Validation study for prognostic scoring system for perihilar cholangiocarcinoma surgery using preoperative factors.

PURPOSE: Recently, systemic inflammatory responses (SIR) have been shown to play a pivotal role in the development and progression of cancer. We previously reported that four factors, serum carcinoembryonic antigen (> 7 ng/dL), serum albumin (< 3.5 g/dL), C-reactive protein (> 0.5 mg/dL), and platelet-lymphocyte ratio (PLR; > 150), were independent prognostic factors after perihilar cholangiocarcinoma (PHCC) surgery. We also advocated a prognosis predictive preoperative prognostic score (PPS) using these four factors and showed that PPS could predict patients' prognosis on survival. This retrospective study sought to validate preoperatively available prognostic factors for survival after major hepatectomy as reported previously, including PPS for PHCC. METHODS: We retrospectively validated our PPS score and reported SIR scoring systems using the data of 125 consecutive patients who underwent PHCC surgery from January 2010 to November 2020. RESULTS: PPS was an independent preoperative prognostic factors for survival. The T and N categories were independent prognostic factors. Other SIR scores were not independent preoperative factors in the univariate analysis. Among SIR scores, only the PPS was found to be associated with OS and disease-free survival. The PPS was also associated with histopathological factors (T and N categories). CONCLUSION: PPS could be useful in predicting long-term survival after PHCC and may be a more useful scoring system than other SIR systems.

Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer.

BACKGROUND: Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon, are known to have favorable survival and dense local immune infiltration. The aim of this study was to see if there is any form of relationship between these seemingly diverse entities. METHODS: Complete clinical and long-term survival data were retrieved for 316 CRC patients operated at Helsinki University Hospital between the years 1998 and 2003. Tissue microarrays were prepared from surgical specimens and further processed and analyzed for local immune cell infiltration using multispectral imaging with a Vectra quantitative pathology imaging system and Inform software. Multiplex immunohistochemistry was applied using antibodies against CD66b, CD8, CD20, FoxP3, CD68 and pan-Cytokeratin. After exclusions, data on immune infiltration were available for 275 patients. Mismatch repair status was determined by immunohistochemistry. RESULTS: CRP was seen to be an independent predictor of cancer-specific survival but not overall survival in uni- and multivariable (HR 1.01 (1.00-1.02); p = 0.028) analyses of non-irradiated patients. There was no significant difference in CRP according to mismatch repair status, but all cases (n = 10) with CRP ≥ 75 mg/l had proficient mismatch repair (pMMR). There was a significant negative correlation between intratumor stromal infiltration by T-regulatory FOXP3+ cells and CRP (p = 0.006). There was significantly lower intratumor stromal infiltration by FOXP3+ cells (p = 0.043) in the right colon compared to the rectum, but no significant difference in CRP (p = 0.44). CRP was not a predictor of overall survival (HR 0.99, 95% CI 0.98-1.01) nor cancer-specific survival in irradiated patients (HR 0.94, 95% CI 0.94-1.02). CONCLUSIONS: There was a significant negative relationship between SIR, defined as an elevated CRP, and intratumor stromal infiltration by T-regulatory FOXP3+ cells. This and the fact that all cases with a CRP > 75 mg/l had pMMR suggests that SIR and dMMR are independent entities in CRC. Indeed, the general lack of difference in CRP between cases with dMMR and pMMR may be evidence of overlap in cases with a less pronounced SIR.

Systemic inflammatory response syndrome in Sepsis-3: a retrospective study.

BACKGROUND: In the new Sepsis-3 definition, sepsis is defined as "life-threatening organ dysfunction due to a dysregulated host response to infection." We tested the predictive validity of the systematic inflammatory response syndrome (SIRS) criteria in patients in the Sepsis-3 cohort. METHODS: Among 1243 electronic health records from 1 January to 31 December 2015 at Sichuan University West China Hospital, we identified patients with sepsis and septic shock according to the Sepsis-3 definition and divided them into 2 subsets: SIRS-positive and SIRS-negative. We compared their characteristics and outcomes as well as the predictive validity of the SIRS criteria for in-hospital mortality. RESULTS: Of the 1243 patients, 631 were enrolled. Among these, 538 (85.3%) patients had SIRS-positive sepsis or septic shock, 168 (31.2%) of whom died, and 93 (14.7%) had SIRS-negative sepsis or septic shock, 20 (21.5%) of whom died (p = 0.06). Over a 1-year period, these groups had similar characteristics and changes in mortality. Among patients of the Sepsis-3 cohort admitted to the intensive care unit, the predictive validity for in-hospital mortality was lower for the SIRS criteria (area under the receiver operating characteristic curve [AUROC], 0.53; 95% confidence interval [95% CI], 0.49-0.57) than for the sequential (sepsis-related) organ failure assessment (SOFA) criteria (AUROC, 0.70; 95% CI, 0.66-0.74; p ≤ 0.01 for both). The SIRS score had poor predictive validity for the risk of in-hospital mortality. CONCLUSIONS: In this cohort study of the new Sepsis-3 definition, we found that the SIRS criteria are weaker than the SOFA criteria with respect to their predictive efficacy for in-hospital death.

