Prognostic Tool In Clinical Practice Research Articles

Fractal Dimension Analysis in Neurological Disorders: An Overview.

Fractal analysis has emerged as a powerful tool for characterizing irregular and complex patterns found in the nervous system. This characterization is typically applied by estimating the fractal dimension (FD), a scalar index that describes the topological complexity of the irregular components of the nervous system, both at the macroscopic and microscopic levels, that may be viewed as geometric fractals. Moreover, temporal properties of neurophysiological signals can also be interpreted as dynamic fractals. Given its sensitivity for detecting changes in brain morphology, FD has been explored as a clinically relevant marker of brain damage in several neuropsychiatric conditions as well as in normal and pathological cerebral aging. In this sense, evidence is accumulating for decreases in FD in Alzheimer's disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, and many other neurological disorders. In addition, it is becoming increasingly clear that fractal analysis in the field of clinical neurology opens the possibility of detecting structural alterations in the early stages of the disease, which highlights FD as a potential diagnostic and prognostic tool in clinical practice.

Machine Learning Classifier for Preoperative Prediction of Early Recurrence After Bronchial Arterial Chemoembolization Treatment in Lung Cancer Patients

Bronchial arterial chemoembolization (BACE) was deemed as an effective and safe approach for advanced standard treatment-ineligible/rejected lung cancer patients. However, the therapeutic outcome of BACE varies greatly and there is no reliable prognostic tool in clinical practice. This study aimed to investigate the effectiveness of radiomics features in predicting tumor recurrence after BACE treatment in lung cancer patients. A total of 116 patients with pathologically confirmed lung cancer who received BACE treatment were retrospectively recruited. All patients underwent contrast-enhanced CT within 2 weeks before BACE treatment and were followed up for more than 6months. We conducted a machine learning-based characterization of each lesion on the preoperative contrast-enhanced CT images. In the training cohort, recurrence-related radiomics features were screened by least absolute shrinkage and selection operator (LASSO) regression. Three predictive radiomics signatures were built with linear discriminant analysis (LDA), support vector machine (SVM) and logistic regression (LR) algorithms, respectively. Univariate and multivariate LR analyses were performed to select the independent clinical predictors for recurrence. The radiomics signature with best predictive performance was integrated with the clinical predictors to form a combined model, which was visualized as a nomogram. The performance of the combined model was assessed by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Nine recurrence-related radiomics features were screened out, and three radiomics signatures (RadscoreLDA, RadscoreSVM and RadscoreLR) were built based on these features. Patients were classified into the low-risk and high-risk groups based on the optimal threshold of three signatures. Progression-free survival (PFS) analysis showed that patients of low-risk group achieved longer PFS than patients of high-risk group (P<0.05). The combined model including RadscoreLDA and independent clinical predictors (tumor size, carcinoembryonic antigen and pro-gastrin releasing peptide) achieved the best predictive performance for recurrence after BACE treatment. It yields AUCs of 0.865 and 0.867 in the training and validation cohorts, with accuracy (ACC) of 0.804 and 0.750, respectively. Calibration curves indicated that the probability of recurrence predicted by the model fits well with the actual recurrence probability. DCA showed that the radiomics nomogram was clinically useful. The radiomics and clinical predictors-based nomogram can predict tumor recurrence after BACE treatment effectively, which allowing oncologists to identify potential recurrence and enable better patient management and clinical decision-making.

