Potential Predictors Of Clinical Outcome Research Articles

NTRK3 exhibits a pro-oncogenic function in upper tract urothelial carcinomas.

Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan-Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression-free survival, cancer-specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K-AKT-mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT-mTOR pathway. Furthermore, the overexpression of NTRK3 in UM-UC-14 cells promoted AKT-mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT-mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.

CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

Predictive Value of Pre-Infusion FDG-PET/CT Parameters for Clinical Outcomes and Toxicities in Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) Following CAR-T Cell Therapy

Introduction: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has demonstrated significant efficacy in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma but is associated with serious adverse effects such CRS and ICANS. Pre-infusion disease burden has been investigated as a potential predictor of clinical outcome and toxicity. FDG-PET/CT derived metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are quantitative indicators of this baseline tumor load. We aim to assess the predictive value of pre-CART PET metrics on outcome and toxicity in R/R large B-Cell Lymphoma (LBCL) following CAR-T cell therapy. Method: We conducted a retrospective single site study of 25 consecutive patients with R/R LBCL treated with CAR-T therapy in our institution between May 2020 and October 2022, All patients underwent FDG-PET/CT imaging pre-CAR-T infusion (PET-0) and at day 30 post infusion (PET-1). The images were reviewed by two expert lymphoma PET physicians. Metabolic parameters including MTV, TLG (both calculated using a relative threshold of 40%), SUVmax and Deauville score were calculated. PET-1 was classified as complete metabolic response (CMR, Deauville score 1-3) or non-CMR (Deauville score 4-5) as per the Lugano classification. Results: 25 patients were analyzed , Based on the median MTV (74,6 mL), TLG (379,4), SUVmax (11,8) values, patients were divided into two groups “low” and “high”. The median follow-up was 12 months. Patients with low pre-infusion MTV and TLG had significantly superior day 30 CMR rates (84,6% vs 25%, p= 0.001 & 80% vs 20%, p = 0.001 respectively). Pre-infusion SUVmax ( p = 0.29 ) and Deauville score ( p = 0.103), however, did not predict response to treatment. In our population, pre-infusion PET parameters were not associated with CRS or ICANS . Patients with low pre-infusion MTV and TLG had significantly superior PFS (MTV: p=0.02; TLG: p=0.019) and OS (MTV: p=0.017; TLG: p=0.05), Pre-infusion SUVmax had no statistical significant impact on OS ( p = 0.61) or PFS ( p = 0.37) Conclusion: In our study, pre-infusion quantitative PET metrics, TLG and MTV, predict response and outcomes of CART therapy in R/R LBCL. Our results highlight the importance of adequate disease control before CAR-T administration and the value of pre-infusion FDG-PET/CT as a predictor of outcomes in R/R LBCL patients treated by CAR-T-therapy.

The relationship between the level of NMLR on admission and the prognosis of patients after cardiopulmonary resuscitation: a retrospective observational study

BackgroundThe inflammatory immune response is involved in the pathophysiology of the post-cardiac arrest syndrome and leads to high mortality. The admission (neutrophil + monocyte) to lymphocyte ratio (NMLR) can help us to assess the immune inflammatory status of patients. We aimed to identify factors that affect the prognosis and explore the association between NMLR and the prognosis of patients after cardiopulmonary resuscitation (CPR).MethodsThis is a retrospective study based on the MIMIC-IV database. We assessed patients admitted to the ICU after cardiopulmonary resuscitation, included demographic characteristics, peripheral blood cell count and blood gas indicators for the first time after admission to the ICU, developed a multivariate COX proportional-hazards model to explore prognostic factors, and divided patients into High NMLR and Low NMLR groups by cutoff values of NMLR. Propensity score matching (PSM) was used to adjust confounding factors.ResultsA total of 955 patients were included in the analysis, with 497 surviving and 458 dying during the follow-up period. In a multivariate Cox proportional-hazards model, age (RR 1.007, p = 0.0411), NMLR levels (RR 1.003, p = 0.0381), lactate (RR 1.097, p < 0.001) and hematocrit (RR 1.101, p < 0.001) were independent risk factors for patient death following CPR. Patients were divided into a high NMLR group (> 14.2) and a low NMLR group (≤ 14.2) based on the optimal threshold for NMLR. Compared to low NMLR group, high NMLR group had higher total vasoactive drugs and lower 28-day survival. After PSM, there were no differences in baseline characteristics. The high NMLR group still had a higher mortality rate (p = 0.001), lower 28-day survival (p = 0.001) and shorter length of stay (p = 0.005) compared to the low NMLR group.ConclusionsAge, NMLR levels, lactate levels and hematocrit were independent risk factors for death in patients after CPR. NMLR > 14.2 was associated with higher mortality and was a potential predictor of clinical outcome in patients after CPR.

