Independent Predictors Of Clinical Response Research Articles

Development and validation of a nomogram model based on pretreatment ultrasound and contrast-enhanced ultrasound to predict the efficacy of neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer

ObjectivesTo develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC).MethodsA total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram’s performance, calibration, discrimination and clinical benefit.ResultsThe multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram.ConclusionsThe nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.

Very Long-Term Follow-Up in Cardiac Resynchronization Therapy: Wider Paced QRS Equals Worse Prognosis.

Background: Different electrocardiogram (ECG) findings are known to be independent predictors of clinical response to cardiac resynchronization therapy (CRT). It remains unknown how these findings influence very long-term prognosis. Methods and Results: A total of 102 consecutive patients (75 males, mean age 65 ± 10 years) referred to our center for CRT implantation had previously been included in this prospective observational study. The same patient group was now re-evaluated for death from all causes over a prolonged median follow-up of 10.3 years (interquartile range 9.4–12.5 years). During follow-up, 55 patients died, and 82% of the clinical non-responders (n = 23) and 44% of the responders (n = 79) were deceased. We screened for univariate associations and found QRS width during biventricular (BIV) pacing (p = 0.02), left ventricular (LV) pacing (p < 0.01), Δ LV paced–right ventricular (RV) paced (p = 0.03), age (p = 0.03), New York Heart Association (NYHA) class (p < 0.01), CHA2DS2-Vasc score (p < 0.01), glomerular filtration rate (p < 0.01), coronary artery disease (p < 0.01), non-ischemic cardiomyopathy (NICM) (p = 0.01), arterial hypertension (p < 0.01), NT-proBNP (p < 0.01), and clinical response to CRT (p < 0.01) to be significantly associated with mortality. In the multivariate analysis, NICM, the lower NYHA class, and smaller QRS width during BIV pacing were independent predictors of better outcomes. Conclusion: Our data show that QRS width duration during biventricular pacing, an ECG parameter easily obtainable during LV lead placement, is an independent predictor of mortality in a long-term follow-up. Our data add further evidence that NICM and lower NYHA class are independent predictors for better outcome after CRT implantation.

Combined detection of peripheral blood VEGF and inflammation biomarkers to evaluate the clinical response and prognostic prediction of non-operative ESCC

An association between angiogenesis/inflammation status and tumor has been reported in various types of cancer. This study sought to assess the role of peripheral blood VEGF and some inflammation biomarkers in evaluating clinical response and prognosis in patients with non-operative esophageal squamous cell carcinoma (ESCC). Peripheral blood of 143 patients with non-operative ESCC at our institute was dynamically collected at 5 time points including 1 day before radiotherapy, during radiotherapy (15f), at the end of radiotherapy, 1 month after radiotherapy, and 3 months after radiotherapy. VEGF expression in the peripheral blood was detected and related inflammation biomarkers such as GPS, CAR and CLR were counted. Logistic regression and Cox regression were implemented respectively to analyze the correlation of each predictor with clinical response and prognosis. The performance of combined testing was estimated using AUCs. Based on independent predictors, a nomogram prediction model was established to predict the probabilities of 1- and 2-year PFS of patients. The effectiveness of the nomogram model was characterized by C-index, AUC, calibration curves and DCA. VEGF and CLR levels at the end of radiotherapy were independent predictors of clinical response, while VEGF and GPS levels at 3 months after radiotherapy were independent prognostic predictors. The efficacy of combined detection of VEGF and CLR is superior to the single detection in evaluating clinical response and prognosis. The nomogram showed excellent accuracy in predicting PFS. The combined detection of VEGF and CLR at the end of radiotherapy can be used to evaluate the clinical response of patients with non-operative ESCC, and the combined detection of VEGF and GPS 3 months after radiotherapy can be used to predict the prognosis. Implemented by nomogram model, it is expected to provide practical and reliable method to evaluate the clinical response and prognosis of patients with non-operative ESCC tool.