Association between uric acid level and contrast-induced acute kidney injury in patients with type 2 diabetes mellitus after coronary angiography: a retrospective cohort study

BackgroundThis study assessed the predictive value of uric acid (UA) for contrast-induced acute kidney injury (CI-AKI) in patients with type 2 diabetes mellitus (T2DM) who underwent coronary angiography (CAG). A nomogram to aid in the prediction of CI-AKI was also developed and validated, and the construction of a prognostic nomogram combined with clinical features was attempted.MethodsThis study retrospectively enrolled T2DM patients who underwent CAG between December 2019 and December 2020 at the Affiliated Zhongda Hospital of Southeast University. Multivariable logistic regression analysis was used for the analysis of clinical outcomes. Receiver operating characteristic (ROC) analyses were performed to determine the area under the ROC curve (AUC) and the cut-off points for continuous clinical data. The prediction accuracies of models for CI-AKI were estimated through Harrell’s concordance indices (C-index). Nomograms of the prognostic models were plotted for individualized evaluations of CI-AKI in T2DM patients after CAG.ResultsA total of 542 patients with T2DM who underwent CAG were included in this study. We found that a high UA level (≥ 425.5 µmol/L; OR = 6.303), BUN level (≥ 5.98 mmol/L; OR = 3.633), Scr level (≥ 88.5 µmol/L; OR = 2.926) and HbA1C level (≥ 7.05%; OR = 5.509) were independent factors for CI-AKI in T2DM patients after CAG. The nomogram model based on UA, BUN, Scr and HbA1C levels presented outstanding performance for CI-AKI prediction (C-index: 0.878). Decision curve analysis (DCA) showed good clinical applicability in predicting the incidence of CI-AKI in T2DM patients who underwent CAG.ConclusionHigh UA levels are associated with an increased incidence of CI-AKI in T2DM patients after CAG. The developed nomogram model has potential predictive value for CI-AKI and might serve as an economic and efficient prognostic tool in clinical practice.

Effect of frailty on in-hospital outcomes after transcatheter mitral valve repair

Abstract Background Mitral regurgitation (MR) is a common valvular disorder associated with significant morbidity and mortality. Transcatheter mitral valve repair (TMVr) is a minimally invasive procedure indicated for the treatment of selected patients with moderate-severe or severe primary MR. Despite a lack of a universal definition, frailty has been associated with poor post-procedural outcomes. Albeit several trials have examined individual prognostic factors in this population, there is a paucity of data regarding the effect of frailty on in-hospital outcomes after TMVr. Purpose To further elucidate the association of frailty with in-hospital outcomes in patients undergoing TMVr. Methods The national inpatient sample (NIS) database, which is part of the Healthcare Cost and Utilization Project (HCUP), was queried from 2016 to 2019 to identify all who underwent TMVr. International classification of diseases, tenth revision clinical modification (ICD-10-CM) codes were used to divide patients into frail and non-frail study groups. Frailty was defined using Johns Hopkins Adjusted Clinical Groups diagnosis cluster for frailty. Multivariate linear and logistic regression analysis was performed to compare in-hospital mortality, hospital length of stay, non-home discharge, and iatrogenic cardiac complications among Frail and Non-Frail groups. Results A total of 30,660 patients who underwent TMVr were identified. The mean age was 76±11.6 years. Of those, 2,950 (9.6%) were identified as frail. The overall in-hospital mortality rate for the entire study population was 1.89%. Compared to non-frail patients, those identified as frail had greater odds of in-hospital mortality (AOR= 2.13, 95% CI 1.29–3.51, p&amp;lt;0.001) and non-home discharge (AOR= 4.34, 95% CI 3.54–5.32, p&amp;lt;0.001). However, there was no statistically significant difference in hospital length of stay and rates of iatrogenic cardiac complications. Conclusions Frailty models continue to be underutilized as a prognostic tool in clinical practice. After following HCUP guidelines, our analysis found that frailty is independently associated with increased in-hospital mortality and non-home discharge in patients undergoing TMVr. Therefore, we recommend that further efforts in incorporating frailty models in the pre-procedural assessment of patients undergoing TMVr should be sought along with a standardized predictive model for defining frailty. Funding Acknowledgement Type of funding sources: None.

Phase angle of bioimpedance at 50 kHz is associated with cardiovascular diseases: systematic review and meta-analysis.