Prognostic value of nutrition and immune­related biomarkers in patients with locally advanced rectal cancer treated with chemoradiotherapy.

The ability of nutrition and immune-related biomarkers to predict outcomes in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant therapy followed by surgery remains controversial due to the lack of evidence regarding the accuracy and reliability of these biomarkers in predicting outcomes for such patients. Therefore, the present study aimed to investigate the prognostic potential of nutrition and immune-related biomarkers in patients with LARC who underwent chemoradiotherapy followed by curative surgery. The clinical data of patients with LARC treated with neoadjuvant therapy followed by surgery between January 2010 and December 2019 were analyzed. In total, 214 consecutive patients were enrolled into the present study, who were then categorized into low and high prognostic nutritional index (PNI) groups. The X-tile 3.6.1 program was used to calculate and then determine the optimal cut-off values for PNI. Disease-free survival (DFS) and overall survival (OS) were compared between the low and high PNI groups. Cox regression analysis demonstrated that low PNI and high post-chemoradiotherapy carcinoembryonic antigen levels were significantly associated with reduced disease-free survival and overall survival. Specifically, a low PNI was associated with inferior 5-year DFS (P=0.025) and OS (P=0.018). These findings suggest that amongst the nutritional and immune-related biomarkers, PNI is a significant predictive factor for disease recurrence and mortality in patients with LARC treated with neoadjuvant therapy followed by surgery.

Perioperative Application of Levosimendan Optimizes Postoperative Renal Function and Organ Perfusion in Patients with Severe Heart Failure.

Background: Renal dysfunction and impaired organ perfusion are common concerns following cardiac surgery. Levosimendan, a calcium sensitizer inotropic drug, is investigated in this study for its potential to improve postoperative renal function and organ perfusion in patients with low preoperative ejection fraction and severe myocardial dysfunction after cardiac surgery. Methods: A retrospective analysis was conducted on 314 patients with preoperative heart failure who underwent cardiac surgery. Among them, 184 patients received perioperative adjunctive therapy with levosimendan, while 130 patients with similar characteristics received conventional treatment. Results: The perioperative administration of levosimendan resulted in a significantly lower need for renal replacement therapy (p < 0.001) and improvements in the serum creatinine levels, glomerular filtration rate, and creatinine clearance. Similarly, the C-reactive protein levels, blood pH, and lactic acid levels showed comparable improvements. Conclusions: The use of levosimendan was associated with a significant enhancement in postoperative renal function and a reduction in the need for renal replacement therapy. Furthermore, it resulted in a decrease in the extent of organ malperfusion. Postoperative inflammatory reactions and metabolic balance also exhibited improvements.

Limited Utility of SIRS Criteria for Identifying Serious Infections in Febrile Young Infants.

(1) Background: Young infants have a high risk of serious infection. The Systematic Inflammatory Response Syndrome (SIRS) criteria can be useful to identify both serious bacterial and viral infections. The aims of this study were to evaluate the diagnostic performance of the SIRS criteria for identifying serious infections in febrile young infants and to identify potential clinical predictors of such infections. (2) Methods: We conducted this prospective cohort study including febrile young infants (aged < 90 days) seen at the emergency department with a body temperature of 38.0 °C or higher. We calculated the diagnostic performance parameters and conducted the logistic regression analysis to identify the predictors of serious infection. (3) Results: Of 311 enrolled patients, 36.7% (n = 114) met the SIRS criteria and 28.6% (n = 89) had a serious infection. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of the SIRS criteria for serious infection was 45.9%, 69.4%, 43.5%, 71.4%, 1.5, and 0.8, respectively. Logistic regression showed that male gender, body temperature ≥ 38.5 °C, heart rate ≥ 178 bpm, and age ≤ 50 days were significant predictors. (4) Conclusions: The performance of the SIRS criteria for predicting serious infections among febrile young infants was poor.

Acute systematic inflammatory response syndrome and serum biomarkers predict outcomes after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce systematic inflammatory response syndrome (SIRS). Serum inflammatory biomarkers and SIRS can predict a poor outcome. The relationship between surgical stress and inflammatory response is well known but described in few reports in the neurosurgical population. We aimed to ascertain whether postoperative SIRS and initial serum biomarkers were associated with outcomes and evaluate whether the postoperative SIRS score differed between those with clipping and coil embolization. We evaluated 87 patients hospitalized within 24 h from onset of nontraumatic SAH. Serum biomarkers, such as levels of C-reactive protein (CRP), white blood cells (WBC), and D-dimer, as well as stress index (SI: blood sugar/K ratio) were obtained at admission. SIRS scores 3 days after admission were derived by adding the number of variables meeting the standard criteria (heart rate [HR] >90, respiratory rate [RR] >20, temperature >38 °C or <36 °C, and WBC count <4000 or >12,000). Clinical variables were compared according to whether they were associated with poor outcomes. Coil embolization was performed in 30 patients and clipping in 57. WBC, SI, D-dimer levels, and SIRS scores were significantly higher in patients with poor-grade SAH and were associated with poor outcomes. SIRS scores were significantly higher with clipping than with coil embolization among patients with good-grade SAH without intracerebral hemorrhage. Acute SIRS and serum biomarkers predict outcomes after SAH. Moreover, our study suggests the influence of surgical invasion via clipping on SIRS after SAH.