Dynamic Changes of Lymphocyte Subsets in the Course of COVID-19

Background: Although the pathophysiology of coronavirus disease 2019 (COVID-19) is not clearly defined, among the proposed mechanisms, immune system dysfunction is more likely than others. The aim of this study was to clarify the characteristics and clinical significance of dynamic changes of lymphocyte subsets in the course of COVID-19. Methods: In this prospective study, the levels of peripheral lymphocyte subsets including CD4⁺, CD8⁺, CD4⁺CD25⁺FOXP3⁺, CD38⁺, CD3⁺HLA-DR⁺, CD19⁺, CD20⁺, and CD16⁺CD56⁺ cells were measured by flow cytometry in 52 confirmed hospitalized patients with COVID-19 at the day of admission and after 7 days of care. Clinical response was defined as improvement in symptoms (fever, dyspnea, and cough as well as blood oxygen saturation), and patients who met these criteria after 1 week of admission were classified as early responders; others who survived and finally discharged from the hospital were classified as late responders and patients who died were categorized as nonresponders. Immunophenotyping of studied cell changes on the first day of admission and 7 days after treatment were compared. Besides, the correlation between cellular subset variation and clinical response and outcome were analyzed. Results: Total counts of white blood cell, T cells, CD4⁺ T cells, CD8⁺ T cells, CD38⁺ lymphocytes, and CD3⁺HLA-DR⁺ lymphocytes were significantly increased in both early and late responders. No statistically significant difference was observed in CD4⁺/CD8⁺ ratio, B cells, FOXP3⁺T_reg lymphocytes, and FOXP3 median fluorescence intensity among studied groups. According to the multivariate analysis, an increase in CD4⁺ T cells (p = 0.019), CD8⁺ T cells (p = 0.001), and administration of interferon (p < 0.001) were independent predictors of clinical response. Conclusion: We found an increasing trend in total T cells, T helpers, cytotoxic T cells, activated lymphocytes, and natural killer cells among responders. This trend was not statistically significant among nonresponders. The findings of this study may enhance our knowledge about the pathogenesis of COVID-19.

Serum Interleukin-6 and -8 as Predictors of Response to Vedolizumab in Inflammatory Bowel Diseases

Vedolizumab, a monoclonal antibody directed against integrin α4β7, is an effective treatment for inflammatory bowel diseases. However, a significant number of patients do not achieve steroid-free clinical remission in the first year of treatment. An early identification of these patients is one of the most important challenges for clinicians and offers the possibility of therapeutic optimization in order to personalize biological therapy. The aim of our study was to test the prediction ability of interleukin (IL)-6 and -8 of clinical response after 12 months of therapy with vedolizumab (T2). We performed a prospective, multicentre study in patients affected by inflammatory bowel disease by analysing cytokines level before starting vedolizumab (T0) and after 10 weeks of therapy (T1). In the overall cohort (n = 54), IL-8 decrease > 2.6 pg/mL in the first 10 weeks of therapy was able to predict clinical response (area under the curve (AUC) = 0.70, sensitivity = 66%, specificity = 75%, p = 0.010), negative C-reactive protein (CRP) (AUC = 0.71, sensitivity = 64%, specificity = 80%, p = 0.009) and calprotectin < 250 mg/kg (AUC = 0.69, sensitivity = 64%, specificity = 78%, p = 0.030) after 44 weeks of therapy. In patients with ulcerative colitis (n = 40), baseline IL-8 values > 8.6 pg/mL and a decrease of IL-6 values > 0.4 pg/mL from T0 to T1 were significant and independent predictors of clinical response after 12 months of vedolizumab therapy (odds ratio (OR) = 6.96, 95% CI 1.27–38.22, p = 0.026 and OR = 7.29, 95% CI 1.42–37.50, p = 0.017, respectively). In patients with Crohn’s disease (n = 14), baseline IL-8 values > 8.6 pg/mL and baseline IL-6 values > 1.6 pg/mL allowed the identification of patients achieving negative CRP at T2 (AUC = 0.75, sensitivity = 74%, specificity = 76%, p < 0.001) and patients with faecal calprotectin values < 250 mg/kg at T2 (AUC = 0.71, sensitivity = 78%, specificity = 63%, p = 0.004). In conclusion, our study highlights a potential clinical role of serum cytokine levels for the prediction of clinical and biochemical steroid-free response in patients treated with vedolizumab.