Increased inflammatory mediators levels are associated with clinical outcomes and prolonged illness in severe COVID-19 patients

ObjectiveThe purpose of this study was to identify potential predictors of clinical outcome in severe COVID-19 patients and to investigate the relationship between immunological parameters and duration of illness. MethodsThis single-center study retrospectively recruited 73 patients with severe or critical COVID-19. Immunological indicators include white blood cell count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, and circulating inflammatory mediators were observed for their association with disease severity, mortality and duration of illness of COVID-19. ResultsSerum inflammatory mediators levels of C-reactive protein (P = 0.015), interleukin 6 (IL-6) (P < 0.001), CX3CL1 (P < 0.001), D-dimer (P < 0.001) and procalcitonin (PCT) (P < 0.001) were increased in critical illness patients compared to those severe COVID-19 patients. CX3CL1 has the highest C-index (0.75) to predict in-hospital mortality in patients with COVID-19. Furthermore, this study shows for the first time that the duration of illness in severe COVID-19 patients is associated with serum levels of CX3CL1 (P = 0.037) and D-dimer (P = 0.014). ConclusionCX3CL1, D-dimer, PCT, and IL-6 could effectively predict mortality in severe COVID-19 patients. In addition, only the circulating levels of CX3CL1 and D-dimer were significantly associated with duration of illness.

Telomere Length in Human Spermatogenic Cells as a New Potential Predictor of Clinical Outcomes in ART Treatment with Intracytoplasmic Injection of Testicular Spermatozoa.

Predicting the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles that use the testicular spermatozoa of azoospermic patients presents a challenge. Thus, the development of additional approaches to assessing the competence of a testicular-sperm-derived embryo without causing damage to gametes or the embryo is necessary. One of the key parameters in determining such developmental competence is telomere length (TL). We aimed to analyze TLs in spermatogenic cells from the testicular biopsy samples of azoospermic patients and determine how this parameter influences embryo competence for pre- and post-implantation development. Using Q-FISH, we studied the TL of the chromosomes in spermatogonia and spermatocytes I from the TESE biopsy samples of 30 azoospermic patients. An increase in TL was detected during the differentiation from spermatogonia to spermatocytes I. The patients' testicular spermatozoa were used in 37 ICSI cycles that resulted in 22 embryo transfers. Nine pregnancies resulted, of which, one was ectopic and eight ended in birth. The analysis of embryological outcomes revealed a dependence between embryo competence for development to the blastocyst stage and the TL in spermatogenic cells. The TLs in spermatogonia and spermatocytes I in the testicular biopsy samples were found to be higher in patients whose testicular sperm ICSI cycles resulted in a birth. Therefore, the length of telomeres in spermatogenic cells can be considered as a potential prognostic criterion in assessing the competence of testicular-sperm-derived embryos for pre- and post-implantation development. The results of this study provide the basis for the development of a laboratory test for the prediction of testicular sperm ICSI cycle outcomes.

Post-reperfusion acute MR diffusion in stroke is a potential predictor for clinical outcome in rats

Middle cerebral artery occlusion (MCAO) models show substantial variability in outcome, introducing uncertainties in the evaluation of treatment effects. Early outcome predictors would be essential for prognostic purposes and variability control. We aimed to compare apparent diffusion coefficient (ADC) MRI data obtained during MCAO and shortly after reperfusion for their potentials in acute-phase outcome prediction. Fifty-nine male rats underwent a 45-min MCAO. Outcome was defined in three ways: 21-day survival; 24 h midline-shift and neurological scores. Animals were divided into two groups: rats surviving 21 days after MCAO (survival group, n = 46) and rats dying prematurely (non-survival/NS group, n = 13). At reperfusion, NS group showed considerably larger lesion volume and lower mean ADC of the initial lesion site (p < 0.0001), while during occlusion there were no significant group differences. At reperfusion, each survival animal showed decreased lesion volume and increased mean ADC of the initial lesion site compared to those during occlusion (p < 10–6), while NS group showed a mixed pattern. At reperfusion, lesion volume and mean ADC of the initial lesion site were significantly associated with 24 h midline-shift and neurological scores. Diffusion MRI performed soon after reperfusion has a great impact in early-phase outcome prediction, and it works better than the measurement during occlusion.