Clinical significance of preoperative serum C-reactive protein in oral squamous cell carcinoma.

C-reactive protein (CRP) is an index of systemic inflammation. However, CRP is not usually assessed preoperatively. Hence the study intended to evaluate the preoperative serum CRP levels in oral squamous cell carcinoma (OSCC) patients and to analyse its relationship with the clinicopathologic characteristics. CRP values for 60 OSCCs and 30 healthy controls were evaluated using a CRP assessment kit and spectrophotometer. The Mann-Whitney U test, χ2 test, receiver operating characteristic (ROC) curve analysis, and logistic regression were applied. The CRP ranged from 0.3 to 86mg/L in OSCCs. CRP was significantly higher in OSCCs than in controls. A raised CRP was seen in 70% of OSCCs. CRP in OSCCs was associated with clinical nodal status and lymph node metastasis (LNM) (P<0.05). CRP was significantly higher in the metastatic than in the non-metastatic group. The area under the ROC was 0.819. The best cut-off value for predicting LNM was 8.65mg/L for the CRP with 0.767 sensitivity and 0.767 specificity (P<0.05). The cut-off revealed a significant association with LNM. Raised CRP may predict LNM. The CRP levels regressed significantly in relation to LNM. CRP could offer prognostic information beyond staging and histology. Hence, CRP can be added as an extension to known clinicopathologic parameters to predict the prognosis in OSCCs.

Effect of vancomycin initial dosing on time to systemic inflammatory response syndrome resolution in patients with methicillin-resistant Staphylococcus aureus bacteremia.

Current guidelines suggest using vancomycin-loading doses for complicated infections despite a lack of evidence to support this practice. To address this gap, we performed a single-centre cohort study of 124 patients with sepsis due to methicillin-resistant Staphylococcus aureus bacteremia. Patients were allocated into two groups based on initial dose of vancomycin, <20 mg/kg or ≥20 mg/kg, and evaluated for time to resolution of systemic inflammatory response syndrome (SIRS). Among a cohort of 124 patients, 87 received vancomycin initial doses <20 mg/kg and 37 received ≥20 mg/kg. The median time to SIRS resolution was 109 h in the <20 mg/kg group compared to 67 h in the ≥20 mg/kg group. Cox proportional hazard modelling showed a faster resolution of SIRS in the ≥20 mg/kg group (HR = 1.72[1.09-2.73]). Vancomycin initial doses of ≥20 mg/kg led to faster resolution of SIRS although further studies are needed to evaluate the safety and efficacy of this approach.

Anti-Inflammatory Effect of Taurine in Burned Patients.

PURPOSE: Burn induced inflammatory response can be mediated by reactive oxygen metabolites and accompanied by multiple organ dysfunction. Taurine has protective effects against various inflammatory conditions. The aim of this study was to determine the effect of Taurine supplement in thermal burn victims. METHODS: Thirty patients with severe thermal burns were enrolled in this randomized double-blinded clinical trial. These patients were randomly divided into two equal groups (namely Control and Taurine groups), where both received isocaloric and isonitrogenous formula. One group was supplemented with 50 mg/kg of Taurine per day for a duration of 10 days. Blood samples were obtained to measure Interleukin-10 (IL-10), high-sensitivity C-reactive protein (hs-CRP), and Tumor Necrosis Factor alpha (TNF-α) levels at the beginning and the end of the study. RESULTS: Change in serum level of IL-10 in Taurine group was more than Control group [-13.60(-31.40, -10.40) compared to -4.00(-20.00, -0.20) respectively; P = 0.030]. This change was significant in patients with more than 30% TBSA of burn [-14.20(-31.40, -10.40) compared to -2.40(-9.60, 0.40) respectively; P = 0.013]. As for the hs-CRP and TNF-α levels, the difference between the two groups were not significant. CONCLUSION: Based on the results obtained, Taurine supplement showed a positive outcome on anti-inflammatory cytokine IL-10 in all burn patients. This effect was even more significant in patients with higher percentage of burn area. Taurine had no significant effect on the inflammatory marker hs-CRP and the pro-inflammatory cytokine TNF-α level. For a more thorough verification, measurement of a wider range of inflammatory cytokines in more frequent time intervals are suggested.