Clinical outcomes and nephrotoxicity of colistin loading dose for treatment of extensively drug-resistant Acinetobacter baumannii in cancer patients.

BackgroundColistin is a last-line defense therapy against extensively drug-resistant Acinetobacter baumannii (XDR-AB). Despite a loading dose of colistin being applied in many clinical practices, studies evaluating the effect of the loading dose of colistin in cancer patients remain limited.Patients and methodsA retrospective cohort study of cancer patients who received either a loading or non-loading dose of colistin for treatment of XDR-AB was conducted. For each group, the clinical response, bacteriological eradication and serum creatinine were recorded. Logistic regression was applied to evaluate the effects of therapy on each of the three aforementioned outcomes.ResultsOne hundred and two patients diagnosed with XDR-AB infections between January 2012 and December 2015 were recruited. Only 75 patients were given a loading dose of colistin. There was no significant clinical and microbiological response in patients in the loading dose group or patients in the non-loading dose group. However, 38 (50.67%) patients in the loading dose group and 6 (22.22%) patients in the non-loading dose group developed nephrotoxicity according to the RIFLE criteria (p = 0.013). Multivariate logistic regression analysis showed that independent predictors of clinical response were Charlson score ≥4 and duration of colistin treatment ≥10 days. Septic shock correlated with both poor clinical and microbiological response. Independent predictors for nephrotoxicity were loading dose colistin and patient’s age ≥60 years.ConclusionAdministration of colistin loading dose did not significantly increase clinical response, microbiological response or mortality rate compared to non-loading dose in cancer patients with XDR-AB-related infections. However, nephrotoxicity was significantly higher when patients received loading dose colistin.

Comment to “Predictors of clinical response of acid suppression in Chinese patients with gastroesophageal reflux disease”

Abstract Background Up to 40% of patients with gastroesophageal reflux disease fail to respond to proton pump inhibitor therapy. Aims To determine predictors of clinical response of proton pump inhibitor therapy. Methods Consecutive patients with gastroesophageal reflux disease were enrolled prospectively. All patients underwent upper endoscopy and 24-h multichannel intraluminal impedance and pH monitoring before receiving esomeprazole 20 mg b.i.d. for 2 months. Multivariate logistic regression analysis was used to determine the independent predictors of clinical response to proton pump inhibitor therapy. Results A total of 204 patients with typical reflux symptoms were recruited and screened. Among them 153 patients (mean age 46.3 ± 10.6 years, 51.0% female) completed all the examinations and were assigned to proton pump inhibitor therapy. Ninety-five patients (62.1%) responded to acid suppression after 2 months. Multivariate logistic analysis showed that the predictor for response was pathological distal esophageal acid reflux ( P = 0.001). The factors associated with proton pump inhibitor therapy failure were the presence of irritable bowel syndrome alone ( P = 0.006), depression ( P = 0.005), and overlap of irritable bowel syndrome and functional dyspepsia ( P = 0.002). Conclusions The clinical response of acid suppression on gastroesophageal reflux disease could be predicted by clinical and pH parameters rather than impedance data.

Translating the Benefits of Cardiac Resynchronization Therapy Widely and Wisely: Challenges Remain

In this issue, Al-Majed and colleagues report a systematic review of 25 trials that suggests that CRT benefits patients with reduced left ventricular ejection fraction, symptoms, and prolonged QRS ...

The Incremental Value of Right Ventricular Indices for Predicting Response to Cardiac Resynchronization Therapy