PROTOCOL: Fear avoidance model psychological factors as predictors for persistent post-concussion clinical outcomes: An integrative review.

Persisting symptoms after concussion (PSaC) include physical, cognitive, and psychological symptoms which contribute to rehabilitation challenges. Previous research has not thoroughly investigated the association between PSaC and pain-related psychological factors. Therefore, there is an opportunity to use current pain models, such as the Fear Avoidance Model (FAM), as a framework to explore these relationships. The goals of this integrative review are to (1) identify and describe range of evidence that explores relationships between psychological factors and clinical outcomes in patients with PSaC, and (2) develop a comprehensive understanding of FAM-specific psychological factors that have been identified as potential predictors of clinical outcomes in patients with PSaC. This review will be based on principles and stages of an integrative review which will allow for inclusion of diverse methodologies: (1) problem formulation, (2) literature search, (3) data evaluation, (4) data analysis, and (5) presentation. Methods for reporting this review will be informed by the 2020 PRISMA guidelines for systematic reviews. The findings from this integrative review will inform healthcare professionals working in post-concussion rehabilitation settings regarding relationships between FAM psychological factors and PSaC-an area that until recently has not been thoroughly explored. Additionally, this review will inform the development of other reviews and clinical studies to further investigate relationships between FAM psychological factors and PSaC. OSF DOI 10.17605/OSF.IO/CNGPW.

Predictive effect of triglyceride-glucose index on clinical events in patients with acute ischemic stroke and type 2 diabetes mellitus

BackgroundThe triglyceride-glucose (TyG) index was significantly related to clinical outcome in patients with cardiovascular disease (CAD) and cerebrovascular disease (CVD). We aim to investigate the association between TyG index and clinical prognosis of acute ischemic stroke (IS) patients with type-2 diabetes mellitus (T2DM).MethodsAmong 19,604 patients with acute IS admitted to the China National Stroke Registry II (CNSRII), 3359 IS patients with T2DM were included in the cross-sectional analysis. The TyG index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into four quartiles. The outcomes included recurrent IS, all-cause death and poor outcome at 1 year were analyzed. The association between the TyG index and adverse cerebrovascular outcomes was assessed by proportional hazards regression analysis.ResultsDuring 1 year follow-up, recurrent IS, all-cause death and poor outcome occurred in 305 (9.08%), 229 (6.82%) and 443 (47.9%) cases, respectively. Multivariable Cox proportional hazards analyses showed that the risk of incident primary endpoints was associated with a higher TyG quartile. After adjustment for confounding factors, patients with a higher TyG index had an association with IS recurrence (adjusted hazard ratio, 1.41; 95% confidence interval, 0.97–2.03; P = 0.048) and all-cause death (adjusted hazard ratio, 1.70; 95% confidence interval, 1.062–2.74; P = 0.028), compared with those in the first quartile at 1 year time follow-up. In addition, there were interactions between TyG index and age (≥ 65), female, hypertensive agents, anticoagulant agents, statins and antidiabetic agents in subgroup analyses, especially patients without taken anticoagulant drugs were significantly related to IS recurrence, all-cause death and poor outcome (P = 0.003, P = 0.006 and P = 0.001, respectively).ConclusionsTyG index is strongly related to the IS recurrence and all-cause death in acute IS patients with T2DM. This finding indicates that the TyG index might be a potential predictor of clinical outcome for acute IS patients with T2DM.

Pallidus Stimulation for Chorea-Acanthocytosis: A Systematic Review and Meta-Analysis of Individual Data.

A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington’s Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

Abstract No. 505 Novel anatomical classification system for femoropopliteal stenosis as a potential predictor of clinical outcomes

Restenosis after endovascular revascularization in the femoropopliteal arterial segment remains an ongoing challenge. This study was conducted to apply a novel classification system for femoropopliteal lesion location and compare clinical outcomes of endovascular intervention between the different zones of the femoropopliteal arterial segment.

D-dimer, CRP, PCT, and IL-6 Levels at Admission to ICU Can Predict In-Hospital Mortality in Patients with COVID-19 Pneumonia.