The phase angle of bioimpedance is an important prognostic tool in clinical practice. The aim of this study was to investigate the association between phase angle and cardiovascular diseases. Electronic searches were carried out on MEDLINE, EMBASE, Cochrane, SCIELO, LILACS, CINAHL, Scopus, and the Web of Science. The PECO was "P" adults over 18 years of age, "E" the presence of cardiovascular disease, "C" absence of cardiovascular disease, and "O" phase angle values. The phase-angle means difference (MD) was analyzed separately by sex. Subgroup metanalysis with age, body mass index, and heart failure disease and meta-regressions were analyzed with random-effects models. Sensitivity analysis was performed considering only studies with high quality. The heterogeneity among studies was assessed using the Q-Cochran test and I² statistics. Four-hundred-thirty-nine articles were identified, and 22 studies were included in this systematic review, totaling 10.010 participants. Eight studies met the criteria for the meta-analysis, involving 2164 participants. The phase angle (PA) was measured at 50 kHz frequency in all studies. Individuals with cardiovascular disease had a smaller PA compared to the control group, for both males (MD -0.70; 95% CI -1.01 to -0.39) and females (MD -0.76; 95% CI -1.39 to -0.13). In the sensitivity analysis, in men, the quality of studies (P &lt; 0.01), and in women, heart failure (P &lt; 0.01) was significantly different between groups.The values of the phase angle were lower in individuals with cardiovascular disease than in control subjects. This result reinforces the importance of this tool in clinical practice, highlighting its potential to assess health status. Registration: The systematic review protocol was registered in the PROSPERO database as CRD42020164178.

Clinical Implications of Inter- and Intratumor Heterogeneity of Immune Cell Markers in Lung Cancer.

Immune cell transcriptome signatures have been widely used to study the lung tumor microenvironment (TME). However, it is unclear to what extent the immune cell composition in the lung TME varies across histological and molecular subtypes (intertumor heterogeneity [inter-TH]) and within tumors (intratumor heterogeneity [ITH]) and whether ITH has any prognostic relevance. Using RNA sequencing in 269 tumor samples from 160 lung cancer patients, we quantified the inter-TH of immune gene expression and immune cell abundance and evaluated the association of median immune cell abundance with clinical and pathological features and overall survival. In 39 tumors with 132 multiregion samples, we also analyzed the ITH of immune cell abundance in relation to overall survival using a variance-weighted multivariate Cox model not biased by the number of samples per tumor. Substantial inter-TH of 14 immune cell types was observed even within the same histological and molecular subtypes, but early stage tumors had higher lymphocyte infiltration across all tumor types. In multiregion samples, an unbiased estimate of low ITH of overall immune cell composition (hazard ratio [HR] = 0.40, 95% confidence interval [CI] = 0.21 to 0.78; P = .007), dendritic cells (HR = 0.24, 95% CI = 0.096 to 0.58; P = .002), and macrophages (HR = 0.50, 95% CI = 0.30 to 0.84; P = .009) was strongly associated with poor survival. The ITH of 3 markers, including CD163 and CD68 (macrophages) and CCL13 (dendritic cells), was enough to characterize the ITH of the corresponding immune cell abundances and its association with overall survival. This study suggests that lack of immune cell diversity may facilitate tumor evasion and progression. ITH inferred from CCL13, CD163, and CD68 could be used as a prognostic tool in clinical practice.

Abstract P459: Inversion of T Waves on Admission is Associated With Mortality in Spontaneous Intracerebral Hemorrhage

