in vitro and reduced ESCC PDX exnograft growth in vivo by reducing ERK1/2 phosphorylation. Furthermore, it directly bound to MEK1 (at Asn78 and Lys97) and MEK2 (at Asp194 and Asp212) kinases to inactivate the ERK1/2 signaling pathway. Our results suggest that Daurisoline is a dual inhibitor of MEK1 and MEK2 and suppresses ESCC growth both in vitro and in vivo by inactivating the ERK1/2 signaling pathway. This is first report on the use of MEK inhibitor for ESCC and highlights its potential applications for ESCC treatment and prevention.

Association Between Smoking Behavior and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

INTRODUCTION: To systematically review the association between smoking behavior and obstructive sleep apnea (OSA). AIMS AND METHODS: PubMed, Medline, the Cochrane Library, EMBASE, and Scopus databases were used to conduct this review. The two researchers independently screened the literatures, conducted the quality assessment, and data extraction according to the inclusion and exclusion criteria. The RevMan 5.3 was used to analysis the apnea hypopnea index (AHI) index, min saturation of oxyhemoglobin (SaO2), Epworth Sleepiness Scale (ESS) score, and oxygen desaturation index (DOI) and publication bias analysis to assess the effect of smoking on OSA patients. Furthermore, we performed subgroup of the severity of OSA, different countries of sample origin (western countries or eastern countries), and pack-years (PYs < 10 or PYs ≥ 20) to analyze the heterogeneity. RESULTS: Thirteen studies were included in this analysis that conformed to inclusion criteria and exclusion criteria. Totally 3654 smokers and 9796 non-smokers have participated. The meta-analysis of 13 studies demonstrated that AHI levels were significantly higher in smoker group compared with non-smoker, ESS scores were also significantly higher in smoker group compared with non-smoker, min SaO2 levels were obviously lower in smoker group compared with non-smoker, however, DOI levels hadn't significantly different between two groups. The subgroup analysis showed that there was an association between severe OSA, eastern countries, pack-years, and smoking. CONCLUSIONS: Smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significantly association with smoking compared with patients with mild or moderate OSA. IMPLICATIONS: The relationship between smoking and OSA was controversial, especially, whether smoking increase or aggravate the risk of OSA. In our review and meta-analysis, we demonstrated that smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significant association with smoking compared with patients with mild or moderate OSA. More prospective long-term follow-up studies about effect of quit smoking on OSA are recommended to establish the further relationship.

The Prediction of Surgery Outcomes in Abdominal Tumor Patients with Sepsis by Pcv-aCO2/Ca-cvO2.

Background: To determine whether Pcv-aCO2/Ca-cvO2 combined with Pcv-aCO2 could predict the outcomes in patients complicated with abdominal infection and sepsis after abdominal tumor operation. Methods: Total 92 patients admitted to our hospital from January 2017 to December 2020 who underwent abdominal tumor operation were enrolled. Blood gas analysis of artery and central vein, various laboratory indexes, SOFA score, hemodynamic parameters at different time points and treatment outcome were recorded. Results: ROC curve analysis showed that hemodynamic parameter alone could not predict ICU treatment outcome and mortality of patients, but 72-hour SOFA score could predict treatment outcome of patients (AUC = 0.930, 95% CI: 0.803-1.000, p = 0.019). The significant hemodynamic parameter for evaluating treatment outcome and prognosis of patients was Pcv-aCO2 + Ratio of T3. Kaplan-Meier univariate survival curve and Log-rank suggested that patients who had higher combined predictive parameter of T3 Ratio + T3 Pcv-aCO2 still had ischemia and hypoxia of tissues and organs after standard fluid resuscitation, and treatment outcome was not good. In subgroup analysis, patients with higher Ratio had higher lactate, higher T72 SOFA score, and poor treatment outcome. Conclusion: The combination of Ratio and Pcv-aCO2 could evaluate clinical treatment outcome of patients complicated with abdominal infection and sepsis after abdominal tumor operation.

A comprehensive mouse brain acetylome-the cellular-specific distribution of acetylated brain proteins.