Introduction Health care workers have had a challenging task since the COVID-19 outbreak. Prompt and effective predictors of clinical outcomes are crucial to recognize potentially critically ill patients and improve the management of COVID-19 patients. The aim of this study was to identify potential predictors of clinical outcomes in critically ill COVID-19 patients. Methods The study was designed as a retrospective cohort study, which included 318 patients treated from June 2020 to January 2021 in the Intensive Care Unit (ICU) of the Clinical Hospital Center “Bezanijska Kosa” in Belgrade, Serbia. The verified diagnosis of COVID-19 disease, patients over 18 years of age, and the hospitalization in ICU were the criteria for inclusion in the study. The optimal cutoff value of D-dimer, CRP, IL-6, and PCT for predicting hospital mortality was determined using the ROC curve, while the Kaplan-Meier method and log-rank test were used to assess survival. Results The study included 318 patients: 219 (68.9%) were male and 99 (31.1%) female. The median age of patients was 69 (60-77) years. During the treatment, 195 (61.3%) patients died, thereof 130 male (66.7%) and 65 female (33.3%). 123 (38.7%) patients were discharged from hospital treatment. The cutoff value of IL-6 for in-hospital death prediction was 74.98 pg/mL (Sn 69.7%, Sp 62.7%); cutoff value of CRP was 81 mg/L (Sn 60.7%, Sp 60%); cutoff value of procalcitonin was 0.56 ng/mL (Sn 81.1%, Sp 76%); and cutoff value of D-dimer was 760 ng/mL FEU (Sn 63.4%, Sp 57.1%). IL-6 ≥ 74.98 pg/mL, CRP ≥ 81 mg/L, PCT ≥ 0.56 ng/mL, and D-dimer ≥ 760 ng/mL were statistically significant predictors of in-hospital mortality. Conclusion IL-6 ≥ 74.98 pg/mL, CRP values ≥ 81 mg/L, procalcitonin ≥ 0.56 ng/mL, and D-dimer ≥ 760 ng/mL could effectively predict in-hospital mortality in COVID-19 patients.

Intermittent Androgen Deprivation Therapy Plus Comprehensive Stereotactic Radiotherapy for Oligometastatic Prostate Cancer (CROP)

<h3>Purpose/Objective(s)</h3> The standard treatment for metastatic prostate cancer is systemic therapy. This prospective phase I/II study assessed the utility of SBRT to all tumor sites plus intermittent androgen deprivation therapy (ADT) in patients with hormone sensitive oligometastatic prostate cancer. Endpoints included incidence of SBRT induced late toxicities and clinical outcomes including cumulative incidences of developing biochemical progression, new metastases, restarting ADT, castration resistant prostate cancer (CRPC), and overall survival (OS). <h3>Materials/Methods</h3> Synchronous and metachronous metastatic disease presentations were eligible if there were ≤ 5 metastases, with ≤ 3 metastases in any one organ system. Conventional scans (CT/bonescan +/- MRI) were used to stage patients at baseline, although novel PET imaging was optional. SBRT was delivered to all sites of disease, including the prostate if not previously treated. SBRT dose was site dependent but was generally 30-35 Gy in 5 fractions for lymph nodes and non-spine bone lesions, 24-28 Gy in 2 fractions for spine, and 35 Gy in 5 fractions to the prostate. ADT was started prior to or immediately after SBRT and was continued for 1 year before moving to an intermittent approach. ADT was to be restarted when the PSA reached ≥ 10 ng/mL or earlier if clinically indicated (development of new metastases or rapidly rising PSA). Toxicity (CTCAE v4.0) and PSA measurements were collected every 4 months during follow-up. Conventional scans were performed at a minimum of once per year, but more frequent imaging was allowed at the discretion of the physician. Time zero was start of ADT or SBRT, whichever was earlier. <h3>Results</h3> 92 patients with 158 metastases were accrued with a median age of 74 years. Median follow-up time was 37 months. Median baseline PSA was 8.5 ng/mL (range 0.78 – 179.8). 39 (42%) patients had Gleason score of 8-10. 32 (35%) patients had synchronous disease presentation. 14 (15%) patients were staged with PET imaging. 5 (5%) patients developed late grade 3 GU toxicity and 6 (7%) patients developed a late SBRT induced bone fracture. There were no grade 4/5 toxicities. Median PSA nadir was 0.02 ng/mL. 50% of patients reached a PSA nadir of ≤ 0.02 ng/mL, while 92% of patients reached a PSA nadir of < 1 ng/mL. The cumulative incidence (CI) of biochemical progression (PSA nadir + 2 ng/mL) was 54% at 4 years. The 4-year CI of developing new metastases and local failure of irradiated sites was 42.8% and 7%, respectively. The 4-year CI of restarting ADT and developing CRPC was 62% and 25%, respectively. OS was 79% at 4 years. <h3>Conclusion</h3> The incidence of grade ≥ 3 toxicity was low when combining SBRT with intermittent ADT for hormone sensitive oligometastatic prostate cancer. With > 3 years of median follow-up, outcomes are promising compared to historical results of using ADT alone, particularly with regards to the development of CRPC. Further work will be done to identify potential predictors of clinical outcomes.