Introduction: Cardiac dysfunction directly caused by spontaneous intracerebral hemorrhage (ICH) is a poorly understood phenomenon, and its impact on outcome is still uncertain. Aim of this study is to investigate the relationship between electrocardiographic (EKG) abnormalities and mortality in ICH. Methods: This is a retrospective study analyzing EKG patterns on admission in patients admitted with ICH at a tertiary care center over eight-year period. For each patient, demographics, medical history, clinical presentation, EKG on admission and repeated during hospitalization, and head CT at presentation were reviewed. Mortality was noted. Results: A total of 301 ICHs were included in the study. The most prevalent EKG abnormalities were QTc prolongation in 56% of patients (n=168) followed by inversion of T waves (TWI) in 37% of patients (n=110). QTc prolongation was associated with ganglionic location (p=0.03) and intraventricular hemorrhage (IVH) (p=0.01), TWI was associated with ganglionic location (p=0.02), PR prolongation with IVH (p=0.01), while QRS prolongation was associated with lobar location (p&lt;0.01). Volume of ICH, hemispheric laterality, and involvement of insular cortex were not correlated with specific EKG patterns. In a logistic regression model, after correcting for ICH severity and prior cardiac history, presence of TWI was independently associated with mortality (OR: 3.04, CI:1.6-5.8, p&lt;0.01). Adding TWI to ICH score improved its prognostic accuracy (AUC 0.81). Disappearance of TWI during hospitalization did not translate in improvement of survival (p=0.5). Conclusion: Presence of TWI on admission is an independent and unmodifiable factor associated with mortality in ICH. TWI may be implemented as an additional early prognostic tool in clinical practice.

Comparision of photo pulse plethysmography module with Mobil-O-graph for measurement of pulse wave velocity

IntroductionPulse wave velocity (PWV) is an indicator of arterial stiffness and one of the prognostic tools in clinical practice. We compared the finger photo pulse plethysmography (PPG) module with the Mobil-O-Graph for assessment of PWV. Material and methods80 healthy subjects and patients have participated in this study, among them, 42 were males, and 38 were females. Recording for the subjects was executed between 9, and 11 a.m., after a light breakfast. Lead – II ECG along with PPG were recorded in dual channel AD converter and Mobil-O-Graph simultaneously. The analogue signals of both the devices of the AD converter were digitized by using the sound card of the computer for the measurement of Pulse Transit Time [PTT]. ResultsThe mean age of the participants was 41.5 ± 5.48 and BMI-26.42 ± 5.80. PWV values measured by the devices were similar (P > 0.05). There is a significant positive correlation of PWV between PPG and Mobil O graph, r-0.92 (p = 0.001). Bland-Altman analysis indicated that a mean difference for PWV is .0.3 m/s, which is limits of agreement (1.4–2.4) between PPG and Mobil-O-Graph. Intra-class correlation (ICC) for PWV was 0.89, and the coefficient of variation (CV) was 9.2%. ConclusionBased on the findings of the present study, we suggest that the measurement of PWV obtained from the PPG is probably a reliable one. It offers the advantages of lower cost and greater practicality about application and usage.

Blood/Brain Biomarkers of Inflammation After Stroke and Their Association With Outcome: From C-Reactive Protein to Damage-Associated Molecular Patterns.

Stroke represents one of the most important causes of disability and death in developed countries. However, there is a lack of prognostic tools in clinical practice to monitor the neurological condition and predict the final outcome. Blood biomarkers have been proposed and studied in this indication; however, no biomarker is currently used in clinical practice. The stroke-related neuroinflammatory processes have been associated with a poor outcome in stroke, as well as with poststroke complications. In this review, we focus on the most studied blood biomarkers of this inflammatory processes, cytokines, and C-reactive protein, evaluating its association with outcome and complications in stroke through the literature, and performing a systematic review on the association of C-reactive protein and functional outcome after stroke. Globally, we identified uncertainty with regard to the association of the evaluated biomarkers with stroke outcome, with little added value on top of clinical predictors such as age or stroke severity, which makes its implementation unlikely in clinical practice for global outcome prediction. Regarding poststroke complications, despite being more practical scenarios in which to make medical decisions following a biomarker prediction, not many studies have been performed, although there are now some candidates for prediction of poststroke infections. Finally, as potential new candidates, we reviewed the pathophysiological actions of damage-associated molecular patterns as triggers of the neuroinflammatory cascade of stroke, and their possible use as biomarkers.

Sleep-stage sequencing of sleep-onset REM periods in MSLT predicts treatment response in patients with narcolepsy.