Nε-lysine acetylation is a reversible posttranslational modification (PTM) involved in multiple physiological functions. Genetic and animal studies have documented the critical roles of protein acetylation in brain development, functions, and various neurological disorders. However, the underlying cellular and molecular mechanism are still partially understood. Here, we profiled and characterized the mouse brain acetylome and investigated the cellular distribution of acetylated brain proteins. We identified 1,818 acetylated proteins, including 5,196 acetylation modification sites, using a modified workflow comprising filter-aided sample preparation (FSAP), acetylated peptides enrichment, and MS analysis without pre- or post-fraction. Bioinformatics analysis indicated these acetylated mouse brain proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and synapse, as well as their involvement in multiple neurological disorders. Manual annotation revealed that a set of brain-specific proteins were acetylation-modified. The acetylation of three brain-specific proteins was verified, including neurofilament light polypeptide (NEFL), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP), and neuromodulin (GAP43). Further immunofluorescence staining illustrated that acetylated proteins were mainly distributed in the nuclei of cortex neurons and axons of hippocampal neurons, sparsely distributed in the nuclei of microglia and astrocytes, and the lack of distribution in both cytoplasm and nuclei of cerebrovascular endothelial cells. Together, this study provided a comprehensive mouse brain acetylome and illustrated the cellular-specific distribution of acetylated proteins in the mouse brain. These data will contribute to understanding and deciphering the molecular and cellular mechanisms of protein acetylation in brain development and neurological disorders. Besides, we proposed some problems that need to be solved in future brain acetylome research.

Overexpression of SmLAC25 promotes lignin accumulation and decreases salvianolic acid content in Salvia miltiorrhiza.

Laccase (LAC) is a blue multicopper oxidase that contains four copper ions, which is involved in lignin polymerization and flavonoid biosynthesis in plants. Although dozens of LAC genes have been identified in Salvia miltiorrhiza Bunge (a model medicinal plant), most have not been functionally characterized. Here, we explored the expression patterns and the functionality of SmLAC25 in S. miltiorrhiza. SmLAC25 has a higher expression level in roots and responds to methyl jasmonate, auxin, abscisic acid, and gibberellin stimuli. The SmLAC25 protein is localized in the cytoplasm and chloroplasts. Recombinant SmLAC25 protein could oxidize coniferyl alcohol and sinapyl alcohol, two monomers of G-lignin and S-lignin. To investigate its function, we generated SmLAC25-overexpressed S. miltiorrhiza plantlets and hairy roots. The lignin content increased significantly in all SmLAC25-overexpressed plantlets and hairy roots, compared with the controls. However, the concentrations of rosmarinic acid and salvianolic acid B decreased significantly in all the SmLAC25-overexpressed lines. Further studies revealed that the transcription levels of some key enzyme genes in the lignin synthesis pathway (e.g., SmCCR and SmCOMT) were significantly improved in the SmLAC25-overexpressed lines, while the expression levels of multiple enzyme genes in the salvianolic acid biosynthesis pathway were inhibited. We speculated that the overexpression of SmLAC25 promoted the metabolic flux of lignin synthesis, which resulted in a decreased metabolic flux to the salvianolic acid biosynthesis pathway.

Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase.

Human esophageal cancer has a global impact on human health due to its high incidence and mortality. Therefore, there is an urgent need to develop new drugs to treat or prevent the prominent pathological subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC). Based upon the screening of drugs approved by the Food and Drug Administration, we discovered that Arbidol could effectively inhibit the proliferation of human ESCC in vitro. Next, we conducted a series of cell-based assays and found that Arbidol treatment inhibited the proliferation and colony formation ability of ESCC cells and promoted G1-phase cell cycle arrest. Phosphoproteomics experiments, in vitro kinase assays and pull-down assays were subsequently performed in order to identify the underlying growth inhibitory mechanism. We verified that Arbidol is a potential ataxia telangiectasia and Rad3-related (ATR) inhibitor via binding to ATR kinase to reduce the phosphorylation and activation of minichromosome maintenance protein 2 at Ser108. Finally, we demonstrated Arbidol had the inhibitory effect of ESCC in vivo by a patient-derived xenograft model. All together, Arbidol inhibits the proliferation of ESCC in vitro and in vivo through the DNA replication pathway and is associated with the cell cycle.

Systematic Analysis and Functional Characterization of R2R3-MYB Genes in Scutellaria baicalensis Georgi.