Optimal glucose, HbA1c, glucose-HbA1c ratio and stress-hyperglycaemia ratio cut-off values for predicting 1-year mortality in diabetic and non-diabetic acute myocardial infarction patients

BackgroundStress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). In addition to glucose, other glucose-related indices, such as HbA1c, glucose-HbA1c ratio (GHR), and stress-hyperglycaemia ratio (SHR) are potential predictors of clinical outcomes following AMI. However, the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting 1-year all cause mortality in diabetic and non-diabetic ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients.MethodsWe undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values using the Youden’s formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-off values in the diabetic and non-diabetic subgroups, stratified by the type of AMI.ResultsThere were 5841 STEMI and 4105 NSTEMI in the study. In STEMI patients, glucose, GHR, and SHR were independent predictors of 1-year all-cause mortality [glucose: OR 2.19 (95% CI 1.74–2.76); GHR: OR 2.28 (95% CI 1.80–2.89); SHR: OR 2.20 (95% CI 1.73–2.79)]. However, in NSTEMI patients, glucose and HbA1c were independently associated with 1-year all-cause mortality [glucose: OR 1.38 (95% CI 1.01–1.90); HbA1c: OR 2.11 (95% CI 1.15–3.88)]. In diabetic STEMI patients, SHR performed the best in terms of area-under-the-curve (AUC) analysis (glucose: AUC 63.3%, 95% CI 59.5–67.2; GHR 68.8% 95% CI 64.8–72.8; SHR: AUC 69.3%, 95% CI 65.4–73.2). However, in non-diabetic STEMI patients, glucose, GHR, and SHR performed equally well (glucose: AUC 72.0%, 95% CI 67.7–76.3; GHR 71.9% 95% CI 67.7–76.2; SHR: AUC 71.7%, 95% CI 67.4–76.0). In NSTEMI patients, glucose performed better than HbA1c for both diabetic and non-diabetic patients in AUC analysis (For diabetic, glucose: AUC 52.8%, 95% CI 48.1–57.6; HbA1c: AUC 42.5%, 95% CI 37.6–47. For non-diabetic, glucose: AUC 62.0%, 95% CI 54.1–70.0; HbA1c: AUC 51.1%, 95% CI 43.3–58.9). The optimal cut-off values for glucose, GHR, and SHR in STEMI patients were 15.0 mmol/L, 2.11, and 1.68 for diabetic and 10.6 mmol/L, 1.72, and 1.51 for non-diabetic patients respectively. For NSTEMI patients, the optimal glucose values were 10.7 mmol/L for diabetic and 8.1 mmol/L for non-diabetic patients.ConclusionsSHR was the most consistent independent predictor of 1-year all-cause mortality in both diabetic and non-diabetic STEMI, whereas glucose was the best predictor in NSTEMI patients.

Co-occurring MET Amplification Predicts Inferior Clinical Response to First-Line Erlotinib in Advanced Stage EGFR-Mutated NSCLC Patients

