Exploring biomarkers for diagnosing and predicting organ dysfunction in patients with perioperative sepsis: a preliminary investigation.

OBJECTIVE: Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients. METHOD: This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models. RESULTS: Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p < 0.001). Logistic regression analysis showed that CatB, S100-A9, VCAM-1, prosaposin, and NGAL could be used for preoperative diagnosis and postoperative prediction of organ dysfunction. CatB and S100-A9 were possible predictive factors for preoperative diagnosis of renal failure in septic patients. Internal validation was assessed using the bootstrapping validation. The preoperative diagnosis of renal failure model displayed good discrimination with a C-index of 0.898 (95% confidence interval 0.843-0.954) and good calibration. CONCLUSION: Serum CatB, S100-A9, VCAM-1, prosaposin, and NGAL may be novel markers for preoperative diagnosis and postoperative prediction of organ dysfunction. Specifically, S100-A9 and CatB were indicators of preoperative renal dysfunction in septic patients. Combining these two biomarkers may improve the accuracy of predicting preoperative septic renal dysfunction. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200060418) on June 1, 2022.

Continuous Erector Spinae Plane Block Using Programmed Intermittent Bolus Regimen versus Intravenous Patient-Controlled Opioid Analgesia Within an Enhanced Recovery Program After Open Liver Resection in Patients with Coagulation Disorder: A Randomized, Controlled, Non-Inferiority Trial.

Purpose: Postoperative pain after open hepatectomy is significant. Preoperative coagulopathy limits the use of epidural analgesia, the gold standard for pain control in open abdominal surgery. Erector spinae plane block (ESPB) is a novel regional anesthesia technique that has been shown to provide effective analgesia in abdominal surgery. In this study, we compared the analgesic efficacy of patient-controlled continuous ESPB (CESPB) with hydromorphone patient-controlled intravenous analgesia (PCIA) after right subcostal incision hepatectomies in hepatocellular carcinoma patients with preoperative coagulopathy. Patients and Methods: In this randomized, controlled, unblinded, and noninferiority trial, 120 patients were randomized to receive either CESPB or PCIA as primary postoperative analgesia together with parecoxib (40mg Q12 h IV) for 3 days after surgery. The primary outcome was the average cough-elicited pain numeric rating scales (NRS) recorded at the seven follow-up time points of 20:00 on the day of surgery and 9:00 and 15:00 on the postoperative day 1 to day 3 (POD1 to POD3). Results: The average cough-elicited pain NRS score was 2.402 in the CESPB group and 2.676 in the PCIA group. The mean difference (95% CI) was -0.274 (-0.620 to 0.072), which demonstrated the noninferiority of CESPB to PCIA. Patients in the CESPB group had less intraoperative opioid consumption, a lower incidence of moderate-to-severe pain and PONV at POD3, and early resumption of oral intake. Conclusion: CESPB provides analgesic efficacy noninferior to opioid PCIA in the context of multimodal analgesia after right subcostal incision open hepatectomy.

The effect of perineural dexamethasone on rebound pain after ropivacaine single-injection nerve block: a randomized controlled trial.

BACKGROUND: Rebound pain after a single-shot nerve block challenges the real benefit of this technique. We aimed to investigate whether perineural dexamethasone addition decreased the incidence of rebound pain after a single-shot nerve block. METHODS: We randomly allocated 132 patients scheduled for open reduction internal fixation of an upper extremity closed fracture under single-shot peripheral nerve block and sedation into two groups. Patients in the dexamethasone group received nerve block with 0.375% ropivacaine and 8 mg dexamethasone, while those in the control group received ropivacaine only. Sixty-three patients in the dexamethasone group and 60 patients in the control group were analyzed for the incidence of rebound pain 48 h after block administration, which was the primary outcome. The secondary outcomes included the highest self-reported numeric rating scale (NRS) pain score, and NRS at 8, 12, 24, and 48 h after the block, sufentanil consumption, sleep quality on the night of surgery, patient satisfaction with the pain therapy, blood glucose at 6 h after the block, pain and paresthesia at 30 days after surgery. RESULTS: The incidence of rebound pain was significantly lower in the dexamethasone group (7 [11.1%] of 63 patients) than in the control group (28 [48.8%] of 60 patients [RR = 0.238, 95% CI (0.113-0.504), p = 0.001]. Dexamethasone decreased opioid consumption in 24 h after surgery (p < 0.001) and improved the sleep quality score on the night of surgery (p = 0.01) and satisfaction with pain therapy (p = 0.001). Multivariate logistic regression analysis showed that only group allocation was associated with the occurrence of rebound pain [OR = 0.062, 95% CI (0.015-0.256)]. Patients in the dexamethasone group reported later onset pain (19.7 ± 6.6 h vs 14.7 ± 4.8 h since block administration, mean ± SD, p < 0.001) and lower peak NRS scores [5 (3, 6) vs 8 (5, 9), median (IQR), p < 0.001] than those in the control group. CONCLUSIONS: The perineural administration of 8 mg dexamethasone reduces rebound pain after a single-shot nerve block in patients receiving ORIF for an upper limb fracture. TRIAL REGISTRATION: This study was retrospectively registered in the Chinese Clinical Trial Registry ( ChiCTR-IPR-17011365 ) on May 11th, 2017.

Increases in the risk of cognitive impairment and alterations of cerebral ß-amyloid metabolism in mouse model of heart failure.

Epidemiological and clinico-pathological studies indicate a causal relationship between heart disease and Alzheimer's disease (AD). To learn whether heart disease causes an onset of AD, mice with myocardial infarction (MI) and congestive heart failure (HF) were used to test neuropsychiatric and cognitive behaviors as well as for measurements of AD related protein markers. To this end, adult mice were subjected to ligation of left anterior descending artery (LAD) and about two weeks later high-frequency echocardiography was performed to exam the resulting cardiac structure and function. Three months after successful induction of chronic heart failure (CHF) these mice showed an impairment of learning in the Morris Water Maze task. In addition, the expression of selected molecules, which are involved in ß-amyloid metabolism, apoptosis and inflammation on the level of gene transcription and translation, was altered in CHF mice. Our findings provide a plausible explanation that CHF increases the risk of cognitive impairments and alters cerebral ß-amyloid metabolism. In addition, our data indicate that the cerebral compensatory mechanisms in response to CHF are brain area and gender specific.