R2R3-MYB transcription factors participate in multiple critical biological processes, particularly as relates to the regulation of secondary metabolites. The dried root of Scutellaria baicalensis Georgi is a traditional Chinese medicine and possesses various bioactive attributes including anti-inflammation, anti-HIV, and anti-COVID-19 properties due to its flavonoids. In the current study, a total of 95 R2R3-MYB genes were identified in S. baicalensis and classified into 34 subgroups, as supported by similar exon-intron structures and conserved motifs. Among them, 93 R2R3-SbMYBs were mapped onto nine chromosomes. Collinear analysis revealed that segmental duplications were primarily responsible for driving the evolution and expansion of the R2R3-SbMYB gene family. Synteny analyses showed that the ortholog numbers of the R2R3-MYB genes between S. baicalensis and other dicotyledons had a higher proportion compared to that which is found from the monocotyledons. RNA-seq data indicated that the expression patterns of R2R3-SbMYBs in different tissues were different. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that 36 R2R3-SbMYBs from different subgroups exhibited specific expression profiles under various conditions, including hormone stimuli treatments (methyl jasmonate and abscisic acid) and abiotic stresses (drought and cold shock treatments). Further investigation revealed that SbMYB18/32/46/60/70/74 localized in the nucleus, and SbMYB18/32/60/70 possessed transcriptional activation activity, implying their potential roles in the regulatory mechanisms of various biological processes. This study provides a comprehensive understanding of the R2R3-SbMYBs gene family and lays the foundation for further investigation of their biological function.

The Specifically Androgen-Regulated Gene (SARG) Promotes Papillary Thyroid Carcinoma (PTC) Lymphatic Metastasis Through Vascular Endothelial Growth Factor C (VEGF-C) and VEGF Receptor 3 (VEGFR-3) Axis.

The papillary thyroid carcinoma (PTC) metastasizes through lymphatic spread, but the follicular thyroid cancer (FTC) metastasis occurs by following hematogenous spread. To date, the molecular mechanism underlying different metastatic routes between PTC and FTC is still unclear. Here, we showed that specifically androgen-regulated gene (SARG) was significantly up-regulated in PTC, while obviously down-regulated in FTC through analyzing the Gene Expression Omnibus (GEO) database. Immunohistochemistry assay verified that the PTC lymph node metastasis was associated with higher levels of SARG protein in clinical PTC patient samples. SARG-knockdown decreased TPC-1 and CGTH-W3 cells viability and migration significantly. On the contrary, SARG-overexpressed PTC cells possessed more aggressive migratory ability and viability. In vivo, SARG overexpression dramatically promoted popliteal lymph node metastasis of xenografts from TPC-1 cells mouse footpad transplanting. Mechanistically, SARG overexpression and knockdown significantly increased and decreased the expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3), respectively, thereby facilitating or inhibiting the tube formation in HUVECs. The tube formation experiment showed that SARG overexpression and knockdown promoted or inhibited the number of tube formations in HUVEC cells, respectively. Taken together, we showed for the first time the differential expression profile of SARG between PTC and FTC, and SARG promotes PTC lymphatic metastasis via VEGF-C/VEGFR-3 signal. It indicates that SARG may represent a target for clinical intervention in lymphatic metastasis of PTC.

Hadrosauroid eggs and embryos from the Upper Cretaceous (Maastrichtian) of Jiangxi Province, China.

BACKGROUND: Dinosaur eggs containing embryos are rare, limiting our understanding of dinosaur development. Recently, a clutch of subspherical dinosaur eggs was discovered while blasting for a construction project in the Upper Cretaceous red beds (Hekou Formation) of the Ganzhou Basin, Jiangxi Province, China. At least two of the eggs contain identifiable hadrosauroid embryos, described here for the first time. RESULTS: The eggs, attributable to Spheroolithidae indet., are thin-walled and small (~ 660 mL) compared to those of Lambeosaurinae. The shape of the embryonic squamosal is reminiscent of that seen in the Late Cretaceous hadrosauroids Levnesovia transoxiana, Tanius sinensis, and Nanningosaurus dashiensis, suggestive of possible affinities. CONCLUSION: The small size of the eggs and embryos, similar to those of Hadrosaurinae, indicates that the larger eggs and hatchlings typical of Lambeosaurinae are evolutionarily derived.

Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway.

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of esophageal cancer (EC). ESCC accounts for 90% of EC. Recurrence after primary treatment is the main reason for poor survival. Therefore, recurrence prevention is a promising strategy for extending the 5-year survival rate. Here, we found tegaserod maleate could inhibit ESCC proliferation both in vivo and in vitro. Proteomics analysis revealed that tegaserod maleate suppressed the peroxisome signaling pathway, in which the key molecules peroxisome membrane protein 11B (PEX11B) and peroxisome membrane protein 13 (PEX13) were downregulated. The immunofluorescence, catalase activity assay, and reactive oxygen species (ROS) confirmed that downregulation of these proteins was related to impaired peroxisome function. Furthermore, we found that PEX11B and PEX13 were highly expressed in ESCC, and knockout of PEX11B and PEX13 further demonstrated the antitumor effect of tegaserod maleate. Importantly, tegaserod maleate repressed ESCC tumor growth in a patient-derived xenograft (PDX) model in vivo. Our findings conclusively demonstrated that tegaserod maleate inhibits the proliferation of ESCC by suppressing the peroxisome pathway.