BackgroundIntrinsic resistance is a major obstacle in treatment of non-small cell lung cancer (NSCLC) patients with an activating mutation in the epidermal growth factor receptor (EGFR). We investigated co-occurring genetic alterations in circulating tumor DNA (ctDNA) as predictive markers of clinical response to first-line erlotinib. MethodsPretreatment plasma samples were collected from 76 patients with EGFR-mutated, advanced-stage NSCLC treated with first-line erlotinib. We isolated ctDNA from plasma for next-generation sequencing. ResultsCo-occurring oncogenic drivers were detected in 21% of pretreatment samples and correlated with decreased progression-free survival (PFS) (6.9 months vs 14.4 months; hazard ratio [HR], 2.088; 95% confidence interval [CI], 0.8119-5.370; P = .0355). Concurrent MET amplification was identified in 9 samples (12%), predicting inferior PFS (5.5 months vs 14.4 months; HR, 4.750; 95% CI, 0.5923-38.10; P = .0007) and overall survival (7.6 months vs 28.3 months; HR, 3.952; 95% CI, 0.8441-18.50; P = .0005). Co-occurring non-MET-amplification oncogenic alterations showed a tendency for shorter PFS (9.9 months vs 14.4 months; HR, 1.199; 95% CI, 0.3373-4.265; P = .7586). Clearing EGFR-mutated ctDNA during erlotinib treatment is a positive predictor of clinical outcomes. Among patients who cleared the EGFR mutation, 12% had a co-occurring oncogenic driver, with a tendency toward inferior PFS (8.7 months vs 16.1 months; HR, 1.703; 95% CI, 0.5347-5.424; P = .2508). ConclusionCo-occurring MET amplification in pretreatment ctDNA samples predict inferior clinical response to first-line erlotinib in advanced-stage, EGFR-mutated NSCLC patients. Co-occurring oncogenic alterations were associated with inferior response and may be potential predictors of clinical outcome.

Cardiac autonomic functioning and clinical outcome in adolescent borderline personality disorder over two years

The present study aimed to expand on previous findings that pre-treatment autonomic nervous system (ANS) functioning serves as a predictor of clinical outcome in adolescent borderline personality disorder (BPD), while examining whether the relationship between ANS functioning and treatment outcome may vary as a function of early life maltreatment (ELM). ANS stress response was examined considering changes in heart rate (HR) and vagally-mediated heart rate variability (vmHRV) over different conditions of the Montreal Imaging Stress Task (MIST) in a clinical sample of N = 27 adolescents across the spectrum of BPD severity. Participants received in- and/or outpatient treatment, while clinical data was assessed at routine follow-ups. Clinical outcome was defined by change in the number of fulfilled BPD criteria (as measured using the SCID-II), severity of psychopathology (CGI-S), and global level of functioning (GAF), measured 12 and 24 months after baseline assessments. Mixed-effects (random-intercept/random slope) linear regression models were calculated to examine markers of ANS function as potential predictors of clinical outcome. Irrespective of the presence of ELM exposure, both vmHRV resting-state and stress recovery measures were identified as significant predictors of clinical outcome over time. This study adds to the existing literature by replicating and expanding on preliminary findings, considering also physiological reactivity and recovery in addition to resting-state measures of ANS functioning. The present results further highlight the potential of markers of ANS functioning to serve as objective measures in the process of monitoring patient progress and to make predictions regarding treatment outcome in psychiatry research.

Proximal tubular dysfunction in patients with COVID-19: what have we learnt so far?

Recent studies have reported a variety of urine abnormalities in patients hospitalized due to severe acute respiratory syndrome coronavirus 2 infection. In a single-center study from Belgium, Werion et al. present a concise investigation of tubular dysfunction in patients with coronavirus disease 2019, identifying potential risk factors for increased disease severity. These data complement current evidence regarding severe acute respiratory syndrome coronavirus 2 presence and potential infection in the kidney.

Prognostic value of platelet recovery degree before and after achieving minimal residual disease negative complete remission in acute myeloid leukemia patients

BackgroundRisk stratification and prognosis prediction of acute myeloid leukemia (AML) are largely dependent on pre-treatment information. However, post-treatment data also provides much useful information. In this retrospective study, we explored whether the level of blood count recovery before and after the first minimal residual disease (MRD) negative complete remission (CR) is relevant to clinical outcomes of AML patients.MethodsFor each included patient, peripheral platelet counts were measured on the day before initial treatment (PLTpre), whereas platelet peak values (PLTpeak) were recorded after marrow recovery following the chemotherapy course inducing the first MRD-negative CR. The difference (DPLT) between these two values (DPLT = PLTpeak−PLTpre) was calculated. X-tile software was utilized to establish the optimal cut-point for DPLT, which was expected to distinguish CR patients with different clinical outcomes. A cross validation analysis was conducted to confirm the robustness of the established cut-point. The results were further tested by a Cox multivariate analysis.ResultsThe optimal cut-point of DPLT was determined as 212 × 109/L. Patients in high DPLT group were observed to have a significantly better PFS (p = 0.016) and a better OS (without statistical significance, p = 0.106). Cox multivariate analysis showed that higher DPLT was associated with longer PFS (HR = 2.894, 95% CI: 1.320–6.345, p = 0.008) and longer OS (HR = 3.077, 95% CI: 1.130–8.376, p = 0.028).ConclusionPlatelet recovery degree before and after achieving MRD-negative CR (DPLT) is a potential predictor of clinical outcomes in CR patients. Higher DPLT value is associated with longer PFS and OS. Our findings may help to develop simple methods for AML prognosis evaluation.