Current treatment recommendations for narcolepsy suggest that modafinil should be used as a first-line treatment ahead of conventional stimulants or sodium oxybate. In this study, performed in a tertiary sleep disorders centre, treatment responses were examined following these recommendations, and the ability of sleep-stage sequencing of sleep-onset rapid eye movement periods in the multiple sleep latency test to predict treatment response. Over a 3.5-year period, 255 patients were retrospectively identified in the authors' database as patients diagnosed with narcolepsy, type 1 (with cataplexy) or type 2 (without) using clinical and polysomnographic criteria. Eligible patients were examined in detail, sleep study data were abstracted and sleep-stage sequencing of sleep-onset rapid eye movement periods were analysed. Response to treatment was graded utilizing an internally developed scale. Seventy-five patients were included (39% males). Forty (53%) were diagnosed with type 1 narcolepsy with a mean follow-up of 2.37 ± 1.35 years. Ninety-seven percent of the patients were initially started on modafinil, and overall 59% reported complete response on the last follow-up. Twenty-nine patients (39%) had the sequence of sleep stage 1 or wake to rapid eye movement in all of their sleep-onset rapid eye movement periods, with most of these diagnosed as narcolepsy type 1 (72%). The presence of this specific sleep-stage sequence in all sleep-onset rapid eye movement periods was associated with worse treatment response (P = 0.0023). Sleep-stage sequence analysis of sleep-onset rapid eye movement periods in the multiple sleep latency test may aid the prediction of treatment response in narcoleptics and provide a useful prognostic tool in clinical practice, above and beyond their classification as narcolepsy type 1 or 2.

Enhanced Liver Fibrosis (ELF) Immunoassay Test for Identification of Significant Liver Diseases: Recent Developments

Liver Fibrosis (LF) is a common outcome in chronic liver disease (CLD). Over a period of time, the process results in cirrhosis leading to disruption in functional capacity of liver. Further serious complications may occur including portal hypertension, liver failure and cancer. The magnitude of CLD has increased being recognized as a major cause for morbidity and mortality globally and it is increasing progressively in Bangladesh also. Question arises "Is the transabdominal needle biopsy of liver, the traditional reference standard method, sufficient and efficient enough for detecting and assessing liver fibrosis particularly in the early stages of significant liver disease?" More simpler, convenient and less expensive blood tests such as 'Enhanced Liver Fibrosis (ELF) immunoassay test', Fibrotest and Aspartate transaminase-platelet ratio index (APRI), have been developed and reported for identification of significant CLD and use as prognostic tool in clinical practice. Among them, the ELF test had been found to be statistically the best for diagnosing and predicting clinical outcomes in patients with CLD and may be a useful prognostic tool in clinical practice. This ELF immunoassay test has been briefly reviewed in this article. Short title: ELF immunoassay test for CLDAnwer Khan Modern Medical College Journal Vol. 6, No. 1: January 2015, Pages 38-41

Neutrophil/lymphocyte ratio: A promising prognostic marker in patients with chronic kidney disease

Chronic kidney disease (CKD), especially end-stage renal disease (ESRD), is associated with high morbidity and mortality due to cardiovascular disease (CVD) and infection, two common complications of ESRD that may be related, in part, to chronic inflammation and protein-energy wasting (PEW). Recently, in a Japanese prospective cohort study, we reported that there was significantly higher risk for CVD-related events in CKD patients with an increased neutrophil/lymphocyte ratio (NLR) at the start of their dialysis therapy. Because higher neutrophil count reflects inflammation and lower lymphocyte count may reflect malnutrition, NLR is hypothesized to be a more sensitive index than other existing inflammatory markers for detecting those at high risk for CVD-related events. This research highlight describes the potentials of NLR as a prognostic marker in patients with CKD. Although further studies are required to better understand its value as prognostic tool in clinical practice, current data suggest that NLR may be a useful and inexpensive marker for identifying CKD patients at high risk for CVD-related complications.