Right ventricular (RV) dysfunction in chronic heart failure (HF) is associated with poor prognosis. Cardiac resynchronization therapy (CRT) is an established method of improving prognosis in HF. However, the majority of known indices predictive of response to CRT are based on left ventricular (LV) assessment. The authors hypothesized that baseline RV function and tissue Doppler-derived dyssynchrony may have incremental value over LV dyssynchrony measures for predicting CRT response. In this retrospective study, echocardiographic examinations were performed in 90 patients before pacemaker implantation and up to 18 months afterward. CRT results were evaluated using clinical criteria (death, hospitalization for decompensation, change in New York Heart Association class ≥1, and 10% decreases in both peak ventilatory oxygen uptake and 6-min walking distance) and reverse remodeling (>15% reduction in LV end-systolic volume). Baseline RV dyssynchrony during isovolumic contraction of 26 msec facilitated the segregation of responders from nonresponders with 85% sensitivity and 100% specificity, as well as synchrony in peak deformation of 54 msec, with 89% sensitivity and 67% specificity. The minor axis of the RV inflow tract predicted reverse remodeling after CRT with sensitivity of 73% and specificity of 58% with a cutoff value of 35 mm. According to the clinical criteria, LV indices (end-diastolic and end-systolic volumes) and interventricular delay gave an overall R(2) value of 0.20 (86.2% correctly classified patients; area under the curve, 0.80). The addition of RV dyssynchrony parameters (measured in peak strain and isovolumic contraction peak velocities) significantly increased the power of the model (R(2) = 0.86; 100% of patients correctly classified; area under the curve, 1; P for change in R(2) < .0001). The value of baseline RV function analysis is incremental to LV indices for the prediction of clinical response to CRT but not reverse remodeling. RV synchronous longitudinal deformation and RV dyssynchronous isovolumic velocity are independent predictors of clinical response to CRT.

Comparison of segmental and global markers of dyssynchrony in predicting clinical response to cardiac resynchronization

Cardiac resynchronization therapy (CRT) reduces inter- and intraventricular dyssynchrony and shortens total isovolumic time (t-IVT). We compared the extent to which the values of ventricular dyssynchrony and t-IVT predict clinical benefits of CRT. Ventricular dyssynchrony was assessed in 39 patients with heart failure before and 6 months after CRT. Segmental dyssynchrony was identified from time to onset and peak systolic velocity of wall motion. T-IVT (s/min) was derived as [60-(total ejection time+total filling time)]. The difference between ventricular pre-ejection periods (D-PEP) was calculated. Outcome measures were fall in New York Heart Association (NYHA) class and increase in cardiac output (CO). Following CRT, NYHA class fell in 29/39 patients, CO increased (by 1.0 L/min, P < 0.001), and intraventricular delay (Intra-VD), interventricular delay (Inter-VD), t-IVT, and D-PEP shortened (by 25 ms, 72 ms, 6 s/min, and 38 ms, P < 0.01). NYHA class and CO were unchanged with CRT in 10/39, and Intra-VD, Inter-VD, t-IVT, and D-PEP lengthened (by 43 ms, 52 ms, 7 s/min, and 35 ms, P < 0.05). Though univariate predictors of CO increment with CRT were Intra-VD, Inter-VD, t-IVT, and D-PEP, only pre-CRT values of CO (P < 0.001), t-IVT (P < 0.001), and D-PEP (P = 0.025) were independent. Global, rather than segmental, measures of ventricular dyssynchrony are powerful, independent predictors of clinical response to CRT.

Early changes in serum IL-6 and VEGF levels predict clinical outcome following first-line therapy in aggressive non-Hodgkin’s lymphoma

Inflammatory cytokines play important roles in the pathogenesis of lymphomas and may reflect underlying biological processes including tumour-host interactions with prognostic information that is not afforded by conventional clinical parameters. Several lines of evidence suggest that serum levels of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) are independent indicators of long-term outcome in non-Hodgkin's lymphoma (NHL), but the clinical impact of early serial monitoring of these cytokines has not been reported. Serum samples from 64 newly diagnosed patients with aggressive NHL were obtained before the first cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and then weekly until the second cycle was given. Serum IL-6 and VEGF were measured by commercial enzyme-linked immunosorbent assays (ELISA). Pre-treatment serum IL-6 and VEGF levels were significantly correlated to response rate and overall survival. A significant decrease of IL-6 and VEGF levels was observed in the first weeks after CHOP therapy in patients achieving a complete remission after treatment. Multivariate analysis indicated that early changes of IL-6 and VEGF serum levels within the first 3 weeks after initiation of chemotherapy were independent predictors of clinical response even when corrected for the influence of clinical prognostic factors. Only changes in serum IL-6 level had borderline significance for the prediction of overall survival. The data indicate that serial measurements of serum IL-6 and VEGF may be early prognostic indicators and support the hypothesis of a clinical impact by early recognition of poor-risk patients and candidates for new treatment options.