The relationship between pulse waveform analysis indices, endothelial function and clinical outcomes in patients with peripheral artery disease treated using percutaneous transluminal angioplasty during a one-year follow-up period

Several predictors of clinical outcomes after percutaneous transluminal angioplasty (PTA) interventions in patients with peripheral arterial disease (PAD) have been investigated. Indices of endothelial function, arterial pulse waveform analysis (aPWA) and markers of peripheral artery ischemia were among the most commonly examined. The aim of the current study was to assess the relationship between potential predictors of clinical outcomes after peripheral artery PTA during a 1-year follow-up period. The study included 72 individuals with PAD at a mean age of 66.3 ± 7.2 (79.1% males). All patients underwent PTA of the peripheral arteries. Among them, 42.8% presented critical limb ischemia (CLI). During the first visit and at 1 month and 6 months after PTA, endothelial function and aPWA measurements were taken. Ankle-brachial index (ABI), toe-brachial index (TBI) and physical evalu-ation of the limbs took place during the first visit and at 1, 6 and 12 months after the PTA. The study endpoints included myocardial infarction, amputation, death, stroke and reintervention. All subjects included in the study were observed for 386 days after the PTA. A significant improvement was noted in walking distance after PTA at the following time points, as well as transient improvement of ABI and flow-mediated dilatation (FMD) and no significant change in aPWA indices and reactive-hyperaemia index (RHI). The mean ABI, TBI, FMD and RHI values did not correlate with each other at baseline. There were 25 study endpoints which occurred in 16 patients during the follow-up period (22.2%). Patients with CLI, hypercholesterolemia, lower dias-tolic blood pressure, higher subendocardial viability ratio, a greater number of pack-years and lower TBI at baseline presented significantly poorer clinical outcomes in terms of endpoint events. Endothelial function assessed as FMD and reactive hyperemia-peripheral arterial tonometry (RH-PAT) before PTA in patients with advanced PAD do not predict clinical outcomes during the 1-year follow-up.

Effects of STAT3 polymorphisms and pharmacokinetics on the clinical outcomes of gefitinib treatment in patients with EGFR-mutation positive non-small cell lung cancer.

We investigated the correlations among signal transducer and activator of transcription 3 (STAT3) rs4796793C >G polymorphism, gefitinib pharmacokinetics and clinical responses in Japanese patients with non-small cell lung cancer receiving gefitinib therapy. Forty-five patients were enrolled in this study. Plasma trough concentrations (C0 ) of gefitinib at the steady-state were measured by high-performance liquid chromatography. Patients having a gefitinib C0 of at least ≥200ng/mL had significantly longer PFS than patients having a C0 of <200ng/mL (median [95% confidence interval (CI)] PFS: 11.0 [8.2-13.7] and 5.3 [0.0-12.0] months, respectively, P=.042). There were no significant differences in PFS between patients with STAT3 rs4796793C/C and G alleles; however, patients with STAT3 rs4796793C/C having a gefitinib C0 of ≥200ng/mL had significantly longer progression-free survival (PFS) and overall survival (OS) than those with a C0 of <200ng/mL (median [95% CI] PFS: 11.4 [4.1-18.6] and 3.0 [0.0-7.0] months, respectively, P=.008; median [95% CI] OS: 20.6 [7.4-33.7] and 12.6 [10.1-15.1] months, respectively, P=.042). In patients with the STAT3 rs4796793G allele, there were no significant differences in PFS and OS between the two gefitinib C0 groups. In addition, there were no significant differences in PFS or OS according to smoking, presence of proton pump inhibitor combination, or onset of side effects. Clinical outcomes of gefitinib in patients with the STAT3 rs4796793C/C genotype depended on plasma concentrations of gefitinib. In addition to information regarding EGFR mutations, the STAT3 rs4796793C >G polymorphism and gefitinib C0 may be potential predictors of clinical outcomes after beginning of gefitinib therapy.