Prevalence and structure of periodontal disease in patients with coronary heart disease preparing for coronary artery bypass surgery

Aim. To study the prevalence and structure of periodontal disease in in-patients with coronary heart disease preparing for coronary artery bypass surgery.Methods. The study included 144 male in-patients with coronary heart disease who were prepared for coronary artery bypass surgery in the department of cardiac surgery. The diagnosis of periodontal disease was set according to the World Health Organization recommendations based on the comprehensive dental examination. Exclusion criteria were: diabetes mellitus, survived blood transfusions and all teeth missing. A prognostic model based on binary logistic regression method was created for estimation of risk factors on periodontal disease risk.Results.The prevalence of chronic generalized periodontitis in patients with coronary heart disease preparing for coronary artery bypass surgery reaches 73.6%. Mild (51.9%) and moderately severe (48.1%) chronic generalized periodontitis were the most common. Among the risk factors for periodontal disease patients, we have identified older age, smoking, hypertension and survived acute ischemic episodes. For the created model, χ2 value was assessed as 42.7, meaning statistical significance of pConclusion. In in-patients with coronary heart disease, prophylaxis for periodontal disease should be performed to decrease the risk for exacerbations. Using the created prognostic tool in clinical practice may be used for outlining patients with higher risk for periodontal disease.

Evaluation of the Predictive Value of a Clinical Worsening Definition Using 2-Year Outcomes in Patients With Pulmonary Arterial Hypertension: A REVEAL Registry Analysis

Time to clinical worsening has been proposed as a primary end point in clinical trials of pulmonary arterial hypertension (PAH); however, neither standardized nor validated definitions of clinical worsening across PAH trials exist. This study aims to evaluate a proposed definition of clinical worsening within a large prospective, observational registry of patients with PAH with respect to its value as a predictor of proximate (within 1 year) risk for subsequent major events (ie, death, transplantation, or atrial septostomy).We assessed overall 2-year survival and survival free from major events to determine the relationship between clinical worsening and major events among adults with hemodynamically defined PAH (N = 3,001). Freedom from clinical worsening was defined as freedom from worsening functional class (FC), a ≥ 15% reduction in 6-min walk distance (6MWD), all-cause hospitalization, or the introduction of parenteral prostacyclin analog therapy.In the 2 years of follow-up, 583 patients died. Four hundred twenty-six died after a documented clinical worsening event, including FC worsening (n = 128), a ≥ 15% reduction in 6MWD (n = 118), all-cause hospitalization (n = 370), or introduction of a prostacyclin analog (n = 91). Patients who experienced clinical worsening had significantly poorer subsequent 1-year survival postworsening than patients who did not worsen (P &lt; .001).Clinical worsening was highly predictive of subsequent proximate mortality in this analysis from an observational study. These results validate the use of clinical worsening as a meaningful prognostic tool in clinical practice and as a primary end point in clinical trial design.ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.

Abstract 4039: Validation Of The Totaled Heath Risks in Vascular Events (THRIVE) Score For Predicting Outcomes After Endovascular Stroke Treatment