The characteristics and impact indicator of vancomycin pharmacokinetics in cancer patients complicated with severe pneumonia.

OBJECTIVE: This study was designed to investigate the characteristics and impact indicator of vancomycin pharmacokinetics in cancer patients complicated with severe pneumonia. METHODS: Fifty-seven cancer patients complicated with severe pneumonia were included in this research. Vancomycin serum trough concentrations were measured using the fluorescence polarization immunoassay (FPIA) method. The Bayesian estimator was used to calculate the pharmacokinetic parameters. RESULTS: The average initial therapeutic dose of vancomycin was 15.18 ± 3.29 mg/kg (q12 h). Our study shows that vancomycin initial trough concentrations measured in cancer patients are significantly reduced (6.54 ± 3.11 mg/L; p < 0.0001) compared with the recommended standard vancomycin trough concentration (10-15 or 15-20 mg/L). Meanwhile, the clearance (CL) and volume of distribution (Vd) of vancomycin was increased significantly in cancer patients. Multivariate linear regression analysis revealed that Cys-C was the most important variable for vancomycin trough concentration (r2 = 0.439). The relationships between vancomycin trough concentrations and Cys-C were further evaluated after the 57 patients were grouped by cut-off point (1.44 mg/L) of the serum Cys- C levels before vancomycin was administered. Compared with group Early group (Cys-C>1.44 mg/L), Delayed group (Cys-C≤1.44 mg/L) had much lower trough concentrations. Meanwhile, CL and CLcr were significantly increased in Delayed group (Cys-C≤1.44 mg/L). Although the clinical outcomes were similar between two groups, the duration of vasoactive agent in Early group was considerably shorter compared with Delayed group (χ2 = 4.213; p < 0.05). CONCLUSIONS: The serum trough concentration of vancomycin was significantly reduced in cancer patients complicated with severe pneumonia. Higher dosage regimen is needed to ensure clinical effectiveness. The Cys-C level measured prior to administration of vancomycin is suggested to be the most suitable parameter to predict whether vancomycin trough concentration is up to standard dosage. Especially for patients with baseline Cys-c less than 1.44 mg/L, it is more likely to need higher dosage algorithm.

Risk factors of invasive candidiasis in critical cancer patients after various gastrointestinal surgeries: A 4-year retrospective study.

For early diagnosis and treatment of invasive candidiasis (IC), the well-known risk factors may not apply in the intensive care unit (ICU). This retrospective study identified the risk factors predicting IC and candidemia in cancer patients under intensive care after gastrointestinal surgery.Enrolled were 229 cancer patients admitted to our oncology surgical ICU after gastrointestinal surgery between January 1, 2010 and October 31, 2014.The most common types of solid gastrointestinal cancers were gastric (49.8%), colon (20.1%), and esophageal (18.3%). The percentage of patients with corrected Candida colonization index (CCI) ≥0.4 was 31.9%. IC was confirmed in 19 patients (8.3%), and the ICU mortality was 15.8%. Candida albicans accounted for 52.6% of the total number of pathogenic Candida isolates. Among patients with CCI ≥0.4, the cancers with the highest prevalence were cardiac (45%) and gastric (36%), with ICU mortalities of 20% and 4.9%, respectively. For the diagnosis of candidemia, (1-3)-ß-D-glucan (BDG) ≥80 pg/mL showed a sensitivity and specificity of 25% and 82.7%, respectively, positive and negative predictive values 6.7% and 95.7%, and area under the receiver operating characteristic curve 0.512. CCI ≥0.4 was the only significant predictor of IC, and number of organ failures was the only predictor of candidemia (P = .000 and .026).CCI ≥0.4 was the only significant risk factor predicting IC, with greater prediction of intra-abdominal candidiasis but failure to predict candidemia. Blood culture and BDG detection are recommended to supplement diagnosis. Patients may have multifocal and high-grade Candida colonization after cardiac surgery, and; therefore, are at high risk of IC, which should be taken seriously.