Background: We recently developed a novel clinical prediction tool, the Totaled Health Risks in Vascular Events (THRIVE) score, that predicts outcomes after endovascular stroke treatment. The THRIVE score, which incorporates age, NIH Stroke Scale (NIHSS) score, and three medical comorbidities (hypertension, diabetes mellitus, and atrial fibrillation), was developed using data from the MERCI and Multi MERCI Trials, two clinical trials of the Merci family of endovascular stroke treatment devices. Methods: In order to perform external validation to demonstrate the reliability of our prediction tool, we applied the THRIVE score to patients from the Merci Registry, the largest clinical series of patients to date undergoing endovascular stroke treatment. We examined the predictive utility of the THRIVE score across the range of clinical outcomes and used Receiver-Operator Characteristics curve analysis and ordinal logistic regression to formally compare score performance in the two data sets. Results: We find that the THRIVE score predicts good outcome, death, and the full range of the modified Rankin Scale in a similar fashion between the MERCI Trials and the Merci Registry. In Receiver-Operator Characteristics curve comparisons, the area under the curve (AUC) for the ROC curves for good outcome was not significantly different between MERCI Trial patients (AUC = 0.293, 95% C.I. = 0.231 to 0.355) and Merci Registry patients (AUC = 0.266, 95% C.I. = 0.230 to 0.302) (P = 0.47), and the AUC for the ROC curves for death was not significantly different between MERCI Trial patients (AUC = 0.692, 95% C.I. = 0.632 to 0.752) and Merci Registry patients (AUC = 0.717, 95% C.I. = 0.683 to 0.750) (P = 0.48). The THRIVE score (0 to 9) predicts mRS (0 to 6) in ordinal logistic regression in a similar fashion for the MERCI Trials (OR = 1.47, 95% C.I. 1.31 to 1.65, P &lt; 0.001) and the Merci Registry (OR = 1.61, 95% C.I. 1.51 to 1.72, P &lt; 0.001). Conclusion: The THRIVE score reliably predicts outcomes after endovascular stroke treatment. The THRIVE score may be useful as a prognostic tool in clinical practice and as a means to perform severity adjustments in clinical stroke research. A THRIVE score calculator is available at www.thrivescore.org

Usefulness of the multidimensional prognostic index (MPI) in the management of older patients with chronic kidney disease

In older patients, given the central role of prognosis in clinical decision-making, there is an urgent need to develop accurate, validated, and rigorously tested prognostic indices. Current data suggest that in older patients not only physical but also psychological, cognitive, functional, nutritional, biological, and social factors may contribute to the increased risk of negative outcomes including institutionalization, hospitalization, and mortality. Recently, a Multidimensional Prognostic Index (MPI), derived from a standardized comprehensive geriatric assessment that included information from eight domains, i.e. basal and instrumental activities of daily living, cognitive and nutritional status, the risk for pressure sores, comorbidities, drug use, and co-habitation status was effective in predicting short- and long-term all-cause mortality risk in hospitalized patients with various acute and chronic conditions, including chronic kidney disease (CKD). In a consecutive cohort of patients with CKD the MPI accuracy in predicting mortality was significantly higher than the accuracy of the estimated glomerular filtration rate (eGFR). More recently, findings from hospital-based cohorts suggest that adding MPI information to the eGFR markedly improved the prediction of two-year all-cause mortality in older patients with CKD. While further studies are needed to assess the potential usefulness of this prognostic tool in clinical practice, a multidimensional assessment for all-cause mortality risk prediction should be considered in older patients with CKD. These findings support the concept that considering multidimensional aggregate information is very important for predicting short- and long-term all-cause mortality in older subjects with CKD, and that it may be important for the identification of more suitable management of these patients.

Spotlight Issue: Microcirculation—From a Clinical Perspective

This spotlight issue of Microcirculation contains five articles written from a clinical perspective on the role of microcirculatory abnormalities in the pathogenesis of cardiovascular disease. The reviews address issues such as the impact of modifiable (life style and environmental risk factors) and non modifiable (age) on microvascular form and function; inter- and intra-cell signaling pathways underlying microvascular dysfunction; microvascular assessment as a prognostic tool in clinical practice; and the potential impact of targeted therapeutic intervention on microvascular health. The articles also describe and evaluate methodological approaches to the assessment of microvascular function in organs such as the skin, retina, muscle and adipose tissue, and provide a perspective on how such approaches might be employed in future in disease risk stratification in large epidemiological studies. This timely edition of the journal Microcirculation highlights that while there is currently no identified unifying mechanism to explain the association between microvascular phenotype and susceptibility to disease, there is accumulating evidence that deficits in microvascular structure and function may be an early and important prodromal indicator and risk determinant in a wide range of chronic non-communicable disorders, including cardiovascular and metabolic disease.

Serum Interleukin-18 in Children with Henoch-Schönlein Purpura: A Promising Marker of Disease Activity?

Henoch-Schönlein purpura (HSp) is the most common systemic vasculitis of childhood with typical skin involvement and concurrent signs involving joints, gastrointestinal tract, and kidney. HSp pathogenesis is still far from being completely understood, though a knotty cytokine complex is believed to contribute to its intimate processes. The aim of our evaluation is to establish the relationship between serum levels of interleukin (IL)-18 and disease outcome and establish its feasibility to provide a marker of disease activity or even a prognostic tool in clinical practice. We examined clinical/laboratory variables and serum IL-18 in 17 children hospitalized during a year for HSp, diagnosed by EULAR/PRINTO/PRES criteria; the same patients were re-evaluated after 6 months. All results were compared with 25 age-matched healthy controls. IL-12 and IL-6 were also evaluated in a cohort of the same patients and compared with controls. General and clinical variables (sex, edema of the extremities, gastrointestinal or renal complications, relapses and renal involvement at 6 months) had no relationship with cytokine levels. Serum IL-18 and IL-6 levels were found significantly increased at diagnosis in HSp patients when compared with healthy controls. After 6 months, serum IL-18 and IL-12 levels were significantly decreased in patients, while IL-12 and IL-6 levels were significantly increased compared to healthy controls. Though preliminary and expecting further confirmation on a larger sample, our data support the conclusion that serum IL-18 levels reflect HSp activity.

Follicular lymphoma prognostic factors in the modern era: what is clinically meaningful?

Follicular lymphomas (FL) account for 30% of non-Hodgkin's lymphomas (NHL). Their evolution is heterogeneous. Some patients present with indolent forms undergoing several relapses while in other patients the disease evolves abruptly toward aggressive NHL. This is why accurate prognostic indices are required so that treatment strategies may be optimized for each patient and so that trials may be conducted in groups of patients that are as homogeneous as possible. The Follicular Lymphoma International Prognostic Index (FLIPI) has been designed to separate patients into 3 groups with significantly different hazard ratios for death. Its accuracy has been confirmed in several studies. The FLIPI2 was designed more recently to separate patients with significantly different hazard ratios for progression/relapse in the era of anti-CD20 monoclonal antibody treatments. Gene profile studies have shown that the prognosis of FL is mainly related to the type, number, and activation of immune cells in the microenvironment of lymphomatous follicles. Immunohistochemical studies suggest that macrophages, CD4+ T cells and among them T-regulatory cells (T-regs) and programed death-1 cells (PD-1 cells) play a major role in the outcome of FLs. However, additional confirmatory studies are required due to discrepancies in results. Up to now, these biological study results are more useful for approaching the pathophysiology of FL rather than to be used as prognostic tools in clinical practice.

MicroRNA Expression Profiles Associated with Mutational Status and Survival in Malignant Melanoma

Malignant cutaneous melanoma is a highly aggressive form of skin cancer. Despite improvements in early melanoma diagnosis, the 5-year survival rate remains low in advanced disease. Therefore, novel biomarkers are urgently needed to devise new means of detection and treatment. In this study, we aimed to improve our understanding of microRNA (miRNA) deregulation in melanoma development and their impact on patient survival. Global miRNA expression profiles of a set of melanoma lymph node metastases, melanoma cell lines, and melanocyte cultures were determined using Agilent array. Deregulated miRNAs were evaluated in relation with clinical characteristics, patient survival, and mutational status for BRAF and NRAS. Several miRNAs were differentially expressed between melanocytes and melanomas as well as melanoma cell lines. In melanomas, miR-193a, miR-338, and miR-565 were underexpressed in cases with a BRAF mutation. Furthermore, low expression of miR-191 and high expression of miR-193b were associated with poor melanoma-specific survival. In conclusion, our findings show miRNA dysregulation in malignant melanoma and its relation to established molecular backgrounds of BRAF and NRAS oncogenic mutations. The identification of an miRNA classifier for poor survival may lead to the development of miRNA detection as a complementary prognostic tool in clinical practice.